Yiqi Jiedu Xiaoying Decoction Improves Experimental Autoimmune Thyroiditis in Rats by Regulating Th17/Treg Cell Balance.

BACKGROUND: Experimental autoimmune thyroiditis (EAT) is a widely used animal model to study the pathogenesis and treatment of autoimmune thyroid diseases. Yiqi Jiedu Xiaoying Decoction (YJXD) is a traditional Chinese medicine formula with potential immunomodulatory effects. In this study, we investigated the therapeutic effects of YJXD on EAT in rats and explored its underlying mechanisms. METHODS: Female Wistar rats were induced to develop EAT by immunization with thyroglobulin (Tg) and taken sodium iodide water (0.05%) and then treated with YJXD or sodium selenite. HE staining was used to observe the pathological changes of thyroid tissue in EAT rats. Th17 and Treg cell frequencies were analyzed by flow cytometry, and the expression levels of Th17- and Treg-related cytokines and thyroid autoantibody were determined by enzyme-linked immunosorbent assay (ELISA). The expression of Th17- and Treg-related transcriptional factors was detected by real-time polymerase chain reaction (RT-PCR) and Immunohistochemistry (IHC). RESULTS: Our results demonstrated that treatment with YJXD significantly attenuated the severity of EAT, as evidenced by reduced thyroid gland inflammatory infiltration and decreased serum thyroglobulin autoantibody levels. Importantly, YJXD treatment effectively modulated the Th17/Treg cell balance by suppressing Th17 cell differentiation and promoting Treg cell expansion. Moreover, YJXD was also found to regulate the expression levels of Th17- and Tregrelated cytokines and transcriptional factors, further supporting its immunomodulatory effects in EAT. CONCLUSION: YJXD exerted therapeutic effects on EAT by regulating the Th17/Treg cell balance, modulating the production of Th17- and Treg-related cytokines and the expression of transcriptional factors.

Obesity Metabolic Phenotypes and Unplanned Readmission Risk in Diabetic Kidney Disease: An Observational Study from the Nationwide Readmission Database.

BACKGROUND AND AIM: Obesity is a potentially modifiable factor for reducing readmissions, with heterogeneity that varies according to the metabolic status. Our objective was to examine the independent or mutual relationship between obesity and metabolic abnormalities and diabetic kidney disease (DKD)-related hospitalizations. METHODS: 493,570 subjects with DKD were enrolled in the 2018 Nationwide Readmission Database (NRD, United States). The at-risk population was reclassified into refined obesity subtypes based on the body mass index (BMI) classification of metabolic abnormalities (hypertension and/or dyslipidemia) to investigate the 180 d readmission risk and hospitalization costs related to DKD. RESULTS: The overall readmission rate was 34.1%. Patients with metabolic abnormalities, regardless of obesity, had a significantly higher risk of readmission compared to non-obese counterparts (adjusted HR, 1.11 [95% CI, 1.07-1.14]; 1.12 [95% CI, 1.08-1.15]). Hypertension appeared to be the only metabolic factor associated with readmission among individuals with DKD. Obesity without metabolic abnormalities was independently associated with readmission (adjusted HR,1.08 [1.01,1.14]), especially among males and those >65 years (adjusted HR,1.10 [1.01-1.21]; 1.20 [1.10-1.31]). Women or those ≤65 years with metabolic abnormalities (all p <0.050) had elevated readmission rates, regardless of obesity; however, no such trend was observed in obese subjects without metabolic abnormalities (adjusted HR, 1.06 [0.98,1.16]). Additionally, obesity and metabolic abnormalities were associated with elevated hospitalization costs (all p <0.0001). CONCLUSIONS: Increased BMI and hypertension are positively associated with readmissions and related costs among patients with DKD, which should be considered in future studies.

The Hidden Burden-Exploring Depression Risk in Patients with Diabetic Nephropathy: A Systematic Review and Meta-Analysis.

INTRODUCTION: Diabetic nephropathy is a common complication among patients with diabetes mellitus, and it has been linked to a higher risk of depression. However, the magnitude of this association remains unclear. This study aimed to systematically review and meta-analyse the risk of depression in patients with diabetic nephropathy compared to diabetes patients without nephropathy. METHODS: We conducted a systematic literature review, searching multiple databases from January 1964 to March 2023, and included randomized controlled trials, non-randomized controlled trials, and observational studies. We assessed the risk of bias using the Newcastle Ottawa scale for observational studies. The statistical analysis was performed using STATA version 14.2, and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. A total of 60 studies were included. RESULTS: The pooled OR for the risk of depression among patients with diabetic nephropathy was 1.78 (95% CI 1.56-2.04; I2 = 83%; n = 56), indicating a significantly higher risk compared to diabetes patients without nephropathy (p < 0.001). Pooling the effect size across these studies showed that the pooled OR was 1.15 (95% CI 1.14-1.16; I2 = 88%; n = 32). Subgroup analyses based on the type of diabetes and study region revealed no significant differences in the pooled estimates. CONCLUSION: This study demonstrates that patients with diabetic nephropathy have a significantly higher risk of depression compared to diabetes patients without nephropathy. These findings highlight the importance of assessing and addressing the mental health of patients with diabetic nephropathy as part of their overall healthcare management.

Explore the Mechanism of Astragalus mongholicus Bunge against Nonalcoholic Fatty Liver Disease Based on Network Pharmacology and Experimental Verification.

Objective: Astragalus mongholicus Bunge [Fabaceae] (AMB), a traditional Chinese medicine (TCM), has been widely used to treat liver diseases in the clinic. However, the efficacy and mechanism of AMB in the treatment of nonalcoholic fatty liver disease (NAFLD) remain unclear. The purpose of this study was to systematically investigate the active components and mechanisms of AMB against NAFLD based on network pharmacology, molecular docking, and experimental verification. Methods: First, the bioactive components and relevant targets of AMB were screened from the Traditional Chinese Medicine Systematic Pharmacology (TCMSP) database, and NAFLD-related targets were obtained from the GeneCards database. Then, the AMB-NAFLD protein target interaction network was built by the STRING database. GO and KEGG pathway enrichment analyses were performed using the DAVID database. The component targets were visualized using Cytoscape software. Finally, molecular docking and experiments were used to verify the results of network pharmacological prediction. Results: Network pharmacology predicted that quercetin may be the main active component in AMB, and the TNF and MAPK signaling pathways may be the key targets of AMB against NAFLD. Molecular docking validation results demonstrated that quercetin, as the main active component of AMB, had the highest binding affinity with TNF. Furthermore, quercetin played a distinct role in alleviating NAFLD through in vitro experiments. Quercetin upregulated the phosphorylation levels of AMPK and inhibited the expression of p-MAPK and TNF-α. In addition, we further discovered that quercetin could increase ACC phosphorylation and CPT1α expression in PA-induced HepG2 cells. Conclusions: Our results indicated that quercetin, as the main active component in AMB, exerts an anti-NAFLD effect by regulating the AMPK/MAPK/TNF-α and AMPK/ACC/CPT1α signaling pathways to inhibit inflammation and alleviate lipid accumulation.

Saponins of Momordica charantia increase insulin secretion in INS-1 pancreatic ß-cells via the PI3K/Akt/FoxO1 signaling pathway.

Saponins are the main bioactive substances with anti-hyperglycemic activities of Momordica charantia. This study aimed to verify the effects of M. charantia saponins on insulin secretion and explore the potential underlying mechanisms in INS-1 pancreatic ß-cells. We injured INS-1 cells with 33.3mM glucose and then treated them with saponins. Saponins improved cell morphology and viability as demonstrated by inverted microscopy and CCK8 detection and significantly increased insulin secretion in a concentration-dependent manner as shown by ELISA. Thus, we obtained the optimal concentration for the subsequent experiments. Potential mechanisms were explored by immunofluorescence, western blotting, and RT-qPCR techniques. First, saponins increased the mRNA and protein levels of IRS-2 but decreased the serine 731 phosphorylation level of IRS-2. Moreover, saponins increased the phosphorylation of Akt protein and decreased the protein level of FoxO1, which were both reversed by the PI3K inhibitor ly294002. Furthermore, saponins increased the protein level of the downstream molecule and insulin initiating factor PDX-1, which was also reversed by ly294002. Saponins also increased Akt and PDX-1 mRNA and decreased FoxO1 mRNA, which were both reversed by ly294002. Saponins increased glucose-stimulated insulin secretion (GSIS) and intracellular insulin content, which were reversed by ly294002, as determined by ELISA. The immunofluorescence results also confirmed this tendency. In conclusion, our findings improve our understanding of the function of saponins in INS-1 pancreatic ß-cells and suggest that saponins may increase insulin secretion via the PI3K/Akt/FoxO1 signaling pathway.

Saponins of Momordica charantia increase insulin secretion in INS-1 pancreatic ß-cells via the PI3K/Akt/FoxO1 signaling pathway.

Saponins are the main bioactive substances with anti-hyperglycemic activities of Momordica charantia. This study aimed to verify the effects of M. charantia saponins on insulin secretion and explore the potential underlying mechanisms in INS-1 pancreatic ß-cells. We injured INS-1 cells with 33.3mM glucose and then treated them with saponins. Saponins improved cell morphology and viability as demonstrated by inverted microscopy and CCK8 detection and significantly increased insulin secretion in a concentration-dependent manner as shown by ELISA. Thus, we obtained the optimal concentration for the subsequent experiments. Potential mechanisms were explored by immunofluorescence, western blotting, and RT-qPCR techniques. First, saponins increased the mRNA and protein levels of IRS-2 but decreased the serine 731 phosphorylation level of IRS-2. Moreover, saponins increased the phosphorylation of Akt protein and decreased the protein level of FoxO1, which were both reversed by the PI3K inhibitor ly294002. Furthermore, saponins increased the protein level of the downstream molecule and insulin initiating factor PDX-1, which was also reversed by ly294002. Saponins also increased Akt and PDX-1 mRNA and decreased FoxO1 mRNA, which were both reversed by ly294002. Saponins increased glucose-stimulated insulin secretion (GSIS) and intracellular insulin content, which were reversed by ly294002, as determined by ELISA. The immunofluorescence results also confirmed this tendency. In conclusion, our findings improve our understanding of the function of saponins in INS-1 pancreatic ß-cells and suggest that saponins may increase insulin secretion via the PI3K/Akt/FoxO1 signaling pathway.

Correlation Between Thioredoxin-Interacting Protein and Nerve Conduction Velocity in Patients With Type 2 Diabetes Mellitus.

Aims: To investigate the correlation between thioredoxin-interacting protein (TXNIP) and peripheral nerve conduction velocity (NCV) in patients with type 2 diabetes mellitus. Methods: In total, 338 patients with type 2 diabetes mellitus (T2DM) were included in this study. We collected the clinical data and measured the motor conduction velocities of the bilateral ulnar nerve, median nerve, tibial nerve, and common peroneal nerve, and the sensory conduction velocities of the ulnar nerve, median nerve, sural nerve, and superficial peroneal nerve. According to the results, the patients were divided into two groups: normal peripheral nerve conduction group (NCVN group) and abnormal peripheral nerve conduction group (NCVA group). The two groups were then compared in terms of the conventional biochemical index and the sugar metabolic index as well as the serum levels of TXNIP, reduced glutathione (GSH), total superoxide dismutase (SOD), malondialdehyde (MDA), and tumor necrosis factor alpha (TNF-α). The correlation between TXNIP and NCV was also analyzed. Results: Compared with the NCVN group, the TXNIP and MDA values were significantly increased in the NCVA group (P < 0.05). Among the patients with T2DM, age, fasting glucose, SDBG, and TXNIP were risk factors for NCV abnormality, while vitamin D3 was a protective factor. After adjusting for related confounding factors, TXNIP was significantly correlated with NCV (P < 0.05). Among the patients with T2DM, TXNIP was an independent risk factor for left ulnar motor conduction velocity (MCV), right ulnar MCV, left median MCV, and right median MCV. TNF-α was identified as a positive influencing factor for serum TXNIP, while serum TXNIP was a positive factor for TNF-α and MDA (both P < 0.05). Conclusion: Serum TXNIP is related to NCV in T2DM patients. In combination with oxidative stress and inflammation, TXNIP may affect diabetic peripheral neuropathy (DPN).

Amelioration of hepatic steatosis is associated with modulation of gut microbiota and suppression of hepatic miR-34a in Gynostemma pentaphylla (Thunb.) Makino treated mice.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a chronic and progressive liver disease with an increased risk of morbidity and mortality. However, so far no specific pharmacotherapy has been approved. Gynostemma pentaphylla (Thunb.) Makino (GP) is a traditional Chinese medicine that is widely used against hyperlipemia as well as hyperglycemia. This study aims to evaluate the effect of GP on NAFLD and explore the possible mechanism. METHODS: High-fat-diet induced NAFLD mice model were orally administrated with GP at dose of 11.7 g/kg or equivalent volume of distilled water once a day for 16 weeks. Body weight, food intake and energy expenditure were assessed to evaluate the general condition of mice. The triglycerides, total cholesterol content in the liver and liver histopathology, serum lipid profile and serum insulin level, fecal microbiome, hepatic microRNAs and relative target genes were analyzed. RESULTS: Mice in GP treatment group displayed improved hepatic triglycerides content with lower lipid droplet in hepatocyte and NAFLD activity score. Besides, GP treatment altered the composition of gut microbiota and the relative abundance of some of the key components that are implicated in metabolic disorders, especially phylum Firmicutes (Eubacterium, Blautia, Clostridium and Lactobacillus). Several hepatic microRNAs were downregulated by GP treatment such as miR-130a, miR-34a, miR-29a, miR-199a, among which the expression miR-34a was altered by more than four-fold compared to that of HFD group (3:14). The correlation analysis showed that miR-34a was strongly related to the change of gut microbiota especially phylum Firmicutes (R = 0.796). Additionally, the target genes of miR-34a (HNF4α, PPARα and PPARα) were restored by GP both in mRNA and protein levels. CONCLUSION: Our results suggested that GP modulated the gut microbiota and suppressed hepatic miR-34a, which was associated with the amelioration of hepatic steatosis.

[Discussion on the Right of Medical Equipment Purchasing Operation Method and Effect].

Medical equipment procurement authority provides sunshine supervisory channel for hospital staff by power operation monitoring software, which could operate in the open. The exercise of purchase rights should upload the content in accordance with the provisions of "internal control point". It could strengthen the procurement process control and ensure the orderly supervision links to further regulate bidding and purchasing behavior, which can prevent the exercise of uncontrolled power.

Diosgenin induces apoptosis in IGF-1-stimulated human thyrocytes through two caspase-dependent pathways.

Insulin-like growth factor-1 (IGF-1) is a growth factor of the thyroid that has been shown in our previous study to possess proliferative and antiapoptotic effects in FRTL-5 cell lines through the upregulation of cyclin D and Fas-associated death domain-like interleukin-1-converting enzyme (FLICE)-inhibitory protein (FLIP). Diosgenin, a natural steroid sapogenin from plants, has been shown to induce apoptosis in many cell lines, with the exception of thyroid cells. In this report, we investigated the apoptotic effect and mechanism of diosgenin in IGF-1-stimulated primary human thyrocytes. Primary human thyrocytes were preincubated with or without IGF-1 for 24h and subsequently exposed to varying concentrations of diosgenin for different times. We found that diosgenin induced apoptosis in human thyrocytes pretreated with IGF-1 in a dose-dependent manner through the activation of caspase cascades. Moreover, diosgenin inhibited FLIP and activated caspase-8 in the FAS-related apoptotic pathway. Diosgenin increased the production of ROS, regulated the balance of Bax and Bcl-2 and cleaved caspase-9 in the mitochondrial apoptotic pathway. These results indicate that diosgenin induces apoptosis in IGF-1-stimulated primary human thyrocytes through two caspase-dependent pathways.