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Overwhelming responses are seen at preclinical and clinical levels to understand and combat coronavirus disease 2019 [COVID-19] pandemic that is caused by severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]. Encouraging successes are achieved in view of diagnostic, therapeutic and preventive measures including vaccines development. In fact, structural information of SARS-CoV-2 and molecular steps that help this virus to target AECs are appreciably studied. Furthermore, the heterogeneous and complex nature of COVID-19 is extensively revealed at molecular, genetic, and epigenetic and microenvironment levels. In spite of these developments in COVID-19 pathogenesis, reasons behind the targeted infection by SARS-CoV-2 to AECs are poorly understood. In this mini-review, we highlight the roles of pH and temperature of airway surface liquid [ASL] as a key determining factor that may contribute towards enhanced targeted infection by SARS-CoV-2 leading to COVID-19.Hepatitis B virus [HBV], the best-described hepadnavirus, distributed all around the world and may lead to chronic and acute liver disease, cirrhosis, and hepatocellular carcinoma. Despite the advancement in treatment against HBV, an error-prone reverse transcriptase which is require for HBV replication as well as host immune pressure lead to constant evolution and emergence of genotypes, sub-genotypes and mutant viruses; so, HBV will be remained as a major healthcare problem around the world. This review article mainly focuses on the HBV mutations which correlated to occult HBV infection, Immune scape, vaccine failure and eventually liver cirrhosis and HCC. Current study indicated that preS/S region mutations are related to vaccine failure, immune escape, occult HBV infection and the occurrence of HCC. Whereas, P region Mutations may lead to drug resistance to NA antivirals. PreC/C region mutations are associated to HBeAg negativity, immune escape, and persistent hepatitis. Moreover, X region Mutations play an important role in HCC development.Diabetic mellitus is a worldwide endocrine and metabolic disorder with insulin insensitivity or deficiency or both whose prevalence could rise up to 592 million by 2035. Consistent hyperglycemia leads to one of the most common comorbidities like Diabetic Peripheral Neuropathy (DPN). DPN is underlined with unpleasant sensory experience such as tingling and burning sensation, hyperalgesia, numbness etc. Globally, 50-60% of the diabetic population is suffering from such symptoms like microvascular complication. Consistent hyperglycemia during DM causes activation/inhibition of various pathways playing important role in homeostasis of neurons and other cells. Disruption of these pathways results into apoptosis and mitochondrial dysfunctions causing neuropathy. Among these pathways, pathways like Polyol pathway and PARP pathway are some of the most intensively studied pathways whereas pathways like Wnt pathway, Mitogen activated protein kinase (MAPK), mTOR pathway are comparatively newly discovered. Understanding of these pathways and their role in pathophysiology of DN underlines a few molecules of immense therapeutic value. The inhibitors or activators of these molecules can be of therapeutic importance in management of DPN. This review hence, focuses on these underlying molecular mechanisms intending to provide therapeutically effective molecular targets for treatment of DPN.

Doxorubicin-induced cardiotoxicity (DIC) has greatly limited the clinical benefits of this frontline drug in oncotherapy. Drug combination with natural compounds (NCs) that possess potency against DIC is considered as a promising intervention strategy. However, the mechanisms of action (MoAs) underlying such drug interactions remain poorly understood. The aim of this study was to systematically pursuit of the molecular mechanisms of NCs against DIC.

First, the gene expression signatures of DIC were characterized from transcriptomics datasets with doxorubicin-treated and untreated cardiomyocytes using differentially expressed gene identification, functional enrichment analysis, and protein-protein interaction network analysis. Secondly, reverse pharmacophore mapping-based network pharmacology was employed to illustrate the MoAs of 82 publicly reported NCs with anti-DIC potency. Cluster analysis based on their enriched pathways was performed to gain systematic insights into the anti-DIC mechanisms of the NCs. Finally, the typical compounds were validated using gene set enrichment analysis (GSEA) of the relevant gene expression profiles from a public gene expression database.

Based on their anti-DIC MoAs, the 82 NCs could be divided into four groups, which corresponded to ten MoA clusters. GSEA and literature evidence on these compounds were provided to validate the MoAs identified through this bioinformatics analysis. The results suggested that NCs exerted potency against DIC through both common and different MoAs.

This strategy integrating different types of bioinformatics approaches is expected to create new insights for elucidating the MoAs of NCs against DIC.

This strategy integrating different types of bioinformatics approaches is expected to create new insights for elucidating the MoAs of NCs against DIC.

As a tumor suppressor or oncogenic gene, abnormal expression of RUNX family transcription factor 3 (RUNX3) has been reported in various cancers. <p> Introduction This study aimed to investigate the role of RUNX3 in melanoma. <p> Methods The expression level of RUNX3 in melanoma tissues was analyzed by immunohistochemistry and the Oncomine database. Based on microarray datasets GSE3189 and GSE7553, differentially expressed genes (DEGs) in melanoma samples were screened, followed by functional enrichment analysis. Gene Set Enrichment Analysis (GSEA) was performed for RUNX3. DEGs that co-expressed with RUNX3 were analyzed, and the transcription factors (TFs) of RUNX3 and its co-expressed genes were predicted. The protein-protein interactions (PPIs) for RUNX3 were analyzed utilizing the GeneMANIA database. MicroRNAs (miRNAs) that could target RUNX3 expression, were predicted. <p> Results RUNX3 expression was significantly up-regulated in melanoma tissues. GSEA showed that RUNX3 expression was positively correlated with melanogenesis and melanoma pathways. Eleven DEGs showed significant co-expression with RUNX3 in melanoma, for example, TLE4 was negatively co-expressed with RUNX3. RUNX3 was identified as a TF that regulated the expression of both itself and its co-expressed genes. PPI analysis showed that 20 protein-encoding genes interacted with RUNX3, among which 9 genes were differentially expressed in melanoma, such as CBFB and SMAD3. These genes were significantly enriched in transcriptional regulation by RUNX3, RUNX3 regulates BCL2L11 (BIM) transcription, regulation of I-kappaB kinase/NF-kappaB signaling, and signaling by NOTCH. A total of 31 miRNAs could target RUNX3, such as miR-326, miR-330-5p, and miR-373-3p. <p> Conclusion RUNX3 expression was up-regulated in melanoma and was implicated in the development of melanoma.

Conclusion RUNX3 expression was up-regulated in melanoma and was implicated in the development of melanoma.

Antimicrobial agents are recommended for disinfection of the cavity following mechanical dental caries removal prior to application of restorative material. There is limited information about stabilized chlorine dioxide (ClO2) as a cavity disinfectant.

The objective of this study is to determine the antimicrobial activity and effect on dentin bond strength of ClO2 compared to chlorhexidine digluconate (CHX), sodium hypochlorite (NaOCl) and ethanolic propolis extract (EPE).

Antimicrobial activities of agents against oral pathogens (Staphylococcus aureus, Enterococcus faecalis, Streptococcus mutans, Lactobacillus acidophilus, Lactobacillus casei, Candida albicans, and Saccharomyces cerevisiae) and analyses of EPE were examined. Seventy-five mandibular third molars were sectioned, prepared and divided into five subgroups (n=15/group). Cavity disinfectants (2% CHX, 2.5% NaOCl, 30% EPE, 0.3% ClO2) were applied to etched dentin prior to adhesive and composite build-up. Shear bond strength (SBS) was evaluated with a universal testing machine at a crosshead speed of 0.5 mm/min. see more The SBS data were analyzed with one-way analysis of variance (ANOVA) and Tukey’s post-hoc test (p <0.05). The failure modes were evaluated with a stereomicroscope.

It was determined that the compared disinfectants were showed different inhibition zone values against oral pathogens. ClO2 exhibited the highest antimicrobial activity, followed by CHX, NaOCI and EPE, respectively. No statistically significant difference was observed in the SBS values between the disinfectant treated groups and control group. The failure modes were predominantly mixed.

The use of 0.3% stabilized ClO2 as a cavity disinfectant agent exhibited high antimicrobial activity against oral pathogens and no adverse effects on SBS to etched dentin.

The use of 0.3% stabilized ClO2 as a cavity disinfectant agent exhibited high antimicrobial activity against oral pathogens and no adverse effects on SBS to etched dentin.

To investigate the effect of Polyphyllin I (PPI) on HBV-related liver cancer through network pharmacology and in vitro experiments, and to explore its mechanism of action.

Use bioinformatics software to predict the active ingredient target of PPI and the disease target of liver cancer, and perform active ingredient-disease target analysis. The results of network pharmacology through molecular docking and in vitro experiments can be further verified. The HepG2 receptor cells (HepG2. 2. 15) were transfected with HBV plasmid for observation, with the human liver cancer HepG2 being used as the control.

Bioinformatics analysis found that PPI had totally 161 protein targets, and the predicted target and liver cancer targets were combined to obtain 13 intersection targets. The results of molecular docking demonstrated that PPI had good affinity with STAT3, PTP1B, IL2, and BCL2L1. The results of the in vitro experiments indicated that the PPI inhibited cell proliferation and metastasis in a concentration-dependent manner (P<0.01). Compared with the vehicle group, the PPI group of 1.5, 3, and 6 μmol/L can promote the apoptosis of liver cancer to different degrees (P<0.01).

The present study revealed the mechanism of PPI against liver cancer through network pharmacology and in vitro experiments. Its mechanism of action is related to the inhibition of PPI on the proliferation of HBV-related liver cancer through promoting the apoptosis of liver cancer cells. Additionally, in vitro experiments have also verified that PPI can promote the apoptosis of HepG2 and HepG2.2.15 cells.

The present study revealed the mechanism of PPI against liver cancer through network pharmacology and in vitro experiments. Its mechanism of action is related to the inhibition of PPI on the proliferation of HBV-related liver cancer through promoting the apoptosis of liver cancer cells. Additionally, in vitro experiments have also verified that PPI can promote the apoptosis of HepG2 and HepG2.2.15 cells.