miRNAs as cornerstones in diabetic microvascular complications.

Diabetes mellitus is usually accompanied by nephropathy, retinopathy, and neuropathy as microvascular complications. MicroRNAs (miRNAs) can affect the kidney, retina, and peripheral neurons through their implication in pathways involved in angiogenesis, inflammation, apoptosis, as well as fibrosis within these tissues and hence, play a crucial role in the pathogenesis of microvascular complications. In this review, the updated knowledge of the role of miRNAs in the pathogenesis of diabetic microvascular complications was summarized. PubMed Central was searched extensively to retrieve data from a wide range of reputable biomedical reports/articles published after the year 2000 to systematically collect and present a review of the key molecular pathways mediating the hyperglycemia-induced adverse effects on vascular tissues, particularly in persons with T2DM. In the present review, miR-126, miR-29b, and miR-125a are implicated in diabetes-induced microvascular complications, while miR-146a is found to be connected to all these complications. Also, vascular endothelial growth factors are noted to be the most impacted targets by miRNAs in all diabetic microvascular problems.

Benzoxazole derivatives as new VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, in silico studies, and antiproliferative evaluation.

In this study, a set of novel benzoxazole derivatives were designed, synthesised, and biologically evaluated as potential VEGFR-2 inhibitors. Five compounds (12d, 12f, 12i, 12l, and 13a) displayed high growth inhibitory activities against HepG2 and MCF-7 cell lines and were further investigated for their VEGFR-2 inhibitory activities. The most potent anti-proliferative member 12 l (IC50 = 10.50 µM and 15.21 µM against HepG2 and MCF-7, respectively) had the most promising VEGFR-2 inhibitory activity (IC50 = 97.38 nM). A further biological evaluation revealed that compound 12l could arrest the HepG2 cell growth mainly at the Pre-G1 and G1 phases. Furthermore, compound 12l could induce apoptosis in HepG2 cells by 35.13%. likely, compound 12l exhibited a significant elevation in caspase-3 level (2.98-fold) and BAX (3.40-fold), and a significant reduction in Bcl-2 level (2.12-fold). Finally, docking studies indicated that 12l exhibited interactions with the key amino acids in a similar way to sorafenib.

The potential relevance of long non-coding RNAs in colorectal cancer pathogenesis and treatment: A review focus on signaling pathways.

Colorectal cancer (CRC) is one of the most frequent cancers in incidence and mortality. Despite advances in cancer biology, molecular genetics, and targeted treatments, CRC prognosis and survival have not kept pace. This is usually due to advanced staging and metastases at diagnosis. Thus, great importance has been placed upon understanding the molecular pathophysiology behind the development of CRC, which has highlighted the significance of non-coding RNA's role and associated intracellular signaling pathways in the pathogenesis of the disease. According to recent studies, long non-coding RNAs (lncRNA), a subtype of ncRNAs whose length exceeds 200 nucleotides, have been found to have regulatory functions on multiple levels. Their actions at the transcription, post-transcriptional, translational levels, and epigenetic regulation have made them prime modulators of gene expression. Due to their role in cellular cancer hallmarks, their dysregulation has been linked to several illnesses, including cancer. Furthermore, their clinical relevance has expanded due to their possible detection in blood which has cemented them as potential future biomarkers and thus, potential targets for new therapy. This review will highlight the importance of lncRNAs and related signaling pathways in the development of CRC and their subsequent clinical applications.

Beneficial and detrimental aspects of miRNAs as chief players in breast cancer: A comprehensive review.

Breast cancer (BC) is the most common cancer in women and poses a serious threat to their health. Despite familiarity with factors affecting its etiology, initiation, progression, treatment strategies, and even resistance to therapy, it is considered a significant problem for women. However, several factors have greatly affected previous aspects affecting BC progression and treatment in the last decades. miRNAs are short non-coding RNA sequences that regulate gene expression by inhibiting the translation of the target mRNA. miRNAs play a crucial role in BC pathogenesis by promoting cancer stem cell (CSCs) proliferation, postponing apoptosis, continuing the cell cycle, and endorsing invasion, angiogenesis, and metastasis. Similarly, miRNAs influence important BC-related molecular pathways such as the PI3K/AKT/mTOR signaling pathway, the Wnt/ß-catenin system, JAK/STAT signaling pathway, and the MAPK signaling pathway. Moreover, miRNAs affect the treatment response of BC to chemo and radiotherapy. Consequently, this review aims to provide an acquainted summary of oncomiRs and tumor suppressor (TS) miRNAs and their potential role in BC pathogenesis and therapy responses by focusing on the molecular pathways that drive them.

The clinical value of ficolin-3 gene polymorphism in rheumatic heart disease. An Egyptian adolescents study.

OBJECTIVE: Ficolin-3 is one of the innate immunity molecules that was thought to play a pivotal role in Streptococcus pyogenes autoimmunity and its complications; rheumatic fever (RF) and rheumatic heart disease (RHD). We aimed to disclose if there is an association between ficolin-3 (FCN3) gene polymorphisms (rs4494157 and rs10794501) and RF with or without RHD for the first time in Egyptian adolescents. RESULTS: Serum ficolin-3 level was significantly elevated in patients suffering from RF with and without RHD in comparison with control. Regarding FCN3 gene (rs4494157) polymorphism, a significant correlation was found between the A allele and the susceptibility to RF with or without RHD (OR = 2.93, P = 0.0002 and OR = 2.23, P = 0.008 respectively). Besides, AA homozygous genotype showed a significant association with RHD risk (OR = 3.47, P = 0.026). Patients carrying the A allele (CA + AA) had significantly higher serum ficolin-3 than those carrying the CC genotype (P ˂ 0.0001). While the frequency of (rs10794501) polymorphism revealed no significant differences between the controls and RF patients with or without RHD (OR = 1.43, P = 0.261 and OR = 1.48, P = 0.208 respectively).