Network pharmacology analysis and experimental validation to explore the mechanism of kaempferol in the treatment of osteoporosis.

Osteoporosis (OP) is a prevalent global disease characterized by bone mass loss and microstructural destruction, resulting in increased bone fragility and fracture susceptibility. Our study aims to investigate the potential of kaempferol in preventing and treating OP through a combination of network pharmacology and molecular experiments. Kaempferol and OP-related targets were retrieved from the public database. A protein-protein interaction (PPI) network of common targets was constructed using the STRING database and visualized with Cytoscape 3.9.1 software. Enrichment analyses for GO and KEGG of potential therapeutic targets were conducted using the Hiplot platform. Molecular docking was performed using Molecular operating environment (MOE) software, and cell experiments were conducted to validate the mechanism of kaempferol in treating OP. Network pharmacology analysis identified 54 overlapping targets between kaempferol and OP, with 10 core targets identified. The primarily enriched pathways included atherosclerosis-related signaling pathways, the AGE/RAGE signaling pathway, and the TNF signaling pathway. Molecular docking results indicated stable binding of kaempferol and two target proteins, AKT1 and MMP9. In vitro cell experiments demonstrated significant upregulation of AKT1 expression in MC3T3-E1 cells (p < 0.001) with kaempferol treatment, along with downregulation of MMP9 expression (p < 0.05) compared to the control group. This study predicted the core targets and pathways of kaempferol in OP treatment using network pharmacology, and validated these findings through in vitro experiments, suggesting a promising avenue for future clinical treatment of OP.

Effect of Health Education Combined with Dietary Guidance on Nutritional Indicator, Immune Level, and Quality of Life of Patients with Pulmonary Tuberculosis.

OBJECTIVE: To investigate the effects of health education combined with dietary guidance on nutritional indicators, immune level, and quality of life of patients with pulmonary tuberculosis. METHOD: A total of 123 patients with pulmonary tuberculosis who were hospitalized to our hospital between October 2019 and October 2020 were chosen for the study and were separated into 60 control cases and 63 observation cases based on the ward they were assigned to. Patients in the two groups were compared in terms of nutritional risk, nutritional indicator levels in serum, immunological function, treatment compliance, sputum culture conversion rate, and quality of life. RESULT: With the prolongation of patients' illness, the total NRS 2002 score gradually increased in both groups and the total NRS 2002 score of patients in the control group was higher than that of patients in the observation group at the same time point after discharge. The difference between the total NRS 2002 score of patients in both groups was significant at 3 and 6 months after discharge. After the intervention, the Hb, ALB, CD4+, and CD4+/CD8+ levels of patients in both groups were higher than those at the time of admission, and the CD8+ levels were lower than those at the time of admission. At 6 months after discharge, the Hb, ALB, CD4+, and CD4+/CD8+ levels of patients in the observation group were significantly higher than those in the control group, and the CD8+ levels were significantly lower than those in the control group. The treatment compliance rate of patients in the observation group (96.83%) was significantly higher than that of the control group (75%), and the negative sputum culture transfer rate (85.71%) was significantly higher than that in the control group (60%). The overall quality of life scores of patients in the observation group was significantly higher than that in the control group. CONCLUSION: Health education combined with dietary guidance for patients with pulmonary tuberculosis can deepen patients' understanding of disease and nutritional knowledge, improve treatment compliance, improve their nutritional status, enhance their immune function, accelerate sputum bacterial conversion, enhance treatment effect, and improve their quality of life.

Clinical characteristics of imported and second-generation coronavirus disease 2019 (COVID-19) cases in Shaanxi outside Wuhan, China: a multicentre retrospective study.

The mortality of coronavirus disease 2019 (COVID-19) differs between countries and regions. This study aimed to clarify the clinical characteristics of imported and second-generation cases in Shaanxi. This study included 134 COVID-19 cases in Shaanxi outside Wuhan. Clinical data were compared between severe and non-severe cases. We further profiled the dynamic laboratory findings of some patients. In total, 34.3% of the 134 patients were severe cases, 11.2% had complications. As of 7 March 2020, 91.8% patients were discharged and one patient (0.7%) died. Age, lymphocyte count, C-reactive protein, erythrocyte sedimentation rate, direct bilirubin, lactate dehydrogenase and hydroxybutyrate dehydrogenase showed difference between severe and no-severe cases (all P < 0.05). Baseline lymphocyte count was higher in survived patients than in non-survivor case, and it increased as the condition improved, but declined sharply when death occurred. The interleukin-6 (IL-6) level displayed a downtrend in survivors, but rose very high in the death case. Pulmonary fibrosis was found on later chest computed tomography images in 51.5% of the pneumonia cases. Imported and second-generation cases outside Wuhan had a better prognosis than initial cases in Wuhan. Lymphocyte count and IL-6 level could be used for evaluating prognosis. Pulmonary fibrosis as the sequelae of COVID-19 should be taken into account.

IL1R1 and IL1R2 polymorphisms were associated with tuberculosis risk: A pilot study.

BACKGROUND: Interleukin (IL)-1 has been reported to be involved in the development of tuberculosis (TB). IL1R1 and IL1R2 encode a cytokine receptor that belongs to the IL-1 receptor family. However, few studies have reported on the polymorphisms of IL1R1 and IL1R2 in TB patients. METHODS: We investigated nine single-nucleotide polymorphisms (SNPs) in IL1R1 and IL1R2 in 300 TB patients and 300 controls, aiming to evaluate their association with TB risk. Odds ratios and 95% confidence intervals were calculated using unconditional logistic regression after adjusting for age and gender. RESULTS: On comparing the allele frequencies of candidate SNPs, we found that the minor allele 'A' of rs4851527 in IL1R2 was associated with a decreased risk of TB, whereas the minor alleles of rs10490571, rs956730 and rs3917225 in IL1R1 were associated with an increased risk of TB (p < 0.05). In the genetic model analysis, we found that the allele 'A' of rs4851527 was correlated with a decreased risk of TB in a log-additive model, whereas the minor alleles of rs719250, rs3218977, rs10490571, rs956730 and rs3917225 were correlated with an increased risk of TB in dominant and log-additive models (p < 0.05). Additionally, we found three haplotypes that were associated with an increased risk of TB: TGCT and TGTT haplotypes constructed by rs11674595, rs4851527, rs719250 and rs3218896, as well as GA haplotype constructed by rs3218977 and rs2072472 (p < 0.05). CONCLUSIONS: Our data shed new light on the association between genetic polymorphisms of IL1R1 and IL1R2 and TB susceptibility in the Chinese Han population.

Genetic polymorphisms of ALDH2 are associated with lumbar disc herniation in a Chinese Han population.

Aldehyde dehydrogenase (ALDH) is a key enzyme for the catalytic oxidation of acetaldehyde to acetic acid. Genetic polymorphisms of ALDH2 have been associated with a wide range of diseases and cancers. However, little information is found about the association between ALDH2 polymorphisms and lumbar disc herniation (LDH) in Chinese Han population. We investigated the association between single nucleotide polymorphisms (SNPs) in ALDH2 and LDH risk in a case-control study that included 380 LDH cases and 692 healthy controls. Eight SNPs were selected and genotyped using the Sequenom MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression after adjusting for gender and age. In the allele model analysis, we found the frequency of the "A" allele of rs671 was significantly higher in LDH cases than in controls (OR = 1.414, 95%CI: 1.109-1.803, P = 0.005). In the genetic model analysis, we found the minor allele "A" of rs671 was associated with increased risk of LDH under log-additive model (OR = 1.42, 95%CI: 1.11-1.82, P = 0.0062); and the minor allele "C" of rs7296651 was associated with decreased risk of LDH under over-dominant model (OR = 0.72, 95%CI: 0.53-0.97, P = 0.031). Additionally, the haplotype "GGCTCACG" constructed by rs886205, rs2238152, rs4648328, rs441, rs4646778, rs671, rs11066028, and rs7296651 was associated with increased risk of LDH (OR = 1.45; 95% CI = 1.11-1.90; P = 0.0071). Our data shed new light on the association between genetic polymorphisms of ALDH2 and LDH susceptibility in a Chinese Han population.

Association of TERT polymorphisms with chronic hepatitis B in a Chinese Han population.

In this study, we investigated the association between the polymorphisms of telomerase reverse transcriptase (TERT) gene and the risk of chronic hepatitis B (CHB) in a Chinese Han population. Four single nucleotide polymorphisms (SNPs) in TERT (rs10069690, rs2242652, rs2853677 and rs2853676) were genotyped from 224 CHB patients and 300 healthy controls using the Sequenom Mass-ARRAY platform. We used genetic model, haplotype analyses, chi-square test, logistic regression analysis to evaluate the association between SNPs and CHB risk. The relative risk was estimated by odd ratios (ORs) and 95% confidence intervals (CIs). We found that rs10069690 was significantly associated with an increased CHB risk in the dominant model (adjusted OR = 1.70, 95% CI: 1.06-2.71, P = 0.031) and additive model (adjusted OR = 1.62, 95% CI: 1.09-2.41, P = 0.018). The haplotype "TA" (rs10069690 and rs2242652) was found to be associated with an increased risk of CHB (adjusted OR = 1.58, 95% CI: 1.05-2.38, P = 0.027). Our results suggested potential genetic contributes for TERT in CHB development in a Chinese Han population. Future functional and association studies with larger sample sizes are required to confirm these findings.

Genetic polymorphism analysis of cytochrome P4502E1 (CYP2E1) in a Chinese Tibetan population.

Cytochrome P4502E1 (CYP2E1) gene genetic polymorphisms vary markedly in frequency among different ethnic and racial groups.We studied the genotype distributions and allele frequencies of 3 CYP2E1 polymorphisms: CYP2E11A, CYP2E17A, and CYP2E17C by polymerase chain reaction technique in a sample of 100 healthy subjects representing Tibetan population.The frequencies of CYP2E11A, 7A, and 7C alleles were 0.705, 0.125, and 0.170, respectively. Compared with other populations, we found that the allele frequencies of the variants -352A>G (rs2070672) and -333A>T (rs2070673) in this Tibetan population have significant differences compared with European-American, African-American, Japanese, Korean, and other different geographic areas in Chinese Han population. Furthermore, the results of protein prediction revealed that the variant 6397G>A (rs61710826) could influence the protein structure and function.These findings in this study would be valuable for pharmacogenetics for drug therapy and drug discovery. However, further studies in larger samples are warranted to confirm our results.

P2X7R Gene Polymorphisms are Associated with Increased Risk of Pulmonary Tuberculosis in the Tibetan Chinese Population.

In this study, we aim to explore the correlation between single nucleotide polymorphisms (SNPs) in the P2X7R gene and pulmonary tuberculosis (PTB) susceptibility in the Tibetan Chinese population in China. We examined 467 patients with active PTB and 504 healthy controls living in Xi'an and the surrounding area. Eight P2X7R SNPs were genotyped, and association analysis was performed. Odds ratios (ORs) and 95% confidence intervals (CIs) were tested by unconditional logistic regression analysis to evaluate the effects of the polymorphisms on PTB risk. P2X7R SNP association analyses were performed using SPSS 17.0 statistical packages and Microsoft Excel, SNP statistics software, Haploview software package (version 4.2), and SHEsis software platform. The results show that the "C" allele of rs656612 in the P2X7R gene was associated with an increased PTB risk by the additive model (OR = 1.307, 95% CI = 1.088-1.570, P = 0.004) and dominant model (rs656612, OR = 1.490, 95% CI = 1.153-1.926, P = 0.002). The "A" allele of rs208290 showed an increased PTB risk by the additive model (OR = 1.418, 95% CI = 1.179-1.706, P < 0.001) and dominant model (OR = 1.680, 95% CI = 1.297-2.177, P < 0.001), whereas the "A" allele of rs7958311 showed an increased risk by the additive model (rs7958311, OR = 1.260, 95% CI = 1.055-1.505, P = 0.011) and recessive model (OR = 1.609, 95% CI = 1.200-2.158, P = 0.001). After Bonferroni correction, rs208290 was found to be associated with PTB in the allele, dominant, and genotype models. In conclusion, our study revealed a significant association between three P2X7R gene polymorphisms (rs656612, rs208290, and rs7958311) and PTB in a Tibetan Chinese population.

SP110 and PMP22 polymorphisms are associated with tuberculosis risk in a Chinese-Tibetan population.

Susceptibility to tuberculosis (TB) is partially dependent on host genetic variability. SP110 and PMP22 are candidate genes identified in this study as associated with human susceptibility to TB. Here we performed an association analysis in a case-control study of a Tibetan population (217 cases and 383 controls). Using bioinformatics methods, we identified two SNPs in SP110 that may decrease susceptibility to TB (rs4327230, p<0.001, OR: 0.37, 95%CI: 0.25-0.55; rs2114591, p<0.001, OR: 0.59, 95%CI: 0.45-0.78), whereas one SNP in PMP22 appeared to increase TB risk (rs13422, p=0.003, OR: 1.45, 95%CI: 1.14-1.84). SNPs rs4327230 and rs2114591 remained significant after Bonferroni correction (p<0.00178). We found that the "GC" haplotype in SP110 was protective against TB, with a 64% reduction in disease risk. "CA" and "CG" in PMP22 were also associated with a protective effect. Our study indicates there is an association between specific gene polymorphisms and TB risk in a Tibetan population, and may help to identify those TB-affected individuals most susceptible to disease.

Protective effects of extracts from Pomegranate peels and seeds on liver fibrosis induced by carbon tetrachloride in rats.

BACKGROUND: Liver fibrosis is a feature in the majority of chronic liver diseases and oxidative stress is considered to be its main pathogenic mechanism. Antioxidants including vitamin E, are effective in preventing liver fibrogenesis. Several plant-drived antioxidants, such as silymarin, baicalin, beicalein, quercetin, apigenin, were shown to interfere with liver fibrogenesis. The antioxidans above are polyphenols, flavonoids or structurally related compounds which are the main chemical components of Pomegranate peels and seeds, and the antioxidant activity of Pomegranate peels and seeds have been verified. Here we investigated whether the extracts of pomegranate peels (EPP) and seeds (EPS) have preventive efficacy on liver fibrosis induced by carbon tetrachloride (CCl4) in rats and explored its possible mechanisms. METHODS: The animal model was established by injection with 50 % CCl4 subcutaneously in male wistar rats twice a week for four weeks. Meanwhile, EPP and EPS were administered orally every day for 4 weeks, respectively. The protective effects of EPP and EPS on biochemical metabolic parameters, liver function, oxidative markers, activities of antioxidant enzymes and liver fibrosis were determined in CCl4-induced liver toxicity in rats. RESULTS: Compared with the sham group, the liver function was worse in CCl4 group, manifested as increased levels of serum alanine aminotransferase, aspartate aminotransferase and total bilirubin. EPP and EPS treatment significantly ameliorated these effects of CCl4. EPP and EPS attenuated CCl4-induced increase in the levels of TGF-ß1, hydroxyproline, hyaluronic acid laminin and procollagen type III. They also restored the decreased superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and inhibited the formation of lipid peroxidized products in rats treated with CCl4. CONCLUSION: The EPP and EPS have protective effects against liver fibrosis induced by CCl4, and its mechanisms might be associated with their antioxidant activity, the ability of decreasing the level of TGF-ß1 and inhibition of collagen synthesis.