The study aims to examine the effects and potential mechanisms of disulfiram (DSF) on cardiac hypertrophic injury, focusing on the role of transforming growth factor-β-activated kinase 1 (TAK1)-mediated pan-apoptosis (PANoptosis). H9C2 cardiomyocytes were treated with angiotensin II (Ang II, 1 µmol/L) to establish an in vitro model of myocardial hypertrophy. DSF (40 µmol/L) was used to treat cardiomyocyte hypertrophic injury models, either along or in combination with the TAK1 inhibitor, 5z-7-oxozeaenol (5z-7, 0.1 µmol/L). We assessed cell damage using propidium iodide (PI) staining, measured cell viability with CCK8 assay, quantified inflammatory factor levels in cell culture media via ELISA, detected TAK1 and RIPK1 binding rates using immunoprecipitation, and analyzed the protein expression levels of key proteins in the TAK1-mediated PANoptosis pathway using Western blot. In addition, the surface area of cardiomyocytes was measured with Phalloidin staining. The results showed that Ang II significantly reduced the cellular viability of H9C2 cardiomyocytes and the binding rate of TAK1 and RIPK1, significantly increased the surface area of H9C2 cardiomyocytes, PI staining positive rate, levels of inflammatory factors [interleukin-1β (IL-1β), IL-18, and tumor necrosis factor α (TNF-α)] in cell culture media and p-TAK1/TAK1 ratio, and significantly up-regulated key proteins in the PANoptosis pathway [pyroptosis-related proteins NLRP3, Caspase-1 (p20), and GSDMD-N (p30), apoptosis-related proteins Caspase-3 (p17), Caspase-7 (p20), and Caspase-8 (p18), as well as necroptosis-related proteins p-MLKL, RIPK1, and RIPK3]. DSF significantly reversed the above changes induced by Ang II. Both 5z-7 and exogenous IL-1β weakened these cardioprotective effects of DSF. These results suggest that DSF may alleviate cardiac hypertrophic injury by inhibiting TAK1-mediated PANoptosis.
Animals ; MAP Kinase Kinase Kinases/physiology* ; Rats ; Myocytes, Cardiac/pathology* ; Disulfiram/pharmacology* ; Cardiomegaly ; Apoptosis/drug effects* ; Cell Line ; Angiotensin II ; Necroptosis/drug effects* ; Interleukin-1beta/metabolism* ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism* ; Lactones ; Resorcinols ; Zearalenone/administration & dosage*

The phase changes and quantity-quality transfer of 17 batches of Ostreae Concha(Ostrea rivularis) during the raw material-calcined decoction pieces-standard decoction process were analyzed. The content of calcium carbonate(CaCO_3), the main component, was determined by chemical titration, and the extract yield and transfer rate were calculated. The CaCO_3 content in the raw material, calcined decoction pieces, and standard decoction was 94.39%-98.80%, 95.03%-99.22%, and 84.58%-90.47%, respectively. The process of raw material to calcined decoction pieces showed the yield range of 96.85% to 98.55% and the CaCO_3 transfer rate range of 96.92% to 99.27%. The process of calcined decoction pieces to standard decoction showed the extract yield range of 2.86% to 5.48% and the CaCO_3 transfer rate range of 2.59% to 5.13%. The results of X-ray fluorescence(XRF) assay showed that the raw material, calcined decoction pieces, and standard decoction mainly contained Ca, Na, Mg, Si, Br, Cl, Al, Fe, Cr, Mn, and K. The chemometric results showed an increase in the relative content of Cr, Fe, and Si from raw material to calcined decoction pieces and an increase in the relative content of Mg, Al, Br, K, Cl, and Na from calcined decoction pieces to standard decoction. X-ray diffraction(XRD) was employed to establish XRD characteristic patterns of the raw material, calcined decoction pieces, and standard decoction. The XRD results showed that the main phase of all three was calcite, and no transformation of crystalline form or generation of new phase was observed. Fourier transform infrared spectroscopy(FTIR) was employed to establish the FTIR characteristic spectra of the raw material, calcined decoction pieces, and standard decoction. The FTIR results showed that the raw material had internal vibrations of O-H, C-H, C=O, C-O, and CO■ groups. Due to the loss of organic matter components after calcination, no information about the vibrations of C-H, C=O, and C-O groups was observed in the spectra of calcined decoction pieces and standard decoction. In summary, this study elucidated the quantity-quality transfer and phase changes in the raw material-calcined decoction pieces-standard decoction process by determining the CaCO_3 content, calculating the extract yield and transfer rate, and comparing the element changes, FTIR characteristic spectra, and XRD characteristic pattern. The results were reasonable and reliable, laying a foundation for the subsequent process research and quality control of the formula granules of calcined Ostreae Concha(O. rivularis Gould), and providing ideas and methods for the quality control of the whole process of raw material-decoction pieces-standard decoction-formula granules of Ostreae Concha and other testacean traditional Chinese medicine.
Drugs, Chinese Herbal/isolation & purification* ; Calcium Carbonate/analysis* ; Quality Control

OBJECTIVE: To elucidate the effect of Huanglian-Renshen-Decoction (HRD) on ameliorating type 2 diabetes mellitus by maintaining islet β -cell identity through regulating paracrine and endocrine glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1R) in both islet and intestine. METHODS: The db/db mice were divided into the model (distilled water), low-dose HRD (LHRD, 3 g/kg), high-dose HRD (HHRD, 6 g/kg), and liraglutide (400 µ g/kg) groups using a random number table, 8 mice in each group. The db/m mice were used as the control group (n=8, distilled water). The entire treatment of mice lasted for 6 weeks. Blood insulin, glucose, and GLP-1 levels were quantified using enzyme-linked immunosorbent assay kits. The proliferation and apoptosis factors of islet cells were determined by immunohistochemistry (IHC) and immunofluorescence (IF) staining. Then, GLP-1, GLP-1R, prohormone convertase 1/3 (PC1/3), PC2, v-maf musculoaponeurotic fibrosarcoma oncogene homologue A (MafA), and pancreatic and duodenal homeobox 1 (PDX1) were detected by Western blot, IHC, IF, and real-time quantitative polymerase chain reaction, respectively. RESULTS: HRD reduced the weight and blood glucose of the db/db mice, and improved insulin sensitivity at the same time (P<0.05 or P<0.01). HRD also promoted mice to secrete more insulin and less glucagon (P<0.05 or P<0.01). Moreover, it also increased the number of islet β cell and decreased islet α cell mass (P<0.01). After HRD treatment, the levels of GLP-1, GLP-1R, PC1/3, PC2, MafA, and PDX1 in the pancreas and intestine significantly increased (P<0.05 or P<0.01). CONCLUSION HRD can maintain the normal function and identity of islet β cell, and the underlying mechanism is related to promoting the paracrine and endocrine activation of GLP-1 in pancreas and intestine.
Animals ; Glucagon-Like Peptide 1/metabolism* ; Diabetes Mellitus, Type 2/metabolism* ; Glucagon-Like Peptide-1 Receptor/metabolism* ; Insulin-Secreting Cells/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Male ; Blood Glucose/metabolism* ; Insulin/blood* ; Mice ; Intestinal Mucosa/pathology* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Islets of Langerhans/pathology*

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

OBJECTIVES: To characterize fine particulate matter (PM _2.5)-bound polycyclic aromatic hydrocarbons (PAHs) emitted from different cooking fumes and their exposure routes and assess their health-associated impact to provide a reference for health risk prevention from PAH exposure across different age and sex groups. METHODS: Sixteen PM _2.5-bound PAHs emitted from 11 cooking styles were analyzed using GC-MS/MS. The health hazards of these PAHs in the Handan City population (stratified by age and sex) were predicted using the incremental lifetime cancer risk ( ILCR) model. The respiratory deposition doses ( RDDs) of the PAHs in children and adults were calculated using the PM _2.5 deposition rates in the upper airway, tracheobronchial, and alveolar regions. RESULTS: The total concentrations of PM _2.5-bound PAHs ranged from 61.10 to 403.80 ng/m ³. Regardless of cooking styles, the ILCR _total values for adults (1.23 × 10 ^-6 to 3.70 × 10 ^-6) and older adults (1.28 × 10 ^-6 to 3.88 × 10 ^-6) exceeded the acceptable limit of 1.00 × 10 ^-6. With increasing age, the ILCR _total value first declined and then increased, varying substantially among the population groups. Cancer risk exhibited particularly high sensitivity to short exposure to barbecue-derived PAHs under equivalent body weights. Furthermore, barbecue, Sichuan and Hunan cuisine, Chinese cuisine, and Chinese fast food were associated with higher RDDs for both adults and children. CONCLUSION ILCR _total values exceeded the acceptable limit for both females and males of adults, with all cooking styles showing a potentially high cancer risk. Our findings serve as an important reference for refining regulatory strategies related to catering emissions and mitigating health risks associated with cooking styles.
Humans ; Polycyclic Aromatic Hydrocarbons/analysis* ; Cooking/methods* ; Male ; Female ; Particulate Matter/analysis* ; Adult ; Child ; Middle Aged ; Air Pollutants/analysis* ; Adolescent ; Air Pollution, Indoor/analysis* ; Young Adult ; Child, Preschool ; Aged ; China ; Inhalation Exposure ; Age Factors ; Sex Factors ; Cities ; Infant

Objective To explore the mechanism of the therapy of promoting blood circulation and nourishing yin(PBCNY)in improving spermatogenesis in rats with varicocele based on Bcl-2/Bax pathway.Methods Thirty 8-week-old male SD rats were randomly divided into six groups(five rats per group):sham,model,levocarnitine(1.0 g/kg),and PBCNY low-dose(5.2 g/kg),PBCNY medium-dose(10.4 g/kg),and PBCNY high-dose(20.8 g/kg)groups.Apart from the sham group,all the groups were built a varicocele model by the classical Turner method.After 4 weeks,the sham group and model group were gavaged with normal saline,and the remaining groups were given with levocarnitine or different doses of PBCNY decoction once a day for 4 weeks.At the end of gavage,the sperm quality of rats in each group was detected by a computer-assisted sperm analyzer,and HE staining was used to observe the testicular tissue morphology of rats in each group and performed with Johnsen score.TUNEL method was used to detect apoptosis,RT-qPCR was used to detect Bcl-2 and Bax mRNA expression,and immunohistochemical method was used to detect cytochrome C protein expression.Results Compared to the sham group,sperm total count,motility rate and percentage of sperm with grade(a+b)motility were lower in the model group of rats(P<0.05).HE staining showed disturbed arrangement of seminiferous tubules in the testicular tissue with significant changes and decreased Johnsen score(P<0.05).The result of TUNEL assay showed that the apoptosis rate was increased in the model group(P<0.05).Bax mRNA expression was increased in testicular tissue(P<0.05).The result of immunohistochemistry showed that the positive expression of cytochrome C was increased in the model group(P<0.05).Compared with the model group,the rat sperm total count in the PBCNY medium-dose group,motility rate in the PBCNY low-and medium-dose groups,and percentage of sperm with grade(a+b)motility in the PBCNY low-dose group increased(P<0.05);the pathological structure of rat testis had different degrees of improvement,and Johnsen score increased in the PBCNY medium-dose group(P<0.05);the apoptosis rate of testicular cells decreased in the levocarnitine group and all doses of PBCNY groups(P<0.05);the expression of Bcl-2 mRNA increased in the PBCNY low-dose and high-dose groups(P<0.05),and the expression of Bax mRNA decreased in the levocarnitine group and the PBCNY medium-dose group(P<0.05);the positive expression of cytochrome C decreased in the PBCNY medium-dose group(P<0.05).Conclusion The therapy of PBCNY can improve sperm quality,repair damaged testicular tissue structure and improve spermatogenic function in rats with varicocele,and its mechanism of action may be related to the activation of Bcl-2/Bax pathway and inhibition of cell apoptosis.

Objective To explore the mechanism of the therapy of promoting blood circulation and nourishing yin(PBCNY)in improving spermatogenesis in rats with varicocele based on Bcl-2/Bax pathway.Methods Thirty 8-week-old male SD rats were randomly divided into six groups(five rats per group):sham,model,levocarnitine(1.0 g/kg),and PBCNY low-dose(5.2 g/kg),PBCNY medium-dose(10.4 g/kg),and PBCNY high-dose(20.8 g/kg)groups.Apart from the sham group,all the groups were built a varicocele model by the classical Turner method.After 4 weeks,the sham group and model group were gavaged with normal saline,and the remaining groups were given with levocarnitine or different doses of PBCNY decoction once a day for 4 weeks.At the end of gavage,the sperm quality of rats in each group was detected by a computer-assisted sperm analyzer,and HE staining was used to observe the testicular tissue morphology of rats in each group and performed with Johnsen score.TUNEL method was used to detect apoptosis,RT-qPCR was used to detect Bcl-2 and Bax mRNA expression,and immunohistochemical method was used to detect cytochrome C protein expression.Results Compared to the sham group,sperm total count,motility rate and percentage of sperm with grade(a+b)motility were lower in the model group of rats(P<0.05).HE staining showed disturbed arrangement of seminiferous tubules in the testicular tissue with significant changes and decreased Johnsen score(P<0.05).The result of TUNEL assay showed that the apoptosis rate was increased in the model group(P<0.05).Bax mRNA expression was increased in testicular tissue(P<0.05).The result of immunohistochemistry showed that the positive expression of cytochrome C was increased in the model group(P<0.05).Compared with the model group,the rat sperm total count in the PBCNY medium-dose group,motility rate in the PBCNY low-and medium-dose groups,and percentage of sperm with grade(a+b)motility in the PBCNY low-dose group increased(P<0.05);the pathological structure of rat testis had different degrees of improvement,and Johnsen score increased in the PBCNY medium-dose group(P<0.05);the apoptosis rate of testicular cells decreased in the levocarnitine group and all doses of PBCNY groups(P<0.05);the expression of Bcl-2 mRNA increased in the PBCNY low-dose and high-dose groups(P<0.05),and the expression of Bax mRNA decreased in the levocarnitine group and the PBCNY medium-dose group(P<0.05);the positive expression of cytochrome C decreased in the PBCNY medium-dose group(P<0.05).Conclusion The therapy of PBCNY can improve sperm quality,repair damaged testicular tissue structure and improve spermatogenic function in rats with varicocele,and its mechanism of action may be related to the activation of Bcl-2/Bax pathway and inhibition of cell apoptosis.

Objective To explore the mechanism of the therapy of promoting blood circulation and nourishing yin(PBCNY)in improving spermatogenesis in rats with varicocele based on Bcl-2/Bax pathway.Methods Thirty 8-week-old male SD rats were randomly divided into six groups(five rats per group):sham,model,levocarnitine(1.0 g/kg),and PBCNY low-dose(5.2 g/kg),PBCNY medium-dose(10.4 g/kg),and PBCNY high-dose(20.8 g/kg)groups.Apart from the sham group,all the groups were built a varicocele model by the classical Turner method.After 4 weeks,the sham group and model group were gavaged with normal saline,and the remaining groups were given with levocarnitine or different doses of PBCNY decoction once a day for 4 weeks.At the end of gavage,the sperm quality of rats in each group was detected by a computer-assisted sperm analyzer,and HE staining was used to observe the testicular tissue morphology of rats in each group and performed with Johnsen score.TUNEL method was used to detect apoptosis,RT-qPCR was used to detect Bcl-2 and Bax mRNA expression,and immunohistochemical method was used to detect cytochrome C protein expression.Results Compared to the sham group,sperm total count,motility rate and percentage of sperm with grade(a+b)motility were lower in the model group of rats(P<0.05).HE staining showed disturbed arrangement of seminiferous tubules in the testicular tissue with significant changes and decreased Johnsen score(P<0.05).The result of TUNEL assay showed that the apoptosis rate was increased in the model group(P<0.05).Bax mRNA expression was increased in testicular tissue(P<0.05).The result of immunohistochemistry showed that the positive expression of cytochrome C was increased in the model group(P<0.05).Compared with the model group,the rat sperm total count in the PBCNY medium-dose group,motility rate in the PBCNY low-and medium-dose groups,and percentage of sperm with grade(a+b)motility in the PBCNY low-dose group increased(P<0.05);the pathological structure of rat testis had different degrees of improvement,and Johnsen score increased in the PBCNY medium-dose group(P<0.05);the apoptosis rate of testicular cells decreased in the levocarnitine group and all doses of PBCNY groups(P<0.05);the expression of Bcl-2 mRNA increased in the PBCNY low-dose and high-dose groups(P<0.05),and the expression of Bax mRNA decreased in the levocarnitine group and the PBCNY medium-dose group(P<0.05);the positive expression of cytochrome C decreased in the PBCNY medium-dose group(P<0.05).Conclusion The therapy of PBCNY can improve sperm quality,repair damaged testicular tissue structure and improve spermatogenic function in rats with varicocele,and its mechanism of action may be related to the activation of Bcl-2/Bax pathway and inhibition of cell apoptosis.