Activity

The recent outbreak of Coronavirus disease (COVID-19), first in Eastern Asia and then essentially across the world has been declared a pandemic by the WHO. COVID-19 is caused by a novel virus SARS-CoV2 (2019-nCoV), against which there is currently no vaccine available; and current antiviral therapies have failed, causing a very high mortality rate. Drug repurposing i.e. utilizing an approved drug for different indication, offers a time- and cost-efficient alternative for making new therapies available to patients. Although there are several reports presenting novel approaches to treat COVID-19, still an attentive review of previous scientific literature is essential to overcome their failure to exhibit efficacy. There is an urgent need to provide a comprehensive outlook toward utilizing drug repurposing as a tool for discovery of new therapies against COVID-19. In this article, we aim to provide a to-the-point review of current literature regarding efficacy of repurposed drugs against COVID-19 and other respiratory infections caused by coronaviruses. We have briefly discussed COVID-19 epidemiology, and then have discussed drug repurposing approaches and examples, specific to respiratory viruses. Limitations of utilization of repurposed drug molecules such as dosage regimen and associated challenges such as localized delivery in respiratory tract have also been discussed in detail.

To explore whether GOLPH3 regulated oxaliplatin (L-OHP) resistance of colon cancer cells via PI3K/AKT/mTOR pathway.

HCT116/L-OHP cells were divided into Blank, Control/GOLPH3 shRNA, BEZ235 (a PI3K/AKT/mTOR inhibitor), and GOLPH3+BEZ235 groups followed by the detection with MTT, soft agar colony formation, flow cytometry and TUNEL assays. Mice bearing HCT116/L-OHP xenografts were randomized into Control, L-OHP, NC/GOLPH3 shRNA, L-OHP+NC/GOLPH3 shRNA groups. The expressions of Ki67, Caspase-3, and PI3K/AKT/mTOR pathway proteins were examined by immunohistochemistry.

HCT116/L-OHP cells had increased GOLPH3 expression compared to HCT116 cells, which positively regulated PI3K/AKT/mTOR pathway in HCT116/L-OHP cells. BEZ235 declined IC50 of HCT116/L-OHP cells to L-OHP, decreased the expressions of ABCB1, ABCC1, ABCG2, ATP7A, ATP7B, MATE1, p-gp, MRP1 and BCRP, induced cell apoptosis, reduced cell proliferation, and arrested cells at G0/G1, which was reversed by GOLPH3 overexpression. L-OHP and GOLPH3 shRNA decreased tumor volume and reduced expression of Ki67 in tumor tissues with the increased Caspase-3. Meanwhile, the combined treatment had the better treatment effect.

GOLPH3 inhibition reduced proliferation and promoted apoptosis of HCT116/L-OHP cells, and also reversed the L-OHP resistance of HCT116/L-OHP, which may be associated with the suppression of P13K/AKT/mTOR pathway.

GOLPH3 inhibition reduced proliferation and promoted apoptosis of HCT116/L-OHP cells, and also reversed the L-OHP resistance of HCT116/L-OHP, which may be associated with the suppression of P13K/AKT/mTOR pathway.

Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies with a significant mortality rate. Despite the great advances in cancer treatment in the last few decades, effective treatment of CRC is still under challenge. One of the main problems associated with CRC treatment is the resistance of cancer cells to chemotherapy drugs.

Many studies have been carried out to identify CRC chemoresistance mechanisms, and shed light on the role of ATP-binding cassette transporters (ABC transporters), enzymes as thymidylate synthase, some signaling pathways, and cancer stem cells (CSC) in chemoresistance and failed CRC chemotherapies. Other studies have also been recently carried out to find solutions to overcome chemoresistance. Some of these studies have identified the role of miRNAs in chemoresistance of the CRC cells and the effective use of these micro-molecules to CRC treatment.

Considering the results of these studies, more focus on miRNAs likely leads to a proper solution to overcome CRC chemoresistance.

The current study has reviewed the related literature while discussing the efficacy of miRNAs as potential clinical tools for overcoming CRC chemoresistance and reviewing the most important chemoresistance mechanisms in CRC cells.

The current study has reviewed the related literature while discussing the efficacy of miRNAs as potential clinical tools for overcoming CRC chemoresistance and reviewing the most important chemoresistance mechanisms in CRC cells.Inflammation is a sophisticated biological tissue response to both extrinsic and intrinsic stimuli. Although the pathological aspects of inflammation are well appreciated, there are still rooms for understanding the physiological functions of the inflammation. Recent studies have focused on mechanisms, context and the role of physiological inflammation. Besides, there have been progress in the comprehension of commensal microbiota, immunometabolism, cancer and intracellular signaling events’ roles that impact on the regulation of inflammation. Despite the fact that inflammatory responses are vital through tissue damage, understanding the mechanisms to turn off the finished or unnecessary inflammation is crucial for restoring homeostasis. Inflammation seems to be a smart process that acts like two edges of a sword, meaning that it has both protective and deleterious consequences. Knowing both edges and the regulation processes will help the future understanding and therapy for various diseases.

Assessing patient fitness prior to high-risk operations is becoming increasingly vital in cardiothoracic surgery. Physical activity (PA) and frailty measures are powerful perioperative tools, albeit underused in clinical practice. This study aimed to assess the influence of patient frailty on PA post-surgery and other short-term outcomes.

Eighty patients undergoing a variety of cardiac surgical procedures (coronary revascularisation, valve repair/replacement, or combination) were recruited to participate. The Reported Edmonton Frailty Scale (REFS) was used to measure pre-operative frailty. As objective measures of PA, participants wore a wrist accelerometer device for 14 days prior to their operation and early in the post-operative period for 30 days.

A global reduction in PA was observed in the early post-operative period. Selleck AZ32 Frailty was a significant predictor of reduced light (coef -2.23, 95% CI -4.21 – -0.25, p=0.028) and moderate activity (coef -1.85, 95% CI -2.99 – -0.70, p=0.002) post-operatively. Neither frailty nor pre-operative PA were predictors of post-operative composite complications.