MicroRNA-510-3p regulated vascular dysfunction in Preeclampsia by targeting Vascular Endothelial Growth Factor A (VEGFA) and its signaling axis.

INTRODUCTION: Preeclampsia (PE) is a pregnancy complication associated with multi-organ damage and vascular dysfunction. Meanwhile, microRNAs or miRNAs are crucial regulators of gene expression in various diseases including PE. Our previous studies reported high expression of miR-510 in the PE patients' blood compared to normal. Hence, we hypothesize that miR-510-3p targets Vascular endothelial growth factor A (VEGFA) in the regulation of PI3K/AKT/eNOS/mTOR axis in PE and miR-510-3p could be a potential therapeutic target for PE. METHODS: The proliferation, migration, and apoptosis of HTR8/SVNeo and BeWo cells were analyzed by manipulating the miR-510-3p and VEGFA expression. Similarly, the inhibition of miR-510-3p through anti-miR-510-3p was analyzed in PE rat models, and the biochemical, hemodynamic parameters, and histopathology were examined between the groups. Moreover, the expression of miR-510-3p and VEGFA/PI3K/AKT/eNOS/mTOR axis was analyzed using qRT-PCR and Western blot. RESULTS: Significant changes were observed in the BP, proteinuria, and other biochemical parameters between PE and control rats. Our results suggest that miR-510-3p targets VEGFA leading to vascular dysfunction in PE, while treatment with anti-miR-510-3p in the PE-induced rat model exhibits a significant change in the expression of miR-510-3p/VEGFA/PI3K/AKT/eNOS/mTOR signaling where miR-510-3p showed lesser expression and vice versa with VEGFA. The gene and protein expression analysis revealed a significant correlation between miR-510-3p and the VEGFA signaling axis in PE. DISCUSSION: Thus, our findings from in vitro and in vivo suggest miR-510-3p as a potential therapeutic target and anti-miR-510-3p as a novel therapeutic molecule for PE.

Expression profiling of signal transducer and activator of transcription3 in oral squamous cell carcinoma in south Indian population.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is widely acknowledged as the most prevalent form of oral malignancy. The annual identification of approximately 540,000 new cases of OSCC highlights its significant impact. The survival rate beyond 5 years postsurgery remains low. The role of signal transducer and activator of transcription3 (STAT3), a signaling protein involved in various cellular processes, has garnered attention. Aberrant activation of STAT3 has been implicated in OSCC progression and aggressiveness. Understanding the impact of STAT3 dysregulation on OSCC outcomes could provide valuable insights for developing targeted therapies. The aim of this study was to evaluate and compare the expression levels of STAT3 in OSCC and normal tissues of the same patients. METHODS: The expression levels of STAT3 in 63 OSCC samples were detected by qRT-PCR and compared to patient-matched-non-tumor oral tissues. Data were normalized to internal controls, and fold change in STAT3 expression was calculated using the ∆∆Ct method. Correlations between expression level and clinicopathologic characteristics like staging and grading of OSCC samples were also analyzed. RESULTS: Our findings demonstrated that STAT3 expression was significantly upregulated (P<0.0001) in OSCC patients compared to normal control tissue. Furthermore, we also observed a positive correlation between elevated STAT3 expression and higher OSCC histological grades when compared to the normal tissue. Well differentiated OSCC showed a slightly lower expression compared to the other two grades. CONCLUSIONS: Our results support the involvement of STAT3 in OSCC tumorigenesis. We propose that STAT3 might be used as a potential biomarker for OSCC. Further investigations are warranted to elucidate the mechanistic basis for the observed associations and to explore STAT3's potential as a therapeutic target in OSCC.

MicroRNA-34a-3p and its target tumor necrosis factor-α in the regulation of South Indian oral squamous cell carcinoma population.

BACKGROUND: The most frequent head and neck cancer is oral squamous cell carcinoma (OSCC), the common histological cancer of the oral cavity and is one of the most prevalent forms of cancer globally. It has been known that there are several biomarkers and therapeutic targets that have been discovered for OSCC, but none of them were effective against the progression of OSCC. Interestingly, small non-coding RNAs termed microRNAs (miRNAs) regulate cellular activity by targeting numerous signaling pathways or genes that either promote or repress the progression of diseases. Surprisingly, among the differentially expressed miRNAs, miR-34a was identified to be highly sensitive and specific to OSCC and widely studied for its role in various cancers, including OSCC. METHODS: The secondary structure of miR-34a-3p was analyzed using bioinformatic analysis and its targets were screened using the TargetScan database. Specimens of 25 OSCC cancer tissues and adjacent normal tissues were collected from the Department of Oral and Maxillofacial Surgery, Saveetha Dental College and Hospitals. The tissues were processed for H&E staining and gene expression analysis of miR-34a-3p and tumor necrosis factor alpha (TNF-α). RESULTS: The minimum free energy for miR-34a-3p was found to be -47.20 kCal which proved the stability of the miRNA. The histopathological examination confirmed the OSCC cases and the gene expression analysis revealed that miR-34a-3p was significantly downregulated in OSCC tissues, whereas TNF-α showed vice versa expression. CONCLUSIONS: miR-34a-3p could be postulated as a potential therapeutic target for OSCC.

Relevance of micro-RNAs and their targets as a diagnostic and prognostic marker in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) ranks sixth among all cancers in the world, affecting various sites of the oral cavity with associated several risk factors. High mortality has been associated with the presence of metastasis during the time of diagnosis and an increase in therapeutic relapses. Micro-RNAs (miRNAs) are a group of small non-coding RNAs with salient roles in the initiation and progression of cancer. The tumorigenesis of OSCC is associated with the dysregulation of several miRNAs. MicroRNAs are an area of recent interest, and numerous studies have been reported and are being undertaken to identify their role in diagnostic and prognostic value for oral cancers. Most of the miRNA processing machinery is considered to be either up-/down-regulated in OSCC, but the underlying mechanism of miRNA dysregulation and their activity as either a tumour suppressor or an oncogene in oral carcinogenesis is not yet clear. The article presents a concise review of the available current literature regarding the various miRNAs' signatures in OSCC and their role as diagnostic/prognostic biomarkers.

Gene expression analysis of microRNA-1285 in the South Indian oral squamous cell carcinoma population.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most common oral malignant tumor, which has poor prognosis. The traditional investigative modality is invasive biopsy which is the gold standard for diagnosis. In recent years, alternative methods like non-invasive biomarkers have been studied for their potential role in early diagnosis and prognosis. Among them, microRNAs (miRNAs or miRs) are short non-coding RNAs that regulate gene expression in various diseases, including OSCC. Several miRNAs are being researched as non-invasive biomarkers as well as novel therapeutic targets in the treatment of OSCC. MiR expression can be upregulated or downregulated in OSCC. Among the reported miRNAs, miR-1285 is an important miRNA found to be involved in OSCC. The aim of the current study was to quantify the levels of miR-1285 in OSCC samples and to validate their potential role as biomarkers for OSCC detection. METHODS: Sixteen samples of cancer tissue and normal tissue were evaluated from a total of 25 patients, in the study, conducted in the Department of Oral and Maxillofacial Surgery. The tissues were processed for H&E staining and gene expression analysis of miR-1285. The samples were collected after proper informed consent from the patients. Total RNA isolated was reverse transcribed into cDNA which was used in the gene expression analysis using qRT-PCR. RESULTS: The histopathological examination confirmed the OSCC cases and the gene expression analysis revealed that miR-1285 was significantly downregulated in OSCC tissues. Since miR-1285 showed significant difference between the OSCC and normal tissues it could be postulated as a potential biomarker and therapeutic target for OSCC. CONCLUSIONS: Further in-vitro and in-vivo studies could validate their functional role in OSCC.

Prospective study: expression levels of microRNA-7-3p and its target STAT3 in head and neck cancer.

BACKGROUND: Head and neck cancer (HNC) is the seventh most prevalent type of cancer in the globe, and it encompasses a wide range of tumors that affect the oral, facial and neck region. Despite breakthroughs in treatment strategies, patients survival has not increased substantially in the last few decades. Therefore, there is need for quick and reliable biomarkers and therapeutic targets for the treatment of HNC. Interestingly, microRNAs (miRNAs) are a small non-coding RNAs (ncRNAs) that have a role in the post-transcriptional regulation of gene expression. Thus, the aim of the study is to evaluate the role of miR-7-3p in the HNC and normal tissues. METHODS: A total of 25 HNC and normal tissues were collected from the Department of Oral and Maxillofacial Surgery, Saveetha Dental College and Hospitals. Bioinformatic tool (TargetScan) was used to predict the target for miR-7-3p. The tissue samples were processed for Hematoxylin and Eosin staining and following that total RNA was extracted and analyzed for expression studies using RT-qPCR. RESULTS: The bioinformatic analysis of the current study have revealed that STAT3 is a direct target for miR-7-3p. The histopathological examination showed damaged epithelial cells and keratin pool formation was observed in HNC tissue. Our results have also revealed that the miR-7-3p levels were significantly reduced and STAT3 levels were significantly higher in the HNC tissues when compared to the normal tissues. CONCLUSIONS: MiR-7-3p can be used as a prognostic, diagnostic biomarker and therapeutic target for the treatment of HNC.

Drivers of heterogeneity in synovial fibroblasts in rheumatoid arthritis.

Inflammation of non-barrier immunologically quiescent tissues is associated with a massive influx of blood-borne innate and adaptive immune cells. Cues from the latter are likely to alter and expand activated states of the resident cells. However, local communications between immigrant and resident cell types in human inflammatory disease remain poorly understood. Here, we explored drivers of fibroblast-like synoviocyte (FLS) heterogeneity in inflamed joints of patients with rheumatoid arthritis using paired single-cell RNA and ATAC sequencing, multiplexed imaging and spatial transcriptomics along with in vitro modeling of cell-extrinsic factor signaling. These analyses suggest that local exposures to myeloid and T cell-derived cytokines, TNF, IFN-γ, IL-1ß or lack thereof, drive four distinct FLS states some of which closely resemble fibroblast states in other disease-affected tissues including skin and colon. Our results highlight a role for concurrent, spatially distributed cytokine signaling within the inflamed synovium.

MicroRNAs as important players in regulating cancer through PTEN/PI3K/AKT signalling pathways.

Cancer being the leading cause of mortality has become a great threat worldwide. Current cancer therapeutics lack specificity and have side effects due to a lack of understanding of the molecular mechanisms and signalling pathways involved in carcinogenesis. In recent years, researchers have been focusing on several signalling pathways to pave the way for novel therapeutics. The PTEN/PI3K/AKT pathway is one of the important pathways involved in cell proliferation and apoptosis, leading to tumour growth. In addition, the PTEN/PI3K/AKT axis has several downstream pathways that could lead to tumour malignancy, metastasis and chemoresistance. On the other hand, microRNAs (miRNAs) are important regulators of various genes leading to disease pathogenesis. Hence studies of the role of miRNAs in regulating the PTEN/PI3K/AKT axis could lead to the development of novel therapeutics for cancer. Thus, in this review, we have focused on various miRNAs involved in the carcinogenesis of various cancer via the PTEN/PI3K/AKT axis.

Inhibition of SARS-CoV2 viral infection with natural antiviral plants constituents: An in-silico approach.

Background and Objective: In 2019, a novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) was declared pandemic. Advancement in computational technology has provided rapid and cost-effective techniques to test the efficacy of newer therapeutic agents. This study evaluated some of the potent phytochemicals obtained from AYUSH (Ayurveda, Yoga, Naturopathy, Unani, Siddha, Sowa-Rigpa, and Homeopathy)-listed medicinal plants against SARS-CoV-2 proteins using computational techniques. Materials and methods: The potential SARS-CoV-2 protein targets were utilized to study the ligand-protein binding characteristics. The bioactive agents were obtained from ashwagandha, liquorice, amla, neem, tinospora, pepper, and stevia. Ivermectin was utilized as a reference agent to compare its efficacy with phytochemicals. Results: The computational analysis suggested that all the bioactive components from the selected plants possessed negative docking scores (ranging from -6.24 to -10.53). The phytoconstituents were well absorbed, distributed in the body except for the CNS, metabolized by liver enzymes, well cleared from the body, and well tolerated. The data suggest that AYUSH-recommended plants demonstrated therapeutic efficacy against SARS CoV-2 virus infection with significantly reduced toxicity. Conclusion: The phytoconstituents were found to hinder the early stages of infection, such as absorption and penetration, while ivermectin prevented the passage of genetic material from the cytoplasm to the nucleus. Additional research involving living tissues and clinical trials are suggested to corroborate the computational findings.

Diagnostic and Therapeutic Application of Exosomal microRNAs Inducing Inflammation in Type 2 Diabetes Mellitus.

Diabetes mellitus is a class of noncommunicable chronic metabolic disorders marked by hyperglycemia due to insulin production, insulin action or both and has reached epidemic levels around the world. The two most frequent types of diabetes are type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Despite substantial improvements in the knowledge and treatment of DM, the associated incidence and mortality rates remain steadily increased. Reliable markers for the early detection, monitoring and focused treatment of DM are desperately required. Conversely, microRNAs (miRNAs) have received much significance due to their regulatory involvement in gene expression. Fascinatingly, exosomes can be enclosed into miRNAs to transport or distribute them into the target cells or tissues in which they have a physiological regulatory action. Thus, exosomal miRNAs are proving to be important regulators in the establishment and maintenance of DM, however, further mode of action will be needed to investigate in order to fully comprehend the pathophysiological process. Hereby, this review outlines the recent findings on the role of exosomal miRNAs intending to understand the precise function in diagnostic and therapeutic aspects in T2DM disease.

The role of microRNAs on the pathogenesis, diagnosis and management of portal hypertension in patients with chronic liver disease.

INTRODUCTION: Portal hypertension (PH) is the elevated pressure in the portal vein, which results in poor functioning of the liver and is influenced by various factors like liver cirrhosis, nonalcoholic fatty liver disease, schistosomiasis, thrombosis, and angiogenesis. Though the diagnosis and treatment have been advanced, early diagnosis of the disease remains a challenge, and the diagnosis methods are often invasive. Hence, the clear understanding of the molecular mechanisms of PH can give rise to the development of novel biomarkers which can pave way for early diagnosis in noninvasive methods, and also the identification of target genes can elucidate an efficient therapeutic target. AREAS COVERED: PubMed and Embase database was used to search articles with search terms 'Portal Hypertension' or 'pathophysiology' and 'diagnosis' and 'treatment' or "role of miRNAs in portal hypertension. EXPERT OPINION: Interestingly, biomarkers like microRNAs (miRNAs) have been studied for their potential role in various diseases including hypertension. In recent years, miRNAs have been proved to be an efficient biomarker and therapeutic target and few studies have assessed the roles of miRNAs in PH. The present paper highlights the potential roles of miRNAs in PH.

MicroRNAs in the epigenetic regulation of disease progression in Parkinson's disease.

Parkinson's disease (PD) is a multifactorial neurodegenerative condition with symptoms such as resting tremor, rigidity, bradykinesia (slowness of moment), and postural instability. Neuroinflammation plays a significant part in the onset and progression of neurodegeneration in a wide range of disorders, including PD. The loss of dopaminergic neurons in the substantia nigra (SN) is thought to be the primary cause of PD disease progression. However, other neurotransmitter systems like serotoninergic, glutamatergic, noradrenergic, adrenergic, cholinergic, tryptaminergic, and peptidergic appear to be affected as well. Epigenetic regulation of gene expression is emerging as an influencing factor in the pathophysiology of PD. In recent years, epigenetic regulation by microRNAs (miRNAs) has been discovered to play an important function in the disease progression of PD. This review explores the role of miRNAs and their signaling pathways in regulating gene expression from development through neurodegeneration and how these mechanisms are linked to the pathophysiology of PD, emphasizing potential therapeutic interventions.

CRISPR/Cas9 and next generation sequencing in the personalized treatment of Cancer.

BACKGROUND: Cancer is caused by a combination of genetic and epigenetic abnormalities. Current cancer therapies are limited due to the complexity of their mechanism, underlining the need for alternative therapeutic approaches. Interestingly, combining the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR/Cas9) system with next-generation sequencing (NGS) has the potential to speed up the identification, validation, and targeting of high-value targets. MAIN TEXT: Personalized or precision medicine combines genetic information with phenotypic and environmental characteristics to produce healthcare tailored to the individual and eliminates the constraints of "one-size-fits-all" therapy. Precision medicine is now possible thanks to cancer genome sequencing. Having advantages over limited sample requirements and the recent development of biomarkers have made the use of NGS a major leap in personalized medicine. Tumor and cell-free DNA profiling using NGS, proteome and RNA analyses, and a better understanding of immunological systems, are all helping to improve cancer treatment choices. Finally, direct targeting of tumor genes in cancer cells with CRISPR/Cas9 may be achievable, allowing for eliminating genetic changes that lead to tumor growth and metastatic capability. CONCLUSION: With NGS and CRISPR/Cas9, the goal is no longer to match the treatment for the diagnosed tumor but rather to build a treatment method that fits the tumor exactly. Hence, in this review, we have discussed the potential role of CRISPR/Cas9 and NGS in advancing personalized medicine.

Liquid biopsy: Exosomal microRNAs as novel diagnostic and prognostic biomarkers in cancer.

BACKGROUND: Detecting cancer at an early stage before clinical manifestation could be an effective strategy to decrease cancer mortality. Thus, identifying liquid biopsy biomarkers with high efficacy could be a promising approach for non-invasive diagnosis of cancer. MAIN TEXT: Liquid biopsies are increasingly used as a supplement to biopsy, as it enables disease progression to be detected months before clinical and radiographic confirmation. Many bodily fluids contain exosomal microRNAs (miRNAs) which could provide a new class of biomarkers for early and minimally invasive cancer diagnosis due to the stability of miRNAs in exosomes. In this review, we mainly focused on the exosomal miRNAs (liquid biopsy) as biomarkers in the diagnosis and prognosis of various cancers. CONCLUSION: Exosomal miRNAs can be used as diagnostic and prognosis biomarkers that provide unique insights and a more dynamic perspective of the progression and therapeutic responses in various malignancies. Therefore, the development of novel and more sensitive technologies that exploit exosomal miRNAs should be a priority for cancer management.

Dietary microRNAs: Current status and perspective in food science.

Food safety and health conditions are global issues that are primarily caused by insufficient nutrition or contaminated food, which have enormous social, economic, and public health implications. Foodomics study mainly involves nutrigenomics, nutrigenetics, and nutritional epigenetics, which help in finding the correlation between genetic variation and nutrient-driven epigenetic alterations that are suggested as a primary challenge to nutritional needs. Micro-ribonucleic acids (miRNAs) are non-coding RNA molecules that have recently gained in popularity as a result of their critical roles in gene regulation and nutritional studies. In this commentary, the relevance of miRNAs to human nutrition is discussed. This study emphasizes the importance of dietary miRNAs based on numerous independent studies, which have explained the unique characteristics of dietary miRNAs in terms of gene expression regulation mechanism. There is an urgent requirement of measurement techniques to detect miRNA in food and evolutionary samples. These techniques may be helpful to find even low levels of miRNAs because of their high susceptibility and selectivity. There is a desperate requisite to evaluate the impact of dietary supplement compounds on circulating and tissue miRNAs. Food science studies in humans may aid in the identification of novel biomarkers and other necessary mode of action of certain dietary compounds, with the goal of facilitating how nutrients and bioactive components can influence miRNAs and enforce biological effects. PRACTICAL APPLICATIONS: Dietary microRNAs may be helpful to find even the low levels of miRNAs due to their high susceptibility and selectivity. There is also desperate need to evaluate the impact of dietary supplement compounds effect on circulating and tissue miRNAs. There is also requirement for new analytical tools to study the role of gene regulations and nutrition in different diseases. The quality of dietary miRNAs should be investigated, particularly the exogenous types which are used as high doses in food supplements. It would also be of great interest to use antagomir technology in food science research, in addition to omics technology. Dietary miRNAs may also aid in the identification of novel biomarkers. These are some of the practical applications of dietary miRNAs.