BACKGROUND: The protective effect of mesenchymal stem cells (MSCs) on cardiac ischemia-reperfusion (I/R) injury has been widely reported. Dental pulp-derived mesenchymal stem cells (DP-MSCs) have therapeutic effects on various diseases, including diabetes and cirrhosis. This study aimed to determine the therapeutic effects of DP-MSCs on I/R injury and elucidate the underlying mechanism. METHODS: Myocardial I/R injury model mice were treated with DP-MSCs or a miR-19a-3p mimic. The infarct volume, fibrotic area, pyroptosis, inflammation level, and cardiac function were measured. Cardiomyocytes exposed to hypoxia-reoxygenation were transfected with the miR-19a-3p mimic, miR-19a-3p inhibitor, or negative control. Pyroptosis and protein expression in the interferon regulatory factor 8/mitogen-activated protein kinase (IRF-8/MAPK) pathway were measured. RESULTS: DP-MSCs protected cardiac function in cardiac I/R-injured mice and inhibited cardiomyocyte pyroptosis. The upregulation of miR-19a-3p protected cardiac function, inhibited cardiomyocyte pyroptosis, and inhibited IRF-8/MAPK signaling in cardiac I/R-injured mice. DP-MSCs inhibited cardiomyocyte pyroptosis and the IRF-8/MAPK signaling by upregulating the miR-19a-3p levels in cardiomyocytes injured by I/R. CONCLUSION DP-MSCs protected cardiac function by inhibiting cardiomyocyte pyroptosis through miR-19a-3p under I/R conditions.
Animals ; MicroRNAs/metabolism* ; Pyroptosis/genetics* ; Mesenchymal Stem Cells/metabolism* ; Myocytes, Cardiac/cytology* ; Mice ; Male ; Mice, Inbred C57BL ; Dental Pulp/cytology* ; Myocardial Reperfusion Injury/therapy* ; MAP Kinase Signaling System/physiology*

BACKGROUND: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037). CONCLUSIONS Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Vascular Diseases/etiology* ; Risk Factors ; China/epidemiology* ; Adult ; Proportional Hazards Models ; Cerebrovascular Disorders/epidemiology* ; East Asian People

Eucommiae Cortex, the dried bark of Eucommia ulmoides( Eucommiaceae), has both medicinal and edible values.Modern research has shown that Eucommiae Cortex contains various components such as flavonoids, lignans, iridoids, phenolic acids,terpenoids, and steroids, which have anti-osteoporosis, antioxidant, anti-inflammatory, blood glucose-lowering, and gastrointestinal tract-protecting effects. Eucommiae Cortex has applications in multiple fields such as healthcare, industry, and animal husbandry,demonstrating broad development prospects. This article reviews the chemical constituents, pharmacological effects, and quality control status of Eucommiae Cortex. Furthermore, according to the concept of quality marker(Q-marker), this article predicts the Q-markers of Eucommiae Cortex from traditional medicinal properties, traditional medicinal effects, new medicinal effects, measurability of chemical components, compatibility, harvesting periods, and geographical origins. The components such as pinoresinol diglucoside,chlorogenic acid, caffeic acid, quercetin, baicalein, baicalin, olivil, coniferyl ferulate, and kaempferol can be used as Q-markers for Eucommiae Cortex, which provide reference for establishing a systematic quality control system for Eucommiae Cortex.
Eucommiaceae/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Quality Control ; Humans ; Animals

Objective To investigate the efficacy of the ultraviolet A-riboflavin cross-linking corneal stromal lenticule punctal plug for the treatment of dry eyes in rabbits.Methods Thirty-two New Zealand white rabbits(64 eyes)were se-lected and randomly divided into a normal group,a model group,a conventional plug group and a cross-linking plug group,with 8 rabbits(16 eyes)in each group.Rabbits in the normal group were not treated.In the model group,moderate-to-se-vere dry eye rabbit models were constructed but no treatment was given.Rabbits in the conventional and cross-linking plug groups were implanted with conventional and cross-linking plugs after model construction,respectively.The tear film func-tions of the experimental rabbits,including tear secretion volume(SIT),corneal fluorescein sodium staining,tear film break-up time(BUT),and tear meniscus height(TMH),were detected before the intervention,1 day,1 week,2 weeks,and 4 weeks after the intervention.In addition,the corneas of each group were collected for hematoxylin and eosin(HE)staining to observe the changes of the corneal epithelium 4 weeks after the intervention.Finally,the non-cross-linking and cross-linking corneal stromal lenticules were placed separately in 1 g·L-1 of type Ⅰ collagenase to observe the change of the lenticule diameter over time.Results In the cross-linking plug group,the SIT,BUT and TMH values 2 and 4 weeks after the intervention were significantly higher than those before the intervention(all P＜0.01).In the conventional plug group,the SIT,BUT and TMH values 4 weeks after intervention were significantly higher than those before the intervention(all P＜0.01).After 4 weeks of intervention,the corneal staining of rabbits in the cross-linking plug group was better than that in the conventional plug group and model group.The HE staining results showed that in the cross-linking plug group,the corneal epithelial thickness of rabbits was basically normal,epithelial cells were basically arranged in order,and a single layer of columnar epithelial cells was observed on the basal layer.The dissolution time of the corneal stromal lenticule after cross-linking was significantly increased,compared with that of the non-cross-linking one.Conclusion The ultraviolet A-riboflavin cross-linking corneal stromal lenticule punctal plug has a more stable therapeutic effect on the rabbit dry-eye model than the conventional one,so it is expected to provide a novel approach for the clinical treatment of dry eyes.

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective To investigate the efficacy of the ultraviolet A-riboflavin cross-linking corneal stromal lenticule punctal plug for the treatment of dry eyes in rabbits.Methods Thirty-two New Zealand white rabbits(64 eyes)were se-lected and randomly divided into a normal group,a model group,a conventional plug group and a cross-linking plug group,with 8 rabbits(16 eyes)in each group.Rabbits in the normal group were not treated.In the model group,moderate-to-se-vere dry eye rabbit models were constructed but no treatment was given.Rabbits in the conventional and cross-linking plug groups were implanted with conventional and cross-linking plugs after model construction,respectively.The tear film func-tions of the experimental rabbits,including tear secretion volume(SIT),corneal fluorescein sodium staining,tear film break-up time(BUT),and tear meniscus height(TMH),were detected before the intervention,1 day,1 week,2 weeks,and 4 weeks after the intervention.In addition,the corneas of each group were collected for hematoxylin and eosin(HE)staining to observe the changes of the corneal epithelium 4 weeks after the intervention.Finally,the non-cross-linking and cross-linking corneal stromal lenticules were placed separately in 1 g·L-1 of type Ⅰ collagenase to observe the change of the lenticule diameter over time.Results In the cross-linking plug group,the SIT,BUT and TMH values 2 and 4 weeks after the intervention were significantly higher than those before the intervention(all P＜0.01).In the conventional plug group,the SIT,BUT and TMH values 4 weeks after intervention were significantly higher than those before the intervention(all P＜0.01).After 4 weeks of intervention,the corneal staining of rabbits in the cross-linking plug group was better than that in the conventional plug group and model group.The HE staining results showed that in the cross-linking plug group,the corneal epithelial thickness of rabbits was basically normal,epithelial cells were basically arranged in order,and a single layer of columnar epithelial cells was observed on the basal layer.The dissolution time of the corneal stromal lenticule after cross-linking was significantly increased,compared with that of the non-cross-linking one.Conclusion The ultraviolet A-riboflavin cross-linking corneal stromal lenticule punctal plug has a more stable therapeutic effect on the rabbit dry-eye model than the conventional one,so it is expected to provide a novel approach for the clinical treatment of dry eyes.