Effect of tissue factor pathway inhibitor on the pyroptosis of vascular smooth muscle cells induced by angiotensin II.

Background: In recent years, a mass of studies have shown that pyroptosis plays an important role in the proliferation of vascular smooth muscle cells (VSMCs). We investigated whether angiotensin II (Ang II) induces the pyroptosis of rat aortic VSMCs and the role of NOD-like receptor family pyrin domain containing 3 (NLRP3) in this process. Additionally, we explored the effect and related mechanism of recombinant tissue factor pathway inhibitor (rTFPI) in Ang II-induced VSMC pyroptosis. Methods: Cultured VSMCs were divided into five groups: control group, Ang II group (1×10-5 mol/L), MCC950 group (NLRP3 inhibitor, 15 nmol/L), Ang II + MCC950 group and Ang II + rTFPI (50 µg/L) group. Cell viability was measured by cell counting kit-8 (CCK8) assays and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays. Propidium iodide (PI) staining and immunofluorescence were performed to determine the pyroptosis of VSMCs. Changes in VSMC ultrastructure were evaluated through transmission electron microscopy. The expression levels of NLRP3, pro-caspase-1, gasdermin D-N (GSDMD-N), and interleukin-1ß (IL-1ß) were determined by western blot analysis. Results: The cell viability, the positive rate of PI staining, and the expression level of GSDMD detected by immunofluorescence in the Ang II group were higher than that in the control group, whereas they all decreased in Ang II + MCC950 group and Ang II + rTFPI group compared with Ang II group (P<0.05). Electron microscopy analysis revealed less extracellular matrix, increased myofilaments, and decreased endoplasmic reticulum, Golgi complex, and mitochondria in Ang II + rTFPI-treated VSMCs than in Ang II-treated VSMCs. The protein expression levels of the pyroptosis-related molecules NLRP3, pro-caspase-1, GSDMD-N, and IL-1ß in Ang II group showed an increasing trend compared with those in control group (P<0.05); however, these expression levels in Ang II + MCC950 and Ang II + rTFPI groups were significantly lower than those in Ang II group (P<0.05). Conclusions: Ang II may induce pyroptosis in VSMCs by activating NLRP3. rTFPI can inhibit Ang II-induced VSMC pyroptosis. Furthermore, rTFPI might exert this effect by inhibiting the NLRP3 pathway and therefore play an important role in the treatment of vascular remodeling induced by hypertension.

Transparent injectable sericin-honey hydrogel with antioxidant and antibacterial activities combined with feeding sericin accelerates diabetic wound healing.

Wound healing in diabetics is often impaired or delayed due to the presence of high reactive oxygen species and low antioxidant levels. Here, a sericin-honey semi-interpenetrating network hydrogel with excellent antioxidant activity was prepared. Besides, the sericin-honey hydrogel is transparent, injectable, sticky, highly porous, and has good swelling properties, antibacterial activity, and cell compatibility. Based on its good performancein vitro, sericin-honey hydrogel achieved effectivein vivotreatment on a mouse diabetic wound model, significantly accelerating the wound healing process. Furthermore, the combined effect of feeding sericin solution played a positive role in strengthening the effect of diabetic wound repair.

Mendelian randomization study supports effect of gut microflora on fractures.

To investigate the possible causal relationship between intestinal microflora and fractures using Mendelian randomization (MR). A 2-sample MR study of gut microbiota and fractures was conducted using a weighted inverse variance analysis with tests for heterogeneity, horizontal pleiotropy, and sensitivity. A causal association between fracture risk and specific bacterial taxa was identified at various taxonomic levels: 2 (Bacteroidia, P = .0304; Deltaproteobacteria P = .0304) at the class level, 3 (Bacteroidales, P = .0428; Desulfovibrionales, P = .0428; Enterobacteriales, P = .0208) at the order level, 2 (FamilyXI, P = .0304; Enterobacteriaceae P = .0332) at the family level, and 1 (Alistipes, P = .0405) at the genus level. This study revealed a causal relationship between gut microflora and fracture risk, demonstrating that the effect of different flora taxa flora abundance on fracture risk differs. It provides a reference for further studies.

The causal relationship between ever smoked and frozen shoulder: A two-sample Mendelian randomization.

To investigate the causal relationship between ever smoked and frozen shoulder using a Mendelian randomization (MR) approach. Pooled data from a large-scale genome-wide association study were used. Genetic loci that were independent of each other and associated with ever smoked and frozen shoulder in populations of European ancestry were selected as instrumental variables. Inverse variance weighting was used as the primary analysis method. Weighted median and MR-Egger were used as complementary analysis methods to assess causal effects. To explore the causal relationship between ever smoked and frozen shoulder. Sensitivity test analysis was performed using heterogeneity test, multiple validity test, and leave-one-out analysis to explore the robustness of the results. Inverse variance weighting results of ever smoked showed an OR = 2.49, 95% CI = 1.05-5.91, P = .038, indicating that ever smoked is a risk factor for a frozen shoulder. And the test revealed no heterogeneity and pleiotropy, and the sensitivity analysis also showed robust results. This study used two-sample MR analysis to analyze and explore the genetic data, and the results showed a higher prevalence of frozen shoulder in patients with ever smoked, suggesting that active control of ever smoked may reduce the occurrence of frozen shoulder.

The causal relationship between depression and frozen shoulder: A two-sample Mendelian randomization.

To investigate the causal relationship between depression and frozen shoulder using a Mendelian randomization (MR) approach. Pooled data from a large-scale genome-wide association study were used. Genetic loci that were independent of each other and associated with depression and frozen shoulder in populations of European ancestry were selected as instrumental variables. Inverse variance weighting was used as the primary analysis method. Weighted median and MR-Egger were used as complementary analysis methods to assess causal effects. To explore the causal relationship between depression and frozen shoulder. Sensitivity test analysis was performed using heterogeneity test, multiple validity test, and leave-one-out analysis to explore the robustness of the results. Inverse variance weighting results showed an odds ratio (95% confidence interval) of 1.18 (0.91-1.53), P = .204, indicating that depression was not causally related to the development of frozen shoulder. And the test revealed no heterogeneity and pleiotropy, and the sensitivity analysis also showed robust results. In this study, genetic data were analyzed and explored using a two-sample MR analysis, and the results showed no causal relationship between depression and the occurrence of frozen shoulder, requiring the inclusion of a larger sample for the study.

The causal relationship between breast cancer and frozen shoulder: A two-sample Mendelian randomization.

To investigate the causal relationship between breast cancer and frozen shoulder using a Mendelian randomization (MR) approach. Pooled data from a large-scale genome-wide association study were used. Genetic loci that were independent of each other and associated with breast cancer and frozen shoulder in populations of European ancestry were selected as instrumental variables. Inverse variance weighting was used as the primary analysis method. Weighted median (WME) and MR-Egger were used as complementary analysis methods to assess causal effects. To explore the causal relationship between breast cancer and frozen shoulder. Sensitivity test analysis was performed using heterogeneity test, multiple validity test, and leave-one-out analysis to explore the robustness of the results. Inverse variance weighting results showed an OR (95% CI) of 1.02 (1.00-1.04), P = .048, indicating that breast cancer is a risk factor for a frozen shoulder. And the test revealed no heterogeneity and pleiotropy, and the sensitivity analysis also showed robust results. In this study, genetic data were analyzed and explored using two-sample MR analysis, and the results showed that the incidence of frozen shoulder was higher in breast cancer patients, suggesting that screening for frozen shoulder in breast cancer patients should be increased.

Causal association of metformin and osteoporosis: A 2-sample Mendelian randomization study.

To investigate the causal relationship between metformin use and osteoporosis and different subtypes of osteoporosis using a 2-sample Mendelian randomization method. Data from genome-wide association studies were analyzed, with the exposure factor being metformin and the outcome variables being osteoporosis and different subtypes. Mendelian randomization was performed using Inverse Variance Weighted (IVW), MR-Egger, and weight median (WM) methods, and heterogeneity tests, horizontal multivariate analyses, and sensitivity analyses were performed. The IVW method analysis with metformin and osteoporosis showed P = 1.53E-04, OR (95%CI) = 1.81E-02 (2.27E-02-1.44E-01); the IVW method analysis with metformin and postmenopausal osteoporosis with pathologic fracture showed P = 2.22E-01, OR (95%CI) = 4.89E-02 (3. 83E-04-6.23E + 00); the IVW method using metformin with osteoporosis with pathological fracture showed that P = 2.14E-01, OR (95%CI) = 1.64E + 00(5.78E-02-6.44E-04); the IVW method using metformin with pharmacological osteoporosis with pathological fracture showed that P = 9. 83E- 01, OR (95%CI) = 1.11E + 00 (3.99E-05-3.11E + 04); IVW method of metformin use and pharmacological osteoporosis showed that P = 5.99E-01, OR (95%CI) = 2.27E + 01 (2.00E-04-2.57E + 06); there is a causal relationship between metformin use and osteoporosis, but there is no causal relationship between metformin use and postmenopausal osteoporosis with pathological fracture, osteoporosis with pathological fracture, pharmacological osteoporosis, and pharmacological osteoporosis with pathological fracture, and metformin use is a protective factor for osteoporosis.

The causal relationship between hypothyroidism and frozen shoulder: A two-sample Mendelian randomization.

To investigate the causal relationship between hypothyroidism and frozen shoulder using a Mendelian randomization (MR) approach. Pooled data from a large-scale genome-wide association study (GWAS) were used. Genetic loci that were independent of each other and associated with hypothyroidism and frozen shoulder in populations of European ancestry were selected as instrumental variables. Inverse variance weighting (IVW) was used as the primary analysis method. Weighted median (WME) and MR-Egger were used as complementary analysis methods to assess causal effects. To explore the causal relationship between hypothyroidism and frozen shoulder. Sensitivity test analysis was performed using heterogeneity test, multiple validity test, and leave-one-out analysis to explore the robustness of the results. IVW results showed an OR (95% CI) of 1.07 (1.01-1.14), P = .024, indicating that hypothyroidism is a risk factor for a frozen shoulder. And no pleiotropy was found by the test, and sensitivity analysis also showed robust results. This study used 2-sample MR analysis to analyze and explore the genetic data, and the results showed a higher prevalence of frozen shoulder in patients with hypothyroidism, suggesting that active control of hypothyroidism may reduce the occurrence of frozen shoulder.

Sericin from Fibroin-Deficient Silkworms Served as a Promising Resource for Biomedicine.

Sericin, a fascinating natural biomaterial derived from silkworms, has received increasing interest in recent years for its unique bioactivity and high compatibility. Silkworms can be divided into wild-type or silk fibroin-deficient mutants according to whether they synthesize and secrete silk fibroin. Silk fibroin-deficient mutant silkworms and their cocoons are convenient for us to obtain diverse and high-quality sericin, which has been applicated in various fields such as cell culture, tissue engineering, drug delivery, and cosmetics. Here, we present an overview of our silkworm varieties resources, especially silk fibroin-deficient mutant silkworms. We optimized various extraction methods of sericin and summarized the characteristics and advantages of sericin. Finally, we developed and discussed a series of sericin-based biomaterials for promising applications for a diverse set of needs.

Resveratrol loaded native silk fiber-sericin hydrogel double interpenetrating bioactive wound dressing facilitates full-thickness skin wound healing.

Wound repair is challenging for traditional wound dressings. New bioactive dressings need to be developed urgently. Herein, we reported a highly bioactive silk protein wound dressing (SPD) with natural silk fiber-sericin hydrogel interpenetrating double network structure, which combines the dual characteristics of natural silk and sericin hydrogel. Silk fiber scaffolds were secreted directly from silkworms bred by regulating their spinning behaviors. Sericin in SPD is obtained by dissolving silkworm cocoons at high temperature and high pressure, while it remains intact activities to self-assemble a hydrogel. To explore the effect of SPD, we first systematically evaluated its physicochemical properties and biological activitiesin vitro. The SPD exhibits high porosity, prominent mechanical strength, pH-responsive degradability, and excellent anti-oxidation and cell compatibility. Besides, SPD can load and maintain long-term drug release. Based on the satisfactory performance of SPDin vitro, effectivein vivotreatment was achieved in a mouse full-thickness wound model, as demonstrated by a significantly accelerated wound healing process, promote the regeneration of hair follicles and sebaceous glands, increased expression of vascular endothelial growth factor, and reduced inflammation. Further, resveratrol was loaded into SPD to enhance the effects of anti-oxidation and anti-inflammation for wound healing. Our investigation shows that SPD with excellent physicochemical and biological properties applied in a murine full-thickness skin wound model resulted in remarkable and efficient acceleration of healing process, which may inspire the design of new, effective, and safer medical materials for tissue regeneration.

Monitoring Wheat Powdery Mildew Based on Hyperspectral, Thermal Infrared, and RGB Image Data Fusion.

Powdery mildew severely affects wheat growth and yield; therefore, its effective monitoring is essential for the prevention and control of the disease and global food security. In the present study, a spectroradiometer and thermal infrared cameras were used to obtain hyperspectral signature and thermal infrared images data, and thermal infrared temperature parameters (TP) and texture features (TF) were extracted from the thermal infrared images and RGB images of wheat with powdery mildew, during the wheat flowering and filling periods. Based on the ten vegetation indices from the hyperspectral data (VI), TF and TP were integrated, and partial least square regression, random forest regression (RFR), and support vector machine regression (SVR) algorithms were used to construct a prediction model for a wheat powdery mildew disease index. According to the results, the prediction accuracy of RFR was higher than in other models, under both single data source modeling and multi-source data modeling; among the three data sources, VI was the most suitable for powdery mildew monitoring, followed by TP, and finally TF. The RFR model had stable performance in multi-source data fusion modeling (VI&TP&TF), and had the optimal estimation performance with 0.872 and 0.862 of R2 for calibration and validation, respectively. The application of multi-source data collaborative modeling could improve the accuracy of remote sensing monitoring of wheat powdery mildew, and facilitate the achievement of high-precision remote sensing monitoring of crop disease status.