Body Weight Loss Research Articles

Antihyperglycemic potential of fermented Digitaria exilis polysaccharide partially substituted with Clendendrum volubile leaf extract

Digitaria exilis and Clendendrum volubile are underutilized food resources common in Africa. Clendendrum volubile leaf has a history of being used in traditional medicine to treat or manage hyperglycemia. Despite Clendendrum volubile nutritive and pharmaceutical significance, no scientific study has explored its application in functional food development. In this study, the inhibitory activities of Clendendrum volubile leaf extract (CVLE) against α-amylase and α-glucosidase was determined. Fermented Digitaria exilis polysaccharide (FDEP) was partially substituted with CVLE at different percentages (0.8 % and 1.2 %) and its antihyperglycemic effect was investigated in alloxan-induced diabetic rat models. Results showed that the IC50 (CVLE extract concentration causing 50 % enzyme inhibition) for α-amylase and α-glucosidase were 330 μg/mL and 120 μg/mL, respectively, compared to acarbose, a standard inhibitor of starch-digesting enzymes, which had IC50 values of 370 μg/mL and 170 μg/mL for α-amylase and α-glucosidase, respectively. The animal study showed that FDEP containing 0.8 % CVLE lowered the blood glucose level of diabetic rats by 45.31 % after 24 days. Increasing CVLE concentration in the FDEP to 1.2 % not only reduced blood glucose by 72.97 % after 24 days, comparable to metformin's 74.29 % reduction, but also alleviated body weight loss and improved liver function by lowering alanine transaminase, aspartate transaminase, and alkaline phosphatase.

Dantrolene paradoxically exacerbates short-term brain glucose hypometabolism, hippocampal damage and neuroinflammation induced by status epilepticus in the rat lithium-pilocarpine model.

Status epilepticus (SE) is a neurologic emergency characterized by prolonged or rapidly recurring seizures. Increased intracellular calcium concentration ([Ca2+]i) occurring after SE is a key mediator of excitotoxicity that contributes to the brain damage associated with the development of epilepsy. Accumulated evidence indicates that dantrolene, a ryanodine receptor (RyR) blocker may have protective effects against the SE-induced damage. We evaluated whether dantrolene (10mg/kg, i.p.) administered twice, 5min and 24h after the lithium-pilocarpine-induced SE in rats, had neuroprotective effects. Dantrolene by itself had no effects on control rats. However, it exacerbated the signs of damage in rats that underwent SE, increasing brain glucose hypometabolism as measured by PET neuroimaging 3 days after SE. Likewise, the neurohistochemical studies revealed that dantrolene aggravated signs of hippocampal neurodegeneration, neuronal death and microglia-induced neuroinflammation. Besides, the damaging effects were reflected by severe body weight loss. Overall, our results point towards a deleterious effect of dantrolene in the lithium-pilocarpine-induced SE model. Nonetheless, our results are in opposition to the reported neuroprotective effects of dantrolene. Whether the mechanisms underlying [Ca2+]i increase might significantly differ depending on the particularities of the model of epilepsy used and general experimental conditions need further studies. Besides, it is yet to be determined which isoform of RyRs significantly contributes to Ca2+-induced excitotoxicity in the lithium-pilocarpine SE rat model.

Abstract PR008: Cross-talk between metastatic cells and host systems: Neutrophil metabolic adaptation, immune profiling, and systemic metabolic shifts in tumor progression and cachexia

Abstract Oral squamous cell carcinoma (OSCC) is a prevalent type of head and neck cancer with a high mortality rate, partly due to late diagnosis often accompanied by metastasis. Cachexia, a complex syndrome marked by severe weight loss and muscle wasting, frequently accompanies advanced cancers including OSCC. Notably, 50-70% of OSCC patients exhibit cachexia at diagnosis, which persists post-treatment, hinting at a metastatic contribution to this syndrome. One significant challenge in studying cancer cachexia is the lack of well-characterized pre-clinical models that accurately reflect human disease. Traditional mouse models often involve subcutaneously transplanted cells, which fail to mimic the natural tumor-host interactions and metastatic progression seen in patients. These models do not typically exhibit metastasis and differ significantly from the genetic and molecular landscape of human cancers. To address these limitations, we developed a syngeneic mouse model by orthotopically transplanting MOC2 murine OSCC cells into the tongues of B6J mice, thereby closely mimicking the tumor microenvironment and metastatic behavior of human OSCC. By enhancing metastasis with a palm-enriched high-fat diet, we observed progressive tumor growth, metastasis, and body weight loss, independent of food intake reduction, indicating metabolic dysregulation rather than anorexia. Comprehensive analyses, including single-cell RNA sequencing (scRNAseq) of immune cells and transcriptomic and metabolomic profiling of tumor and host tissues, identified significant gene expression changes associated with metastasis and cachexia. Enhanced metastasis correlated with lipid metabolism changes in lung metastases, suggesting that metastatic cells exploit lipids for growth. Further, immune profiling revealed neutrophils' metabolic adaptation in metastasis, with implications for both tumor progression and cachexia. Targeting key metabolic and inflammatory pathways in tumor and immune cells holds potential for mitigating metastasis and cachexia. Early-stage serum metabolomics indicated systemic metabolic shifts, emphasizing the need to understand the interplay between tumor metastasis and host metabolism. These findings underscore the complex mechanisms underlying OSCC-induced cachexia, and the need for new targeted therapeutic strategies to disrupt this lethal synergy between cancer progression and metabolic deterioration of the host. Citation Format: Blanca Majem, Josefina Martin, Liudmila Shevkova, Claudia Bigas, Gloria Pascual, Salvador Aznar-Benitah. Cross-talk between metastatic cells and host systems: Neutrophil metabolic adaptation, immune profiling, and systemic metabolic shifts in tumor progression and cachexia [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr PR008.

Obesity, Metabolic Syndrome, and Obesity Paradox in Heart Failure: A Critical Evaluation.

Since the turn of the millennium, obesity has been on the rise worldwide, and particularly so throughout the United States. Even more concerning is the rate at which persons with severe obesity continue to trend upwards. Given the detrimental effects of obesity on cardiac structure and function, it is not surprising that obesity stands as one of the leading risk factors for developing heart failure (HF). This state-of-the-art article aims to review the updated literature on the obesity paradox to help further understand its relationship to body composition, weight loss, fitness, and exercise. An intriguing phenomenon appears to exist in which obesity is associated with a better prognosis in those with HF, compared to patients with lesser body mass. Recent studies suggest, however, that weight loss induced by pharmacologic strategies might be beneficial in patients with HF with preserved ejection fraction. Despite the presence of an obesity paradox, recent data suggest that obesity could be targeted in HF, however, long-term data are currently lacking. Consequently, definitive guidelines for managing obesity, and specifically the body composition of these patients, remain amiss.

Regulation of Colonic Inflammation and Macrophage Homeostasis of IFN-γ-Primed Canine AMSCs in Experimental Colitis in Mice

Mesenchymal stem cells (MSCs) have shown potential in treating immune-mediated diseases due to their immunomodulatory properties, which can be enhanced by priming with inflammatory cytokines like interferon-gamma (IFN-γ). This study evaluates the therapeutic effects of IFN-γ-primed canine adipose tissue-derived MSCs (AMSCs) in a mouse model of inflammatory bowel disease (IBD). Canine AMSCs were primed with 50 ng/mL recombinant canine IFN-γ for 48 h, and the effects were compared to those seen in naïve (unprimed) AMSCs. IBD was induced in mice using dextran sodium sulfate (DSS), and AMSCs were injected intraperitoneally on days 1 and 3. The mice treated with IFN-γ-primed AMSCs showed improved clinical outcomes, including a reduced disease activity index (DAI), less body weight loss, and longer colon length compared to the mice treated with naïve AMSCs. A histological analysis revealed less damage to the intestinal structures and reduced inflammatory cell infiltration. IFN-γ priming led to a shift in the immune cell balance in the gut, decreasing pro-inflammatory macrophages (Ly6Chi) and increasing anti-inflammatory macrophages (Ly6Clo/MHC-IIhi). This was associated with the reduced expression of inflammatory cytokine genes (Il-1β, Il-6, and Il-18) and increased expression of the intestinal stem cell marker Lgr5. These findings suggest that IFN-γ-primed AMSCs offer enhanced therapeutic potential for treating CE in veterinary medicine.

Pristimerin Alleviates DSS-Induced Colitis in Mice by Modulating Intestinal Barrier Function, Gut Microbiota Balance and Host Metabolism.

Pristimerin is a pentacyclic triterpenoid mainly derived from Celastraceae plants such as Maytenus ilicifolia, which has been traditionally used for the treatment of gastrointestinal disorders. Pharmacological studies have shown that pristimerin exhibited anti-inflammatory, antioxidant, anticancer and antibacterial activities. However, the potential mechanism of pristimerin for the treatment of ulcerative colitis (UC) remains elusive. In the present study, pristimerin could effectively inhibit the NO generation induced by LPS in RAW 264.7 cells and upregulate the decreased expression of tight junction proteins such as occludin and claudin-1. In vivo, oral administration of pristimerin (0.5 mg/kg and 1 mg/kg) could significantly relieve UC symptoms such as body weight loss, disease activity index, shortened colon length and colonic pathological damage. Meanwhile, pristimerin decreased the TNF-α, MPO and MDA levels and increased the levels of IL-10, IL-22, SOD activity, occludin and claudin-1 in colon tissues. Gut microbiota analysis of cecum contents revealed that pristimerin treatment effectively alleviated gut microbiota dysbiosis. Additionally, serum metabolomics showed that 33 potential biomarkers involving lipid and tryptophan metabolism were identified, which may account for the therapeutic effects of pristimerin on UC mice. In conclusion, our findings indicate that pristimerin attenuates UC symptoms in DSS-induced mice through modulating intestinal barrier integrity, gut microbiota composition, lipid and tryptophan metabolism.

Anti-obesity effect of irreversible MAO-B inhibitors in patients with Parkinson's disease.

We read with great interest the report on the new anti-obesity potential in mice models of reversible monoamine oxidase B inhibitors by Moonsun et al., as opposed to the lack of such effects observed with irreversible MAO-B inhibitors (iMAO-Bi). Our research aimed to explore the potential anti-obesity effects of iMAO-Bi in patients with Parkinson's disease (PD). This retrospective study included 37 PD in-patients from 2018 to 2023. Patients who took iMAO-Bi were assigned to the iMAO-Bi group, and those who never took iMAO-Bi were assigned to the control. The major outcomes were changes in body weight and body mass index (BMI) during follow-up. A subgroup analysis was conducted to compare the anti-obesity effect between the short-term and long-term administrations of the iMAO-Bi group. The results showed a slight yet insignificant trend of bodyweight loss among the iMAO-Bi group of PD patients. Subgroup analysis showed that short-term treatment of iMAO-Bi (less than six months) led to reductions in BMI and body weight, while the long-term treatment of iMAO-Bi displayed a slight increase in BMI and body weight. The results suggested that short-term administration of iMAO-Bi may have potential weight-loss effects. Further studies with larger sample sizes are needed to evaluate the weight-loss effect of iMAO-Bi.

Oral Semaglutide Use in Type2 Diabetes: A Pooled Analysis of Clinical and Patient-Reported Outcomes from Seven PIONEER REAL Prospective Real-World Studies.

Oral semaglutide is a glucagon-like peptide1 receptor agonist (GLP-1RA) approved for improving glycemic control in adults with type2 diabetes (T2D). The PIONEER REAL program evaluates clinical and patient-reported outcomes of oral semaglutide treatment as part of routine clinical practice across 13 countries. Here, data from Canada, Denmark, Italy, the Netherlands, Sweden, Switzerland, and the UK are pooled and analyzed to address treatment satisfaction as well as glycated hemoglobin (HbA1C) and body weight changes in relevant subgroup analyses. This pooled analysis encompasses seven country-specific, non-interventional, multicenter, phase4, prospective, single-arm clinical studies assessing the use of oral semaglutide in adults with T2D. Primary endpoint was the change in HbA1C from baseline to end of study (EOS), and secondary endpoints included changes in body weight and treatment satisfaction. For the analyses, results were stratified by age, T2D duration, and oral semaglutide dose at EOS as well as baseline HbA1C, body weight, and body mass index. Oral semaglutide treatment was initiated by 1615 participants. At EOS, 1222 (76%) participants out of the 1483 (92%) who completed the study were on treatment. Estimated changes in HbA1C and body weight from baseline to week38 were - 1.0%-point (95%CI - 1.08 to - 0.97; P < 0.0001) and - 5.0% (CI - 5.37 to - 4.72; P < 0.0001). Treatment satisfaction increased significantly during the study. Shorter T2D duration interacted with higher HbA1C reduction and body weight loss. Interaction was also observed between higher baseline HbA1C and more pronounced decrease in HbA1C. No significant interactions were detected between clinical outcomes and age or physician setting. The PIONEER REAL pooled analysis shows that people initiating oral semaglutide treatment experience improved glycemic control and body weight loss across age groups and T2D duration. This occurs regardless of specialist or primary care practice setting and is accompanied by an increased treatment satisfaction. NCT04559815 (Canada), NCT04537637 (Denmark), NCT05230615 (Italy), NCT04601740 (the Netherlands), NCT04601753 (Sweden), NCT04537624 (Switzerland), NCT04862923 (UK).

Effect of 3-year changes in adiposity measures on the pre-diabetes regression and progression: a community-based cohort study.

We assessed the impact of a 3-year change-percent in adiposity measures on regression and pre-diabetes (Pre-DM) progression among Iranian adults. Three-year change-percent in body weight (BW), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and visceral adiposity index (VAI) were calculated for 1458 Pre-DM subjects (mean age of 53.0 ± 13.7, 46.8% men), participated in the third examination of the Tehran Lipid and Glucose Study (2006-2008). Multinomial logistic regression models were used to estimate relative risk ratios (RRRs) of the outcomes [i.e., regression to normal glucose regulation (NGR), persistence in Pre-DM, and progression to newly diagnosed type 2 diabetes (T2D)] across 3-year change categories of adiposity measures (i.e., ≥ 5% decrease, 0-5% decrease, increase). Over nine years of follow-up, 37.7 and 39.0% returned to NGR and progressed to T2D, respectively. Decreased BW (0-5 and ≥ 5%) was associated with regression to NGR (RRRs = 1.44, 95% CIs = 1.05-1.98, and 2.64, 1.63-4.28, respectively). Decreased BMI and WC ≥ 5% were also associated with regression to NGR (RRRs = 1.63, 95% CI = 1.01-2.64; 1.69, 1.20-2.37, respectively). Changes in WHR and VAI were not associated with Pre-DM regression or progression. Pre-DM subjects with ≥ 5% BW loss had a constant FSG level overtime and a lower overall mean of FSG (116 vs. 111 and 112mg/dL, P = 0.023 and 0.009, respectively) and 2h-SG (154 vs. 165 and 168mg/dL) compared to those had 0-5% BW loss or BW gain. Short-term management of adiposity measures increases the regression probability to NGR. Targeting BW loss seems a more potent predictor of Pre-DM reversion among the adiposity measures.

BS SO10 - Predictive Factors in the Development of Dumping Syndrome After Bariatric Surgery

Abstract Background Dumping syndrome (DS) is a recognised complication of Roux En-Y Gastric Bypass (RYGB) and rarely Sleeve Gastrectomy (SG). The prevalence of DS is unclear, with current literature ranging from 10-50%. The condition is characterised by gastrointestinal and vasomotor symptoms resulting in a significant impact on quality of life. This study aimed to prospectively utilise Sigstad scoring to evaluate post-operative patients, investigating the timing of symptom onset and its correlation with pre-existing diabetes, revision surgery, and percentage of Total Body Weight Loss (TBWL). Method We used the Sigstad scoring questionnaire, administered by our bariatric Clinical Nurse Specialists (CNS) at outpatient clinics to assess patients for DS between January to May 2024. Data collected included patient demographics, surgery type and date, TBWL, Body Mass Index (BMI), and whether the patient had a diagnosis of Diabetes Mellitus type II (DMII). A diagnosis of DS was confirmed if a patients score ³7 points on the Sigstad questionnaire. We explored factors influencing the development of DS. Results In total, 64 patients were evaluated for DS of whom 86% were female and the median age was 44 years (IQR: 35-45). Most patients (67%) had undergone primary RYGB, 19% SG, 11% conversion from SG to RYGB and 70% were assessed within one year of surgery. DS symptoms emerged in 25% of patients, predominantly within the first-year post-operation (60%). The median TBWL was 12% (IQR: 9-22%), showing no correlation to DS onset. Patients with DMII exhibited a higher propensity for DS (66% vs 20%, p=0.029). Patients undergoing revisional surgery also had a higher incidence of DS (33% vs 6%, p=0.117). Conclusion A quarter of patients undergoing bariatric surgery will develop DS, most of whom within the first-year post-surgery. Revisional surgery and pre-existing DMII are the primary predictors in developing DS. There was no observed association between TBWL and DS onset. Further extensive studies are needed to confirm these observations.

A02 - BS Ethnic and Social Deprivation Influence Weight Regain Following Roux En-Y Gastric Bypass

Abstract Background Weight regain is a prevalent issue following Roux-En-Y Gastric Bypass (RYGB) surgery for obesity. This study aims to assess the impact of ethnicity and social deprivation on the likelihood of weight regain post-RYGB. Method We analysed data from Luton &amp; Dunstable Hospital. Key variables included patient demographics such as sex, age, ethnicity, social deprivation (Indices of Multiple Deprivation – IMD), American Society of Anesthesiologists (ASA) classification, and weight and Body Mass Index (BMI) at the time of surgery. Weight regain was defined as the regaining of more than 25% of the Total Body Weight Loss (TBWL) achieved after RYGB. Results Out of 1,346 patients who underwent RYGB, 80% were female. The median age was 48 years (IQR: 39-55), and the median BMI was 44.7 kg/m^2 (IQR: 40.6-50.1). At a median follow-up of 39 months, 20.7% experienced weight regain. Multivariable analysis showed that patients from Black (HR: 1.63, 95% CI: 1.33-1.81, p=0.009) and Asian (HR: 1.40, 95% CI: 1.23-1.71, p=0.011) ethnic groups, as well as those from more socially deprived backgrounds (HR: 2.39, 95% CI: 1.99 – 3.13, p&amp;lt;0.001), were more likely to experience weight regain compared to their White and more affluent counterparts. Conclusion Ethnicity and social deprivation significantly influence the likelihood of weight regain following RYGB. The factors contributing to these disparities are likely multifaceted, encompassing genetic, social, and educational elements. Early identification of patients at increased risk of weight regain and the provision of tailored resources can help mitigate this risk and enhance surgical outcomes.

Sodium-Glucose Cotransporter 2 Inhibitors Improve Body Composition by Increasing the Skeletal Muscle Mass/Fat Mass Ratio in Patients with Type 2 Diabetes: A 52-Week Prospective Real-Life Study

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) induce body weight loss, but their effect on skeletal muscle mass (SMM) and strength needs to be better elucidated. Objectives: This study aimed to evaluate the effects of SGLT2i on SMM in a real-life population setting of patients with type 2 diabetes (T2D). Secondary outcomes included changes in liver steatosis and in anthropometric and glucometabolic parameters. Methods: Seventy-one patients were treated with SGLT2is as an add-on to metformin for 52 consecutive weeks. Visits were scheduled at baseline (T0) and after 6 (T6) and 12 months of therapy (T12) and included the checking of laboratory tests, measurement of anthropometric parameters, bioimpedance analysis of body composition, and abdominal ultrasound (US). Results: Fat mass (FM) and visceral adipose tissue (VAT) progressively decreased compared to the baseline (FM: −2.9 ± 0.6 kg at T6; −2.8 ± 0.6 kg at T12; VAT: −0.3 ± 0.1 L at T6; −0.4 ± 0.1 L at T12; all p &lt; 0.01). Changes in SMM were less pronounced (−0.4 ± 0.3 kg at T6, ns; −0.7 ± 0.4 kg at T12, p &lt; 0.05), yielding a beneficial increase in the SMM/FM ratio (+0.3 ± 0.05 at T6 and +0.2 ± 0.05 at T12, all p &lt; 0.01). No significant changes in sarcopenia, sarcopenic obesity, fat-free mass, muscle strength, and water compartments were observed at the end of the follow-up period. Anthropometric and glucometabolic parameters, insulin resistance, liver enzymes, and biometric indices and US grading of hepatic steatosis improved throughout this study. Conclusions: In a real-life setting, SGLT2i therapy is associated with weight loss attributable to FM rather than SMM loss without any relevant deterioration in muscle strength. In addition, SGLT2is proved to have beneficial effects on steatotic liver disease.

A Novel Synbiotic Protects Against DSS-Induced Colitis in Mice via Anti-inflammatory and Microbiota-Balancing Properties.

Inflammatory bowel disease (IBD) is a chronic immune-inflammatory disease. Gut microbes, intestinal immunity, and gut barrier function play a critical role in IBD. Growing evidence suggests that synbiotic may offer therapeutic benefits for individuals with colitis, suggesting an alternative therapy against colitis. With this in mind, we creatively prepared a new synbiotic combination consisting of a probiotic strain (Limosilactobacillus reuteri) along with one prebiotic chitooligosaccharides (COS). The protective effects of the synbiotic on DSS-induced colitis and the underlying mechanisms were investigated. We demonstrated that the synbiotic ameliorated colitis in mice, as evidenced by a significant remission in body weight loss and colon shortening, and a decreased disease activity index (DAI). Notably, synbiotic reduced the intestinal inflammation and injury by synergistically decreasing inflammatory factors, inhibiting TLR4/Myd88/NF-κB/NLRP3 signaling, preventing macrophage infiltration, and enhancing the integrity of the intestinal barrier. Moreover, synbiotic selectively promoted the growth of beneficial bacteria (e.g., Akkermansia, Lactobacillus) but decreased the pathogenic bacteria (e.g., Helicobacter). BugBase's analysis supported its ameliorated role in reducing pathogenic bacteria. Collectively, our findings revealed the novel synbiotic had a potential to treat colitis, which was associated with its anti-inflammatory and microbiota-balancing properties. This study will contribute to the development of functional synbiotic products for IBD therapy and will provide valuable insights into their mechanisms.

Association between self-reported weight loss and new long-term care insurance certifications: A 9-year Japanese older adult cohort study.

This cohort study aimed to assess weight loss associated with new long-term care insurance (LTCI) certifications over a 9-year period, accounting for the competing risk of death. We analyzed data from 3749 Japanese individuals aged ≥65 years in Kami Town, Hyogo Prefecture, Japan. Weight loss was assessed using the Kihon Checklist during the baseline survey. Data regarding LTCI certifications were collected until March 2022. Cox proportional hazards models were used to calculate adjusted hazard ratios (HRs) of 9-year LTCI certification because of weight loss, adjusted for confounding factors. To exclude the effect of competing risks, Fine-Gray regression was used to estimate subdistribution HRs. Subgroup analyses were carried out after the examination of potential interactions between subjective cognitive function, body mass index categories and weight loss. The incidence rate of new LTCI certifications was 5.16 per 100 person-years overall - broken down into 7.02 for those with weight loss and 4.97 for those without. The adjusted HR for weight loss to new LTCI certifications was 1.35 (95% CI 1.15-1.59). Considering mortality as a competing risk, the adjusted subdistribution HR was 1.37 (95% CI 1.16-1.61). Conversely, no interaction was observed between weight loss and subjective cognitive function or body mass index categories. Excluding the effect of mortality, weight loss was identified as a risk factor for new LTCI certifications. However, no interaction was observed between weight loss and subjective cognitive function or body mass index categories. Geriatr Gerontol Int 2024; ••: ••-••.

Ren-Shen-Bu-Qi decoction alleviates exercise fatigue through activating PI3K/AKT/Nrf2 pathway in mice.

Fatigue is a prevalent issue that can lead individuals to a sub-health condition, impacting their work efficiency and quality of life. There are limited effective treatment options available for fatigue. Ren-Shen-Bu-Qi decoction (RSBQD) is a proprietary herbal remedy that is designed to address fatigue. However, the specific pharmacological mechanisms and basis of RSBQD are not yet fully understood. This study aimed to investigate the pharmacological effects and mechanisms of RSBQD in a mouse model of exercise fatigue. UPLC-Q-Orbitrap HRMS was used to analyze the chemical composition of RSBQD. The pharmacological basis and molecular mechanism of RSBQD on exercise fatigue were predicted using network pharmacology analysis. Subsequently, an exercise fatigue mouse model was established and used to analysis the effects of RSBQD. The potential mechanisms were verified by hematoxylin-eosin (HE) staining, real-time fluorescence quantitative PCR (RT-qPCR), Western blot (WB) and molecular docking. The results showed that 88 main components of RSBQD were identified, which have mainly belonged to flavonoids and carboxylic acid compounds. The network pharmacology analysis indicated that RSBQD ameliorate fatigue through PI3K/AKT signaling pathway. Notably, RSBQD prolonged the swimming time and diminished body weight loss of exercise fatigue mice (P < 0.05). Meanwhile, RSBQD significantly alleviated the injury of liver and kidney induced by exhaustive exercise, and decreasing the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea and BUN levels (P < 0.05). In addition, RSBQD was found could relieve exercise fatigue by decreasing the content of creatine kinase (CK), lactate dehydrogenase (LDH), and lactic acid (LA), but increasing the blood glucose (GLU) and liver glycogen (HG) levels (P < 0.05). RSBQD also significantly increased the hepatic superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) but decreased hepatic malondialdehyde (MDA) levels. Moreover, RSBQD was able to upregulate protein level of activated Nrf2 and PI3K/AKT signaling pathways. RSBQD mitigates exercise fatigue by reversing metabolic changes and reducing oxidative damage through the PI3K/AKT/Nrf2 signaling pathway. This study offers pharmacological support for the utilization of RSBQD in exercise fatigue treatment.

The protective effect of Auricularia auricula polysaccharides on cyclophosphamide-induced immunosuppression and intestinal injury: A fecal microbiota transplantation study

Auricularia auricula polysaccharides (AHP) have potential immunomodulatory activities. However, the relationship between polysaccharides, intestinal microbiota, and immune activity remains unclear. Therefore, to explore this relationship, we performed immunosuppressive donor, fecal microbiota transplantation (FMT), and pseudo-sterile mouse validation experiments. Our results showed that AHP enhanced immunomodulatory activity, as evidenced by the alleviation of cyclophosphamide (Cy)-induced body weight loss, spleen and thymus atrophy, and splenic and colonic lesions. Additionally, AHP effectively regulated antioxidant enzyme activities (SOD, T-AOC, CAT, GSH-Px), lipid peroxidation product content (MDA), levels of immune factors (TNF-α, IFN-γ, IL-2, IL-4, IL-6), immunoglobulins (sIgA), and the expression of tight junction proteins (Muc2, ZO-1, Occuldin, and Claudin-1) in the colon of immunosuppressed mice. FMT results demonstrated that FAHP displayed superior immunomodulatory ability and could further affect the abundance of Dehydroepiandrosterone, Prostaglandin E2, Cholesterol and Pregnenolone by increasing the abundance of unclassified_Muribaculaceae, Desulfovibrio, Alloprevotella, and unclassified_Oscillospiraceae and decreasing that of Staphylococcus, Bacteroides, and Corynebacterium. Pseudo-sterilization experiments showed that AHP was unable to increase antioxidant enzyme activity, reduce lipid peroxidation content, or promote the release of immune factors. In brief, AHP did not alleviate Cy-induced immunosuppression after microbiota elimination. In summary, AHP exerted a protective effect against Cy-induced immunosuppression and intestinal damage by modulating intestinal microbiota and its metabolites. These findings provide new insights into the mechanisms by which AHP, as a functional food or drug, promotes immune response regulation and maintains intestinal health.

Intensified outpatient nutrition management improves body weight and skeletal muscle loss after esophageal cancer surgery: a single-center, retrospective, single-arm clinical study

BackgroundThe progression of malnutrition and sarcopenia after esophagectomy for esophageal cancer negatively influences long-term prognosis. To improve nutritional status after esophagectomy, we introduced an intensified nutrition management (iNM) protocol, in which nutritional counselling by dietitians was provided more frequently. The aim of this study was to evaluate the efficacy of iNM compared with the conventional NM (cNM).MethodsWe included 126 patients who underwent esophagectomy before and after NM revision, and compared nutritional status and changes in body composition after esophagectomy between the cNM and iNM groups. Nutritional parameters were assessed, and we also calculated skeletal muscle index (SMI), skeletal muscle density (SMD), and visceral fat area (VFA) using computed tomography volumetry.ResultsThere were no significant differences in baseline characteristics or surgical outcomes between the groups. Compared with the cNM group, nutritional counselling was provided more frequently (P < 0.001) in the iNM group, and compliance rate increased from 56.3 to 91.9% (P < 0.001). Body weight loss at 4 and 6 months and SMI reduction at 6 months were significantly improved in the iNM group compared with the cNM group (P < 0.001, P = 0.032, and P = 0.023, respectively). There were no significant differences in the changes in SMD, VFA, serum albumin level, and prealbumin level between the two groups.ConclusionsOutpatient iNM significantly mitigated the reduction in body weight and SMI 3–6 months after esophagectomy.

Dietary bile acids alleviate corticosterone-induced fatty liver and hepatic glucocorticoid receptor suppression in broiler chickens.

The aim of this study was to investigate the alleviating effects and mechanisms of bile acids (BA) on corticosterone-induced fatty liver in broiler chickens. Male Arbor Acres chickens were randomly divided into three groups: control group (CON), stress model group (CORT), and BA-treated group (CORT-BA). The CORT-BA group received a diet with 250mg/kg BA from 21 days of age. From day 36 to 43, both the CORT and CORT-BA groups received subcutaneous injections of corticosterone to simulate chronic stress. The results indicated that BA significantly mitigated the body weight loss, liver enlargement, and hepatic lipid deposition caused by corticosterone (P < 0.05). Liver RNA-seq analysis showed that BA alleviated corticosterone-induced fatty liver by inhibiting lipid metabolism pathways, including fatty acid biosynthesis, triglyceride biosynthesis, and fatty acid transport. Additionally, BA improved corticosterone-induced downregulation of glucocorticoid receptor (GR) expression (P < 0.05). Molecular docking and cellular thermal shift assays revealed that hyodeoxycholic acid (HDCA), a major component of compound bile acids, could bind to GR and enhance its stability. In conclusion, BA alleviated corticosterone-induced fatty liver in broilers by inhibiting lipid synthesis pathways and mitigating the suppression of hepatic GR expression.

Extended oxygen supplementation after thoracotomy in rats may improve welfare.

A retrospective comparison of welfare indicators in male rats undergoing thoracotomy for intrapleural dosing is presented. The initial cohort (n = 7) breathed room air after recovery from anaesthesia, while later cohorts (n = 12) had oxygen supplementation for up to 48 h post-surgery. Rats breathing room air sustained a statistically significant average body-weight loss of -1.62% (±1.7%) 2 days after surgery, compared with rats given oxygen supplementation, which maintained a mean weight gain of 0.87% (±1.75%) (p = 0.009). Oxygen-supplemented rats also had lower pain scores on the evening after surgery (median 0.075 [range 0-1.75] vs. median 1.5 [range 0.5-2]). This difference was not statistically significant (p = 0.063) but may be of clinical significance. All rats displayed transient sedation after post-operative opioid administration on the day of surgery, and hypoxaemia (SpO2 <90%) was observed in rats maintained on room air. Use of an oxygen concentrator to provide post-operative extended oxygen supplementation was easy to implement and may improve animal welfare post-thoracotomy.

F-Box and WD repeat domain containing 7 induces infectious osteomyelitis by regulating MYB stability and ubiquitination.

Osteomyelitis is a bone inflammation initiated by invading pathogens. Macrophages and inflammation play essential roles in osteomyelitis. F-Box and WD repeat domain containing 7 (Fbxw7) is a tumour suppressor and E3 ubiquitin ligase. In the present study, the potential roles of Fbxw7 in osteomyelitis were explored. The mRNA level of Fbxw7 was measured in bone marrow cells from patients with osteomyelitis and Staphylococcus aureus (S. aureus)-infected macrophages. The conditional knockout mice with Fbxw7 deficiency in myeloid cells were generated. The expression of interleukin (IL)-6, IL-23a and nitric oxide synthase 2 (Nos2) was measured in S. aureus-infected Fbxw7-deficient bone marrow-derived macrophages (BMDMs). The body weight loss, bacterial burden, bone loss and formation and serum level of IL-6, IL-23 and TNF-α were measured in S. aureus-infected Fbxw7 conditional KO mice. The interacting partners of Fbxw7 were predicted using STRING and the interaction were tested. Elevated expression of Fbxw7 was observed in bone marrow cells from patients with osteomyelitis and in S. aureus-infected macrophages. The expression of IL-6, IL-23a and Nos2 was remarkably suppressed in S. aureus-infected Fbxw7-deficient BMDMs. Fbxw7 conditional knockout mice had less body weight loss, higher bacterial burden, less bone loss and formation and decreased serum level of cytokines. Fbxw7 interacted with MYB. S. aureus-infected Fbxw7-deficient BMDMs had higher level of MYB and less ubiquitination of MYB. Fbxw7 promotes osteomyelitis symptoms by regulating ubiquitination and stability of MYB.