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Abstract: Background: As the prevalence of atrial fibrillation rises with age and older patients increasingly receive transplants, the perioperative management of this common arrhythmia and its impact on outcomes in liver transplantation is of relevance. Methods: Retrospective review of 757 recipients of liver transplantation from January 2002 through December 2011. Results: Nineteen recipients (2.5%) had documented pre-transplantation atrial fibrillation. Sixteen patients underwent liver and 3 a combined liver-kidney transplantation. Three patients died within 30 days (84.2% 1-month survival) and another 3 within 1 year of transplantation (68.4% 1-year survival). Compared with patients without atrial fibrillation, the relative risk of death in the atrial fibrillation group was 5.29 at 1 month (P = .0034; 95% confidence interval [CI], 1.73–16.18) and 3.28 at 1 year (P = .0008; 95% CI, 1.63–6.59). Time to extubation and intensive care unit (ICU) and hospital readmissions were not different from the control cohort. Rapid ventricular response requiring treatment occurred in 4 patients during surgery and 7 after surgery, resulting in 3 ICU and 3 hospital readmissions. Conclusions: The results suggest that patients with atrial fibrillation may be at increased risk of mortality after liver transplantation. Optimization of medical therapy may decrease ICU and hospital readmission due to rapid ventricular response. [Copyright &y& Elsevier]

Carnosine, a compound with plethora of benefits, was originally discovered in 1900 and is formed by the amide linkage of β-alanine and L-histidine. Carnosine production is limited by β-alanine whereas the imidazole ring of histidine moiety makes it a suitable buffer in physiological pH range. It is reported to be found in the skeletal muscle, brain, heart, and gastrointestinal tissues of humans. This review focuses on the biological properties of carnosine including pH buffering ability, antioxidant activity, anti-inflammatory activity, anti-aging effect, enhancement of cognitive function, and immunomodulation. The relevance of carnosine in muscle function attributing to enhancement of physical performance has also been highlighted. Studies spanning several years have proved the preclinical effectiveness of carnosine in treating diverse pathological diseases. A complete summary of all key activities of carnosine from in vivo investigations and clinical trials has been compiled. Considering its numerous advantages, carnosine may be a promising option for the development of a nutraceutical., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Redox homeostasis is a crucial phenomenon that is obligatory for maintaining the healthy status of cells. However, the loss of redox homeostasis may lead to numerous diseases that ultimately result in a compromised quality of life. Skeletal muscle is an endocrine organ that secretes hundreds of myokines. Myokines are peptides and cytokines produced and released by muscle fibers. Skeletal muscle secreted myokines act as a robust modulator for regulating cellular metabolism and redox homeostasis which play a prime role in managing and improving metabolic function in multiple organs. Further, the secretory myokines maintain redox homeostasis not only in muscles but also in other organs of the body via stabilizing oxidants and antioxidant levels. Myokines are also engaged in maintaining mitochondrial dynamics as mitochondria is a central point for the generation of reactive oxygen species (ROS). Ergo, myokines also act as a central player in communicating signals to other organs, including the pancreas, gut, liver, bone, adipose tissue, brain, and skin via their autocrine, paracrine, or endocrine effects. The present review provides a comprehensive overview of skeletal muscle-secreted myokines in managing redox homeostasis and quality of life. Additionally, probable strategies will be discussed that provide a solution for a better quality of life., (© 2024 International Union of Biochemistry and Molecular Biology.)

The burden of growing concern about the dysregulation of metabolic processes arises due to complex interplay between environment and nutrition that has great impact on genetics and epigenetics of an individual. Thereby, any abnormality at the level of food intake regulating hormones may contribute to the development of metabolic diseases in any age group due to malnutrition, overweight, changing lifestyle, and exposure to extreme environments such as heat stress (HS), cold stress, or high altitude (HA). Hormones such as leptin, adiponectin, ghrelin, and cholecystokinin regulate appetite and satiety to maintain energy homeostasis. Leptin, an adipokine and a pleiotropic hormone, play major role in regulating the food intake, energy gain and energy expenditure. Using in silico approach, we have identified the major genes (LEP, LEPR, JAK2, STAT3, NPY, POMC, IRS1, SOCS3) that play crucial role in leptin signaling pathway. Further, eight miRNAs (hsa-miR-204-5p, hsa-miR-211-5p, hsa-miR-30, hsa-miR-3163, hsa-miR-33a-3p, hsa-miR-548, hsa-miR-561-3p, hsa-miR-7856-5p) from TargetScan 8.0 database were screened out that commonly target these genes. The role of these miRNAs should be explored as they might play vital role in regulating the appetite, energy metabolism, metabolic diseases (obesity, type 2 diabetes, cardiovascular diseases, inflammation), and to combat extreme environments. The miRNAs regulating leptin signaling and appetite may be useful for developing novel therapeutics for metabolic diseases., (© 2024 The Author(s). Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

The present study aims to analyze the role of microRNA-1 in the regulation of skeletal muscle loss under hypobaric hypoxia (HH). Male Sprague Dawley rats (n = 10) weighing 230-250 g are divided into two groups, control and HH exposure for 7 days at 25 000 ft. After the hypoxia exposure, the animals are sacrificed and hindlimb skeletal muscles are excised for further analysis. Studies found the potential role of miR-1 (myomiR) as a biomarker under different atrophic conditions. Prolonged exposure to HH leads to enhanced expression of miR-1 in skeletal muscle as compared to unexposed controls. The Bioinformatics approach is used to identify the validated targets and the biological processes of miR-1. The target prediction tools identify PAX3 and HSP70 as major targets for miR-1. Exposure to HH significantly reduces PAX3 and HSP70 expression during 7 days of HH exposure, which further enhances the activity of FOXO3, MSTN, and ATROGIN known for the progression of skeletal muscle atrophy in relation to control rats. This study indicates the increased expressions of miR-1 and reduced expression of PAX3 and HSP70 lead to impaired myogenesis in skeletal muscle under HH. Further, enhanced expression of muscle degradation genes such as FOXO3, MSTN, and ATROGIN under HH exposure causes skeletal muscle protein loss., (© 2023 Wiley-VCH GmbH.)

Rathor, Richa, Sukanya Srivastava, and Geetha Suryakumar. A comparative biochemical study between L-carnosine and β-alanine in amelioration of hypobaric hypoxia-induced skeletal muscle protein loss. High Alt Med Biol . 24:302-311, 2023. Background: Carnosine (CAR; β-alanyl-L-histidine), a biologically active dipeptide is known for its unique pH-buffering capacity, metal chelating activity, and antioxidant and antiglycation property. β-Alanine (ALA) is a nonessential amino acid and used to enhance performance and cognitive functions. Hypobaric hypoxia (HH)-induced muscle protein loss is regulated by multifaceted signaling pathways. The present study investigated the beneficial effects of CAR and ALA against HH-associated muscle loss. Methodology: Simulated HH exposure was performed in an animal decompression chamber. Gastric oral administration of CAR (50 mg·kg -1 ) and ALA (450 mg·kg -1 ) were given daily for 3 days and at the end of the treatment, hindlimb skeletal muscle tissue was excised for western blot and biochemical assays. Results: Cosupplementation of CAR and ALA alone was able to ameliorate the hypoxia-induced inflammation, oxidative stress (FOXO), ER stress (GRP-78), and atrophic signaling (MuRF-1) in the skeletal muscles. Creatinine phospho kinase activity and apoptosis were also decreased in CAR- and ALA-supplemented rats. However, CAR showed enhanced protection in HH-induced muscle loss as CAR supplementation was able to enhance protein concentration, body weight, and decreased the protein oxidation and ALA administration was not able to restore the same. Conclusions: Hence, the present comprehensive study supports the fact that CAR (50 mg·kg -1 ) is more beneficial as compared with ALA (450 mg·kg -1 ) in ameliorating the hypoxia-induced skeletal muscle loss.

Background: The present study aimed to analyse the role of myokines and the regeneration capacity of skeletal muscle during chronic hypobaric hypoxia (CHH)., Methods: Male Sprague-Dawley rats were exposed to hypobaric hypoxia (HH) for 1d, 3d and 7d., Results: Exposure to HH enhanced the levels of decorin, irisin, IL-6 and IL-15 till 3 days of hypoxia and on 7 day of exposure, no significant changes were observed in relation to control. A significant upregulation in myostatin, activated protein kinase, SMAD3, SMAD4, FOXO-1, MURF-1 expression was observed with prolonged HH exposure as compared to normoxic control. Further, myogenesis-related markers, PAX-7, Cyclin D1 and myogenin were downregulated during CHH exposure in comparison to control. Energy metabolism regulators such as Sirtuin 1, proliferator-activated receptor gamma coactivator-1α and GLUT-4, were also increased on 1-d HH exposure that showed a declining trend on CHH exposure., Conclusions: These results indicated the impairment in the levels of myokines and myogenesis during prolonged hypoxia. CHH exposure enhanced the levels of myostatin and reduced the regeneration or repair capacity of the skeletal muscles. Myokine levels could be a predictive biomarker for evaluating skeletal muscle performance and loss at high altitudes.

High altitude is an environmental stress that is accompanied with numerous adverse biological responses, including skeletal muscle weakness and muscle protein loss. Skeletal muscle wasting is an important clinical problem, progressing to critical illness, associated with increased morbidity and mortality. The present study explores the protective efficacy of endogenous dipeptide, carnosine (CAR), supplementation in ameliorating skeletal muscle protein loss under hypobaric hypoxia (HH). Male Sprague-Dawley rats (n = 5) were randomly divided into control group, HH-exposed group (3 days HH exposure equivalent to 7,620 m), and HH-exposed rats supplemented with carnosine (3 days; 150 mg/kg b.w, orally) (HH + CAR). HH-exposed rats supplemented with CAR ameliorated HH-induced oxidative protein damage, lipid peroxidation, and maintained pro-inflammatory cytokines levels. HH-associated muscle protein degradative pathways, including calpain, ubiquitination, endoplasmic reticulum stress, autophagy, and apoptosis were also regulated in carnosine-supplemented rats. Further, the muscle damage marker, the levels of serum creatine phosphokinase were also reduced in HH + CAR co-supplemented rats which proved the protective efficacy of CAR against hypobaric hypoxia-induced muscle protein loss. Altogether, CAR supplementation ameliorated HH-induced skeletal muscle protein loss via performing multifaceted ways, mainly by maintaining redox homeostasis and proteostasis in skeletal muscle., (© 2021 International Union of Biochemistry and Molecular Biology.)

Competing Interests: There are no conflicts of interest.

Several chronic diseases lead to skeletal muscle loss and a decline in physical performance. MicroRNAs (miRNAs) are small, noncoding RNAs, which have exhibited their role in the development and diseased state of the skeletal muscle. miRNA regulates gene expression by binding to the 3' untranslated region of its target mRNA. Due to the robust stability in biological fluids, miRNAs are ideal candidate as biomarker. These miRNAs provide a novel avenue in strengthening our awareness and knowledge about the factors governing skeletal muscle functions such as development, growth, metabolism, differentiation, and cell proliferation. It also helps in understanding the therapeutic strategies in improving or conserving skeletal muscle health. This review outlines the evidence regarding the present knowledge on the role miRNA as a potential biomarker in skeletal muscle diseases and their exploration might be a unique and potential therapeutic strategy for various skeletal muscle disorders.

High altitude exposure leads to compromised physical performance with considerable weight loss. The major stressor at high altitude is hypobaric hypoxia which leads to disturbance in redox homeostasis. Oxidative stress is a well-known trigger for many high altitude illnesses and regulates several key signaling pathways under stressful conditions. Altered redox homeostasis is considered the prime culprit of high altitude linked skeletal muscle atrophy. Hypobaric hypoxia disturbs redox homeostasis through increased RONS production and compromised antioxidant system. Increased RONS disturbs the cellular homeostasis via multiple ways such as inflammation generation, altered protein anabolic pathways, redox remodeling of RyR1 that contributed to dysregulated calcium homeostasis, enhanced protein degradation pathways via activation calcium-regulated protein, calpain, and apoptosis. Ultimately, all the cellular signaling pathways aggregately result in skeletal muscle atrophy. Dietary supplementation of phytochemicals could become a safe and effective intervention to ameliorate skeletal muscle atrophy and enhance the physical performance of the personnel who are staying at high altitude regions. The present evidence-based review explores few dietary supplementations which regulate several signaling mechanisms and ameliorate hypobaric hypoxia induced muscle atrophy and enhances physical performance. However, a clinical research trial is required to establish proof-of-concept., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Hypobaric hypoxic stress leads to oxidative stress, inflammation, and disturbance in protein turnover rate. Aggregately, this imbalance in redox homeostasis is responsible for skeletal muscle protein loss and a decline in physical performance. Hence, an urgent medical need is required to ameliorate skeletal muscle protein loss. The present study investigated the efficacy of ursolic acid (UA), a pentacyclic triterpene acid to ameliorate hypobaric hypoxia (HH)-induced muscle protein loss. UA is a naturally occurring pentacyclic triterpene acid present in several edible herbs and fruits such as apples. It contains skeletal muscle hypertrophy activity; still its potential against HH-induced muscle protein loss is unexplored. To address this issue, an in vivo study was planned to examine the beneficial effect of UA supplementation on HH-induced skeletal muscle loss. Male Sprague Dawley rats were exposed to HH with and without UA supplementation (20 mg/kg; oral) for 3 continuous days. The results described the beneficial role of UA as supplementation of UA with HH exposure attenuated reactive oxygen species production and oxidative protein damage, which indicate the potent antioxidant activity. Furthermore, UA supplementation enhanced Akt, pAkt, and p70S6kinase activity (Akt pathway) and lowered the pro-inflammatory cytokines in HH exposed rats. UA has potent antioxidant and anti-inflammatory activity, and it enhanced the protein content via upregulation of Akt pathway-related proteins against HH exposure. These three biological activities of UA make it a novel candidate for amelioration of HH-induced skeletal muscle damage and protein loss., (© 2020 International Union of Biochemistry and Molecular Biology.)

In early December 2019, a novel coronavirus disease 2019 (COVID-19), the global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) commenced in Wuhan, China, and WHO declared the outbreak a pandemic and Public Health Emergency of International Concern. An ample number of clinical trials with multiple drugs is underway to overcome the current perilous condition. Still, the situation is alarming with no therapeutic measure in our hand at present. Keeping the present scenario in mind, this review comprises the research, clinical knowledge, and repurposed herbals with regard to COVID-19. Preventive measures such as yoga, nasal breathing, and herbal administration could also provide protection and beneficial effects against coronavirus. Innumerable clinical trials are ongoing to manage COVID-19 and the drugs were selected on the basis of life cycle of coronavirus. The selection of herbals was done on the basis of the previous reported pharmacological activities and docking study. The results concluded that garlic, liquorice, and Ashwagandha have a potential against SARS-CoV-2, which was further proved via a docking study and their reported biological functions. The very well-known fact "prevention is always better than cure" is applied to overcome with coronavirus infection. It is expected that following the preventive measures could impede or lessen the adverse effect of SARS-CoV-2.

Introduction: Emerging data have demonstrated increased mortality of COVID-19 patients suffering from comorbid conditions such as Type II diabetes, hypertension, and cardiovascular diseases. Underlying risk in all these patients is an increase in bodyweight or obesity. The adverse health effects of obesity and how these factors enhance the risk of mortality in COVID-19 patients is still unexplored., Objective: The enhanced fat deposition might be a risk factor for increased mortality in COVID-19 patients., Method: We have reviewed and collected the information from online databases: Pubmed, Google scholar, Researchgate, to highlight the systematic link between obesity with associated risks in COVID-19., Result: We have reported the first study during the pandemic from France and New York, to a currently reported study in Mexico and found individuals with BMI ≥35 kg/m 2 or >40 kg/m 2 have greater risk of developing critical illness due to COVID-19, thereby increasing mortality., Conclusion: Our study suggests obesity in childhood, adolescence, and adulthood can be considered a profound risk factor for greater susceptibility and severity of COVID-19 and is associated with nutritional, lifestyle, cardiac, respiratory, renal, and immunological alterations, which may potentiate the complications of SARS-CoV-2 infection. Further suggesting to check on BMI during this pandemic situation., (© 2021. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

At extreme altitude, prolonged and severe hypoxia menaces human function and survival, and also associated with profound loss of muscle mass which results into a debilitating critical illness of skeletal muscle atrophy. Hypobaric hypoxia altered redox homeostasis and impaired calcium ion handling in skeletal muscles. Dysregulated Ca 2+ homeostasis and activated calpain is the prime stressor in high altitude hypoxia while the reason for subsequent abnormal release of pathological Ca 2+ into cytoplasm is largely unexplored. The present study identified the redox remodeling in the Ca 2+ release channel, Ryanodine Receptor (RyR1) owing to its hypernitrosylation state in skeletal muscles in chronic hypobaric hypoxia exposed rats. RyR1-hypernitrosylation decreases the binding of FKBP12/calstabin-1 and other complexes from the channel, causing "leakiness" in RyR1 ion-channel. A strong RyR1 stabilizer, S107 enhanced binding affinity of FKBP12 with hypernitrosylated RyR1, reduced Sarco(endo)plasmic reticulum (SR) Ca 2+ leak and improved muscle strength and function under chronic hypoxia. Administration of S107 inhibited the skeletal muscle damage, maintained ultrastructure of sarcomere and sarcolemmal integrity. Histological analysis proved the increase in cross-sectional area of myofibers. Further, the number of apoptotic cells was also reduced by S107 treatment. Conclusively, we proposed that the redox remodeling of RyR1 (hypernitrosylated-RyR1) might be responsible for dysregulated Ca 2+ homeostasis which consequently impaired muscle strength and function in response to chronic hypoxic stress. Reduced SR Ca 2+ leak and enhanced binding affinity of FKBP12 may provide a novel therapeutic avenue in ameliorating skeletal muscle atrophy at high altitude., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The misbehaving attitude of Ca 2+ signaling pathways could be the probable reason in many muscular disorders such as myopathies, systemic disorders like hypoxia, sepsis, cachexia, sarcopenia, heart failure, and dystrophy. The present review throws light upon the calcium flux regulating signaling channels like ryanodine receptor complex (RyR1), SERCA (Sarco-endoplasmic Reticulum Calcium ATPase), DHPR (Dihydropyridine Receptor) or Cav1.1 and Na+/Ca 2+ exchange pump in detail and how remodelling of these channels contribute towards disturbed calcium homeostasis. Understanding these pathways will further provide an insight for establishing new therapeutic approaches for the prevention and treatment of muscle atrophy under stress conditions, targeting calcium ion channels and associated regulatory proteins.

Background: High altitude associated hypobaric hypoxia is one of the cellular and environmental perturbation that alters proteostasis network and push the healthy cell towards loss of muscle mass. The present study has elucidated the robust proteostasis network and signaling mechanism for skeletal muscle atrophy under chronic hypobaric hypoxia (CHH)., Methods: Male Sprague Dawley rats were exposed to simulated hypoxia equivalent to a pressure of 282 torr for different durations (1, 3, 7 and 14 days). After CHH exposure, skeletal muscle tissue was excised from the hind limb of rats for biochemical analysis., Results: Chronic hypobaric hypoxia caused a substantial increase in protein oxidation and exhibited a greater activation of ER chaperones, glucose-regulated protein-78 (GRP-78) and protein disulphide isomerase (PDI) till 14d of CHH. Presence of oxidized proteins triggered the proteolytic systems, 20S proteasome and calpain pathway which were accompanied by a marked increase in [Ca2+]. Upregulated Akt pathway was observed upto 07d of CHH which was also linked with enhanced glycogen synthase kinase-3β (GSk-3β) expression, a negative regulator of Akt. Muscle-derived cytokines, tumor necrosis factor-α (TNF-α), interferon-ϒ (IFN-©) and interleukin-1β (IL-1β) levels significantly increased from 07d onwards. CHH exposure also upregulated the expression of nuclear factor kappa-B (NF-κB) and E3 ligase, muscle atrophy F-box-1 (Mafbx-1/Atrogin-1) and MuRF-1 (muscle ring finger-1) on 07d and 14d. Further, severe hypoxia also lead to increase expression of ER-associated degradation (ERAD) CHOP/ GADD153, Ub-proteasome and apoptosis pathway., Conclusions: The disrupted proteostasis network was tightly coupled to degradative pathways, altered anabolic signaling, inflammation, and apoptosis under chronic hypoxia. Severe and prolonged hypoxia exposure affected the protein homeostasis which overwhelms the muscular system and tends towards skeletal muscle atrophy., Competing Interests: The authors have declared that no competing interests exist.

While numerous maladies are associated with hypobaric hypoxia, muscle protein loss is an important under studied topic. Hence, the present study was designed to investigate the mechanism of muscle protein loss at HH. SD rats were divided into normoxic rats, while remaining rats were exposed to simulated hypoxia equivalent to 282-torr pressure (equal to an altitude of 7620 m, 8% oxygen), at 25 °C for 6, 12, and 24 h. Post-exposure rats were sacrificed and analysis was performed. Ergo, muscle loss-related changes were observed at 12 and 24 h post-HH exposure. An increased reactive oxygen species production and decreased thiol content was observed in HH-exposed rats. This disturbance caused substantial protein oxidative modification in the form of protein carbonyl content and advanced oxidation protein products. The analysis showed increase levels of bityrosine, oxidized tryptophan, lysine conjugate, lysine conjugate with MDA, protein hydroperoxide, and protein-MDA product. These changes were also in agreement with increase in lipid hydroperoxides and MDA content. HSP-70 and HSP-60 were upregulated significantly, and this finding is corroborated with increase in ER stress biomarker, GRP-78. Overloading of cells with misfolded proteins further activated degradative machinery. Consequently, pro-apoptotic signaling cascade, caspase-3, and C/EBP homologous protein were also activated in 24-h HH exposure. Release of tryptophan and tyrosine was also increased with 24-h HH exposure, indicated protein degradation. Elevation in resting intracellular calcium ion, [Ca 2+ ]i, was also observed at 12- and 24-h HH exposure. The present study provides a detailed mechanistic representation of muscle protein loss during HH exposure.

Hippophae salicifolia (HS) and Hippophae rhamnoides turkestanica (HRT) are abundantly found species of Hippophae in Himalayan region of India. As these plants thrive under extreme climatic conditions, it is suspected that these plants must have a unique adaptogenic property against high-altitude stress. To keeping these views in our mind, the present study was planned to evaluate the mechanism of action of aqueous extract of HS and aqueous extract of HRT against multiple stress [cold-hypoxia-restraint (C-H-R)] for their adaptogenic activity. The present study reported the adaptogenic activity of HS in facilitating tolerance to multiple stress, CHR in rats. Pre-treatment with aqueous extract of HS significantly attenuated reactive oxygen species (ROS) production, protein oxidation, and lipid peroxidation and also showed role in maintaining antioxidant status as similar to control rats. Since protein oxidation was decreased by pre-treatment of HS, protein homeostasis was also sustained by regulation of heat shock proteins (HSP70 and HSP60). Interestingly, heme oxygenase-1 (HO-1), Vascular Endothelial Growth Factor (VEGF), and nitric oxide (NO) level was also increased in HS pre-treated rats depicted its adaptogenic activity against multiple stress, CHR. Conclusively, aqueous extract of HS could use an adaptogen for high altitude-associated multiple stress (CHR).