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Journal of Advanced Research Dec 2023Crush syndrome (CS) is a kind of traumatic and ischemic injury that seriously threatens life after prolonged compression. It is characterized by systemic inflammatory... (Review)
Review
BACKGROUND
Crush syndrome (CS) is a kind of traumatic and ischemic injury that seriously threatens life after prolonged compression. It is characterized by systemic inflammatory reaction, myoglobinuria, hyperkalemia and acute kidney injury (AKI). Especially AKI, it is the leading cause of death from CS. There are various cell death forms in AKI, among which ferroptosis is a typical form of cell death. However, the role of ferroptosis has not been fully revealed in CS-AKI.
AIM OF REVIEW
This review aimed to summarize the evidence of ferroptosis in CS-AKI and its related molecular mechanism, discuss the therapeutic significance of ferroptosis in CS-AKI, and open up new ideas for the treatment of CS-AKI.
KEY SCIENTIFIC CONCEPTS OF REVIEW
One of the main pathological manifestations of CS-AKI is renal tubular epithelial cell dysfunction and cell death, which has been attributed to massive deposition of myoglobin. Large amounts of myoglobin released from damaged muscle deposited in the renal tubules, impeding the normal renal tubules function and directly damaging the tubules with oxidative stress and elevated iron levels. Lipid peroxidation damage and iron overload are the distinguishing features of ferroptosis. Moreover, high levels of pro-inflammatory cytokines and damage-associated molecule pattern molecules (HMGB1, double-strand DNA, and macrophage extracellular trap) in renal tissue have been shown to promote ferroptosis. However, how ferroptosis occurs in CS-AKI and whether it can be a therapeutic target remains unclear. In our current work, we systematically reviewed the occurrence and underlying mechanism of ferroptosis in CS-AKI.
Topics: Humans; Acute Kidney Injury; Cell Death; Crush Syndrome; Ferroptosis; Myoglobin
PubMed: 36702249
DOI: 10.1016/j.jare.2023.01.016 -
Nutrients Aug 2023This paper presents a systematic review of studies investigating the effects of fatty acid supplementation in potentially preventing and treating sarcopenia. PubMed,... (Review)
Review
This paper presents a systematic review of studies investigating the effects of fatty acid supplementation in potentially preventing and treating sarcopenia. PubMed, Embase, and Web of Science databases were searched using the keywords 'fatty acid' and 'sarcopenia'. Results: A total of 14 clinical and 11 pre-clinical (including cell and animal studies) studies were included. Of the 14 clinical studies, 12 used omega-3 polyunsaturated fatty acids (PUFAs) as supplements, 1 study used ALA and 1 study used CLA. Seven studies combined the use of fatty acid with resistant exercises. Fatty acids were found to have a positive effect in eight studies and they had no significant outcome in six studies. The seven studies that incorporated exercise found that fatty acids had a better impact on elderlies. Four animal studies used novel fatty acids including eicosapentaenoic acid, trans-fatty acid, and olive leaf extraction as interventions. Three animal and four cell experiment studies revealed the possible mechanisms of how fatty acids affect muscles by improving regenerative capacity, reducing oxidative stress, mitochondrial and peroxisomal dysfunctions, and attenuating cell death. Conclusion: Fatty acids have proven their value in improving sarcopenia in pre-clinical experiments. However, current clinical studies show controversial results for its role on muscle, and thus the mechanisms need to be studied further. In the future, more well-designed randomized controlled trials are required to assess the effectiveness of using fatty acids in humans.
Topics: Animals; Humans; Muscles; Cell Death; Databases, Factual; Dietary Supplements; Eicosapentaenoic Acid; Fatty Acids; Sarcopenia
PubMed: 37630803
DOI: 10.3390/nu15163613 -
Journal of Cachexia, Sarcopenia and... Jun 2024Proliferating cancer cells shift their metabolism towards glycolysis, even in the presence of oxygen, to especially generate glycolytic intermediates as substrates for...
BACKGROUND
Proliferating cancer cells shift their metabolism towards glycolysis, even in the presence of oxygen, to especially generate glycolytic intermediates as substrates for anabolic reactions. We hypothesize that a similar metabolic remodelling occurs during skeletal muscle hypertrophy.
METHODS
We used mass spectrometry in hypertrophying C2C12 myotubes in vitro and plantaris mouse muscle in vivo and assessed metabolomic changes and the incorporation of the [U-C]glucose tracer. We performed enzyme inhibition of the key serine synthesis pathway enzyme phosphoglycerate dehydrogenase (Phgdh) for further mechanistic analysis and conducted a systematic review to align any changes in metabolomics during muscle growth with published findings. Finally, the UK Biobank was used to link the findings to population level.
RESULTS
The metabolomics analysis in myotubes revealed insulin-like growth factor-1 (IGF-1)-induced altered metabolite concentrations in anabolic pathways such as pentose phosphate (ribose-5-phosphate/ribulose-5-phosphate: +40%; P = 0.01) and serine synthesis pathway (serine: -36.8%; P = 0.009). Like the hypertrophy stimulation with IGF-1 in myotubes in vitro, the concentration of the dipeptide l-carnosine was decreased by 26.6% (P = 0.001) during skeletal muscle growth in vivo. However, phosphorylated sugar (glucose-6-phosphate, fructose-6-phosphate or glucose-1-phosphate) decreased by 32.2% (P = 0.004) in the overloaded muscle in vivo while increasing in the IGF-1-stimulated myotubes in vitro. The systematic review revealed that 10 metabolites linked to muscle hypertrophy were directly associated with glycolysis and its interconnected anabolic pathways. We demonstrated that labelled carbon from [U-C]glucose is increasingly incorporated by ~13% (P = 0.001) into the non-essential amino acids in hypertrophying myotubes, which is accompanied by an increased depletion of media serine (P = 0.006). The inhibition of Phgdh suppressed muscle protein synthesis in growing myotubes by 58.1% (P < 0.001), highlighting the importance of the serine synthesis pathway for maintaining muscle size. Utilizing data from the UK Biobank (n = 450 243), we then discerned genetic variations linked to the serine synthesis pathway (PHGDH and PSPH) and to its downstream enzyme (SHMT1), revealing their association with appendicular lean mass in humans (P < 5.0e-8).
CONCLUSIONS
Understanding the mechanisms that regulate skeletal muscle mass will help in developing effective treatments for muscle weakness. Our results provide evidence for the metabolic rewiring of glycolytic intermediates into anabolic pathways during muscle growth, such as in serine synthesis.
Topics: Glucose; Muscle, Skeletal; Animals; Mice; Humans; Hypertrophy; Muscle Fibers, Skeletal; Insulin-Like Growth Factor I; Metabolomics
PubMed: 38742477
DOI: 10.1002/jcsm.13468 -
Open Access Emergency Medicine : OAEM 2023Heatstroke (HS) is a severe form of heat-related illness (HRI) associated with high morbidity and mortality, representing a condition that includes long-term multiorgan...
INTRODUCTION
Heatstroke (HS) is a severe form of heat-related illness (HRI) associated with high morbidity and mortality, representing a condition that includes long-term multiorgan dysfunction and susceptibility to further heat illness.
METHODS
In a systematic review searching Medline PubMed from the studies conducted between 2009 and 2020, 16 papers were identified.
RESULTS
A hallmark symptom of heat stroke is CNS dysfunction (a hallmark sign of HS) which manifests as mental status changes, including agitation, delirium, epilepsy, or coma at the time of the collapse. Acute kidney injury (AKI), gut ischemia, blood clots in the stomach and small intestine, cytoplasmic protein clumps in the spleen, and injury of skeletal muscle (rhabdomyolysis) are all characteristics of peripheral tissue damage. Severe heat stroke tends to be complicated by rhabdomyolysis, especially in patients with exertional heat stroke. Rhabdomyolysis may lead to systemic effects, including the local occurrence of compartment syndrome, hyperkalemic cardiac arrest, and/or lethal disseminated intravascular coagulopathy. Untreated heat stroke might exacerbate psychosis, lactic acidosis, consumptive coagulopathy, hematuria, pulmonary edema, renal failure, and other metabolic abnormalities. Core body temperature and level of consciousness are the most significant indicators to diagnose the severity of heat stroke and prevent unfavorable consequences. Heatstroke is a life-threatening illness if not promptly recognized and effectively treated.
DISCUSSION
This review highlighted that core body temperature and white blood cell count are significant contributing factors affecting heat stroke outcomes. Other factors contributing to the poor outcome include old age, low GCS, and prolonged hospital stay. The prevalence of both classic and exertional heatstroke can be reduced by certain simple preventive measures, such as avoiding strenuous activity in hot environments and reducing exposure to heat stress.
PubMed: 37771523
DOI: 10.2147/OAEM.S419028 -
Nutrients Oct 2023Vitamin D deficiency, prevalent worldwide, is linked to muscle weakness, sarcopenia, and falls. Muscle regeneration is a vital process that allows for skeletal muscle... (Review)
Review
Vitamin D deficiency, prevalent worldwide, is linked to muscle weakness, sarcopenia, and falls. Muscle regeneration is a vital process that allows for skeletal muscle tissue maintenance and repair after injury. PubMed and Web of Science were used to search for studies published prior to May 2023. We assessed eligible studies that discussed the relationship between vitamin D, muscle regeneration in this review. Overall, the literature reports strong associations between vitamin D and skeletal myocyte size, and muscle regeneration. In vitro studies in skeletal muscle cells derived from mice and humans showed vitamin D played a role in regulating myoblast growth, size, and gene expression. Animal studies, primarily in mice, demonstrate vitamin D's positive effects on skeletal muscle function, such as improved grip strength and endurance. These studies encompass vitamin D diet research, genetically modified models, and disease-related mouse models. Relatively few studies looked at muscle function after injury, but these also support a role for vitamin D in muscle recovery. The human studies have also reported that vitamin D deficiency decreases muscle grip strength and gait speed, especially in the elderly population. Finally, human studies reported the benefits of vitamin D supplementation and achieving optimal serum vitamin D levels in muscle recovery after eccentric exercise and surgery. However, there were no benefits in rotator cuff injury studies, suggesting that repair mechanisms for muscle/ligament tears may be less reliant on vitamin D. In summary, vitamin D plays a crucial role in skeletal muscle function, structural integrity, and regeneration, potentially offering therapeutic benefits to patients with musculoskeletal diseases and in post-operative recovery.
Topics: Aged; Humans; Animals; Mice; Vitamin D; Muscle, Skeletal; Vitamins; Vitamin D Deficiency; Muscular Diseases; Models, Animal; Regeneration
PubMed: 37892452
DOI: 10.3390/nu15204377 -
World Journal of Urology Jul 2023To analyze and summarize the efficacy of immune checkpoint inhibitor (ICI) alone or in combination therapy for renal cell carcinoma (RCC) and urothelial carcinoma (UC)... (Meta-Analysis)
Meta-Analysis
PURPOSE
To analyze and summarize the efficacy of immune checkpoint inhibitor (ICI) alone or in combination therapy for renal cell carcinoma (RCC) and urothelial carcinoma (UC) stratified by sex.
METHODS
Three databases were queried in October 2022 for randomized controlled trials (RCTs) analyzing RCC and UC patients treated with ICIs. We analyzed the association between sex and the efficacy of ICIs in RCC and UC patients across several clinical settings. The outcomes of interest were overall survival (OS) and progression-free survival for the metastatic setting and disease-free survival (DFS) for the adjuvant setting.
RESULTS
Overall, 16 RCTs were included for meta-analyses and network meta-analyses. In the first-line treatment of metastatic RCC (mRCC) and UC (mUC) patients, ICI-based combination therapies significantly improved OS compared to the current standard of care, regardless of sex. Adjuvant ICI monotherapy reduced the risk of disease recurrence in female patients with locally advanced RCC (pooled hazard ratio [HR]: 0.71, 95% confidence interval [CI] 0.55-0.93) but not in male patients, and, conversely, in male patients with muscle-invasive UC (pooled HR: 0.80, 95%CI 0.68-0.94) but not in female patients. Treatment ranking analyses in the first-line treatment of mRCC and mUC showed different results between sexes. Of note, regarding adjuvant treatment for RCC, pembrolizumab (99%) had the highest likelihood of improved DFS in males, whereas atezolizumab (84%) in females.
CONCLUSIONS
OS benefit of first-line ICI-based combination therapy was seen in mRCC and mUC patients regardless of sex. Sex-based recommendations for ICI-based regimens according to the clinical setting may help guide clinical decision-making.
Topics: Female; Male; Humans; Immune Checkpoint Inhibitors; Carcinoma, Renal Cell; Neoplasm Recurrence, Local; Carcinoma, Transitional Cell; Urinary Bladder Neoplasms; Kidney; Adjuvants, Immunologic; Kidney Neoplasms
PubMed: 37209143
DOI: 10.1007/s00345-023-04412-0 -
Sports Medicine (Auckland, N.Z.) Sep 2023Well programmed strength and conditioning training is an indispensable part of the long-term training process for athletes in individual and team sports to improve...
BACKGROUND
Well programmed strength and conditioning training is an indispensable part of the long-term training process for athletes in individual and team sports to improve performance and prevent injuries. Yet, there is a limited number of studies available that examine the effects of resistance training (RT) on muscular fitness and physiological adaptations in elite female athletes.
OBJECTIVES
This systematic review aimed to summarize recent evidence on the long-term effects of RT or combinations of RT with other strength-dominated exercise types on muscular fitness, muscle morphology, and body composition in female elite athletes.
MATERIALS AND METHODS
A systematic literature search was conducted in nine electronic databases (Academic Search Elite, CINAHL, ERIC, Open Access Theses and Dissertations, Open Dissertations, PsycINFO, PubMed/MEDLINE, Scopus, and SPORTDiscus) from inception until March 2022. Key search terms from the MeSH database such as RT and strength training were included and combined using the operators "AND," "OR," and "NOT". The search syntax initially identified 181 records. After screening for titles, abstracts, and full texts, 33 studies remained that examined the long-term effects of RT or combinations of RT with other strength-dominated exercise types on muscular fitness, muscle morphology, and body composition in female elite athletes.
RESULTS
Twenty-four studies used single-mode RT or plyometric training and nine studies investigated the effects of combined training programs such as resistance with plyometric or agility training, resistance and speed training, and resistance and power training. The training duration lasted at least 4 weeks, but most studies used ~ 12 weeks. Studies were generally classified as 'high-quality' with a mean PEDro score of 6.8 (median 7). Irrespective of the type or combination of RT with other strength-dominated exercise regimens (type of exercise, exercise duration, or intensity), 24 out of 33 studies reported increases in muscle power (e.g., maximal and mean power; effect size [ES]: 0.23 < Cohen's d < 1.83, small to large), strength (e.g., one-repetition-maximum [1RM]; ES: 0.15 < d < 6.80, small to very large), speed (e.g., sprint times; ES: 0.01 < d < 1.26, small to large), and jump performance (e.g., countermovement/squat jump; ES: 0.02 < d < 1.04, small to large). The nine studies that examined the effects of combined training showed significant increases on maximal strength (ES: 0.08 < d < 2.41, small to very large), muscle power (ES: 0.08 < d < 2.41, small to very large), jump and sprint performance (ES: 0.08 < d < 2.41, small to very large). Four out of six studies observed no changes in body mass or percentage of body fat after resistance or plyometric training or combined training (ES: 0.026 < d < 0.492, small to medium). Five out of six studies observed significant changes in muscle morphology (e.g., muscle thickness, muscle fiber cross-sectional area; ES: 0.23 < d < 3.21, small to very large). However, one study did not find any changes in muscle morphology (i.e., muscle thickness, pennation angle; ES: 0.1 < d < 0.19, small).
CONCLUSION
Findings from this systematic review suggest that RT or combined RT with other strength-dominated exercise types leads to significant increases in measures of muscle power, strength, speed, and jump performance in elite female athletes. However, the optimal dosage of programming parameters such as training intensity and duration necessary to induce large effects in measures of muscular fitness and their physiological adaptations remain to be resolved in female elite athletes.
Topics: Humans; Female; Resistance Training; Athletic Performance; Muscle Strength; Body Composition; Athletes; Muscle Fibers, Skeletal
PubMed: 37289331
DOI: 10.1007/s40279-023-01859-4 -
Advances in Clinical and Experimental... May 2024Atherosclerosis is a complex process involving endothelial dysfunction, vascular inflammation, vascular smooth muscle cell (VSMC) proliferation, angiogenesis, and... (Review)
Review
Atherosclerosis is a complex process involving endothelial dysfunction, vascular inflammation, vascular smooth muscle cell (VSMC) proliferation, angiogenesis, and calcification. One of the pathomechanisms of atherosclerosis is the upregulation of Wnt signaling. This study aimed to summarize the current knowledge regarding the role of Wnt signaling and sclerostin in atherosclerosis, vascular calcification, aneurysms, and mortality based on the PubMed database. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendation and identified 160 papers that were included in this systematic review. The published data highlight that the upregulation of Wnt components facilitates the initiation and progression of atherosclerosis, arterial remodeling, VSMCs proliferation and phenotypic transition to the osteoblastic lineage in the arterial wall. This results in protein secretion, cell migration, calcification, fibrosis and aneurysm formation. The transformation of VSMCs into osteoblast-like cells that is observed in atherosclerosis results in sclerostin expression inhibiting the Wnt pathway. Furthermore, it was shown that sclerostin, expressed in atherosclerotic plaques, inhibits aneurysm formation in a mouse model. However, in humans, while the antisclerostin antibody romosozumab inhibits bone resorption, biochemical parameters of endothelial activation and inflammation are not affected, and the incidence of aneurysms is not increased. It was suggested that detecting sclerostin in the calcified aortic atherosclerotic plaques reflects a defense mechanism against Wnt activation and inhibition of atherosclerosis, although this has only been shown in animal models. Moreover, an increased number of vascular cells converted to osteogenic phenotypes results in increased plasma sclerostin concentrations. Therefore, plasma sclerostin derived from bone limits its importance as a global marker of vascular calcification.
Topics: Humans; Vascular Calcification; Atherosclerosis; Animals; Wnt Signaling Pathway; Adaptor Proteins, Signal Transducing; Genetic Markers
PubMed: 37676098
DOI: 10.17219/acem/169567 -
International Journal of Molecular... Sep 2023Intracranial aneurysms (IAs) are abnormal dilations of the cerebral vessels, which pose a persistent threat of cerebral hemorrhage. Inflammation is known to contribute... (Review)
Review
Intracranial aneurysms (IAs) are abnormal dilations of the cerebral vessels, which pose a persistent threat of cerebral hemorrhage. Inflammation is known to contribute to IA development. The nuclear factor "kappa-light-chain-enhancer" of activated B-cells (NF-κB) is the major driver of inflammation. It increases the expression of inflammatory markers and matrix metalloproteinases (MMPs), which contribute heavily to the pathogenesis of IAs. NF-κB activation has been linked to IA rupture and resulting subarachnoid hemorrhage. Moreover, NF-κB activation can result in endothelial dysfunction, smooth muscle cell phenotypic switching, and infiltration of inflammatory cells in the arterial wall, which subsequently leads to the initiation and progression of IAs and consequently results in rupture. After a systematic search, abstract screening, and full-text screening, 30 research articles were included in the review. In this systematic review, we summarized the scientific literature reporting findings on NF-κB's role in the pathogenesis of IAs. In conclusion, the activation of the NF-κB pathway was associated with IA formation, progression, and rupture.
Topics: Humans; NF-kappa B; Intracranial Aneurysm; Signal Transduction; Arteries; Inflammation
PubMed: 37762520
DOI: 10.3390/ijms241814218 -
Asian Pacific Journal of Cancer... Dec 2023Allogeneic hematopoietic cell transplantation (allo-HCT) serves as a potentially curative intervention for various hematologic disorders. However, its utility can be...
INTRODUCTION
Allogeneic hematopoietic cell transplantation (allo-HCT) serves as a potentially curative intervention for various hematologic disorders. However, its utility can be limited by the emergence of chronic graft-versus-host disease (cGVHD). The clinical manifestations of cGVHD result from a complex immune response characterized by the involvement of both B and T cells. Ibrutinib, a pharmacological agent, acts as an inhibitor of Bruton's tyrosine kinase (BTK) pathway, which becomes activated through the B-cell receptor and regulates B-cell survival. By exerting inhibitory effects on both BTK and inhibitor of interleukin-2 inducible T-cell kinase (ITK), ibrutinib exhibits promise as a therapeutic approach for managing cGVHD. Ibrutinib may be considered as a viable treatment option for active cGVHD in cases where patients exhibit an inadequate response to corticosteroid-based therapies. This systematic review seeks to assess the efficacy and safety of ibrutinib in the context of cGVHD patient management.
METHOD
We incorporated search engines from PubMed, Embase, Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov. The study was performed following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 and Assessing The Methodological Quality of Systematic Review (AMSTAR). We used Risk of Bias- 2 (RoB-2) tool for assess the risk of bias in randomized controlled studies (RCTs) and Newcastle Ottawa Scale (NOS) for observational and open-label studies.
RESULTS
A total of 7 studies were included in this study consisted of four open-label studies, two retrospective cohort studies, and one RCT study. These studies compared Ibrutinitib with standard therapies. Two studies investigated the pediatric population, and five studies investigated the adult population. Overall, these studies reported the overall response rate (ORR) of ibrutinib for cGVHD were 54%-78%. The results showed that in pediatric patients, the ORR were 54-78%. The results also showed that in adult patients, the ORR were 67%-76%. The most common adverse effects observed across the seven studies included pyrexia, diarrhea, abdominal pain, cough, nausea, stomatitis, vomiting, headache, bleeding and bruising, infection, muscle aches, fatigue, oral bleeding, elevated transaminases, lower gastrointestinal bleeding, persistent dizziness, sepsis, pneumonia, reduced platelet count, exhaustion, sleeplessness, peripheral edema, and fatigue.
CONCLUSION
The majority of studies have indicated that ibrutinib exhibits a high ORR and provides long-lasting responses, while also having manageable side effects.
Topics: Adult; Humans; Child; Bronchiolitis Obliterans Syndrome; Graft vs Host Disease; B-Lymphocytes; Fatigue
PubMed: 38156834
DOI: 10.31557/APJCP.2023.24.12.4025