In vitro activity of itraconazole against SARS‐CoV‐2

alkiviadis.1961 shared this article with you from Inoreader In vitro activity of itraconazole against SARS‐CoV‐2 Via Journal of Medical Virology Abstract Although vaccination campaigns are currently being rolled out to prevent coronavirus disease (COVID‐19), antivirals will remain an important adjunct to vaccination. Antivirals against coronaviruses do not exist, hence global drug repurposing efforts have been carried out to identify agents that may provide clinical benefit to patients with COVID‐19. Itraconazole, an antifungal agent, has been reported to have activity against animal coronaviruses. Using cell‐based phenotypic assays, the in vitro antiviral activity of itraconazole and 17‐OH itraconazole was assessed against clinical isolates from a German and Belgian patient infected with SARS‐CoV‐2. Itraconazole demonstrated antiviral activity in human Caco‐2 cells (EC50 = 2.3 µM; MTT assay). Similarly, its primary metabolite, 17‐OH itraconazole, showed inhibition of SARS‐CoV‐2 activity (EC50 = 3.6 µM). Remdesivir inhibited viral replication with an EC50 = 0.4 µM. Itraconazol e and 17‐OH itraconazole resulted in a viral yield reduction in vitro of approximately 2‐log10 and approximately 1‐log10, as measured in both Caco‐2 cells and VeroE6‐eGFP cells, respectively. The viral yield reduction brought about by remdesivir or GS‐441524 (parent nucleoside of the antiviral prodrug remdesivir; positive control) was more pronounced, with an approximately 3‐log10 drop and >4‐log10 drop in Caco‐2 cells and VeroE6‐eGFP cells, respectively. Itraconazole and 17‐OH itraconazole exert in vitro low micromolar activity against SARS‐CoV‐2. Despite the in vitro antiviral activity, itraconazole did not result in a beneficial effect in hospitalized COVID‐19 patients in a clinical study (EudraCT Number: 2020‐001243‐15). This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Baseline serum exosome‐derived miRNAs predict HBeAg seroconversion in chronic hepatitis B patients treated with peginterferon

alkiviadis.1961 shared this article with you from Inoreader Baseline serum exosome‐derived miRNAs predict HBeAg seroconversion in chronic hepatitis B patients treated with peginterferon Via Journal of Medical Virology Abstract Objective This study aimed to explore the value of baseline serum exosome‐derived miRNAs for predicting HBeAg seroconversion in chronic hepatitis B (CHB) patients treated with peginterferon (Peg‐IFN). Methods A total of 120 treatment‐naïve HBeAg‐positive CHB patients who received Peg‐IFN therapy (48 weeks) were enrolled. Next‐generation sequencing was performed to screen the serum exosomal miRNAs that were associated with Peg‐IFN treatment outcome, and qRT‐PCR was used to validate them. The area under receiver operating characteristic curve (AUROC) was used to evaluate the predictive efficacy of biomarkers. Results Thirty‐three patients (27.5%) achieved HBeAg seroconversion (response group), and 87 patients (72.5%) did not achieve HBeAg seroconversion (non‐response group). In the identification cohort, forty serum exosome‐derived miRNAs were differentially expressed between the response group (4 patients) and the non‐response group (4 patients). In the confirmation cohort, the expression levels of serum exosomal miR‐194‐5p (p < 0.001) and miR‐22‐3p (p < 0.001) were significantly downregulated in the response group (29 patients) compared to the non‐response group (83 patients). Multivariate analysis identified baseline serum exosomal miR‐194‐5p, miR‐22‐3p, alanine aminotransferase (ALT) and HBV DNA as independent predictors of HBeAg seroconversion (all p < 0.05). The AUROCs of serum exosomal miRNAs (0.77 and 0.75 for miR‐194‐5p and miR‐22‐3p, respectively) were higher than that of ALT (0.70) and HBV DNA (0.69). The combination of exosomal miR‐194‐5p and miR‐22‐3p further improved the predictive performance with an AUROC of 0.82. Conclusion Baseline serum exosomal miR‐194‐5p and miR‐22‐3p may serve as novel biomarkers to predict HBeAg seroconversion in CHB patients treated with Peg‐IFN. This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Healthcare disparities among anticoagulation therapies for severe COVID‐19 patients in the multi‐site VIRUS registry

alkiviadis.1961 shared this article with you from Inoreader Healthcare disparities among anticoagulation therapies for severe COVID‐19 patients in the multi‐site VIRUS registry Via Journal of Medical Virology Abstract Here we analyze hospitalized and ICU COVID‐19 patient outcomes from the international VIRUS registry (https://clinicaltrials.gov/ct2/show/NCT04323787). We find that COVID‐19 patients administered unfractionated heparin but not enoxaparin have a higher mortality‐rate (390 of 1,012 = 39%) compared to patients administered enoxaparin but not unfractionated heparin (270 of 1,939 = 14%), presenting a risk ratio of 2.79 (95% C.I.: [2.42, 3.16]; p‐value: 4.45e‐52). This difference persists even after balancing on a number of covariates including demographics, comorbidities, admission diagnoses, and method of oxygenation, with an increased mortality rate on discharge from the hospital of 37% (268 of 733) for unfractionated heparin vs. 22% (154 of 711) for enoxaparin, presenting a risk ratio of 1.69 (95% C.I.: [1.4 2, 2.00]; p‐value: 1.5e‐8). In these balanced cohorts, a number of complications occurred at an elevated rate for patients administered unfractionated heparin compared to patients administered enoxaparin, including acute kidney injury, acute cardiac injury, septic shock, and anemia. Furthermore, a higher percentage of Black/African American COVID patients (414 of 1,294 [32%]) were noted to receive unfractionated heparin compared to White/Caucasian COVID patients (671 of 2,644 [25%]), risk ratio 1.26 (95%CI [1.14, 1.40], p‐value: 7.5e‐5). After balancing upon available clinical covariates, this difference in anticoagulant use remained statistically significant (311 of 1,047 [30%] for Black/African American vs. 263 of 1,047 [25%] for White/Caucasian, p‐value: 0.02, risk ratio 1.18, 95%CI [1.03, 1.36]). While retrospective studies cannot suggest any causality, these findings motivate the need for follow‐up prospective research into the observed racial disparity in anticoagu lant use and outcomes for severe COVID‐19 patients. This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Anti-Inflammatory Investigations of Extracts of Zanthoxylum rhetsa

alkiviadis.1961 shared this article with you from Inoreader Anti-Inflammatory Investigations of Extracts of Zanthoxylum rhetsa Via Hindawi Publishing Corporation Zanthoxylum rhetsa has been consumed in the diet in northern Thailand and also used as a medicament in ancient scripture for arthropathies. Thus, this study aimed to evaluate the activity of various extracts from differential parts of Z. rhetsa via inhibition of inflammatory mediators (NO, TNF-α, and PGE2) in RAW264.7 macrophages. The chemical composition in active extracts was also analyzed by GC/MS. The parts of this plant studied were whole fruits (F), pericarp (P), and seed (O). The methods of extraction included maceration in hexane, 95% ethanol and 50% ethanol, boiling in water, and water distillation. The results demonstrated that the hexane and 95% ethanolic extract from pericarp (PH and P95) and seed essential oil (SO) were the most active extracts. PH and P95 gave the highest inhibi tion of NO production with IC50 as 11.99 ± 1.66 μg/ml and 15.33 ± 1.05 μg/ml, respectively, and they also showed the highest anti-inflammatory effect on TNF-α with IC50 as 36.08 ± 0.55 μg/ml and 34.90 ± 2.58 μg/ml, respectively. PH and P95 also showed the highest inhibitory effect on PGE2 but less than SO with IC50 as 13.72 ± 0.81 μg/ml, 12.26 ± 0.71 μg/ml, and 8.61 ± 2.23 μg/ml, respectively. 2,3-Pinanediol was the major anti-inflammatory compound analyzed in PH (11.28%) and P95 (19.82%) while terpinen-4-ol constituted a major anti-inflammatory compound in SO at 35.13%. These findings are the first supportive data for ethnomedical use for analgesic and anti-inflammatory activity in acute (SO) and chronic (PH and P95) inflammation. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Development and Application of Artificial Intelligence in Auxiliary TCM Diagnosis

alkiviadis.1961 shared this article with you from Inoreader Development and Application of Artificial Intelligence in Auxiliary TCM Diagnosis Via Hindawi Publishing Corporation As an emerging comprehensive discipline, artificial intelligence (AI) has been widely applied in various fields, including traditional Chinese medicine (TCM), a treasure of the Chinese nation. Realizing the organic combination of AI and TCM can promote the inheritance and development of TCM. The paper summarizes the development and application of AI in auxiliary TCM diagnosis, analyzes the bottleneck of artificial intelligence in the field of auxiliary TCM diagnosis at present, and proposes a possible future direction of its development. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Tian-Huang Formula, a Traditional Chinese Medicinal Prescription, Improves Hepatosteatosis and Glucose Intolerance Targeting AKT-SREBP Nexus in Diet-Induced Obese Rats

alkiviadis.1961 shared this article with you from Inoreader Tian-Huang Formula, a Traditional Chinese Medicinal Prescription, Improves Hepatosteatosis and Glucose Intolerance Targeting AKT-SREBP Nexus in Diet-Induced Obese Rats Via Hindawi Publishing Corporation The progressive increase of metabolic diseases underscores the necessity for developing effective therapies. Although we found Tian-Huang formula (THF) could alleviate metabolic disorders, the underlying mechanism remains to be fully understood. In the present study, firstly, male Sprague-Dawley rats were fed with high-fat diet plus high-fructose drink (HFF, the diet is about 60% of calories from fat and the drink is 12.5% fructose solution) for 14 weeks to induce hepatosteatosis and glucose intolerance and then treated with THF (200 mg/kg) for 4 weeks. Then, metabolomics analysis was performed with rat liver samples and following the clues illustrated by Ingenuity Pathway Analysis (IPA) with the metabolomics discoveries, RT-qPCR and Western blotting were carried out to validate the putative pathways. Our results showed that THF treatment reduced the body weight from 735.1 ± 81.29 to 616.3 ± 52.81 g and plasma triglyceride from 1.5 ± 0.42 to 0.88 ± 0.33 mmol/L; meanwhile, histological examinations of hepatic tissue and epididymis adipose tissue showed obvious alleviation. Compared with the HFF group, the fasting serum insulin and blood glucose level of the THF group were improved from 20.77 ± 6.58 to 9.65 ± 5.48 mIU/L and from 8.96 ± 0.56 to 7.66 ± 1.25 mmol/L, respectively, so did the serum aspartate aminotransferase, insulin resistance index, and oral glucose tolerance ( = 0.0019, 0.0053, and 0.0066, respectively). Furthermore, based on a list of 32 key differential endogenous metabolites, the molecular networks generated by IPA suggested that THF alleviated glucose intolerance and hepatosteatosis by activating phosphatidylinositol-3 kinase (PI3K) and low-density lipoprotein receptor (LDL-R) involved pathways. RT-qP CR and Western blotting results confirmed that THF alleviated hepatic steatosis and glucose intolerance partly through protein kinase B- (AKT-) sterol regulatory element-binding protein (SREBP) nexus. Our findings shed light on molecular mechanisms of THF on alleviating metabolic diseases and provided further evidence for developing its therapeutic potential. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Video-based eye tracking performance for computer-assisted diagnostic support of diabetic neuropathy

alkiviadis.1961 shared this article with you from Inoreader Video-based eye tracking performance for computer-assisted diagnostic support of diabetic neuropathy Via ScienceDirect Publication: Artificial Intelligence in Medicine Publication date: Available online 5 March 2021 Source: Artificial Intelligence in Medicine Author(s): Luis David Avendaño-Valencia, Knud B. Yderstræde, Esmaeil S. Nadimi, Victoria Blanes-Vidal View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

50, 100 & 150 Years Ago: March 2021

alkiviadis.1961 shared this article with you from Inoreader 50, 100 & 150 Years Ago: March 2021 Via Scientific American Content: Global Lethal gas fights crime, 1921; baby energy powers cleaning, 1871 -- Read more on ScientificAmerican.com Attachments: View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Impact of the extent of axillary surgery in patients with N2–3 disease in the de-escalation era: a propensity score-matched study

alkiviadis.1961 shared this article with you from Inoreader Impact of the extent of axillary surgery in patients with N2–3 disease in the de-escalation era: a propensity score-matched study Via Latest Results for Clinical and Translational Oncology Abstract Background Reduction of surgeries in axillary has been proved feasible in breast cancer with negative and limited involved axillary lymph nodes. However, for women with a heavy axillary burden, the extent of dissection is still arguable. Patients and methods From a total of 7042 patients with breast cancer who underwent surgical treatments between 2008 and 2014, 692 (9.85%) patients with the axillary staging of N2–3M0 were classified into Level I–II dissection group and Level I–III dissection group. 203 pairs of patients were matched by the propensity score. Results The positive rate of level-III lymph nodes is 62.4% in patients who underwent Level I–III dissection. There are 67 (22.1%) patients who experienced rise in staging from N2 to N3 due to level-III dissection. With a median follow-up of 62.4 months, no significant difference was observed in RFS (P = 0.897), MFS (P = 0.610) and OS (P = 0.755) between level I–II group and level I–III group. The same results were observed in the independent analysis of neoadjuvant and non-neoadjuvant subgroups. The binary regression model showed the positivity of level-III is only associated with involved lymph nodes in level-II. Conclusion Additional level-III dissection has a limited impact on survival but still valuable in an accurate stage. The reduction of surgeries in axillary should be treated with discretion in breast cancer patients with a heavy axillary burden. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Bevacizumab in recurrent ovarian cancer: could it be particularly effective in patients with clear cell carcinoma?

alkiviadis.1961 shared this article with you from Inoreader Bevacizumab in recurrent ovarian cancer: could it be particularly effective in patients with clear cell carcinoma? Via Latest Results for Clinical and Translational Oncology Abstract Purpose Treatment of recurrent ovarian carcinoma is a challenge, particularly for the clear cell (CCC) subtype. However, there is a preclinical rationale that these patients could achieve a benefit from antiangiogenic therapy. To assess this hypothesis, we used the growth modulation index (GMI), which represents an intrapatient comparison of two successive progression-free survival (PFS). Methods We conducted a retrospective real-world study performed on 34 patients with recurrent ovarian cancer, treated with bevacizumab-containing regimens from January 2009 to December 2017. The primary endpoint was GMI. An established cut-off > 1.33 was defined as a sign of drug activity. Results 73.5% of patients had high-grade serous ovarian carcinoma (HGSOC), and 17.7% had CCC; 70.6% of patients received carboplatin/gemcitabine/bevacizumab, and 29.4% received weekly paclitaxel/bevacizumab. According to histological subtype, the overall response rate and median PFS were 52% and 14 months for HGSOC and 83.3% and 20 months for CCC, respectively. The overall population median GMI was 0.99; it was 0.95 and 2.36 for HGSOC and CCC, respectively. CCC subtype was significantly correlated with GMI > 1.33 (odds ratio 41.67; 95% confidence interval 3.6–486.94; p = .03). Conclusion Adding bevacizumab to chemotherapy in recurrent CCC is associated with a remarkable benefit in this cohort. The efficacy of antiangiogenic drugs in CCC warrants further prospective evaluation. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Noncoding RNAs as potential biomarkers for DIPG diagnosis and prognosis: XIST and XIST-210 involvement

alkiviadis.1961 shared this article with you from Inoreader Noncoding RNAs as potential biomarkers for DIPG diagnosis and prognosis: XIST and XIST-210 involvement Via Latest Results for Clinical and Translational Oncology Abstract Purpose Diffuse intrinsic pontine gliomas (DIPGs) are the most fatal primary brainstem tumors in pediatric patients. The identification of new molecular features, mediating their formation and progression, as non-coding RNAs (ncRNAs), would be of great importance for the development of effective treatments. Methods We analyzed the DIPGs transcriptome with the HTA2.0 array and it was compared with pediatric non-brainstem astrocytoma expression profiles (GSE72269). Results More than 50% of the differentially expressed transcripts were ncRNAs and based on this, we proposed a DIPGs ncRNA signature. LncRNAs XIST and XIST-210, and the HBII-52 and HBII-85 snoRNA clusters were markedly downregulated in DIPGs. qPCR assays demonstrated XIST downregulation in all non-brainstem astrocytomas, in a gender, age, and brain location-independent manner, as well as in DIPGs affecting boys; however, DIPGs affecting girls showed both downregulation and upregulation of XIST. Girls' with longer survival positively correlated with XIST expression. Conclusions The involvement of ncRNAs in DIPGs is imminent and their expression profile is useful to differentiate them from non-neoplastic tissues and non-brain stem astrocytomas, which suggests their potential use as DIPG biomarkers. In fact, XIST and XIST-210 are potential DIPG prognostic biomarkers. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

MiR-92 overexpression suppresses immune cell function in ovarian cancer via LATS2/YAP1/PD-L1 pathway

alkiviadis.1961 shared this article with you from Inoreader MiR-92 overexpression suppresses immune cell function in ovarian cancer via LATS2/YAP1/PD-L1 pathway Via Latest Results for Clinical and Translational Oncology Abstract Purpose Increasing evidence suggested that microRNA plays an important role in ovarian cancer. In this study, the role of miR-92 in ovarian cancer was investigated. Methods In this study, miR-92 expression in clinical sample was evaluated, role of miR-92 was investigated in vitro, and underlying mechanism was investigated using Chip, co-IP, and western blot. Results In this study, we show that miR-92 is overexpressed in ovarian cancer tissue compared with normal cancer tissue. Transfection of miR-92 increased proliferation of ovarian cancer cell, and increased migration capacity and colony formation were observed after miR-92 transfection; we found that expression of LATS2 was decreased by miR-92, and this was further confirmed by luciferase assay, which proved that miR-92 is targeting 3′ of the endogenous LATS2 gene. Downregulation of LATS2 resulted in increased translocation of YAP1 and upregulation of PD-L1, which subsequently suppressed NK cell function and promoted T cell apoptosis. Moreover, co-transfection of YAP1-targeted shRNA could relieve miR-92-induced immune suppression effect. Mechanically, immunoprecipitation (IP) was used to show that LATS2 interacted with YAP1 and subsequently limited nuclear translocation of YAP1; chromatin immunoprecipitation (ChIP) was used to confirm that YAP1 could bind to enhance r region of PD-L1 to enhance transcription activity of PD-L1. Conclusions Our data revealed a novel mechanism which finally resulted in immune suppression in ovarian cancer. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.