New Insights into the Roles of Nogo-A in CNS Biology and Diseases.

Nogos have become a hot topic for its well-known number Nogo-A's big role in clinical matters. It has been recognized that the expression of Nogo-A and the receptor NgR1 inhibit the neuron's growth after CNS injuries or the onset of the MS. The piling evidence supports the notion that the Nogo-A is also involved in the synaptic plasticity, which was shown to negatively regulate the strength of synaptic transmission. The occurrence of significant schizophrenia-like behavioral phenotypes in Nogo-A KO rats also added strong proof to this conclusion. This review mainly focuses on the structure of Nogo-A and its corresponding receptor-NgR1, its intra- and extra-cellular signaling, together with its major physiological functions such as regulation of migration and distribution and its related diseases like stroke, AD, ALS and so on.

Interconnections between urolithiasis and oral health: a cross-sectional and bidirectional Mendelian randomization study.

Introduction: Urolithiasis is one of the most common diseases for urologists and it is a heavy burden for stone formers and society. The theory of the oral-genitourinary axis casts novel light on the pathological process of genitourinary system diseases. Hence, we performed this study to characterize the crosstalk between oral health conditions and urolithiasis to provide evidence for prevention measures and mechanisms of stone formation. Materials and methods: This population-based cross-sectional study included 86,548 Chinese individuals who had undergone a comprehensive examination in 2017. Urolithiasis was diagnosed depending on the results of ultrasonographic imaging. Logistic models were utilized to characterize the association between oral health conditions and urolithiasis. We further applied bidirectional Mendelian randomization to explore the causality between oral health conditions and urolithiasis. Results: We observed that presenting caries indicated a negative correlation with the risk for urolithiasis while presenting gingivitis [OR (95% CI), 2.021 (1.866-2.187)] and impacted tooth [OR (95% CI), 1.312 (1.219-1.411)] shown to be positively associated with urolithiasis. Furthermore, we discovered that genetically predicted gingivitis was associated with a higher risk of urolithiasis [OR (95% CI), 1.174 (1.009-1.366)] and causality from urolithiasis to impacted teeth [OR(95% CI), 1.207 (1.027-1.418)] through bidirectional Mendelian randomization. Conclusion: The results cast new light on the risk factor and pathogenesis of kidney stone formation and could provide novel evidence for the oral-genitourinary axis and the systematic inflammatory network. Our findings could also offer suggestions for tailored clinical prevention strategies against stone diseases.

Enhanced hydrogen evolution activity of CsPbBr3 nanocrystals achieved by dimensionality change.

Dimensionality plays a vital role at the nanoscale in tuning the electronical and photophysical properties and surface features of perovskite nanocrystals. Here, 3D and 1D all-inorganic CsPbBr3 nanocrystals were chosen as model materials to systemically reveal the dimensionality-dependent effect in photocatalytic H2 evolution. In terms of facilitating photoinduced electron-hole pair separation and charge transfer, as well as inducing proton reduction potential with the presence of fewer Br vacancies, 1D CsPbBr3 nanorods gave about a 5-fold improvement for solar H2 evolution.

Establishment of a novel indicator of pyroptosis regulated gene transcription level and its application in pan-cancer.

Pyroptosis is a type of programmed cell death and plays a dual role in distinct cancers. It is elusive to evaluate the activation level of pyroptosis and to appraise the involvement of pyroptosis in the occurrence and development of diverse tumors. Accordingly, we herein established an indicator to evaluate pyroptosis related gene transcription levels based on the expression level of genes involved in pyroptosis and tried to elaborated on the association between pyroptosis and tumors across diverse tumor types. We found that pyroptosis related gene transcription levels could predict the prognosis of patients, which could act as either a favorable or a dreadful factor in diverse cancers. According to signaling pathway analyses we observed that pyroptosis played a significant role in immune regulation and tumorigenesis and had strong links with other forms of cell death. We also performed analysis on the crosstalk between pyroptosis and immune status and further investigated the predictive potential of pyroptosis level for the efficacy of immunotherapy. Lastly, we manifested that pyroptosis status could serve as a biomarker to the efficacy of chemotherapy across various cancers. In summary, this study established a quantitative indicator to evaluate pyroptosis related gene transcription levels, systematically explored the role of pyroptosis in pan-cancer. These results could provide potential research directions targeting pyroptosis, and highlighted that pyroptosis may be used to develop a novel strategy for the treatment of cancer.

Identification and validation of a twelve immune infiltration-related lncRNA prognostic signature for bladder cancer.

The prognosis of bladder cancer patients is strongly related to both the immune-infiltrating cells and the expression of lncRNAs. In this study, we analyzed the infiltration of immune cells in 403 bladder cancer samples obtained from TCGA by applying the ssGSEA to these samples, then dividing them into high/low immune cell infiltration groups. Based on these groupings, we found 404 differentially expressed immune infiltration-related lncRNAs, which were successively analyzed by univariate Cox regression, then Least Absolute Shrinkage and Selection Operator (LASSO), and finally stepwise multiple Cox regression. Then 12 differentially expressed immune infiltration-related lncRNAs were identified and used to construct a prognostic signature for bladder cancer. Subsequently, Kaplan-Meier analysis, univariate Cox regression, multivariate Cox regression, and multivariate time-dependent ROC analyses (for 1, 3, 5 years) all revealed that this signature performed well in predicting overall survival and served as an independent prognostic factor for patients with bladder cancer. Finally, both TIMER and CIBESORT showed that this 12-lncRNA prognostic signature for bladder cancer was associated with the infiltration of immune cell subtypes. Besides, nomogram considered risk score and clinical characteristics was assembled and showed great performance. More importantly, we found our signature could well distinguish the drug response of patients with bladder cancer. High risk patients showed a better response to cisplatin, doxorubicin, and anti- CTLA4 immunotherapy, low risk patients showed a better response to methotrexate and anti-PD1 immunotherapy compared with each other.

Sex disparities and the risk of urolithiasis: a large cross-sectional study.

BACKGROUND: Urolithiasis is one of the most common diseases in urology, with a lifetime prevalence of 14% and is more prevalent in males compared to females. We designed to explore sex disparities in the Chinese population to provide evidence for prevention measures and mechanisms of stone formation. MATERIALS AND METHODS: A total of 98232 Chinese individuals who had undergone a comprehensive examination in 2017 were included. Fully adjusted odds ratios for kidney stones were measured using restricted cubic splines. Multiple imputations was applied for missing values. Propensity score matching was utilised for sensitivity analysis. RESULTS: Among the 98232 included participants, 42762 participants (43.53%) were females and 55470 participants (56.47%) were males. Patients' factors might cast an influence on the development of kidney stone disease distinctly between the two genders. A risk factor for one gender might have no effect on the other gender. The risk for urolithiasis in females continuously rises as ageing, while for males the risk presents a trend to ascend until the age of around 53 and then descend. CONCLUSIONS: Patients' factors might influence the development of kidney stones distinctly between the two genders. As age grew, the risk to develop kidney stones in females continuously ascended, while the risk in males presented a trend to ascend and then descend, which was presumably related to the weakening of the androgen signals.Key messagesWe found that patients' factors might cast an influence on the development of kidney stone disease distinctly between the two sexes.The association between age and urolithiasis presents distinct trends in the two sexesThe results will provide evidence to explore the mechanisms underlying such differences can cast light on potential therapeutic targets and promote the development of tailored therapy strategies in prospect.

A Novel Nomogram for Predicting Post-Operative Sepsis for Patients With Solitary, Unilateral and Proximal Ureteral Stones After Treatment Using Percutaneous Nephrolithotomy or Flexible Ureteroscopy.

Background: The postoperative sepsis is a latent fatal complication for both flexible ureteroscopy (fURS) and percutaneous nephrolithotomy (PNL). An effective predictive model constructed by readily available clinical markers is urgently needed to reduce postoperative adverse events caused by infection. This study aims to determine the pre-operative predictors of sepsis in patients with unilateral, solitary, and proximal ureteral stones after fURS and PNL. Methods: We retrospectively enrolled 910 patients with solitary proximal ureteral stone with stone size 10-20 mm who underwent fURS or PNL from Tongji Hospital's database, including 412 fURS cases and 498 PNL cases. We used the least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression analysis to identify the risk factors for sepsis. Finally, a nomogram was assembled utilizing these risk factors. Results: In this study, 49 patients (5.4%) developed sepsis after fURS or PNL surgery. Lasso regression showed postoperative sepsis was associated with gender (female), pre-operative fever, serum albumin (<35 g/L), positive urine culture, serum WBC (≥10,000 cells/ml), serum neutrophil, positive urine nitrite and operation type (fURS). The multivariate logistic analysis indicated that positive urine culture (odds ratio [OR] = 5.9092, 95% CI [2.6425-13.2140], p < 0.0001) and fURS (OR = 1.9348, 95% CI [1.0219-3.6631], p = 0.0427) were independent risk factors of sepsis and albumin ≥ 35g/L (OR = 0.4321, 95% CI [0.2054-0.9089], p = 0.0270) was independent protective factor of sepsis. A nomogram was constructed and exhibited favorable discrimination (area under receiver operating characteristic curve was 0.78), calibration [Hosmer-Lemeshow (HL) test p = 0.904], and net benefits displayed by decision curve analysis (DCA). Conclusions: Patients who underwent fURS compared to PNL or have certain pre-operative characteristics, such as albumin <35 g/L and positive urine culture, are more likely to develop postoperative sepsis. Cautious preoperative evaluation and appropriate operation type are crucial to reducing serious infectious events after surgery, especially for patients with solitary, unilateral, and proximal ureteral stones sized 10-20 mm.

Identification of a Twelve Epithelial-Mesenchymal Transition-Related lncRNA Prognostic Signature in Kidney Clear Cell Carcinoma.

Background: Epithelial-mesenchymal transition (EMT) plays a vital role in tumor metastasis and drug resistance. It has been reported that EMT is regulated by several long noncoding RNAs (lncRNAs). We aimed to identify EMT-related lncRNAs and develop an EMT-related lncRNA prognostic signature in kidney renal clear cell carcinoma (KIRC). Materials and Methods: In total, 530 ccRCC patients with 611 transcriptome profiles were included in this study. We first identified differentially expressed EMT-related lncRNAs. Then, all the samples with transcriptional data and clinical survival information were randomly split into training/test sets at a ratio of 1 : 1. Accordingly, we further developed a twelve differentially expressed EMT-related lncRNA prognostic signature in the training set. Following this, risk analysis, survival analysis, subgroup analysis, and the construction of the ROC curves were applied to verify the efficacy of the signature in the training set, test set, and all patients. Besides, we further investigated the differential immune infiltration, immune checkpoint expression, and immune-related functions between high-risk patients. Finally, we explored the different drug responses to targeted therapy (sunitinib and sorafenib) and immunotherapy (anti-PD1 and anti-CTLA4). Results: A twelve differentially expressed EMT-related lncRNA prognostic signature performed superior in predicting the overall survival of KIRC patients. High-risk patients were observed with a significantly higher immune checkpoint expression and showed better responses to the targeted therapy and immunotherapy. Conclusions: Our study demonstrates that the twelve differentially expressed EMT-related lncRNA prognostic signature could act as an efficient prognostic indicator for KIRC, which also contributes to the decision-making of the further treatment.

Sex Disparities in the Association of Serum Uric Acid With Kidney Stone: A Cross-Sectional Study in China.

BACKGROUND AND AIMS: Urolithiasis is characterized by high rates of prevalence and recurrence. Hyperuricemia is related to various diseases. We hope to determine the association between serum uric acid (UA) level and kidney stone (KS). METHODS: In this population-based cross-sectional study, a total of 82,017 Chinese individuals who underwent a comprehensive examination in 2017 were included. The KS was diagnosed based on ultrasonography examination outcomes. Fully adjusted odds ratio (OR) for KS, and mean difference between the two groups were applied to determine the association of UA level with KS. RESULTS: Among the 82,017 participants included in this study (aged 18~99 years), 9,435 participants (11.5%) are diagnosed with KS. A proportion of 56.3% of individuals is male. The mean UA level of overall participants is 341.77 µmol/L. The participants with KS report higher UA level than the participants without KS [mean UA level 369.91 vs. 338.11 µmol/L; mean difference (MD), 31.96 (95% CI, 29.61~34.28) µmol/L]. In men, the OR for KS significantly increases from 330 µmol/L UA level. Every 50 µmol/L elevation of UA level increases the risk of KS formation by about 10.7% above the UA level of 330 µmol/L in men. The subgroup analysis for male is consistent with the overall result except for the participants presenting underweight [adjusted OR, 1.035 (0.875~1.217); MD, -5.57 (-16.45~11.37)], low cholesterol [adjusted OR, 1.088 (0.938~1.261); MD, 8.18 (-7.93~24.68)] or high estimated glomerular filtration rate (eGFR) [adjusted OR, 1.044 (0.983~1.108); MD, 5.61 (-1.84~13.36)]. However, no significant association is observed in women between UA and KS either in all female participants or in female subgroups. CONCLUSION: Among Chinese adults, UA level is associated with KS in a dose-response manner in men but not in women. However, the association becomes considerably weak in male participants with malnutrition status.

Construction of a Novel Immune-Related lncRNA Pair Signature with Prognostic Significance for Kidney Clear Cell Renal Cell Carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is one of the most common aggressive malignant tumors in the urinary system, among which the clear cell renal cell carcinoma (ccRCC) is the most common subtype. The immune-related long noncoding ribonucleic acids (irlncRNAs) which are abundant in immune cells and immune microenvironment (IME) have potential significance in evaluating the prognosis and effects of immunotherapy. The signature based on irlncRNA pairs and independent of the exact expression level seems to have a latent predictive significance for the prognosis of patients with malignant tumors but has not been applied in ccRCC yet. METHOD: In this article, we retrieved The Cancer Genome Atlas (TCGA) database for the transcriptome profiling data of the ccRCC and performed coexpression analysis between known immune-related genes (ir-genes) and lncRNAs to find differently expressed irlncRNA (DEirlncRNA). Then, we adopted a single-factor test and a modified LASSO regression analysis to screen out ideal DEirlncRNAs and constructed a Cox proportional hazard model. We have sifted 28 DEirlncRNA pairs, 12 of which were included in this model. Next, we compared the area under the curve (AUC), found the cutoff point by using the Akaike information criterion (AIC) value, and distinguished the patients with ccRCC into a high-risk group and a low-risk group using this value. Finally, we tested this model by investigating the relationship between risk score and survival, clinical pathological characteristics, cells in tumor immune microenvironment, chemotherapy, and targeted checkpoint biomarkers. RESULTS: A novel immune-related lncRNA pair signature consisting of 12 DEirlncRNA pairs was successfully constructed and tightly associated with overall survival, clinical pathological characteristics, cells in tumor immune microenvironment, and reactiveness to immunotherapy and chemotherapy in patients with ccRCC. Besides, the efficacy of this signature was verified in some commonly used clinicopathological subgroups and could serve as an independent prognostic factor in patients with ccRCC. CONCLUSIONS: This signature was proven to have a potential predictive significance for the prognosis of patients with ccRCC and the efficacy of immunotherapy.

Efficacy and toxicity in scheduled intravesical gemcitabine versus Bacille Calmette-Guérin for Ta and T1 bladder cancer: a systematic review and meta-analysis.

BACKGROUND: We conducted a meta-analysis to compare the efficacy and toxicity of scheduled intravesical gemcitabine (GEM) and Bacille Calmette-Guérin (BCG) for Ta and T1 non-muscle invasive bladder cancer (NMIBC). METHODS: The database search was performed in Ovid Medline, Embase, Web of Science, Cochrane Library from the commencement of the database to July 7, 2020. Trials using immediate instillation were excluded and we present the included studies in accordance with the PRISMA 2020 reporting checklist. The data extracted was analyzed using Stata 11.0 software. RESULTS: Six studies of 466 patients comparing GEM and BCG were finally included. No significant difference was detected between GEM and BCG group in recurrence free survival [hazard ratio (HR) =0.80, 95% confidence interval (95% CI), 0.46-1.37, P=0.410], progression free survival (HR =0.82, 95% CI, 0.38-1.77, P=0.621), and total adverse events [odds ratio (OR) =0.70, 95% CI, 0.38-1.29, P=0.253). However, patients receiving GEM treatment are less likely to develop urinary adverse events, such as dysuria (OR =0.50, 95% CI, 0.29-0.87) and hematuria (OR =0.40, 95% CI, 0.18-0.91). We performed subgroup analysis and found that the effects of GEM and BCG were similar even on patients with high recurrence risk tumor. Sensitivity analysis showed the robustness of the results. DISCUSSION: Scheduled intravesical GEM instillation has a similar effect with BCG instillation in preventing NMIBC recurrence and progression, but GEM therapy causes a lower incidence of dysuria and hematuria than BCG. GEM may be an alternative therapy for BCG. However, the results should be treated with caution due to the low to moderate quality of the included studies.

Toll-Like Receptor 4 as a Favorable Prognostic Marker in Bladder Cancer: A Multi-Omics Analysis.

BACKGROUND: The toll-like receptor 4 (TLR4) agonist, Bacille Calmette-Guérin, has exhibited gratifying effects in treating bladder cancer. The study aims to explore the expression pattern, prognostic value, and potential mechanism of TLR4 in bladder cancer. METHODS: The transcriptome file from the GSE13507 dataset in the Gene Expression Omnibus database and the promoter methylation file from the bladder cancer dataset in The Cancer Genome Atlas database were downloaded for analysis. The prognostic value of the TLRs was assessed by univariate Cox regression. Immunohistochemistry was applied to verify the expression of TLR4 in bladder cancer. The drug response is estimated through the R package "pRRophetic." The CIBERSORT algorithm was carried out to estimate the infiltrating immune cells of samples. Gene Set Enrichment Analysis (GSEA) was performed to identify the pathways involved under varied TLR4 expression levels. RESULTS: TLR4 is decreased in tumor tissues compared with surrounding tumor tissues or normal tissue, which is also positively correlated to the overall survival rate (hazard ratio [HR] = 0.38) and cancer-specific survival rate (HR = 0.15) of patients with bladder cancer. Low expression of TLR4 is observed in tumors with malignant performance (high pathological grade, higher tumor stage, and progression). Patients with low TLR4 levels are more sensitive to gemcitabine rather than cisplatin. The promoter methylation level of TLR4 is positively associated with TLR4 expression (P < 0.001). The cg14629571 methylation site largely contributes to the overall methylation level. The CIBERSORT analysis shows that high TLR4 expression is associated with lower levels of plasma cells, M0 macrophages, and M1 macrophages. The GSEA results indicate that the TGF-ß pathway and apoptosis are activated in high TLR4 bladder cancer, while G2M checkpoint and E2F targets pathways are enriched in low TLR4 bladder cancer. CONCLUSION: This research discusses the abnormal expression and prognostic value of TLR4 in bladder cancer. The TLR4 expression can effectively predict oncological outcomes and drug sensitivity of bladder cancer patients. TLR4 is also associated with infiltrating immune cell variation and cancer pathway dysregulation. The results provide a novel prognostic marker and potential drug targets for bladder cancer.

Percutaneous Nephrolithotomy Can Reduce the Incidence of Sepsis Compared with Flexible Ureteroscopy in Treating Solitary Proximal Ureteral Stone Patients with Positive Urine Culture.

BACKGROUND: Sepsis is a potentially lethal complication for both flexible ureteroscopy (fURS) and percutaneous nephrolithotomy (PCNL). This study is aimed at comparing the sepsis rate after fURS and PCNL and the risk factors for sepsis in patients with solitary proximal ureteral stone. METHODS: We reviewed the data of patients with calculi between 10 mm to 20 mm who underwent fURS or PCNL surgery from Tongji Hospital's database. A total of 910 patients were eligible with 412 fURS cases and 498 PCNL cases. We used univariate analysis and multivariate logistic regression analysis to identify the risk factors for sepsis. Subgroup analysis was performed using logistic regression analysis. RESULTS: In the cohort, 27 (6.6%) and 19 (3.8%) patients developed sepsis after fURS and PCNL, respectively. Multivariate analysis shows that the risk factors for sepsis are fURS (OR = 3.160, P = 0.004), serum WBC ≥ 10,000 cells/µL (OR = 3.490, P = 0.008), albumin - globulin ratio < 1.2 (OR = 2.192, P = 0.029), positive urine culture (OR = 6.145, P < 0.001), and prolonged operation time (OR = 1.010, P = 0.046). Subgroup analysis was conducted using potential risk factors: stone size, serum WBC, urine culture, and albumin-globulin ratio (AGR). In subgroup of positive urine culture, patients were more likely to develop sepsis after fURS than PCNL. CONCLUSIONS: PCNL may be a better choice than fURS to reduce postoperative sepsis, especially for patients with positive urine culture.

Development and Validation of a Nine-Redox-Related Long Noncoding RNA Signature in Renal Clear Cell Carcinoma.

BACKGROUND: Redox plays an essential role in the pathogeneses and progression of tumors, which could be regulated by long noncoding RNA (lncRNA). We aimed to develop and verify a novel redox-related lncRNA-based prognostic signature for clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: A total of 530 ccRCC patients from The Cancer Genome Atlas (TCGA) were included in this study. All the samples were randomly split into training and test group at a 1 : 1 ratio. Then, we screened differentially expressed redox-related lncRNAs and constructed a novel prognostic signature from the training group using the least absolute shrinkage and selection operation (LASSO) and COX regression. Next, to verify the accuracy of the signature, we conducted risk and survival analysis, as well as the construction of ROC curve, nomogram, and calibration curves in the training group, test group, and all samples. Finally, the redox gene-redox-related lncRNA interaction network was constructed, and gene set enrichment analysis (GSEA) was performed to investigate the status of redox-related functions between high/low-risk groups. RESULTS: A nine-redox-related lncRNA signature consisted of AC025580.3, COLCA1, AC027601.2, DLEU2, AC004918.3, AP006621.2, AL031670.1, SPINT1-AS1, and LAMA5-AS1 was significantly associated with overall survival in ccRCC patients. The signature proved efficient, and thus, a nomogram was successfully assembled. In addition, the GSEA results demonstrated that two major redox-related functions were enhanced in the high-risk group ccRCC patients. CONCLUSIONS: Our findings robustly demonstrate that the nine-redox-related lncRNA signature could serve as an efficient prognostic indicator for ccRCC.

Efficacy of intravesical therapies on the prevention of recurrence and progression of non-muscle-invasive bladder cancer: A systematic review and network meta-analysis.

Intravesical instillation therapy is the mainstay of prophylaxis of tumor recurrence and progression in non-muscle-invasive bladder cancer. However, there is no study evaluating the superiority of monotherapy. The aim of this study is to compare the efficacy of preventing recurrence and progression of intravesical monotherapies via network meta-analysis (NMA) of randomized controlled trials. Database searches were conducted on Embase, Ovid Medline, Web of Science, ScienceDirect, Cochrane Library, and ClinicalTrials.com from the time of establishment to February 6, 2020. The monotherapies included Bacille Calmette-Guérin (BCG), mitomycin C (MMC), interferon (IFN), adriamycin, epirubicin, gemcitabine (GEM), and thiotepa (THP). A Bayesian consistency network model was generated under a random-effects model. The superiority of therapy was identified based on the surface under the cumulative ranking curve (SUCRA). Fifty-seven studies with 12462 patients are included. NMA shows that GEM (SUCRA = 0.92), BCG (SUCRA = 0.82), and IFN (SUCRA = 0.78) are the top three effective drugs to reduce recurrence. GEM (SUCRA = 0.87) is the most effective therapy to prevent progress, followed by BCG, MMC, THP, and IFN with similar efficacy. Subgroup analysis of pairwise meta-analysis and NMA was performed on publication year, trial initiation year, study origin, center involvement, sample size, drug schedule, tumor characteristics, and trial quality to address confounding factors, which suggests the robustness of the results with stable effect sizes. Network meta-regression also indicates consistent rank by analyzing year, sample size, and quality. Compared with BCG, GEM is also a promising therapy with favorable efficacy to reduce tumor recurrence and progression. IFN and MMC could be alternative therapies for BCG with slightly inferior efficacy in recurrence prevention and similar efficacy in progression prevention. However, the results of this study should be treated with caution since most of the included studies are of moderate to high risk of bias.

Network pharmacology and molecular docking analyses on Lianhua Qingwen capsule indicate Akt1 is a potential target to treat and prevent COVID-19.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) is rapidly spreading worldwide. Lianhua Qingwen capsule (LQC) has shown therapeutic effects in patients with COVID-19. This study is aimed to discover its molecular mechanism and provide potential drug targets. MATERIALS AND METHODS: An LQC target and COVID-19-related gene set was established using the Traditional Chinese Medicine Systems Pharmacology database and seven disease-gene databases. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein-protein interaction (PPI) network were performed to discover the potential mechanism. Molecular docking was performed to visualize the patterns of interactions between the effective molecule and targeted protein. RESULTS: A gene set of 65 genes was generated. We then constructed a compound-target network that contained 234 nodes of active compounds and 916 edges of compound-target pairs. The GO and KEGG indicated that LQC can act by regulating immune response, apoptosis and virus infection. PPI network and subnetworks identified nine hub genes. The molecular docking was conducted on the most significant gene Akt1, which is involved in lung injury, lung fibrogenesis and virus infection. Six active compounds of LQC can enter the active pocket of Akt1, namely beta-carotene, kaempferol, luteolin, naringenin, quercetin and wogonin, thereby exerting potential therapeutic effects in COVID-19. CONCLUSIONS: The network pharmacological strategy integrates molecular docking to unravel the molecular mechanism of LQC. Akt1 is a promising drug target to reduce tissue damage and help eliminate virus infection.

Activin Receptor-Like Kinase 1 Combined With VEGF-A Affects Migration and Proliferation of Endothelial Cells From Sporadic Human Cerebral AVMs.

Heterozygous loss of activin receptor-like kinase 1 (Alk1) can lead to hereditary hemorrhagic telangiectasia (HHT), which is a kind of vascular disease characterized by direct connections between arteries and veins with the lacking of capillaries, and develops into arteriovenous malformations (AVMs) in later stage. However, the changes of Alk1 in human sporadic cerebral AVMs (cAVMs) remain unknown. In the present study, we used endothelial cells (ECs) derived from human cAVMs (cAVM-ECs) specimens, to explore the characteristics of cAVM-ECs and the relationship between Alk1 and human sporadic cAVMs. Our data showed that there were obvious morphological changes in cAVM-ECs, and they could trans-differentiate into mesenchyme-like cells easily in a short period. In addition, the abilities of migration of cAVM-ECs were poorer than that in human aortic endothelial cells (HA-ECs). The abilities of proliferation of cAVM-ECs in patients with different ages were lower than HA-ECs. Immunofluorescent staining and Western blot showed that the levels of Alk1 mRNA and protein in the HA-ECs were both higher than that in cAVM-ECs. In addition, the levels of Alk1 mRNA had no significant differences between different ages in cAVM-ECs groups. The levels of VEGF-A mRNA in the cAVM were higher than HA-ECs. Besides, levels of VEGF-A mRNA expression were lower in older cAVM patients. Therefore, we conclude that Alk1 might induce the formation of sporadic human cAVMs through affecting migration and proliferation of endothelial cells combined with VEGF-A.