Significant Weight Change Research Articles

Effect of Plyometric Training on Flexibility of Balochistan Female Cricket Athletes

The study sought to determine the impact of a 12-week plyometric workout regimen on the flexibility of female cricket players in Balochistan. Twenty participants were divided into two groups: an experimental group that received plyometric workouts, and a control group that wasn't involved in any specific physical activity program. Flexibility was assessed using the sit-and-reach test, and anthropometric characteristics were measured before and after the training period. The results showed a significant increase in flexibility in the experimental group compared to the control group. Additionally, the experimental group exhibited significant changes in weight and waist-hip ratio post-intervention. These findings suggest that plyometric training can effectively improve flexibility in female cricket athletes.Additional studies might concentrate on the long-term consequences of plyometric training and address potential limitations such as diet and weather conditions to enhance understanding further.

Preparation of Temperature-Sensitive Colour-Changing Materials and Their Applications to Clothing Fabrics: Taking a Compound Composed of Crystal Violet Lactone, Bisphenol A, and Octadecanol as an Example

A compound was prepared using crystal violet lactone, bisphenol A, and octadecanol. An in-situ polymerization method was used to prepare temperature-sensitive colour-changing microcapsules. It was printed on fabrics using printing technology. The colour-changing performance of the composite material, thermal weight changes of the microcapsules, and properties of the fabric coated with microcapsules were analyzed using cases. Printed fabric properties of colour fastness to washing, rubbing, strength and colour strength (K/S) were measured in terms of binder (%), a crosslinking agent (%), and temperature variations. The results indicated that the compound gradually changed from purple to blue within the temperature range of 3 °C to 60 °C and eventually faded into a colourless state. The weight of the microcapsule powder decreased as the temperature rose, with no significant change in weight before reaching 100 °C. Between 100 °C and 200 °C, there was a rapid decrease in weight, followed by a slow decrease between 200 °C and 350 °C. After reaching 350 °C, the weight tended to stabilize. When the mass fraction of the cross-linker was 3%, the mass fraction of the binder was 25%, and the baking temperature was 120 °C, the colour fastness, fabric strength, and K/S value (colour intensity) of the cotton fabric coated with microcapsules were optimal.

Effects of a Math-Integrated Afterschool Physical Activity Program: A Case Study

This case study aims to evaluate the impact of an afterschool physical activity (PA) program integrated with mathematics on elementary school students’ Body Mass Index (BMI), fitness levels, and comprehension of geometry concepts–a recommended strategy for preventing child obesity. Utilizing descriptive statistics and t-tests, the study analyzes pre- and post-geometry assessments and FITNESSGRAM® assessments. Despite no significant weight change, the findings reveal improved cognitive understanding of geometry concepts and enhanced fitness levels. This research contributes valuable evidence supporting the positive effects of integrating PA into math learning environments, particularly benefiting low socioeconomic status (SES) and underrepresented children, addressing the decline in both physical activity and math performance during childhood.

Umbilical cord mesenchymal stromal cells in serum-free defined medium display an improved safety profile

BackgroundSafety evaluations in preclinical studies are needed to confirm before translating a cell-based product into clinical application. We previously developed a serum-free, xeno-free, and chemically defined media (S&XFM–CD) for the derivation of clinical-grade umbilical cord-derived MSCs (UCMSCs), and demonstrated that intraperitoneal administration of UCMSCs in S&XFM–CD (UCMSCS&XFM−CD) exhibited better therapeutic effects than UCMSCs in serum-containing media (SCM, UCMSCSCM). However, a comprehensive investigation of the safety of intraperitoneal UCMSCS&XFM−CD treatment should be performed before clinical applications.MethodsIn this study, the toxicity, immunogenicity and biodistribution of intraperitoneally transplanted UCMSCS&XFM−CD were compared with UCMSCSCM in rats via general vital signs, blood routine, blood biochemistry, subsets of T cells, serum cytokines, pathology of vital organs, antibody production and the expression of human-specific gene. The tumorigenicity and tumor-promoting effect of UCMSCS&XFM−CD were compared with UCMSCSCM in nude mice.ResultsWe confirmed that intraperitoneally transplanted UCMSCS&XFM−CD or UCMSCSCM did not cause significant changes in body weight, temperature, systolic blood pressure, diastolic blood pressure, heart rate, blood routine, T lymphocyte subsets, and serum cytokines, and had no obvious histopathology change on experimental rats. UCMSCS&XFM−CD did not produce antibodies, while UCMSCSCM had very high chance of antibody production to bovine serum albumin (80%) and apolipoprotein B-100 (60%). Furthermore, intraperitoneally injected UCMSCS&XFM−CD were less likely to be blocked by the lungs and migrated more easily to the kidneys and colon tissue than UCMSCSCM. In addition, UCMSCS&XFM−CD or UCMSCSCM showed no obvious tumorigenic activity. Finally, UCMSCS&XFM−CD extended the time of tumor formation of KM12SM cells, and decreased tumor incidence than that of UCMSCSCM.ConclusionsTaken together, our data indicate that UCMSCS&XFM−CD display an improved safety performance and are encouraged to use in future clinical trials.

In vitro degradation analysis and mechanical characterization of PLA-CF composites prepared by fused filament fabrication technique for bio-medical applications

The objective of this research work is to study the in vitro degradation behavior of as-fabricated and annealed Poly Lactic Acid (PLA) composites reinforced with varying volume fractions of carbon fiber (CF).The composites are prepared by fused filament fabrication technique (FFF). Specimens are immersed in simulated body fluid (SBF) for 8 weeks to study the degradation behavior of the composites by examining the change in weight, change in pH and degradation in mechanical properties. The obtained results show that the addition of carbon fiber reinforcement reduces the tensile strength, flexural strength, impact strength and compressive strength of the composites. Further, CF addition enhances the tensile modulus of the composite. The mechanical properties of annealed composites are enhanced when compared to as-fabricated composites. Differential Scanning Calorimeter (DSC) is employed to study the thermal characteristics of the composites and % crystallinity of the composites. CF addition reduces the crystallinity of the composites. Fractographs of the tensile fractured specimens are studied using a scanning electron microscope (SEM). The addition of the carbon fiber reinforcement is found to accelerate the degradation behavior of the composites. There is significant change in weight and pH as well as degradation in mechanical properties of PLA-CF composites immersed in SBF than pure PLA composites. Annealed composites show better degradation resistance than as-fabricated composites. SEM is employed to study the surface morphology of the composites immersed in SBF.

Исследование биораспределения биомедицинского клеточного продукта на основе хондроцитов человека при имплантации мышам линии BALB/C nude

Despite the prospects of the approach to cell therapy of cartilage damage in humans involving autologous chondrocytes, similar technologies are just beginning to be introduced into medical practice in the Russian Federation. In this regard, the development of biomedical cell products (BCPs) for cartilage tissue repair is quite topical, while the use of organoid technology is the most close to the native tissue conditions. According to requirements of legislation of the Russian Federation, it is necessary to assess biodistribution characterizing migration potential of the cells, their tropism for body tissues following implantation within the framework of preclinical trials. The study was aimed to assess biodistribution of novel BCP based on human chondrocytes in the form of chondrospheres after subcutaneous implantation in Balb/c nude mice. Implantation to 12 mice was performed during the first phase, along with administration of saline to 12 control animals. Weighting and follow-up were conducted for 90 days. Then mice were withdrawn from the experiment to collect samples of organs and tissues for histological analysis of the implant, estimation of its viability, integration. During the second phase biodistribution was assessed by PCR in order to detect human DNA in the organ and tissue samples. Chondrospheres successfully integrated in the tissues surrounding the inoculation zones and formed cartilage tissue. No significant (p < 0.05) changes in weight were reported. No human DNA found in chondrosphere implantation zones was detected in the samples collected from other organs and tissues. BCP demonstrated no biodistribution across other tissues and organs of mice 90 days after implantation, which suggested that the product developed was safe.

Feasibility of the CART In‐Home Technology Platform in a Pilot Study of Hispanic Older Adults Residing in South Texas

AbstractBackgroundAs Alzheimer’s disease (AD) prevalence rises, the development of effective screening tools is necessary to aid in earlier AD diagnosis. In the USA, Hispanic and Non‐Hispanic Black adults are at a disproportionately higher risk of developing dementia than non‐Hispanic whites but are poorly represented in AD research. A digital assessment system ‐ the Collaborative Aging Research using Technology (CART) platform, has been developed to remotely and continuously detect early declines in cognition by analyzing changes in everyday activity levels. Although the platform is promising, installing digital technology in a home can cause concerns over privacy and user friendliness, especially in older adults. In our CART pilot study at UTHSCSA, we sought to determine the feasibility of deploying the CART platform in an underrepresented, mostly Hispanic population and to gain insight from their experiences.MethodSeven cognitively intact participants were enrolled in our year‐long pilot study. The CART platform consisted of a watch‐actigraph, digital scale, electronic pillbox, bed mat (measuring sleep), and wall‐mounted motion sensors. Participants completed weekly online surveys including mood assessments, the UDS3 neuropsychological battery at baseline and one‐year follow‐up, and an end‐of‐study user experiences survey. Wilcoxon signed rank exact tests were used to determine significance.ResultOur cohort consisted of five Hispanic, one non‐Hispanic Black, and one non‐Hispanic white participant, ages 65‐80. There were no significant changes in cognition, daily steps, sleep, weight, or heart and respiratory rate measured during sleep over the course of the study (p>0.05). Self‐reported depressive symptoms decreased (p = 0.034) (Figure 1J). Weekly survey results supported this finding because self‐reported feelings of loneliness and “blue mood” also decreased. Responses to the user experience survey demonstrated that participants found the technology installation satisfactory (43%) or very satisfactory (57%) and thought that their privacy concerns were addressed satisfactorily (43%) or very satisfactorily (57%) (Figure 2).ConclusionOur results suggest that the CART platform was widely accepted by our mostly Hispanic older adult participants and that they were comfortable with the study devices. The findings support the feasibility of increasing representation of diverse older adults in dementia prevention research using digital devices.

Effect of 90 Days Sub-chronic Administration of Omeprazole (A Proton Pump Inhibitor) on Haematological, Biochemical, Antioxidant, Reproductive and Histopathological Parameters in Male and Female Rats

Abstract Despite the widespread use of omeprazole (OME), there are still concerns about its long-term safety and tolerability, especially with long-term or indiscriminate use. This study was designed to evaluate the effect of 90 days sub-chronic administration of OME on haematological, biochemical, antioxidant, reproductive and histopathological parameters in male and female rats. Forty-eight (48) Wistar rats of both sexes were divided into 4 groups of 6 male and 6 female animals each. Group I received 10 mL/kg normal saline, while Groups II – IV received 0.12 mg/kg, 0.57 mg/kg, 2.85 mg/kg of OME respectively for 90 days. At the end of 90 days, 5 mL blood sample was collected, and vital organs were harvested for relevant analyses. In this study, OME did not elicit any significant (P>0.05) change in the body weight or weight of vital organs, but elicited a significant (P<0.05) reduction in sperm count at the supratherapeutic dose (2.85 mg/kg). The supratherapeutic dose of OME produced significant increase in cholesterol (P<0.0001) and LDL (P<0.0001) in female rats. OME did not generally produce a significant change in haematological parameters. OME elicited a significant decrease in CAT (P<0.05) in female and combined animals. Additionally, histopathological presentations of vital organs were generally non-abnormal. From this study, it can be concluded that long term administration of OME is generally safe and tolerable, especially at lower doses. Findings from this study suggest that OME may potentially induce changes in sperm characteristics (in relation to male rats), hepatoxicity, hypercholesteremia, hyperlipidemia and thrombocytosis over a long duration, at higher doses and especially in female animals.

Abstract LB_C04: Novel orally bioavailable macrocycles that target cyclin A and B elicit antitumor activity in breast cancer patient-derived xenograft models

Abstract Background: Cyclin/cyclin-dependent kinase (CDK) complexes regulate the activity of RB1 and E2F to drive cell cycle progression while ensuring fidelity of DNA replication. The interaction between cyclins and a critical subset of their substrates, including RB1 and E2F, is mediated by a conserved short linear RxL motif. RxL peptides have been shown to inhibit substrate phosphorylation by CDK2/cyclin A (AACR 2022 poster #5379). Previously, we have shown that macrocycles that selectively inhibit RxL-mediated binding to cyclins A and B (RxL inhibitors) lead to growth inhibitory activity in multiple cancer cell lines, and result in tumor regression in small cell lung cancer (SCLC) and ovarian cancer xenograft models (AACR 2023 poster #1560). Here, we test the antitumor activity of CID-016 in patient-derived xenograft (PDX) models from breast cancer. Methods: Bioinformatic analyses using RNA sequencing (RNAseq) and whole exome sequencing (WES) data from 39 breast cancer cell lines was employed to identify biomarker profiles that associate with sensitivity to CID-016. The antiproliferative activity of CID-016 was assessed by GI50 after 4-8 days of treatment. Hallmark pathway scores were calculated by Gene Set Variation Analysis (GSVA) method using MSigDb Hallmark collection from cell lines and existing PDX models. Based on the calculated hallmark pathway score, triple negative breast cancer (TNBC) PDX models were selected to test the anti-tumor activity of CID-016. In vivo, NMRI-Foxn1nu/nu mice were implanted with tumor fragments in the lower flank and treated with vehicle or CID-016 oral formulation of 50-100 mg/kg BID or 100 mg/kg QD, respectively for at least 28 days. Tumor volume and body weight were measured biweekly. Pharmacodynamic (PD) analyses will be conducted after treatment with CID-016. Results: Treatment of the breast cancer cell line panel with CID-016 demonstrated greater potency by GI50 in TNBC compared to other breast cancer cell lines (p=0.009). Gene expression levels of CCNB1, CCNA2, CCNE1 as well as target hallmark scores for “E2F targets”, “G2M checkpoint” and “Mitotic spindle” were significantly higher in TNBC vs other breast cancer cell lines. Oral treatment with CID-016 resulted in tumor regression in at least one triple-negative breast cancer PDX model and was well tolerated with no significant body weight changes. In vivo PD analyses will be assessed after 5 days of treatment with CID-016. Conclusions: The selective cyclin A/B RxL inhibitor CID-016 exhibits potent antitumor activity in TNBC preclinical models, consistent with the proposed mechanism of RB1/E2F pathway dysregulation. Given their compelling characteristics, orally bioavailable RxL inhibitors are advancing as the only first-in-class orally bioavailable dual inhibitors of cyclins A and B into clinical development. Citation Format: Mariana Paes Dias, Li-Fen Liu, Bernard Levin, Cristina Molina, Marta Guzmán, Olga Rodríguez, Evelyn W. Wang, Violeta Serra. Novel orally bioavailable macrocycles that target cyclin A and B elicit antitumor activity in breast cancer patient-derived xenograft models [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr LB_C04.

Combinational Antidiabetic effects of Curcuma longa L. and Trigonella foenum-graecum L. extracts in alloxan induced type-1 diabetic rats

Diabetes mellitus is a metabolic disorder that is one of the leading causes of death globally. The current study aimed to determine the combined protective effect of Curcuma longa (CL) and Trigonella foenum-graecum (TFG) on alloxan-induced oxidative stress in liver tissue of albino Wister rats. Rats were divided into 8 groups with 6 individuals each. Group I served as control, group II, III and IV were treated with CL, TFG and CL+TFG respectively. Group V, VI, VII and VIII were alloxan-induced diabetic rats, whereas group V served as negative control and group VI, VII and VIII were treated with CL, TFG and CL+TFG respectively. Blood glucose, body weight, oxidative enzymes and histopathological changes were evaluated. Group V showed significant increase in blood glucose levels after induction of alloxan, whereas, group VI, VII and VIII showed significantly decreased levels. However, the best hypoglycaemic activity was found in group VIII. The body weights were slightly increased in groups II, III and IV after the treatment of plant extracts, whereas, decreased body weights were noticed in group V. though no significant weight changes were observed in groups VI, VII and VIII. A significant decrease in oxidative enzyme levels as compared to group V were recorded. The histopathological investigation of liver tissue showed morphological alteration in group V and ameliorative effects in group VI, VII and VIII due to administration of CL, TFG and CL+TFG. Therefore, the combined administration of CL+ TFG exhibits the highest hypoglycemic activity by reducing the oxidative enzyme levels and regeneration of liver tissue.

A novel human single-domain antibody-drug conjugate targeting CEACAM5 exhibits potent in vitro and in vivo antitumor activity.

Leveraging the specificity of antibody to deliver cytotoxic agent into tumor, antibody-drug conjugates (ADCs) have become one of the hotspots in the development of anticancer therapies. Although significant progress has been achieved, there remain challenges to overcome, including limited penetration into solid tumors and potential immunogenicity. Fully human single-domain antibodies (UdAbs), with their small size and human nature, represent a promising approach for addressing these challenges. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is a glycosylated cell surface protein that rarely expressed in normal adult tissues but overexpressed in diverse cancers, taking part in tumorigenesis, progression, and metastasis. In this study, we investigated the therapeutic potential of UdADC targeting CEACAM5. We performed biopanning in our library and obtained an antibody candidate B9, which bound potently and specifically to CEACAM5 protein (KD = 4.84 nM) and possessed excellent biophysical properties (low aggregation tendency, high homogeneity, and thermal stability). The conjugation of B9 with a potent cytotoxic agent, monomethyl auristatin E (MMAE), exhibited superior antitumor efficacy against CEACAM5-expressing human gastric cancer cell line MKN-45, human pancreatic carcinoma cell line BxPC-3 and human colorectal cancer cell line LS174T with IC50 values of 38.14, 25.60, and 101.4 nM, respectively. In BxPC-3 and MKN-45 xenograft mice, administration of UdADC B9-MMAE (5 mg/kg, i.v.) every 2 days for 4 times markedly inhibited the tumor growth without significant change in body weight. This study may have significant implications for the design of next-generation ADCs.

Receptor activity-modifying proteins of adrenomedullin (RAMP2/3): Roles in the pathogenesis of ARDS.

Acute respiratory distress syndrome (ARDS) is a life-threatening lung condition characterized by widespread inflammation and pulmonary edema. Adrenomedullin (AM), a bioactive peptide with various functions, is expected to be applied in treating ARDS. Its functions are regulated primarily by two receptor activity-modifying proteins, RAMP2 and RAMP3, which bind to the AM receptor calcitonin receptor-like receptor (CLR). However, the roles of RAMP2 and RAMP3 in ARDS remain unclear. We generated a mouse model of ARDS via intratracheal administration of lipopolysaccharide (LPS), and analyzed the pathophysiological significance of RAMP2 and RAMP3. RAMP2 expression declined with LPS administration, whereas RAMP3 expression increased at low doses and decreased at high doses of LPS. After LPS administration, drug-inducible vascular endothelial cell-specific RAMP2 knockout mice (DI-E-RAMP2−/−) showed reduced survival, increased lung weight, and had more apoptotic cells in the lungs. DI-E-RAMP2−/− mice exhibited reduced expression of Epac1 (which regulates vascular endothelial cell barrier function), while RAMP3 was upregulated in compensation. In contrast, after LPS administration, RAMP3−/− mice showed no significant changes in survival, lung weight, or lung pathology, although they exhibited significant downregulation of iNOS, TNF-α, and NLRP3 during the later stages of inflammation. Based on transcriptomic analysis, RAMP2 contributed more to the circulation-regulating effects of AM, whereas RAMP3 contributed more to its inflammation-regulating effects. These findings indicate that, while both RAMP2 and RAMP3 participate in ARDS pathogenesis, their functions differ distinctly. Further elucidation of the pathophysiological significance and functional differences between RAMP2 and RAMP3 is critical for the future therapeutic application of AM in ARDS.

Intra-patient analysis of individual weight gain or loss between IVF cycles: cycle now and transfer later.

What is the impact of clinically significant weight change on outcomes related to IVF cycle performance? While individual weight loss did not significantly impact ovarian response to stimulation or other cycle outcome parameters in our study, some positive associations were found for individual weight gain. The role of weight-change in patients undergoing IVF has been largely studied by comparing weight loss in different cohorts of patients stratified by a static BMI. Specifically, obesity has been extensively studied in relation to its negative effects on assisted or unassisted conception outcomes and ovulatory function. Previous research has shown conflicting results, while BMI, which is commonly used as a marker of obesity, may not accurately reflect the underlying factors affecting fertility in obese patients. This study utilized a retrospective within-patient repeated measurement analysis design to assess the impact of weight change on IVF outcomes in cycles where all embryos were cryopreserved at the blastocyst stage for transfer at a later date. The study was conducted at an academically affiliated fertility center. The data included 961 women who underwent at least two IVF cycles between December 2014 and June 2020, with documented short-term weight gain (n = 607) or weight loss (n = 354) within 1year from their initial IVF cycle. Multivariable generalized estimating equations (GEE) and generalized linear mixed models (GLMM) were employed to assess associations between weight change and outcomes across cycles. The multivariable models indicated that weight loss did not show any significant associations with the numbers of oocytes retrieved, or mature oocytes, the fertilization rate or the blastulation rate. However, weight gain demonstrated a minor positive association with the number of oocytes retrieved in both GEE models (coefficient: 0.01, 95% CI: 0.00-0.01) and GLMM models (0.01, 95% CI: 0.01-0.00). There was also a potential increase in the fertilization rate with weight gain, as indicated by a positive coefficient in both GEE models (coefficient: 0.01, 95% CI: 0.00-0.02) and GLMM models (coefficient: 0.01, 95% CI: 0.00-0.01). However, the association between weight gain and the embryo blastulation rate was not statistically significant in any model. This study focused on cycle performance parameters instead of reproductive outcomes, which restricted our ability to evaluate the impact of weight change on cumulative live birth rates. Additionally, the study did not account for variables such as stimulation protocols, potentially introducing confounding factors and limiting the generalizability of the results. Although obesity is associated with adverse obstetrical risks, there is less evidence of adverse reproductive outcomes in IVF cycles. We therefore recommend that an IVF cycle should not be delayed due to weight, so that the patient is not adversely affected by increasing age. The IVF cycle should aim to freeze all embryos, so that embryo transfer can then occur after weight loss, so as to limit the recognized obstetrical risks. The study was not funded and there were no competing interests. N/A.

Weight change in chronic kidney disease: Association with mortality and kidney function.

Excess body weight is a risk factor for the progression of chronic kidney disease (CKD), but weight loss in CKD has been associated with higher mortality. Consequently, blanket weight loss recommendations in this population are controversial. Little data is available on the patterns of weight-change in CKD. The authors aimed to describe weight-changes in moderate/severe CKD and explore associations with mortality and renal endpoints in patients with overweight and obesity. Non-dialysis Canberra Hospital patients with estimated glomerular filtration (eGFR)<60mL/min/1.73m2 and body mass index (BMI) ≥25kg/m2 were followed for up to 5.5years. Weight-change ≥5% was considered clinically significant. The renal endpoint was defined as the commencement of dialysis or transplant or a ≥40% fall in eGFR. Relationships between weight-change in the first year of follow-up and mortality or the renal endpoint were assessed using Cox-regression. Three hundred ten patients (median age 75, median BMI 31kg/m2) were identified. 68% had Stage-4 CKD at baseline. Over 4.4-years median follow-up, 128 died and 140 had significant weight-change. During the first year of follow-up, 42 patients lost and 23 gained ≥5% body weight, of whom only 3 had intentionally lost weight. On multivariate regression, significant weight loss/gain at 1-year was associated with 2.74 (p<0.0005) and 2.67 (p=0.003) hazard of subsequent death and with 2.51 (p=0.004) and 2.20 (p=0.05) hazard of the renal endpoint respectively. There was no association between baseline eGFR and subsequent weight change. Patients with moderate/severe CKD experience significant weight-change, but this has no relationship to baseline kidney function. Significant weight-change is associated with higher subsequent mortality and loss of kidney function, but this association is likely significantly affected by confounding.

Whole-Body Cryostimulation in Post-COVID Rehabilitation for Patients with Obesity: A Multidisciplinary Feasibility Study.

A post-COVID condition can reduce activity and quality of life, resulting in a significant socioeconomic and health burden. Understanding its impact on patients' health is important for the development of personalized rehabilitation interventions. An independent association between obesity and post-COVID condition was found because of complications and comorbidities. Sixteen patients with obesity and post-COVID symptoms (i.e., dyspnea, pain, poor sleep quality, muscle fatigue), admitted to the Istituto Auxologico Italiano, Piancavallo (VB), Italy, were recruited for a four-week rehabilitation program including conventional exercise therapy, nutritional intervention, psychological support and whole-body cryostimulation (WBC). All participants attended all sessions of the program. Anthropometric data showed statistically significant changes in weight, waist circumference and body mass index. Biochemical analyses showed significant reductions in lipid and inflammatory profiles. There was a significant improvement in physical performance, reduction in pain and improvement in psychological well-being. A multidisciplinary rehabilitation protocol including WBC, designed for patients with obesity and a post-COVID condition, is safe and feasible. The overall improvements demonstrate that multidisciplinary rehabilitation was effective on post COVID patients and suggest that the use of WBC is safe and could play a role as a booster in rehabilitation programs.

Human umbilical cord mesenchymal stem cell-derived exosomes promote microcirculation in aged diabetic mice by TGF-β1 signaling pathway

BackgroundMicrovascular dysfunction is one of the most common pathological characteristics in Type 2 diabetes. Human mesenchymal stem cell-derived exosomes (hUCMSCs-Exo) have diverse functions in improving microcirculation; however, the molecular mechanism of hUCMSCs-Exo in regulating burn-induced inflammation is not well understood.MethodshUCMSCs-Exo were extracted by hypervelocity centrifugation method, and exosome morphology was observed by transmission electron microscopy, exosome diameter distribution was detected by particle size analysis, and exosome specific proteins were identified by Western blot.2. DB/DB mice were randomly divided into exosomes group and PBS group. Exosomes and PBS were injected into the tail vein, respectively, and the calf muscle tissue was taken 28 days later. 0.5% Evans blue fluorescence assessment microvascular permeability. The expression of CD31 was detected by immunofluorescence.The morphology and function of microvessels in muscle tissue of lower limbs was evaluated by transmission electron microscopy.3. TMT proteomics was used to detect the changes of differential protein expression in lower limb muscle tissues of the PBS group and the exosome group, and data analysis was performed to screen key signal molecules and their involved biological pathways. Key signal molecules CD105 were verified by Western blot. The expression of TGF-β1 in exosomes were evaluated by Western blot.ResultsElectron microscopy showed that hUCMSCs-Exo presented a uniform vesicle structure, and NTA showed that its diameter was about 160 nm. Western blot showed positive expression of specific proteins CD9, CD81 and TSG101 on exosomes.2. There is no significant change in blood glucose and body weight before and after the exosome treatment. The exosome group can significantly reduce the exudation of Evans blue. Compared with the PBS group. Meanwhile, CD31 immunofluorescence showed that the red fluorescence of exosome treatment was significantly increased, which was higher than that of PBS group. Transmission electron microscopy showed smooth capillary lumen and smooth and complete surface of endothelial cells in the exosome group, while narrow capillary lumen and fingerlike protrusion of endothelial cells in the PBS group.3.Quantitative analysis of TMT proteomics showed that there were 82 differential proteins, including 49 down-regulated proteins and 33 up-regulated proteins. Go enrichment analysis showed that the differential proteins were involved in molecular function, biological process, cell components,among which CD105 was one of the up-regulated proteins. Through literature search, CD105 was found to be related to endothelial cell proliferation. Therefore, this study verified the changes of CD105 in the exosome group, and it was used as the mechanism study of this study. 4. Western blot analysis showed that the expression of CD105 protein in lower limb muscle tissue of exosome group was significantly increased compared with that of PBS group. Based on the fact that CD105 is a component of the TGF-β1 receptor complex and exosomes are rich in growth factors and cytokines, this study further examined the expression of TGF-β1 in exosomes, and the results showed that exosomes had high expression of TGF-β1.ConclusionBy improving the integrity of microvascular endothelial cells, hUCMSCs-Exo can improve the permeability of microvessels in diabetic lower muscle tissue, further promote the proliferation of lower limb muscle cells and inhibit the apoptosis of tissue cells. The mechanism may be associated with exosomes rich in TGF-β1, which is likely to promote endothelial cell proliferation and improve permeability through binding to the endothelial CD105/TβR-II receptor complex, while promoting angiogenesis and protecting skeletal muscle cells from apoptosis.

Effects of Hesperidin Supplementation on Anthropometric Indices in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Although some studies have reported that flavonoids can be associated with anti-obesity effects, the putative effects of hesperidin, as a subgroup of flavonoids, on anthropometric parameters are inconclusive. Therefore, this systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to determine the effect of hesperidin supplementation on anthropometric measures in adults. Methods: A comprehensive literature search was performed until February 2022 in electronic databases such as PubMed, Scopus, Web of Science, and Google Scholar. The pooled results were obtained by a random-effects model. Results: A total of nine RCTs enrolling 493 participants were identified. Seven studies had illustrated the effect of hesperidin on weight, eight on body mass index (BMI), five on waist circumference (WC), two on waist to hip ratio (WHR), and two on hip circumference (HC). The results of the pooled analysis showed no significant changes in body weight (0.01 kg, 95% CI: -0.22, 0.24), BMI (-0.02 kg/m2, 95% CI: -0.16, 0.13), and WC (-0.48 cm, 95% CI: -1.52, 0.55) after hesperidin supplementation compared to the control group (P &gt; 0.05). Qualitative assessment of other anthropometric indices also showed no beneficial effect of hesperidin in reducing WHR and HC values; however, these findings are not conclusive because of the limited number of studies. Conclusion: The present study provides no evidence that hesperidin supplementation is effective in improving anthropometric measures. More high-quality RCTs especially among overweight and obese individuals are needed to strengthen the evidence.

Safety Assessment of AYUSH SC-3 through Acute and 90 Days Repeated Dose Oral Toxicity Study

The present study is focused on establishing the safety of the formulation through acute and 90 days of repeated oral dose toxicity as per the Organization for Economic Cooperation and Development (OECD) guidelines. During the acute toxicity test, the drug was orally administered at a limited test dose of 2000 mg/kg. Clinical signs, feed and body weight were recorded. At the end of 14 days, the animals were euthanized and subjected to a detailed post-mortem examination (necropsy). As per OECD, 408 the 90 days repeated dose oral toxicity study was carried out with three different doses of test drug i.e., 1500, 1000 and 500 mg/kg. Cage side observations, body weight and feed intake were recorded. Upon termination of the study, urine analysis, haematology and clinical biochemical examinations were performed. Finally, the rats were subjected to euthanasia, a gross necropsy was conducted and vital organs were weighed and made prone for histopathological evaluation. Cage-side observation of AYUSH-SC-3 treated animals showed no signs of toxicity, and the mortality or moribund state was observed in both of the studies. No significant change in body weight and feed intake was seen in AYUSH-SC-3 treated animals. Gross morphology and necropsy findings of the animals revealed no treatment-related. Haematological and biochemical parameters of rats treated with AYUSH-SC-3 were found to be non-significant when compared to the control group. Necropsy findings and relative organ weights did not change significantly. Further, the histopathological analysis of major organs showed no major lesions and treatment-related changes. The LD50 of AYUSH SC-3 is greater than 2000 mg/kg and NOAEL is up to 1500 mg/kg.

Abstract 13242: Annual Body Weight Change and Subsequent Prognosis in Heart Failure With Preserved Ejection Fraction: Insights From the PURSUIT-HFpEF Registry

Introduction: Maintaining optimal body weight is important in heart failure management. Weight gain (WG) may signal excessive caloric intake and fluid retention, whereas weight loss (WL) would imply cachexia. Both conditions could affect the prognosis of heart failure with reduced ejection fraction. However, the significance of WG and WL in patients with heart failure and preserved ejection fraction (HFpEF) has not been well established. Methods: An analysis was performed from a prospective multicenter observational registry for HFpEF (PURSUIT-HFpEF Registry) conducted in the Osaka region of Japan. Of 1231 patients who enrolled in the registry, we enrolled 662 patients (age, 82±9 years; females, 54.1%; body mass index, 22.3±4.3kg/m 2 ; atrial fibrillation, 38.3%) whose weight at discharge and one year later were both available. WG and WL were defined as a gain or loss of ≥5% weight between baseline and 1 year, respectively. Other patients who did not demonstrate a significant change in weight were categorized as having a stable weight (SW). All-cause mortality was the primary endpoint. Results: During 1-year, the median body weight slightly increased from 52.1 (interquartile range [IQR]: 45.1-61.9) to 53.0 kg (IQR 45.0-63.0) kg (p &lt;0.001), with a median change of 0.6 kg (IQR: -1.8-2.8). A total of 182 (27%), 125 (19%), and 355 (54%) patients experienced WG, WL, and SW, respectively. During a follow-up of 603 days (IQR: 329-982), 149 patients died. The mortality rate was highest in patients experiencing WL, followed by those experiencing WG and SW (30.2% vs. 21.5% vs. 18.0%, respectively; log-rank p = 0.006). After adjusting for potential confounders, Cox regression analysis revealed that WL, not WG, was independently associated with higher mortality (hazard ratio 2.44 [95% CI 1.51-3.95], p &lt;0.001). Conclusions: Significant number of patients with HFpEF experienced WG and WL within a year. Patients who experienced WL had a higher risk of mortality compared to those who experienced WG and SW. These results highlight the importance of monitoring body weight changes in the management of HFpEF.

Disruption of hypoxia-inducible factor-2α in neutrophils decreases colitis-associated colon cancer.

Neutrophils are abundant immune cells in the colon tumor microenvironment. Studies have shown that neutrophils are recruited into hypoxic foci in colon cancer. However, the impact of hypoxia signaling on neutrophil function and its involvement in colon tumorigenesis remain unclear. To address this, we generated mice with a deletion of hypoxia-inducible factor (HIF)-1α or HIF-2α in neutrophils driven by the MRP8Cre (HIF-1αΔNeu) or (HIF-2αΔNeu) and littermate controls. In an azoxymethane (AOM)/dextran sulfate sodium (DSS) model of colon cancer, the disruption of neutrophils-HIF-1α did not result in any significant changes in body weight, colon length, tumor size, proliferation, or burden. However, the disruption of HIF-2α in neutrophils led to a slight increase in body weight, a significant decrease in the number of tumors, and a reduction in tumor size and volume compared with their littermate controls. Histological analysis of colon tissue from mice with HIF-2α-deficient neutrophils revealed notable reductions in proliferation as compared with control mice. In addition, we observed reduced levels of proinflammatory cytokines, such as TNF-α and IL-1β, in neutrophil-specific HIF-2α-deficient mice in both the tumor tissue as well as the neutrophils. Importantly, it is worth noting that the reduced tumorigenesis associated with HIF-2α deficiency in neutrophils was not evident in already established syngeneic tumors or a DSS-induced inflammation model, indicating a potential role of HIF-2α specifically in colon tumorigenesis. In conclusion, we found that the loss of neutrophil-specific HIF-2α slows colon tumor growth and progression by reducing the levels of inflammatory mediators.NEW & NOTEWORTHY Despite the importance of hypoxia and neutrophils in colorectal cancer (CRC), the contribution of neutrophil-specific HIFs to colon tumorigenesis is not known. We describe that neutrophil HIF-1α has no impact on colon cancer, whereas neutrophil HIF-2α loss reduces CRC growth by decreasing proinflammatory and immunosuppressive cytokines. Furthermore, neutrophil HIF-2α does not reduce preestablished tumor growth or inflammation-induced colitis. The present study offers novel potential of neutrophil HIF-2α as a therapeutic target in CRC.