Decoding the secrets of longevity: unraveling nutraceutical and miRNA-Mediated aging pathways and therapeutic strategies.

MicroRNAs (miRNAs) are short RNA molecules that are not involved in coding for proteins. They have a significant function in regulating gene expression after the process of transcription. Their participation in several biological processes has rendered them appealing subjects for investigating age-related disorders. Increasing data indicates that miRNAs can be influenced by dietary variables, such as macronutrients, micronutrients, trace minerals, and nutraceuticals. This review examines the influence of dietary factors and nutraceuticals on the regulation of miRNA in relation to the process of aging. We examine the present comprehension of miRNA disruption in age-related illnesses and emphasize the possibility of dietary manipulation as a means of prevention or treatment. Consolidating animal and human research is essential to validate the significance of dietary miRNA control in living organisms, despite the abundance of information already provided by several studies. This review elucidates the complex interaction among miRNAs, nutrition, and aging, offering valuable insights into promising areas for further research and potential therapies for age-related disorders.

The potential role of miRNAs in the pathogenesis of schizophrenia - A focus on signaling pathways interplay.

microRNAs (miRNAs) play a crucial role in brain growth and function. Hence, research on miRNA has the potential to reveal much about the etiology of neuropsychiatric diseases. Among these, schizophrenia (SZ) is a highly intricate and destructive neuropsychiatric ailment that has been thoroughly researched in the field of miRNA. Despite being a relatively recent area of study about miRNAs and SZ, this discipline has advanced enough to justify numerous reviews that summarize the findings from the past to the present. However, most reviews cannot cover all research, thus it is necessary to synthesize the large range of publications on this topic systematically and understandably. Consequently, this review aimed to provide evidence that miRNAs play a role in the pathophysiology and progression of SZ. They have also been investigated for their potential use as biomarkers and therapeutic targets.

Tuning into miRNAs: A comprehensive analysis of their impact on diagnosis, and progression in asthma.

Asthma is a diverse inflammatory illness affecting the respiratory passages, leading to breathing challenges, bouts of coughing and wheezing, and, in severe instances, significant deterioration in quality of life. Epigenetic regulation, which involves the control of gene expression through processes such as post-transcriptional modulation of microRNAs (miRNAs), plays a role in the evolution of various asthma subtypes. In immune-mediated diseases, miRNAs play a regulatory role in the behavior of cells that form the airway structure and those responsible for defense mechanisms in the bronchi and lungs. They control various cellular processes such as survival, growth, proliferation, and the production of chemokines and immune mediators. miRNAs possess chemical and biological characteristics that qualify them as suitable biomarkers for diseases. They allow for the categorization of patients to optimize drug selection, thus streamlining clinical management and decreasing both the economic burden and the necessity for critical care related to the disease. This study provides a concise overview of the functions of miRNAs in asthma and elucidates their regulatory effects on the underlying processes of the disease. We provide a detailed account of the present status of miRNAs as biomarkers for categorizing asthma, identifying specific asthma subtypes, and selecting appropriate treatment options.

The emerging role of miRNAs in epilepsy: From molecular signatures to diagnostic potential.

Epilepsy is a medical condition characterized by intermittent seizures accompanied by changes in consciousness. Epilepsy significantly impairs the daily functioning and overall well-being of affected individuals. Epilepsy is a chronic neurological disorder characterized by recurrent seizures resulting from various dysfunctions in brain activity. The molecular processes underlying changes in neuronal structure, impaired apoptotic responses in neurons, and disruption of regenerative pathways in glial cells in epilepsy remain unknown. MicroRNAs (miRNAs) play a crucial role in regulating apoptosis, autophagy, oxidative stress, neuroinflammation, and the body's regenerative and immune responses. miRNAs have been shown to influence many pathogenic processes in epilepsy including inflammatory responses, neuronal necrosis and apoptosis, dendritic growth, synaptic remodeling, and other processes related to the development of epilepsy. Therefore, the purpose of our current analysis was to determine the role of miRNAs in the etiology and progression of epilepsy. Furthermore, they have been examined for their potential application as biomarkers and therapeutic targets.

Unveiling the regulatory role of miRNAs in stroke pathophysiology and diagnosis.

Stroke, a major global cause of mortality, leads to a range of problems for those who survive. Besides its brutal events, stroke also tends to have a characteristic of recurrence, making it a complex disease involving intricate regulatory networks. One of the major cellular regulators is the non-coding RNAs (ncRNA), specifically microRNAs (miRNAs), thus the possible functions of miRNAs in the pathogenesis of stroke are discussed as well as the possibility of using miRNA-based therapeutic approaches. Firstly, the molecular mechanisms by which miRNAs regulate vital physiological processes, including synaptic plasticity, oxidative stress, apoptosis, and the integrity of the blood-brain barrier (BBB) are reviewed. The miRNA indirectly impacts stroke outcomes by regulating BBB function and angiogenesis through the targeting of transcription factors and angiogenic factors. In addition, the tendency for some miRNAs to be upregulated in response to hypoxia, which is a prevalent phenomenon in stroke and various neurological disorders, highlights the possibility that it controls hypoxia-inducible factor (HIF) signaling and angiogenesis, thereby influencing the integrity of the BBB as examples of the discussed mechanisms. Furthermore, this review explores the potential therapeutic targets that miRNAs may offer for stroke recovery and highlights their promising capacity to alleviate post-stroke complications. This review provides researchers and clinicians with valuable resources since it attempts to decipher the complex network of miRNA-mediated mechanisms in stroke. Additionally, the review addresses the interplay between miRNAs and stroke risk factors as well as clinical applications of miRNAs as diagnostic and prognostic markers.

The emerging role of miRNAs in myocardial infarction: From molecular signatures to therapeutic targets.

Globally, myocardial infarction (MI) and other cardiovascular illnesses have long been considered the top killers. Heart failure and mortality are the results of myocardial apoptosis, cardiomyocyte fibrosis, and cardiomyocyte hypertrophy, all of which are caused by MI. MicroRNAs (miRNAs) play a crucial regulatory function in the progression and advancement of heart disease following an MI. By consolidating the existing data on miRNAs, our aim is to gain a more comprehensive understanding of their role in the pathological progression of myocardial injury after MI and to identify potential crucial target pathways. Also included are the primary treatment modalities and their most recent developments. miRNAs have the ability to regulate both normal and pathological activity, including the key signaling pathways. As a result, they may exert medicinal benefits. This review presents a comprehensive analysis of the role of miRNAs in MI with a specific emphasis on their impact on the regeneration of cardiomyocytes and other forms of cell death, such as apoptosis, necrosis, and autophagy. Furthermore, the targets of pro- and anti-MI miRNAs are comparatively elucidated.

miRNAs as modulators of neuroinflammation and excitotoxicity: Implications for stroke therapeutics.

Stroke is a widespread neurological disorder associated with physical disabilities, mortality, and economic burden. In recent decades, substantial progress has been achieved in reducing the impact of this public health problem. However, further understanding of the pathophysiology of stroke and the underlying genetic pathways is required. The pathological mechanisms of stroke comprise multifaceted molecular cascades regulated by various microRNAs (miRNAs). An increasing number of studies have highlighted the role of miRNAs, which have received much attention during the last decades as an important class of post-transcriptional regulators. It was shown that miRNAs exert their role in the etiology of stroke via mediating excitotoxicity and neuroinflammation. Additionally, miRNAs could be helpful as non-invasive or minimally invasive biomarkers and therapeutic agents. Thus, the current review focused on the interplay of these miRNAs in stroke pathology to upgrade the existing therapeutic strategies.

Unraveling the role of miRNAs in the diagnosis, progression, and therapeutic intervention of Alzheimer's disease.

Alzheimer's disease (AD) is a multifaceted, advancing neurodegenerative illness that is responsible for most cases of neurological impairment and dementia in the aged population. As the disease progresses, affected individuals may experience cognitive decline, linguistic problems, affective instability, and behavioral changes. The intricate nature of AD reflects the altered molecular mechanisms participating in the affected human brain. MicroRNAs (miRNAs, miR) are essential for the intricate control of gene expression in neurobiology. miRNAs exert their influence by modulating the transcriptome of brain cells, which typically exhibit substantial genetic activity, encompassing gene transcription and mRNA production. Presently, comprehensive studies are being conducted on AD to identify miRNA-based signatures that are indicative of the disease pathophysiology. These findings can contribute to the advancement of our understanding of the mechanisms underlying this disorder and can inform the development of therapeutic interventions based on miRNA and related RNA molecules. Therefore, this comprehensive review provides a detailed holistic analysis of the latest advances discussing the emerging role of miRNAs in the progression of AD and their possible application as potential biomarkers and targets for therapeutic interventions in future studies.

Unraveling the role of miRNAs in the diagnosis, progression, and therapeutic intervention of Parkinson's disease.

Parkinson's disease (PD) is a debilitating neurological disorder characterized by the impairment of the motor system, resulting in symptoms such as resting tremor, cogwheel rigidity, bradykinesia, difficulty with gait, and postural instability. The occurrence of striatal dopamine insufficiency can be attributed to a notable decline in dopaminergic neurons inside the substantia nigra pars compacta. Additionally, the development of Lewy bodies serves as a pathological hallmark of PD. While current therapy approaches for PD aim to preserve dopaminergic neurons or replenish dopamine levels in the brain, it is important to acknowledge that achieving complete remission of the condition remains elusive. MicroRNAs (miRNAs, miR) are a class of small, non-coding ribonucleic acids involved in regulating gene expression at the post-transcriptional level. The miRNAs play a crucial part in the underlying pathogenic mechanisms of several neurodegenerative illnesses, including PD. The aim of this review is to explore the role of miRNAs in regulating genes associated with the onset and progression of PD, investigate the potential of miRNAs as a diagnostic tool, assess the effectiveness of targeting specific miRNAs as an alternative therapeutic strategy to impede disease advancement, and discuss the utilization of newly developed nanoparticles for delivering miRNAs as neurodegenerative therapies.

A multidisciplinary approach to the antioxidant and hepatoprotective activities of Arbutus pavarii Pampan fruit; in vitro and in Vivo biological evaluations, and in silico investigations.

The Libyan Strawberry, Arbutus pavarii Pampan (ARB), is an endemic Jebel Akhdar plant used for traditional medicine. This study presents the antioxidant and hepatoprotective properties of ARB fruit-extract. ARB phytochemical analysis indicated the presence of 354.54 GAE and 36.2 RE of the phenolics and flavonoids. LC-MS analysis identified 35 compounds belonging to phenolic acids, procyanidins, and flavonoid glycosides. Gallic acid, procyanidin dimer B3, ß-type procyanidin trimer C, and quercetin-3-O-glucoside were the major constituents of the plant extract. ARB administration to paracetamol (PAR)-intoxicated rats reduced serum ALT, AST, bilirubin, hepatic tissue MDA and proinflammatory markers; TNF-α and IL-6 with an increase in tissue GSH level and SOD activity. Histological and immunohistochemical studies revealed that ARB restored the liver histology and significantly reduced the tissue expression of caspase 3, IL-1B, and NF-KB in PAR-induced liver damage. Docking analysis disclosed good binding affinities of some compounds with XO, COX-1, 5-LOX, and PI3K.

Unraveling the role of miRNAs in the diagnosis, progression, and drug resistance of oral cancer.

Oral cancer (OC) is a widely observed neoplasm on a global scale. Over time, there has been an increase in both its fatality and incidence rates. Oral cancer metastasis is a complex process that involves a number of cellular mechanisms, including invasion, migration, proliferation, and escaping from malignant tissue through either lymphatic or vascular channels. MicroRNAs (miRNAs) are a crucial class of short non-coding RNAs recognized as significant modulators of diverse cellular processes and exert a pivotal influence on the carcinogenesis pathway, functioning either as tumor suppressors or as oncogenes. It has been shown that microRNAs (miRNAs) have a role in metastasis at several stages, including epithelial-mesenchymal transition, migration, invasion, and colonization. This regulation is achieved by targeting key genes involved in these pathways by miRNAs. This paper aims to give a contemporary analysis of OC, focusing on its molecular genetics. The current literature and emerging advancements in miRNA dysregulation in OC are thoroughly examined. This project would advance OC diagnosis, prognosis, therapy, and therapeutic implications.

Harnessing the power of miRNAs: The molecular architects of asthma pathogenesis and potential targets for therapeutic innovation.

Asthma is a chronic non-communicable respiratory disease that is characterized by airway inflammation and hyperreactivity. Defective functions of airway smooth muscle and dysregulated signaling pathways play a crucial role in the pathogenesis of asthma. Anti-inflammatories and targeted therapy are mainly used for the treatment of asthma. Recent studies have investigated the role of non-coding RNAs, especially microRNAs (miRNAs; miR) in regulating gene expression and their involvement in the dysfunctional signaling pathways. In immune-mediated diseases, including asthma, miRNAs govern the actions of cells that form the airway structure and those responsible for the defense mechanisms in the bronchi and lungs. miRNAs control cell survival, proliferation, and growth, as well as the cells' capacity to produce and release chemokines and immune mediators. Moreover, miRNAs have an important role in the response to therapeutic interventions. Collectively, this review highlights the regulatory roles of miRNAs in modulating the different signaling pathways and therapeutic responses in asthma. Patients who suffer from asthma, particularly those with severe disease characteristics, may benefit from the prospective treatment options that include targeting miRNAs in order to reduce airway inflammation, hyperreactivity, and mucus production.

Decoding the role of miRNAs in oral cancer pathogenesis: A focus on signaling pathways.

Oral cancer (OC) is the predominant type originating in the head and neck region. The incidence of OC is mostly associated with behavioral risk factors, including tobacco smoking and excessive alcohol intake. Additionally, there is a lower but still significant association with viral infections such as human papillomaviruses and Epstein-Barr viruses. Furthermore, it has been observed that heritable genetic variables are linked to the risk of OC, in addition to the previously mentioned acquired risk factors. The current absence of biomarkers for OC diagnosis contributes to the frequent occurrence of advanced-stage diagnoses among patients. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs, and circular RNAs, have been observed to exert a significant effect on the transcriptional control of target genes involved in cancer, either through direct or indirect mechanisms. miRNAs are a class of short ncRNAs that play a role in regulating gene expression by enabling mRNA degradation or translational repression at the post-transcriptional phase. miRNAs are known to play a fundamental role in the development of cancer and the regulation of oncogenic cell processes. Notch signaling, PTEN/Akt/mTOR axis, KRAS mutation, JAK/STAT signaling, P53, EGFR, and the VEGFs have all been linked to OC, and miRNAs have been shown to have a role in all of these. The dysregulation of miRNA has been identified in cases of OC and is linked with prognosis.

Deciphering signaling pathway interplay via miRNAs in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a highly invasive form of lung cancer that adversely affects the pleural and other linings of the lungs. MPM is a very aggressive tumor that often has an advanced stage at diagnosis and a bad prognosis (between 7 and 12 months). When people who have been exposed to asbestos experience pleural effusion and pain that is not explained, MPM should be suspected. After being diagnosed, most MPM patients have a one- to four-year life expectancy. The life expectancy is approximately six months without treatment. Despite the plethora of current molecular investigations, a definitive universal molecular signature has yet to be discovered as the causative factor for the pathogenesis of MPM. MicroRNAs (miRNAs) are known to play a crucial role in the regulation of gene expression at the posttranscriptional level. The association between the expression of these short, non-coding RNAs and several neoplasms, including MPM, has been observed. Although the incidence of MPM is very low, there has been a significant increase in research focused on miRNAs in the past few years. In addition, miRNAs have been found to have a role in various regulatory signaling pathways associated with MPM, such as the Notch signaling network, Wnt/ß-catenin, mutation of KRAS, JAK/STAT signaling circuit, protein kinase B (AKT), and Hedgehog signaling pathway. This study provides a comprehensive overview of the existing understanding of the roles of miRNAs in the underlying mechanisms of pathogenic symptoms in MPM, highlighting their potential as viable targets for therapeutic interventions.

Possible role of miRNAs in pheochromocytoma pathology - Signaling pathways interaction.

Pheochromocytoma (PCC) is a type of neuroendocrine tumor that originates from adrenal medulla or extra-adrenal chromaffin cells and results in the production of catecholamine. Paroxysmal hypertension and cardiovascular crises were among the clinical signs experienced by people with PCC. Five-year survival of advanced-stage PCC is just around 40% despite the identification of various molecular-level fundamentals implicated in these pathogenic pathways. MicroRNAs (miRNAs, miRs) are a type of short, non-coding RNA (ncRNA) that attach to the 3'-UTR of a target mRNA, causing translational inhibition or mRNA degradation. Evidence is mounting that miRNA dysregulation plays a role in the development, progression, and treatment of cancers like PCC. Hence, this study employs a comprehensive and expedited survey to elucidate the potential role of miRNAs in the development of PCC, surpassing their association with survival rates and treatment options in this particular malignancy.

From diagnosis to resistance: a symphony of miRNAs in pheochromocytoma progression and treatment response.

Pheochromocytoma (PCC) is a neuroendocrine tumor that produces and secretes catecholamine from either the adrenal medulla or extra-adrenal locations. MicroRNAs (miRNAs, miR) can be used as biomarkers to detect cancer or the return of a previously treated disease. Blood-borne miRNAs might be envisioned as noninvasive markers of malignancy or prognosis, and new studies demonstrate that microRNAs are released in body fluids as well as tissues. MiRNAs have the potential to be therapeutic targets, which would greatly increase the restricted therapy options for adrenal tumors. This article aims to consolidate and synthesize the most recent studies on miRNAs in PCC, discussing their potential clinical utility as diagnostic and prognostic biomarkers while also addressing their limitations.

The role of miRNAs in multiple sclerosis pathogenesis, diagnosis, and therapeutic resistance.

In recent years, microRNAs (miRNAs) have gained increased attention from researchers around the globe. Although it is twenty nucleotides long, it can modulate several gene targets simultaneously. Their mal expression is a signature of various pathologies, and they provide the foundation to elucidate the molecular mechanisms of each pathology. Among the debilitating central nervous system (CNS) disorders with a growing prevalence globally is the multiple sclerosis (MS). Moreover, the diagnosis of MS is challenging due to the lack of disease-specific biomarkers, and the diagnosis mainly depends on ruling out other disabilities. MS could adversely affect patients' lives through its progression, and only symptomatic treatments are available as therapeutic options, but an exact cure is yet unavailable. Consequently, this review hopes to further the study of the biological features of miRNAs in MS and explore their potential as a therapeutic target.

The interplay between toxoplasmosis and host miRNAs: Mechanisms and consequences.

Toxoplasmosis is one of the highly prevalent zoonotic diseases worldwide caused by the parasite Toxoplasma gondii (T. gondii). The infection with T. gondii could pass unidentified in immunocompetent individuals; however, latent cysts remain dormant in their digestive tract, but they could be shed and excreted with feces infesting the environment. However, active toxoplasmosis can create serious consequences, particularly in newborns and infected persons with compromised immunity. These complications include ocular toxoplasmosis, in which most cases cannot be treated. Additionally, it caused many stillbirths and miscarriages. Circulating miRNAs are important regulatory molecules ensuring that the normal physiological role of various organs is harmonious. Upon infection with T. gondii, the tightly regulated miRNA profile is disrupted to favor the parasite's survival and further participate in the disease pathogenesis. Interestingly, this dysregulated profile could be useful in acute and chronic disease discrimination and in providing insights into the pathomechanisms of the disease. Thus, this review sheds light on the various roles of miRNAs in signaling pathways regulation involved in the pathogenesis of T. gondii and provides insights into the application of miRNAs clinically for its diagnosis and prognosis.

Melodic maestros: Unraveling the role of miRNAs in the diagnosis, progression, and drug resistance of malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a highly lethal form of pleural cancer characterized by a scarcity of effective therapeutic interventions, resulting in unfavorable prognoses for afflicted individuals. Besides, many patients experience substantial consequences from being diagnosed in advanced stages. The available diagnostic, prognostic, and therapeutic options for MPM are restricted in scope. MicroRNAs (miRNAs) are a subset of small, noncoding RNA molecules that exert significant regulatory influence over several cellular processes within cell biology. A wide range of miRNAs have atypical expression patterns in cancer, serving specific functions as either tumor suppressors or oncomiRs. This review aims to collate, epitomize, and analyze the latest scholarly investigations on miRNAs that are believed to be implicated in the dysregulation leading to MPM. miRNAs are also discussed concerning their potential clinical usefulness as diagnostic and prognostic biomarkers for MPM. The future holds promising prospects for enhancing diagnostic, prognostic, and therapeutic modalities for MPM, with miRNAs emerging as a potential trigger for such advancements.

Rumex vesicarius L. boosts the effectiveness of sorafenib in triple-negative breast cancer by downregulating BCl2, mTOR, and JNK, and upregulating p21 expression.

BACKGROUND/AIM: Triple-negative breast cancer (TNBC) is characterized by poor prognosis, rapid progression, serious clinical behavior, an elevated risk of metastasis, and resistance to standard treatments. Traditional medicine practitioners value Rumex vesicarius L. (RMV) for a variety of reasons, including the plant's antioxidant capabilities. Our study's goals were to ascertain the efficacy of RMV alone and in combination with sorafenib (SOR) against the aggressive TNBC cell line (MDA-MB-231) and use in vitro and in silico analysis to deduce the fundamental mechanism of action. METHODS: In the current study, molecular operating environment (MOE, 2019.0102) software was used for performing molecular docking. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used to determine the cytotoxicity of RMV, SOR or RMV/SOR combination against the TNBC cell line MDA-MB-231 cells. The effects of RMV, SOR, and RMV and SOR combining on mRNAs expressions of the target genes including mTOR, p21, JNK, and BCl2 were evaluated. In TNBC cells, the relative expressions of mRNAs of the genes were examined by using real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: In our experiments, we discovered that both RMV extracts alone and in combination with SOR considerably reduced cancer cell proliferation (IC50 = 0.83 and 0.19 µM, respectively). Additionally, the expression of the tumor suppressor gene p21 was elevated whereas the expression of the invasion and anti-apoptosis genes BCl2, mTOR, and JNK were significantly decreased after treatment with RMV and SOR. Based on in silico analysis, it was found that RMV extract contains bioactive chemicals with a high affinity for inhibiting JNK and VEGFR-2. CONCLUSION: In conclusion, in vitro and in silico investigations show that the RMV extract improves the anticancer efficiency of SOR through molecular processes involving the downregulation of mTOR, BCl2, and JNK1 and overexpression of p21 tumor suppressor gene. Finally, we suggest conducting additional in vivo investigations on RMV and its bioactive components to verify their potential in cancer therapy.