miPEP31 alleviates Ang II-induced hypertension in mice by occupying Cebpα binding sites in the pri-miR-31 promoter.

BACKGROUND: Previous studies have shown that peptides encoded by noncoding RNAs (ncRNAs) can be used as peptide drugs to alleviate diseases. We found that microRNA-31 (miR-31) is involved in the regulation of hypertension and that the peptide miPEP31, which is encoded by the primary transcript of miR-31 (pri-miR-31), can inhibit miR-31 expression. However, the role and mechanism of miPEP31 in hypertension have not been elucidated. METHODS: miPEP31 expression was determined by western blot analysis. miPEP31-deficient mice (miPEP31-/-) were used, and synthetic miPEP31 was injected into Ang II-induced hypertensive mice. Blood pressure was monitored through the tail-cuff method. Histological staining was used to evaluate renal damage. Regulatory T (Treg) cells were assessed by flow cytometry. Differentially expressed genes were analysed through RNA sequencing. The transcription factors were predicted by JASPAR. Luciferase reporter and electrophoretic mobility shift assays (EMSAs) were used to determine the effect of pri-miR-31 on the promoter activity of miPEP31. Images were taken to track the entry of miPEP31 into the cell. RESULTS: miPEP31 is endogenously expressed in target organs and cells related to hypertension. miPEP31 deficiency exacerbated but exogenous miPEP31 administration mitigated the Ang II-induced systolic blood pressure (SBP) elevation, renal impairment and Treg cell decreases in the kidney. Moreover, miPEP31 deletion increased the expression of genes related to Ang II-induced renal fibrosis. miPEP31 inhibited the transcription of miR-31 and promoted Treg differentiation by occupying the Cebpα binding site. The minimal functional domain of miPEP31 was identified and shown to regulate miR-31. CONCLUSION: miPEP31 was identified as a potential therapeutic peptide for treating hypertension by promoting Treg cell differentiation in vivo. Mechanistically, we found that miPEP31 acted as a transcriptional repressor to specifically inhibit miR-31 transcription by competitively occupying the Cebpα binding site in the pri-miR-31 promoter. Our study highlights the significant therapeutic effect of miPEP31 on hypertension and provides novel insight into the role and mechanism of miPEPs.

Single-Cell Transcriptome Analysis Reveals Dynamic Populations of Vascular Cells in Neointimal Hyperplasia.

BACKGROUND: Neointimal hyperplasia (NIH) is the pathological basis of vascular injury disease. Vascular cells are the dominant cells in the process of NIH, but the extent of heterogeneity amongst them is still unclear. METHODS: A mouse model of NIH was constructed by inducing carotid artery ligation. Single-cell sequencing was then used to analyze the transcriptional profile of vascular cells. Cluster features were determined by functional enrichment analysis, gene set scoring, pseudo-time analysis, and cell-cell communication analysis. Additionally, immunofluorescence staining was conducted on vascular tissues from fibroblast lineage-traced (PdgfraDreER-tdTomato) mice to validate the presence of Pecam1+Pdgfra+tdTomato+ cells. RESULTS: The left carotid arteries (ligation) were compared to right carotid arteries (sham) from ligation-induced NIH C57BL/6 mice. Integrative analyses revealed a high level of heterogeneity amongst vascular cells, including fourteen clusters and seven cell types. We focused on three dominant cell types: endothelial cells (ECs), vascular smooth muscle cells (vSMCs), and fibroblasts. The major findings were: (1) four subpopulations of ECs, including ECs4, mesenchymal-like ECs (ECs1 and ECs2), and fibro-like ECs (ECs3); (2) four subpopulations of fibroblasts, including pro-inflammatory Fibs-1, Sca1+ Fibs-2, collagen-producing Fibs-3, and mesenchymal-like Fibs-4; (3) four subpopulations of vSMCs, including vSMCs-1, vSMCs-2, vSMCs-3, and vSMCs-3-derived vSMCs; (4) ECs3 express genes related to extracellular matrix (ECM) remodeling and cell migration, and fibro-like vSMCs showed strong chemokine secretion and relatively high levels of proteases; (5) fibro-like vSMCs that secrete Vegfa interact with ECs mainly through vascular endothelial growth factor receptor 2 (Vegfr2). CONCLUSIONS: This study presents the dynamic cellular landscape within NIH arteries and reveals potential relationships between several clusters, with a specific focus on ECs3 and fibro-like vSMCs. These two subpopulations may represent potential target cells for the treatment of NIH.

Evaluating the impact of exercise on intermediate disease markers in overweight and obese individuals through a network meta-analysis of randomized controlled trials.

The aim of this study is to investigate the impact of exercise on intermediate disease markers in populations with overweight and obesity, providing evidence-based recommendations for clinicians to utilize these markers in developing exercise prescriptions for this group. The study was conducted by retrieving data from PubMed, Embase, Cochrane Library, Web of Science, and CNKI and only including Randomized Controlled Trials (RCTs) to examine the effect of different exercise interventions on intermediate disease markers in overweight and obese people. The quality of the included studies was evaluated using the Cochrane Bias Risk Assessment tool and the data was analyzed using Stata 15.1 data analysis software. The RCTs were collected from January 2017 to March 2024. A total of 56 RCTs were included and the results of 10 outcomes were analyzed using random effects meta-analysis. The total sample size used in the study was 3193 The results showed that resistance training significantly reduced total cholesterol (SUCRA: 99.9%), triglycerides (SUCRA: 100.0%), low-density lipoprotein (SUCRA: 100.0%), systolic pressure (SUCRA: 92.5%), and increased high-density lipoprotein (SUCRA: 100.0%). Aerobic exercise significantly reduced insulin (SUCRA: 89.1%) and HbA1c (SUCRA: 95.3%). Concurrent training significantly reduced HOMA-IR (SUCRA: 93.8%), diastolic blood pressure (SUCRA: 71.2%) and Glucose (SUCRA: 87.6%). Exercise has a significant impact on intermediate disease markers in populations with overweight and obese. Compared with no exercise, exercise lowers total cholesterol, triglycerides, LDL, systolic blood pressure, diastolic blood pressure, HOMA-IR, insulin, and HbA1c, and increases HDL in people with overweight and obese. These findings provide evidence-based recommendations for exercise interventions aimed at weight reduction and the prevention of chronic diseases in individuals with overweight and obese.

Brisk walking improves motor function and lower limb muscle strength in Chinese women aged 80 years and older.

This study investigates the effects of a 12-week brisk walking exercise regimen on motor function improvements in elderly women. Twenty-six elderly women, aged 84.2 ± 3.2 years, participated in a 12-week brisk walking exercise program. Fitness assessments and blood biomarker analyses (including CHO, HDLC, LDLC, TC) were conducted pre- and post-intervention. Additionally, targeted metabolomics was employed to measure short-chain fatty acids, amino acids, and vitamin metabolites. The intervention led to significant enhancements in participants' flexibility (p < 0.05), lower limb muscle strength (p < 0.01), and cardiorespiratory endurance (p < 0.01), while muscle mass showed no significant changes. Fifteen significant differential metabolites were identified (VIP > 1.0, FC > 1.2 or < 0.8, and p < 0.05), with arginine, ornithine, aspartic acid, glutamine, phenylalanine, tyrosine, and pantothenic acid playing key roles across seven metabolic pathways. A 12-week brisk walking exercise program significantly enhanced flexibility, lower limb muscle strength, and cardiorespiratory endurance among elderly women. These improvements did not extend to muscle mass or upper limb muscle strength. The observed enhancement in exercise capacity may be attributed to improved regulation of neurotransmitters.

CKBA suppresses mast cell activation via ERK signaling pathway in murine atopic dermatitis.

Atopic dermatitis (AD) is a common inflammatory skin disorder. Mast cells play an important role in AD because they regulate allergic reactions and inflammatory responses. However, whether and how the modulation of mast cell activity affects AD has not been determined. In this study, we aimed to determine the effects and mechanisms of 3-O-cyclohexanecarbonyl-11-keto-ß-boswellic acid (CKBA). This natural compound derivative alleviates skin inflammation by inhibiting mast cell activation and maintaining skin barrier homeostasis in AD. CKBA markedly reduced serum IgE levels and alleviated skin inflammation in calcipotriol (MC903)-induced AD mouse model. CKBA also restrained mast cell degranulation both in vitro and in vivo. RNA-seq analysis revealed that CKBA downregulated the extracellular signal-regulated kinase (ERK) signaling in BM-derived mast cells activated by anti-2,4-dinitrophenol/2,4-dinitrophenol-human serum albumin. We proved that CKBA suppressed mast cell activation via ERK signaling using the ERK activator (t-butyl hydroquinone) and inhibitor (selumetinib; AZD6244) in AD. Thus, CKBA suppressed mast cell activation in AD via the ERK signaling pathway and could be a therapeutic candidate drug for AD.

Optimal exercise to improve physical ability and performance in older adults with sarcopenia: a systematic review and network meta-analysis.

OBJECTIVE: The study aimed to pool and analyze the effects of different forms of exercise on muscle strength (handgrip strength [HGS]), and physical performance (timed up and go test [TUGT], gait speed [GS] and chair stand test [CS]) in older adults with sarcopenia. METHODS: The effect sizes of all studies retrieved and included by the four databases were analyzed using the network meta-analysis and expressed as standardized mean differences (SMD) and the corresponding 95% confidence intervals (CI). RESULTS: Twenty studies were included in this study with 1347 older adults with sarcopenia. Compared with control and other intervention groups, resistance training (RT) improved HGS [SMD=3.8, 95% CI (1.3, 6.0), p<0.05] and TUGT [SMD = -1.99, 95% CI (-2.82, -1.16), p<0.05] significantly. comprehensive training (CT) [SMD = -2.04, 95% CI (-3.05, -1.06), Pp<0.05] and Comprehensive training under self-management (CT_SM) [SMD = -2.01, 95% CI (-3.24, -0.78), p<0.05] improved TUGT significantly. CONCLUSION: In older adults with sarcopenia, RT could improve HGS and TUGT, CT and CT_SM could improve TUGT. There were no significant changes in CS and GS with any of the exercise training modes.

Possible-sarcopenic screening with disturbed plasma amino acid profile in the elderly.

BACKGROUND: The mass and strength of skeletal muscle decline with age, leading to its progressive dysfunction. High-throughput metabolite profiling provides the opportunity to reveal metabolic mechanisms and the identification of biomarkers. However, the role of amino acid metabolism in possible sarcopenia remains unclear. OBJECTIVES: The aim of this study included exploring variations in plasma amino acid concentrations in elderly individuals who have possible sarcopenia and further attempting to characterize a distinctive plasma amino acid profile through targeted metabolomics. METHODS: A cross-sectional, correlational research design was used for this study. Thirty possible-sarcopenic elderly participants were recruited (n = 30), as determined by the Asian Working Group for Sarcopenia (AWGS). Meanwhile, a reference group of non-sarcopenic (sex-, age-, and Appendicular Skeletal muscle Mass Index (ASMI)-matched non-sarcopenic controls, n = 36) individuals was included to compare the potential differences in metabolic fingerprint of the plasma amino acids associated with sarcopenia. Both groups were conducted the body composition analysis, physical function examination, and plasma amino acid-targeted metabolomics. The amino acids in plasma were measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS). Also, orthogonal partial least-squares-discriminant analysis (OPLS-DA) was applied to characterize the plasma amino acid profile. RESULTS: With respect to Handgrip Strength (HGS), the Five-Repetition Chair Stand Test (CS-5), the Six-Minute Walking Test (6MWT), the arm curl, the 30 s-Chair Stand Test (CST), the 2-Minute Step Test (2MST), the Timed Up-and-Go Test (TUGT), there was a decline in skeletal muscle function in the possible-sarcopenic group compared to the non-sarcopenic group. The mean plasma concentrations of arginine, asparagine, phenylalanine, serine, lysine, glutamine, and threonine were significantly lower in the possible sarcopenia group, whereas cirulline, proline, serine, and glutamic acid concentrations were higher. According to the multi-analysis, glutamine, serine, lysine, threonine, and proline were determined as the potential markers that indicated possible sarcopenia. CONCLUSIONS: The findings characterize significantly altered plasma amino acid metabolisms in the elderly with possible sarcopenia, which aids to screening people who are at a high risk of developing condition, and motivating to design new preventive and therapeutic approaches.

Antibacterial, injectable, and adhesive hydrogel promotes skin healing.

With the development of material science, hydrogels with antibacterial and wound healing properties are becoming common. However, injectable hydrogels with simple synthetic methods, low cost, inherent antibacterial properties, and inherent promoting fibroblast growth are rare. In this paper, a novel injectable hydrogel wound dressing based on carboxymethyl chitosan (CMCS) and polyethylenimine (PEI) was discovered and constructed. Since CMCS is rich in -OH and -COOH and PEI is rich in -NH2, the two can interact through strong hydrogen bonds, and it is theoretically feasible to form a gel. By changing their ratio, a series of hydrogels can be obtained by stirring and mixing with 5 wt% CMCS aqueous solution and 5 wt% PEI aqueous solution at volume ratios of 7:3, 5:5, and 3:7. Characterized by morphology, swelling rate, adhesion, rheological properties, antibacterial properties, in vitro biocompatibility, and in vivo animal experiments, the hydrogel has good injectability, biocompatibility, antibacterial (Staphylococcus aureus: 56.7 × 107 CFU/mL in the blank group and 2.5 × 107 CFU/mL in the 5/5 CPH group; Escherichia coli: 66.0 × 107 CFU/mL in the blank group and 8.5 × 107 CFU/mL in the 5/5 CPH group), and certain adhesion (0.71 kPa in the 5/5 CPH group) properties which can promote wound healing (wound healing reached 98.02% within 14 days in the 5/5 CPH group) and repair of cells with broad application prospects.

MicroRNA-31 regulates TNF-α and IL-17A co-induced-endothelial cell apoptosis by repressing E2F6.

Vascular endothelial cell (VEC) apoptosis is the fundamental cause of pulmonary arterial hypertension. MicroRNA-31 (MiR-31) is a novel target for hypertension treatment. However, the role and mechanism of miR-31 in the apoptosis of VECs remain unclear. The purpose of this study is to determine whether miR-31 plays an important role in VEC apoptosis as well as the detailed mechanisms involved. We found that pro-inflammatory cytokines IL-17A and TNF-α were highly expressed in serum and aorta, and the expression of miR-31 was significantly increased in aortic intimal tissue from Angiotensin II (AngII)- induced hypertensive mice (WT-AngII) compared with control mice (WT-NC). In vitro, co-stimulation of VECs with IL-17A and TNF-α resulted in increased expression of miR-31 and VEC apoptosis. MiR-31 inhibition strikingly decreased TNF-α and IL-17A co-induced VEC apoptosis. Mechanistically, in IL-17A and TNF-α co-stimulated VECs (co-induced VECs), we found that the activation of the NF-κB signal effectively increased the expression of miR-31. Dual-luciferase reporter gene assay revealed that miR-31 directly targeted and inhibited the expression of the E2F transcription factor 6 (E2F6). The expression of E2F6 was decreased in Co-induced VECs. MiR-31 inhibition significantly alleviated the decreased expression of E2F6 in co-induced VECs. Consistent with the co-stimulated effect of IL-17A and TNF-α on VECs, transfection of siRNA E2F6 induced cell apoptosis without the stimulation of the above cytokines. In conclusion, TNF-α and IL-17A generated in the aortic vascular tissue and serum from Ang II-induced hypertensive mice could trigger VECs apoptosis by the miR-31/E2F6 axis. To sum up, our study suggests that the key factor between cytokine co-stimulation effect and VEC apoptosis was miR-31/E2F6 axis, which was mainly regulated by NF-қB signaling pathway. This gives us a new sight to treat hypertension-associated VR.

Functional graphene oxide for organic pollutants removal from wastewater: a mini review.

Graphene oxide (GO), an important derivative of graphene, with a variety of active oxygen-containing groups (hydroxyl, carboxyl and epoxy) on its surface is easy to be functionalized to obtain adsorbent with high adsorption capacity. To date, the adsorption behaviour of organic pollutants by functionalized GO adsorbents have been extensively studied, but there has been no systematic review regarding the functionalization method of GO for the purpose to remove organic pollutants from wastewater. The leading objective of this review is to (i) summarize the functionalization strategies of GO for organic pollutants removal (covalent functionalization and non-covalent functionalization), (ii) evaluate the adsorption performance of functional GO towards organic pollutants by taking aromatic pollutants and dyes as examples and (iii) discuss the regeneration property and adsorption mechanism of functional GO adsorbent. In addition, the problems of existing studies and future research directions are also identified briefly.

Sloshing Resonance of an Acoustically Levitated Air-in-Liquid Compound Drop.

An acoustically levitated air-in-liquid compound drop is set into an out-of-phase azimuthal sloshing resonance by a modulated frequency with modes n = 4-9. Waveforms of the inner and outer liquid-air interfaces conform to the classical Saffren model. Resonance peaks and their harmonics in the frequency spectrum are found to be a function of drop dimension and resonance modes. Drops with multiple small air bubbles do not resonate in sync because of asymmetry. This work has significant implications in the dynamics of core-shell compound drops.

De novo Explorations of Sarcopenia via a Dynamic Model.

Background: The cause of sarcopenia has been observed over decades by clinical trials, which, however, are still insufficient to systematically unravel the enigma of how resistance exercise mediates skeletal muscle mass. Materials and Methods: Here, we proposed a minimal regulatory network and developed a dynamic model to rigorously investigate the mechanism of sarcopenia. Our model is consisted of eight ordinary differential equations and incorporates linear and Hill-function terms to describe positive and negative feedbacks between protein species, respectively. Results: A total of 720 samples with 10 scaled intensities were included in simulations, which revealed the expression level of AKT (maximum around 3.9-fold) and mTOR (maximum around 5.5-fold) at 3, 6, and 24 h at high intensity, and non-monotonic relation (ranging from 1.2-fold to 1.7-fold) between the graded intensities and skeletal muscle mass. Furthermore, continuous dynamics (within 24 h) of AKT, mTOR, and other proteins were obtained accordingly, and we also predicted the delaying effect with the median of maximized muscle mass shifting from 1.8-fold to 4.6-fold during a 4-fold increase of delay coefficient. Conclusion: The de novo modeling framework sheds light on the interdisciplinary methodology integrating computational approaches with experimental results, which facilitates the deeper understandings of exercise training and sarcopenia.

Evaluation for the effects of nutritional education on Chinese elite male young soccer players: The application of adjusted dietary balance index (DBI).

OBJECTIVES: To evaluate the effect of nutrition education on Chinese elite male young soccer players through the knowledge, attitude, behavior (KAP) survey and an adjusted dietary balance index (DBI). METHODS: 30 Chinese elite male young soccer players were randomly divided into two groups: lecture group (N = 15, Age: 16.7 ±â€¯1.8 years, Height: 173.9 ±â€¯9.0 cm; Weight: 62.4 ±â€¯13.0 kg; Training years: 5.6 ±â€¯2.7 years) and non-lecture group (N = 15, Age: 16.8 ±â€¯1.7 years, Height: 175.5 ±â€¯7.9 cm; Weight: 62.5 ±â€¯12.3 kg; Training years: 6.2 ±â€¯3.3). The comics book was given to the non-lecture group, while the a four-week nutritional quality education along with comic books were given to the lecture group. Before and after 4 weeks nutritional education, dietary nutritional status of both groups was assessed. The main outcome measurements included the scores for each part of the KAP survey, diet status (food-weighing method) and the dietary index in the adjusted DBI-07 system (DBI-low bound score, LBS; DBI-high bound score, HBS; and DBI-diet quality distance, DQD). RESULTS: In the lecture group, significant differences were found in the scores of general nutrition knowledge, sports nutrition knowledge and total scores of KAP dietary questionnaire after 4 weeks nutritional education (P < 0.01). However, there is no significant difference in dietary attitude and dietary behavior (P > 0.05) on both two groups. There is no significant change in the DBI-low bound score (LBS), DBI-high bound score (HBS) and DBI-diet quality distance (DQD) of dietary quality index (P > 0.05) in both two groups. CONCLUSIONS: Four weeks nutritional quality education improved the understanding of dietary nutrition among Chinese elite male young soccer players.

Effects of Three Commercially Available Sports Drinks on Substrate Metabolism and Subsequent Endurance Performance in a Postprandial State.

Purpose: To examine the effects of commercially available sports beverages with various components on substrate metabolism and subsequent performance. Methods: Two studies were conducted in a double-blinded, counterbalanced manner. Study I was designed to determine the glycemic index, while study II determined the utilization of substrates and subsequent exercise performance. Ten healthy male participants (age 21.70 ± 2.41 years, height 176.60 ± 5.23 cm, weight 66.58 ± 5.38 kg, V̇O2max 48.1 ± 8.4 mL/kg/min) participated in both study I and study II. Three types of commercially available sports beverage powders were used. The powders consisted primarily of oligosaccharides (low molecular weight carbohydrates, L-CHO), hydrolyzed starch (high molecular weight CHO, H-CHO), and whey protein powder with carbohydrate (CHO-PRO). They were dissolved in purified water with identical CHO concentration of 8% (w/v). In study I, each participant underwent two oral glucose tolerance tests (OGTT) and one glycemic response test for each sports drink. In study II, participants cycled for 60 min at 70% V̇O2max, one hour after consuming a standardized breakfast. One of four prescribed beverages (L-CHO, H-CHO, CHO-PRO, and Placebo control, PLA) was served at 0, 15, 30, 45 min during the exercise. Six hours after the first exercise session, participants came back for a "time to exhaustion test" (TTE). Blood samples were drawn at 0, 30, and 60 min in the first exercise session, while arterial blood gas analysis was conducted at 0, 30, and 60 min in both sessions. Subjective feelings (rating of perceived exertion and abdominal discomfort) were also evaluated every 30 min during exercise. Results: Compared to the reference standardized glucose solution, the glycemic index of the L-CHO beverage was 117.70 ± 14.25, while H-CHO was 105.50 ± 12.82, and CHO-PRO was 67.23 ± 5.88. During the exercise test, the insulin level at 30 and 60 min was significantly lower than baseline following the treatment of L-CHO, H-CHO, and PLA (p < 0.05). The CHO oxidation rate at 60 min in the first exercise session was significantly higher than that at 60 min in the second exercise session following the L-CHO treatment (p < 0.05). Time to exhaustion was not significantly different (p > 0.05). Conclusion: The CHO sports beverage with additional PRO maintains insulin production during endurance cycling at 70% V̇O2max in the postprandial state. L-CHO sports beverage suppresses fat utilization during the subsequent exercise performance test. The subsequent exercise performance (as evaluated by TTE) was not influenced by the type of CHO or the addition of PRO in the commercially available sports beverages used in the present study.