bims-kracam Biomed News
on K-Ras in cancer metabolism
Issue of 2022–12–25
forty papers selected by
Yasmin Elkabani, Egyptian Foundation for Research and Community Development
  1. Reprogramming of Cellular Metabolism and Its Therapeutic Applications in Thyroid Cancer.
  2. Promising bioactive properties of quercetin for potential food applications and health benefits: A review.
  3. Injectable Nano Drug Delivery Systems for the Treatment of Breast Cancer.
  4. The Emerging Role of Ferroptosis in Liver Cancers.
  5. Anticancer Applications of Essential Oils Formulated into Lipid-Based Delivery Nanosystems.
  6. Revisiting the Warburg Effect with Focus on Lactate.
  7. Tumor microenvironment penetrating chitosan nanoparticles for elimination of cancer relapse and minimal residual disease.
  8. Nanoparticles in Drug Delivery: From History to Therapeutic Applications.
  9. Metabolic reprogramming of glutamine involved in tumorigenesis, multidrug resistance and tumor immunity.
  10. Modified Curcumins as Potential Drug Candidates for Breast Cancer: An Overview.
  11. Modern Nanocarriers as a Factor in Increasing the Bioavailability and Pharmacological Activity of Flavonoids.
  12. Enhanced Photodynamic Therapy: A Review of Combined Energy Sources.
  13. Chemotherapeutic Potential of Saikosaponin D: Experimental Evidence.
  14. Biochemistry of Antioxidants: Mechanisms and Pharmaceutical Applications.
  15. Oxygen therapy accelerates apoptosis induced by selenium compounds via regulating Nrf2/MAPK signaling pathway in hepatocellular carcinoma.
  16. One-Carbon and Polyamine Metabolism as Cancer Therapy Targets.
  17. Mitochondrial-targeted nanoparticles: delivery and therapeutic agents in cancer.
  18. Recent Advances of Polymer Based Nanosystems in Cancer Management.
  19. Biological Properties and Health-Promoting Functions of Laminarin: A Comprehensive Review of Preclinical and Clinical Studies.
  20. Recent Advances in Natural Polyphenol Research.
  21. A Review on Biomedical Application of Polysaccharide-Based Hydrogels with a Focus on Drug Delivery Systems.
  22. Biomaterials for enhanced immunotherapy.
  23. Advances and Challenges of Cannabidiol as an Anti-Seizure Strategy: Preclinical Evidence.
  24. Niosomes-loaded selenium nanoparticles as a new approach for enhanced antibacterial, anti-biofilm, and anticancer activities.
  25. pH-Responsive Nanocomposite Hydrogel for Simultaneous Prevention of Postoperative Adhesion and Tumor Recurrence.
  26. Nanodelivery of Dietary Polyphenols for Therapeutic Applications.
  27. Pectin Based Hydrogels for Drug Delivery Applications: A Mini Review.
  28. Nanoparticle-Mediated Delivery of STAT3 Inhibitors in the Treatment of Lung Cancer.
  29. A comprehensive overview of Artemisinin and its derivatives as anticancer agents.
  30. Potential of ginsenoside Rh2and its derivatives as anti-cancer agents.
  31. Ursolic Acid Analogs as Potential Therapeutics for Cancer.
  32. Combined Photodynamic and Photothermal Therapy and Immunotherapy for Cancer Treatment: A Review.
  33. Metabolic switch in cancer - Survival of the fittest.
  34. Cell proliferation, drug distribution and therapeutic effects in relation to the vascular system of solid tumours.
  35. Berberine a traditional Chinese drug repurposing: Its actions in inflammation-associated ulcerative colitis and cancer therapy.
  36. Facile synthesis of phycocyanin/polydopamine hierarchical nanocomposites for synergizing PTT/PDT against cancer.
  37. The Synergistic Hepatoprotective Activity of Rosemary Essential Oil and Curcumin: The Role of the MEK/ERK Pathway.
  38. Metabolomic profiling of triple negative breast cancer cells suggests that valproic acid can enhance the anticancer effect of cisplatin.
  39. Phytochemicals as Chemo-Preventive Agents and Signaling Molecule Modulators: Current Role in Cancer Therapeutics and Inflammation.
  40. Interactions between Natural Products-A Review.
  1. Metabolites. 2022 Dec 03. pii: 1214. [Epub ahead of print]12(12):
    Reprogramming of Cellular Metabolism and Its Therapeutic Applications in Thyroid Cancer.
    Yuji Nagayama, Koichiro Hamada.
      Metabolism is a series of life-sustaining chemical reactions in organisms, providing energy required for cellular processes and building blocks for cellular constituents of proteins, lipids, carbohydrates and nucleic acids. Cancer cells frequently reprogram their metabolic behaviors to adapt their rapid proliferation and altered tumor microenvironments. Not only aerobic glycolysis (also termed the Warburg effect) but also altered mitochondrial metabolism, amino acid metabolism and lipid metabolism play important roles for cancer growth and aggressiveness. Thus, the mechanistic elucidation of these metabolic changes is invaluable for understanding the pathogenesis of cancers and developing novel metabolism-targeted therapies. In this review article, we first provide an overview of essential metabolic mechanisms, and then summarize the recent findings of metabolic reprogramming and the recent reports of metabolism-targeted therapies for thyroid cancer.
    Keywords:  TCA cycle; electron transport chain; glutaminolysis; glycolysis; lipid metabolism; metabolomics; the Warburg effect; thyroid cancer
    DOI:  https://doi.org/10.3390/metabo12121214
  2. Front Nutr. 2022 ;9 999752
    Promising bioactive properties of quercetin for potential food applications and health benefits: A review.
    Irtiqa Shabir, Vinay Kumar Pandey, Rafeeya Shams, Aamir Hussain Dar, Kshirod Kumar Dash, Shafat Ahmad Khan, Iqra Bashir, G Jeevarathinam, Alexandru Vasile Rusu, Tuba Esatbeyoglu, R Pandiselvam.
      Naturally occurring phytochemicals with promising biological properties are quercetin and its derivatives. Quercetin has been thoroughly studied for its antidiabetic, antibacterial, anti-inflammatory, anti-Alzheimer's, anti-arthritic, antioxidant, cardiovascular, and wound-healing properties. Anticancer activity of quercetin against cancer cell lines has also recently been revealed. The majority of the Western diet contains quercetin and its derivatives, therefore consuming them as part of a meal or as a food supplement may be sufficient for people to take advantage of their preventive effects. Bioavailability-based drug-delivery systems of quercetin have been heavily studied. Fruits, seeds, vegetables, bracken fern, coffee, tea, and other plants all contain quercetin, as do natural colors. One naturally occurring antioxidant is quercetin, whose anticancer effects have been discussed in detail. It has several properties that could make it an effective anti-cancer agent. Numerous researches have shown that quercetin plays a substantial part in the suppression of cancer cells in the breast, colon, prostate, ovary, endometrial, and lung tumors. The current study includes a concise explanation of quercetin's action mechanism and potential health applications.
    Keywords:  antimicrobial properties; antioxidant; bioactive compounds; nutraceutical properties; quercetin
    DOI:  https://doi.org/10.3389/fnut.2022.999752
  3. Pharmaceutics. 2022 Dec 13. pii: 2783. [Epub ahead of print]14(12):
    Injectable Nano Drug Delivery Systems for the Treatment of Breast Cancer.
    Urmila Kafle, Satish Agrawal, Alekha K Dash.
      Breast cancer is the most diagnosed type of cancer, with 2.26 million cases and 685,000 deaths recorded in 2020. If left untreated, this deadly disease can metastasize to distant organs, which is the reason behind its incurability and related deaths. Currently, conventional therapies are used to treat breast cancer, but they have numerous shortcomings such as low bioavailability, short circulation time, and off-target toxicity. To address these challenges, nanomedicines are preferred and are being extensively investigated for breast cancer treatment. Nanomedicines are novel drug delivery systems that can improve drug stability, aqueous solubility, blood circulation time, controlled release, and targeted delivery at the tumoral site and enhance therapeutic safety and effectiveness. Nanoparticles (NPs) can be administered through different routes. Although the injectable route is less preferred than the oral route for drug administration, it has its advantages: it helps tailor drugs with targeted moiety, boosts payload, avoids first-pass metabolism, and improves the pharmacokinetic parameters of the active pharmaceutical ingredients. Targeted delivery of nanomedicine, closer to organelles such as the mitochondria and nuclei in breast cancer, reduces the dosage requirements and the toxic effects of chemotherapeutics. This review aims to provide the current status of the recent advances in various injectable nanomedicines for targeted treatment of breast cancer.
    Keywords:  breast cancer; controlled release; injectable; inorganic nanoparticles; metastasis; nano-drug delivery systems; nanomedicine; organic nanoparticles
    DOI:  https://doi.org/10.3390/pharmaceutics14122783
  4. Life (Basel). 2022 Dec 16. pii: 2128. [Epub ahead of print]12(12):
    The Emerging Role of Ferroptosis in Liver Cancers.
    Arianna Casini, Stefano Leone, Rosa Vaccaro, Giorgio Vivacqua, Ludovica Ceci, Luigi Pannarale, Antonio Franchitto, Paolo Onori, Eugenio Gaudio, Romina Mancinelli.
      Liver cancer represents a global health challenge with worldwide growth. Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Indeed, approximately 90% of HCC cases have a low survival rate. Moreover, cholangiocarcinoma (CC) is another malignant solid tumor originating from cholangiocytes, the epithelial cells of the biliary system. It is the second-most common primary liver tumor, with an increasing course in morbidity and mortality. Tumor cells always show high metabolic levels, antioxidant modifications, and an increased iron uptake to maintain unlimited growth. In recent years, alterations in iron metabolism have been shown to play an important role in the pathogenesis of HCC. Several findings show that a diet rich in iron can enhance HCC risk. Hence, elevated iron concentration inside the cell may promote the development of HCC. Growing evidence sustains that activating ferroptosis may potentially block the proliferation of HCC cells. Even in CC, it has been shown that ferroptosis plays a crucial role in the treatment of tumors. Several data confirmed the inhibitory effect in cell growth of photodynamic therapy (PDT) that can induce reactive oxygen species (ROS) in CC, leading to an increase in malondialdehyde (MDA) and a decrease in intracellular glutathione (GSH). MDA and GSH depletion/modulation are crucial in inducing ferroptosis, suggesting that PDT may have the potential to induce this kind of cell death through these ways. A selective induction of programmed cell death in cancer cells is one of the main treatments for malignant tumors; thus, ferroptosis may represent a novel therapeutic strategy against HCC and CC.
    Keywords:  cholangiocarcinoma; ferroptosis; hepatocarcinoma; iron metabolism; liver cancer
    DOI:  https://doi.org/10.3390/life12122128
  5. Pharmaceutics. 2022 Dec 01. pii: 2681. [Epub ahead of print]14(12):
    Anticancer Applications of Essential Oils Formulated into Lipid-Based Delivery Nanosystems.
    Josef Jampilek, Katarina Kralova.
      The use of natural compounds is becoming increasingly popular among patients, and there is a renewed interest among scientists in nature-based bioactive agents. Traditionally, herbal drugs can be taken directly in the form of teas/decoctions/infusions or as standardized extracts. However, the disadvantages of natural compounds, especially essential oils, are their instability, limited bioavailability, volatility, and often irritant/allergenic potential. However, these active substances can be stabilized by encapsulation and administered in the form of nanoparticles. This brief overview summarizes the latest results of the application of nanoemulsions, liposomes, solid lipid nanoparticles, and nanostructured lipid carriers used as drug delivery systems of herbal essential oils or used directly for their individual secondary metabolites applicable in cancer therapy. Although the discussed bioactive agents are not typical compounds used as anticancer agents, after inclusion into the aforesaid formulations improving their stability and bioavailability and/or therapeutic profile, they indicated anti-tumor activity and became interesting agents with cancer treatment potential. In addition, co-encapsulation of essential oils with synthetic anticancer drugs into nanoformulations with the aim to achieve synergistic effect in chemotherapy is discussed.
    Keywords:  anticancer activity; essential oils; herbal drugs; liposomes; nanoemulsions; nanostructured lipid carriers; solid lipid nanoparticles
    DOI:  https://doi.org/10.3390/pharmaceutics14122681
  6. Cancers (Basel). 2022 Dec 07. pii: 6028. [Epub ahead of print]14(24):
    Revisiting the Warburg Effect with Focus on Lactate.
    Eva Kocianova, Viktoria Piatrikova, Tereza Golias.
      Rewired metabolism is acknowledged as one of the drivers of tumor growth. As a result, aerobic glycolysis, or the Warburg effect, is a feature of many cancers. Increased glucose uptake and glycolysis provide intermediates for anabolic reactions necessary for cancer cell proliferation while contributing sufficient energy. However, the accompanying increased lactate production, seemingly wasting glucose carbon, was originally explained only by the need to regenerate NAD+ for successive rounds of glycolysis by the lactate dehydrogenase (LDH) reaction in the cytosol. After the discovery of a mitochondrial LDH isoform, lactate oxidation entered the picture, and lactate was recognized as an important oxidative fuel. It has also been revealed that lactate serves a variety of signaling functions and helps cells adapt to the new environment. Here, we discuss recent findings on lactate metabolism and signaling in cancer while attempting to explain why the Warburg effect is adopted by cancer cells.
    Keywords:  Warburg effect; glucose metabolism; lactate; lactate dehydrogenase; lactate oxidation; lactate shuttle; lactate signaling; lactylation
    DOI:  https://doi.org/10.3390/cancers14246028
  7. Front Oncol. 2022 ;12 1054029
    Tumor microenvironment penetrating chitosan nanoparticles for elimination of cancer relapse and minimal residual disease.
    Hossein Mahmudi, Mohammad Amin Adili-Aghdam, Mohammad Shahpouri, Mehdi Jaymand, Zohreh Amoozgar, Rana Jahanban-Esfahlan.
      Chitosan and its derivatives are among biomaterials with numerous medical applications, especially in cancer. Chitosan is amenable to forming innumerable shapes such as micelles, niosomes, hydrogels, nanoparticles, and scaffolds, among others. Chitosan derivatives can also bring unprecedented potential to cross numerous biological barriers. Combined with other biomaterials, hybrid and multitasking chitosan-based systems can be realized for many applications. These include controlled drug release, targeted drug delivery, post-surgery implants (immunovaccines), theranostics, biosensing of tumor-derived circulating materials, multimodal systems, and combination therapy platforms with the potential to eliminate bulk tumors as well as lingering tumor cells to treat minimal residual disease (MRD) and recurrent cancer. We first introduce different formats, derivatives, and properties of chitosan. Next, given the barriers to therapeutic efficacy in solid tumors, we review advanced formulations of chitosan modules as efficient drug delivery systems to overcome tumor heterogeneity, multi-drug resistance, MRD, and metastasis. Finally, we discuss chitosan NPs for clinical translation and treatment of recurrent cancer and their future perspective.
    Keywords:  chitosan; drug delivery; minimal residual disease; recurrent cancer; tumor heterogeneity; tumor microenvironment
    DOI:  https://doi.org/10.3389/fonc.2022.1054029
  8. Nanomaterials (Basel). 2022 Dec 19. pii: 4494. [Epub ahead of print]12(24):
    Nanoparticles in Drug Delivery: From History to Therapeutic Applications.
    Obaid Afzal, Abdulmalik S A Altamimi, Muhammad Shahid Nadeem, Sami I Alzarea, Waleed Hassan Almalki, Aqsa Tariq, Bismillah Mubeen, Bibi Nazia Murtaza, Saima Iftikhar, Naeem Riaz, Imran Kazmi.
      Current research into the role of engineered nanoparticles in drug delivery systems (DDSs) for medical purposes has developed numerous fascinating nanocarriers. This paper reviews the various conventionally used and current used carriage system to deliver drugs. Due to numerous drawbacks of conventional DDSs, nanocarriers have gained immense interest. Nanocarriers like polymeric nanoparticles, mesoporous nanoparticles, nanomaterials, carbon nanotubes, dendrimers, liposomes, metallic nanoparticles, nanomedicine, and engineered nanomaterials are used as carriage systems for targeted delivery at specific sites of affected areas in the body. Nanomedicine has rapidly grown to treat certain diseases like brain cancer, lung cancer, breast cancer, cardiovascular diseases, and many others. These nanomedicines can improve drug bioavailability and drug absorption time, reduce release time, eliminate drug aggregation, and enhance drug solubility in the blood. Nanomedicine has introduced a new era for drug carriage by refining the therapeutic directories of the energetic pharmaceutical elements engineered within nanoparticles. In this context, the vital information on engineered nanoparticles was reviewed and conferred towards the role in drug carriage systems to treat many ailments. All these nanocarriers were tested in vitro and in vivo. In the coming years, nanomedicines can improve human health more effectively by adding more advanced techniques into the drug delivery system.
    Keywords:  drug delivery; nanomedicine; nanoparticles; personalized medicine; therapeutics
    DOI:  https://doi.org/10.3390/nano12244494
  9. Eur J Pharmacol. 2022 Dec 16. pii: S0014-2999(22)00584-2. [Epub ahead of print] 175323
    Metabolic reprogramming of glutamine involved in tumorigenesis, multidrug resistance and tumor immunity.
    Wang Xiao-Yan, Yang Xiao-Xia, Shang Peng-Fei, Zheng Zong-Xue, Guo Xiu-Li.
      Glutamine, as the most abundant amino acid in the body, participates in the biological synthesis of nucleotides and other non-essential amino acids in the process of cell metabolism. Recent studies showed that glutamine metabolic reprogramming is an important signal during cancer development and progression. This metabolic signature in cancer cells can promote the development of cancer by activating multiple signaling pathways and oncogenes. It can also be involved in tumor immune regulation and promote the development of drug resistance to tumors. In this review, we mainly summarize the role of glutamine metabolic reprogramming in tumors, including the regulation of multiple signaling pathways. We further discussed the promising tumor treatment strategy by targeting glutamine metabolism alone or in combination with chemotherapeutics.
    Keywords:  Glutamine; Multidrug resistance; Tumor immunotherapy; Tumor metabolism
    DOI:  https://doi.org/10.1016/j.ejphar.2022.175323
  10. Molecules. 2022 Dec 14. pii: 8891. [Epub ahead of print]27(24):
    Modified Curcumins as Potential Drug Candidates for Breast Cancer: An Overview.
    Abigail L Flint, David W Hansen, LaVauria D Brown, Laura E Stewart, Eduardo Ortiz, Siva S Panda.
      Breast cancer (BC), the most common malignancy in women, results from significant alterations in genetic and epigenetic mechanisms that alter multiple signaling pathways in growth and malignant progression, leading to limited long-term survival. Current studies with numerous drug therapies have shown that BC is a complex disease with tumor heterogeneity, rapidity, and dynamics of the tumor microenvironment that result in resistance to existing therapy. Targeting a single cell-signaling pathway is unlikely to treat or prevent BC. Curcumin (a natural yellow pigment), the principal ingredient in the spice turmeric, is well-documented for its diverse pharmacological properties including anti-cancer activity. However, its clinical application has been limited because of its low solubility, stability, and bioavailability. To overcome the limitation of curcumin, several modified curcumin conjugates and curcumin mimics were developed and studied for their anti-cancer properties. In this review, we have focused on the application of curcumin mimics and their conjugates for breast cancer.
    Keywords:  breast cancer; conjugates; curcumin; curcumin mimic; drug development; synthesis
    DOI:  https://doi.org/10.3390/molecules27248891
  11. Appl Biochem Microbiol. 2022 ;58(9): 1002-1020
    Modern Nanocarriers as a Factor in Increasing the Bioavailability and Pharmacological Activity of Flavonoids.
    Ya F Zverev, A Ya Rykunova.
      This review is devoted to modern systems of nanocarriers that ensure the targeted delivery of flavonoids to various organs and systems. Flavonoids have wide range of effects on the human body due to their antioxidant, anti-inflammatory, antitumor, antimicrobial, antiplatelet and other types of activity. However, the low bioavailability of flavonoids significantly limits their practical application. To overcome this disadvantage, serious efforts have been made in recent years to develop nanoscale carriers for flavonoids. This is particularly important in view of the known antitumor effect of these compounds, which allows them to target tumor cells without affecting surrounding healthy tissues. Nanocarriers provide increased penetration of biologicals into specific organs in combination with controlled and prolonged release, which markedly improves their effectiveness. This review summarizes data on the use of phytosomes, lipid-based nanoparticles, as well as polymeric and inorganic nanoparticles; their advantages and drawbacks are analyzed; the prospect of their use is discussed that opens new possibilities for the clinical application of flavonoids.
    Keywords:  drug delivery systems; flavonoid nanobiomaterials; flavonoids; nanoparticles
    DOI:  https://doi.org/10.1134/S0003683822090149
  12. Cells. 2022 Dec 10. pii: 3995. [Epub ahead of print]11(24):
    Enhanced Photodynamic Therapy: A Review of Combined Energy Sources.
    José A Rodrigues, José H Correia.
      Photodynamic therapy (PDT) has been used in recent years as a non-invasive treatment for cancer, due to the side effects of traditional treatments such as surgery, radiotherapy, and chemotherapy. This therapeutic technique requires a photosensitizer, light energy, and oxygen to produce reactive oxygen species (ROS) which mediate cellular toxicity. PDT is a useful non-invasive therapy for cancer treatment, but it has some limitations that need to be overcome, such as low-light-penetration depths, non-targeting photosensitizers, and tumor hypoxia. This review focuses on the latest innovative strategies based on the synergistic use of other energy sources, such as non-visible radiation of the electromagnetic spectrum (microwaves, infrared, and X-rays), ultrasound, and electric/magnetic fields, to overcome PDT limitations and enhance the therapeutic effect of PDT. The main principles, mechanisms, and crucial elements of PDT are also addressed.
    Keywords:  electric field; magnetic field; non-visible radiation; photodynamic therapy; synergistic strategies; ultrasound
    DOI:  https://doi.org/10.3390/cells11243995
  13. J Xenobiot. 2022 Dec 17. 12(4): 378-405
    Chemotherapeutic Potential of Saikosaponin D: Experimental Evidence.
    Suryaa Manoharan, Bhuvaneshwari Deivendran, Ekambaram Perumal.
      Saikosaponin D (SSD), an active compound derived from the traditional plant Radix bupleuri, showcases potential in disease management owing to its antioxidant, antipyretic, and anti-inflammatory properties. The toxicological effects of SSD mainly include hepatotoxicity, neurotoxicity, hemolysis, and cardiotoxicity. SSD exhibits antitumor effects on multiple targets and has been witnessed in diverse cancer types by articulating various cell signaling pathways. As a result, carcinogenic processes such as proliferation, invasion, metastasis, and angiogenesis are inhibited, whereas apoptosis, autophagy, and differentiation are induced in several cancer cells. Since it reduces side effects and strengthens anti-cancerous benefits, SSD has been shown to have an additive or synergistic impact with chemo-preventive medicines. Regardless of its efficacy and benefits, the considerations of SSD in cancer prevention are absolutely under-researched due to its penurious bioavailability. Diverse studies have overcome the impediments of inadequate bioavailability using nanotechnology-based methods such as nanoparticle encapsulation, liposomes, and several other formulations. In this review, we emphasize the association of SSD in cancer therapeutics and the discussion of the mechanisms of action with the significance of experimental evidence.
    Keywords:  Radix bupleuri; Saikosaponin D; anticancer effects; apoptosis; chemotherapy
    DOI:  https://doi.org/10.3390/jox12040027
  14. Biomedicines. 2022 Nov 25. pii: 3051. [Epub ahead of print]10(12):
    Biochemistry of Antioxidants: Mechanisms and Pharmaceutical Applications.
    Sonia Losada-Barreiro, Zerrin Sezgin-Bayindir, Fátima Paiva-Martins, Carlos Bravo-Díaz.
      Natural antioxidants from fruits and vegetables, meats, eggs and fish protect cells from the damage caused by free radicals. They are widely used to reduce food loss and waste, minimizing lipid oxidation, as well as for their effects on health through pharmaceutical preparations. In fact, the use of natural antioxidants is among the main efforts made to relieve the pressure on natural resources and to move towards more sustainable food and pharmaceutical systems. Alternative food waste management approaches include the valorization of by-products as a source of phenolic compounds for functional food formulations. In this review, we will deal with the chemistry of antioxidants, including their molecular structures and reaction mechanisms. The biochemical aspects will also be reviewed, including the effects of acidity and temperature on their partitioning in binary and multiphasic systems. The poor bioavailability of antioxidants remains a huge constraint for clinical applications, and we will briefly describe some delivery systems that provide for enhanced pharmacological action of antioxidants via drug targeting and increased bioavailability. The pharmacological activity of antioxidants can be improved by designing nanotechnology-based formulations, and recent nanoformulations include nanoparticles, polymeric micelles, liposomes/proliposomes, phytosomes and solid lipid nanoparticles, all showing promising outcomes in improving the efficiency and bioavailability of antioxidants. Finally, an overview of the pharmacological effects, therapeutic properties and future choice of antioxidants will be incorporated.
    Keywords:  antioxidants; bioactivity; bioavailability; nano antioxidants delivery systems; oxidative stress
    DOI:  https://doi.org/10.3390/biomedicines10123051
  15. Pharmacol Res. 2022 Dec 20. pii: S1043-6618(22)00570-9. [Epub ahead of print] 106624
    Oxygen therapy accelerates apoptosis induced by selenium compounds via regulating Nrf2/MAPK signaling pathway in hepatocellular carcinoma.
    Cheng Wang, Tingting Cheng, Qianqian Lu, Wenzhen Li, Ben Liu, Lijun Yue, Maoru Du, Wenxue Sheng, Zhaochen Lu, Jingnan Yang, Feng Geng, Xue Gao, Junhong Lü, Xiaohong Pan.
      Selenium has good antitumor effects in vitro, but the hypoxic microenvironment in solid tumors makes its clinical efficacy unsatisfactory. We hypothesized that the combination with oxygen therapy might improve the treatment efficacy of selenium in hypoxic tumors through the changes of redox environment. In this work, two selenium compounds, Na2SeO3 and CysSeSeCys, were selected to interrogate their therapeutic effects on hepatocellular carcinoma (HCC) under different oxygen levels. In tumor-bearing mice, both selenium compounds significantly inhibited the tumor growth, and combined with oxygen therapy further reduced the tumor volume about 50%. In vitro HepG2 cell experiments, selenium induced autophagy and delayed apoptosis under hypoxia (1% O2), while inhibited autophagy and accelerated apoptosis under hyperoxia (60% O2). We found that, in contrast to hypoxia, the hyperoxic environment facilitated the H2Se, produced by the selenium metabolism in cells, to be rapidly oxidized to generate H2O2, leading to inhibit the expression level of Nrf2 and to increase that of phosphorylation of p38 and MKK4, resulting in inhibiting autophagy and accelerating apoptosis. Once the Nrf2 gene was knocked down, selenium compounds combined with hyperoxia treatment would further activate the MAPK signaling pathway and further increase apoptosis. These findings highlight oxygen can significantly enhance the anti-HCC effect of selenium compounds through regulating the Nrf2 and MAPK signaling pathways, thus providing novel therapeutic strategy for the hypoxic tumors and pave the way for the application of selenium in clinical treatment.
    Keywords:  MAPK; Nrf2; hepatocellular carcinoma; oxygen therapy; selenium compounds
    DOI:  https://doi.org/10.1016/j.phrs.2022.106624
  16. Biomolecules. 2022 Dec 19. pii: 1902. [Epub ahead of print]12(12):
    One-Carbon and Polyamine Metabolism as Cancer Therapy Targets.
    Anowarul Islam, Zeeshan Shaukat, Rashid Hussain, Stephen L Gregory.
      Cancer metabolic reprogramming is essential for maintaining cancer cell survival and rapid replication. A common target of this metabolic reprogramming is one-carbon metabolism which is notable for its function in DNA synthesis, protein and DNA methylation, and antioxidant production. Polyamines are a key output of one-carbon metabolism with widespread effects on gene expression and signaling. As a result of these functions, one-carbon and polyamine metabolism have recently drawn a lot of interest for their part in cancer malignancy. Therapeutic inhibitors that target one-carbon and polyamine metabolism have thus been trialed as anticancer medications. The significance and future possibilities of one-carbon and polyamine metabolism as a target in cancer therapy are discussed in this review.
    Keywords:  autophagy; cancer; metabolic therapy; methionine; one-carbon metabolism; polyamines; reactive oxygen species
    DOI:  https://doi.org/10.3390/biom12121902
  17. Drug Discov Today. 2022 Dec 15. pii: S1359-6446(22)00462-7. [Epub ahead of print] 103469
    Mitochondrial-targeted nanoparticles: delivery and therapeutic agents in cancer.
    Chaithaithanya Ganji, Veda Muppala, Musaab Khan, Ganji Purnachandra Nagaraju, Batoul Farran.
      Mitochondria are the powerhouses of cells and modulate the essential metabolic functions required for cellular survival. Various mitochondrial pathways, such as oxidative phosphorylation or production of reactive oxygen species (ROS) are dysregulated during cancer growth and development, rendering them attractive targets against cancer. Thus, the delivery of antitumor agents to mitochondria has emerged as a potential approach for treating cancer. Recent advances in nanotechnology have provided innovative solutions for overcoming the physical barriers posed by the structure of mitochondrial organelles, and have enabled the development of efficient mitochondrial nanoplatforms. In this review, we examine the importance of mitochondria during neoplastic development, explore the most recent smart designs of nano-based systems aimed at targeting mitochondria, and highlight key mitochondrial pathways in cancer cells. Teaser: Dysregulation of mitochondria is a hallmark of cancer development. Nanotechnology has allowed the development of mitochondria-targeted agents that enhance cancer cell death through the generation of reactive oxygen species and reduced mitochondrial membrane potential.
    Keywords:  cancer; drug; mitochondria; nanoparticles; therapy
    DOI:  https://doi.org/10.1016/j.drudis.2022.103469
  18. J Biomater Sci Polym Ed. 2022 Dec 21. 1-73
    Recent Advances of Polymer Based Nanosystems in Cancer Management.
    Chetan Janrao, Shivani Khopade, Akshay Bavaskar, Shyam Sudhakar Gomte, Tejas Girish Agnihotri, Aakanchha Jain.
      Cancer is still one of the leading causes of death worldwide. Nanotechnology, particularly nanoparticle-based platforms, is at the leading edge of current cancer management research. Polymer-based nanosystems have piqued the interest of researchers owing to their many benefits over other conventional drug delivery systems. Polymers derived from both natural and synthetic sources have various biomedical applications due to unique qualities like porosity, mechanical strength, biocompatibility, and biodegradability. Polymers such as poly (lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), and polyethylene glycol (PEG) have been approved by the USFDA and are being researched for drug delivery applications. They have been reported to be potential carriers for drug loading and are used in theranostic applications. In this review, we have primarily focused on the aforementioned polymers and their conjugates. In addition, the therapeutic and diagnostic implications of polymer-based nanosystems have been briefly reviewed. Furthermore, the safety of the developed polymeric formulations is crucial, and we have discussed their biocompatibility in detail. This article also discusses recent developments in block co-polymer-based nanosystems for cancer treatment. The review ends with the challenges of clinical translation of polymer-based nanosystems in drug delivery for cancer therapy.
    Keywords:  PCL; PLGA; Polymeric nanosystems; cancer; nanoparticles; polymers
    DOI:  https://doi.org/10.1080/09205063.2022.2161780
  19. Mar Drugs. 2022 Dec 10. pii: 772. [Epub ahead of print]20(12):
    Biological Properties and Health-Promoting Functions of Laminarin: A Comprehensive Review of Preclinical and Clinical Studies.
    Shanmugapriya Karuppusamy, Gaurav Rajauria, Stephen Fitzpatrick, Henry Lyons, Helena McMahon, James Curtin, Brijesh K Tiwari, Colm O'Donnell.
      Marine algal species comprise of a large portion of polysaccharides which have shown multifunctional properties and health benefits for treating and preventing human diseases. Laminarin, or β-glucan, a storage polysaccharide from brown algae, has been reported to have potential pharmacological properties such as antioxidant, anti-tumor, anti-coagulant, anticancer, immunomodulatory, anti-obesity, anti-diabetic, anti-inflammatory, wound healing, and neuroprotective potential. It has been widely investigated as a functional material in biomedical applications as it is biodegradable, biocompatible, and is low toxic substances. The reported preclinical and clinical studies demonstrate the potential of laminarin as natural alternative agents in biomedical and industrial applications such as nutraceuticals, pharmaceuticals, functional food, drug development/delivery, and cosmeceuticals. This review summarizes the biological activities of laminarin, including mechanisms of action, impacts on human health, and reported health benefits. Additionally, this review also provides an overview of recent advances and identifies gaps and opportunities for further research in this field. It further emphasizes the molecular characteristics and biological activities of laminarin in both preclinical and clinical settings for the prevention of the diseases and as potential therapeutic interventions.
    Keywords:  algal polysaccharide; bioactive compounds; biological activity; biomedical application; clinical; human health; laminarin; preclinical
    DOI:  https://doi.org/10.3390/md20120772
  20. Molecules. 2022 Dec 11. pii: 8777. [Epub ahead of print]27(24):
    Recent Advances in Natural Polyphenol Research.
    Irene Dini, Lucia Grumetto.
      Polyphenols are secondary metabolites produced by plants, which contribute to the plant's defense against abiotic stress conditions (e.g., UV radiation and precipitation), the aggression of herbivores, and plant pathogens. Epidemiological studies suggest that long-term consumption of plant polyphenols protects against cardiovascular disease, cancer, osteoporosis, diabetes, and neurodegenerative diseases. Their structural diversity has fascinated and confronted analytical chemists on how to carry out unambiguous identification, exhaustive recovery from plants and organic waste, and define their nutritional and biological potential. The food, cosmetic, and pharmaceutical industries employ polyphenols from fruits and vegetables to produce additives, additional foods, and supplements. In some cases, nanocarriers have been used to protect polyphenols during food processing, to solve the issues related to low water solubility, to transport them to the site of action, and improve their bioavailability. This review summarizes the structure-bioactivity relationships, processing parameters that impact polyphenol stability and bioavailability, the research progress in nanocarrier delivery, and the most innovative methodologies for the exhaustive recovery of polyphenols from plant and agri-waste materials.
    Keywords:  agri-food wastes; antioxidant; bioavailability; circular economy; cosmeceuticals; flavonoids; functional food; health; nano-delivery; nutraceuticals; polyphenols activity; polyphenols bioavailability; sustainability
    DOI:  https://doi.org/10.3390/molecules27248777
  21. Polymers (Basel). 2022 Dec 12. pii: 5432. [Epub ahead of print]14(24):
    A Review on Biomedical Application of Polysaccharide-Based Hydrogels with a Focus on Drug Delivery Systems.
    Bahareh Farasati Far, Mohammad Reza Naimi-Jamal, Maryam Safaei, Kimia Zarei, Marzieh Moradi, Hamed Yazdani Nezhad.
      Over the last years of research on drug delivery systems (DDSs), natural polymer-based hydrogels have shown many scientific advances due to their intrinsic properties and a wide variety of potential applications. While drug efficacy and cytotoxicity play a key role, adopting a proper DDS is crucial to preserve the drug along the route of administration and possess desired therapeutic effect at the targeted site. Thus, drug delivery technology can be used to overcome the difficulties of maintaining drugs at a physiologically related serum concentration for prolonged periods. Due to their outstanding biocompatibility, polysaccharides have been thoroughly researched as a biological material for DDS advancement. To formulate a modified DDS, polysaccharides can cross-link with different molecules, resulting in hydrogels. According to our recent findings, targeted drug delivery at a certain spot occurs due to external stimulation such as temperature, pH, glucose, or light. As an adjustable biomedical device, the hydrogel has tremendous potential for nanotech applications in involved health areas such as pharmaceutical and biomedical engineering. An overview of hydrogel characteristics and functionalities is provided in this review. We focus on discussing the various kinds of hydrogel-based systems on their potential for effectively delivering drugs that are made of polysaccharides.
    Keywords:  bioengineering; biomedical application; drug delivery; hydrogel; polysaccharide
    DOI:  https://doi.org/10.3390/polym14245432
  22. APL Bioeng. 2022 Dec;6(4): 041502
    Biomaterials for enhanced immunotherapy.
    Nicholas Cunningham, Réjean Lapointe, Sophie Lerouge.
      Cancer immunotherapies have revolutionized the treatment of numerous cancers, with exciting results often superior to conventional treatments, such as surgery and chemotherapy. Despite this success, limitations such as limited treatment persistence and toxic side effects remain to be addressed to further improve treatment efficacy. Biomaterials offer numerous advantages in the concentration, localization and controlled release of drugs, cancer antigens, and immune cells in order to improve the efficacy of these immunotherapies. This review summarizes and highlights the most recent advances in the use of biomaterials for immunotherapies including drug delivery and cancer vaccines, with a particular focus on biomaterials for immune cell delivery.
    DOI:  https://doi.org/10.1063/5.0125692
  23. Int J Mol Sci. 2022 Dec 19. pii: 16181. [Epub ahead of print]23(24):
    Advances and Challenges of Cannabidiol as an Anti-Seizure Strategy: Preclinical Evidence.
    Cecilia Zavala-Tecuapetla, Hiram Luna-Munguia, María-Leonor López-Meraz, Manola Cuellar-Herrera.
      The use of Cannabis for medicinal purposes has been documented since ancient times, where one of its principal cannabinoids extracted from Cannabis sativa, cannabidiol (CBD), has emerged over the last few years as a promising molecule with anti-seizure potential. Here, we present an overview of recent literature pointing out CBD's pharmacological profile (solubility, metabolism, drug-drug interactions, etc.,), CBD's interactions with multiple molecular targets as well as advances in preclinical research concerning its anti-seizure effect on both acute seizure models and chronic models of epilepsy. We also highlight the recent attention that has been given to other natural cannabinoids and to synthetic derivatives of CBD as possible compounds with therapeutic anti-seizure potential. All the scientific research reviewed here encourages to continue to investigate the probable therapeutic efficacy of CBD and its related compounds not only in epilepsy but also and specially in drug-resistant epilepsy, since there is a dire need for new and effective drugs to treat this disease.
    Keywords:  cannabidiol; drug resistant epilepsy; epilepsy; phytocannabinoids; preclinical models; seizure
    DOI:  https://doi.org/10.3390/ijms232416181
  24. Sci Rep. 2022 Dec 19. 12(1): 21938
    Niosomes-loaded selenium nanoparticles as a new approach for enhanced antibacterial, anti-biofilm, and anticancer activities.
    Abbas Haddadian, Farnoush Falahi Robattorki, Hedieh Dibah, Ali Soheili, Erfan Ghanbarzadeh, Nasrin Sartipnia, Shadi Hajrasouliha, Kamal Pasban, Romina Andalibi, Mojtaba Hedayati Ch, Arezou Azari, Arman Chitgarzadeh, Aliasghar Bagheri Kashtali, Fatemeh Mastali, Hassan Noorbazargan, Amir Mirzaie.
      Targeted drug delivery and increasing the biological activity of drugs is one of the recent challenges of pharmaceutical researchers. Niosomes are one of the new targeted drug delivery systems that enhances the biological properties of drugs. In this study, for the first time, the green synthesis of selenium nanoparticles (SeNPs), and its loading into niosome was carried out to increase the anti-bacterial and anti-cancer activity of SeNPs. Different formulations of noisome-loaded SeNPs were prepared, and the physical and chemical characteristics of the prepared niosomes were investigated. The antibacterial and anti-biofilm effects of synthesized niosomes loaded SeNPs and free SeNPs against standard pathogenic bacterial strains were studied, and also its anticancer activity was investigated against breast cancer cell lines. The expression level of apoptotic genes in breast cancer cell lines treated with niosome-loaded SeNPs and free SeNPs was measured. Also, to evaluate the biocompatibility of the synthesized niosomes, their cytotoxicity effects against the human foreskin fibroblasts normal cell line (HFF) were studied using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. The results illustrated that the optimal formulation had an average size of 177.9 nm, a spherical shape, and an encapsulation efficiency of 37.58%. Also, the results revealed that the release rate of SeNPs from niosome-loaded SeNPs and free SeNPs was 61.26% and 100%, respectively, in 72 h. Also, our findings demonstrated that the niosome-loaded SeNPs have significant antibacterial, anti-biofilm, and anticancer effects compared to the free SeNPs. In addition, niosome-loaded SeNPs can upregulate the expression level of Bax, cas3, and cas9 apoptosis genes while the expression of the Bcl2 gene is down-regulated in all studied cell lines, significantly. Also, the results of the MTT test indicated that the free niosome has no significant cytotoxic effects against the HFF cell line which represents the biocompatibility of the synthesized niosomes. In general, based on the results of this study, it can be concluded that niosomes-loaded SeNPs have significant anti-microbial, anti-biofilm, and anti-cancer effects, which can be used as a suitable drug delivery system.
    DOI:  https://doi.org/10.1038/s41598-022-26400-x
  25. Acta Biomater. 2022 Dec 20. pii: S1742-7061(22)00828-5. [Epub ahead of print]
    pH-Responsive Nanocomposite Hydrogel for Simultaneous Prevention of Postoperative Adhesion and Tumor Recurrence.
    Juan Zhou, Hong Wang, Hao Chen, Yan Ling, Ziqi Xi, Mingting Lv, Jinghua Chen.
      Abdominal adhesion and tumor recurrence are two thorny problems in the postoperative treatment of abdominal tumors. Although important progress has been made in the application of hydrogels in adjuvant therapy after tumor surgery, most of the products can not effectively combine the prevention of abdominal adhesion and the removal of residual cancer cells. In this study, a nanocomposite hydrogel (Col-APG-Cys@HHD) was prepared by crosslinking collagen and recombinant albumin nanoparticles (HHD NPs) with aldehydeylated polyethylene glycol (APG6K) followed by immobilizing zwitterionic cysteine (Cys) to one surface. One surface of the hydrogel adhered to the postoperative wound due to the adhesive properties of collagen, while the other surface coated with cysteine formed a hydration layer to hinder the stick of proteins and cells, thereby reducing the adhesion between tissues. Additionally, Col-APG-Cys@HHD hydrogel disintegrated under acidic condition and released HHD NPs that targeted into cancer cells and released drugs in response to low pH environment. The in vivo experiments' results demonstrated that Col-APG-Cys@HHD hydrogel could prevent intraperitoneal adhesions and inhibit tumor growth with minimal side effects, providing a potential strategy for the hydrogel-based drug delivery system in postoperative adjuvant therapy of tumors. STATEMENT OF SIGNIFICANCE: : Tissue adhesion and tumor recurrence usually occur after abdominal tumor surgery. Hydrogels have been widely studied in adjuvant treatment of abdominal tumors, but their synergy in terms of controllable drug release and anti-peritoneal adhesion still needs to be improved. Herein, a nanocomposite hydrogel (Col-APG-Cys@HHD) was designed and constructed with one side that was tissue adhesive and the other side as antifouling. Additionally, the Col-APG-Cys@HHD hydrogel showed controlled drug release behavior in response to a pH gradient (6.5 to 5.5). This was conducive to its dissociation in an acidic tumor environment followed by the release of nanoparticles that entered into tumor cells and delivered docetaxel . To sum up, the Col-APG-Cys@HHD hydrogel demonstrated synergistic therapy for prevention of abdominal adhesion and tumor recurrence after abdominal tumor surgery.
    Keywords:  anti-postoperative adhesion; anti-tumor recurrence; nanocomposite hydrogels; pH-response; recombinant protein
    DOI:  https://doi.org/10.1016/j.actbio.2022.12.025
  26. Molecules. 2022 Dec 08. pii: 8706. [Epub ahead of print]27(24):
    Nanodelivery of Dietary Polyphenols for Therapeutic Applications.
    Mithun Rudrapal, Ashwini K Mishra, Laxmi Rani, Khomendra K Sarwa, James H Zothantluanga, Johra Khan, Mehnaz Kamal, Santwana Palai, Atul R Bendale, Swati G Talele, Vasim T Pathan, Laxmikant B Borse, Vishnu S Neharkar, Pravat K Sahoo.
      Advancement in nanotechnology has unleashed the therapeutic potentials of dietary polyphenols by enhancing bioavailability, improving biological half-life, and allowing site-specific drug delivery. In this review, through citation of relevant literature reports, we discuss the application of nano-pharmaceutical formulations, such as solid lipid nanoparticles, nano-emulsions, nano-crystals, nano-polymersomes, liposomes, ethosomes, phytosomes, and invasomes for dietary polyphenols. Following this, we highlight important studies concerning different combinations of nano formulations with dietary polyphenols (also known as nanophytopolyphenols). We also provide nano-formulation paradigms for enhancing the physicochemical properties of dietary polyphenols. Finally, we highlight the latest patents that were granted on nano-formulations of dietary polyphenols. Based on our review, we observe that nanosized delivery of herbal constituents, spices, and dietary supplements have the ability to improve biological processes and address issues connected with herbal treatments.
    Keywords:  dietary polyphenols; nanodelivery; nanoformulation; nanophytomedicine; nanotechnology
    DOI:  https://doi.org/10.3390/molecules27248706
  27. Gels. 2022 Dec 17. pii: 834. [Epub ahead of print]8(12):
    Pectin Based Hydrogels for Drug Delivery Applications: A Mini Review.
    Sung Soo Han, Seong Min Ji, Min Jung Park, Maduru Suneetha, Uluvangada Thammaiah Uthappa.
      Over the past few decades, hydrogel systems using natural polymers have been expansively employed in drug delivery applications. Among the various reported biopolymer-based hydrogel drug delivery systems, pectin (Pec) is an exceptional natural polymer due to its unique functionalities and excellent properties such as biocompatibility, biodegradability, low-cost, and simple gelling capability, which has received considerable interest in the drug delivery fields. Since there is an increasing need for biomaterials with unique properties for drug delivery applications, in this review, hydrogels fabricated from natural pectin polymers were thoroughly investigated. Additionally, the present mini review aims to bring collectively more concise ways such as sources, extraction, properties, and various forms of Pec based hydrogel drug delivery systems and their toxicity concerns are summarized. Finally, the potential objectives and challenges based on pectin-based hydrogel drug delivery systems are also discussed.
    Keywords:  biopolymers; controlled release; hydrogels; pectins; targeted drug delivery
    DOI:  https://doi.org/10.3390/gels8120834
  28. Pharmaceutics. 2022 Dec 13. pii: 2787. [Epub ahead of print]14(12):
    Nanoparticle-Mediated Delivery of STAT3 Inhibitors in the Treatment of Lung Cancer.
    Qiyi Feng, Kai Xiao.
      Lung cancer is a common malignancy worldwide, with high morbidity and mortality. Signal transducer and activator of transcription 3 (STAT3) is an important transcription factor that not only regulates different hallmarks of cancer, such as tumorigenesis, cell proliferation, and metastasis but also regulates the occurrence and maintenance of cancer stem cells (CSCs). Abnormal STAT3 activity has been found in a variety of cancers, including lung cancer, and its phosphorylation level is associated with a poor prognosis of lung cancer. Therefore, the STAT3 pathway may represent a promising therapeutic target for the treatment of lung cancer. To date, various types of STAT3 inhibitors, including natural compounds, small molecules, and gene-based therapies, have been developed through direct and indirect strategies, although most of them are still in the preclinical or early clinical stages. One of the main obstacles to the development of STAT3 inhibitors is the lack of an effective targeted delivery system to improve their bioavailability and tumor targetability, failing to fully demonstrate their anti-tumor effects. In this review, we will summarize the recent advances in STAT3 targeting strategies, as well as the applications of nanoparticle-mediated targeted delivery of STAT3 inhibitors in the treatment of lung cancer.
    Keywords:  STAT3; cancer stem cells; drug delivery; lung cancer; nanoparticles
    DOI:  https://doi.org/10.3390/pharmaceutics14122787
  29. Eur J Med Chem. 2022 Dec 16. pii: S0223-5234(22)00902-3. [Epub ahead of print]247 115000
    A comprehensive overview of Artemisinin and its derivatives as anticancer agents.
    Zi-Wei Zeng, Di Chen, Lei Chen, Bin He, Yan Li.
      Artemisinin is the crucial ingredient of artemisia annua, a traditional Chinese medicine used for the therapy of malaria in China for hundreds of years. In recent years, the anticancer properties of artemisinin and its derivatives have also been reported. This review has summarized the research and development of artemisinin and its derivatives as anticancer agents, which included both natural and synthetic monomers as well as their dimers. In addition, it highlights the antitumor effects of artemisinin and its derivatives after site-modification or after transformation to a nano-delivery system. Moreover, we have further explored their potential mechanisms of action and also discussed the clinical trials of ARTs used to treat cancer, which will facilitate in further development of novel anticancer drugs based on the scaffold of artemisinin.
    Keywords:  Anticancer; Antimalarial; Artemisinin; Derivatives; Mechanism
    DOI:  https://doi.org/10.1016/j.ejmech.2022.115000
  30. Chin J Nat Med. 2022 Dec;pii: S1875-5364(22)60193-6. [Epub ahead of print]20(12): 881-901
    Potential of ginsenoside Rh2and its derivatives as anti-cancer agents.
    Keke Li, Zhongyu Li, Lei Men, Wei Li, Xiaojie Gong.
      As a steroid skeleton-based saponin, ginsenoside Rh2 (G-Rh2) is one of the major bioactive ginsenosides from the plants of genus Panax L. Many studies have reported the notable pharmacological activities of G-Rh2 such as anticancer, antiinflammatory, antiviral, antiallergic, antidiabetic, and anti-Alzheimer's activities. Numerous preclinical studies have demonstrated the great potential of G-Rh2 in the treatment of a wide range of carcinomatous diseases in vitro and in vivo. G-Rh2 is able to inhibit proliferation, induce apoptosis and cell cycle arrest, retard metastasis, promote differentiation, enhance chemotherapy and reverse multi-drug resistance against multiple tumor cells. The present review mainly summarizes the anticancer effects and related mechanisms of G-Rh2 in various models as well as the recent advances in G-Rh2 delivery systems and structural modification to ameliorate its anticancer activity and pharmacokinetics characteristics.
    Keywords:  Anticancer; Drug delivery systems; Ginsenoside Rh(2); Mechanisms of action; Synergistic effect
    DOI:  https://doi.org/10.1016/S1875-5364(22)60193-6
  31. Molecules. 2022 Dec 16. pii: 8981. [Epub ahead of print]27(24):
    Ursolic Acid Analogs as Potential Therapeutics for Cancer.
    Siva S Panda, Muthusamy Thangaraju, Bal L Lokeshwar.
      Ursolic acid (UA) is a pentacyclic triterpene isolated from a large variety of vegetables, fruits and many traditional medicinal plants. It is a structural isomer of Oleanolic Acid. The medicinal application of UA has been explored extensively over the last two decades. The diverse pharmacological properties of UA include anti-inflammatory, antimicrobial, antiviral, antioxidant, anti-proliferative, etc. Especially, UA holds a promising position, potentially, as a cancer preventive and therapeutic agent due to its relatively non-toxic properties against normal cells but its antioxidant and antiproliferative activities against cancer cells. Cell culture studies have shown interference of UA with multiple pharmacological and molecular targets that play a critical role in many cells signaling pathways. Although UA is considered a privileged natural product, its clinical applications are limited due to its low absorption through the gastro-intestinal track and rapid elimination. The low bioavailability of UA limits its use as a therapeutic drug. To overcome these drawbacks and utilize the importance of the scaffold, many researchers have been engaged in designing and developing synthetic analogs of UA via structural modifications. This present review summarizes the synthetic UA analogs and their cytotoxic antiproliferative properties reported in the last two decades.
    Keywords:  anticancer; antitumor; cell lines; modifications; synthesis; ursolic acid
    DOI:  https://doi.org/10.3390/molecules27248981
  32. Int J Nanomedicine. 2022 ;17 6427-6446
    Combined Photodynamic and Photothermal Therapy and Immunotherapy for Cancer Treatment: A Review.
    Cunqing Kong, Xingcai Chen.
      Photoactivation therapy based on photodynamic therapy (PDT) and photothermal therapy (PTT) has been identified as a tumour ablation modality for numerous cancer indications, with photosensitisers and photothermal conversion agents playing important roles in the phototherapy process, especially in recent decades. In addition, the iteration of nanotechnology has strongly promoted the development of phototherapy in tumour treatment. PDT can increase the sensitivity of tumour cells to PTT by interfering with the tumour microenvironment, whereas the heat generated by PTT can increase blood flow, improve oxygen supply and enhance the PDT therapeutic effect. In addition, tumour cell debris generated by phototherapy can serve as tumour-associated antigens, evoking antitumor immune responses. In this review, the research progress of phototherapy, and its research effects in combination with immunotherapy on the treatment of tumours are mainly outlined, and issues that may need continued attention in the future are raised.
    Keywords:  cancer; immunotherapy; photodynamic therapy; photothermal therapy; tumor
    DOI:  https://doi.org/10.2147/IJN.S388996
  33. Eur J Cancer. 2022 Nov 26. pii: S0959-8049(22)01770-1. [Epub ahead of print]180 30-51
    Metabolic switch in cancer - Survival of the fittest.
    Hans Raskov, Shruti Gaggar, Asma Tajik, Adile Orhan, Ismail Gögenur.
      Cell metabolism is characterised by the highly coordinated conversion of nutrients into energy and biomass. In solid cancers, hypoxia, nutrient deficiencies, and tumour vasculature are incompatible with accelerated anabolic growth and require a rewiring of cancer cell metabolism. Driver gene mutations direct malignant cells away from oxidation to maximise energy production and biosynthesis while tumour-secreted factors degrade peripheral tissues to fuel disease progression and initiate metastasis. As it is vital to understand cancer cell metabolism and survival mechanisms, this review discusses the metabolic switch and current drug targets and clinical trials. In the future, metabolic markers may be included when phenotyping individual tumours to improve the therapeutic opportunities for personalised therapy.
    Keywords:  Biosynthesis; Energy production; Hypoxia; Metabolic reprogramming; Nutrient exploitation; Wasting syndrome
    DOI:  https://doi.org/10.1016/j.ejca.2022.11.025
  34. Br J Cancer. 2022 Dec 23.
    Cell proliferation, drug distribution and therapeutic effects in relation to the vascular system of solid tumours.
    Ian F Tannock, G Gordon Steel.
      In this perspective, the authors summarise some properties of the solid tumour micro-environment that have been explored during the last 55 years. It is well established that the concentrations of nutrients, including oxygen, decrease with increasing distance from tumour blood vessels, and that low extracellular pH is found in nutrient-poor regions. Cell proliferation is dependent on nutrient metabolites and decreases in regions distal from patent blood vessels. Proliferating cells cause migration of neighbouring cells further from blood vessels where they may die, and their breakdown products pass into regions of necrosis. Anticancer drugs reach solid tumours via the vascular system and establish concentration gradients such that drug concentration within tumours may be quite variable. Treatment with chemotherapy such as doxorubicin or docetaxel can kill well-nourished proliferating cells close to blood vessels, thereby interrupting migration toward necrotic regions and lead to re-oxygenation and renewed proliferation of distal cells, as can occur with radiotherapy. This effect leads to the paradox that cancer treatment can rescue cells that were destined to die in the untreated tumour. Renewed and sometimes accelerated repopulation of surviving tumour cells can counter the effects of cell killing from repeated treatments, leading to tumour shrinkage and regrowth without changes in the intrinsic sensitivity of cells to the administered treatment. Strategies to prevent these effects include the combined use of chemotherapy with agents that selectively kill hypoxic tumour cells, including inhibitors of autophagy, since this is a process that may allow recycling of cellular macromolecules from dying cells and improve their survival.
    DOI:  https://doi.org/10.1038/s41416-022-02109-6
  35. Front Immunol. 2022 ;13 1083788
    Berberine a traditional Chinese drug repurposing: Its actions in inflammation-associated ulcerative colitis and cancer therapy.
    Cuipeng Zhu, Kaiqi Li, Xiao-Xu Peng, Tong-Jia Yao, Zi-Yu Wang, Ping Hu, Demin Cai, Hao-Yu Liu.
      Berberine (BBR), an isoquinoline alkaloid extracted from Coptidis Rhizoma, has a long history of treating dysentery in the clinic. Over the past two decades, the polytrophic, pharmacological, and biochemical properties of BBR have been intensively studied. The key functions of BBR, including anti-inflammation, antibacterial, antioxidant, anti-obesity, and even antitumor, have been discovered. However, the underlying mechanisms of BBR-mediated regulation still need to be explored. Given that BBR is also a natural nutrition supplement, the modulatory effects of BBR on nutritional immune responses have attracted more attention from investigators. In this mini-review, we summarized the latest achievements of BBR on inflammation, gut microbes, macrophage polarization, and immune responses associated with their possible tools in the pathogenesis and therapy of ulcerative colitis and cancer in recent 5 years. We also discuss the therapeutic efficacy and anti-inflammatory actions of BBR to benefit future clinical applications.
    Keywords:  berberine; cancer; inflammation; microbes; ulcerative colitis
    DOI:  https://doi.org/10.3389/fimmu.2022.1083788
  36. RSC Adv. 2022 Dec 06. 12(54): 34815-34821
    Facile synthesis of phycocyanin/polydopamine hierarchical nanocomposites for synergizing PTT/PDT against cancer.
    Huazhen Liang, Yaling Sun, Chaoming Li, Huaming Lin, Qiwen Huang, Changguo Li.
      The exceptional biocompatibility and biosafety of natural proteins have made them a popular choice for tumor therapy in recent years, but their therapeutic effectiveness is severely constrained by factors including physiological instability, insufficient delivery, limited accumulation in tumor cells, etc. Here, a novel Mn-doped phycocyanin (Pc)/polydopamine (PDA) hierarchical nanostructure (MnPc@P) with excellent optical absorption, photothermal conversion, and photodynamic performances, is first designed and fabricated by a simply one-pot reaction, which not only successfully encapsulates natural protein Pc with intact activity in the nanostructure of MnPc@P but also gives them better biocompatibility. Upon laser irradiation, PDA-mediated hyperthermia and Pc-induced ROS elevation in tumor cells have been demonstrated, leading to drastic tumor cell death via combined PTT/PDT effect, greater than single PTT or PDT. In general, the expert fusion of Pc and PDA into a single nanomedicine opens fascinating perspectives in the delivery of natural proteins and tumor therapy.
    DOI:  https://doi.org/10.1039/d2ra05863d
  37. Molecules. 2022 Dec 15. pii: 8910. [Epub ahead of print]27(24):
    The Synergistic Hepatoprotective Activity of Rosemary Essential Oil and Curcumin: The Role of the MEK/ERK Pathway.
    Maged E Mohamed, Nancy S Younis, Hossam S El-Beltagi, Omar M Mohafez.
       BACKGROUND: Curcumin is a natural product obtained from the rhizome of Curcuma longa. Rosemary (Rosmarinus officinalis) is a medicinal and aromatic plant that is widely spread in the Mediterranean region. Both Curcumin and rosemary essential oil are natural products of high medicinal and pharmacological significance. The hepatoprotective effect of both natural products is well-established; however, the mechanism of such action is not fully understood. Thus, this study is an attempt to explore the hepatoprotective mechanism of action of these remedies through their effect on MEK and ERK proteins. Furthermore, the effect of rosemary essential oil on the plasma concentration of curcumin has been scrutinized.
    MATERIALS AND METHODS: The major constituents of REO were qualitatively and quantitatively determined by GC/MS and GC/FID, respectively. Curcumin and rosemary essential oil were given to mice in a pre-treatment model, followed by induction of liver injury through a high dose of paracetamol. Serum liver enzymes, lipid peroxidation, antioxidant activities, the inflammatory and apoptotic biomarkers, as well as the MEK and ERK portions, were verified. The plasma levels of curcumin were determined in the presence and absence of rosemary essential oil.
    RESULTS: The major constituents of REO were 1,8-cineole (51.52%), camphor (10.52%), and α-pinene (8.41%). The results revealed a superior hepatoprotective activity of the combination when compared to each natural product alone, as demonstrated by the lowered liver enzymes, lipid peroxidation, mitigated inflammatory and apoptotic biomarkers, and enhanced antioxidant activities. Furthermore, the combination induced the overexpression of MEK and ERK proteins, providing evidence for the involvement of this cascade in the hepatoprotective activity of such natural products. The administration of rosemary essential oil with curcumin enhanced the curcuminoid plasma level.
    CONCLUSION: The co-administration of both curcumin and rosemary essential oil together enhanced both their hepatoprotective activity and the level of curcumin in plasma, indicating a synergistic activity between both natural products.
    Keywords:  1,8-cineole; Curcuma longa; Rosmarinus officinalis; camphor; hepatotoxicity; paracetamol; α-pinene
    DOI:  https://doi.org/10.3390/molecules27248910
  38. Front Cell Dev Biol. 2022 ;10 1014798
    Metabolomic profiling of triple negative breast cancer cells suggests that valproic acid can enhance the anticancer effect of cisplatin.
    Avital Granit, Kumudesh Mishra, Dinorah Barasch, Tamar Peretz-Yablonsky, Sara Eyal, Or Kakhlon.
      Cisplatin is an effective chemotherapeutic agent for treating triple negative breast cancer (TNBC). Nevertheless, cisplatin-resistance might develop during the course of treatment, allegedly by metabolic reprograming, which might influence epigenetic regulation. We hypothesized that the histone deacetylase inhibitor (HDACi) valproic acid (VPA) can counter the cisplatin-induced metabolic changes leading to its resistance. We performed targeted metabolomic and real time PCR analyses on MDA-MB-231 TNBC cells treated with cisplatin, VPA or their combination. 22 (88%) out of the 25 metabolites most significantly modified by the treatments, were acylcarnitines (AC) and three (12%) were phosphatidylcholines (PCs). The most discernible effects were up-modulation of AC by cisplatin and, contrarily, their down-modulation by VPA, which was partial in the VPA-cisplatin combination. Furthermore, the VPA-cisplatin combination increased PCs, sphingomyelins (SM) and hexose levels, as compared to the other treatments. These changes predicted modulation of different metabolic pathways, notably fatty acid degradation, by VPA. Lastly, we also show that the VPA-cisplatin combination increased mRNA levels of the fatty acid oxidation (FAO) promoting enzymes acyl-CoA synthetase long chain family member 1 (ACSL1) and decreased mRNA levels of fatty acid synthase (FASN), which is the rate limiting enzyme of long-chain fatty acid synthesis. In conclusion, VPA supplementation altered lipid metabolism, especially fatty acid oxidation and lipid synthesis, in cisplatin-treated MDA-MB-231 TNBC cells. This metabolic reprogramming might reduce cisplatin resistance. This finding may lead to the discovery of new therapeutic targets, which might reduce side effects and counter drug tolerance in TNBC patients.
    Keywords:  cisplalin; metabolism; metabolomics; triple negative breast cancer; valproic acid
    DOI:  https://doi.org/10.3389/fcell.2022.1014798
  39. Int J Mol Sci. 2022 Dec 12. pii: 15765. [Epub ahead of print]23(24):
    Phytochemicals as Chemo-Preventive Agents and Signaling Molecule Modulators: Current Role in Cancer Therapeutics and Inflammation.
    Muhammad Bilal Ahmed, Salman Ul Islam, Abdullah A A Alghamdi, Muhammad Kamran, Haseeb Ahsan, Young Sup Lee.
      Cancer is one of the deadliest non communicable diseases. Numerous anticancer medications have been developed to target the molecular pathways driving cancer. However, there has been no discernible increase in the overall survival rate in cancer patients. Therefore, innovative chemo-preventive techniques and agents are required to supplement standard cancer treatments and boost their efficacy. Fruits and vegetables should be tapped into as a source of compounds that can serve as cancer therapy. Phytochemicals play an important role as sources of new medication in cancer treatment. Some synthetic and natural chemicals are effective for cancer chemoprevention, i.e., the use of exogenous medicine to inhibit or impede tumor development. They help regulate molecular pathways linked to the development and spread of cancer. They can enhance antioxidant status, inactivating carcinogens, suppressing proliferation, inducing cell cycle arrest and death, and regulating the immune system. While focusing on four main categories of plant-based anticancer agents, i.e., epipodophyllotoxin, camptothecin derivatives, taxane diterpenoids, and vinca alkaloids and their mode of action, we review the anticancer effects of phytochemicals, like quercetin, curcumin, piperine, epigallocatechin gallate (EGCG), and gingerol. We examine the different signaling pathways associated with cancer and how inflammation as a key mechanism is linked to cancer growth.
    Keywords:  apoptosis; cancer; cell cycle; chemoprevention; inflammation; phytochemicals; signaling pathways
    DOI:  https://doi.org/10.3390/ijms232415765
  40. Metabolites. 2022 Dec 14. pii: 1256. [Epub ahead of print]12(12):
    Interactions between Natural Products-A Review.
    Nemanja Rajčević, Danka Bukvički, Tanja Dodoš, Petar D Marin.
      Plant-based natural products have been used as a source for therapeutics since the dawn of civilization. According to the World Health Organization (WHO), more than 80% of the world's population relies on traditional medicine for their primary healthcare. Numerous natural extracts, widely known in Traditional Chinese Medicine, Indian Ayurveda medicine and other practices, have led to the modern discovery and development of new drugs. Plants continuously interact with their environment, producing new compounds and ever-changing combinations of existing ones. Interestingly, some of the compounds have shown lower therapeutic activity in comparison to the extract they were isolated from. These findings suggest that the higher therapeutic activity of the source extract was due to the synergistic effect of several compounds. In other words, the total therapeutic potential of the extract cannot be explained only by the sum of its parts alone. In traditional medicine, most herbal remedies are based on a mixture of plants, and it is the interaction between different constituents that amplifies their therapeutic potential. Considering the significant influence traditional medicine has on human healthcare, knowing and studying the synergistic effect of compounds is paramount in designing smart therapeutic agents.
    Keywords:  bioactive compounds; extracts; in vitro and in vivo studies; natural products; synergistic effect; therapeutic
    DOI:  https://doi.org/10.3390/metabo12121256
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