Jiegeng decoction ameliorated acute pharyngitis through suppressing NF-κB and MAPK signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiegeng decoction (JGD), consisting of Glycyrrhizae Radix et Rhizoma and Platycodonis Radix at the ratio of 2:1, is a classical Chinese medicine prescription firstly recorded in "Treatise on Febrile Diseases". JGD has been extensively utilized to treat sore throat and lung diseases for thousands of years in China. However, the pharmacological effect and mechanism of JGD on acute pharyngitis (AP) remain unclear. AIM OF THE STUDY: Our research aimed to reveal the pharmacological effect of JGD on AP and its potential mechanisms. MATERIALS AND METHODS: The chemical components of JGD were analyzed based on the UPLC-MS analysis. The anti-inflammatory effect of JGD was evaluated by NO production using the Griess assay in RAW.246.7 cells. The mRNA expression of iNOS, IL-1ß, IL-10, TNF-α, IL-6 and MCP-1 was determined by qRT-PCR in vitro. A 15% ammonia-induced AP model was established. The histopathology, the inflammatory cytokines IL-6 and MCP-1 in serum and the apoptosis-related genes caspease-8 and caspease-3 were determined by H&E staining, ELISA and qRT-PCR, respectively. The expression levels of p-p65, p65, p-JNK, JNK, p-p38, p38, p-ERK1/2, ERK1/2, and COX2 were measured through western blotting. RESULTS: Nine compounds, including liquiritin, liquiritin apiosde, liquiritigenin, platycodin D, platycoside A, licorice saponin J2, licorice saponin G2, glycyrrhizic acid, and licochalcone A, were identified. JGD significantly inhibited NO production and regulated the mRNA expression levels of cytokines in LPS-stimulated RAW264.7 cells. The results of in vivo experiments confirmed that JGD ameliorated AP through improving the pathological state of pharyngeal tissue, decreasing the serum levels of IL-6 and MCP-1 and preventing the tissue mRNA expression of caspease-8 and caspease-3. Furthermore, JGD also inhibited the NF-κB and MAPK pathways in the AP model. CONCLUSIONS: This study suggested that JGD could alleviate AP through its anti-inflammation via NF-κB and MAPK pathways, which supported the traditional application of JGD for the treatment of throat diseases.

An Industrially Applicable Passivation Strategy for Significantly Improving Cyclability of Zinc Metal Anodes in Aqueous Batteries.

The cycling instability of metallic Zn anodes hinders the practicability of aqueous Zn-ion batteries, though aqueous Zn-ion batteries may be the most credible alternative technology for future electrochemical energy storage applications. Commercially available trivalent chromium conversion films (TCCF) are successfully employed as robust artificial interphases on Zn metal anodes (ZMAs). Fabricated through a simple immersion method, the TCCF-protected Zn (TCCF@Zn) electrode enables a superlow nucleation overpotential for Zn plating of 6.9 mV under 1 mA cm-2 , outstanding Coulombic efficiency of 99.7% at 3 mA cm-2 for 1600 cycles in Zn||Cu asymmetric cells and superior cyclability in symmetric Zn||Zn batteries at 0.2, 2, and 5 mA cm-2 for 2500 h and 10 mA cm-2 for 1200 h. More importantly, the TCCF@Zn||V2 O5 full cell exhibits a specific capacity of 118.5 mAh g-1 with a retention of 53.4% at 3 A g-1 for 3000 cycles, which is considerably larger than that of the pristine Zn||V2 O5 full cell (59.7 mAh g-1 with a retention of 25.7%). This study demonstrates a highly efficient and low-cost surface modification strategy derived from an industrially applicable trivalent chromium passivation technique aimed at obtaining dendrite-free ZMAs with high reversibility for practical Zn batteries in the near future.

Diagnostic value of high sensitivity cardiac troponin T (hs-cTnT) in dialysis patients with myocardial infarction.

Background: As a sensitive diagnostic marker for myocardial infarction (MI) in people with normal renal function, elevated high sensitivity cardiac troponin T (hs-cTnT) was often found in chronic kidney disease (CKD) patients requiring dialysis. However, the accuracy of baseline hs-cTnT in the diagnosis of MI (including Type 1 MI (T1MI) and Type 2 MI (T2MI)) in dialysis patients is still controversial. The aim of this study was to retrospectively explore whether there were any clinical indices that could increase the predictive value of hs-cTnT on admission for MI occurrence in dialysis patients. Methods: Here, 136 patients with uremia who underwent regular dialysis with coronary angiography in the First Affiliated Hospital of Nanjing Medical University from August 2017 to October 2021 were enrolled. According to the coronary angiography results and the presence of clinical symptoms, the patients were divided into: (1). AMI group (n = 69; angiography positive) and Control group (n = 67; angiography negative); (2). T1MI group (n = 69; angiography positive), T2MI group (n = 7; angiography negative & symptomatic), and Control group (n = 60; angiography negative & asymptomatic). Results: Here, we found the mean hs-cTnT on admission in the Control group was much lower than that in the AMI group. Hs-cTnT alone had a mediocre predictive performance, with an AUROC of 0.7958 (95% CI: 0.7220, 0.8696). Moreover, the ROC curve of hs-cTnT combined with the Triglyceride (TG), Time of dialysis, and Albumin (Alb) showed a higher sensitivity area [0.9343 (95% CI: 0.8901, 0.9786)] than that of single hs-cTnT. Next, hs-cTnT combined with the TG, Time of dialysis, and Alb also presented a better performance in predicting T1MI [0.9150 (95% CI: 0.8678, 0.9621)] or T2MI (0.9167 [0.9167 (95% CI: 0.8427, 0.9906)] occurrences. Last, these combined variables could better distinguish patient between T1MI and T2MI group than hs-cTnT alone. Conclusions: On admission, a combination of hs-cTnT, TG, Time of dialysis, and Alb presented a higher sensitivity than hs-cTnT alone in predicting MI occurrence in dialysis patients, suggesting a better diagnostic approach for future clinical applications.

Vitamin D receptor deficiency increases systolic blood pressure by upregulating the renin-angiotensin system and autophagy.

The vitamin D receptor (VDR) may regulate blood pressure via multiple pathways. The present study investigated the underlying mechanism by which VDR deficiency increases blood pressure. A total of 16 8-week-old male littermate mice were randomly divided into the VDR knockout and wild-type groups (VDR-/- and VDR+/+ , respectively). Blood pressure was measured using a four-channel PowerLab data acquisition and ADI software analysis system. After euthanasia, vascular smooth muscle cells (VSMCs) were isolated from the VDR-/- and VDR+/+ mice. Oxidative stress, renin-angiotensin system (RAS) activation and autophagy markers were measured in the isolated VSMCs using reverse transcription-quantitative PCR (RT-qPCR), western blotting and transmission electron microscopy (TEM) assays. Mean systolic pressure was significantly higher in the VDR-/- mice compared with the VDR+/+ mice. RT-qPCR and western blotting analyses indicated that RAS markers (angiotensin II and II type 1 receptor) were significantly upregulated, oxidative stress was increased (evidenced by reduced superoxide dismutase and peroxiredoxin-4) and autophagy was activated (upregulation of autophagy related protein 7, Beclin 1 and microtubule-associated proteins 1A/1B light chain 3A) in the VDR-/- VSMCs compared with the VDR+/+ VSMCs. TEM demonstrated that there were more autophagy bodies in the VDR-/- VSMCs compared with the VDR+/+ VSMCs. In conclusion, VDR deficiency was associated with high blood pressure. The mechanism underlying the increase in blood pressure caused by VDR deficiency may involve activation of the RAS, as well as increased oxidative stress and autophagy of VSMCs.

MicroRNA-210-5p alleviates cardiac fibrosis via targeting transforming growth factor-beta type I receptor in rats on high sodium chloride (NaCl)-based diet.

The present study was designed to explore whether high sodium chloride (NaCl)-based diet (HSD) caused cardiac fibrosis regardless of blood pressure in Sprague-Dawley (SD) rats, and to further determine the effects and the underlying mechanisms of microRNA (miR)-210-5p on HSD-induced cardiac fibrosis in rats or NaCl-induced cardiac fibroblast activation in neonatal rat cardiac fibroblasts (NRCFs). The SD rats received 8% HSD, and NRCFs were treated with NaCl. The levels of collagen I, alpha-smooth muscle actin (α-SMA) and transforming growth factor-beta 1 (TGF-ß1) were increased in the heart of hypertension (HTN), hypertension-prone (HP) and hypertension-resistant (HR) rats on HSD in vivo. NaCl increased the levels of collagen I, α-SMA and TGF-ß1 in NRCFs in vitro. The level of miR-210-5p was reduced in both NBD-induced rats' hearts and NaCl-treated NRCFs, which was consistent with the results of miR high-throughput sequencing in NRCFs. The HSD or NaCl-induced increases of collagen I, α-SMA and TGF-ß1 were inhibited by miR-210-5p agomiR in vitro and in vivo, respectively. miR-210-5p antagomiR could mimic the pathological effects of NaCl in NRCFS. Bioinformatics analysis and luciferase reporter assays demonstrated that TGF-ß type I receptor (TGFBR1) was a direct target gene of miR-210-5p. These results indicated that HSD resulted in cardiac fibrosis regardless of blood pressure. The upregulation of miR-210-5p could attenuate cardiac fibroblast activation in NRCFS via targeting TGFBR1. Thus, upregulating miR-210-5p might be a strategy for the treatment of cardiac fibrosis.

Girdin Knockdown Increases Gemcitabine Chemosensitivity to Pancreatic Cancer by Modulating Autophagy.

Chemotherapy is crucial for the treatment of pancreatic cancer (PC). Gemcitabine (GEM) as the first-line chemotherapy drug has a high resistance rate. Increasing the sensitivity of gemcitabine is currently the objectives and challenges of this study. Our previous study showed Girdin was closely related to the progression and prognosis of PC, indicating that Girdin may be associated with chemosensitivity. In the current study, we use recombinant adenovirus to specifically knockdown Girdin in PC cell lines to determine the effect of Girdin in the process of gemcitabine chemosensitivity. Autophagy is one of the pathways affecting the gemcitabine chemosensitivity in PC. Further research validated that Girdin may activate autophagy by interacting with autophagy protein p62/SQSTM1, which could enhance chemotherapy resistance to gemcitabine in PC. Down-regulation of Girdin may therefore increase gemcitabine chemosensitivity in PC. Our results reveal that Girdin acted as a negative regulator of gemcitabine chemosensitivity in PC. Increased autophagy activity caused by abnormally high Girdin expression may be one of the main factors for the reduction in chemosensitivity, which may provide new perspectives on understanding chemosensitization in PC.

The CYP17A1 gene polymorphisms are associated with hypercholesterolemia in Han Chinese.

BACKGROUND: The CYP17A1 gene has been identified to associate with hypertension in Chinese population. However, the association between CYP17A1 polymorphisms and hypertension-related factors is unclear. The present study aimed to investigate the relation between CYP17A1 single nucleotide polymorphisms (SNPs) and serum lipid profiles. METHODS: In total, 1350 participants were included in the study. Six SNPs in or near CYP17A1 gene were genotyped in a Han Chinese population in two stages. RESULTS: There was a statistically significant association of rs1004467 (adjusted odds ratio = 0.783, 95% confidence interval = 0.667-0.919, p < 0.05) and rs11191548 (adjusted odds ratio = 0.788, 95% confidence interval = 0.672-0.925, p < 0.05) with hypercholesterolemia after adjustment for potential factors. Additionally, the rs1004467 minor G-allele and the rs11191548 minor C-allele were significantly associated with the lower serum total cholesterol levels (p < 0.05 for all). CONCLUSIONS: The rs1004467 and rs11191548 in the CYP17A1 gene are associated with a decreased risk of hypercholesterolemia and lower serum TC levels in Han Chinese.

Associations of genetic polymorphisms of the vitamin D pathway with blood pressure in a Han Chinese population.

Vitamin D deficiency can lead to high blood pressure. Polymorphisms in the vitamin D hydroxylase gene have been associated with serum vitamin D levels in some Western countries. The aim of this study was to investigate whether polymorphisms of hydroxylase genes in the vitamin D metabolic pathway contribute to hypertension by affecting serum vitamin D status in a Han Chinese population. We selected four single nucleotide polymorphisms (SNPs; rs1993116 and rs10741657 of CYP2R1; rs4809957 and rs6068816 of CYP24A1) for genotyping in 525 control subjects and 324 hypertensive patients, and detected vitamin D levels in blood in subsets of these groups. The results showed that rs1993116 and rs10741657 were associated with a reduced risk of hypertension. The odds ratios, 95% confidence intervals, and p values from the adjusted additive and dominant models were 0.788 (0.644-0.963, p = 0.02) and 0.719 (0.545-0.949, p = 0.02) for rs1993116 and 0.805 (0.66-0.983, p = 0.033) and 0.733 (0.556-0.966, p = 0.028) for rs10741657. A protective effect of CYP2R1 with regard to hypertension was also found in males and non-smokers. The TT genotypes of rs1993116 and rs10741657 were associated with significantly lower systolic blood pressure in treated hypertensive patients (both p = 0.002). No association with hypertension was found for the two SNPs of CYP24A1, and no difference in vitamin D level was found among the three genotypes of the four SNPs. Our results suggest that CYP2R1 polymorphisms are associated with a reduced risk of hypertension independent of the vitamin D level in the Han Chinese population.

Girdin regulates the proliferation and apoptosis of pancreatic cancer cells via the PI3K/Akt signalling pathway.

Girdin functions as an Akt phosphorylation enhancer (APE), which expedites the proliferation and survival of many types of tumours. However, the influence of Girdin on pancreatic cancer and the underlying molecular mechanisms have yet to be uncovered. Hence, in the present study, we sought to elucidate the function of Girdin in pancreatic cancer malignancy, particularly its role in pancreatic cancer cell proliferation, migration and apoptosis. Immunohistochemistry (IHC) was used to evaluate Girdin expression in pancreatic cancer tissues and to analyse its correlation with pathological grade. Girdin expression was further validated in pancreatic cancer cell lines (AsPC­1, BxPC­3 and PANC­1), and human pancreatic ductal epithelial (HPNE) cells were used as a control. Recombinant adenovirus vectors containing Girdin­siRNA were constructed to inhibit Girdin expression and were used in subsequent experiments to determine the effects of Girdin silencing on pancreatic cancer cells. Girdin silencing suppressed pancreatic cancer cell proliferation and induced pancreatic cancer cell apoptosis in vitro and in vivo. According to the results of further mechanistic investigations, Girdin may regulate cell processes through the phosphatidylinositol­3­kinase/protein kinase B (PI3K/Akt) signalling pathway to exert additive effects on pancreatic cancer.

Common variant rs11191548 near the CYP17A1 gene is associated with hypertension and the serum 25(OH) D levels in Han Chinese.

The CYP17A1 gene, which encodes17α-hydroxylase and 17,20-lyase, has been identified as a common hypertension susceptibility locus in a European population. However, the association between CYP17A1 polymorphisms and hypertension is unclear in the Chinese population as well as in the role of serum 25(OH) D levels. Six single nucleotide polymorphisms (SNPs) in CYP17A1 were genotyped in two stages in a Han Chinese population, and the serum 25(OH) D levels were measured. Analysis in stage 1 showed that the rs1004467 minor G-allele and rs11191548 minor C-allele in CYP17A1 were significantly associated with a decreased risk of hypertension and higher serum 25(OH) D levels (all P < 0.05). The larger sample in stage 2 also showed that a mutation in rs11191548 was significantly associated with a decreased risk of hypertension (adjusted OR = 0.707, 95% CI: 0.553-0.904, P = 0.006). The rs11191548 minor C-allele was associated with higher serum 25(OH) D levels in hypertensive subjects (ßadj ± SEM = 0.094 ± 0.949, P = 0.003) and controls (ßadj ± SEM = 0.128 ± 1.025, P < 0.001). In conclusion, the rs11191548 CYP17A1 gene mutation was associated with hypertension and the serum 25(OH) D levels in Han Chinese.