Activation of heme oxygenase-1 by laminar shear stress ameliorates high glucose-induced endothelial cell and smooth muscle cell dysfunction.

High glucose (HG)-induced endothelial cell (EC) and smooth muscle cell (SMC) dysfunction is critical in diabetes-associated atherosclerosis. However, the roles of heme oxygenase-1 (HO-1), a stress-response protein, in hemodynamic force-generated shear stress and HG-induced metabolic stress remain unclear. This investigation examined the cellular effects and mechanisms of HO-1 under physiologically high shear stress (HSS) in HG-treated ECs and adjacent SMCs. We found that exposure of human aortic ECs to HSS significantly increased HO-1 expression; however, this upregulation appeared to be independent of adenosine monophosphate-activated protein kinase, a regulator of HO-1. Furthermore, HSS inhibited the expression of HG-induced intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and reactive oxygen species (ROS) production in ECs. In an EC/SMC co-culture, compared with static conditions, subjecting ECs close to SMCs to HSS and HG significantly suppressed SMC proliferation while increasing the expression of physiological contractile phenotype markers, such as α-smooth muscle actin and serum response factor. Moreover, HSS and HG decreased the expression of vimentin, an atherogenic synthetic phenotypic marker, in SMCs. Transfecting ECs with HO-1-specific small interfering (si)RNA reversed HSS inhibition on HG-induced inflammation and ROS production in ECs. Similarly, reversed HSS inhibition on HG-induced proliferation and synthetic phenotype formation were observed in co-cultured SMCs. Our findings provide insights into the mechanisms underlying EC-SMC interplay during HG-induced metabolic stress. Strategies to promote HSS in the vessel wall, such as continuous exercise, or the development of HO-1 analogs and mimics of the HSS effect, could provide an effective approach for preventing and treating diabetes-related atherosclerotic vascular complications.

Hierarchical Micro- and Mesoporous Zeolitic Imidazolate Framework-8-Based Enzyme Hybrid for Combination Antimicrobial by Lysozyme and Lactoferrin.

Pathogenic bacteria have consistently posed a formidable challenge to human health, creating the critical need for effective antibacterial solutions. In response, enzyme-metal-organic framework (MOF) composites have emerged as a promising class of antibacterial agents. This study focuses on the development of an enzyme-MOF composite based on HZIF-8, incorporating the advantages of simple synthesis, ZIF-8 antibacterial properties, lysozyme hydrolysis, and high biological safety. Through a one-pot method, core-shell nanoparticles (HZIF-8) were synthesized. This structure enables efficient immobilization of lysozyme and lactoferrin within the HZIF-8, resulting in the formation of the lysozyme-lactoferrin@HZIF-8 (LYZ-LF@HZIF-8) composite. Upon exposure to light irradiation, HZIF-8 itself possessed antibacterial properties. Lysozyme initiated the degradation of bacterial peptidoglycan and lactoferrin synergistically enhanced the antibacterial effect of lysozyme. All of the above ultimately contributed to comprehensive antibacterial activity. Antibacterial assessments demonstrated the efficacy of the LYZ-LF@HZIF-8 composite, effectively eradicating Staphylococcus aureus at a cell density of 1.5 × 106 CFU/mL with a low dosage of 200 µg/mL and completely inactivating Escherichia coli at 400 µg/mL with the same cell density. The enzyme-MOF composite exhibited significant and durable antibacterial efficacy, with no apparent cytotoxicity in vitro, thereby unveiling expansive prospects for applications in the medical and food industries.

Effect of stress on the rehabilitation performance of rats with repetitive mild fluid percussion-induced traumatic brain injuries.

Animal models of traumatic brain injury (TBI) have shown that impaired motor and cognitive function can be improved by physical exercise. However, not each animal with TBI can be well rehabilitated at the same training intensity due to a high inter-subject variability. Hence, this paper presents a two-stage wheel-based mixed-mode rehabilitation mechanism by which the effect of stress on the rehabilitation performance was investigated. The mixed-mode rehabilitation mechanism consists of a two-week adaptive and a one-week voluntary rehabilitation program as Stages 1 and 2, respectively. In Stage 1, the common over and undertraining problem were completely resolved due to the adaptive design, and rats ran voluntarily over a 30-min duration in Stage 2. The training intensity adapted to the physical condition of all the TBI rats at all times in Stage 1, and then the self-motivated running rats were further rehabilitated under the lowest level of stress in Stage 2. For comparison purposes, another group of rats took a 3-week adaptive rehabilitation program. During the 3-week program, the rehabilitation performance of the rats were assessed using modified neurologic severity score (mNSS) and an 8-arm radial maze. Surprisingly, the group taking the mixed mode program turned out to outperform its counterpart in terms of mNSS. The mixed-mode rehabilitation mechanism was validated as an effective and efficient way to help rats restore motor, neurological and cognitive function after TBI. It was validated that the rehabilitation performance can be optimized under the lowest level of stress.

Christensenella minuta interacts with multiple gut bacteria.

Introduction: Gut microbes form complex networks that significantly influence host health and disease treatment. Interventions with the probiotic bacteria on the gut microbiota have been demonstrated to improve host well-being. As a representative of next-generation probiotics, Christensenella minuta (C. minuta) plays a critical role in regulating energy balance and metabolic homeostasis in human bodies, showing potential in treating metabolic disorders and reducing inflammation. However, interactions of C. minuta with the members of the networked gut microbiota have rarely been explored. Methods: In this study, we investigated the impact of C. minuta on fecal microbiota via metagenomic sequencing, focusing on retrieving bacterial strains and coculture assays of C. minuta with associated microbial partners. Results: Our results showed that C. minuta intervention significantly reduced the diversity of fecal microorganisms, but specifically enhanced some groups of bacteria, such as Lactobacillaceae. C. minuta selectively enriched bacterial pathways that compensated for its metabolic defects on vitamin B1, B12, serine, and glutamate synthesis. Meanwhile, C. minuta cross-feeds Faecalibacterium prausnitzii and other bacteria via the production of arginine, branched-chain amino acids, fumaric acids and short-chain fatty acids (SCFAs), such as acetic. Both metagenomic data analysis and culture experiments revealed that C. minuta negatively correlated with Klebsiella pneumoniae and 14 other bacterial taxa, while positively correlated with F. prausnitzii. Our results advance our comprehension of C. minuta's in modulating the gut microbial network. Conclusions: C. minuta disrupts the composition of the fecal microbiota. This disturbance is manifested through cross-feeding, nutritional competition, and supplementation of its own metabolic deficiencies, resulting in the specific enrichment or inhibition of the growth of certain bacteria. This study will shed light on the application of C. minuta as a probiotic for effective interventions on gut microbiomes and improvement of host health.

Photoredox Catalyzed Synthesis of gem-Difluoroalkenes and Monofluorinated Cyclooctenes via 1,5-HAT Process.

gem-Difluoroalkenes and monofluorinated cycloalkenes have emerged as basic structural units in a variety of bioactive molecules and natural products. Thus, developing straightforward and efficient methods for synthesizing fluorinated alkene compounds is of considerable significance. Herein, we disclose a visible-light-induced defluorination of 2-trifluoromethyl-1-alkene via a 1,5-HAT process using N-alkoxyphtalimides as both radical precursor and potential nucleophile. The mild and stepwise reaction leads to a variety of structurally diverse gem-difluoroalkenes and monofluorinated cyclooctenes with high efficiency, respectively.

Impact of Interprofessional Collaborative Practice on Functional Improvements Among Post-Acute Stroke Survivors: A Retrospective Cross-Sectional Study.

Background: Stroke survivors in post-acute care frequently experience physiological dysfunction and reduced quality of life. This study aims to assess the impact of the Post-Acute Care Interprofessional Collaborative Practice (PAC-IPCP) program across different care settings, and to identify sensitive tools for assessing physiological functions among post-acute stroke survivors. Methods: This retrospective study involved 210 stroke survivors in Taiwan. Participants who self-selection for their preferred between hospital care setting and home care setting under PAC-IPCP. Multiple assessment tools were utilized, including the Barthel Index (BI), Functional Oral Intake Scale (FOIS), Mini Nutritional Assessment (MNA), EQ-5D-3L, and Instrumental Activities of Daily Living (IADL). The logistic regression was used to estimate the odds ratios of various functional assessment tools between hospital and home care settings. Additionally, the area under the ROC curves was used to determine which functional assessment tools had higher accuracy in measuring the association between care settings. Results: Of the study population, 138 stroke survivors (65.71%) selection hospital care setting and 72 stroke survivors (34.29%) selection home care setting. The PAC-IPCP program was equally effective in both care settings for physical function status and quality of life improvements. Specifically, the BI emerged as the most sensitive tool for assessing care settings, with an adjusted OR of 1.04 (95% CI:1.02-1.07, p < 0.0001; AUC = 0.7557). IPCP-based hospital and home care models are equally effective in facilitating improved functional outcomes in post-acute stroke survivors. Conclusion: The PAC-IPCP program is versatile and effective across care settings. The BI stands out as a robust assessment tool for physiological functions, endorsing its broader clinical application. Future studies should also consider swallowing and nutritional status for a more holistic approach to rehabilitation.

Heart rate variability biofeedback enhances cognitive, motor, psychological, and autonomic functions in post-stroke rehabilitation.

Post-stroke patients often experience psychological distress and autonomic nervous system (ANS) dysregulation, impacting their well-being. This study evaluated the effectiveness of heart rate variability (HRV) biofeedback on cognitive, motor, psychological, and ANS functions in sixty-two ischemic stroke patients (43 males, mean age = 60.1) at a Medical Center in southern Taiwan. To prevent interaction, we allocated patients to the HRV biofeedback or control (usual care) group based on their assigned rehabilitation days, with 31 patients in each group. Assessments conducted at baseline, three, and six months included the Montreal Cognitive Assessment (MoCA), Fugl-Meyer Assessment for Upper Extremities (FMA-UE), Perceived Stress Scale, Hospital Anxiety and Depression Scales (HADS), and HRV indices. Mixed-effect models were used to analyze Group by Time interactions. The results revealed significant interactions across all functions. At 3 months, significant improvements in the HRV biofeedback group were observed only in MoCA, FMA-UE, and HADS-depression scores compared to the control group. By 6 months, all measured outcomes demonstrated significant improvements in the biofeedback group relative to the control group. These results suggest that HRV biofeedback may be an effective complementary intervention in post-stroke rehabilitation, warranting further validation.

Effects of Thermal Stimulation and Transcutaneous Electrical Nerve Stimulation on Sensory and Motor Function of Upper Extremity in Acute Stroke Survivors: A Randomized Controlled Pilot Study.

Objective Upper-limb coordination is crucial for daily activities, especially among stroke survivors who may encounter obstacles during upper-limb rehabilitation. This study aimed to investigate the effects of thermal stimulation (TS) and transcutaneous electrical nerve stimulation (TENS) on sensory and motor function during recovery in acute stroke patients. Design This is a parallel study with a randomized controlled design. The experiment was conducted in the E-Da Hospital Rehabilitation Department, Kaohsiung, Taiwan. Intervention Thirty participants were in-patients with acute stroke at the E-Da Hospital. Participants were randomly assigned to three groups for a one-week intervention: exercise combined with TS, exercise combined with TENS, or conventional physical therapy with exercise alone. The Fugl-Meyer upper extremity scale, Brunnstrom stage, minimal current perception (MCP), and modified Ashworth scale were collected for the assessment. Results The outcomes demonstrated considerable improvement in MCP in all the groups after treatment. Specifically, the groups receiving TS and TENS showed significant improvements in the Brunnstrom stage, suggesting that both treatments improved distal motor recovery. Conclusion The results, following a one-week intervention period, suggested that both TS and TENS contributed to the improvement of motor and sensory function, with a significant impact on the Brunnstrom stage in the upper extremity, particularly in the distal region. The inclusion of TS or TENS in rehabilitation protocols improved distal motor function compared to baseline measures, suggesting these treatments as effective components in acute stroke rehabilitation.

Effect of electroacupuncture on expression of protein phosphorylation in hippocampus tissues of rats with chronic fatigue syndrome. / ç”µé’ˆå¹²é¢„å¯¹æ ¢æ€§ç–²åŠ³ç»¼åˆå¾å¤§é¼ æµ·é©¬ç»„ç»‡è›‹ç™½è´¨ç£·é ¸åŒ–è¡¨è¾¾çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on behavior and hippocampal protein phosphorylation in rats with chronic fatigue syndrome (CFS), so as to explore its mechanisms underlying improvement of CFS. METHODS: Male SD rats were randomly divided into control, model and EA groups (n=12 rats in each group). The CFS model was established by chronic multifactor combined with stress stimulation (treadmill training + restraint stress + sleep disturbance + crowded environment). For rats of the EA group, EA (1 mA, frequency of 10 Hz) was applied to "Shenting" (GV24) (with an acupuncture needle penetrated from GV24 to "Baihui" ï¼»GV20ï¼½) and "Dazhui" (GV14) for 15 min, once daily for 28 days. After treatment, the body weight, food intake and water intake of rats in each group were observed. The fatigue degree of rats was evaluated by Semi-quantitative score observation table of the general condition of experimental rats.The open field test (OFT) was used to assess the rats'anxiety severity by detecting the total number of grid-crossing and the times of the central area entered in 5 min, and Morris water maze test was employed to assess the rats' learning-memory ability by detecting the escape latency in 1 min, and the times of the original platform quadrant crossing in 1 min. The hippocampaus was taken for phosphorylated Label-free quantitative proteomics analysis by using Maxquant technology based on full scan mode to calculate the integral of each peptide signal of liquid chromatography-mass spectrometry(LC-MS). The differentially-expressed proteins (>1.5 folds for up-regulation or <0.67 folds for down-regulation) were evaluated by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. RESULTS: Compared with the control group, the body weight, food intake, and the times of original-platform quadrant crossing of spatial exploring of Morris water maze test were significantly decreased (P<0.01, P<0.05) , and the score of general conditions, times of grid-crossing and center area-entering of OFT, and the escape latency of navigation task were apparently increased (P<0.01) in rats of the model group. After EA intervention, the decreased original-platform quadrant crossing, and the increased score of general conditions, times of grid-crossing and the escape latency of navigation task were all reversed (P<0.01, P<0.05). Outcomes of proteomics analysis indicated that compared with the model group, there were 297 differentially expressed peptide (48 up-regulated and 249 down-regulated) segments in the control group, and there were 245 differentially expressed peptide (185 up-regulated and 60 down-regulated) segments in the EA group, in which, 25 overlapping peptide segments were reversed after EA treatment, corresponding to 24 proteins, mainly involving cytoskeletal structure. GO function annotation analysis showed that the top three differentially expressed phosphorylated proteins involved in the effect of EA intervention were the actin filament polymerization, protein depolymerization and cytoskeletal tissue in the biological process, the actin binding, structural molecular activity and cytoskeletal protein binding in the molecular function, and the cytoskeleton, dendrites and dendritic trees in the cellular component, respectively. The KEGG pathway annotation analysis for differentially expressed phosphorylated proteins showed that theinsulin secretion, axon guidance, phosphatidylinositol signaling system and lysine biosynthesis, etc. were involved in the effect of EA intervention. CONCLUSIONS: EA of GV24-GV20 and GV14 can improve the general state, anxiety and learning-memory ability of CFS model rats, which may be related to its functions in regulating the hippocampal protein phosphorylation level, and repairing the structure and function of synapses in hippocampus.

Christensenella strain resources, genomic/metabolomic profiling, and association with host at species level.

The gut commensal bacteria Christensenellaceae species are negatively associated with many metabolic diseases, and have been seen as promising next-generation probiotics. However, the cultured Christensenellaceae strain resources were limited, and their beneficial mechanisms for improving metabolic diseases have yet to be explored. In this study, we developed a method that enabled the enrichment and cultivation of Christensenellaceae strains from fecal samples. Using this method, a collection of Christensenellaceae Gut Microbial Biobank (ChrisGMB) was established, composed of 87 strains and genomes that represent 14 species of 8 genera. Seven species were first described and the cultured Christensenellaceae resources have been significantly expanded at species and strain levels. Christensenella strains exerted different abilities in utilization of various complex polysaccharides and other carbon sources, exhibited host-adaptation capabilities such as acid tolerance and bile tolerance, produced a wide range of volatile probiotic metabolites and secondary bile acids. Cohort analyses demonstrated that Christensenellaceae and Christensenella were prevalent in various cohorts and the abundances were significantly reduced in T2D and OB cohorts. At species level, Christensenellaceae showed different changes among healthy and disease cohorts. C. faecalis, F. tenuis, L. tenuis, and Guo. tenuis significantly reduced in all the metabolic disease cohorts. The relative abundances of C. minuta, C. hongkongensis and C. massiliensis showed no significant change in NAFLD and ACVD. and C. tenuis and C. acetigenes showed no significant change in ACVD, and Q. tenuis and Geh. tenuis showed no significant change in NAFLD, when compared with the HC cohort. So far as we know, this is the largest collection of cultured resource and first exploration of Christensenellaceae prevalences and abundances at species level.

Comparing verum and sham acupoint catgut embedding for adults with obesity: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Previous clinical trials have reported that acupoint catgut embedding (ACE) is a useful modality for weight loss. However, no study has specifically investigated the effectiveness and safety of comparing verum and sham ACE in adults with obesity. Thus, this study aimed to evaluate the effectiveness and safety of comparing verum and sham ACE in obese adults. METHODS: A comprehensive literature search was conducted in the electronic databases of PUBMED, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, and China Biomedical Literature Service System from inception to April 1, 2022. Randomized clinical trials that focused on evaluating the effectiveness of comparing verum and sham ACE in adults with obesity were included. The primary outcomes included reduction in body weight, body mass index, hip circumference, and waist circumference. The secondary outcomes consisted of a decrease in body fat percentage and the occurrence rate of adverse events. The methodological quality of the included randomized clinical trials was evaluated using the Cochrane Risk-of-bias tool. Statistical analysis was performed using RevMan 5.4 software. RESULTS: Six trials involving 679 adults with obesity were included in this study and entered in the data analysis of systematic review and meta-analysis. Results of the meta-analysis revealed significant reduction in body weight (mean difference [MD] = -1.68, 95% confidence intervals (CI) [-2.34, -1.01], I2 = 51%, P < .001), body mass index (MD = -0.51, 95% CI [-0.81, -0.21], I2 = 74%, P < .001), hip circumference (MD = -1.11, 95% CI [-1.67, -0.55], I2 = 0%, P < .001), waist circumference (MD = -2.42, 95% CI [-3.38, -1.45], I2 = 68%, P < .001), and decrease in body fat percentage (MD = -0.83, 95% CI [-1.30, -0.36], I2 = 16%, P < .001) in comparing verum and sham ACE. However, no significant difference was identified in AEs (odds ratio = 1.53, 95% CI [0.80, 2.95], I2 = 0%, P = .20) between the 2 groups. CONCLUSION: ACE is effective in the treatment of obesity in adults with safety profile. Further studies with higher quality and larger sample size are warranted to confirm the current findings.

DJ1 Ameliorates AD-like Pathology in the Hippocampus of APP/PS1 Mice.

Objective: To explore whether the protein Deglycase protein 1 (DJ1) can ameliorate Alzheimer's disease (AD)-like pathology in Amyloid Precursor Protein/Presenilin 1 (APP/PS1) double transgenic mice and its possible mechanism to provide a theoretical basis for exploring the pathogenesis of AD. Methods: Adeno-associated viral vectors (AAV) of DJ1-overexpression or DJ1-knockdown were injected into the hippocampus of 7-month-old APP/PS1 mice to construct models of overexpression or knockdown. Mice were divided into the AD model control group (MC), AAV vector control group (NC), DJ1-overexpression group (DJ1 +), and DJ1-knockdown group (DJ1 -). After 21 days, the Morris water maze test, immunohistochemistry, immunofluorescence, and western blotting were used to evaluate the effects of DJ1 on mice. Results: DJ1 + overexpression decreased the latency and increased the number of platform traversals in the water maze test. DJ1 - cells were cured and atrophied, and the intercellular structure was relaxed; the number of age spots and the expression of AD-related proteins were significantly increased. DJ1 + increased the protein expression of Nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase-1 (HO-1), light chain 3 (LC3), phosphorylated AMPK (p-AMPK), and B cell lymphoma-2 (BCL-2), as well as the antioxidant levels of total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC), and Glutathione peroxidase (GSH-PX), while decreasing the levels of Kelch-like hydrates-associated protein 1 (Keap1), mammalian target of rapamycin (mTOR), p62/sequestosome1 (p62/SQSTM1), Caspase3, and malondialdehyde (MDA). Conclusion: DJ1-overexpression can ameliorate learning, memory, and AD-like pathology in APP/PS1 mice, which may be related to the activation of the NRF2/HO-1 and AMPK/mTOR pathways by DJ1.