bims-kracam Biomed News
on K-Ras in cancer metabolism
Issue of 2023–01–08
forty papers selected by
Yasmin Elkabani, Egyptian Foundation for Research and Community Development
  1. Effect of nano-curcumin on various diseases: A comprehensive review of clinical trials.
  2. Reactive oxygen species-upregulating nanomedicines towards enhanced cancer therapy.
  3. Nanoparticles augment the therapeutic window of RT and immunotherapy for treating cancers: pivotal role of autophagy.
  4. Recent progress in the development of nanomaterials targeting multiple cancer metabolic pathways: a review of mechanistic approaches for cancer treatment.
  5. Engineering lactate-modulating nanomedicines for cancer therapy.
  6. Phytochemicals and mitochondria: Therapeutic allies against gastric cancer.
  7. Recent advances in drug delivery systems for targeting brain tumors.
  8. Small extracellular vesicles in metabolic remodeling of tumor cells: Cargos and translational application.
  9. Tumor hypoxia: From basic knowledge to therapeutic implications.
  10. STAT proteins in cancer: orchestration of metabolism.
  11. Pharmacotherapeutic values of berberine: A Chinese herbal medicine for the human cancer management.
  12. Polysaccharide-modified liposomes and their application in cancer research.
  13. Promising Clinical Applications of Hydrogels Associated With Precise Cancer Treatment: A Review.
  14. Ursolic acid: a pentacyclic triterpenoid that exhibits anticancer therapeutic potential by modulating multiple oncogenic targets.
  15. Delivery of curcumin within emulsome nanoparticles enhances the anti-cancer activity in androgen-dependent prostate cancer cell.
  16. Self-delivery biomedicine for enhanced photodynamic therapy by feedback promotion of tumor autophagy.
  17. Pectin-based nanoencapsulation strategy to improve the bioavailability of bioactive compounds.
  18. pH-responsive and targeted delivery of chrysin via folic acid-functionalized mesoporous silica nanocarrier for breast cancer therapy.
  19. Light responsive hydrogels for controlled drug delivery.
  20. Guar gum-based nanoformulations: Implications for improving drug delivery.
  21. Manipulate tumor hypoxia for improved photodynamic therapy using nanomaterials.
  22. Mechanisms and strategies to enhance penetration during intravesical drug therapy for bladder cancer.
  23. [A mini-review on anti-tumor effect of cannabidiol].
  24. Progress of potential drugs targeted in lipid metabolism research.
  25. Palmitic acid-modified human serum albumin paclitaxel nanoparticles targeting tumor and macrophages against breast cancer.
  26. Succinylation and redox status in cancer cells.
  27. Chrysin effect against gastric cancer: focus on its molecular mechanisms.
  28. Targeting fatty acid metabolism in glioblastoma.
  29. Molecular Classification, Treatment, and Genetic Biomarkers in Triple-Negative Breast Cancer: A Review.
  30. Metabolism-epigenetic interactions on in vitro produced embryos.
  31. Editorial: Metabolic hormones and inflammation.
  32. Solid lipid nanoparticles (SLNs), the potential novel vehicle for enhanced in vivo efficacy of hesperidin as an anti-inflammatory agent.
  33. Glutamine Metabolism Targeting Liposomes for Synergistic Chemosensitization and Starvation Therapy in Ovarian Cancer.
  34. Emerging Epigenetic-Based Nanotechnology for Cancer Therapy: Modulating the Tumor Microenvironment.
  35. Intracellular and microenvironmental regulation of mitochondrial membrane potential in cancer cells.
  36. Dynamic regulation of RAS and RAS signaling.
  37. The mechanisms and roles of melatonin in gastrointestinal cancer.
  38. DNA methylation and cancer: transcriptional regulation, prognostic, and therapeutic perspective.
  39. Tumor-targeting intravenous lipid emulsion of paclitaxel: Characteristics, stability, toxicity, and toxicokinetics.
  40. Profiling the Epigenetic Landscape of the Tumor Microenvironment Using Chromatin Immunoprecipitation Sequencing.
  1. Biofactors. 2023 Jan 06.
    Effect of nano-curcumin on various diseases: A comprehensive review of clinical trials.
    Shirin Hassanizadeh, Mehrnaz Shojaei, Mohammad Bagherniya, Alexander N Orekhov, Amirhossein Sahebkar.
      The antioxidant, anti-inflammatory, and antibacterial properties of curcumin have made it a valuable herbal product for improving various disorders, such as COVID-19, cancer, depression, anxiety, osteoarthritis, migraine, and diabetes. Recent research has demonstrated that encapsulating curcumin in nanoparticles might improve its therapeutic effects and bioavailability. To our knowledge, the efficacy of nano-curcumin on different aspects of health and disease has not been summarized in a study. Therefore, this review aimed to evaluate nano-curcumin's efficacy in various diseases based on the findings of clinical trials. In order to review publications focusing on nanocurcumin's impact on various diseases, four databases were searched, including PubMed, Scopus, Web of Science, and Google Scholar. This review highlights the potential benefits of nano-curcumin in improving a wide range of human diseases including COVID-19, neurological disorders, chronic disease, oral diseases, osteoarthritis, metabolic syndrome, and other diseases, especially as an adjunct to standard therapy and a healthy lifestyle.
    Keywords:  cancer; chronic diseases; clinical trial; metabolic syndrome; nano-curcumin; neurological disorder; oral disease
    DOI:  https://doi.org/10.1002/biof.1932
  2. Biomater Sci. 2023 Jan 06.
    Reactive oxygen species-upregulating nanomedicines towards enhanced cancer therapy.
    Yuanyuan Ding, Qingqing Pan, Wenxia Gao, Yuji Pu, Kui Luo, Bin He.
      Reactive oxygen species (ROS) play a crucial role in physiological and pathological processes, emerging as a therapeutic target in cancer. Owing to the high concentration of ROS in solid tumor tissues, ROS-based treatments, such as photodynamic therapy and chemodynamic therapy, and ROS-responsive drug delivery systems have been widely explored to powerfully and specifically suppress tumors. However, their anticancer efficacy is still hampered by the heterogeneous ROS levels, and thus comprehensively upregulating the ROS levels in tumor tissues can ensure an enhanced therapeutic effect, which can further sensitize and/or synergize with other therapies to inhibit tumor growth and metastasis. Herein, we review the recently emerging drug delivery strategies and technologies for increasing the H2O2, ˙OH, 1O2, and ˙O2- concentrations in cancer cells, including the efficient delivery of natural enzymes, nanozymes, small molecular biological molecules, and nanoscale Fenton-reagents and semiconductors and neutralization of intracellular antioxidant substances and localized input of mechanical and electromagnetic waves (such as ultrasound, near infrared light, microwaves, and X-rays). The applications of these ROS-upregulating nanosystems in enhancing and synergizing cancer therapies including chemotherapy, chemodynamic therapy, phototherapy, and immunotherapy are surveyed. In addition, we discuss the challenges of ROS-upregulating systems and the prospects for future studies.
    DOI:  https://doi.org/10.1039/d2bm01833k
  3. Theranostics. 2023 ;13(1): 40-58
    Nanoparticles augment the therapeutic window of RT and immunotherapy for treating cancers: pivotal role of autophagy.
    Yuan-Hua Wu, Rong-Jane Chen, Hui-Wen Chiu, Li-Xing Yang, Yung-Li Wang, Yu-Ying Chen, Ya-Ling Yeh, Mei-Yi Liao, Ying-Jan Wang.
      Immunotherapies are now emerging as an efficient anticancer therapeutic strategy. Cancer immunotherapy utilizes the host's immune system to fight against cancer cells and has gained increasing interest due to its durable efficacy and low toxicity compared to traditional antitumor treatments, such as chemotherapy and radiotherapy (RT). Although the combination of RT and immunotherapy has drawn extensive attention in the clinical setting, the overall response rates are still low. Therefore, strategies for further improvement are urgently needed. Nanotechnology has been used in cancer immunotherapy and RT to target not only cancer cells but also the tumor microenvironment (TME), thereby helping to generate a long-term immune response. Nanomaterials can be an effective delivery system and a strong autophagy inducer, with the ability to elevate autophagy to very high levels. Interestingly, autophagy could play a critical role in optimal immune function, mediating cell-extrinsic homeostatic effects through the regulation of danger signaling in neoplastic cells under immunogenic chemotherapy and/or RT. In this review, we summarize the preclinical and clinical development of the combination of immunotherapy and RT in cancer therapy and highlight the latest progress in nanotechnology for augmenting the anticancer effects of immunotherapy and RT. The underlying mechanisms of nanomaterial-triggered autophagy in tumor cells and the TME are discussed in depth. Finally, we suggest the implications of these three strategies combined together to achieve the goal of maximizing the therapeutic advantages of cancer therapy and show recent advances in biomarkers for tumor response in the evaluation of those therapies.
    Keywords:  autophagy; immunotherapy; nanomaterials; radiotherapy; tumor microenvironment
    DOI:  https://doi.org/10.7150/thno.77233
  4. Drug Deliv. 2023 Dec;30(1): 1-18
    Recent progress in the development of nanomaterials targeting multiple cancer metabolic pathways: a review of mechanistic approaches for cancer treatment.
    Ling Zhang, Bing-Zhong Zhai, Yue-Jin Wu, Yin Wang.
      Cancer is a very heterogeneous disease, and uncontrolled cell division is the main characteristic of cancer. Cancerous cells need a high nutrition intake to enable aberrant growth and survival. To do so, cancer cells modify metabolic pathways to produce energy and anabolic precursors and preserve redox balance. Due to the importance of metabolic pathways in tumor growth and malignant transformation, metabolic pathways have also been given promising perspectives for cancer treatment, providing more effective treatment strategies, and target-specific with minimum side effects. Metabolism-based therapeutic nanomaterials for targeted cancer treatment are a promising option. Numerous types of nanoparticles (NPs) are employed in the research and analysis of various cancer therapies. The current review focuses on cutting-edge strategies and current cancer therapy methods based on nanomaterials that target various cancer metabolisms. Additionally, it highlighted the primacy of NPs-based cancer therapies over traditional ones, the challenges, and the future potential.
    Keywords:  Cancer metabolisms; anticancer drugs; drug delivery; nanomedicine; nanoparticles
    DOI:  https://doi.org/10.1080/10717544.2022.2144541
  5. Chem Soc Rev. 2023 Jan 04.
    Engineering lactate-modulating nanomedicines for cancer therapy.
    Jiajie Chen, Yufang Zhu, Chengtie Wu, Jianlin Shi.
      Lactate in tumors has long been considered "metabolic junk" derived from the glycolysis of cancer cells and utilized only as a biomarker of malignancy, but is presently believed to be a pivotal regulator of tumor development, maintenance and metastasis. Indeed, tumor lactate can be a "fuel" for energy supply and functions as a signaling molecule, which actively contributes to tumor progression, angiogenesis, immunosuppression, therapeutic resistance, etc., thus providing promising opportunities for cancer treatment. However, the current approaches for regulating lactate homeostasis with available agents are still challenging, which is mainly due to the short half-life, low bioavailability and poor specificity of these agents and their unsatisfactory therapeutic outcomes. In recent years, lactate modulation nanomedicines have emerged as a charming and efficient strategy for fighting cancer, which play important roles in optimizing the delivery of lactate-modulating agents for more precise and effective modulation and treatment. Integrating specific lactate-modulating functions in diverse therapeutic nanomedicines may overcome the intrinsic restrictions of different therapeutic modalities by remodeling the pathological microenvironment for achieving enhanced cancer therapy. In this review, the most recent advances in the engineering of functional nanomedicines that can modulate tumor lactate for cancer therapy are summarized and discussed, and the fundamental mechanisms by which lactate modulation benefits various therapeutics are elucidated. Finally, the challenges and perspectives of this emerging strategy in the anti-tumor field are highlighted.
    DOI:  https://doi.org/10.1039/d2cs00479h
  6. Phytomedicine. 2022 Dec 18. pii: S0944-7113(22)00696-1. [Epub ahead of print]110 154608
    Phytochemicals and mitochondria: Therapeutic allies against gastric cancer.
    Maoyuan Zhao, Yi Yang, Qing Nian, Caifei Shen, Xiaolin Xiao, Wenhao Liao, Qiao Zheng, Gang Zhang, Nianzhi Chen, Daoyin Gong, Jianyuan Tang, Yueqiang Wen, Jinhao Zeng.
       BACKGROUND: Mitochondria are the energy factories of cells with the ability to modulate the cell cycle, cellular differentiation, signal transduction, growth, and apoptosis. Existing drugs targeting mitochondria in cancer treatment have disadvantages of drug resistance and side effects. Phytochemicals, which are widely found in plants, are bioactive compounds that could facilitate the development of new drugs for gastric cancer. Studies have shown that some phytochemicals can suppress the development of gastric cancer.
    METHODS: We searched for data from PubMed, China National Knowledge Infrastructure, Web of Science, and Embase databases from initial establishment to December 2021 to review the mechanism by which phytochemicals suppress gastric cancer cell growth by modulating mitochondrial function. Phytochemicals were classified and summarized by their mechanisms of action.
    RESULTS: Phytochemicals can interfere with mitochondria through several mechanisms to reach the goal of promoting apoptosis in gastric cancer cells. Some phytochemicals, e.g., daidzein and tetrandrine promoted cytochrome c spillover into the cytoplasm by modulating the members of the B-cell lymphoma-2 protein family and induced apoptotic body activity by activating the caspase protein family. Phytochemicals (e.g., celastrol and shikonin) could promote the accumulation of reactive oxygen species and reduce the mitochondrial membrane potential. Several phytochemicals (e.g., berberine and oleanolic acid) activated mitochondrial apoptotic submission via the phosphatidylinositol-3-kinase/Akt signaling pathway, thereby triggering apoptosis in gastric cancer cells. Several well-known phytochemicals that target mitochondria, including berberine, ginsenoside, and baicalein, showed the advantages of multiple targets, high efficacy, and fewer side effects.
    CONCLUSIONS: Phytochemicals could target the mitochondria in the treatment of gastric cancer, providing potential directions and evidence for clinical translation. Drug discovery focused on phytochemicals has great potential to break barriers in cancer treatment.
    Keywords:  Cancer progression; Gastric cancer; Mitochondria; Phytochemicals
    DOI:  https://doi.org/10.1016/j.phymed.2022.154608
  7. Drug Deliv. 2023 Dec;30(1): 1-18
    Recent advances in drug delivery systems for targeting brain tumors.
    Yi Zhao, Ping Yue, Yao Peng, Yuanyuan Sun, Xing Chen, Ze Zhao, Bingjie Han.
      Brain tumor accounts for about 1.6% of incidence and 2.5% of mortality of all tumors, and the median survival for brain tumor patients is only about 20 months. The treatment for brain tumor still faces many challenges, such as the blood-brain barrier (BBB), blood-brain tumor barrier (BBTB), the overexpressed efflux pumps, the infiltration, invasion, high heterogeneity of tumor cells, drug resistance and immune escape caused by tumor microenvironment (TME) and cancer stem cells (CSC). This review attempts to clarify the challenges for multi-functional nano drug delivery systems (NDDS) to cross the BBB and target the cancer cells or organelles, and also provides a brief description of the different types of targeted multi-functional NDDS that have shown potential for success in delivering drugs to the brain. Further, this review also summarizes the research progress of multi-functional NDDS in the combination therapy of brain tumors from the following sections, the combination of chemotherapy drugs, chemotherapy-chemodynamic combination therapy, chemotherapy-immunization combination therapy, and chemotherapy-gene combination therapy. We also provide an insight into the recent advances in designing multi-functional NDDS for combination therapy.
    Keywords:  Nano drug delivery system; brain targeting; brain tumor; combination therapy; nanoparticle
    DOI:  https://doi.org/10.1080/10717544.2022.2154409
  8. Front Pharmacol. 2022 ;13 1009952
    Small extracellular vesicles in metabolic remodeling of tumor cells: Cargos and translational application.
    Hao Yang, Jingyi Wang, Gang Huang.
      Warburg effect is characterized by excessive consumption of glucose by the tumor cells under both aerobic and hypoxic conditions. This metabolic reprogramming allows the tumor cells to adapt to the unique microenvironment and proliferate rapidly, and also promotes tumor metastasis and therapy resistance. Metabolic reprogramming of tumor cells is driven by the aberrant expression and activity of metabolic enzymes, which results in the accumulation of oncometabolites, and the hyperactivation of intracellular growth signals. Recent studies suggest that tumor-associated metabolic remodeling also depends on intercellular communication within the tumor microenvironment (TME). Small extracellular vesicles (sEVs), also known as exosomes, are smaller than 200 nm in diameter and are formed by the fusion of multivesicular bodies with the plasma membrane. The sEVs are instrumental in transporting cargoes such as proteins, nucleic acids or metabolites between the tumor, stromal and immune cells of the TME, and are thus involved in reprogramming the glucose metabolism of recipient cells. In this review, we have summarized the biogenesis and functions of sEVs and metabolic cargos, and the mechanisms through they drive the Warburg effect. Furthermore, the potential applications of targeting sEV-mediated metabolic pathways in tumor liquid biopsy, imaging diagnosis and drug development have also been discussed.
    Keywords:  drug development; exosomes; glycolysis; liquid biopsy; small extracellular vesicles; tumor metabolism; warburg effect
    DOI:  https://doi.org/10.3389/fphar.2022.1009952
  9. Semin Cancer Biol. 2023 Jan 02. pii: S1044-579X(22)00265-6. [Epub ahead of print]
    Tumor hypoxia: From basic knowledge to therapeutic implications.
    Chengheng Liao, Xijuan Liu, Cheng Zhang, Qing Zhang.
      Diminished oxygen availability, termed hypoxia, within solid tumors is one of the most common characteristics of cancer. Hypoxia shapes the landscape of the tumor microenvironment (TME) into a pro-tumorigenic and pro-metastatic niche through arrays of pathological alterations such as abnormal vasculature, altered metabolism, immune-suppressive phenotype, etc. In addition, emerging evidence suggests that limited efficacy or the development of resistance towards antitumor therapy may be largely due to the hypoxic TME. This review will focus on summarizing the knowledge about the molecular machinery that mediates the hypoxic cellular responses and adaptations, as well as highlighting the effects and consequences of hypoxia, especially for angiogenesis regulation, cellular metabolism alteration, and immunosuppressive response within the TME. We also outline the current advances in novel therapeutic implications through targeting hypoxia in TME. A deep understanding of the basics and the role of hypoxia in the tumor will help develop better therapeutic avenues in cancer treatment.
    Keywords:  Hypoxia; Hypoxia-inducible factors; Tumor microenvironment; angiogenesis; immunotherapy; metabolism
    DOI:  https://doi.org/10.1016/j.semcancer.2022.12.011
  10. Nat Rev Cancer. 2023 Jan 03.
    STAT proteins in cancer: orchestration of metabolism.
    Yi-Jia Li, Chunyan Zhang, Antons Martincuks, Andreas Herrmann, Hua Yu.
      Reprogrammed metabolism is a hallmark of cancer. However, the metabolic dependency of cancer, from tumour initiation through disease progression and therapy resistance, requires a spectrum of distinct reprogrammed cellular metabolic pathways. These pathways include aerobic glycolysis, oxidative phosphorylation, reactive oxygen species generation, de novo lipid synthesis, fatty acid β-oxidation, amino acid (notably glutamine) metabolism and mitochondrial metabolism. This Review highlights the central roles of signal transducer and activator of transcription (STAT) proteins, notably STAT3, STAT5, STAT6 and STAT1, in orchestrating the highly dynamic metabolism not only of cancer cells but also of immune cells and adipocytes in the tumour microenvironment. STAT proteins are able to shape distinct metabolic processes that regulate tumour progression and therapy resistance by transducing signals from metabolites, cytokines, growth factors and their receptors; defining genetic programmes that regulate a wide range of molecules involved in orchestration of metabolism in cancer and immune cells; and regulating mitochondrial activity at multiple levels, including energy metabolism and lipid-mediated mitochondrial integrity. Given the central role of STAT proteins in regulation of metabolic states, they are potential therapeutic targets for altering metabolic reprogramming in cancer.
    DOI:  https://doi.org/10.1038/s41568-022-00537-3
  11. J Biochem Mol Toxicol. 2023 Jan 01. e23278
    Pharmacotherapeutic values of berberine: A Chinese herbal medicine for the human cancer management.
    Nalini Devarajan, Jhansi Nathan, Ramalingam Mathangi, Jaideep Mahendra, Senthil Kumar Ganesan.
      Berberine (BBR), a traditional Chinese phytomedicine extracted from various parts of Berberis plants, is an isoquinoline alkaloid used for centuries to treat diabetes, hypercholesterolemia, hypertension, and so forth. It has recently received immense attention worldwide to treat cancer due to its potent pro-apoptotic, antiproliferative, and anti-inflammatory properties. BBR efficiently induces tumor apoptosis, replicative quiescence and abrogates cell proliferation, epithelial-mesenchymal transition, tumor neovascularization, and metastasis by modulating diverse molecular and cell signaling pathways. Furthermore, BBR could also reverse drug resistance, make tumor cells sensitive to current cancer treatment and significantly minimize the harmful side effects of cytotoxic therapies. This review comprehensively analyzed the pharmacological effects of BBR against the development, growth, progression, metastasis, and therapy resistance in wide varieties of cancer. Also, it critically discusses the significant limitations behind the development of BBR into pharmaceuticals to treat cancer and the future research directions to overcome these limitations.
    Keywords:  berberine; cancer; herbal medicine; phytomedicine
    DOI:  https://doi.org/10.1002/jbt.23278
  12. Chem Biol Drug Des. 2023 Jan 03.
    Polysaccharide-modified liposomes and their application in cancer research.
    Peichun Peng, Zeshan Chen, Miaodong Wang, Bin Wen, Xin Deng.
      Nanodrug delivery systems have been widely used in cancer treatment. Among these, liposomal drug carriers have gained considerable attention due to their biocompatibility, biodegradability, and low toxicity. However, conventional liposomes have several shortcomings, such as poor stability, rapid clearance, aggregation, fusion, degradation, hydrolysis, and oxidation of phospholipids. Polysaccharides are natural polymers of biological origin that exhibit structural stability, excellent biocompatibility and biodegradability, flexibility, non-immunogenicity, low toxicity, and targetability. Therefore, they represent a promising class of polymers for the modification of the surface properties of liposomes to overcome their shortcomings. In addition, polysaccharides can be readily combined with other materials to develop new composite materials. Hence, they represent the optimal choice for liposomal modification to improve pharmacokinetics and clinical utility. Polysaccharide-coated liposomes exhibit better stability, drug release kinetics, and cellular uptake than conventional liposomes. The oncologic application of polysaccharide-coated liposomes has become a research hotspot. We summarize the preparation, physicochemical properties, and antineoplastic effects of polysaccharide-coated liposomes to facilitate antitumor drug development.
    Keywords:  antitumor; drug delivery; liposomes; polysaccharides
    DOI:  https://doi.org/10.1111/cbdd.14201
  13. Technol Cancer Res Treat. 2023 Jan-Dec;22:22 15330338221150322
    Promising Clinical Applications of Hydrogels Associated With Precise Cancer Treatment: A Review.
    Qian-Qian Wang, Chang Tan, Geng Qin, Shu-Kun Yao.
      Gastrointestinal cancer is one of the most malignant tumors with high morbidity and mortality, especially colorectal cancer, which has become the second leading cause of cancer-related deaths worldwide. Targeted drug treatment and precise endoscopic resection can significantly improve the overall survival rate and greatly extend the life span. Promising biomedical applications of hydrogels would represent hopeful therapeutic alternatives for patients with different kinds of diseases, particularly providing precise therapy for cancer patients. Although the intersection field of material science and biomedical science has made tremendous advances, major challenges remain. In this review, the application of hydrogel-based technology in cancer precision medicine is the focus of attention, which is the development trend of multidisciplinary cooperation in the future. First, we provide the current clinical landscape of hydrogel applications, and then we highlight precision oncology, including personalized drug treatment and accurate endoscopic intervention. Finally, we discuss major challenges for their clinical translation that have not yet been overcome and future perspectives on cancer precision medicine.
    Keywords:  biomedical application; cancer treatment; clinical translation; gastrointestinal cancer; hydrogel; precision oncology
    DOI:  https://doi.org/10.1177/15330338221150322
  14. Biotechnol Genet Eng Rev. 2023 Jan 04. 1-31
    Ursolic acid: a pentacyclic triterpenoid that exhibits anticancer therapeutic potential by modulating multiple oncogenic targets.
    Sardul Singh Sandhu, Sharareh Khorami Rouz, Suneel Kumar, Nitin Swamy, Loknath Deshmukh, Arif Hussain, Shafiul Haque, Hardeep Singh Tuli.
      The world is currently facing a global challenge against neoplastic diseases. Chemotherapy, hormonal therapy, surgery, and radiation therapy are some approaches used to treat cancer. However, these treatments are frequently causing side effects in patients, such as multidrug resistance, fever, weakness, and allergy, among others side effects. As a result, current research has focused on phytochemical compounds isolated from plants to treat deadly cancers. Plants are excellent resources of bioactive molecules, and many natural molecules have exceptional anticancer properties. They produce diverse anticancer derivatives such as alkaloids, terpenoids, flavonoids, pigments, and tannins, which have powerful anticancer activities against various cancer cell lines and animal models. Because of their safety, eco-friendly, and cost-effective nature, research communities have recently focused on various phytochemical bioactive molecules. Ursolic acid (UA) and its derivative compounds have anti-inflammatory, anticancer, apoptosis induction, anti-carcinogenic, and anti-breast cancer proliferation properties. Ursolic acid (UA) can improve the clinical management of human cancer because it inhibits cancer cell viability and proliferation, preventing tumour angiogenesis and metastatic activity. Therefore, the present article focuses on numerous bioactivities of Ursolic acid (UA), which can inhibit cancer cell production, mechanism of action, and modulation of anticancer properties via regulating various cellular processes.
    Keywords:  Ursolic acid; anti-cancer; anti-carcinogenic; bioactivities
    DOI:  https://doi.org/10.1080/02648725.2022.2162257
  15. Mol Biol Rep. 2023 Jan 06.
    Delivery of curcumin within emulsome nanoparticles enhances the anti-cancer activity in androgen-dependent prostate cancer cell.
    Zeynep Busra Bolat, Zeynep Islek, Fikrettin Sahin, Mehmet Hikmet Ucisik.
       BACKGROUND: Curcumin, a dietary polyphenol isolated from turmeric, is a potent phytochemical possessing intrinsic anticancer activities against various cancer types including prostate cancer. However, low water solubility and bioavailability of the compound are major challenges against its medical use. The objective of this study is to evaluate the therapeutic potential of curcumin-loaded emulsome nanoparticular system, i.e. CurcuEmulsomes, for the treatment of androgen dependent LNCaP prostate cancer cell line.
    METHODS AND RESULTS: The antiproliferative effect of both free curcumin and CurcuEmulsome were investigated comparatively on LNCaP and PNT1A cells. Cell viability data indicates that the inhibition in proliferation of LNCaP cells becomes more effective when curcumin is provided with its emulsome formulation rather than its free form. Corresponding to a therapeutic index of 2.25, Half maximal inhibitory (IC50) and cytotoxic (CC50) concentrations of CurcuEmulsomes for LNCaP and PNT1A cells were estimated as 17.1 µM and 38.6 µM, respectively. The fluorescence signal of autofluorescence curcumin was preserved within the CurcuEmulsomes at 72 h after the treatment. Thus, CurcuEmulsomes prolonged biological activity of curcumin. Induced apoptotic cell death and stimulated cell cycle arrest at G2/M phase were attributed to antiproliferative activity of CurcuEmulsomes. Treatment of LNCaP cells with CurcuEmulsomes increased expression of caspase-3 significantly by 11.76-fold, whereas decreased cyclin D1, Bcl-2 and AR expression levels significantly by of 0.18, 0.06 and 0.46-fold, respectively.
    CONCLUSIONS: Presented safety and anticancer activity of CurcuEmulsomes on LNCaP cell line highlights the potential of CurcuEmulsomes to benefit intrinsic anticancer activities of curcumin in androgen dependent prostate cancer therapy.
    Keywords:  Androgen dependent prostate cancer; Anti-cancer; Curcumin; Emulsome; Phytochemical
    DOI:  https://doi.org/10.1007/s11033-022-08208-0
  16. Acta Biomater. 2023 Jan 02. pii: S1742-7061(22)00867-4. [Epub ahead of print]
    Self-delivery biomedicine for enhanced photodynamic therapy by feedback promotion of tumor autophagy.
    Shao-Yi Chen, Lin-Ping Zhao, Zu-Xiao Chen, Chu-Yu Huang, Ren-Jiang Kong, Yu-Qing Wang, Da-Wei Zhang, Shi-Ying Li, Hui-Hui Ti, Hong Cheng.
      Reactive oxygen species (ROS) generated during photodynamic therapy (PDT) can induce autophagy to protect tumor cell from PDT-induced apoptosis. In this work, a self-delivery autophagy regulator (designated as CeCe) is developed for autophagy promotion sensitized PDT against tumor. Briefly, CeCe is prepared by the assembly of a photosensitizer of chlorin e6 (Ce6) and autophagy promoter of celastrol. By virtue of intermolecular interactions, Ce6 and celastrol are able to self-assemble into nanomedicine with great photodynamic performance and autophagy regulation capacity. Under light irradiation, CeCe would produce ROS in tumor cells to amplify the oxidative stress and promote cell autophagy. As a result, CeCe exhibits an enhanced photo toxicity by inducing autophagic cell death. In vivo experiments indicate that CeCe can predominantly accumulate in tumor tissue for a robust PDT. Moreover, CeCe has a superior therapeutic efficiency compared to monotherapy and combined treatment of Ce6 and celastrol, suggesting a synergistic antitumor effect of PDT and autophagy promotion. This self-delivery nanomedicine may advance the development of the co-delivery nanoplatform to improve the antitumor efficacy of PDT by promoting autophagy. STATEMENT OF SIGNIFICANCE: Autophagy is a "double-edged sword" in cellular homeostasis and metabolism, which can promote tumor progression but also induce an unknown impact on tumor inhibition. In this work, a self-delivery autophagy regulator (designated as CeCe) was developed for autophagy promotion sensitized photodynamic therapy (PDT). By virtue of intermolecular interactions, Ce6 and celastrol were found to self-assemble into stable CeCe without drug excipients, which exhibited great photodynamic performance and autophagy regulation capacity. In vitro and in vivo findings demonstrated a superior tumor suppression ability of CeCe over the monotherapy as well as the combined treatment of Ce6 and celastrol, suggesting a synergistic antitumor efficacy by PDT and autophagy promotion.
    Keywords:  Autophagy; Drug assembly; Photodynamic therapy; Self-delivery biomedicine; Synergistic effect
    DOI:  https://doi.org/10.1016/j.actbio.2022.12.059
  17. Int J Biol Macromol. 2022 Dec 29. pii: S0141-8130(22)03215-9. [Epub ahead of print]229 11-21
    Pectin-based nanoencapsulation strategy to improve the bioavailability of bioactive compounds.
    Thiécla Katiane Osvaldt Rosales, João Paulo Fabi.
      Pectin is one of the polysaccharides to be used as a coating nanomaterial. The characteristics of pectin are suitable to form nanostructures for protection, increased absorption, and bioavailability of different active compounds. This review aims to point out the structural features of pectins and their use as nanocarriers. It also indicates the principal methodologies for the elaboration and application of foods. The research carried out shows that pectin is easily extracted from natural sources, biodegradable, biocompatible, and non-toxic. The mechanical resistance and stability in different pH ranges and the action of digestive enzymes allow the nanostructures to pass intact through the gastrointestinal system and be effectively absorbed. Pectin can bind to macromolecules, especially proteins, to form stable nanostructures, which can be formed by different methods; polyelectrolyte complexes are the most frequent ones. The pectin-derived nanoparticles could be added to foods and dietary supplements, demonstrating a promising nanocarrier with a broad technological application.
    Keywords:  Bioaccessibility; Bioactive compounds; Nanoencapsulation; Nanoparticles; Pectin; Smart food
    DOI:  https://doi.org/10.1016/j.ijbiomac.2022.12.292
  18. Int J Pharm. 2022 Dec 28. pii: S0378-5173(22)01110-3. [Epub ahead of print]631 122555
    pH-responsive and targeted delivery of chrysin via folic acid-functionalized mesoporous silica nanocarrier for breast cancer therapy.
    Noyel Ghosh, Mousumi Kundu, Sumit Ghosh, Abhishek Kumar Das, Samhita De, Joydeep Das, Parames C Sil.
      Cancer is a disease of global importance. In order to mitigate conventional chemotherapy-related side effects, phytochemicals with inherent anticancer efficacy have been opted. However, the use of nanotechnology is essential to enhance the bioavailability and therapeutic efficacy of these phytochemicals. Herein, we have formulated folic acid conjugated polyacrylic acid capped mesoporous silica nanoparticles (∼47.6 nm in diameter) for pH-dependent targeted delivery of chrysin to breast cancer (MCF-7) cells. Chrysin loaded mesoporous silica nanoparticles (Chr- mSiO2@PAA/FA) have been noted to induce apoptosis in MCF-7 cells through oxidative insult and mitochondrial dysfunction with subsequent G1 arrest. Further, in tumor bearing mice, intravenous incorporation of Chr-mSiO2@PAA/FA has been noticed to enhance the anti-neoplastic effects of chrysin via tumor site-specific accumulation. Enhanced cytotoxicity of chrysin contributed towards in vivo tumor regression, restoration of normalized tissue architecture and maintenance of healthy body weight. Besides, no serious systemic toxicity was manifested in response to Chr-mSiO2@PAA/FA administration in vivo. Thus, the study evokes about the anticancer potentiality of chrysin and its increased therapeutic activity via incorporation into folic acid conjugated mesoporous silica nanoparticles, which may hold greater impact in field of future biomedical research.
    Keywords:  Cancer; Chrysin; Mesoporous silica nanoparticle; Receptor-mediated targeted drug delivery; pH-dependent drug release
    DOI:  https://doi.org/10.1016/j.ijpharm.2022.122555
  19. Front Bioeng Biotechnol. 2022 ;10 1075670
    Light responsive hydrogels for controlled drug delivery.
    Yanghui Xing, Buhui Zeng, Wang Yang.
      Light is an easy acquired, effective and non-invasive external stimulus with great flexibility and focusability. Thus, light responsive hydrogels are of particular interests to researchers in developing accurate and controlled drug delivery systems. Light responsive hydrogels are obtained by incorporating photosensitive moieties into their polymeric structures. Drug release can be realized through three major mechanisms: photoisomerization, photochemical reaction and photothermal reaction. Recent advances in material science have resulted in great development of photosensitizers, such as rare metal nanostructures and black phosphorus nanoparticles, in order to respond to a variety of light sources. Hydrogels incorporated with photosensitizers are crucial for clinical applications, and the use of ultraviolet and near-infrared light as well as up-conversion nanoparticles has greatly increased the therapeutic effects. Existing light responsive drug delivery systems have been utilized in delivering drugs, proteins and genes for chemotherapy, immunotherapy, photodynamic therapy, gene therapy, wound healing and other applications. Principles associated with site-specific targeting, metabolism, and toxicity are used to optimize efficacy and safety, and to improve patient compliance and convenience. In view of the importance of this field, we review current development, challenges and future perspectives of light responsive hydrogels for controlled drug delivery.
    Keywords:  drug delivery; hydrogel; light responsive; photosensitizer; programmed release
    DOI:  https://doi.org/10.3389/fbioe.2022.1075670
  20. Int J Biol Macromol. 2023 Jan 02. pii: S0141-8130(22)03192-0. [Epub ahead of print]
    Guar gum-based nanoformulations: Implications for improving drug delivery.
    Sourbh Suren Garg, Jeena Gupta.
      Poorly soluble drugs are reported to easily degrade in the gastrointestinal tract and contribute in limiting the effect of drug to its targeted site. Oral administration of drug is one of the prominent ways to deliver a drug, although, it experiences barriers like acidic pH, presence of microflora and enzymes in the gastrointestinal tract. Collectively all of these participate in the degradation of drug before it reaches its target site and thus, they impede the sustained effect of drug. A quest of choosing a polymer with good stability profile and releasing the drug to its targeted site is always been a challenge for the scientists worldwide. Many polymers have been reported to prevent the degradation of drug and one such naturally occurring biocompatible polymer is guar gum. Guar gum-based nanoformulations have been extensively used in past decades to achieve controlled drug release which defines its importance. The coating of guar gum over the drug improves the bioavailability of the drug and thus helps in minimizing the risk of drug degradation. This review intends to highlight the beneficial role of guar gum-based nanoformulations to improve drug delivery by ameliorating the bioavailibility.
    Keywords:  Drug delivery; Guar gum; Nanoformulation
    DOI:  https://doi.org/10.1016/j.ijbiomac.2022.12.271
  21. Eur J Med Chem. 2022 Dec 31. pii: S0223-5234(22)00986-2. [Epub ahead of print]247 115084
    Manipulate tumor hypoxia for improved photodynamic therapy using nanomaterials.
    Mengqi Yi, Bei Xiong, Yuyang Li, Wei Guo, Yunhan Huang, Bo Lu.
      Due to its low adverse effects, minimal invasiveness, and outstanding patient compliance, photodynamic therapy (PDT) has drawn a great deal of interest, which is achieved through incomplete reduction of O2 by a photosensitizer under light illumination that produces amounts of reactive oxygen species (ROS). However, tumor hypoxia significantly hinders the therapeutic effect of PDT so that tumor cells cannot be eliminated, which results in tumor cells proliferating, invading, and metastasizing. Additionally, O2 consumption during PDT exacerbates hypoxia in tumors, leading to several adverse events after PDT treatment. In recent years, various investigations have focused on conquering or using tumor hypoxia by nanomaterials to amplify PDT efficacy, which is summarized in this review. This comprehensive review's objective is to present novel viewpoints on the advancement of oxygenation nanomaterials in this promising field, which is motivated by hypoxia-associated anti-tumor therapy.
    Keywords:  Nanomaterials; Photodynamic therapy; Tumor hypoxia
    DOI:  https://doi.org/10.1016/j.ejmech.2022.115084
  22. J Control Release. 2023 Jan 02. pii: S0168-3659(23)00001-9. [Epub ahead of print]
    Mechanisms and strategies to enhance penetration during intravesical drug therapy for bladder cancer.
    Pu Zhang, Guoqing Wu, Dahong Zhang, Wing-Fu Lai.
      Bladder cancer (BCa) is one of the most prevalent cancers worldwide. The effectiveness of intravesical therapy for bladder cancer, however, is limited due to the short dwell time and the presence of permeation barriers. Considering the histopathological features of BCa, the permeation barriers for drugs to transport across consist of a mucus layer and a nether tumor physiological barrier. Mucoadhesive delivery systems or mucus-penetrating delivery systems are developed to enhance their retention in or penetration across the mucus layer, but delivery systems that are capable of mucoadhesion-to-mucopenetration transition are more efficient to deliver drugs across the mucus layer. For the tumor physiological barrier, delivery systems mainly rely on four types of penetration mechanisms to cross it. This review summarizes the classical and latest approaches to intravesical drug delivery systems to penetrate BCa.
    Keywords:  Bladder cancer; Drug delivery; Intravesical therapy; Penetration; Transport
    DOI:  https://doi.org/10.1016/j.jconrel.2023.01.001
  23. Zhongguo Zhong Yao Za Zhi. 2022 Dec;47(24): 6541-6550
    [A mini-review on anti-tumor effect of cannabidiol].
    Ran Xie, Dan-Li Hao, Jia-Ying Yang, Ling-Yu Jia, Peng-Qian Wang, Yu Zhao, Yan-Jun Chen, Qing-He Zhao.
      Cannabidiol is the main non-psychoactive component of Cannabis sativa, which has multiple medicinal activities, such as antiepileptic, immunomodulation, analgesic, antioxidant, anticonvulsant, anti-anxiety and other functions. In recent years, it has been found that cannabidiol can inhibit the proliferation of various tumor cells, induce apoptosis and autophagy of tumor cells, arrest cell cycle, interrupt invasion and metastasis of tumor cells, regulate tumor microenvironment, exert synergistic therapy with other chemotherapeutic drugs, and reduce the toxicity of chemotherapeutic drugs. However, its anti-tumor effect remains controversial and its application is limited. The study of microspheres, nano liposomes and other new drug delivery systems can improve the anti-tumor effect of cannabidiol. In this study, the anti-tumor mechanism and application of cannabidiol were summarized and discussed in order to provide inspirations for its further investigation and application.
    Keywords:  anti-tumor; cannabidiol; mechanism
    DOI:  https://doi.org/10.19540/j.cnki.cjcmm.20220906.601
  24. Front Pharmacol. 2022 ;13 1067652
    Progress of potential drugs targeted in lipid metabolism research.
    Kai Liang, Jian-Ye Dai.
      Lipids are a class of complex hydrophobic molecules derived from fatty acids that not only form the structural basis of biological membranes but also regulate metabolism and maintain energy balance. The role of lipids in obesity and other metabolic diseases has recently received much attention, making lipid metabolism one of the attractive research areas. Several metabolic diseases are linked to lipid metabolism, including diabetes, obesity, and atherosclerosis. Additionally, lipid metabolism contributes to the rapid growth of cancer cells as abnormal lipid synthesis or uptake enhances the growth of cancer cells. This review introduces the potential drug targets in lipid metabolism and summarizes the important potential drug targets with recent research progress on the corresponding small molecule inhibitor drugs. The significance of this review is to provide a reference for the clinical treatment of metabolic diseases related to lipid metabolism and the treatment of tumors, hoping to deepen the understanding of lipid metabolism and health.
    Keywords:  cancer; fatty acid; lipid metabolism; metabolic disease; small molecule inhibitor
    DOI:  https://doi.org/10.3389/fphar.2022.1067652
  25. Eur J Pharm Biopharm. 2022 Dec 30. pii: S0939-6411(22)00311-3. [Epub ahead of print]
    Palmitic acid-modified human serum albumin paclitaxel nanoparticles targeting tumor and macrophages against breast cancer.
    Ling Xiang, Changlong Fang, Jiaxing Feng, Yulu Tan, Qingsi Wu, Xueru Zhou, Jia Li, Tao Gong.
      Breast cancer is the most common malignant tumor in women, and the liver is the main target organ for breast cancer metastasis. Once metastasis occurs, the prognosis is very poor. The uptake of PSA NPs made by our synthesized Palmitic acid-modified human serum albumin (PSA) in macrophages is about 15 times higher than that of HSA NPs. As a first-line chemotherapeutic drug, paclitaxel not only does not kill macrophages, but it can also polarize macrophages into classically activated macrophages (M1). We combined these two characteristics into PTX-PSA NPs, which achieved dual targeting of macrophages and tumor cells, improved the tumor microenvironment, and achieved a more effective anti-breast cancer drug effect than PTX-HSA NPs. On this basis, we also used the pathological characteristics of low vascular perfusion of breast cancer liver metastasis, and used the characteristics of macrophages that can release paclitaxel after internalizing paclitaxel, and use macrophages as the delivery system of breast cancer liver metastasis. Therefore,PTX-PSA NPs is better than PTX-HSA NPs to achieve anti-breast cancer liver metastasis.
    DOI:  https://doi.org/10.1016/j.ejpb.2022.12.016
  26. Front Oncol. 2022 ;12 1081712
    Succinylation and redox status in cancer cells.
    Xiaofeng Dai, Yanyan Zhou, Fei Han, Jitian Li.
      Succinylation is a post-translational modification (PTM) event that associates metabolic reprogramming with various pathological disorders including cancers via transferring a succinyl group to a residue of the target protein in an enzymic or non-enzymic manner. With our incremental knowledge on the roles of PTM played in tumor initiation and progression, relatively little has been focused on succinylation and its clinical implications. By delineating the associations of succinylation with cancer hallmarks, we identify the, in general, promotive roles of succinylation in manifesting cancer hallmarks, and conceptualize two working modes of succinylation in driving oncogenic signaling, i.e., via altering the structure and charge of target proteins towards enhanced stability and activity. We also characterize succinylation as a reflection of cellular redox homeostatic status and metabolic state, and bring forth the possible use of hyper-succinylated genome for early cancer diagnosis or disease progression indication. In addition, we propose redox modulation tools such as cold atmospheric plasma as a promising intervention approach against tumor cells and cancer stemness via targeting the redox homeostatic environment cells established under a pathological condition such as hypoxia. Taken together, we emphasize the central role of succinylation in bridging the gap between cellular metabolism and redox status, and its clinical relevance as a mark for cancer diagnosis as well as a target in onco-therapeutics.
    Keywords:  cancer; cell metabolism; cold atmospheric plasma; redox status; succinylation
    DOI:  https://doi.org/10.3389/fonc.2022.1081712
  27. Curr Mol Pharmacol. 2023 Jan 03.
    Chrysin effect against gastric cancer: focus on its molecular mechanisms.
    Seyyed Mohammad Matin Alavi Dana, Tahereh Farkhondeh, Michael Aschner, Majid Darroudi, Helia Samini, Saeed Samarghandian.
      Gastric cancer is one of the most prevalent cancers in the world. Various therapeutic modalities have been used for its treatment, but all exhibit severe side effects, establishing the need for novel approaches. Chrysin is a phytomedicine compound belonging to the flavonoid group. It is found in honey and many plants. Its antitumor effects have been documented against gastric cancer cell lines in vitro, establishing its effects are mediated via different pathways and the expression of miRNA. In this review, we summarize the available literature on chrysin and its effects on gastric cancer, focusing on the cellular mechanisms it targets.
    Keywords:  5; 7-dihydroxy-flavone; Chrysin; Gastric cancer; Mechanisms of action; Molecular mechanisms; Signaling pathway
    DOI:  https://doi.org/10.2174/1874467216666230103105725
  28. J Clin Invest. 2023 Jan 03. pii: e163448. [Epub ahead of print]133(1):
    Targeting fatty acid metabolism in glioblastoma.
    Jason Miska, Navdeep S Chandel.
      Glioblastoma (GBM) is a primary tumor of the brain defined by its uniform lethality and resistance to conventional therapies. There have been considerable efforts to untangle the metabolic underpinnings of this disease to find novel therapeutic avenues for treatment. An emerging focus in this field is fatty acid (FA) metabolism, which is critical for numerous diverse biological processes involved in GBM pathogenesis. These processes can be classified into four broad fates: anabolism, catabolism, regulation of ferroptosis, and the generation of signaling molecules. Each fate provides a unique perspective by which we can inspect GBM biology and gives us a road map to understanding this complicated field. This Review discusses the basic, translational, and clinical insights into each of these fates to provide a contemporary understanding of FA biology in GBM. It is clear, based on the literature, that there are far more questions than answers in the field of FA metabolism in GBM, and substantial efforts should be made to untangle these complex processes in this intractable disease.
    DOI:  https://doi.org/10.1172/JCI163448
  29. Technol Cancer Res Treat. 2023 Jan-Dec;22:22 15330338221145246
    Molecular Classification, Treatment, and Genetic Biomarkers in Triple-Negative Breast Cancer: A Review.
    Boya Lu, Elango Natarajan, Hanumantha Rao Balaji Raghavendran, Uma Devi Markandan.
      Breast cancer is the most common malignancy and the second most common cause of cancer-related mortality in women. Triple-negative breast cancers do not express estrogen receptors, progesterone receptors, or human epidermal growth factor receptor 2 and have a higher recurrence rate, greater metastatic potential, and lower overall survival rate than those of other breast cancers. Treatment of triple-negative breast cancer is challenging; molecular-targeted therapies are largely ineffective and there is no standard treatment. In this review, we evaluate current attempts to classify triple-negative breast cancers based on their molecular features. We also describe promising treatment methods with different advantages and discuss genetic biomarkers and other prediction tools. Accurate molecular classification of triple-negative breast cancers is critical for patient risk categorization, treatment decisions, and surveillance. This review offers new ideas for more effective treatment of triple-negative breast cancer and identifies novel targets for drug development.
    Keywords:  biomarkers; molecular classification; prediction; treatment; triple-negative breast cancer
    DOI:  https://doi.org/10.1177/15330338221145246
  30. Reprod Fertil Dev. 2022 Dec;35(2): 84-97
    Metabolism-epigenetic interactions on in vitro produced embryos.
    Marcella Pecora Milazzotto, Jessica Ispada, Camila Bruna de Lima.
      Metabolism and epigenetics, which reciprocally regulate each other in different cell types, are fundamental aspects of cellular adaptation to the environment. Evidence in cancer and stem cells has shown that the metabolic status modifies the epigenome while epigenetic mechanisms regulate the expression of genes involved in metabolic processes, thereby altering the metabolome. This crosstalk occurs as many metabolites serve as substrates or cofactors of chromatin-modifying enzymes. If we consider the intense metabolic dynamic and the epigenetic remodelling of the embryo, the comprehension of these regulatory networks will be important not only for understanding early embryonic development, but also to determine in vitro culture conditions that support embryo development and may insert positive regulatory marks that may persist until adult life. In this review, we focus on how metabolism may affect epigenetic reprogramming of the early stages of development, in particular acetylation and methylation of histone and DNA. We also present other metabolic modifications in bovine embryos, such as lactylation, highlighting the promising epigenetic and metabolic targets to improve conditions for in vitro embryo development.
    DOI:  https://doi.org/10.1071/RD22203
  31. Front Cardiovasc Med. 2022 ;9 1102900
    Editorial: Metabolic hormones and inflammation.
    Matthew C Gage, Fawaz Alzaid, Alison Delamere McNeilly, Edward A Fisher.
      
    Keywords:  NPY; endothelium; estrogen; hormone; inflammation; insulin; metabolism; testosterone
    DOI:  https://doi.org/10.3389/fcvm.2022.1102900
  32. Bioorg Chem. 2022 Dec 21. pii: S0045-2068(22)00740-4. [Epub ahead of print]131 106333
    Solid lipid nanoparticles (SLNs), the potential novel vehicle for enhanced in vivo efficacy of hesperidin as an anti-inflammatory agent.
    Omolbanin Shahraki, Mohaddeseh Shayganpour, Mahmoud Hashemzaei, Sara Daneshmand.
      Hesperidin (C28H34O15), a flavanone glycoside abundantly present in citrus fruits, has proven therapeutic effects including anti-inflammatory activities. Herein, we report a novel formulation of HESP loaded solid lipid nanoparticles (SLNs) using hot homogenization and ultrasound to improve the poor solubility and bioavailability. In the present study, the formulation was developed and optimized by response surface method and then characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy (FT-IR), and dynamic light scattering (DLS). Encapsulation efficiency was determined and the anti-inflammatory effect was assessed through in vivo ear edema inflammation model. According to the electron microscopy results, the product has a spherical shape. The optimized parameters produced small size (179.8 ± 3.6 nm) HESP-SLNs with high encapsulation efficiency (93.0 ± 3.8 %). The outcomes exhibited that encapsulation in SLNs carriers improves the anti-inflammatory potential of HESP.
    Keywords:  Anti-inflammatory; Ear edema; Hesperidin; Response surface method; Solid lipid nanoparticle
    DOI:  https://doi.org/10.1016/j.bioorg.2022.106333
  33. Acta Biomater. 2022 Dec 31. pii: S1742-7061(22)00865-0. [Epub ahead of print]
    Glutamine Metabolism Targeting Liposomes for Synergistic Chemosensitization and Starvation Therapy in Ovarian Cancer.
    Xuzi Cai, Si Shi, Gui Chen, Min Zhong, Yuanyuan Yang, Ziyi Mai, Yang Tian, Jinxiu Tan, Lijuan He, Chunhui Cui, Zhiqiang Yu, Xuefeng Wang.
      Platinum-based chemotherapy is a first-line therapeutic regimen against ovarian cancer (OC); however, the therapeutic potential is always reduced by glutamine metabolism. Herein, a valid strategy of inhibiting glutamine metabolism was proposed to cause tumor starvation and chemosensitization. Specifically, reactive oxygen species-responsive liposomes were developed to co-deliver cisplatin (CDDP) and bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl) ethyl sulfide (BPTES) [C@B LPs]. The C@B LPs induced effective tumor cell starvation and significantly sensitized OC cells to CDDP by reducing glutathione generation to prevent CDDP detoxification, suppressing ATP production to avoid CDDP efflux, hindering nucleotide synthesis to aggravate DNA damage induced by CDDP, and blocking mammalian target of rapamycin (mTOR) signaling to promote cell apoptosis. More importantly, C@B LPs remarkably inhibited tumor growth in vivo and reduced the side effects. Taken together, this study provided a successful strategy of synergistic chemosensitization and starvation therapy escalating the rate of therapeutic success in OCs. STATEMENT OF SIGNIFICANCE: : This work proposed a valid strategy of inhibiting glutamine metabolism to cause tumor starvation and chemosensitization. Specifically, ROS-responsive liposomes were developed to co-deliver cisplatin CDDP and BPTES [C@B LPs]. The C@B LPs induced effective tumor cell starvation and significantly sensitized OC cells to cisplatin by reducing glutathione generation to prevent cisplatin detoxification, suppressing ATP production to avoid cisplatin efflux, hindering nucleotide synthesis to aggravate DNA damage induced by cisplatin, and blocking mTOR signaling to promote cell apoptosis. More importantly, C@B LPs remarkably inhibited tumor growth in vivo and reduced the side effects. Taken together, this study provided a successful strategy of synergistic chemosensitization and starvation therapy escalating the rate of therapeutic success in OCs.
    Keywords:  chemotherapy; cisplatin sensitization; glutamine metabolism; ovarian cancer; starvation therapy
    DOI:  https://doi.org/10.1016/j.actbio.2022.12.052
  34. Adv Sci (Weinh). 2023 Jan 04. e2206169
    Emerging Epigenetic-Based Nanotechnology for Cancer Therapy: Modulating the Tumor Microenvironment.
    Jiaxin Zhang, Leaf Huang, Guangbo Ge, Kaili Hu.
      Dysregulated epigenetic modifications dynamically drive the abnormal transcription process to affect the tumor microenvironment; thus, promoting cancer progression, drug resistance, and metastasis. Nowadays, therapies targeting epigenetic dysregulation of tumor cells and immune cells in the tumor microenvironment appear to be promising adjuncts to other cancer therapies. However, the clinical results of combination therapies containing epigenetic agents are disappointing due to systemic toxicities and limited curative effects. Here, the role of epigenetic processes, including DNA methylation, post-translational modification of histones, and noncoding RNAs is discussed, followed by detailed descriptions of epigenetic regulation of the tumor microenvironment, as well as the application of epigenetic modulators in antitumor therapy, with an emphasis on the epigenetic-based advanced drug delivery system in targeting the tumor microenvironment.
    Keywords:  DNA methylation; cancer treatment; histone modification; nanotechnology; tumor microenvironment
    DOI:  https://doi.org/10.1002/advs.202206169
  35. WIREs Mech Dis. 2023 Jan 03. e1595
    Intracellular and microenvironmental regulation of mitochondrial membrane potential in cancer cells.
    Hydari Masuma Begum, Keyue Shen.
      Cancer cells have an abnormally high mitochondrial membrane potential (ΔΨm ), which is associated with enhanced invasive properties in vitro and increased metastases in vivo. The mechanisms underlying the abnormal ΔΨm in cancer cells remain unclear. Research on different cell types has shown that ΔΨm is regulated by various intracellular mechanisms such as by mitochondrial inner and outer membrane ion transporters, cytoskeletal elements, and biochemical signaling pathways. On the other hand, the role of extrinsic, tumor microenvironment (TME) derived cues in regulating ΔΨm is not well defined. In this review, we first summarize the existing literature on intercellular mechanisms of ΔΨm regulation, with a focus on cancer cells. We then offer our perspective on the different ways through which the microenvironmental cues such as hypoxia and mechanical stresses may regulate cancer cell ΔΨm . This article is categorized under: Cancer > Environmental Factors Cancer > Biomedical Engineering Cancer > Molecular and Cellular Physiology.
    Keywords:  intracellular signaling; metastasis; mitochondrial membrane potential (ΔΨm); tumor microenvironment
    DOI:  https://doi.org/10.1002/wsbm.1595
  36. Biochem J. 2023 Jan 13. 480(1): 1-23
    Dynamic regulation of RAS and RAS signaling.
    Walter Kolch, Dénes Berta, Edina Rosta.
      RAS proteins regulate most aspects of cellular physiology. They are mutated in 30% of human cancers and 4% of developmental disorders termed Rasopathies. They cycle between active GTP-bound and inactive GDP-bound states. When active, they can interact with a wide range of effectors that control fundamental biochemical and biological processes. Emerging evidence suggests that RAS proteins are not simple on/off switches but sophisticated information processing devices that compute cell fate decisions by integrating external and internal cues. A critical component of this compute function is the dynamic regulation of RAS activation and downstream signaling that allows RAS to produce a rich and nuanced spectrum of biological outputs. We discuss recent findings how the dynamics of RAS and its downstream signaling is regulated. Starting from the structural and biochemical properties of wild-type and mutant RAS proteins and their activation cycle, we examine higher molecular assemblies, effector interactions and downstream signaling outputs, all under the aspect of dynamic regulation. We also consider how computational and mathematical modeling approaches contribute to analyze and understand the pleiotropic functions of RAS in health and disease.
    Keywords:  RAS proteins; biological networks; cancer; dynamics; signaling
    DOI:  https://doi.org/10.1042/BCJ20220234
  37. Front Oncol. 2022 ;12 1066698
    The mechanisms and roles of melatonin in gastrointestinal cancer.
    Yong-Qiang Gong, Fu-Tao Hou, Cai-Ling Xiang, Cheng-Long Li, Guo-Huang Hu, Chao-Wu Chen.
      Gastrointestinal (GI) cancer is a global health problem with wide lesions and numerous cases. The increased morbidity and mortality of GI cancer is a socio-economic challenge for decades to come. Melatonin, a nature indolamine, exerts a crucial role in molecular interactions involved in multiple functional and physiological processes. Increasing evidence indicates that melatonin can modulate GI tract, decrease the occurrence of GI cancer, and enhance the sensitivity to chemoradiotherapy. However, little is known about the exact role of melatonin in anti-carcinogenesis. In this review, we discuss the action of the beneficial effects of melatonin in GI carcinogenesis. Furthermore, we compile the understanding of the role of melatonin in GI cancer, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), colorectal cancer (CRC), and pancreatic cancer (PC). In addition, the potential therapeutic application and clinical evaluation of melatonin in GI cancer are also discussed.
    Keywords:  carcinogenesis; cellular lifecycle; gastrointestinal cancer; immunity; melatonin
    DOI:  https://doi.org/10.3389/fonc.2022.1066698
  38. Med Oncol. 2023 Jan 05. 40(2): 71
    DNA methylation and cancer: transcriptional regulation, prognostic, and therapeutic perspective.
    Sannidhi Bhootra, Nandana Jill, Geetha Shanmugam, Sudeshna Rakshit, Koustav Sarkar.
      DNA methylation is one among the major grounds of cancer progression which is characterized by the addition of a methyl group to the promoter region of the gene thereby causing gene silencing or increasing the probability of mutations; however, in bacteria, methylation is used as a defense mechanism where DNA protection is by addition of methyl groups making restriction enzymes unable to cleave. Hypermethylation and hypomethylation both pose as leading causes of oncogenesis; the former being more frequent which occurs at the CpG islands present in the promoter region of the genes, whereas the latter occurs globally in various genomic sequences. Reviewing methylation profiles would help in the detection and treatment of cancers. Demethylation is defined as preventing methyl group addition to the cytosine DNA base which could cause cancers in case of global hypomethylation, however, upon further investigation; it could be used as a therapeutic tool as well as for drug design in cancer treatment. In this review, we have studied the molecules that induce and enzymes (DNMTs) that bring about methylation as well as comprehend the correlation between methylation with transcription factors and various signaling pathways. DNA methylation has also been reviewed in terms of how it could serve as a prognostic marker and the various therapeutic drugs that have come into the market for reversing methylation opening an avenue toward curing cancers.
    Keywords:  DNA methylation; DNA methyltransferase; Demethylation; Gene regulation; Prognostic marker; Therapeutic drugs
    DOI:  https://doi.org/10.1007/s12032-022-01943-1
  39. J Pharm Anal. 2022 Dec;12(6): 901-912
    Tumor-targeting intravenous lipid emulsion of paclitaxel: Characteristics, stability, toxicity, and toxicokinetics.
    Jun Ye, Lin Li, Jiye Yin, Hongliang Wang, Renjie Li, Yanfang Yang, Yongbiao Guan, Xuejun Xia, Yuling Liu.
      Lipid nanoemulsions are promising nanodrug delivery carriers that can improve the efficacy and safety of paclitaxel (PTX). However, no intravenous lipid emulsion of PTX has been approved for clinical treatment, and systemic safety profiles have not yet been reported. Here we outline the development of a PTX-loaded tumor-targeting intravenous lipid emulsion (PTX Emul) and describe its characteristics, colloidal stability, and systemic safety profiles in terms of acute toxicity, long-term toxicity, and toxicokinetics. We also compare PTX Emul with conventional PTX injection. Results showed that PTX Emul exhibited an ideal average particle size (approximately 160 nm) with narrow size distribution and robust colloidal stability under different conditions. Hypersensitivity reaction and hemolysis tests revealed that PTX Emul did not induce hypersensitivity reactions and had no hemolytic potential. In addition, where the alleviated systemic toxicity of PTX Emul may be attributed to the altered toxicokinetic characteristics in beagle dogs, including the decreased AUC and increased plasma clearance and volume of distribution, PTX Emul alleviated acute and long-term toxicity as evidenced by the enhanced the median lethal dose and approximate lethal dose, moderate body weight change, decreased bone marrow suppression and organ toxicity compared with those under PTX injection at the same dose. A fundamental understanding of the systemic safety profiles, high tumor-targeting efficiency, and superior antitumor activity in vivo of PTX Emul can provide powerful evidence of its therapeutic potential as a future treatment for breast cancer.
    Keywords:  Colloidal Stability; Lipid emulsion; Nanodrug delivery systems; Paclitaxel; Toxicokinetics
    DOI:  https://doi.org/10.1016/j.jpha.2022.08.002
  40. Methods Mol Biol. 2023 ;2614 313-348
    Profiling the Epigenetic Landscape of the Tumor Microenvironment Using Chromatin Immunoprecipitation Sequencing.
    Marina Fukano, Gabriel Alzial, Raphaëlle Lambert, Geneviève Deblois.
      Cancer cells within a tumor exhibit phenotypic plasticity that allows adaptation and survival in hostile tumor microenvironments. Reprogramming of epigenetic landscapes can support tumor progression within a specific microenvironment by influencing chromatin accessibility and modulating cell identity. The profiling of epigenetic landscapes within various tumor cell populations has significantly improved our understanding of tumor progression and plasticity. This protocol describes an integrated approach using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) optimized to profile genome-wide post-translational modifications of histone tails in tumors. Essential tools amenable to ChIP-seq to isolate tumor cell populations of interest from the tumor microenvironment are also presented to provide a comprehensive approach to perform heterogeneous epigenetic landscape profiling of the tumor microenvironment.
    Keywords:  Cell isolation; Chromatin immunoprecipitation followed by sequencing; Epigenetic heterogeneity; Epigenetic profiling; Phenotypic plasticity; Regional tumor microdissection; Single-cell tumor dissociation; Tumor microenvironment
    DOI:  https://doi.org/10.1007/978-1-0716-2914-7_19
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