Current Molecular Medicine - Volume 20, Issue 2, 2020

Lung cancer is the first cause of cancer death in the world due to its high prevalence, aggressiveness, late diagnosis, lack of effective treatment and poor prognosis. It also shows high rate of recurrence, metastasis and drug resistance. All these problems highlight the urgent needs for developing new strategies using noninvasive biomarkers for early detection, metastasis and recurrence of disease. MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate gene expression post-transcriptionally. These molecules found to be abnormally expressed in increasing number of human disease conditions including cancer. miRNAs could be detected in body fluids such as blood, serum, urine and sputum, which leads us towards the idea of using them as non-invasive biomarker for cancer detection and monitoring cancer treatment and recurrence. miRNAs are found to be deregulated in lung cancer initiation and progression and could regulate lung cancer cell proliferation and invasion. In this review, we summarized recent progress and discoveries in microRNAs regulatory role in lung cancer initiation and progression. In addition, the role of microRNAs in EGFR signaling pathway regulation is discussed briefly.

Background: Infections are one of the leading causes of death worldwide and currently available treatments remain unsatisfactory due to rise in the cases of antimicrobial resistance. Thus, there is a need for the development of new drugs with different mechanisms of action. However, the development of new antimicrobials agents is a long and expensive process. Hence, most of the pharmaceutical companies are looking forward to repurposing the already available drugs against microbial infections. Methodology: The data related to SERMs and microbial infection has been extracted from Pub Med (from January 1997 to December 2018). A total of 101 studies have been published from 1997 -2018 regarding SERMs and microbial infections. Results: On the basis of inclusion and exclusion criteria, 25 studies have been included for the analysis of level of evidence regarding antimicrobial effects of SERMs. Emerging reports have indicated the antimicrobial property of selective estrogen receptor modulators (SERMs) against normal and resistant strains under in vitro and in vivo conditions against wide variety of microorganisms through different mechanisms of action. Conclusion: In conclusion, SERMs could be developed as a broad spectrum antimicrobial agent alone or in combination with existing antimicrobial agents.

Curcumin is a naturally occurring polyphenol that is isolated from the rhizome of Curcuma longa (turmeric). This medicinal compound has different biological activities, including antioxidant, antibacterial, antineoplastic, and anti-inflammatory. It also has therapeutic effects on neurodegenerative disorders, renal disorders, and diabetes mellitus. Curcumin is safe and well-tolerated at high concentrations without inducing toxicity. It seems that curcumin is capable of targeting the Nrf2 signaling pathway in protecting the cells against oxidative damage. Besides, this strategy is advantageous in cancer therapy. Accumulating data demonstrates that curcumin applies four distinct ways to stimulate the Nrf2 signaling pathway, including inhibition of Keap1, affecting the upstream mediators of Nrf2, influencing the expression of Nrf2 and target genes, and finally, improving the nuclear translocation of Nrf2. In the present review, the effects of curcumin on the Nrf2 signaling pathway to exert its therapeutic and biological activities has been discussed.

Diabetes mellitus greatly affects the quality of life of patients and has a worldwide prevalence. Insulin is the most commonly used drug to treat diabetic patients and is usually administered through the subcutaneous route. However, this route of administration is ineffective due to the low concentration of insulin at the site of action. This route of administration causes discomfort to the patient and increases the risk of infection due to skin barrier disturbance caused by the needle. The oral administration of insulin has been proposed to surpass the disadvantages of subcutaneous administration. In this review, we give an overview of the strategies to deliver insulin by the oral route, from insulin conjugation to encapsulation into nanoparticles. These strategies are still under development to attain efficacy and effectiveness that are expected to be achieved in the near future.

Background: The hallmark of obesity is the excessive accumulation of triglyceride (TG) in adipose tissue. Apolipoprotein A5 (ApoA5) has been shown to influence the prevalence and pathogenesis of obesity. However, the underlying mechanisms remain to be clarified. Methods: Human adipose-derived mesenchymal stem cells (AMSCs) were treated with 600 ng/ml human recombinant ApoA5 protein. The effect of ApoA5 on intracellular TG content and adipogenic related factors expression were determined. Furthermore, the effect of ApoA5 on CIDE-C expression was also observed. Results: During the process of adipogenesis, ApoA5 treatment reduced the intracellular accumulation of lipid droplets and the TG levels; meanwhile, ApoA5 down-regulated the expression levels of adipogenic related factors, including CCAAT enhancer-binding proteins α/β (C/EBPα/β), fatty acid synthetase (FAS), and fatty acid-binding protein 4 (FABP4). Furthermore, the suppression of adipogenesis by ApoA5 was mediated through the inhibition of CIDE-C expression, an important factor which promotes the process of adipogenesis. However, over-expressing intracellular CIDE-C could lead to the loss-of-function of ApoA5 in inhibiting AMSCs adipogenesis. Conclusions: In conclusion, ApoA5 inhibits the adipogenic process of AMSCs through, at least partly, down-regulating CIDE-C expression. The present study provides novel mechanisms whereby ApoA5 prevents obesity via AMSCs in humans.

Background: Stearic acid (SA), a saturated long-chain fatty acid consisting of 18 carbon atoms, is widely found in feed ingredients, such as corn, soybeans, and wheat. However, the roles of SA in the renewal of intestinal epithelial cells remain unclear. Methods and Results: In the present study, we found that 0.01-0.1 mM SA promoted IPEC-J2 cell differentiation and did not affect IPEC-J2 cell viability. In addition, the results showed that the viability of IPEC-J2 cells was inhibited by SA in a time- and dose-dependent manner at high concentrations. Flow cytometry and western blot analysis suggested that SA induced apoptosis, autophagy and ER stress in cells. In addition, the amounts of triglyceride were significantly increased upon challenge with SA. Moreover, the decrease in the viability of cells induced by SA could be attenuated by 4-PBA, an inhibitor of ER stress. Conclusion: In summary, SA accelerated IPEC-J2 cell differentiation at 0.01-0.1 mM. Furthermore, SA induced IPEC-J2 cell apoptosis and autophagy by causing ER stress.