Stress Injury Research Articles

Effectiveness of Injection of Ginkgo biloba Leaf Extract Combined with Early Rehabilitation on Functional Recovery in Patients Following Ischemic Stroke

The interest in the development of traditional Chinese medicine for the treatment of ischemic stroke (IS) is growing. In this study, we aim to examine the therapeutic effects of the standardized extract of Ginkgo biloba leaf EGb-761 on neurological behavioral outcomes and brain infarction in rats following cerebral ischemia. Additionally, we evaluated the effectiveness of combining EGb-761 injection with early rehabilitation in improving the functional status of patients with IS. The rats were induced with focal transient cerebral ischemia by means of middle cerebral artery occlusion (MCAO). The rats undergoing MCAO/reperfusion were given an intraperitoneal injection of different doses of EGb-761. A total of 65 patients with IS were recruited and assigned into receiving conventional treatments and intravenous drips of Ginaton injection, followed by early rehabilitation. The results showed that neurological deficit scores, brain infarct volume, neuronal apoptosis, and oxidative stress injury were reduced in the MCAO/reperfusion rats treated with different doses of EGb-761 compared to those without EGb-761 treatment. These reductions were more significant in the high-dose EGb-761 treatment group (P <0.05). Both EGb-761 treatment and conventional treatment combined with early rehabilitation resulted in increased muscle strength and higher total BI scores in the patients. However, these increases were more pronounced in the group receiving Ginaton injection (P <0.05). In conclusion, our study demonstrates that acute administration of EGb-761 may contribute to better neurological behavioral outcomes and reduced area of brain infarction in rats following cerebral ischemia and EGb-761 treatment integrated with early rehabilitation could improve the muscle strength and functional recovery of patients with IS.

Bidirectional regulation mechanism of TRPM2 channel: role in oxidative stress, inflammation and ischemia-reperfusion injury

Bidirectional regulation mechanism of TRPM2 channel: role in oxidative stress, inflammation and ischemia-reperfusion injury

M6A demethylase FTO-stabilized exosomal circBRCA1 alleviates oxidative stress-induced granulosa cell damage via the miR-642a-5p/FOXO1 axis

BackgroundPremature ovarian insufficiency (POI) is an important cause of female infertility and seriously impacts the physical and psychological health of patients. Human umbilical cord mesenchymal stem cell-derived exosomes (HucMSCs-Exs, H-Exs) have exhibited protective effects on ovarian function with unclear mechanisms.MethodsA comprehensive analysis of the Gene Expression Omnibus (GEO) database were used to identify POI-associated circRNAs and miRNAs. The relationship between HucMSC-derived exosomal circBRCA1/miR-642a-5p/FOXO1 axis and POI was examined by RT-qPCR, Western blotting, reactive oxygen species (ROS) staining, senescence-associated β-gal (SA-β-gal) staining, JC-1 staining, TEM, oxygen consumption rate (OCR) measurements and ATP assay in vivo and in vitro. RT-qPCR detected the expression of circBRCA1 in GCs and serum of patients with normal ovarian reserve function (n = 50) and patients with POI (n = 50); then, the correlation of circBRCA1 with ovarian reserve function indexes was analyzed.ResultsHerein, we found that circBRCA1 was decreased in the serum and ovarian granulosa cells (GCs) of patients with POI and was associated with decreased ovarian reserve. H-Exs improved the disorder of the estrous cycles and reproductive hormone levels, reduced the number of atretic follicles, and alleviated the apoptosis and senescence of GCs in rats with POI. Moreover, H-Exs mitigated mitochondrial damage and reversed the reduced circBRCA1 expression induced by oxidative stress in GCs. Mechanistically, FTO served as an eraser to increase the stability and expression of circBRCA1 by mediating the m6A demethylation of circBRCA1, and exosomal circBRCA1 sponged miR-642a-5p to block its interaction with FOXO1. CircBRCA1 insufficiency aggravated mitochondrial dysfunction, mimicking FTO or FOXO1 depletion effects, which was counteracted by miR-642a-5p inhibition.ConclusionH-Exs secreted circBRCA1 regulated by m6A modification, directly sponged miR-642a-5p to upregulate FOXO1, resisted oxidative stress injuries in GCs and protected ovarian function in rats with POI. Exosomal circBRCA1 supplementation may be a general prospect for the prevention and treatment of POI.Graphical

Mitochondria fission accentuates oxidative stress in hyperglycemia-induced H9c2 cardiomyoblasts in vitro by regulating fatty acid oxidation.

Oxidative stress plays a pivotal role in the development of diabetic cardiomyopathy (DCM). Previous studies have revealed that inhibition of mitochondrial fission suppressed oxidative stress and alleviated mitochondrial dysfunction and cardiac dysfunction in diabetic mice. However, no research has confirmed whether mitochondria fission accentuates hyperglycemia-induced cardiomyoblast oxidative stress through regulating fatty acid oxidation (FAO). We used H9c2 cardiomyoblasts exposed to high glucose (HG) 33 mM to simulate DCM in vitro. Excessive mitochondrial fission, poor cell viability, and lipid accumulation were observed in hyperglycemia-induced H9c2 cardiomyoblasts. Also, the cells were led to oxidative stress injury, lower adenosine triphosphate (ATP) levels, and apoptosis. Dynamin-related protein 1 (Drp1) short interfering RNA(siRNA) decreased targeted marker expression, inhibited mitochondrial fragmentation and lipid accumulation, suppressed oxidative stress, reduced cardiomyoblast apoptosis, and improved cell viability and ATP levels in HG-exposed H9c2 cardiomyoblasts, but not in carnitine palmitoyltransferase 1 (CPT1) inhibitor etomoxir treatment cells. We also found subcellular localization of CPT1 on the mitochondrial membrane, FAO, and levels of nicotinamide adenine dinucleotide phosphate(NADPH) were suppressed after exposure to HG treatment, whereas Drp1 siRNA normalized mitochondrial CPT1, FAO, and NADPH. However, the blockade of FAO with etomoxir abolished the above effects of Drp1 siRNA in hyperglycemia-induced H9c2 cardiomyoblasts. The preservation of mitochondrial function through the Drp1/CPT1/FAO pathway is the potential mechanism of inhibited mitochondria fission in attenuating oxidative stress injury of hyperglycemia-induced H9c2 cardiomyoblasts.

Environmentally responsive hydrogel promotes vascular normalization to enhance STING anti-tumor immunity

The immunosuppressive microenvironment of malignant tumors severely hampers the effectiveness of anti-tumor therapy. Moreover, abnormal tumor vasculature interacts with immune cells, forming a vicious cycle that further interferes with anti-tumor immunity and promotes tumor progression. Our pre-basic found excellent anti-tumor effects of c-di-AMP and RRx-001, respectively, and we further explored whether they could be combined synergistically for anti-tumor immunotherapy. We chose to load these two drugs on PVA-TSPBA hydrogel scaffolds that expressly release drugs within the tumor microenvironment by in situ injection. Studies have shown that c-di-AMP activates the STING pathway, enhances immune cell infiltration, and reverses tumor immunosuppression. Meanwhile, RRx-001 releases nitric oxide, which increases oxidative stress injury in tumor cells and promotes apoptosis. Moreover, the combination of the two presented more powerful pro-vascular normalization and reversed tumor immunosuppression than the drug alone. This study demonstrates a new design option for anti-tumor combination therapy and the potential of tumor environmentally responsive hydrogel scaffolds in combination with anti-tumor immunotherapy.

Hip and core exercise programme prevents running-related overuse injuries in adult novice recreational runners: a three-arm randomised controlled trial (Run RCT)

ObjectiveThis study aims to investigate the efficacy of two exercise interventions in reducing lower extremity (LE) injuries in novice recreational runners.MethodsNovice runners (245 female, 80 male) were randomised into hip...

Zinc-Based ROS Amplifiers Trigger Cancer Chemodynamic/Ion Interference Therapy Through Self-Cascade Catalysis.

Nanozyme-mediated chemodynamic therapy has emerged as a promising strategy due to its tumor specificity and controlled catalytic activity. However, the poor efficacy caused by low hydrogen peroxide (H2O2) levels in the tumor microenvironment (TME) poses challenges. Herein, an H2O2 self-supplying nanozyme is constructed through loading peroxide-like active platinum nanoparticles (Pt NPs) on zinc peroxide (ZnO2) (denoted as ZnO2@Pt). ZnO2 releases H2O2 in response to the acidic TME. Pt NPs catalyze the hydroxyl radical generation from H2O2 while reducing the mitigation of oxidative stress by glutathione, serving as a reactive oxygen (ROS) amplifier through self-cascade catalysis. In addition, Zn2+ released from ZnO2 interferes with tumor cell energy supply and metabolism, enabling ion interference therapy to synergize with chemodynamic therapy. In vitro studies demonstrate that ZnO2@Pt induces cellular oxidative stress injury through enhanced ROS generation and Zn2+ release, downregulating ATP and NAD+ levels. In vivo assessment of anticancer effects showed that ZnO2@Pt could generate ROS at tumor sites to induce apoptosis and downregulate energy supply pathways associated with glycolysis, resulting in an 89.7% reduction in tumor cell growth. This study presents a TME-responsive nanozyme capable of H2O2 self-supply and ion interference therapy, providing a paradigm for tumor-specific nanozyme design.

Prevalence of text neck syndrome, its impact on neck dysfunction, and its associated factors among medical students: A cross-sectional study.

Students increasingly rely on digital devices, leading to text neck syndrome, a common overuse syndrome caused by repetitive forward neck flexion. This study aimed to determine the prevalence of text neck syndrome among medical students and the resulting neck dysfunction and to investigate the possible associated factors. This cross-sectional study used an online self-developed questionnaire among medical students. Students' characteristics and data about smartphone usage were evaluated for diagnosis. Individuals with at least 3 of the 6 text neck syndrome symptoms and a history of more than four hours a day spent on a smartphone were diagnosed with text neck syndrome. Neck dysfunction was measured using the neck disability index. Descriptive statistics and the chi-square test were used. P values < 0.05 were considered statistically significant. The study found that 31.7% of students with text neck syndrome have mild neck disabilities, with a higher proportion of females (40%). The characteristics that have a significant relation to text neck syndrome include being female (p < 0.0001), overweight (p = 0.025), being right-handed (p = 0.001), using four digital devices or more (p = 0.002), having low levels of physical activity (P = 0.018), and spending more than three hours a day sitting down (P = 0.027). More than a quarter of medical students had text neck syndrome, and most of them had a mild neck disability. Text Neck Syndrome was linked to an increased number of gadgets used, low exercise, and more time spent in a sitting position.

Discrepancies in the prevalence, risk factors, diagnosis, and treatment of stress fractures between long-distance runners and sprinters: A qualitative review of systematic reviews

This qualitative review of systematic reviews consolidates current knowledge on stress fractures among endurance athletes and sprinters, including epidemiology, risk factors, diagnosis, and treatment strategies. A search across PubMed, Web of Science, SCOPUS, Science Direct, and Google Scholar, limiting results to articles published within the last year, yielded 90 relevant articles. Initial search results were narrowed down to 56 articles following abstract screening, with an additional article obtained through direct author correspondence. Stress fractures, a subset of bone stress injuries, result from persistent mechanical pressure surpassing bone regeneration capacity. They predominantly affect lower extremities, notably the tibia and metatarsals in endurance runners, and the toe phalanx in sprinters. Various risk factors contribute to stress fracture susceptibility, including gender, nutritional deficiencies, biomechanical factors, and psychological aspects like perfectionism and fear of failure. Diagnosis involves detailed patient history, clinical examination, and imaging modalities such as MRI, which remains the gold standard. Treatment emphasizes rest, gradual return to activity, and addressing underlying risk factors. Surgical intervention is reserved for high-risk fractures or cases of non-union. Preventive measures encompass nutritional optimization, biomechanical assessment, appropriate footwear, and psychological support. Notably, strategies targeting the Female Athlete Triad and ensuring adequate energy availability are crucial in both endurance and sprinting athletes. While more research directly comparing distance runners to sprinters is warranted, along with more sprinting-related research in general, this review provides a comprehensive understanding of stress fractures in endurance athletes and sprinters, aiding clinicians in diagnosis, management, and prevention strategies to optimize athlete health and performance.

Determination of the signaling proteins responsible for the antioxidant potential of the Yishenhuoxue formula for treating asthenospermia in rats.

Asthenospermia is a predominant cause of male infertility, and antioxidant supplements can be effective in treating asthenospermia. We demonstrate the antioxidant potential of traditional Chinese medicine, the Yishenhuoxue (YSHX) formula, in treating polyglycosides of Tripterygium wilfordii (GTW)-induced asthenospermia in rats. Fifty male rats were randomly divided into the normal, model, and treatment groups. HE staining was used to evaluate the improvement of spermatogenic function of rats, and TBA reaction, qRT-PCR, Western Blot and other methods were used to determine the changes of oxidative stress indicators and to evaluate the improvement of antioxidant capacity of rats by YSHX. Comparison with the model group showed significant improvement in pathological damage caused by GTW to seminiferous tubules. MDA and NO content in rat testes decreased, especially in middle- and high-dosage groups. No significant changes were observed in SOD and CAT activity or mRNA expression. GSH-Px activity and GSH mRNA expression were significantly higher in the low-dosage group than in the model group. Compared to the model group, GR activity was significantly lower in the middle and high dosage groups, while the mRNA expression was higher. The PKC-beta level increased, while p-ERK1/2, NF-κB, and the ratio of p-ERK1/2*(ERK1/2)-1 decreased significantly in the treatment groups. Therefore, YSHX can alleviate GTW-induced testicular damage, enhance GSH-Px activity, regulate GSH redox cycling, and mitigate oxidative stress injury. Furthermore, YSHX can promote PKC-beta expression and inhibit the phosphorylation of ERK1/2 and NF-κB. Using YSHX may be an effective way to increase sperm motility via the PKC-ERK1/2-NF-ĸB axis.

Icariin improves oxidative stress injury during ischemic stroke via inhibiting mPTP opening

BackgroundIschemic stroke presents a significant threat to human health due to its high disability rate and mortality. Currently, the clinical treatment drug, rt-PA, has a narrow therapeutic window and carries a high risk of bleeding. There is an urgent need to find new effective therapeutic drugs for ischemic stroke. Icariin (ICA), a key ingredient in the traditional Chinese medicine Epimedium, undergoes metabolism in vivo to produce Icaritin (ICT). While ICA has been reported to inhibit neuronal apoptosis after cerebral ischemia-reperfusion (I/R), yet its underlying mechanism remains unclear.MethodsPC-12 cells were treated with 200 µM H2O2 for 8 h to establish a vitro model of oxidative damage. After administration of ICT, cell viability was detected by Thiazolyl blue tetrazolium Bromide (MTT) assay, reactive oxygen species (ROS) and apoptosis level, mPTP status and mitochondrial membrane potential (MMP) were detected by flow cytometry and immunofluorescence. Apoptosis and mitochondrial permeability transition pore (mPTP) related proteins were assessed by Western blotting. Middle cerebral artery occlusion (MCAO) model was used to establish I/R injury in vivo. After the treatment of ICA, the neurological function was scored by ZeaLonga socres; the infarct volume was observed by 2,3,5-Triphenyltetrazolium chloride (TTC) staining; HE and Nissl staining were used to detect the pathological state of the ischemic cortex; the expression changes of mPTP and apoptosis related proteins were detected by Western blotting.ResultsIn vitro: ICT effectively improved H2O2-induced oxidative injury through decreasing the ROS level, inhibiting mPTP opening and apoptosis. In addition, the protective effects of ICT were not enhanced when it was co-treated with mPTP inhibitor Cyclosporin A (CsA), but reversed when combined with mPTP activator Lonidamine (LND). In vivo: Rats after MCAO shown cortical infarct volume of 32–40%, severe neurological impairment, while mPTP opening and apoptosis were obviously increased. Those damage caused was improved by the administration of ICA and CsA.ConclusionsICA improves cerebral ischemia-reperfusion injury by inhibiting mPTP opening, making it a potential candidate drug for the treatment of ischemic stroke.Graphical

Auxiliary osseous findings in fetlocks of non-racing sports horses with sagittal groove disease of the proximal phalanx on low-field magnetic resonance imaging.

Sagittal groove disease of the proximal phalanx in equine athletes is commonly considered a bone stress injury. Repetitive hyperextension of the fetlock under high load is thought to contribute to its development. Concurrent changes are often reported in the dorsal sagittal ridge of the third metacarpus/metatarsus (MC3/MT3). To describe the spectrum of associated osseous abnormalities that are present in the fetlock in a large group of horses diagnosed with sagittal groove disease on low-field magnetic resonance imaging (MRI). Retrospective, cross-sectional. MRI images of horses diagnosed with sagittal groove disease at Equitom Equine Clinic between March 2014 and March 2023 were evaluated using semi-quantitative grading schemes and a sagittal groove disease MRI classification system. MRIs of 132 limbs were evaluated, predominantly from warmbloods used for showjumping (n = 83) and dressage (n = 18). Osseous densification and bone oedema-like signal grades were higher in the dorsal sagittal ridge than palmarly/plantarly (p < 0.001 and p < 0.05, respectively). Grades of both osseous densification and bone oedema-like signal in the dorsal sagittal ridge did not significantly differ between the different sagittal groove disease MRI classifications (both p > 0.05). Inclusion based on original MRI reports, absence of control group, small numbers within some grading groups hindering statistical analyses. Findings support the aetiological theories of chronic bone-stress due to loaded fetlock hyperextension however the severity of osseous changes of the dorsal sagittal ridge does not appear to be associated with the severity of sagittal groove disease classification.

The association between overuse and musculoskeletal injuries and the female athlete triad in Division I collegiate athletes.

Although the female athlete triad (Triad) has been associated with increased risk of bone-stress injuries (BSIs), limited research among collegiate athletes has addressed the associations between the Triad and non-BSI injuries. To elucidate the relationship between Triad and both BSI and non-BSI in female athletes. Retrospective cohort study. Primary and tertiary care student athlete clinic. National Collegiate Athletic Association Division I female athletes at a single institution. Participants completed a pre-participation questionnaire and dual-energy x-ray absorptiometry, which was used to generate a Triad cumulative risk assessment score (Triad score). The number of overuse musculoskeletal injuries that occurred while the athletes were still competing collegiately were identified through chart review. BSI and non-BSI were treated as count variables. The association between BSI, non-BSI, and Triad score was measured using Poisson regression to calculate rate ratios. Of 239 athletes, 43% of athletes (n = 103) sustained at least one injury. Of those, 40% (n = 95) sustained at least one non-BSI and 10% (n = 24) sustained at least one BSI over an average follow-up 2.5 years. After accounting for sport type (non-lean, runner, other endurance sport, or other lean advantage sport) and baseline age, we found that every additional Triad score risk point was associated with a significant 17% increase in the rate of BSI (rate ratio [RR] 1.17, 95% confidence interval [CI] 1.03-1.33; p = .016). However, Triad score was unrelated to non-BSI (1.00, 95% CI 0.91-1.11; p = .99). Compared with athletes in non-lean sports (n = 108), athletes in other lean advantage sports (n = 30) had an increased rate of non-BSI (RR: 2.09, p = .004) whereas distance runners (n = 46) had increased rates of BSI (RR: 7.65, p < .001) and non-BSI (RR: 2.25, p < .001). Higher Triad score is associated with an increased risk of BSI but not non-BSI in collegiate athletes.

Phytochemical Identification and Anti-Oxidative Stress Effects Study of Cimicifugae Rhizoma Extract and Its Major Component Isoferulic Acid

Background and Objectives: Cimicifugae Rhizoma, also known as ‘Sheng ma’ in Madeiran, is a widely used Chinese herbal medicine that has several pharmacological qualities, one of which is its antioxidant activity. Isoferulic acid, a prominent phenolic compound found in Cimicifugae Rhizoma, has potent antioxidant properties. This study was aimed to comprehensively analyze the components in Cimicifugae Rhizoma and rat plasma to evaluate the in vitro antioxidant and anti-inflammatory properties of Cimicifugae Rhizoma extract and Isoferulic acid as potential candidates for developing herbal formulations targeting podocyte injury in diabetic nephropathy for further clinical utilization. Materials and Methods: UPLC/Q-TOF-MS and HPLC were utilized as analytical tools to identify components of Cimicifugae Rhizoma extract or rat plasma after administrating it. MPC5 cells were cultured with H2O2 and high glucose and subjected to oxidative stress injury. The CXCL12/CXCR4 system plays a crucial role at certain stages of multiple kidney diseases’ injury. Apoptosis-related and target CXCL12/CXCR4/mTOR/Caspase-3 and Cask protein levels were assessed, and the levels of inflammatory-related factors, motility, morphology, ROS level, and apoptosis in podocytes were tested. Results: A total of 82 and 39 components were identified in the Cimicifugae Rhizoma extract and plasma, and Isoferulic acid content was determined as 6.52 mg/g in the Cimicifugae Rhizoma extract. The Cimicifugae Rhizoma extract (1 μg/mL) and Isoferulic acid (10, 25, 50 μM) considerably decreased high glucose and oxidative-stress-mediated toxicity, impaired mobility and adhesion and apoptotic changes in MPC5 cells, and reversed inflammation response. Moreover, the Cimicifugae Rhizoma extract and Isoferulic acid down-regulated Cask, mTOR, and Caspase-3, while significantly blocking the overactivation of CXCL12/CXCR4 in podocytes stimulated by oxidative stress and high glucose. Conclusions: These results indicate that the renal protective mechanism of the Cimicifugae Rhizoma extract and Isoferulic acid on simulating H2O2-induced podocyte injury involves mainly the of CXCL12/CXCR4 pathways and the inactivation of oxidative-stress-mediated apoptotic pathways after comprehensive qualitative and quantitative research by UPLC/Q-TOF-MS and HPLC. These findings provide an important efficacy and ingredient basis for further study on the clinical utilities of Cimicifugae Rhizoma and Isoferulic acid on podocyte and kidney impairment.

Perspectives of Ballet Dancers on Causes of Their Injuries and Implementation of Injury Preventive Measures by Ballet Teachers and Masters.

Ballet dancers have a high injury risk. We aimed to gain insight into the causes for acute and overuse injuries in ballet dancers and the level of implementation of injury prevention by ballet teachers/masters, as perceived by dancers. An international cross-sectional online-survey was based on the Fit-to-Dance Questionnaire and literature. Adult amateur, pre-professional, and professional ballet dancers reported the perceived causes of their injuries sustained in the previous 2 years. Multiple answers per injury were possible. Also, dancers rated the level of implementation of measures to prevent injury by their ballet teachers and ballet masters based on 21 items using a 5-point Likert scale. Causes were analyzed per-injury as well as per-dancer. 188 ballet ensembles and 51 dance organizations were contacted, from which 192 ballet dancers (mean age 27 ±7.8 yrs, 83% females) responded. 119 dancers (62%) reported 203 acute and 164 (85%) reported 469 overuse injuries. Fatigue was the most frequently perceived cause for acute injuries in the per-injury (n=89, 43.8%) and per-dancer analysis (n=63, 32.8%). For overuse injuries, pressure from the teacher/master was most frequently perceived as cause in the per-injury analysis (n=240, 51.2%), specifically in pre-/professional dancers (n=233, 61.3%). In the per-dancer analysis, fatigue/overtraining scored highest for overuse injuries (n=107; 55.7%). Other causes were previous/repetitive injuries (acute-per-injury 26.1%, acute-per-dancer 22.4%; overuse-per-injury 46.3%, overuse-per-dancer 53.1%) or erroneous dance technique (acute-per-injury 24.6%, acute-per-dancer 21.9%; overuse-per-injury 47.8%, overuse-per-dancer 45.3%). With regard to perceived level of implementation of injury preventive measures by ballet teachers/masters to prevent musculoskeletal injuries, 2 items received high ratings, 12 moderate ratings and 6 low ratings. Fatigue and pressure accounted for the majority of perceived causes for injuries. Perceived support by ballet teachers/masters regarding injury prevention was moderate to low. Future research should focus on the awareness, attitudes, and the important role of ballet teachers/masters for injury prevention in dancers.

Staying in the Game: Interventions for Managing Achilles Tendinopathy in the In-Season Athlete.

Achilles tendinopathy is a common overuse injury that is traditionally managed with activity modification and a progressive eccentric strengthening program. This narrative review describes the available evidence for adjunctive procedural interventions in the management of midportion and insertional AT, specifically in the athletic population. Safety and efficacy data from available literature on extracorporeal shockwave therapy, platelet-rich plasma, high-volume injectate with or without tendon scraping, and percutaneous needle tenotomy are used to propose an algorithm for treatment of Achilles tendinopathy for the in-season athlete.

Umbilical Cord Mesenchymal Stem Cells Combined with Fufang Xueshuantong Capsule Attenuate Oxidative Stress and Vascular Lesions in Diabetic Rats by Activating Nrf-2/HO-1 Signaling Pathway

Background:: Macrovascular lesions are the main cause of death and disability in diabetes mellitus, and excessive accumulation of cholesterol and lipids can lead to long-term and repeated damage of vascular endothelial cells. Umbilical cord mesenchymal stem cells (UCMSCs) can attenuate vascular endothelial damage in type 1 diabetic mice, while Fufang Xueshuantong capsule (FXC) has a protective effect on endothelial function; however, whether FXC in combination with UCMSCs can improve T2DM macrovascular lesions as well as its mechanism of action are not clear. Therefore, the aim of this study was to reveal the role of FXC + UCMSCs in T2DM vasculopathy and their potential mechanism in the treatment of T2DM. Methods:: The control and T2DM groups were intragastrically administered with equal amounts of saline, the UCMSCs group was injected with UCMSCs (1×106, resuspended cells with 0.5 mL PBS) in the tail vein, the FXC group was intragastrically administered with 0.58 g/kg FXC, and the UCMSCs + FXC group was injected with UCMSCs (1×106) in the tail vein, followed by FXC (0.58 g/kg), for 8 weeks. Results:: We found that FXC+UCMSCs effectively reduced lipid levels (TG, TC, and LDL-C) and ameliorated aortic lesions in T2DM rats. Meanwhile, Nrf2 and HO-1 expression were upregulated. We demonstrated that inhibition of Nrf-2 expression blocked the inhibitory effect of FXC+UCMSCs-CM on apoptosis and oxidative stress injury. Conclusion:: Our data suggest that FXC+UCMSCs may attenuate oxidative stress injury and macroangiopathy in T2DM by activating the Nrf-2/HO-1 pathway.

Attenuating intervertebral disc degeneration through spermidine-delivery nanoplatform based on polydopamine for persistent regulation of oxidative stress

As one of the most widespread musculoskeletal diseases worldwide, intervertebral disc degeneration (IVDD) remains an intractable clinical problem. Currently, oxidative stress has been widely considered as a significant risk factor in the IVDD pathological changes, and targeting oxidative stress injury to improve the harsh microenvironment may provide a novel and promising strategy for disc repair. It is evident that spermidine (SPD) has the ability to attenuate oxidative stress across several disease models. However, limited research exists regarding its impact on oxidative stress within the intervertebral disc. Moreover, enhancing the local utilization rate of SPD holds great significance in IVDD management. This study aimed to develop an intelligent biodegradable mesoporous polydopamine (PDA) nanoplatform for sustained release of SPD. The obtained PDA nanoparticles with spherical morphology and mesoporous structure released loaded-therapeutic molecules under low pH and H2O2. Combined treatment with SPD loaded into PDA nanoparticles (SPD/PDA) resulted in better therapeutic potential than those with SPD alone on oxidative stress injury. Furthermore, both SPD and SPD/PDA could induce anti-inflammatory M2 macrophage polarization. Upon injection into degenerative IVDs, the SPD/PDA group achieved a good repair efficacy with a long-term therapeutic effect. These findings indicated that the synergized use of SPD with responsive drug delivery nanocarriers may steadily scavenge reactive oxygen species and provide an effective approach toward the treatment of IVDD.

Zhi-zi-chi decoction mitigates depression by enhancing lncRNA Six3os1 expression and promoting histone H3K4 methylation at the BDNF promoter.

Traditional Chinese medicine, particularly Zhi-zi-chi decoction (ZZCD), is gaining recognition as a potential treatment for depression. This study aimed to uncover the molecular mechanisms behind ZZCD's antidepressant effects, focusing on lncRNA Six3os1 and histone H3K4 methylation at the BDNF promoter. Network pharmacology and invivo experiments were conducted to identify ZZCD targets and evaluate its impact on depression-related behaviours and neuron injury. The role of Six3os1 in recruiting KMT2A to the BDNF promoter and its effects on oxidative stress and neuron injury were investigated. ZZCD reduced depression-like behaviours and neuron injury in mice subjected to chronic stress. It upregulated Six3os1, which facilitated KMT2A recruitment to the BDNF promoter, leading to increased histone H3K4 methylation and enhanced BDNF expression. ZZCD also inhibited CORT-induced neuron injury, inflammatory response and oxidative stress invitro. ZZCD's antidepressant properties involve Six3os1 upregulation, which exerts neuroprotective effects by inhibiting oxidative stress and neuron injury, thereby alleviating depressive symptoms. Targeting Six3os1 upregulation may offer a potential therapeutic intervention for depression.

Advances in Stretchable Organic Photovoltaics: Flexible Transparent Electrodes and Deformable Active Layer Design.

Stretchable organic photovoltaics (OPVs) have attracted significant attention as promising power sources for wearable electronic systems owing to their superior robustness under repetitive tensile strains and their good compatibility. However, reconciling a high power-conversion efficiency and a reasonable flexibility is a tremendous challenge. In addition, the development of stretchable OPVs must be accelerated to satisfy the increasing requirements of niche markets for mechanical robustness. Stretchable OPV devices can be classified as either structurally or intrinsically stretchable. This paper reviews recent advances in stretchable OPVs, including the design of mechanically robust transparent electrodes, photovoltaic materials, and devices. Initially, we provide an overview of the characteristics and recent research progress in the areas of structurally and intrinsically stretchable OPVs. Subsequently, research into flexible and stretchable transparent electrodes that directly affect the performances of stretchable OPVs is summarized and analyzed. Overall, this review aims to provide an in-depth understanding of the intrinsic properties of highly efficient and deformable active materials, whilst also emphasizing advanced strategies for simultaneously improving the photovoltaic performance and mechanical flexibility of the active layer, including material design, multi-component settings, and structural optimization. This article is protected by copyright. All rights reserved.