Search

Purpose The number of persons living with post–coronavirus disease 2019 (COVID-19) conditions or long COVID continues to rise worldwide; however, the etiology and the treatment of long COVID remain nebulous. Therefore, efficient, feasible, and cost-effective therapeutic strategies for a large population with long COVID remain warranted. Physical exercise–based rehabilitation is a promising strategy for long COVID, although its therapeutic effects remain to be determined. This systematic review and meta-analysis aimed to examine the effects of physical exercise–based rehabilitation on long COVID. Methods The electronic databases Medline, Embase, Global Health (Ovid), CINAHL (EBSCO), Web of Science, WHO Global Research Database on COVID-19, LitCovid, and Google Scholar were searched from their inception to November 2022. The identified articles were independently screened by three reviewers, and a random-effects model was used to determine the mean differences in the meta-analysis. Results Twenty-three studies involving 1579 individuals who had COVID-19 (752 women) were included. Physical exercise–based rehabilitation showed beneficial effects on long COVID-related symptoms characterized by dyspnea, fatigue, and depression, as well as on the 6-min walk test, forced expiratory volume in 1 s/forced vital capacity, and quality of life in people who had COVID-19. Conclusions Physical exercise–based rehabilitation is a potential therapeutic strategy against long COVID and can be applied as a routine clinical practice in people who have recovered from COVID-19. However, customized physical exercise–based rehabilitation programs and their effects on specific types of long COVID require future large-scale studies.

Despite the well-described discrepancy between ATG (macroautophagy/autophagy-related) genes in the regulation of hematopoiesis, varying essentiality of core ATG proteins in vertebrate definitive hematopoiesis remains largely unclear. Here, we employed zebrafish (Danio rerio) to compare the functions of six core atg genes, including atg13, becn1 (beclin1), atg9a, atg2a, atg5, and atg3, in vertebrate definitive hematopoiesis via clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 ribonucleoprotein and morpholino targeting. Zebrafish with various atg mutations showed autophagic deficiency and presented partially consistent hematopoietic abnormalities during early development. All six atg mutations led to a declined number of spi1b+ (Spi-1 proto-oncogene b) myeloid progenitor cells. However, only becn1 mutation resulted in the expansion of myb+ (v-myb avian myeloblastosis viral oncogene homolog) hematopoietic stem and progenitor cells (HSPCs) and transiently increased coro1a+ (coronin, actin binding protein, 1A) leukocytes, whereas atg3 mutation decreased the number of HSPCs and leukocytes. Proteomic analysis of caudal hematopoietic tissue identified sin3aa (SIN3 transcription regulator family member Aa) as a potential modulator of atg13- and becn1-regulated definitive hematopoiesis. Disruption of sin3aa rescued the expansion of HSPCs and leukocytes in becn1 mutants and exacerbated the decrease of HSPCs in atg13 mutants. Double mutations were also performed to examine alternative functions of various atg genes in definitive hematopoiesis. Notably, becn1 mutation failed to induce HSPCs expansion with one of the other five atg mutations. These findings demonstrated the distinct roles of atg genes and their interplays in zebrafish definitive hematopoiesis, thereby suggesting that the vertebrate definitive hematopoiesis is regulated in an atg gene-dependent manner.

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 data-bases were systematically searched from inception until September 2022. Human studies that explored potential effects of physical exercise on autop-hagy 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 pro-teins 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 signifi-cant 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 autop-hagy activating kinase (ULK1)S317, ULK1S757, Beclin-1, ATG12, BCL2/adeno-virus 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

Despite well-known systemic immune reactions in peripheral trauma, little is known about their roles in posttraumatic neurological disorders, such as anxiety, sickness, and cognitive impairment. Leukocyte invasion of the brain, a common denominator of systemic inflammation, is involved in neurological disorders that occur in peripheral inflammatory diseases, whereas the influences of peripheral leukocytes on the brain after peripheral trauma remain largely unclear. In this study, we found that leukocytes, largely macrophages, transiently invaded the brain of zebrafish larvae after peripheral trauma through vasculature-independent migration, which was a part of the systemic inflammation and was mediated by interleukin-1b (il1b). Notably, myeloid cells in the brain that consist of microglia and invading macrophages were implicated in posttraumatic anxiety-like behaviors, such as hyperactivity (restlessness) and thigmotaxis (avoidance), while a reduction in systemic inflammation or myeloid cells can rescue these behaviors. In addition, invading leukocytes together with microglia were found to be responsible for the clearance of apoptotic cells in the brain; however, they also removed the nonapoptotic cells, which suggested that phagocytes have dual roles in the brain after peripheral trauma. More importantly, a category of conserved proteins between zebrafish and humans or rodents that has been featured in systemic inflammation and neurological disorders was determined in the zebrafish brain after peripheral trauma, which supported that zebrafish is a translational model of posttraumatic neurological disorders. These findings depicted leukocyte invasion of the brain during systemic inflammation after peripheral trauma and its influences on the brain through il1b-dependent mechanisms. © 2022, The Author(s).

Despite the well-known senolytic effects of physical exercise on immune cells in older adults, the effect of physical activity (PA) on premature immune senescence in sedentary adults with obesity remains largely unknown. This pilot study aimed to investigate the role of objectively measured physical behaviors and Fitbit watch-based free-living PA intervention in premature senescence of immune cells in sedentary adults with obesity. Forty-five participants were recruited in the cross-sectional analysis, and forty of them further participated in the randomized controlled trial. We found that objectively measured moderate–vigorous PA was independently and inversely correlated with the expression of p16INK4a and p21Cip1 in the peripheral blood mononuclear cell (PBMCs) of adults with obesity; however, chronological age, body mass index, body fat, maximal oxygen consumption, light PA, sedentary behaviors, and sleep duration were not. More importantly, the 12-week PA intervention mitigated the elevated p16INK4a levels in PBMCs, though it showed no effect on p21Cip1 and senescence-associated secretory phenotypes. Taken together, physical inactivity is an independent determinant of premature senescence in immune cells, while the 12-week PA intervention is a promising strategy to alleviate premature immune senescence in adults with obesity. © 2022 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

1-phenyl 2-thiourea (PTU) is a Tyr (tyrosinase) inhibitor that is extensively used to block pigmentation and improve optical transparency in zebrafish (Danio rerio) embryo. Here, we reported a previously undescribed effect of PTU on macroautophagy/autophagy in zebrafish embryos. Upon 0.003% PTU treatment, aberrant autophagosome and autolysosome formation, accumulation of lysosomes, and elevated autophagic flux were observed in various tissues and organs of zebrafish embryos, such as skin, brain, and muscle. Similar to PTU treatment, autophagic activation and lysosomal accumulation were also observed in the somatic tyr mutant zebrafish embryos, which suggest that Tyr inhibition may contribute to PTU-induced autophagic activation. Furthermore, we demonstrated that autophagy contributes to pigmentation inhibition, but is not essential to the PTU-induced pigmentation inhibition. With the involvement of autophagy in a wide range of physiological and pathological processes and the routine use of PTU in zebrafish research of autophagy-related processes, these observations raise a novel concern in autophagy-related studies using PTU-treated zebrafish embryos. Abbreviations: 3-MA: 3-methyladenine; Atg: autophagy-related; BSA: bovine serum albumin; CHT: caudal hematopoietic tissue; CQ: chloroquine; GFP: green fluorescent protein; hpf: hour-post-fertilization; Map1lc3/Lc3: microtubule-associated protein 1 light chain 3; NGS: normal goat serum; PtdIns3K: class III phosphatidylinositol 3-kinase; PTU: 1-phenyl 2-thiourea; RFP: red fluorescent protein; Sqstm1: sequestosome 1; tyr: tyrosinase. © 2020 Informa UK Limited, trading as Taylor & Francis Group.

Cellular senescence, a state of irreversible growth arrest triggered by various stressors, engages in a category of pathological processes, whereby senescent cells accumulate in mitotic tissues. Senolytics as novel medicine against aging and various diseases through the elimination of senescent cells has emerged rapidly in recent years. Exercise is a potent anti-aging and anti-chronic disease medicine, which has shown the capacity to lower the markers of cellular senescence over the past decade. However, whether exercise is a senolytic medicine for aging and various diseases remains unclear. Here, we have conducted a systematic review of the published literature studying the senolytic effects of exercise or physical activity on senescent cells under various states in both human and animal models. Exercise can reduce the markers of senescent cells in healthy humans, while it lowered the markers of senescent cells in obese but not healthy animals. The discrepancy between human and animal studies may be due to the relatively small volume of research and the variations in markers of senescent cells, types of cells/tissues, and health conditions. These findings suggest that exercise has senolytic properties under certain conditions, which warrant further investigations. © 2020 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

BACKGROUND: Increasing lines of evidence demonstrate that systemic immune responses triggered by either sterile or infectious inflammation can activate neuroimmune responses, resulting in developing Alzheimer’s pathology, such as phosphorylation of tau protein. Systemic inflammation can be a risk factor for developing cognitive dysfunctions and even Alzheimer’s disease. We have been using a laboratory murine model, laparotomy, to demonstrate that systemic immune responses stimulate production of cytokines and activation of microglia in the brain. However, it is still unclear how systemic monocytes/macrophages responses after sterile inflammation. As zebrafish embryo has transparent body that suitable for imaging monocytes/macrophages, we aim to use zebrafish and tail amputation for investigating which factor can affect the influence of systemic inflammation in the brain. METHOD: Zebrafish was used as experimental model. Tg(coro1a:DsRed) transgenic fish was used to monitor microglia and macrophages. Tg(mpx:mCherry) was used for monitoring neutrophils, Tg(mepg1:GFP) was used for monitoring macrophages. We have used TALEN method to make knockout or mutation of IL-1b in zebrafish. Quantitative PCR and immunohistochemical staining were used for examination. Acridine orange and TUNEL were employed for labeling apoptotic cells. Tail amputation was performed at day 3 of embryos under anesthetization with tricaine. RESULT: Tail amputation recruited accumulation of monocytes/macrophages into the wound site in zebrafish tail. Surprisingly, increased number of macrophages and microglia were also found in the brain, which was tissue specific as no other organs showed similar phenomenon. Expression of mRNA for different cytokines was examined in the brain. Among which, IL-1b was significantly increased. Therefore, we prepared IL-1b knockout and mutated zebrafish. After amputation, the number of macrophages in the brain did not show any significant increase. To further understand