Investigation into molecular mechanisms and high-frequency core TCM for pulmonary fibrosis secondary to COVID-19 based on network pharmacology and data mining.

BACKGROUND: The complication, pulmonary fibrosis (PF) secondary to COVID-19, may have a second wave of late mortality, given the huge number of individuals infected by COVID-19. However, the molecular mechanisms of PF secondary to COVID-19 haven't been fully elucidated, making the identification of novel strategies for targeted therapy challenging. This study aimed to systematically identify the molecular mechanisms and high-frequency core traditional Chinese medicine (TCM) targeting PF secondary to COVID-19 through network pharmacology and data mining. METHODS: The molecular mechanisms of PF secondary to COVID-19 were identified by mapping the COVID-19 differentially expressed gene and known targets associated with PF, protein-protein interactions network analysis, and enrichment pathway analysis; then the high-frequency core TCM targeting PF secondary to COVID-19 were identified by data mining and "Key targets related to PF secondary to COVID-19 - Ingredients" and "Key ingredients-key herbs" network analysis; and last we validated the interaction between the key ingredients and key targets by molecular docking. RESULTS: The molecular mechanisms of PF secondary to COVID-19 were mainly related to tumor necrosis factor (TNF) signaling pathway, cytokine-cytokine receptor interaction pathway, and NF-κB signaling pathway. Among these, cytokines interleukin 6 (IL-6), TNF, and IL-1ß were identified as the key targets associated with PF secondary to COVID-19. The high-frequency core TCM targeting these key targets were identified, including ingredients of quercetin, epigallocatechin-3-gallate, emodin, triptolide, resveratrol, and herb of Polygonum cuspidatum. Finally, our results were validated by quercetin and resveratrol both well docked to IL-6, TNF, and IL-1ß protein, with the estimated docking energy <0 kcal/mol. CONCLUSIONS: This study identified the cytokines-related molecular mechanisms of PF secondary to COVID-19, and the high-frequency core TCM against PF by targeting IL-6, TNF, and IL-1ß. Which provides new ideas for the discovery of small molecular compounds with potential therapeutic effects on PF secondary to COVID-19.

Compound XiongShao Capsule ameliorates streptozotocin-induced diabetic peripheral neuropathy in rats via inhibiting apoptosis, oxidative - nitrosative stress and advanced glycation end products.

ETHNOPHARMACOLOGICAL RELEVANCE: Compound XiongShao Capsule (CXSC), a traditional herb formula, has been approved for using to treat diabetic peripheral neuropathy (DPN) by the Shanghai Food and Drug Administration, with significant efficacy in clinic. AIM OF THE STUDY: This study aimed to investigate the multidimensional pharmacological mechanisms and synergism of CXSC against DPN in rats. METHODS: The quality analysis of CXSC was performed by high-performance liquid chromatography (HPLC) and thin-layer chromatography. Rats with DPNinduced by streptozotocin/high-fat diet for 4 weeks were treated with CXSC at three doses (1.2 g/kg, 0.36 g/kg, and 0.12 g/kg), or epalrestat (15 mg/kg) daily for 8 weeks continuously. During the treatment period, body weight, serum glucose levels, and nerve function, including nerve conduction velocity (NCV), and mechanical and thermal hyperalgesia were tested and assessed every 4 weeks. In the 13th week, the histopathological examination in the sciatic nerve was performed using a transmission electron microscope. The expression of apoptosis-related proteins of BAX, BCL2, and caspase-3 in the sciatic nerve was examined using hematoxylin and eosin staining. The serum levels of advanced glycation end products (AGEs), oxidative-nitrosative stress biomarkers of superoxide dismutase (SOD), and nitric oxide synthase (NOS) were measured using a rat-specific ELISA kit. RESULTS: CXSC had no significant effect on body weight or serum glucose levels (P > 0.05), but it significantly improved mechanical hyperalgesia (F5,36 = 18.24, P < 0.0001), thermal hyperalgesia (F5,36 = 8.45, P < 0.0001), and NCV (motor NCV: F5,36 = 7.644, P < 0.0001, sensory NCV: F5,36 = 12.83, P < 0.0001). Besides, it maintained myelin and axonal structure integrity, downregulated the expression of apoptosis-related proteins in the sciatic nerve tissue, reduced AGEs and NOS levels, and enhanced antioxidant enzyme SOD activities in the serum. CONCLUSION: CXSC exerted neuroprotective effects against rats with DPN through multidimensional pharmacological mechanisms including antiapoptotic activity in the sciatic nerve and downregulation of the level of serum NOS, SOD and AGEs.

Validation of the Key Active Ingredients and Anti-Inflammatory and Analgesic Effects of Shenjin Huoxue Mixture Against Osteoarthritis by Integrating Network Pharmacology Approach and Thin-Layer Chromatography Analysis.

BACKGROUND: Shenjin Huoxue Mixture (SHM), a classic traditional herb mixture has shown significant clinical efficacy against osteoarthritis (OA). Our previous experimental study has confirmed its anti-inflammatory and analgesic effect on acute soft tissue injury in rats, with the compound of glycyrrhizinate in SHM identified and the content of paeoniflorin in SHM determined by high-performance liquid chromatography (HPLC). However, the components and its pharmacological mechanisms of SHM against OA have not been systematically elucidated yet. Thus this study aimed to predict the key active ingredients and potential pharmacological mechanisms of SHM in the treatment of OA by network pharmacology approach and thin-layer chromatography (TLC) validation. METHODS: The active ingredients of SHM and their targets, as well as OA-related targets, were identified from databases. The key active ingredients were defined and ranked by the number of articles retrieved in PubMed using the keyword "(the active ingredients [Title/Abstract]) AND Osteoarthritis[Title/Abstract] ", and validated partially by TLC. The pharmacological mechanisms of SHM against OA were displayed by GO term and Reactome pathway enrichment analysis with Discovery Studio 3.0 software docking to testing the reliability. RESULTS: Finally, 16 key active ingredients were identified and ranked, including quercetin validated through TLC. Inflammatory response, IL-6 signaling pathway and toll-like receptor (TLR) cascades pathway were predicted as the main pharmacological mechanisms of SHM against OA. Especially, 12 out of 16 key active ingredients, including validated quercetin, were well docked to IL-6 proteins. CONCLUSION: Our results confirmed the anti-inflammatory and analgesic effect of SHM against OA through multiple components, multiple targets and multiple pathways, which revealed the theoretical basis of SHM against OA and may provide a new drug option for treating OA.

How do passengers influence drivers' propensities for angry driving? Different effects of supervisors versus friends.

A lot of researchers discussed the influence of passengers on drivers' behaviors without reaching a consistent conclusion. This study aimed to offer some new evidence concerning this issue. The study examined different effects of supervisors and friends as passengers on drivers' propensities for angry driving. In Study 1, drivers were asked to freely imagine a passenger either as their supervisor or friend. Results showed that compared with driving alone, drivers' propensities for angry driving increased when the passenger was a friend but decreased when the passenger was a supervisor. These findings were consistent with the generally accepted social norm. In Study 2, drivers read a description about either an aggressive supervisor or a cautious friend. Results showed that the effects of passengers on drivers' angry driving propensities were correspondingly reversed, indicating that a clearer behavior standard conveyed by a passenger had a stronger effect on drivers. Self-monitoring propensity showed a main effect on drivers' propensities for angry driving in a standard-free situation. And self-monitoring propensity moderated the effect of a passenger's role on angry driving propensities in a standard-set situation. Impression management processes were discussed with respect to these findings.

Association of sterol regulatory element-binding protein-1c gene polymorphism with type 2 diabetes mellitus, insulin resistance and blood lipid levels in Chinese population.

AIMS: The sterol regulatory element-binding protein (SREBP)-1c gene has been identified as a susceptibility gene in metabolic diseases such as type 2 diabetes mellitus (T2DM), obesity, dyslipidemia and insulin resistance. Previous studies suggest that SNP17 (rs2297508, exon18c and G952G) of SREBP-1c gene and a common SREBP-1c SNP6 (rs11868035) are associated with an increased risk of T2DM. The present study aimed to confirm the previously reported association in a Chinese population and to examine the two SREBP-1c SNPs for their associations with insulin resistance and blood lipid. METHODS: We genotyped two SREBP-1c SNPs in a case-control study (n=327) from Chinese, including 156 patients with T2DM and 171 healthy controls, using polymerase chain reaction-denaturing high-performance liquid chromatography (PCR-DHPLC) and tested for association with type 2 diabetes, insulin resistance and blood lipid, respectively. Genotype and allele distributions and haplotype construction were analysed. RESULTS: The genotype and allele distributions of rs2297508 and rs11868035 polymorphisms were significantly different in type 2 diabetic patients compared to controls (P=0.002 and P=0.013; 0.00 and 0.001, respectively). Haplotype analyses showed significant association with diabetes risk and confirmed the results of the single SNP analyses. The plasma levels of LDL-c of the minor allele-C carriers of the two SNPs were both significantly higher than the noncarriers in the control group (P<0.05). Furthermore, insulin resistance index (HOMA-IRI) of the rare homozygotes C/C of rs11868035 was significantly lower than that of T/T in the T2DM group (P<0.05). CONCLUSIONS: These findings indicate that the SREBP-1c SNPs rs2297508 and rs11868035 are associated with a significantly increased risk of T2DM and dyslipidemia in the Chinese population. Moreover, the SNP (rs11868035) is closely related to insulin resistance (IR) in diabetic patients.

[Investigation and application of fluorescence reaction of cerium-L-tryptophan in Triton X-100 microemulsion].

In the present article, the sensitizing effect of Triton X-100 microemulsion media (Triton X-100-M) on the determination of L-tryptophan by fluorescence spectrophotometry was studied, which was based on a strong fluorescence substance produced when L-tryptophan was oxidized by Ce4+ in acid medium. Compared with Triton X-100 micelle (Triton X-100-m), it was found that in the medium of Triton X-100-M the intensity of fluorescence was enhanced by 225 times. Various factors that influence fluorescence determination and interfering ions were examined. The mechanism of sensitizing effect of Triton X-100 microemulsion was also discussed. Under the optimum conditions, the liner range and detection limit are 0.1-1.0 g x mL(-1) and 0.09 microg x mL(-1) (correlation coefficient r = 0.998 4), respectively. The linear equation was F = 342.37+30.45c. The proposed method has been successfully applied to determine food samples.

Long-term effects of simultaneous subconjunctival and subscleral mitomycin C application in repeat trabeculectomy.

PURPOSE: To assess the efficacy and safety of simultaneous mitomycin C application under conjunctival and scleral flaps in patients with repeat trabeculectomy. METHODS: A total of 44 patients (44 eyes) with previous failed filtering surgery were randomized to one of two groups. The both-flaps group comprised 22 patients (22 eyes) with trabeculectomy and intraoperative mitomycin C application under conjunctival and scleral flaps, whereas the subconjunctival group comprised 22 patients (22 eyes) with subconjunctival application of mitomycin C. Particular attention was paid to intraocular pressure, postoperative medications, visual acuity, filtering bleb appearance, and complications. The mean follow-up time was 38.18 +/- 12.48 months. RESULTS: The mean preoperative intraocular pressure decreased from 39.1 +/- 7.3 mm Hg to the postoperative level of 15.6 +/- 4.8 mm Hg in the both-flaps group (P = 0.014), and from 39.4 +/- 8.4 to 18.7 +/- 5.8 mm Hg in the subconjunctival group (P = 0.018). There was a statistically significant difference in intraocular pressure at all follow-up times, except at 1 week and 1 month postoperatively. Kaplan-Meier survival analysis showed there was no significant difference in total success rate (complete plus qualified success) between the two groups (P = 0.622, log-rank test). However, the two survival curves for the complete success subgroups (without additional medications) confirmed that mitomycin C applications under both flaps had a higher success rate than subconjunctival application (P = 0.043, log-rank test). No statistically significant difference in medications was present between the two groups, and no severe complications developed in either group. CONCLUSIONS: Trabeculectomy augmented with mitomycin C application at both sites could produce a greater lowering of intraocular pressure with low incidence of postoperative complications, and could provide an increased chance of long-term success. The procedure is effective and safe in patients with repeat trabeculectomy.