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This study assessed changes in blood muscle damage indicators and DNA damage indicators in lymph and urine after 8 weeks of high-intensity intermittent running and weight training in male and female college students majoring in skiing. This study aimed to find an effective training method by investigating differences in the effectiveness between men and women. A total of 20 male and female ski major college students conducted short-term high-intensity intermittent running and weight training in the morning and afternoon, respectively, 3 days a week for 8 weeks for 24 times in total. After 8 weeks of high-intensity intermittent running and weight training, changes in DNA damage indicators in the lymph and urine and muscle damage indicators in the blood were analyzed. The creatine kinase level significantly differed at rest pre-graded exercise testing (GXT) and 60 min of recovery post-GXT after training from that before training between the male and female groups. Although lactate dehydrogenase (LDH) levels decreased in both groups over time, no significant differences in LDH were found between the two groups. Second, DNA 8-hydroxydeoxyguanosine (8-OHdG) in the lymph was significantly different between the two groups at rest pre-GXT and 60 min of recovery post-GXT. 8-OHdG in the urine was significantly lower in the female group only at 60 min of recovery post-GXT. Partial sex differences were found in the reduction of muscle damage and DNA damage after 8 weeks of high-intensity intermittent running and weight training.

Introduction: The changes in brain structure caused by a sports-related concussion may initially be indistinguishable, however, the irreversible deleterious effects are noted in the long term. An early diagnosis may provide the patient with a better recovery chance and increased survival. For this purpose, this paper studies the feasibility of a diagnosis for concussion by microRNA (mi-RNA) biomarkers contained in the saliva of athletes. Objective: Verify whether salivary miRNAs could be considered good biomarkers for sports concussion. Methodology: Salivary mi-RNA levels were determined from 120 saliva samples of 120 players. There were 43 with a diagnosis of concussion and 77 without a diagnosis of concussion. Samples from players with a concussion were collected 30 minutes prior to activity, samples from individuals who did not engage in physical activity were also compared. Results: On the evaluation of 30 miRNA from individuals with a concussion between contact and non-contact sports there was high detection reliability(P

Introduction: Hyperglycemia is the principal characteristic component of type 2 diabetes. High blood glucose concentrations for long periods can be countered with postprandial exercise by increasing glucose retention involuntary muscles. However, no research is present on the relationship between exercise time and glucose levels. Objective: This study evaluates the relationship between sports activity and postprandial glycemia levels. Methodology: Forty-five individuals were included in the study, 10 males and 35 females with an age of 27.11±2.8 years; a body fat percentage of 25.02% ±5.04%; and a body mass index of 22.74±4.55 kg/m2. Participants were included via WhatsApp for daily information on postprandial activity levels. WhatsApp messages were forwarded to a total of 2,500 people at different colleges and universities. Out of the total 60 active people (2.40%) who responded, 45 individuals participated in the study. They were divided into three categories based on self-reported postprandial activity: not very active (15), quite active (15), highly active (15). All active individuals completed an oral glucose intake test with blood samples obtained for evaluation at 15, 30, 45, 60, 90, and 120 minutes post-rest. On a gender basis, the groups could not be associated (P =.057). Results: All active groups showed a remarkable effect on blood glucose level at one hour (P =.031). A mean increase in blood glucose level in the first hour of 1.50 mmol/L was observed for every extra 1.0 mmol/L of standard glycemic amount, on average, women had a higher blood glucose amount of 1.35 mmol/L than men. Conclusion: It can be concluded that a high amount of postprandial activity generates a good outcome on glycemic parameters. Evidence Level II; Therapeutic Studies – Investigating the results. RESUMO Introdução: A hiperglicemia é o principal componente característico na diabetes tipo 2. Altas concentrações de glicose por longos períodos podem ser combatidas com o exercício pós-prandial, aumentando a retenção de glicose nos músculos voluntários. Porém, ainda não há estudos sobre a relação entre o tempo de exercício e os níveis de glicose. Objetivo: Este estudo tem como objetivo avaliar a relação entre a atividade esportiva e os dados temporais de glicemia pós-prandial. Metodologia: Foram incluídos 45 indivíduos no estudo, sendo 10 do sexo masculino e 35 do sexo feminino com idade de 27,11± 2,8 anos; percentual de gordura corporal de 25,02% ±5,04%; e índice de massa corporal de 22,74±4,55 kg/m2. Os participantes foram incluídos via WhatsApp para obter informações diárias sobre os níveis de atividade pós-prandial. As mensagens de WhatsApp foram encaminhadas para um total de 2.500 pessoas em diferentes faculdades e universidades. No total de 60 pessoas ativas (2,40%) que responderam, participaram do estudo 45 indivíduos. Eles foram divididos em três categorias com base na atividade pós-prandial autorrelatada: pouco ativos (15), bastante ativos (15), altamente ativos (15). Todos os indivíduos ativos finalizaram um teste de ingestão de glicose oral com amostras de sangue obtidas para avaliação em 15, 30, 45, 60, 90 e 120 minutos pós-repouso. Na base de gênero, os grupos não puderam ser associados (P =.057). Resultados: Todos os grupos ativos revelaram um efeito notável do nível de glicose no sangue em uma hora (P =.031). Foi observado um aumento médio no nível de glicemia na primeira hora de 1,50 mmol/L para cada 1,0 mmol/L extra de quantidade glicêmica padrão, em média, as mulheres tiveram uma quantidade glicêmica no sangue de 1,35 mmol/L superior aos homens. Conclusão: Conclui-se que a alta quantidade de atividade pós-prandial gera um bom desfecho nos parâmetros glicêmicos. Nível de evidência II; Estudos Terapêuticos - Investigação de Resultados. RESUMEN Introducción: La hiperglucemia es el principal componente característico de la diabetes de tipo 2. Las concentraciones elevadas de glucosa durante largos periodos pueden combatirse con el ejercicio postprandial, aumentando la retención de glucosa en los músculos voluntarios. Sin embargo, todavía no hay estudios sobre la relación entre el tiempo de ejercicio y los niveles de glucosa. Objetivo: Este estudio pretende evaluar la relación entre la actividad deportiva y los datos de glicemia postprandial. Metodología: Se incluyeron 45 individuos en el estudio, siendo 10 hombres y 35 mujeres con una edad de 27,11±2,8 años; un porcentaje de grasa corporal de 25,02% ±5,04%; y un índice de masa corporal de 22,74±4,55 kg/m2. Se inscribió a los participantes a través de WhatsApp para obtener información diaria sobre los niveles de actividad postprandial. Se enviaron mensajes de WhatsApp a un total de 2.500 personas de diferentes colegios y universidades. Del total de 60 personas activas (2,40%) que respondieron, 45 individuos participaron en el estudio. Fueron divididos en tres categorías basadas en la actividad postprandial auto declarada: poco activos (15), bastante activos (15), muy activos (15). Todos los individuos activos completaron una prueba de ingesta de glucosa oral con muestras de sangre obtenidas para su evaluación a los 15, 30, 45, 60, 90 y 120 minutos después del reposo. En lo que respecta al género, los grupos no pudieron asociarse (P = 0,057). Resultados: Todos los grupos activos revelaron un efecto notable del nivel de glucosa en la sangre a una hora (P = 0,031). Se observó un aumento medio del nivel de glucosa en la sangre en la primera hora de 1,50 mmol/L por cada 1,0 mmol/L adicional de la cantidad de glucemia estándar; por término medio, las mujeres tuvieron una cantidad de glucosa en la sangre más alta de 1,35 mmol/L que los hombres. Conclusión: Se concluye que la elevada actividad postprandial genera un buen resultado en los parámetros glucémicos. Nivel de evidencia II; Estudios terapéuticos - Investigación de resultados.

Secreted phosphoprotein 1 (SPP1) is involved in immune regulation, cell survival, and tumor progression. Studies have demonstrated that SPP1 plays an important role in certain individual tumors. However, the expression profile and oncogenic features of SPP1 in diverse cancers are remaining unknown. Therefore, we performed a comprehensive analysis using The Cancer Genome Atlas (TCGA) database. Raw data of 33 cancer types were download from the University of California Santa Cruz (UCSC) Xena website. The expression of SPP1 and its relationship with tumor prognosis, immune invasion, tumor microenvironment, and immunotherapy were analyzed using the R language. The function analysis was conducted using Gene Set Enrichment Analysis (GSEA). The oncogenic features of SPP1 was validated by wound-healing assay and EdU staining assay. SPP1 highly expressed in most cancers. The expression of SPP1 was significant related to prognosis, tumor mutation burden (TMB), microsatellite instability (MSI), and immune checkpoint genes, suggested that SPP1 plays an essential role in the tumor immune microenvironment and immune cell infiltration. The immune/stromal scores correlated positively with the SPP1 expression, and the relationship was affected by tumor heterogeneity and immunotherapy. In addition, SPP1 could predict the response of tumor immunotherapy. Functional analysis revealed the SPP1-associated terms and pathways. Finally, SPP1 significantly elevated cell proliferation and migration in A549, Huh7, HT-29, A2780 tumor cell lines. In conclusion, this study indicated that SPP1 involved in tumorigenesis, tumor progression, and regulated tumor immune microenvironment, revealing SPP1 might be a potential target for evaluating prognosis and immunotherapy in multiple cancers.

Irritable bowel syndrome (IBS) is a common functional bowel disorder characterized with visceral hypersensitivity. Previous studies indicated gut microbiota alteration associated short-chain fatty acids (SCFAs) dysregulation is associated with IBS development. The aim of the study is to explore the potential role of microbiota dysbiosis mediated visceral hypersensitivity in postinfectious-IBS (PI-IBS) mouse model.Four-week-old NIH mice were randomly allocated into four groups: control mice, PI-IBS mice, PI-IBS mice co-housing with normal mice, and PI-IBS mice were administrated with a cocktail of antibiotics. Trichinella spiralis infection established PI-IBS mouse model. Microbiota in cecal contents and feces were analyzed by 16S rDNA sequencing. SCFAs were detected by gas chromatography. 5-hydroxytryptamine (5-HT) was evaluated by ELISA, and N-methyl-D-aspartate receptors (NMDARs) were examined by western blot. Visceral sensitivity was determined by abdominal withdrawal reflex in response to colorectal distention.Increased SCFAs were observed in cecal contents and feces in PI-IBS mice accompanied with higher 5-HT and NMDAR subunits expressions in ileum and colon. Visceral hypersensitivity was observed in PI-IBS mice compared to control mice. When administrated with antibiotics cocktails and co-housing with normal mice, PI-IBS mice showed decreased SCFAs, 5-HT, NMDAR subunits expressions, and improved visceral hypersensitivity.Gut microbiota alteration induced increased SCFAs, 5-HT and NMDAR subunits expressions were associated with visceral hypersensitivity in PI-IBS mice. The critical role of gut microbiota in improving visceral hypersensitivity was further identified by treatment of antibiotics cocktail and co-housing.

Autoimmune hepatitis is an interface hepatitis characterized by the progressive destruction of the liver parenchyma, the cause of which is still obscure. Interleukin (IL)-17A is a major driver of autoimmunity, which can be produced by innate immune cells against several intracellular pathogens. Here, we investigated the involvement of IL-17A in a mice model of immune-mediated hepatitis with the intestine exposed to Salmonella typhimurium. Our results showed more severe Concanavalin (Con) A-induced liver injury and gut microbiome dysbiosis when the mice were treated with a gavage of S. typhimurium. Then, the natural killer (NK) T cells were overactivated by the accumulated IL-17A in the liver in the Con A and S. typhimurium administration group. IL-17A could activate NKT cells by inducing CD178 expression via IL-4/STAT6 signaling. Furthermore, via the portal tract, the laminae propria mucosal-associated invariant T (MAIT)-cell-derived IL-17A could be the original driver of NKT cell overactivation in intragastric administration of S. typhimurium and Con A injection. In IL-17A-deficient mice, Con A-induced liver injury and NKT cell activation were alleviated. However, when AAV-sh-mIL-17a was used to specifically knock down IL-17A in liver, it seemed that hepatic IL-17a knock down did not significantly influence the liver injury. Our results suggested that, under Con A-induction, laminae propria MAIT-derived IL-17A activated hepatic NKT, and this axis could be a therapeutic target in autoimmune liver disease.

Slow colon transit and visceral hypersensitivity are recognized as major pathophysiological mechanisms in irritable bowel syndrome with constipation (IBS-C). However, there is a lack of therapies targeting both abdominal pain and colonic motility. This study was designed to investigate the long-term effects and possible mechanisms of transcutaneous electrical acustimulation (TEA) in patients with IBS-C.Fifty-two patients with IBS-C were randomized into 2 groups: daily TEA for 4 weeks (n = 26) and daily sham-TEA for 4 weeks (n = 26). The number of complete spontaneous bowel movements per week (CSBMs/week, primary outcome), Irritable Bowel Syndrome Severity Scoring System, Patient Assessment of Constipation Quality of Life, visual analog scale (VAS) pain score, colonic transit time, and anorectal physiology were evaluated before treatment and at the end of the treatment. Colonic transit was assessed with radiopaque markers. Electrocardiograms were recorded for assessing autonomic functions.(i) TEA improved constipation and abdominal pain. After the treatment, the number of CSBMs/week during the last week in the TEA group was higher than that in the sham-TEA group (3.5 ± 1.6 vs 2.3 ± 0.6, P = 0.002). Similar effects were also noted in the visual analog scale pain score ( P = 0.002) and Irritable Bowel Syndrome Severity Scoring System score ( P = 0.025). In addition, there was a significant improvement in the quality of life of patients with constipation. The Patient Assessment of Constipation Quality of Life total score was significantly decreased in the TEA group ( P = 0.004). (ii) Compared with sham-TEA, TEA improved colon transit ( P = 0.002) and increased the threshold of rectal sensation (desire to defecate, P = 0.004; maximum tolerability, Plt; 0.001). (iii) TEA increased vagal activity, compared with sham-TEA ( Plt; 0.05); at the end of the treatment, the vagal activity was significantly correlated with colon transit and the CSBMs/week.TEA improves constipation and symptoms of IBS by accelerating colon transit and reducing rectal sensation, possibly mediated by using the autonomic mechanisms.

Background: Long non-coding RNAs (lncRNAs) are emerging as important regulators in the modulation of virus infection by targeting mRNA transcription. However, their roles in chronic hepatitis B (CHB) remain to be elucidated. Objective: The study aimed to explore the lncRNAs and mRNA expression profiles in CHB and asymptomatic HBsAg carriers (ASC) and construct mRNA-lncRNA co-expression profile and ceRNA networks to identify the potential targets of diagnosis and treatment in CHB. Methods: We determined the expression profiles of lncRNAs and mRNAs in CHB and ASC using microarray analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore their function. We also constructed coexpression, cis-regulatory, and competing endogenous RNA (ceRNA) networks with bioinformatics methods. Results: We identified 1634 mRNAs and 5550 lncRNAs that were differentially expressed between CHB and ASC. Significantly enriched GO terms and pathways were identified, many of which were linked to immune processes and inflammatory responses. Co-expression analysis showed 1196 relationships between the top 20 up/downregulated lncRNAs and mRNA, especially 213 lncRNAs interacted with ZFP57. The ZFP57-specific ceRNA network covered 3 lncRNAs, 5 miRNAs, and 17 edges. Cis-correlation analysis showed that lncRNA T039096 was paired with the most differentially expressed gene, ZFP57. Moreover, by expending the clinical samples size, the qRT-PCR results showed that the expression of ZFP57 and T039096 increased in CHB compared to ASC. Conclusion: Our study provides insights into the roles of mRNA and lncRNA networks in CHB, highlighting potential applications of lncRNA-T039096 and mRNA-ZFP57 for diagnosis and treatment.

BackgroundChronic liver fibrosis is an inevitable stage for the development of patients with chronic hepatitis B (CHB). However, anti-fibrotic therapies have been unsuccessful so far. The biological functions and molecular mechanisms of long non-coding RNAs (lncRNAs) in the host immune system during chronic hepatitis B virus (HBV) infection, especially in fibrosis, are still largely unknown.MethodThe total RNA of peripheral blood mononuclear cells (PBMCs) from asymptomatic carriers (ASCs) or CHB receiving at least 8 years of anti-viral treatments was analyzed using Arraystar microarray and validated via quantitative real-time PCR (qRT-PCR). Correlation analysis was conducted based on correlation coefficients, Clusterprofile, and RNA Interactome Database (RAID). The functions of lncRNA in monocytes were determined via loss-of-function RNAi or gain-of-function lentivirus assays. The expression levels of mRNAs or proteins were evaluated using qRT-PCR, western blotting assay, or enzyme linked immunosorbent assays (ELISA).ResultsA total of 1,042 mRNA transcripts (630 up-regulated and 412 down-regulated) were identified being differentially expressed between ASC and CHB patients. Through enrichment analysis we focused on the transforming growth factor beta (TGF-β) signaling pathway and validated their expression in a larger cohort. Moreover, we found that lncRNA ENST00000519726 (lncRNA-HEIM) was highly expressed in monocytes and further up-regulated upon HBV infection. LncRNA-HEIM played an important role in CHB patients with long-term antiviral treatments, and its elevated expression was remarkably correlated with the TGF-β signaling pathway, especially with the two members namely TGF-β and SMAD4. Furthermore, altering the endogenous lncRNA-HEIM level in monocytes significantly affected the production of TGF-β, as well as the fibrosis of hepatic stellate cells by affecting the expression of collagen I and α-smooth muscle actin (α-SMA).ConclusionThese findings not only added knowledge to the understanding of the roles of which lncRNA-HEIM played in the activation of HSCs in CHB patients with long-term medication, but also provided a promising therapeutic target in the future treatment for liver fibrosis.

BackgroundThere are multiple promising treatment strategies for central nervous system trauma and disease. However, to develop clinically potent and safe treatments, models of human-specific conditions are needed to complement in vitro and in vivo animal model-based studies.MethodsWe established human brain stem and spinal cord (cross- and longitudinal sections) organotypic cultures (hOCs) from first trimester tissues after informed consent by donor and ethical approval by the Regional Human Ethics Committee, Stockholm (lately referred to as Swedish Ethical Review Authority), and The National Board of Health and Welfare, Sweden. We evaluated the stability of hOCs with a semi-quantitative hOC score, immunohistochemistry, flow cytometry, Ca2+signaling, and electrophysiological analysis. We also applied experimental allogeneic human neural cell therapy after injury in the ex vivo spinal cord slices.ResultsThe spinal cord hOCs presented relatively stable features during 7–21 days in vitro (DIV) (except a slightly increased cell proliferation and activated glial response). After contusion injury performed at 7 DIV, a significant reduction of the hOC score, increase of the activated caspase-3+cell population, and activated microglial populations at 14 days postinjury compared to sham controls were observed. Such elevation in the activated caspase-3+population and activated microglial population was not observed after allogeneic human neural cell therapy.ConclusionsWe conclude that human spinal cord slice cultures have potential for future structural and functional studies of human spinal cord development, injury, and treatment strategies.

The purpose of this study was to investigate the effects of continuous and intermittent running on the aerobic capacity and body composition of male college students. In this study 20 male college students attending G-city University without medical history were selected as subjects. These subjects were randomly assigned to continuous exercise group (n=10) and intermittent exercise group (n=10). The exercise program was performed at 50 minutes per day for 10 weeks, 3 times a week and at 50-80% of the maximum heart rate. The maximum oxygen uptake, oxygen uptake at anaerobic threshold, cardiac output, ventilation, and duration of exercise were measured as the aerobic capacity. Also, body composition, body fat percentage, waist to hip ratio, body fat mass, were measured and analyzed. Based on the results of the study, the following results were obtained. First, there was a significant difference (p

Dendritic cells (DCs), a bridge for innate and adaptive immune responses, play a key role in the development of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Administration of tolerogenic DCs has been used as an immunotherapy in autoimmune diseases. Deficiency of vitamin D is an environmental risk factor of MS. In this study, we induced tolerogenic DCs by 1,25-dihydroxyvitamin D3 and transferred the tolerogenic DCs (VD3 -DCs) into EAE mice by adoptive transfer. We found that VD3 -DCs inhibited the infiltrations of T helper type 1 (Th1) and Th17 cells into spinal cord and increased the proportions of regulatory T cells (CD4+ CD25+ Foxp3+ ), CD4+ IL-10+ T cells and regulatory B cells (CD19+ CD5+ CD1d+ ) in peripheral immune organs, which resulted in attenuated EAE. However, the proportions of T helper type 1 (Th1) and Th17 cells in spleen and lymph nodes and the levels of pro-inflammatory cytokines and IgG in serum also increased after transfer of VD3 -DCs. We conclude that transfer of VD3 -DCs suppressed EAE by increasing proportions of regulatory T cells, CD4+ IL-10+ T cells and regulatory B cells in spleen and reducing infiltration of Th1 and Th17 cells into spinal cord, which suggests a possible immunotherapy method using VD3 -DCs in MS.

Additional file 2 : Supplementary Table 1. Antibodies used in immunohistochemistry. Supplementary Table 2: Antibodies used in flow cytometry. Information of the antibodies used in immunohistochemistry and flow cytometry.

The growth hormone (GH) replacement therapy in adult growth hormone deficiency (AGHD) is now well developed, nevertheless, the safety of GH replacement, especially the incidence of cancer in these patients remains to be further clarified. To summarize the evidence on the safety of using GH in AGHD, we conduct this meta-analysis to assess the relationship between the risk of cancer and GH replacement therapy. Randomized controlled trials and cohort studies involved in GH therapy for AGHD were selected. Meta-analysis was performed and risk ratio (RR) was pooled with 95% confidence interval (CI) to investigate the relationship between GH replacement and the risk of cancer. The result indicated that there was no evidence to draw a conclusion that GH replacement therapy will increase the risk of cancer (P = 0.001, RR = 0.77, 95% CI [0.65, 0.90]). Meanwhile, according to the calculated analysis, the replacement therapy might even reduce the risk of cancer. Furthermore, subgroup analysis demonstrated that there was no correlation between replacement therapy of GH and the risk of cancer both in prospective and retrospective cohort design research, and in prospective group, the risk of cancer even decreased (P = 0.0002, RR = 0.71, 95%CI [0.59, 0.85]). In conclusion, our study corroborates evidence from previous studies showing that GH replacement therapy in AGHD patients would not increase the risk of cancer; instead, it might be even decrease cancer risk. The results suggested that GH replacement therapy in AGHD patients was safe.

Additional file 3: Table S2. Analysis of clinical features of ccA and ccB in C 6 subgroup.

Follicular helper CD4+T (TFH) cells play a fundamental role in humoral immunity deriving from their ability to provide help for germinal center (GC) formation, B cell differentiation into plasma cells and memory cells, and antibody production in secondary lymphoid tissues. TFH cells can be identified by a combination of markers, including the chemokine receptor CXCR5, costimulatory molecules ICOS and PD-1, transcription repressor Bcl-6, and cytokine IL-21. It is difficult and impossible to get access to secondary lymphoid tissues in humans, so studies are usually performed with human peripheral blood samples as circulating counterparts of tissue TFH cells. A balance of TFH cell generation and function is critical for protective antibody response, whereas overactivation of TFH cells or overexpression of TFH-associated molecules may result in autoimmune diseases. Emerging data have shown that TFH cells and TFH-associated molecules may be involved in the pathogenesis of neuroautoimmune diseases including multiple sclerosis (MS), neuromyelitis optica (NMO)/neuromyelitis optica spectrum disorders (NMOSD), and myasthenia gravis (MG). This review summarizes the features of TFH cells, including their development, function, and roles as well as TFH-associated molecules in neuroautoimmune diseases and their animal models.