The association between serum selenium levels and pathological features of papillary thyroid cancer in 284 patients.

Objective: The relationship between serum selenium levels and papillary thyroid cancer (PTC), especially the pathological features, still remains controversial. We conducted this study to investigate the relationship between serum selenium levels and PTC in a Chinese population. Methods: Cross-sectional data of 284 patients with PTC were collected from the First Affiliated Hospital of Shandong First Medical University. The general clinical characteristics, serum selenium levels, and tumor pathological features were described in PTC. The association between serum selenium levels and pathological features in PTC was analyzed using SPSS 26.0 statistical software. Results: Our results showed that the median serum selenium level was 79.15 µg/L (IQR: 71.00 - 86.98 µg/L) in PTC patients. Serum selenium levels were lower in females than males (p = 0.035). Serum selenium levels were negatively correlated with the number of lymph node metastases (p = 0.048). High serum selenium (OR = 0.397, 95%CI: 0.217 - 0.725) and diastolic blood pressure (OR = 1.028, 95%CI: 1.005 - 1.051) were related factors for the incidence of bilateral tumors. High serum selenium (OR = 0.320, 95%CI: 0.166 - 0.617) and diastolic blood pressure (OR = 1.066, 95%CI: 1.031 - 1.103) were related factors for tumor multifocal incidence. Conclusions: The serum selenium levels of PTC patients in females were lower than males. High serum selenium levels might be a protective factor in PTC patients. Further research is necessary to better understand the influence of selenium on PTC progression.

Repair effect of Centella asiatica (L.) extract on damaged HaCaT cells studied by atomic force microscopy.

People's choice of cosmetics is no longer just 'Follow the trend', but pays more attention to the ingredients of cosmetics, whether the ingredients of cosmetics are beneficial to people's skin health; therefore, more and more skin-healthy ingredients have been discovered and used in cosmetics. In this work, atomic force microscope (AFM) is used to provide physical information about biomolecules and living cells; it brings us a new method of high-precision physical measurement. Centella asiatica (L.) extract has the ability to promote skin wound healing, but its healing effect on damaged HaCaT cells needs to be investigated, which plays a key role in judging the effectiveness of skincare ingredients. The objective of this study was to explore the impact of Centella asiatica (L.) extract on ethanol-damaged human immortalised epidermal HaCaT cells based on AFM. We established a model of cellular damage and evaluated cell viability using the MTT assay. The physical changes of cell height, roughness, adhesion and Young's modulus were measured by AFM. The findings indicated that the Centella asiatica (L.) extract had a good repair effect on injured HaCaT cells, and the optimal concentration was 75 µg/mL.

Recombinant Human Thyrotropin-Stimulated Radioiodine Therapy in Patients with Multinodular Goiters: A Meta-Analysis of Randomized Controlled Trials.

A potential reduction of goiter volume (GV) of recombinant human thyrotropin (rhTSH) on multinodular goiters (MNG) was previously reported but controversial. Hence we conducted a meta-analysis to estimate the effect of rhTSH-stimulated radioiodine therapy in patients with MNG. PubMed, Cochrane, CNKI, VIP, and Wanfang databases were searched. Mean difference (MD) and odds ratios with 95% confidence intervals (95% CI) were derived by using an inverse variance random-effects model and fixed-effects model, respectively. Six studies (n=237) were involved in the analysis. For 12 months follow up, high dose (>0.1 mg) of rhTSH significantly reduced GV (MD=17.61; 95% CI=12.17 to 23.04; p<0.00001) compared with placebo. No effective pooled results of low dose of rhTSH (<0.1 mg) were applicable for only one study included. For 6 months follow up, the source of heterogeneity was determined by subgroup and sensitivity analysis. High dose group showed vast improvement in GV reduction (MD=16.62; 95% CI=1.34 to 31.90; p=0.03). The reduction of low dose group compared with placebo was inferior to high dose group. No available data were obtained to assess the influence of rhTSH after 36 months follow up for the only included study. Hypothyroidism incidence was higher for rhTSH group. No publication bias was seen. High dose of rhTSH treatment-stimulated radioactive 131I therapy after 6 months and 12 months follow up had a better effect in reducing GV, but with higher incidence of hypothyroidism. Owing to the limited methodological quality, more clinical researches are warranted in the future.

Mechanisms of Spica Prunellae against thyroid-associated Ophthalmopathy based on network pharmacology and molecular docking.

BACKGROUND: Thyroid-associated ophthalmopathy (TAO) is an autoimmune inflammatory disorder, which lacks effective treatment currently. Spica Prunellae (SP) is popularly used for its anti-inflammatory and immune-regulating properties, indicating SP may have potential therapeutic value in TAO. Therefore, the purpose of this study is to identify the efficiency and potential mechanism of SP in treating TAO. METHODS: A network pharmacology integrated molecular docking strategy was used to predict the underlying molecular mechanism of treating TAO. Firstly, the active compounds of SP were obtained from TCMSP database and literature research. Then we collected the putative targets of SP and TAO based on multi-sources databases to generate networks. Network topology analysis, GO and KEGG pathway enrichment analysis were performed to screen the key targets and mechanism. Furthermore, molecular docking simulation provided an assessment tool for verifying drug and target binding. RESULTS: Our results showed that 8 targets (PTGS2, MAPK3, AKT1, TNF, MAPK1, CASP3, IL6, MMP9) were recognized as key therapeutic targets with excellent binding affinity after network analysis and molecular docking-based virtual screening. The results of enrichment analysis suggested that the underlying mechanism was mainly focused on the biological processes and pathways associated with immune inflammation, proliferation, and apoptosis. Notably, the key pathway was considered as the PI3K-AKT signaling pathway. CONCLUSION: In summary, the present study elucidates that SP may suppress inflammation and proliferation and promote apoptosis through the PI3K-AKT pathway, which makes SP a potential treatment against TAO. And this study offers new reference points for future experimental research and provides a scientific basis for more widespread clinical application.

Hongjingtian Injection Inhibits Proliferation and Migration and Promotes Apoptosis in High Glucose-Induced Vascular Smooth Muscle Cells.

BACKGROUND: Hongjingtian injection (HJT) is administered in the treatment of vascular diseases, including diabetic angiopathies (DA). However, its underlying mechanisms have not been examined systematically. METHODS: In this research, we explored potential mechanisms of HJT through network pharmacology. HG-stimulated A7r5 cells served as the cell model. Cell proliferation, migration and apoptosis were investigated. The effects on key targets and the AKT pathway were verified by Western blotting in experiments with the AKT inhibitor LY294002 or activator SC79. RESULTS: Network analysis predicted that HJT targeted 10 candidate targets and 15 pathways including cell proliferation, migration and apoptosis in response to DA. Functional experiments showed that HJT markedly suppressed the proliferation and migration and promoted the apoptosis of HG-induced VSMCs, which validated the prediction. Mechanistically, HJT significantly downregulated the expression of pAKT, MMP9, and PCNA, upregulated the expression of p53 and cleaved caspase-3 and increased the Bax/Bcl-2 ratio compared with the HG group. SC79, an AKT activator, partially reversed the inhibitory effects of HJT on HG-induced VSMCs, confirming the involvement of the AKT pathway. Furthermore, the presence of the AKT inhibitor LY294002 had a similar inhibitory effect as HJT. CONCLUSION: These findings systematically evaluate the potential mechanisms of HJT for the treatment of DA. HJT suppressed the proliferation and migration and promoted the apoptosis of HG-induced VSMCs partly by inhibiting the AKT pathway. Additionally, this study may provide a quick and effective way to investigate the molecular mechanisms of traditional Chinese medicine.

Integrated Treatment of Prostaglandin E1 and Angiotensin-Converting Enzyme Inhibitor in Diabetic Kidney Disease Rats: Possible Role of Antiapoptosis in Renal Tubular Epithelial Cells.

To investigate the therapeutic mechanisms underlying prostaglandin E1 (PGE1) and angiotensin-converting enzyme inhibitor (ACEI) on reducing urinary protein in diabetic kidney disease (DKD). DKD rats were established and randomly divided into four groups: PGE1 (10 µg/kg/day) (P group), ACEI (10 mg/kg/day) (A group), combination of PGE1 with ACEI treatment (P + A group), and saline treatment group (DKD group). Untreated rats were used as normal control (N group). Urinary albumin, endothelin-1 (ET-1), angiotensin II (AngII), TUNEL assay, Masson's trichrome staining, and immunohistochemistry staining for CD68 were evaluated in all groups. Ten days after treatment, urinary albumin was significantly decreased in the P and P + A groups (p < 0.01 vs. the DKD group). At the end of 8 weeks, the albumin was still significantly reduced in the P + A group (p < 0.05 vs. the A group). ET-1 and AngII were also significantly decreased in three treatment groups (p < 0.01 vs. the DKD group), especially in the P + A group. Few cells underwent apoptosis in glomerular regions in DKD rats, while amounts of apoptotic cells were seen in tubules regions. Further, apoptosis and the areas of fibrosis in tubulointerstitial were both decreased most in the P + A group compared with the DKD group. Apoptosis of renal tubular epithelial cells may participate in the development and progression of DKD in rats. Combination of PGE1 with AGEI remarkably protects renal function compared with PGE1 or ACEI monotherapy. The potential therapeutic mechanisms of PGE1 and AGEI might be via multiple targets and, at least in part, through inhibiting the apoptosis of renal tubular epithelial cells.

Efficacy and safety of vitamin D3 in patients with diabetic nephropathy: a meta-analysis of randomized controlled trials.

BACKGROUND: Several studies found that vitamin D3 might alter glucose metabolism, protect kidney from injury and even proposed the mechanisms. But results from previous studies have been conflicting. The aim of this study was to evaluate the efficacy and safety of vitamin D3 in patients with diabetic nephropathy. The underlying mechanism of vitamin D3 decreasing proteinuria is also discussed. METHODS: We conducted a search of English and Chinese articles using database of Pubmed, Embase, Sinomed, CNKI, Wanfang and clinical trial register centers, for randomized controlled trials of vitamin D3 in diabetic nephropathy patients. Two reviewers performed independently. Meta-analysis was used when studies were homogeneous enough. RESULTS: Twenty studies, including 1 497 patients with diabetic nephropathy, were involved in this systemic review. Vitamin D3-treated patients with diabetic nephropathy had a statistically significant reduction in 24-hour proteinuria (weighted mean difference -0.44, 95% CI -0.54 to -0.34, Z = 8.80, P < 0.000 01) and urine albumin/creatine ratio (standardized mean difference -0.29, 95% CI -0.48 to -0.10, Z = 2.96, P = 0.003). But vitamin D3 supplementation did not significantly reduce blood pressure and hemoglobin A1c compared with control group. The potential mechanisms about the renal protection of vitamin D3, including the inhibition of rennin-angiotensin system, the protection of kidney from inflammation, fibrosis and the structure change of kidney are discussed. In addition, vitamin D3 did not significantly increase the incidence of adverse effects, including total adverse effects, gastrointestinal adverse effects and fluctuation of blood pressure. CONCLUSIONS: Vitamin D3 can ameliorate proteinuria and protect kidney from injury in patients with diabetic nephropathy. This renoprotective effect is independent of blood pressure and glucose reduction. And it does not increase any adverse effects than control, even in combination therapy with angiotensin converting enzyme inhibitors/angiotensin receptor blockers. But due to the limited randomized controlled trials of high quality, more clinical researches should be taken in the future.

First-principles calculation of kinetic barriers and metastability for the corundum-to-Rh2O3(II) transition in Al2O3.

We demonstrate that the rhombohedral corundum crystal and the orthorhombic Rh(2)O(3)(II) crystal are structurally related by a diffusionless monoclinic common subgroup pathway, along which the intermediate structures have the space group P 2/c symmetry. This transformation pathway is energetically favored because the majority of Al-O bonds are preserved during the transition. Only 1/3 of the four-coordinated anions and 1/2 of the six-coordinated cations break and reform a single bond. No other bonds are broken in the transformation. Our calculated forward (corundum-to-Rh(2)O(3)(II)) enthalpy barrier (about 140 meV/atom) in Al(2)O(3) is not pressure-sensitive at least up to 160 GPa, which is consistent with the observed metastability of the corundum phase around room temperature. In contrast, we predict a significantly decreasing backward (Rh(2)O(3)(II)-to-corundum) enthalpy barrier on decompression, which suggests that the high-pressure Rh(2)O(3)(II) phase of Al(2)O(3) is unlikely to be recoverable at ambient conditions. In addition, we propose a general, common subgroup-based approach to compare elastic properties of two phases with different Bravais lattices. By treating both rhombohedral and orthorhombic phases with common monoclinic P 2/c unit cells (non-primitive for the corundum phase), we show that the elastic properties of the high-pressure Rh(2)O(3)(II) phase are very comparable to those of the ambient corundum phase.