bims-kimdis Biomed News
on Ketones, inflammation and mitochondria in disease
Issue of 2023–08–13
seventeen papers selected by
Matías Javier Monsalves Álvarez, Universidad de O’Higgins
  1. The Ketogenic Diet and Cardiovascular Diseases.
  2. [Potential implications of ketone body metabolism changes and ketogenic therapy in the treatment of heart failure].
  3. EPOtential target for endurance performance: the effect of exogenous ketone supplementation on circulating erythropoietin levels.
  4. β-HB treatment reverses sorafenib resistance by shifting glycolysis-lactate metabolism in HCC.
  5. A comparison of the portfolio low-carbohydrate diet and the ketogenic diet in overweight and obese women with polycystic ovary syndrome: study protocol for a randomized controlled trial.
  6. Mitochondrial fission fueled by fasting.
  7. Insulin signaling is preserved in skeletal muscle during early diabetic ketoacidosis.
  8. Acute Ingestion of a Ketone Monoester without Co-Ingestion of Carbohydrate Improves Running Economy in Male Endurance Runners.
  9. Prebiotic effect of poly-D-3-hydroxybutyrate prevents dyslipidemia in obese mice.
  10. Under-fuelling the fire: mitochondrial implications for energy deficiency and muscle protein synthesis.
  11. Ketogenic diet: Assessing YouTube video information using quality, reliability, and text analytics methods.
  12. Inflammation o'clock: interactions of circadian rhythms with inflammation-induced skeletal muscle atrophy.
  13. Characterizing substrate utilization during the fasted state using plasma high-resolution metabolomics.
  14. Whey protein-enriched and carbohydrate-rich breakfasts attenuate insulinaemic responses to an ad-libitum lunch relative to extended morning fasting; a randomised crossover trial.
  15. Cell type-specific roles of NLRP3, inflammasome-dependent and -independent, in host defense, sterile necroinflammation, tissue repair, and fibrosis.
  16. Sodium glucose cotransporter 2 inhibitor-induced ketoacidosis is unlikely in patients without diabetes.
  17. Investigating the effect of exercise on the expression of genes related to cardiac physiological hypertrophy.
  1. Nutrients. 2023 Jul 28. pii: 3368. [Epub ahead of print]15(15):
    The Ketogenic Diet and Cardiovascular Diseases.
    Damian Dyńka, Katarzyna Kowalcze, Anna Charuta, Agnieszka Paziewska.
      The most common and increasing causes of death worldwide are cardiovascular diseases (CVD). Taking into account the fact that diet is a key factor, it is worth exploring this aspect of CVD prevention and therapy. The aim of this article is to assess the potential of the ketogenic diet in the prevention and treatment of CVD. The article is a comprehensive, meticulous analysis of the literature in this area, taking into account the most recent studies currently available. The ketogenic diet has been shown to have a multifaceted effect on the prevention and treatment of CVD. Among other aspects, it has a beneficial effect on the blood lipid profile, even compared to other diets. It shows strong anti-inflammatory and cardioprotective potential, which is due, among other factors, to the anti-inflammatory properties of the state of ketosis, the elimination of simple sugars, the restriction of total carbohydrates and the supply of omega-3 fatty acids. In addition, ketone bodies provide "rescue fuel" for the diseased heart by affecting its metabolism. They also have a beneficial effect on the function of the vascular endothelium, including improving its function and inhibiting premature ageing. The ketogenic diet has a beneficial effect on blood pressure and other CVD risk factors through, among other aspects, weight loss. The evidence cited is often superior to that for standard diets, making it likely that the ketogenic diet shows advantages over other dietary models in the prevention and treatment of cardiovascular diseases. There is a legitimate need for further research in this area.
    Keywords:  CVD; HDL; KD; LDL; blood pressure; cardiomyocytes; cardiovascular disease; cholesterol; diastolic; diet; endothelium; fatty acids; heart; heart metabolism; high fat; inflammation; ketogenic diet; ketone; ketone bodies; lipid profile; low carb; obesity; prevention; reduction; systolic; treatment; triglyceride; weight loss
    DOI:  https://doi.org/10.3390/nu15153368
  2. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2023 Jul;35(7): 769-772
    [Potential implications of ketone body metabolism changes and ketogenic therapy in the treatment of heart failure].
    Qiong Wang, Siyu Yan, Shuyu Kuang, Mengmeng Zhou, Chunling Jiang.
      Heart failure (HF) has become a major challenge in the treatment of global cardiovascular diseases. Great progress has been made in the drug treatment of HF, however, rehospitalization rate and mortality of patients with HF are still high. Hence, there is an urgent need to explore new treatment strategy and new underlying pathogenic mechanisms. In recent years, some researchers have suggested that regulation of ketone body metabolism may become a potentially promising therapeutic approach for HF. Some studies showed that the oxidative utilization of fatty acids and glucose was decreased in the failing heart, accompanied by the increase of ketone body oxidative metabolism. The enhancement of ketone body metabolism in HF is a compensatory change during HF. The failing heart preferentially uses ketone body oxidation to provide energy, which helps to improve the body's cardiac function. This review will discuss the potential significance of ketone body metabolism in the treatment of HF from three aspects: normal myocardial ketone body metabolism, the change of ketone body metabolism in HF, the effect of ketogenic therapy on HF and its treatment.
    DOI:  https://doi.org/10.3760/cma.j.cn121430-20221008-00891
  3. J Physiol. 2023 Aug 11.
    EPOtential target for endurance performance: the effect of exogenous ketone supplementation on circulating erythropoietin levels.
    Alexa A Robertson, Bridget M Lynagh, Kyle M A Thompson, Devin G McCarthy.
      
    Keywords:  erythropoietin; ketosis; monoester
    DOI:  https://doi.org/10.1113/JP285257
  4. Biomed Pharmacother. 2023 Aug 09. pii: S0753-3322(23)01084-3. [Epub ahead of print]166 115293
    β-HB treatment reverses sorafenib resistance by shifting glycolysis-lactate metabolism in HCC.
    Fat-Moon Suk, Chien-Ying Wu, Cheng-Chieh Fang, Tzu-Lang Chen, Yi-Jen Liao.
      Hepatocellular carcinoma (HCC) is the most common primary malignant tumor. Although sorafenib and regorafenib have been approved for first-line and second-line treatment, respectively, of patients with advanced HCC, long-term treatment often results in acquired resistance. Given that glycolysis-mediated lactate production can contribute to drug resistance and impair HCC treatment efficacy, we investigated the effects of ketone body treatment on the metabolic shift in sorafenib-resistant HCC cells. We discovered differential expression of 3-hydroxymethyl glutaryl-CoA synthase 2 (HMGCS2) and the ketone body D-β-hydroxybutyrate (β-HB) in four sorafenib-resistant HCC cell lines. In sorafenib-resistant HCC cells, lower HMGCS2 and β-HB levels were correlated with more glycolytic alterations and higher lactate production. β-HB treatment enhanced pyruvate dehydrogenase (PDH) expression and decreased lactate dehydrogenase (LDHA) expression and lactate production in sorafenib-resistant HCC cells. Additionally, β-HB combined with sorafenib or regorafenib promoted the antiproliferative and antimigratory abilities of sorafenib-resistant HCC cells by inhibiting the B-raf/mitogen-activated protein kinase pathway and mesenchymal N-cadherin-vimentin axis. Although the in vivo β-HB administration did not affect tumor growth, the expression of proliferative and glycolytic proteins was inhibited in subcutaneous sorafenib-resistant tumors. In conclusion, exogenous β-HB treatment can reduce lactate production and reverse sorafenib resistance by inducing a glycolytic shift; it can also synergize with regorafenib for treating sorafenib-resistant HCC.
    Keywords:  Hepatocellular carcinoma; Regorafenib; Sorafenib resistance; β-HB
    DOI:  https://doi.org/10.1016/j.biopha.2023.115293
  5. Trials. 2023 Aug 09. 24(1): 509
    A comparison of the portfolio low-carbohydrate diet and the ketogenic diet in overweight and obese women with polycystic ovary syndrome: study protocol for a randomized controlled trial.
    Maryam Sharifi Najafabadi, Jalal Moludi, Yahya Salimi, Amir Saber.
       BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most frequent endocrine disorders among women of fertile age. Women with PCOS manifest clinical symptoms like menstrual dysfunction, hirsutism, insulin resistance, and hyperinsulinemia. As excessive amounts of insulin levels directly increase ovarian production of androgens, hyperinsulinemia and insulin resistance are considered as the pathogenesis factors of PCOS. The portfolio low-carbohydrate diet (PLCD) is a plant-based diet with 40% carbohydrates combined with five cholesterol-lowering foods and nutrients. On the other hand, the ketogenic diet (KD) is a nutritional protocol with 10% carbohydrates. The purpose of this study is to determine whether PLCD or KD is more effective in alleviating PCOS symptoms.
    METHODS: Forty-six overweight or obese women diagnosed with PCOS will be randomly stratified to receive either PLCD or KD for 8 weeks. Measures related to anthropometric and body composition, glucose, and insulin level, HOMA-IR, sex hormones, lipid profile, quality of life, dietary intake, physical activity, and Ferriman-Gallwey score of all participants will be accessed before and after the intervention.
    DISCUSSION: Since the first line treatment of PCOS is lifestyle adjustment including diet control and exercise, there has not been determined the optimal diet for this population of women yet. Hence, the goal of conducting this study is to determine whether the PLCD or the KD could have more advantageous effects on attenuating PCOS manifestations. The result of this investigation will give us new insight into curing this disease and will provide evidence-based recommendations for prescribing an optimal diet for PCOS women.
    TRIAL REGISTRATION: IRCT20200912048693N3, Trial registered 2022-12-14. https://www.irct.ir/trial/67548.
    Keywords:  Ketogenic diet; Polycystic ovary syndrome; Portfolio low-carbohydrate diet
    DOI:  https://doi.org/10.1186/s13063-023-07569-6
  6. Sci Signal. 2023 08 08. 16(797): eadk1008
    Mitochondrial fission fueled by fasting.
    Wei Wong.
      Fasting activates mTORC2 to stimulate mitochondrial fission and support mitochondrial respiration.
    DOI:  https://doi.org/10.1126/scisignal.adk1008
  7. J Clin Endocrinol Metab. 2023 Aug 09. pii: dgad464. [Epub ahead of print]
    Insulin signaling is preserved in skeletal muscle during early diabetic ketoacidosis.
    Frederikke A Fisker, Thomas S Voss, Mads V Svart, Ulla Kampmann, Mikkel H Vendelbo, Mads B Bengtsen, Esben S Lauritzen, Niels Møller, Niels Jessen.
       BACKGROUND AND AIMS: During diabetic ketoacidosis (DKA), muscle tissue develops a profound insulin resistance and this complicates reversal of this potentially lethal condition. We have investigated mediators of insulin action in human skeletal muscle during total insulin withdrawal (IW) in patients with type 1 diabetes, under the hypothesis that initial phases of DKA are associated with impaired post-receptor signaling.
    MATERIALS AND METHODS: Muscle biopsies were obtained during a randomized, controlled, crossover trial involving nine patients with type 1 diabetes. The subjects were investigated during a high-dose insulin clamp preceded by either: (1) insulin-controlled euglycemia (control) or (2) total insulin withdrawal for 14 hours. Insulin action in skeletal muscle and whole-body substrate metabolism were investigated using western blot analysis and indirect calorimetry respectively.
    RESULTS: During IW, insulin-stimulated de-phosphorylation of glycogen synthase (GS) was decreased by ∼ 30% (p<0.05) compared to the control situation. This was associated with a decrease in glucose oxidation by ∼ 30% (p<0.05). Despite alterations in glucose metabolism, insulin transduction to glucose transport and protein synthesis (Akt, AS160, mTOR and 4eBP1) was intact, and glucose transporter (GLUT4) and mitochondrial proteins (SDHA and PHB1) protein expression were unaffected by the intervention.
    CONCLUSION: Diabetic ketoacidosis (DKA) impairs insulin-stimulated activation of GS while insulin signal transduction to glucose transport and protein synthesis remains intact. Reversal of insulin resistance during treatment of DKA should target post-receptor mediators of glucose uptake.
    Keywords:  Diabetes mellitus; Diabetic ketoacidosis; Insulin action; Skeletal muscle
    DOI:  https://doi.org/10.1210/clinem/dgad464
  8. Med Sci Sports Exerc. 2023 Aug 11.
    Acute Ingestion of a Ketone Monoester without Co-Ingestion of Carbohydrate Improves Running Economy in Male Endurance Runners.
    Aidan J Brady, Brendan Egan.
       PURPOSE: Acute ingestion of a ketone monoester, with and without co-ingestion of carbohydrate, was investigated for effects on running economy (RE), time to exhaustion (TTE), and other related indices of endurance running performance.
    METHODS: Using a three condition, placebo-controlled, randomized crossover design, eleven male middle- and long- distance runners ran at five submaximal speeds (10 to 14 km.h-1) on a motorized treadmill for 8 min each, immediately followed by a ramp test to volitional exhaustion. Participants consumed either a 10% carbohydrate solution (CHO), a 10% carbohydrate solution with 750 mg.kg-1 body mass of a (R)-3-hydroxybutyl (R)-3-hydroxybutyrate ketone monoester (CHO + KE), or 750 mg.kg-1 body mass of the ketone monoester in flavored water (KE) before (2/3 of the dose) and during (1/3 of the dose) exercise.
    RESULTS: βHB concentration averaged 1.8 ± 0.3 mM and 2.1 ± 0.3 mM during exercise in CHO + KE and KE, respectively. RE was lower at each submaximal running speed (ES = 0.48 to 0.98) by an average of 4.1% in KE compared to CHO, but not between CHO + KE and CHO. TTE did not differ between CHO (369 ± 116 s), CHO + KE (342 ± 99 s), or KE (333 ± 106 s) (P = 0.093).
    CONCLUSIONS: Acute ingestion of a ketone monoester without carbohydrate, but not when co-ingested with carbohydrate, improved RE in middle- and long- distance runners at a range of submaximal running speeds, and did not alter TTE in a short duration ramp test to volitional exhaustion. Further investigation is required to examine if these differences translate into positive performance outcomes over longer durations of exercise.
    DOI:  https://doi.org/10.1249/MSS.0000000000003278
  9. FASEB J. 2023 09;37(9): e23121
    Prebiotic effect of poly-D-3-hydroxybutyrate prevents dyslipidemia in obese mice.
    Mayuko Mishima, Shiro Takeda, Masaki Nagane, Takehito Suzuki, Masaya Ogata, Ayaka Shima, Naoyuki Aihara, Junichi Kamiie, Rimina Suzuki, Hinano Mizugaki, Yuko Okamatsu-Ogura, Takumi Satoh, Tadashi Yamashita.
      Obesity is a global health problem caused by genetic, environmental, and psychological factors and is associated with various health disorders. As such, there is a growing focus on the prevention of obesity and related diseases. The gut microbiota plays a crucial role in these diseases and has become a therapeutic target. Prebiotics, such as poly-d-3-hydroxybutyric acid (PHB), have gained attention for their potential to alter the gut microbiota, promote beneficial bacterial growth, and alleviate obesity. In this study, we examined the prebiotic effects of PHB in obese mice. We found that, in C57BL/6N mice, PHB reduced blood lipid levels. Analysis of the intestinal microflora also revealed an increase in short-chain fatty acid-producing bacteria. When PHB was administered to obese mice, subcutaneous fat and dyslipidemia were reduced, and the number of beneficial bacteria in the intestinal microflora increased. Furthermore, fatty degradation and oxidative stress were suppressed in the liver. PHB regulates gut bacterial changes related to obesity and effectively inhibits dyslipidemia, suggesting that it could be a prebiotic agent for curing various obesity-related diseases. In summary, PHB increases the beneficial gut microbiota, leading to an alleviation of obesity-associated dyslipidemia.
    Keywords:  dyslipidemia; microbiome; obesity; poly-D-3-hydroxybutyrate; prebiotics; short-chain fatty acid
    DOI:  https://doi.org/10.1096/fj.202301191R
  10. J Physiol. 2023 Aug 09.
    Under-fuelling the fire: mitochondrial implications for energy deficiency and muscle protein synthesis.
    Rachel M Handy, Geneviève J DesOrmeaux.
      
    Keywords:  low energy availability; mitochondrial function; muscle protein synthesis
    DOI:  https://doi.org/10.1113/JP285175
  11. Nutr Health. 2023 Aug 09. 2601060231193789
    Ketogenic diet: Assessing YouTube video information using quality, reliability, and text analytics methods.
    Avinash Rana, Monika Arora.
       OBJECTIVE: Patients and the general audience refer social media platforms, such as YouTube, to learn and apply contemporary dietary methods. It is difficult for users to analyze the correctness and quality of information available on open platforms. Using scientific evaluation, this study assessed the quality, reliability, and content of YouTube videos on ketogenic diet (KD).
    METHODS: Three experienced medical practitioners reviewed and evaluated 95 videos. The quality and reliability of the videos were assessed using the quality criteria for consumer health information and the global quality scale (GQS). Topic modeling and sentiment analysis were employed to determine the dominant themes and polarity of the information.
    RESULTS: Three types of publishers (doctors, educational institutions, and influencers) were identified for the study. The mean length of videos posted by doctors was high at 42.24 min. The reliability and quality scores ranging from 0 (low) to 5 (high) had an average of 3.08 ± 1.14 and 3.18 ± 1.18, respectively, for sampled videos. One-way analysis of variance reveals significant differences in DISCERN and GQS scores among doctors, educational institutions, and influencers. Topic discovery identified four themes: keto versus glucose, diabetes, KD food, and major chronic diseases. Sentiment analysis reveals positive content polarity, some content shared by doctors had a neutral sentiment.
    CONCLUSION: Content creators should augment the content by citing medical information and terminology. Viewers relied more on doctors for information related to KD. The aesthetic quality is high for all types of publishers. Publishers could focus on the discovered themes to create more content. Publishers should produce high-quality videos by improving esthetics (to increase engagement), and reliable medical information (to increase impact).
    Keywords:  Ketogenic; YouTube; health; quality; reliability; sentiment; topic models
    DOI:  https://doi.org/10.1177/02601060231193789
  12. J Physiol. 2023 Aug 10.
    Inflammation o'clock: interactions of circadian rhythms with inflammation-induced skeletal muscle atrophy.
    Francielly Morena da Silva, Karyn A Esser, Kevin A Murach, Nicholas P Greene.
      Circadian rhythms are ∼24 h cycles evident in behaviour, physiology and metabolism. The molecular mechanism directing circadian rhythms is the circadian clock, which is composed of an interactive network of transcription-translation feedback loops. The core clock genes include Bmal1, Clock, Rev-erbα/β, Per and Cry. In addition to keeping time, the core clock regulates a daily programme of gene expression that is important for overall cell homeostasis. The circadian clock mechanism is present in all cells, including skeletal muscle fibres, and disruption of the muscle clock is associated with changes in muscle phenotype and function. Skeletal muscle atrophy is largely associated with a lower quality of life, frailty and reduced lifespan. Physiological and genetic modification of the core clock mechanism yields immune dysfunction, alters inflammatory factor expression and secretion and is associated with skeletal muscle atrophy in multiple conditions, such as ageing and cancer cachexia. Here, we summarize the possible interplay between the circadian clock modulation of immune cells, systemic inflammatory status and skeletal muscle atrophy in chronic inflammatory conditions. Although there is a clear disruption of circadian clocks in various models of atrophy, the mechanism behind such alterations remains unknown. Understanding the modulatory potential of muscle and immune circadian clocks in inflammation and skeletal muscle health is essential for the development of therapeutic strategies to protect skeletal muscle mass and function of patients with chronic inflammation.
    Keywords:  ageing; cancer cachexia; immune system; muscle clock; skeletal muscle; type 2 diabetes mellitus
    DOI:  https://doi.org/10.1113/JP284808
  13. Nutrition. 2023 Jul 13. pii: S0899-9007(23)00188-0. [Epub ahead of print]116 112160
    Characterizing substrate utilization during the fasted state using plasma high-resolution metabolomics.
    Kaitlin R Taibl, Moriah P Bellissimo, Matthew Ryan Smith, Ken H Liu, ViLinh T Tran, Dean P Jones, Thomas R Ziegler, Jessica A Alvarez.
       OBJECTIVES: High-resolution metabolomics enables global assessment of metabolites and molecular pathways underlying physiologic processes, including substrate utilization during the fasted state. The clinical index for substrate utilization, respiratory exchange ratio (RER), is measured via indirect calorimetry. The aim of this pilot study was to use metabolomics to identify metabolic pathways and plasma metabolites associated with substrate utilization in healthy, fasted adults.
    METHODS: This cross-sectional study included 33 adults (mean age 27.7 ± 4.9 y, mean body mass index 24.8 ± 4 kg/m2). Participants underwent indirect calorimetry to determine resting RER after an overnight fast. Untargeted metabolomics was performed on fasted plasma samples using dual-column liquid chromatography and ultra-high-resolution mass spectrometry. Linear regression and pathway enrichment analyses identified pathways and metabolites associated with substrate utilization measured with indirect calorimetry.
    RESULTS: RER was significantly associated with 1389 metabolites enriched within 13 metabolic pathways (P < 0.05). Lipid-related findings included general pathways, such as fatty acid activation, and specific pathways, such as C21-steroid hormone biosynthesis and metabolism, butyrate metabolism, and carnitine shuttle. Amino acid pathways included those central to metabolism, such as glucogenic amino acids, and pathways needed to maintain reduction-oxidation reactions, such as methionine and cysteine metabolism. Galactose and pyrimidine metabolism were also associated with RER (all P < 0.05).
    CONCLUSIONS: The fasting plasma metabolome reflects the diverse macronutrient pathways involved in carbohydrate, amino acid, and lipid metabolism during the fasted state in healthy adults. Future studies should consider the utility of metabolomics to profile individual nutrient requirements and compare findings reported here to clinical populations.
    Keywords:  Energy; Indirect calorimetry; Metabolism; Metabolomics; Nutrition; Substrate utilization
    DOI:  https://doi.org/10.1016/j.nut.2023.112160
  14. J Nutr. 2023 Aug 07. pii: S0022-3166(23)72532-7. [Epub ahead of print]
    Whey protein-enriched and carbohydrate-rich breakfasts attenuate insulinaemic responses to an ad-libitum lunch relative to extended morning fasting; a randomised crossover trial.
    Harry A Smith, Jonathan D Watkins, Jean-Philippe Walhin, Javier T Gonzalez, Dylan Thompson, James A Betts.
       BACKGROUND: Typical breakfast foods are rich in carbohydrate, so elevate blood glucose during the morning, but also elicit a second-meal effect that can attenuate blood glucose responses in the afternoon.
    OBJECTIVE: To determine whether a reduced-carbohydrate protein-enriched breakfast can elicit similar effects on glucose control later in the day but without hyperglycemia in the morning.
    METHODS: In a randomised cross-over design, twelve healthy men and women (age 22 ± 2 y, BMI 24.1 ± 3.6 kg∙m-2; Mean ± SD) completed three experimental conditions. In all conditions participants consumed an ad libitum lunch at 1200 ± 1 h but differed in terms of whether they had fasted all morning (control) or had consumed a standardised porridge breakfast at 0900 ± 1 h (320 ± 50 kcal; prescribed relative to resting metabolic rate) that was either carbohydrate-rich (50 ± 10 g CHO) or protein-enriched (i.e., isoenergetic substitution of carbohydrate for 15 g whey protein isolate).
    RESULTS: The protein-enriched breakfast reduced the morning glycemic response (iAUC 87 ± 36 mmol·L-1·180 min) relative to the carbohydrate-rich breakfast (119 ± 37 mmol·L-1·180 min; p=0.03). Despite similar energy intake at lunch in all three conditions (protein-enriched 769 ± 278 kcal; carbohydrate-rich 753 ± 223 kcal; fasting 790 ± 227 kcal), post-lunch insulinemic responses were markedly attenuated when breakfasts had been consumed that were either protein-enriched (18.0 ± 8.0 nmol·L-1·120 min; p=0.05) or carbohydrate-rich (16.0 ± 7.7 nmol·L-1·120 min; p=0.005), relative to when lunch was consumed in an overnight fasted-state (26.9 ± 13.5 nmol·L-1·120 min).
    CONCLUSIONS: Breakfast consumption attenuates insulinemic responses to a subsequent meal, achieved with consumption of energy matched breakfasts typically high in carbohydrates or enriched with whey protein isolate relative to extended morning fasting.
    Keywords:  energy balance; metabolism; sugar; thermogenesis
    DOI:  https://doi.org/10.1016/j.tjnut.2023.08.008
  15. Front Immunol. 2023 ;14 1214289
    Cell type-specific roles of NLRP3, inflammasome-dependent and -independent, in host defense, sterile necroinflammation, tissue repair, and fibrosis.
    Tamisa Seeko Bandeira Honda, John Ku, Hans-Joachim Anders.
      The NLRP3 inflammasome transforms a wide variety of infectious and non-infectious danger signals that activate pro-inflammatory caspases, which promote the secretion of IL-1β and IL-18, and pyroptosis, a pro-inflammatory form of cell necrosis. Most published evidence documents the presence and importance of the NLRP3 inflammasome in monocytes, macrophages, and neutrophils during host defense and sterile forms of inflammation. In contrast, in numerous unbiased data sets, NLRP3 inflammasome-related transcripts are absent in non-immune cells. However, an increasing number of studies report the presence and functionality of the NLRP3 inflammasome in almost every cell type. Here, we take a closer look at the reported cell type-specific expression of the NLRP3 inflammasome components, review the reported inflammasome-dependent and -independent functions, and discuss possible explanations for this discrepancy.
    Keywords:  infection; inflammation; innate immunity; interleukin; regulated necrosis
    DOI:  https://doi.org/10.3389/fimmu.2023.1214289
  16. Med J Aust. 2023 Aug 07.
    Sodium glucose cotransporter 2 inhibitor-induced ketoacidosis is unlikely in patients without diabetes.
    Lisa M Raven, Christopher A Muir, Jerry R Greenfield.
      
    Keywords:  Diabetes mellitus, type 2; Kidney diseases; Pharmacovigilance
    DOI:  https://doi.org/10.5694/mja2.52067
  17. Cell Mol Biol (Noisy-le-grand). 2023 May 31. 69(5): 63-69
    Investigating the effect of exercise on the expression of genes related to cardiac physiological hypertrophy.
    Yunhui Xiong, Juan Wang, Shuxia Huang, Yizhong Cao.
      Physiological hypertrophy of the heart is associated with an increase in the normal function of the heart, and it directly relates to regular exercise, especially among elite athletes. Researches about special signaling pathways that create physiological hypertrophy have recently received more attention. As a result, the present study was conducted to investigate the effect of aerobic exercise intensity on the expression of genes involved in heart physiological hypertrophy. For this purpose, 30 male Wistar rats were prepared and randomly divided into three groups: control, intense intermittent training, and submaximal continuous training. The intensive intermittent training protocol included 30 minutes of intermittent running, each interval including 4 minutes of running with an intensity of 85-90% VO2max and 2 minutes of active recovery with an intensity of 50-60% VO2max three days a week for 8 weeks. Also, the submaximal continuous exercise group had activity intensity equal to 50-55% of the maximum oxygen consumption. The expression of genes related to cardiac hypertrophy such as MMP-I, TGF-ß1, and TIMP was evaluated through real-time PCR technique. The results showed that the expression of studied genes in the three groups had significant differences (p<0.05). Both training methods led to a significant increase in TGF-ß1 and TIMP gene expression in the heart of rats. But the changes in MMP-I in the intermittent group were not significant compared to the control group. In general, it seems that exercise leads to the improvement of the factors involved in the physiological hypertrophy of the heart. Therefore, the findings of the current research are expressed with caution and more research is needed in the future.
    DOI:  https://doi.org/10.14715/cmb/2023.69.5.11
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