The role of apoptosis in muscle remodeling

Apoptosis has been implicated in mediating the process of muscle loss during muscle disuse and with aging. However, the physiologic role of apoptosis in muscle remodeling is largely unknown. The purposes of this dissertation were to examine the role of apoptosis in different muscle remodeling conditions including muscle denervation, hindlimb suspension, muscle unloading following overload, endurance treadmill training, and muscle overload in mice, rats, or quails. Apoptotic signaling components and cellular stress markers including Bax, Bcl-2, Apaf-1, cytochrome c, caspases, Smac/DIABLO, XIAP, ARC, FLIP, AIF, p53, Id2, p21, c-Myc, PARP, HSP70, HSP27, HSP60, MnSOD, CuZnSOD, catalase, H2O2, MDA/4-HAE, nitrotyrosine or 8-OHdG were assessed. The incidence of apoptosis, activation of the pro-apoptotic signaling, and elevation of oxidative stress were generally evident in the skeletal muscles following denervation, hindlimb suspension, and unloading following overload in mice, rats, or quails. Moreover, p53 and Id2 were responsive to muscle unloading or overload in a subcellular compartmentalized manner. Furthermore, anti-apoptotic alterations were found in the muscles following endurance training or muscle overloading. These findings are consistent with the hypotheses that apoptosis has a role in regulating muscle loss and exercise training is able to alter the apoptotic signaling in skeletal muscle

The Novel Perspectives of Adipokines on Brain Health

First seen as a fat-storage tissue, the adipose tissue is considered as a critical player in the endocrine system. Precisely, adipose tissue can produce an array of bioactive factors, including cytokines, lipids, and extracellular vesicles, which target various systemic organ systems to regulate metabolism, homeostasis, and immune response. The global effects of adipokines on metabolic events are well defined, but their impacts on brain function and pathology remain poorly defined. Receptors of adipokines are widely expressed in the brain. Mounting evidence has shown that leptin and adiponectin can cross the blood–brain barrier, while evidence for newly identified adipokines is limited. Significantly, adipocyte secretion is liable to nutritional and metabolic states, where defective circuitry, impaired neuroplasticity, and elevated neuroinflammation are symptomatic. Essentially, neurotrophic and anti-inflammatory properties of adipokines underlie their neuroprotective roles in neurodegenerative diseases. Besides, adipocyte-secreted lipids in the bloodstream can act endocrine on the distant organs. In this article, we have reviewed five adipokines (leptin, adiponectin, chemerin, apelin, visfatin) and two lipokines (palmitoleic acid and lysophosphatidic acid) on their roles involving in eating behavior, neurotrophic and neuroprotective factors in the brain. Understanding and regulating these adipokines can lead to novel therapeutic strategies to counteract metabolic associated eating disorders and neurodegenerative diseases, thus promote brain health

Does Exercise Regulate Autophagy in Humans? A Systematic Review and Meta-Analysis

Background Macroautophagy/autophagy is an essential recycling process that is involved in a wide range of biological functions as well as in diseases. The regulation of autophagy by exercise and the associated health benefits have been revealed by rodent studies over the past decade, but the evidence from human studies remains inconclusive. Methods The MEDLINE, Embase, Cochrane, Scopus, and Web of Science databases were systematically searched from inception until September 2022. Human studies that explored potential effects of physical exercise on autophagy at the protein level were selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A random-effects model was used for the meta-analysis. Results Twenty-six studies were included in the meta-analysis. Subgroup analyses revealed that an acute bout of resistance exercise attenuated autophagy, as characterized by lower levels of microtubule-associated proteins 1A/1B light chain 3B (LC3-II) and higher levels of sequestosome 1 (SQSTM1). In contrast, the long-term resistance exercise elevated autophagy, as shown by higher levels of LC3-II and lower levels of SQSTM1. No significant changes in LC3-II levels were observed with moderate- or vigorous-intensity endurance exercise either as an acute bout or long-term. In terms of tissue types, exercise exerted opposite effects between skeletal muscles and peripheral blood mononuclear cells (PBMCs), whereby autophagy was suppressed in skeletal muscles when activated in the PBMCs. Other meta-analyses have also shown significant alterations in the level of many canonical autophagic and mitophagic proteins, including unc-51 like autophagy activating kinase (ULK1)S317, ULK1S757, Beclin-1, ATG12, BCL2/adenovirus E1B 19 kDa protein-interacting protein 3, and PARKIN following exercise, suggesting the activation of canonical autophagy and mitophagy, although the scope of those analyses was more limited. Conclusion Our findings demonstrate that physical exercise probably regulates autophagy in an exercise modality- and tissue-dependent manner in humans, although further investigation is needed. Customized exercise prescriptions should be aimed for when implementing exercise to regulate autophagy in humans. Abbreviations: ATG: autophagy-related gene; BCL2L13: BCL2-like 13; BECN1: beclin1; BNIP3: BCL2/adenovirus E1B 19 kDa protein-interacting protein 3; GABARAP: gamma-aminobutyric acid receptor-associated protein; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; LAMP2: lysosome-associated membrane protein 2; LC3B: microtubule-associated proteins 1A/1B light chain 3B; MD: mean difference; mTOR: mammalian target of rapamycin; PBMC: peripheral blood mononuclear cells; PINK1: PTEN-induced kinase 1; PRISMA: preferred reporting items for systematic review and meta-analysis; SD: standard deviation; SQSTM1: sequestosome 1; ULK1: unc-51 like autophagy activating kinase 1; VDAC1: voltage-dependent anion-selective channel 1

Muscle mass, structural and functional investigations of senescence-accelerated mouse P8 (SAMP8)

©2015 Japanese Association for Laboratory Animal Science. Sarcopenia is an age-related systemic syndrome with progressive deterioration in skeletal muscle functions and loss in mass. Although the senescence-accelerated mouse P8 (SAMP8) was reported valid for muscular ageing research, there was no report on the details such as sarcopenia onset time. Therefore, this study was to investigate the change of muscle mass, structure and functions during the development of sarcopenia. Besides the average life span, muscle mass, structural and functional measurements were also studied. Male SAMP8 animals were examined at month 6, 7, 8, 9, and 10, in which the right gastrocnemius was isolated and tested for ex vivo contractile properties and fatigability while the contralateral one was harvested for muscle fiber cross-sectional area (FCSA) and typing assessments. Results showed that the peak of muscle mass appeared at month 7 and the onset of contractility decline was observed from month 8. Compared with month 8, mo st of the functional parameters at month 10 decreased significantly. Structurally, muscle fiber type IIA made up the largest proportion of the gastrocnemius, and the fiber size was found to peak at month8. Based on the altered muscle mass, structural and functional outcomes, it was concluded that the onset of sarcopenia in SAMP8 animals was at month 8. SAMP8 animals at month 8 should be at pre-sarcopenia stage while month 10 at sarcopenia stage. It is confirmed that SAMP8 mouse can be used in sarcopenia research with established time line in this study.Link_to_subscribed_fulltex

Current and future molecular diagnostics in non-small-cell lung cancer

© 2015 Informa UK, Ltd.. The molecular investigation of lung cancer has opened up an advanced area for the diagnosis and therapeutic management of lung cancer patients. Gene alterations in cancer initiation and progression provide not only information on molecular changes in lung cancer but also opportunities in advanced therapeutic regime by personalized targeted therapy. EGFR mutations and ALK rearrangement are important predictive biomarkers for the efficiency of tyrosine kinase inhibitor treatment in lung cancer patients. Moreover, epigenetic aberration and microRNA dysregulation are recent advances in the early detection and monitoring of lung cancer. Although a wide range of molecular tests are available, standardization and validation of assay protocols are essential for the quality of the test outcome. In this review, current and new advancements of molecular biomarkers for non-small-cell lung cancer will be discussed. Recommendations on future development of molecular diagnostic services will also be explored.Link_to_subscribed_fulltex