Effects of exercise interventions on cancer-related fatigue in breast cancer patients: an overview of systematic reviews.

OBJECTIVE: This overview of systematic reviews aims to critically appraise and consolidate evidence from current systematic reviews (SRs)/meta-analyses on the effects of exercise interventions on cancer-related fatigue (CRF) in breast cancer patients. METHODS: SRs/meta-analyses that explored the effects of exercise interventions on CRF in breast cancer patients compared with the routine methods of treatment and care were retrieved from nine databases. The methodological quality of the included SRs was appraised using A MeaSurement Tool to Assess systematic Reviews II (AMSTAR II). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to calculate the grading of outcomes in the included SRs. The exercise type, frequency, duration, and inclusion/absence of supervision were further evaluated with subgroup analyses. The Stata 16.0 software was utilized for data analysis. RESULTS: Twenty-nine reviews were included. The overall methodological quality and level of evidence of the included reviews were unsatisfactory, with only three reviews rated as high methodological quality and no review identified as high-quality evidence. Moderate certainty evidence indicated that exercise could improve fatigue in breast cancer patients (SMD = - 0.40 [95%CI - 0.58, - 0.22]; P = 0.0001). Subgroup analysis based on the types of exercise showed that yoga (SMD = - 0.30 [95%CI - 0.56, - 0.05]; I2 = 28.7%) and aerobic exercise (SMD = - 0.29 [95%CI - 0.56, - 0.02]; I2 = 16%) had a significantly better effect on CRF in breast cancer patients; exercising for over 6 months (SMD = - 0.88 [95%CI - 1.59, - 0.17]; I2 = 42.7%; P = 0.0001), three times per week (SMD = - 0.77 [95%CI - 1.04, - 0.05]; I2 = 0%; P = 0.0001), and for 30 to 60 min per session (SMD = - 0.81 [95%CI - 1.15, - 0.47]; I2 = 42.3%; P = 0.0001) can contribute to a moderate improvement of CRF. Supervised exercise (SMD = - 0.48 [95%CI - 0.77, - 0.18]; I2 = 87%; P = 0.001) was shown to relieve CRF. CONCLUSION: Exercise played a favorable role in alleviating CRF in breast cancer. Yoga was recommended as a promising exercise modality for CRF management in the majority of the included studies. Exercising for at least three times per week with 30 to 60 min per session could be recommended as a suitable dosage for achieving improvement in CRF. Supervised exercise was found to be more effective in alleviating CRF than unsupervised exercise. More rigorously designed clinical studies are needed to specify the exact exercise type, duration, frequency, and intensity to have an optimal effect on CRF in breast cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: CRD42020219866.

Increased number and activation of peripheral basophils in adult-onset minimal change disease.

Nowadays, the pathogenesis of minimal change disease (MCD) is still not well-known, and the current understanding on MCD is mainly based on data derived from children, and very few adults. Here, we comprehensively analysed the correlation between the changes of peripheral basophils and the incidence rate and relapse of adult-onset MCD. The results showed that in patients at the onset of MCD, the ratio and activation of basophils were all higher than those of healthy controls (all P < .05). In vitro test results showed that basophils from healthy controls can be activated by the serum taken from patients with MCD. Among 62 patients at the onset of MCD, with complete remission after treatment and 1 year of follow-up, the relative and absolute basophil counts before treatment were higher in the long-term remission group (n = 33) than that of the relapse group (n = 29). The basophil counts were significantly higher in the infrequent relapse group (n = 13) than that of the frequent relapse group (n = 16; P < .05). These findings suggested that basophil may play a pathogenic role in adult-onset MCD, and the increased number and activation of peripheral basophils could predict recurrence in adult MCD.

Podocytes are likely the therapeutic target of IgA nephropathy with isolated hematuria: Evidence from repeat renal biopsy.

Background: The present study aimed to prove the progression of immunoglobulin A nephropathy (IgAN) patients with isolated hematuria based on repeat renal biopsy data for the first time. Methods: 29 IgAN patients with isolated hematuria who received repeat renal biopsies were analyzed retrospectively, while 29 non-isolated hematuria IgAN patients with similar age and background were randomly selected as the control group. Clinical parameters were collected at the time of biopsy. The treatment strategies (conservative treatment with RASS blocker or immunosuppressive treatment) were choosen according to the pathological results at the first renal biopsy. The activity and chronicity indexes of renal lesions were evaluated. Markers of cell inflammation and proliferation were tseted by immunochemistry. The ultrastructure of podocytes was observed by transmission electron microscopy (TEM). Podocyte and oxidative stress marker (NPHS2 and 4-HNE) were detected by immunofluorescence. Results: The IgAN patients with isolated hematuria had better clinical indicators than those with no-isolated hematuria, such as better renal function, higher albumin and lower uric acid. The interval between two biopsies in IgAN patients with isolated hematuria was 630 (interquartile range, 409.5-1,171) days. The hematuria of the patients decreased significantly from 30 (IQR, 4.00-35.00) RBC/ul in the first biopsy to 11 (IQR, 2.50-30.00) RBC/ul in the repeated biopsy (p < 0.05). The level of triglyceride decreased significantly (p < 0.05). The other clinical indicators were not statistically significant (p > 0.05). Deposits of IgA and C3 in the glomerulus were persistent. The activity index decreased, especially cellular crescent formation, while the chronicity index increased. The ultrastructure of podocytes was improved after treatment. The oxidative stress products of podocytes reduced after treatment. Conclusion: Although the clinical indicators of the IgAN patients with isolated hematuria were in the normal range, various acute and chronic pathological changes have occurred, and irreversible chronic changes have been progressing. Cell inflammation and proliferation persisted. Oxidative stress of podocytes was likely to be the therapeutic target. This study provided a strong basis for the progress of IgAN with isolated hematuria through pathological changes before and after treatment. This study will help clinicians recognize the harm of hematuria, change the traditional treatment concept, and help such patients get early treatment.

Revisited Cyclophosphamide in the Treatment of Lupus Nephritis.

Lupus nephritis (LN) is the most common serious complication of systemic lupus erythematosus (SLE). The pathogenesis of LN is complex, and the majority causes of LN are the renal deposition of circulating or/and in situ-formed immune complexes. These immune complexes trigger glomerular and tubulointerstitial inflammation, which finally leads to proteinuria and loss of renal function. Despite the emergence of new biological agents, cyclophosphamide (CY), an alkylating agent, is still the first-line drug widely used to treat patients with severe LN. In this review, we outline the application history, molecular structure, and pharmacokinetics of CY in the treatment of LN. We also detail its latest known immunopharmacological mechanisms, with a focus on supplemental regulation and inhibition of CD4 and CD8 positive T cells, differences in the use of various guidelines, and the combination with other drugs. The side effects of CY are also mentioned in this review.

[Effect of bone morphogenetic protein-7 on aristolochic acid induced renal tubular epithelial cells transdifferentiation].

OBJECTIVE: To observe the effect of bone morphogenetic protein-7 (BMP-7) on aristolchic acid induced renal tubular epithelial cell trans-differentiation to look for new therapeutic approach for aristolchic acid nephropathy (AAN). METHODS: In vitro cultured human proximal renal tubular epithelial cell line HK-2 cells were treated with different concentrations of BMP-7 (75 ng/mL, 150 ng/mL and 300 ng/mL) after trans-differentiation of the cells was induced by AA (10 microg/mL). Levels of alpha-SMA mRNA and protein expressions were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blotting respectively. RESULTS: BMP-7 reversed the AA inducing alpha-SMA expressions in HK-2 cells in a dose-dependent manner. CONCLUSION: BMP-7 can inhibit the trans-differentiation of human renal tubular epithelial cell induced by AA, thereby might be a new potential drug for AAN prevention and treatment.

IgA nephropathy patients with partial crescent formation benefit from immunosuppressants: evidence from repeat renal biopsy.

BACKGROUND: Crescent formation is a serious pathological change in the IgA nephropathy (IgAN) which is believed to be primarily mediated by a mixture of parietal epithelial cells, macrophages, and myofibroblasts. It was recommended that IgAN patients with rapid renal hypofunction with a crescent body >50% should begin treatment with corticosteroids combined with cyclophosphamide. However, for patients with partial crescent formation, whether immunosuppressive therapy is necessary is a contested topic. MATERIALS AND METHODS: Data from IgAN patients with partial crescent formation who underwent repeat renal biopsy were retrospectively analyzed. RESULTS: From the first to the second renal biopsy, the mean hemoglobin level and albumin level increased significantly (P < 0.05), and uric acid and triglyceride levels decreased significantly (P < 0.05). Also, the 24-hour urinary protein excretion decreased significantly (P < 0.001), but no differences in blood pressure, creatinine level, or estimated glomerular filtration rate. For pathological indices, there were no differences in fluorescence intensity of IgA or C3 deposition (P > 0.05), but the mesangial cell proliferation decreased significantly (P < 0.05), and the proportions of global glomerulosclerosis and tubulointerstitial fibrosis increased significantly (P < 0.05, respectively). In addition, a decreased tendency in the proportion of crescent formation was observed in the second renal biopsy. CONCLUSIONS: Immunosuppressive therapy for IgAN patients with partial crescent formation can reduce proteinuria, stabilize renal function, improve anemia, and mitigate acute kidney injury in the short term.

Updated advances of linking psychosocial factors and sex hormones with systemic lupus erythematosus susceptibility and development.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that primarily affects women, especially those of reproductive age. Genetics, environment, and gene-environment interactions play key roles in the development of SLE. Despite the numerous susceptibility genes of SLE identified to date, gene therapy is far from a clinical reality. Thus, more attention should be paid to the risk factors and underlying mechanisms of SLE. Currently, it is reported that psychosocial factors and sex hormones play vital roles in patients with SLE, which still need further investigated. The purpose of this review is to update the roles and mechanisms of psychosocial factors and sex hormones in the susceptibility and development of SLE. Based on review articles and reports in reputable peer-reviewed journals and government websites, this paper summarized psychosocial factors (e.g., alexithymia, depression, anxiety, negative emotions, and perceived stress) and sex hormones (e.g., estrogens, progesterone, androgens, and prolactin) involved in SLE. We further explore the mechanisms linking these factors with SLE susceptibility and development, which can guide the establishment of practical measures to benefit SLE patients and offer new ideas for therapeutic strategies.

Cross-regulation between exosomal and autophagic pathways: promising therapy targets in disease.

Exosomes are vesicles secreted by a variety of cell types. They can release their cargo into the extracellular environment or transfer their contents to other cells, as a form of intercellular communication. Therefore, exosomes are vital to both physiological and pathological functions. Autophagy is a process of intracellular degradation of unnecessary or dysfunctional cellular components such as damaged organelles and misfolded proteins. It is initiated by various environmental stressors and mediated by lysosomes. Under physiological conditions, autophagy exists in cells at basal levels to support cellular metabolism and help maintain self-homeostasis. In other circumstances, autophagy can contribute to the initiation and progression of disease. Recent studies have revealed that exosomal and autophagic pathways can be regulated by each other and play important roles in health and disease. However, the cross-regulation between these pathways is highly intricate, and the effects on exosomal trafficking and autophagy are environment-dependent. Here, we summarize the recent advances in understanding the cross-regulation between the exosomal and autophagic pathways, and their involvement in multiple diseases, which can help develop novel strategies for their prevention and treatment. From the evidence summarized in this review, we conclude: 1) exosomal trafficking plays a beneficial or harmful role in disease through the regulation of autophagy; 2) autophagy is vital in disease by regulating the generation of exosomes; and 3) the cross-regulation between exosomal and autophagic pathways may be promising targets for disease prevention and treatment, while this needs to be clarified in future investigations.

Current mechanistic insights into the role of infection in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by inflammation and abnormal production of autoantibody, but the mechanisms of the aberrant immune responses are currently unknown. Recently, growing evidence has suggested that infection plays a pivotal role in SLE. Here, we investigate the role of infectious agents (e.g., Epstein-Barr virus, parvovirus B19, human T-lymphotropic virus type 1, human immunodeficiency virus type 1, and endogenous retroviruses) in the pathogenesis of SLE. More importantly, we explore the known mechanisms underlying the involvement of infectious agents in the pathogenesis of SLE, including molecular mimicry, epitope spreading, superantigen production, bystander activation, persistent viral infection, altered apoptosis, clearance deficiency, and epigenetic alterations (e.g., DNA methylation and microRNAs). However, some infectious agents (e.g., malaria parasites, hepatitis B virus, Toxoplasma gondii, and Helicobacter pylori) may exert protective effects on SLE. Therefore, the relationship between infection and SLE is multifaceted and multidirectional, including causative and/or protective associations, which warrant further investigation in the future.

Asiatic acid protects against cisplatin-induced acute kidney injury via anti-apoptosis and anti-inflammation.

Cisplatin is a well-known chemotherapeutic drug applied for the treatment of numerous human cancers. However, the use of cisplatin in clinic is limited by certain serious side effects, such as nephrotoxicity. Unfortunately, there is currently no effective therapeutic approach to prevent cisplatin-induced AKI. Increasing evidence suggests that apoptosis of tubular epithelial cells and renal inflammation mainly determine the progression and outcome of cisplatin-induced AKI. Asiatic acid (AA) has been reported have the functions of anti-inflammation and anti-apoptosis, etc. But the effects of AA on kidney injury induced by cisplatin are still not known. The current study aimed to determine the potential renoprotective effects of AA on kidney injury induced by cisplatin. Twenty-four C57BL/6 male mice were randomly divided into four groups: normal control (CON), cisplatin-induced AKI (CIS), AKI with 50 mg/kg AA pretreatment (CIS + AA50), and AKI with 100 mg/kg AA pretreatment (CIS + AA100). Mice were anesthetized and sacrificed at 72 h after the cisplatin injection. Blood and kidney samples were collected for analyses. Compared with CON mice, cisplatin-treated mice exhibited severe tubular necrosis and elevated serum creatinine level. However, AA pretreatment (50 mg/kg or 100 mg/kg) markedly suppressed the elevated serum creatinine, blood urea nitrogen and histological changes. Moreover, AA pretreatment notably downregulated tubular expression of kidney injury molecule-1 (KIM-1) and the number of apoptotic cells, and upregulated the expression of the apoptosis inhibitor survivin and promoted tubular proliferation as evidenced by an increase in the number of proliferating cell nuclear antigen-positive cells. In addition, AA suppressed the enhanced mRNA expression of proinflammatory cytokines IL-1ß, TNF-α, MCP-1 and caspase-1 in the kidneys. Furthermore, AA pretreatment inhibited NF-κB activation and the inflammatory response, which may result from Smad7 up-regulation. In conclusion, AA protects against cisplatin-induced AKI via anti-apoptosis and anti-inflammation.

Continuation of immunosuppressive treatment may be necessary in IgA nephropathy patients with remission of proteinuria: Evaluation by repeat renal biopsy.

The present study aimed to evaluate the effects of an individualized, low-dose multi-drug immunosuppressive regimen for the treatment of immunoglobulin A nephropathy (IgAN). A preliminary investigation of the course of IgAN following immunosuppressive treatment was conducted based on repeat renal biopsies. Clinical and pathological data of 17 patients with IgAN who received repeat renal biopsies were analyzed retrospectively. In addition to basic treatment, 16 patients regularly received an individualized low-dose immunosuppressive regimen according to their clinical manifestations and pathological patterns following the first biopsy. Clinical parameters, including 24-h urinary protein excretion and levels of serum albumin, uric acid and total cholesterol were collected. Glomerular deposits of IgA and C3, as well as the activity and chronicity indexes of renal lesions were evaluated by semi-quantitative methods. The 24-h urinary protein excretion of the patients decreased significantly from the first biopsy (2.53±2.17 g/day) to the repeated biopsy (0.26±0.55 g/day) (P<0.001). Deposits of IgA and C3 in the glomerulus were persistent, but were reduced in quantity at the second biopsy. Although active renal lesions were observed in the majority of patients, the activity index decreased significantly from 3.18±1.33 prior to therapy to 2.47±0.80 following therapy (P<0.05), while the chronicity index did not change significantly (2.59±2.00 versus 2.76±1.89, respectively). The individualized, low-dose multi-drug immunosuppressive regimen used in the present study significantly minimized proteinuria, stabilized renal function and alleviated histological lesions in patients with IgAN without causing overt adverse effects during the short-term follow-up. In addition to proteinuria, renal pathological changes should be appraised when considering the withdrawal of immunosuppressants from IgAN treatment.

[Evaluation of the relationship between IL-18 levels in urine and parameters of renal pathological changes in patients with lupus nephritis].

AIM: To evaluate the relationship between IL-18 levels in urine and parameters of renal pathological changes in patients with lupus nephritis (LN). METHODS: IL-18 levels in morning free urine and 24-hour's urine in 19 normal persons and 55 patients with LN were measured by ELISA. The correlation between IL-18 levels and parameters of renal pathological changes, namely activity index (AI) and chronicity index (CI), were analyzed by liner correlation analysis method. RESULTS: IL-18 levels in morning free urine and 24-hour's urine in LN group were elevated significantly compared with control group. In both groups IL-18 levels in morning free urine were (247.1+/-317.5) ng/L and (20.3+/-14.5) ng/L, respectively, P<0.001; those in 24-hour's urine were (192.1+/-170.1) ng/d and (21.0+/-3.8) ng/d, respectively, (P<0.001). There was close positive correlation between IL-18 levels in morning free urine and 24-hour's urine and LN patient's AI (for morning free urine: r=0.602, P<0.001; for 24-hour's urine: r=0.461, P<0.005) but there was no correlation between IL-18 levels in morning urine and 24-hour's urine and CI (P>0.05). Patients with LN were divided into three groups (high, moderate and low) according to AI value. There was distinct difference of IL-18 levels in urine among the three groups: IL-18 levels in morning urine were (69.2+/-82.7) ng/L, (193.5+/-106.1) ng/L and (580.7+/-453.1) ng/L, respectively, (P<0.001); those in 24-hour's urine were (103.5+/-141.4) ng/d, (188.8+/-124.0) ng/d and (333.1+/-183.2) ng/d, respectively. CONCLUSION: It is very simple and convenient to detect IL-18 levels in morning free urine, so it is a good method for evaluating renal pathological activity of LN.