MicroRNA-98: the multifaceted regulator in human cancer progression and therapy.

MicroRNA-98 (miR-98) stands as an important molecule in the intricate landscape of oncology. As a subset of microRNAs, these small non-coding RNAs have accompanied a new era in cancer research, underpinning their significant roles in tumorigenesis, metastasis, and therapeutic interventions. This review provides a comprehensive insight into the biogenesis, molecular properties, and physiological undertakings of miR-98, highlighting its double-edged role in cancer progression-acting both as a tumor promoter and suppressor. Intriguingly, miR-98 has profound implications for various aspects of cancer progression, modulating key cellular functions, including proliferation, apoptosis, and the cell cycle. Given its expression patterns, the potential of miR-98 as a diagnostic and prognostic biomarker, especially in liquid biopsies and tumor tissues, is explored, emphasizing the hurdles in translating these findings clinically. The review concludes by evaluating therapeutic avenues to modulate miR-98 expression, addressing the challenges in therapy resistance, and assessing the efficacy of miR-98 interventions. In conclusion, while miR-98's involvement in cancer showcases promising diagnostic and therapeutic avenues, future research should pivot towards understanding its role in tumor-stroma interactions, immune modulation, and metabolic regulation, thereby unlocking novel strategies for cancer management.

Plasma microRNA-195, -34c, and - 1246 as novel biomarkers for the diagnosis of trastuzumab-resistant HER2-positive breast cancer patients.

Recently, miRNAs have been regarded as potential candidates for mediating therapeutic functions by targeting genes related to drug response. In this study, we suggested that plasma miRNAs may be correlated with response to trastuzumab in HER2-positive breast cancer patients. To determine whether miR-195, miR-23b-3p, miR-1246, and miR-34c-3p are involved in trastuzumab resistance, we screened their expressions in the BT-474 cell line, which was followed by plasma analysis from 20 trastuzumab-resistant HER2-positive breast cancer patients and 20 nonresistance subjects. Then, TargetScan, Pictar, and miRDB were applied to find the possible targets of the selected miRNAs. In addition, the expression status of admitted targets was evaluated. Our results showed that in resistant BT-474 cells, miR-1246, and miR-23b-3p were significantly upregulated, and miR-195-5p and miR-34c-3p were downregulated. In plasma analysis, we found miR-195-5p, miR-34c-3p, and miR-1246 meaningfully diminished in the resistant group, while the expression of miR-23b-3p was not statistically different. The expression levels of confirmed targets by qRT-PCR showed that the expression of RAF1, AKT3, c-MET, CCND1, PHLPP2, MYB, MAP2K1, and PTEN was significantly upregulated, while the expression of CCNG2 was significantly downregulated. The networks of miRNAs with their confirmed targets improved comprehension of miRNA-mediated therapeutic responses to trastuzumab and might be proposed for more characterization of miRNA functions. Moreover, these data indicated that miR-195-5p, miR-34c-3p, and miR-1246 could be possible biomarkers for prognosis and early detection of the trastuzumab-resistant group from the sensitive group of HER2-positive breast cancer patients.

The importance of hsa-miR-28 in human malignancies.

MicroRNA production in tumorigenesis is dysregulated by a variety of processes, such as proliferation and removal of microRNA genes, aberrant transcriptional regulation of microRNAs, disrupted epigenetic alterations, and failures in the miRNA biogenesis machinery. Under some circumstances, miRNAs may act as tumorigenic and maybe anti-oncogenes. Tumor aspects such as maintaining proliferating signals, bypassing development suppressors, delaying apoptosis, stimulating metastasis and invasion, and promoting angiogenesis have been linked to dysfunctional and dysregulated miRNAs. MiRNAs have been found as possible biomarkers for human cancer in a great deal of research, which requires additional evaluation and confirmation. It is known that hsa-miR-28 can function as an oncogene or tumor suppressor in many malignancies, and it does this by modulating the expression of several genes and the downstream signaling network. MiR-28-5p and miR-28-3p, which originate from the same RNA hairpin precursor miR-28, have essential roles in a variety of cancers. This review outlines the function and mechanisms of miR-28-3p and miR-28-5p in human cancers and illustrates the miR-28 family's potential utility as a diagnostic biomarker for prognosis and early detection of cancers.

The Tumor Suppressor Roles and Mechanisms of MiR-491 in Human Cancers.

MicroRNAs (miRNAs) are short non-coding RNAs that bind to the 3' untranslated region (3'' UTR) of target mRNAs to control gene expression post-transcriptionally. Recent indications have highlighted their important roles in a variety of pathophysiological conditions as well as human malignancies. Dysregulated miRNAs act as tumor suppressor genes or oncogenes in a variety of cancers. MiR-491 has been shown to have a major effect on tumorigenesis in multiple malignancies through binding to specific genes and signaling cascades, thereby preventing cancer progression. This review provides an overview of miR-491 expression in regulatory mechanisms and biological procedures of tumor cells, as well as the prospective possible treatment effects of various types of human cancers.

The significance of the SDF-1/CXCR4 signaling pathway in the normal development.

Chemokines are chemoattractants that can regulate cell movement and adhesion. SDF-1 [stromal cell-derived factor-1 (SDF-1)] is a homeostatic CXC chemokine. SDF-1 and its receptors [CXC chemokine receptor 4 (CXCR4)] form a signaling pathway that plays critical roles in different pathological and physiological mechanisms, including embryogenesis, wound healing, angiogenesis, tumor growth, and proliferation. Therefore, the current review aimed to summarize the related studies that addressed the molecular signature of the SDF-1/CXCR4 pathway and to explain how this axis is involved in normal events.

Molecular Insights into COVID-19 Pathophysiology, Immune Pathogenesis, Detection, and Treatment.

In late December 2019, a new kind of Coronavirus called severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) was officially identified in Wuhan, China. In March 2020, SARS-CoV-2 was declared a pandemic by the World Health Organization (WHO), and it has infected millions of people worldwide. SARS-CoV-2 is a highly contagious Coronavirus, which has led to an outbreak of acute respiratory tract infection called "Coronavirus disease 2019" (COVID-19), resulting in mild to severe respiratory infections in humans. The design of appropriate therapeutic approaches is dependent on the understanding of molecular and cellular pathways of Coronavirus infections. In this study, we summarized the characteristic features of SARS-CoV-2. In addition, we considered the recent information regarding COVID-19 molecular immune pathogenesis, diagnosis, and potential treatment, which may provide novel perspectives and therapeutic goals in combating SARS-CoV-2.

MicroRNAs Involved in Inflammatory Breast Cancer: Oncogene and Tumor Suppressors with Possible Targets.

Inflammatory breast cancer (IBC) as a rare and highly aggressive type of breast cancer displays phenotypic characteristics. To date, the IBC-associated molecular mechanisms are entirely unknown. In addition, there is an urgent need to identify the new biomarkers involved in the diagnosis and therapeutic purposes of IBC. MicroRNAs, a category of short noncoding RNAs, are capable of controlling the post-transcriptional expression of genes and thus can act as diagnostic predictive tools. In this review, we addressed the status of oncogenic and tumor suppressor miRNA-mediated IBC in current studies. Furthermore, based on their targets, their involvement in cancer progression, angiogenesis, metastasis, and apoptosis were determined.

Sonochemical incorporated of cytosine in Cu-H2bpdc as an antibacterial agent against standard and clinical strains of Proteus mirabilis with rsbA gene.

The cytosine embedded copper based metal-organic framework (Bio-MOF) was synthesized by facile one-step sonochemical method by simply mixing of 4-4, biphenyldicarboxylic, cytosine and copper nitrate (Bio-Cu-H2bpdc-Cy). The prepared bio-MOF was characterized by XRD, FTIR and FE-SEM techniques. The effect of Cu-H2bpdc-Cy on the expression of the rsbA gene was evaluated in the clinical and standard Proteus mirabilis and study of MIC of Cu-H2bpdc-Cy by microdilution against them that have the rsbA gene. According to different concentrations of MIC, MBC concentrations was cultured on blood agar culture medium. Regarding to the concentration of MIC, gene expression changes were obtained by real-time PCR. MIC for standard and clinical strains of Proteus mirabilis was 1.6 and 1.8 mg/ml, and also MBC was obtained to be 1.8 and 2.0 mg/ml, respectively. Finally, in the real time PCR method, expression of the rsbA gene in presences of bio-Cu-H2bpdc-Cy was reduced, but has no effect on the gene expression of the Housekeeping DNA Gyrase-B gene. Considering the effect of Cu-H2bpdc-Cy on the rsbA gene in Proteus mirabilis bacteria, it is possible to use of Cu-H2bpdc-Cy agent as a therapeutic supplement against this bacterium.

Sonochemical-solvothermal synthesis of guanine embedded copper based metal-organic framework (MOF) and its effect on oprD gene expression in clinical and standard strains of Pseudomonas aeruginosa.

The guanine incropped Cu based metal-organic framework (Guanine-Cu-MOF) was synthesized by facile one-step sonochemical method by simply mixing of 4-4, biphenyldicarboxylic, guanine and copper nitrate (Bio-Cu-H2bpdc-Gu). The prepared guanine-MOF was characterized by using X-Ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and Field emission scanning electron microscopy (FE-SEM) techniques. The morphology of prepared material was sponge-shaped which it was well documented, together with the presence of existing functional groups. The effect of prepared material on oprD Gene Expression was investigated in Clinical and Standard Strains of Pseudomonas aeruginosa (PAO-1) and minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of prepared samples against P. aeruginosa strains were determined through the broth micro-dilution method. The expression of oprD gene in strains affected by Cu-H2bpdc-Gu was quantitatively investigated through real-time PCR. MIC of Bio-Cu-H2bpdc-Gu was 400 µg/mL for the standard and clinical strains of P. aeruginosa, while, MBC of this compound was 700 µg/mL for standard strain and 800 µg/mL for clinical strains. The highest and the lowest rate of oprD gene expression were found to be 3.6 and 1.1 fold in the strains, respectively.

Safflower Seed Oil, Containing Oleic Acid and Palmitic Acid, Enhances the Stemness of Cultured Embryonic Neural Stem Cells through Notch1 and Induces Neuronal Differentiation.

Embryonic neural stem cells (eNSCs) could differentiate into neurons, astrocytes and oligodendrocytes. This study was aimed to determine the effect of safflower seed oil, which contains linoleic acid (LA), oleic acid (OA), and palmitic acid (PA), on cultured eNSC proliferation and differentiation, in comparison to linoleic acid alone. Results showed that safflower seed oil, but not LA, increased significantly the viability and proliferation of eNSCs. Moreover, treatment of NSCs by safflower seed oil, but not LA, resulted in a significant increase in mRNA levels of notch1, hes1, and Ki-67, and protein levels of notch intracellular domain (NICD), in comparison to controls, indicating an enhancement of stemness. Finally, safflower seed oil, but not LA, caused an increase in the number of oligodendrocytes (MBP+), astrocytes (GFAP+) and neurons (ß-III tubulin+) of which only the increase in ß-III tubulin positive cells was statistically significant. In summary, OA and PA, present in safflower seed oil may prove beneficial for the enhancement of eNSCs and their neuronal differentiation.

The ratio of 1/3 linoleic acid to alpha linolenic acid is optimal for oligodendrogenesis of embryonic neural stem cells.

During neural development, embryonic neural stem cells (eNSCs) differentiate toward glial, oligodendrocytic, and neuronal cells. Dysregulation of polyunsaturated fatty acids (PUFAs) induce a wide range of neurological and developmental disorders. In this study, we investigated the effect of various concentrations and ratios of linoleic acid (LA) and alpha linolenic acid (ALA), which belong respectively to omega-6 and omega-3 PUFAs, on the proliferation and differentiation of eNSCs.Results showed that low (25 and 50µM) or high (100 and 200µM) concentrations of ALA, but not LA, and the ratio of 1:3 of LA/ALA significantly increased neurospheres size, frequency and cell numbers, in comparison to controls. Moreover, low or high concentrations of ALA, but not LA, and different ratios of LA/ALA resulted in a significant increase in mRNA expression levels of Notch1, Hes1 and Ki-67, and the differentiation of eNSCs toward astrocytes (GFAP) and oligodendrocytes (MBP), but not neurons (ß-III Tubulin), with the highest increase being for LA/ALA ratio of 1:3, in comparison to controls. These results demonstrate the importance of higher concentrations of ALA in enhancing proliferation and differentiation of eNSCs, which could be used in diet to help preventing neurodevelopmental syndromes, cognitive decline during aging, and various psychiatric disorders.