The efficacy of exercise training for improving body composition in patients with breast cancer: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: To evaluate the efficacy of exercise in improving body composition in patients with breast cancer; the effects of exercise on weight and BMI were evaluated as secondary outcomes. DATA SOURCES: Cochrane Library, EMBASE, PubMed and Web of Science were searched for randomized controlled trials published in English from database inception to 29 November 2023. METHODS: The effects of exercise on body composition in patients with breast cancer were explored. After separately extracting the data, two reviewers assessed the overall quality of the evidence as well as the methodological quality of the included studies. RESULTS: Fourteen studies with 1241 participants were included, of which 12 studies were eligible for meta-analysis. Exercise significantly reduced body fat (mean difference [MD], -0.33; 95% CI, -0.37 to -0.29; P < 0.00001) and increased lean mass (MD, 0.42; 95% CI, 0.34 to 0.49; P < 0.00001) in patients with breast cancer. Further, exercise intervention was associated with increased BMI of patients with breast cancer (MD, 0.03; 95% CI, 0.01 to 0.06; P = 0.01), while no significant difference in weight was detected between the exercise and the non-exercise groups. Subgroup analysis results showed that only resistance exercise reduced fat mass (MD, -0.22; 95% CI, -0.27 to -0.16; P < 0.00001). CONCLUSIONS: Exercise effectively improves body composition in patients with breast cancer. Clinicians should encourage patients to engage in exercise and develop optimized exercise prescriptions.

Regulation of cholesterol homeostasis in osteoporosis mechanisms and therapeutics.

Osteoporosis is a metabolic bone disease that affects hundreds of millions of people worldwide and is characterized by excessive loss of bone protein and mineral content. The incidence and mortality of osteoporosis increase with age, creating a significant medical and economic burden globally. The importance of cholesterol levels has been reported in the development of diseases including osteoporosis. It is important to note that key enzymes and molecules involved in cholesterol homeostasis are closely related to bone formation. Excessive cholesterol may cause osteoporosis, cholesterol and its metabolites affect bone homeostasis by regulating the proliferation and stimulation of osteoblasts and osteoclasts. Therefore, antagonism of elevated cholesterol levels may be a potential strategy to prevent osteoporosis. There is sufficient evidence to support the use of bisphosphonates and statin drugs for osteoporosis in the clinic. Therefore, in view of the aggravation of the aging problem, we summarize the intracellular mechanism of cholesterol homeostasis and its relationship with osteoporosis (including cholesterol and cholesterol oxidation products (COPs) in osteoporosis). Furthermore, the current clinical cholesterol-lowering drugs for osteoporosis were also summarized, as are new and promising therapies (cell-based therapies (e.g., stem cells) and biomaterial-delivered target drug therapies for osteoporosis as well).

[Corrigendum] Incremental load training improves renal fibrosis by regulating the TGF­ß1/TAK1/MKK3/p38MAPK signaling pathway and inducing the activation of autophagy in aged mice.

Following the publication of the above article, an interested reader drew to the authors' attention that, for the immunofluorescence staining experiments shown in Fig. 3A on p. 1681, the 'E­cadherin / YC' and 'E­cadherin / OC' data panels were overlapping, such that they may have been derived from the same original source; moreover, with the transmission electron microscopic images shown in Fig. 6G on p. 1683, the 'OC' and 'OY' panels were similarly overlapping. After having re­examined their figures, the authors have realized that the data shown for the 'E­cadherin / YC' experiment in Fig. 3A and the 'OC' experiment in Fig. 6G were selected incorrectly. The authors were able, however, to identify the correct data for both of these figures, and the revised versions of Figs. 3 and 6 are shown on the next page. Note that the errors made during the assembly of these figures did not affect the overall conclusions reported in the paper. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this. They also apologize to the readership for any inconvenience caused. [International Journal of Molecular Medicine 44: 1677­1686, 2019; DOI: 10.3892/ijmm.2019.4344].

Evaluation of the effect of physical therapy on pain and dysfunction of knee osteoarthritis based on fNIRS: a randomized controlled trial protocol.

BACKGROUND: Knee osteoarthritis (KOA) is a chronic musculoskeletal disease that can cause joint pain and dysfunction, affecting the quality of life of patients. Nonsurgical treatment is the conventional treatment of KOA, among which physical therapy is widely used because of its simplicity, convenience and effectiveness. The functional biomarker will add to the clinical fidelity and diagnostic accuracy. Therefore, our study chose a more objective evaluation indicator, functional near-infrared spectroscopy (fNIRS), to identify between healthy people and KOA patients, and to detect the pain change before and after treatment of KOA patients. METHODS: The study will be conducted in the Rehabilitation Medical Center of West China Hospital of Sichuan University and divided into 2 stages. In the first stage, we will compare and determine the differences in baseline data between healthy volunteers and KOA patients. In the second stage, 72 KOA patients will be randomly divided into two groups: the drug therapy group (DT) and the combination therapy group (CT) for 10 treatments. Outcome measures will be measured at baseline and on the 5th and 10th days after the intervention, including the numerical rating scale (NRS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), pain catastrophizing scale (PCS), the association of pain severity with task-state functional connectivity fNIRS and association of pain severity with task-activated fNIRS. DISCUSSION: By analyzing the fNIRS data of healthy volunteers and KOA patients, our study will be determined whether fNIRS can be used as a new indicator to reflect the severity of pain in KOA patients. Subsequently, the same fNIRS data for KOA patients before and after the intervention will be collected to provide an accurate evaluation criterion for the effect of physical therapy on KOA. TRIAL REGISTRATION: The study was registered on the Chinese Registry website (registered in ChiCTR.org with the identifiers ChiCTR2200064175 and 29/09/2022).

Roles of IL-11 in the regulation of bone metabolism.

Bone metabolism is the basis for maintaining the normal physiological state of bone, and imbalance of bone metabolism can lead to a series of metabolic bone diseases. As a member of the IL-6 family, IL-11 acts primarily through the classical signaling pathway IL-11/Receptors, IL-11 (IL-11R)/Glycoprotein 130 (gp130). The regulatory role of IL-11 in bone metabolism has been found earlier, but mainly focuses on the effects on osteogenesis and osteoclasis. In recent years, more studies have focused on IL-11's roles and related mechanisms in different bone metabolism activities. IL-11 regulates osteoblasts, osteoclasts, BM stromal cells, adipose tissue-derived mesenchymal stem cells, and chondrocytes. It's involved in bone homeostasis, including osteogenesis, osteolysis, bone marrow (BM) hematopoiesis, BM adipogenesis, and bone metastasis. This review exams IL-11's role in pathology and bone tissue, the cytokines and pathways that regulate IL-11 expression, and the feedback regulations of these pathways.

HK2: a potential regulator of osteoarthritis via glycolytic and non-glycolytic pathways.

Osteoarthritis (OA) is an age-related chronic degenerative joint disease where the main characteristics include progressive degeneration of cartilage, varying degrees of synovitis, and periarticular osteogenesis. However, the underlying factors involved in OA pathogenesis remain elusive which has resulted in poor clinical treatment effect. Recently, glucose metabolism changes provide a new perspective on the pathogenesis of OA. Under the stimulation of external environment, the metabolic pathway of chondrocytes tends to change from oxidative phosphorylation (OXPHOS) to aerobic glycolysis. Previous studies have demonstrated that glycolysis of synovial tissue is increased in OA. The hexokinase (HK) is the first rate limiting enzyme in aerobic glycolysis, participating and catalyzing the main pathway of glucose utilization. An isoform of HKs, HK2 is considered to be a key regulator of glucose metabolism, promotes the transformation of glycolysis from OXPHOS to aerobic glycolysis. Moreover, the expression level of HK2 in OA synovial tissue (FLS) was higher than that in control group, which indicated the potential therapeutic effect of HK2 in OA. However, there is no summary to help us understand the potential therapeutic role of glucose metabolism in OA. Therefore, this review focuses on the properties of HK2 and existing research concerning HK2 and OA. We also highlight the potential role and mechanism of HK2 in OA. Video abstract.

The role and therapeutic potential of MSC-derived exosomes in osteoarthritis.

Osteoarthritis (OA) is the most common painful disease with chronic articular cartilage degeneration. The pathological process of OA is complex and characterized by the imbalance between the synthesis and catabolism of chondrocytes and extracellular matrix, leading to the progressive destruction of articular cartilage damage. Because of the self-renewal and differentiation of mesenchymal stem cells (MSCs), various exogenous MSC-based cell therapies have been developed to treat OA. Moreover, the efficacy of MSC- based therapy is mainly attributed to the paracrine of cytokines, growth factors, and exosomes. Exosomes derived from MSCs can deliver various DNAs, RNAs, proteins and lipids, thus promoting MSCs migration and cartilage repair. Therefore, MSC-derived exosomes are considered as a promising alternative therapy for OA. In this review, we summarized properties of MSC-derived exosomes and the new role of MSC-derived exosomes in the treatment of OA. We also proposed possible perspectives of MSC-derived exosomes as cell-free regenerative reagents in the treatment of OA.

Aerobic exercise training decreases cognitive impairment caused by demyelination by regulating ROCK signaling pathway in aging mice.

Recent studies have discovered a strong link between physical exercise and the prevention of neuro-degenerative symptoms, especially in elderly subjects, nonetheless, the exact underlying mechanism remains unclear. In this study, we hypothesized that aerobic exercise training may have a protective effect on myelin sheath in aged mice by regulating the ROCK signal pathway, which is considered as a crucial mechanism for decreasing apoptosis and promoting regeneration. Briefly, C57/BL aged mice underwent an exercise training (5 days/week, lasting 6 weeks). Memory and cognitive impairment were examined using Novel object recognition (NOR) test and Morris water maze test (MWM). Demyelination was explored using Luxol fast blue staining and transmission electron microscopy in the corpus callosum (CC), and the expression of ROCK and apoptotic protein were analyzed via western blot. We demonstrated the impairment of memory and cognitive and the decrease of myelin sheath thickness in aged mice. In addition, severe demyelination was observed in aged mice, accompanied with increased expression of RhoA, ROCK, ATF3, and Caspase 3, and reduced expression of MBP, Olig2, and NG2. Aerobic exercise training improved behavioral functions, increased the expression of MBP and myelin sheath thickness, reduced apoptosis and promoted myelination. To sum up, our data indicate that aerobic exercise training protects demyelination from aging-related white matter injury, which is associated with the up-regulation of ROCK signal pathway.

Inhibition of RhoA/ROCK Pathway in the Early Stage of Hypoxia Ameliorates Depression in Mice via Protecting Myelin Sheath.

Neuroplasticity and connectivity in the central nervous system (CNS) are easily damaged after hypoxia. Long-term exposure to an anoxic environment can lead to neuropsychiatric symptoms and increases the likelihood of depression. Demyelination is an important lesion of CNS injury that may occur in depression. Previous studies have found that the RhoA/ROCK pathway is upregulated in neuropsychiatric disorders such as multiple sclerosis, stroke, and neurodegenerative diseases. Therefore, the chief aim of this study is to explore the regulatory role of the RhoA/ROCK pathway in the development of depression after hypoxia by behavioral tests, Western blotting, immunostaining as well as electron microscopy. Results showed that HIF-1α, S100ß, RhoA/ROCK, and immobility time in FST were increased, sucrose water preference ratio in SPT was decreased, and the aberrant activity of neurocyte and demyelination occurred after hypoxia. After the administration of Y-27632 and fluoxetine in hypoxia, these alterations were improved. Lingo1, a negative regulatory factor, was also overexpressed after hypoxia and its expression was decreased when the pathway blocked. However, fluoxetine had no effect on the expression of Lingo1. Then, we demonstrated that demyelination was associated with failures of oligodendrocyte precursor cell proliferation and differentiation and increased apoptosis of oligodendrocytes. Collectively, our data indicate that the RhoA/ROCK pathway plays a vital role in the initial depression during hypoxia. Blocking this pathway in the early stage of hypoxia can enhance the effectiveness of antidepressants, rescue myelin damage, and reduce the expression of the negative regulatory protein of myelination. The findings provide new insight into the prophylaxis and treatment of depression.

Aerobic Endurance Exercise Ameliorates Renal Vascular Sclerosis in Aged Mice by Regulating PI3K/AKT/mTOR Signaling Pathway.

Renal vascular sclerosis caused by aging plays an important role in the occurrence and development of chronic kidney disease. Clinical studies have confirmed that endurance exercise is able to delay the aging of skeletal muscle and brain tissue. However, to date, few studies have assessed whether endurance exercise is able to improve the occurrence of renal vascular sclerosis caused by natural aging and its related mechanisms. In this study, we investigated the protective effect of aerobic endurance exercise on renal vascular sclerosis in aged mice and its effect on the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. The results suggested that aerobic endurance exercise preserved kidney morphology and renal function. Glomerular basement membrane thickness was evidently increased, podocyte foot processes were effaced in aged mice, and aerobic endurance exercise significantly ameliorated the overall lesion range. The protein expression of vascular endothelial growth factor (VEGF) and JG12 was lower in the senile control group (OC group). The protein expression of VEGF and JG12 was significantly increased after aerobic endurance exercise. Furthermore, aerobic endurance exercise resulted in downregulation of Bax, Caspase 3, IL-6, and senescent cells and upregulation of Bcl-2. The upregulation of PI3K and its downstream signal molecules AKT and mTOR after aerobic endurance exercise was further observed. Our observations indicated that aerobic endurance exercise may inhibit renal vascular sclerosis in aged mice by regulating the PI3K/AKT/mTOR signaling pathway.

Incremental load training improves renal fibrosis by regulating the TGF­ß1/TAK1/MKK3/p38MAPK signaling pathway and inducing the activation of autophagy in aged mice.

Recent studies have confirmed that kidney tissue fibrosis is closely linked to the natural aging of organs. One of its major characteristics is the reduction of autophagic activity. However, to date, few studies have assessed whether incremental load training is able to improve the occurrence of renal fibrosis caused by natural aging and the underlying mechanisms. In the present study involving male C57/BL mice, an elderly exercise group (OY group) was subjected to progressive load­increasing rotary­bar training (5 days/week, lasting for 6 weeks), with an elderly control group (OC group) and a young control group (YC group) used as controls. Renal fibrosis and autophagy­associated indicators were assessed by Masson's staining, reverse transcription­quantitative PCR analysis, western blotting, immunofluorescence and transmission electron microscopy. The results suggested that collagen deposition in the basal part of the renal tubular epithelium and glomeruli in the OY group was significantly lower than that in the OC group. In the OC group, the protein expression levels of E­cadherin, Beclin 1 and light chain 3 were significantly decreased, and increases in α­smooth muscle actin­positive signals were observed in the glomerular matrix and renal capsule wall. Furthermore, the expression of transforming growth factor (TGF)­ß1 and its downstream signaling molecules TGF­ß­activated kinase 1 (TAK1), mitogen­activated protein kinase (MAPK) kinase (MKK3) and p38MAPK were downregulated following training. The present study confirmed that incremental load training may improve renal fibrosis in aged mice by regulating the TGF­ß1/TAK1/MMK3/p38MAPK signaling pathway and inducing the activation of autophagy to reduce the synthesis of extracellular matrix and delay the epithelial­mesenchymal transition. The present study provides a novel experimental basis for the intervention of incremental load training to prevent senile renal fibrosis.