Unraveling the miRNA Puzzle in Atherosclerosis: Revolutionizing Diagnosis, Prognosis, and Therapeutic Approaches.

PURPOSE OF REVIEW: To eradicate atherosclerotic diseases, novel biomarkers, and future therapy targets must reveal the burden of early atherosclerosis (AS), which occurs before life-threatening unstable plaques form. The chemical and biological features of microRNAs (miRNAs) make them interesting biomarkers for numerous diseases. We summarized the latest research on miRNA regulatory mechanisms in AS progression studies, which may help us use miRNAs as biomarkers and treatments for difficult-to-treat diseases. RECENT FINDINGS: Recent research has demonstrated that miRNAs have a regulatory function in the observed changes in gene and protein expression during atherogenesis, the process that leads to atherosclerosis. Several miRNAs play a role in the development of atherosclerosis, and these miRNAs could potentially serve as non-invasive biomarkers for atherosclerosis in various regions of the body. These miRNAs have the potential to serve as biomarkers and targets for early treatment of atherosclerosis. The start and development of AS require different miRNAs. It reviews new research on miRNAs affecting endothelium, vascular smooth muscle, vascular inflammation, lipid retention, and cholesterol metabolism in AS. A miRNA gene expression profile circulates with AS everywhere. AS therapies include lipid metabolism, inflammation reduction, and oxidative stress inhibition. Clinical use of miRNAs requires tremendous progress. We think tiny miRNAs can enable personalized treatment.

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.

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.

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.

The potential role of miRNAs in the pathogenesis of testicular germ cell tumors - A Focus on signaling pathways interplay.

Testicular germ cell tumors (TGCTs) are the most common testicular neoplasms in adolescents and young males. Understanding the genetic basis of TGCTs represents a growing need to cope with the increased incidence of these neoplasms. Although the cure rates have been comparatively increased, investigation of mechanisms underlying the incidence, progression, metastasis, recurrence, and therapy resistance is still necessary. Early diagnosis and non-compulsory clinical therapeutic agents without long-term side effects are now required to reduce the cancer burden, especially in the younger age groups. MicroRNAs (miRNAs) control an extensive range of cellular functions and exhibit a pivotal action in the development and spreading of TGCTs. Because of their dysregulation and disruption in function, miRNAs have been linked to the malignant pathophysiology of TGCTs by influencing many cellular functions involved in the disease. These biological processes include increased invasive and proliferative perspective, cell cycle dysregulation, apoptosis disruption, stimulation of angiogenesis, epithelial-mesenchymal transition (EMT) and metastasis, and resistance to certain treatments. Herein, we present an up-to-date review of the biogenesis of miRNAs, miRNA regulatory mechanisms, clinical challenges, and therapeutic interventions of TGCTs, and role of nanoparticles in the treatment of TGCTs.

miRNAs orchestration of testicular germ cell tumors - Particular emphasis on diagnosis, progression and drug resistance.

Testicular cancer (TC) is one of the most frequently incident solid tumors in males. A growing prevalence has been documented in developed countries. Although recent advances have made TC an exceedingly treatable cancer, numerous zones in TC care still have divisive treatment decisions. In addition to physical examination and imaging techniques, conventional serum tumor markers have been traditionally used for the diagnosis of testicular germ cell tumors (TGCT). Unlike other genital and urinary tract tumors, recent research methods have not been broadly used in TGCTs. Even though several challenges in TC care must be addressed, a dedicated group of biomarkers could be particularly beneficial to help classify patient risk, detect relapse early, guide surgery decisions, and tailor follow-up. Existing tumor markers (Alpha-fetoprotein, human chorionic gonadotrophin, and lactate dehydrogenase) have limited accuracy and sensitivity when used as diagnostic, prognostic, or predictive markers. At present, microRNAs (miRNA or miR) play a crucial role in the process of several malignancies. The miRNAs exhibit pronounced potential as novel biomarkers since they reveal high stability in body fluids, are easily detected, and are relatively inexpensive in quantitative assays. In this review, we aimed to shed light on the recent novelties in developing microRNAs as diagnostic and prognostic markers in TC and discuss their clinical applications in TC management.

Long non-coding RNAs and rheumatoid arthritis: Pathogenesis and clinical implications.

Long non-coding RNAs (lncRNAs) are a class of noncoding RNAs with a length larger than 200 nucleotides that participate in various diseases and biological processes as they can control gene expression by different mechanisms. Rheumatoid arthritis (RA) is an inflammatory autoimmune disorder characterized by symmetrical destructive destruction of distal joints as well as extra-articular involvement. Different studies have documented and proven the abnormal expression of lncRNAs in RA patients. Various lncRNAs have proven potential as biomarkers and targets for diagnosing, prognosis and treating RA. This review will focus on RA pathogenesis, clinical implications, and related lncRNA expressions that help to identify new biomarkers and treatment targets.

miRNAs as potential game-changers in bone diseases: Future medicinal and clinical uses.

MicroRNAs (miRNAs), short, highly conserved non-coding RNA, influence gene expression by sequential mechanisms such as mRNA breakdown or translational repression. Many biological processes depend on these regulating substances, thus changes in their expression have an impact on the maintenance of cellular homeostasis and result in the emergence of a variety of diseases. Relevant studies have shown in recent years that miRNAs are involved in many stages of bone development and growth. Additionally, abnormal production of miRNA in bone tissues has been closely associated with the development of numerous bone disorders, such as osteonecrosis, bone cancer, and bone metastases. Many pathological processes, including bone loss, metastasis, the proliferation of osteosarcoma cells, and differentiation of osteoblasts and osteoclasts, are under the control of miRNAs. By bringing together the most up-to-date information on the clinical relevance of miRNAs in such diseases, this study hopes to further the study of the biological features of miRNAs in bone disorders and explore their potential as a therapeutic target.

An emphasis on the interaction of signaling pathways highlights the role of miRNAs in the etiology and treatment resistance of gastric cancer.

Gastric cancer (GC) is 4th in incidence and mortality rates globally. Several genetic and epigenetic factors, including microRNAs (miRNAs), affect its initiation and progression. miRNAs are short chains of nucleic acids that can regulate several cellular processes by controlling their gene expression. So, dysregulation of miRNAs expressions is associated with GC initiation, progression, invasion capacity, apoptosis evasions, angiogenesis, promotion and EMT enhancement. Of important pathways in GC and controlled by miRNAs are Wnt/ß-catenin signaling, HMGA2/mTOR/P-gp, PI3K/AKT/c-Myc, VEGFR and TGFb signaling. Hence, this review was conducted to review an updated view of the role of miRNAs in GC pathogenesis and their modulatory effects on responses to different GC treatment modalities.

miRNAs as potential game-changers in renal cell carcinoma: Future clinical and medicinal uses.

Renal cell carcinoma (RCC) has the highest mortality rate of all genitourinary cancers, and its prevalence has grown over time. While RCC can be surgically treated and recurrence is only probable in a tiny proportion of patients, early diagnosis is crucial. Mutations in a large number of oncogenes and tumor suppressor genes contribute to pathway dysregulation in RCC. MicroRNAs (miRNAs) have considerable promise as biomarkers for detecting cancer due to their special combination of properties. Several miRNAs have been proposed as a diagnostic or monitoring tool for RCC based on their presence in the blood or urine. Moreover, the expression profile of particular miRNAs has been associated with the response to chemotherapy, immunotherapy, or targeted therapeutic options like sunitinib. The goal of this review is to go over the development, spread, and evolution of RCC. Also, we emphasize the outcomes of studies that examined the use of miRNAs in RCC patients as biomarkers, therapeutic targets, or modulators of responsiveness to treatment modalities.

The role of miRNAs in liver diseases: Potential therapeutic and clinical applications.

MicroRNAs (miRNAs) are a class of short, non-coding RNAs that function post-transcriptionally to regulate gene expression by binding to particular mRNA targets and causing destruction of the mRNA or translational inhibition of the mRNA. The miRNAs control the range of liver activities, from the healthy to the unhealthy. Considering that miRNA dysregulation is linked to liver damage, fibrosis, and tumorigenesis, miRNAs are a promising therapeutic strategy for the evaluation and treatment of liver illnesses. Recent findings on the regulation and function of miRNAs in liver diseases are discussed, with an emphasis on miRNAs that are highly expressed or enriched in hepatocytes. Alcohol-related liver illness, acute liver toxicity, viral hepatitis, hepatocellular carcinoma, liver fibrosis, liver cirrhosis, and exosomes in chronic liver disease all emphasize the roles and target genes of these miRNAs. We briefly discuss the function of miRNAs in the etiology of liver diseases, namely in the transfer of information between hepatocytes and other cell types via extracellular vesicles. Here we offer some background on the use of miRNAs as biomarkers for the early prognosis, diagnosis, and assessment of liver diseases. The identification of biomarkers and therapeutic targets for liver disorders will be made possible by future research into miRNAs in the liver, which will also help us better understand the pathogeneses of liver diseases.

Ellagic acid ameliorates high fructose-induced hyperuricemia and non-alcoholic fatty liver in Wistar rats: Focusing on the role of C1q/tumor necrosis factor-related protein-3 and ATP citrate lyase.

AIMS: High-fructose intake (HF) represents an inducible risk factor for non-alcoholic fatty liver disease (NAFLD). Present study aimed to illustrate the effect of HF diet (HFD) on the induction of NAFLD, hyperuricemia and role of ellagic acid as modulator. MAIN METHODS: Twenty-four adult male albino rats were randomly divided into four groups (6/each). The first group received normal chow diet only while the others received 60 % HFD for 4 weeks and subdivided later into 3 groups. The first and second groups received allopurinol and ellagic acid, respectively while the third group received HFD only for extra 4 weeks. KEY FINDINGS: Rats fed on HFD for 8 weeks displayed body weight gain, insulin resistance (IR), hyperglycemia, dyslipidemia, hyperuricemia with increased oxidative stress and hepatic lipogenic enzymes such as ATP citrate lyase (ACL), aldolase B, and fatty acid synthase (FAS), sterol regulatory element-binding protein 1 (SERBP-1c). C1q /tumor necrosis factor-related protein -3 (CTRP3), and phosphorylated AMP-activated protein kinase (p-AMPK) however showed significant decreases. Ellagic acid or allopurinol administration significantly decreased serum lipids, uric acid, glucose, insulin levels and hepatic contents of enzymes. Malondialdehyde (MDA), FAS, aldolase B, SERBP-1c, and xanthine oxidase (XO) hepatic contents showed significant decreases along with glutathione (GSH) increase as compared to fructose group where ellagic acid was more remarkable compared with allopurinol. SIGNIFICANCE: Our findings indicated that ellagic acid had alleviated HFD-induced hyperuricemia, its associated NAFLD pattern as mediated through activation of CTRP3 and inhibition of ACL activities in a pattern more remarkable than allopurinol.

Response of faba bean to intercropping, biological and chemical control against broomrape and root rot diseases.

Multispecies cropping systems contribute to sustainable agriculture with multiple ecosystem services. Effects of intercropping of various crops with faba beans on growth and yield parameters and disease severity of root rot, damping off and broomrape were investigated. This study was implemented in the laboratory, greenhouse and field to investigate the effect of the intercropping systems (fenugreek + faba bean, lupine + faba bean, garlic + faba bean and sole faba bean). The intercropping systems were combined with the application of arbuscular mycorrhiza fungi (AMF) and yeast as bio-control agents, compared to chemical application of herbicides (Glyphosate) and fungicides (Rizolex-T50), to control rot root diseases and broomrape weeds, Orobanche spp., of faba bean plants in vivo and under the naturally infested field. In vitro, yeast and Rizolex-T50 significantly inhibited mycelial growth of root pathogenic fungi. Intercropping with garlic and/or application of Rizolex-T, significantly decreased the incidence and disease index of root rot and damping-off diseases, meanwhile increased percentage of survival plants. In vivo, intercropping with fenugreek and/or application of Glyphosate, significantly reduced the number/weight of spikes/plot of broomrapes. Intercropping with fenugreek combined with AMF application promoted crop growth and significantly increased yield components. The AMF enhanced seed yield/ha when applied to the intercropping of faba bean + fenugreek and faba bean + garlic, showing the highest seed yield/ha with 3.722 and 3.568 ton/ha, respectively. Intercropping of faba bean with garlic integrated with AMF revealed the highest values of LER, 2.45, and net return, 2341 US$/ha. Our results suggested that using faba bean-garlic intercrop along with AMF inoculation can reduce root rot disease, damping off and broomrapes, as well as enhance the profitability of Egyptian farmer and sustainable production.

Maximizing land utilization efficiency and competitive indices of roselle and cluster bean plants by intercropping pattern and foliar spray with lithovit.

To maximize the land utilization efficiency of Hibiscus sabdariffa L. (roselle) and Cyamopsis tetragonoloba, Taub (cluster bean), this experiment was executed successfully at Experimental Farm, Fac. Agric., Zagazig Univ., Egypt during 2018 and 2019 at summer season. Intercropping pattern treatments as main plots (sole planting of each component as control, 1: 2, 1: 3 and 2: 3 of roselle: cluster bean as row ratio, respectively), lithovit as sub-plots (CO2 nano-material) at various rates (0.0, 2.0, 4.0 and 6.0 g/l) as well as their interaction effects were estimated. In addition, from calculating competitive indices, it was clear that, the highest land equivalent ratio (abbreviated as LER), area time equivalent ratio (abbreviated as ATER), land utilization efficiency percentage (abbreviated as LUE%) and relative crowding coefficient (abbreviated as RCC) values 1.24 and 1.12, 1.16 and 1.03, 120.57% and 108.06% as well as 0.82 and 0.41 were achieved by the treatment of intercropping pattern of 1 row of roselle alternating with 3 rows of cluster bean during the 1st and 2nd seasons, respectively. The highest values in this concern were achieved with 1: 3 planting pattern combined with 0.0 lithovit rate in the first seasonas well as 1: 2 planting pattern combined with 6.0 g/l lithovit rate in the second one. Also, the highest values of competitive ratio for roselle (Crr) were achieved by combination between 4.0 g/l lithovit rate under 1: 3 pattern, in contrary, the highest values of competitive ratio for cluster bean (Crc) were recorded by combination between 1: 2 pattern with 2.0 g/l lithovit rate in first season. Regardless of the planting patterns combined with different lithovit rates, aggressivity, based on the results, therewas a positive sign for roselle and a negative sign for the intercropped cluster bean, indicating that roselle was dominant, while, cluster bean was dominated.

Algae as Bio-fertilizers: Between current situation and future prospective.

Bio-fertilization is a sustainable agricultural practice that includes using bio-fertilizers to increase soil nutrient content resulting in higher productivity. Soil micro-flora has been exposed to improve soil fertility and increase biomass productivity and identified as a correct environmentally friendly bio-based fertilizer for pollution-free agricultural applies. The majority of cyanobacteria can fix nitrogen from the atmosphere and several species including Anabaena sp., Nostoc sp., and Oscillatoria angustissima is known to be effective cyanobacterial based bio fertilizers. Acutodesmus dimorphus, Spirulina platensis Chlorella vulgaris, Scenedesmus dimorphus, Anabaena azolla, and Nostoc sp. are some of the green microalgae and cyanobacteria species that have been successfully used as bio fertilizers to boost crop growth. Also, Chlorella vulgaris is one of the most commonly used microalgae in bio fertilizer studies. The addition of seaweed species that are Sargassum sp. and Gracilaria verrucosa leads to chemical changes as a soil fertility indicator on clay and sandy soils, and the addition of seaweed conditioner to soil can improve its organic content, return pH to normal, and reduce C/N ratio in both sandy and clay soil. This review provides an effective approach to increase soil fertility via environmentally friendly bio-based fertilizer using micro and macro algae. Instead of the usage of inorganic and organic fertilizers that have polluted impacts to soil as aggregation of heavy metals, in addition to there their human carcinogenic effects.

Controlling of Meloidgyne incognita (Tylenchida: Heteroderidae) using nematicides, Linum usitatissimum extract and certain organic acids on four peppers cultivars under greenhouse conditions.

Organic acids and plant extracts, which have a nemacidal action and may be used instead of nematicides that pollute the environment, are one way for controlling the pepper root-knot nematode. We provide in this study for a first time a new strategy for management Meloidgyne incognita (Kofoid and White) by using organic acids and plant extract compared to nematicides on four peppers cultivars (Super amarr, Super mard, Super noura and Werta) under greenhouse conditions compared to nematicides. This study aimed to evaluate 0.1% of organic acids (humic and salicylic acid) and 0.1% of Linum usitatissimum extract on plant parameters of pepper varieties (Super amarr, Super mard, Super noura and Werta) and control of M. incognita under greenhouse conditions compared to four nematicides (Oxamyl 24% SL, Fosthiazates 75% EC, Ethoprophos N40% EC and Fenamiphos 40% EC). Our data obtained four nematicides were more effectiveness than other treatments in reduced galls and egg masses of M. incognita. Whilst, humic and salicylic acids have remarkably higher nematicidal activity than L. usitatissimum in all lines of pepper. Therefore, plant extract and organic acids may be used a best alternative of nematicides to control PPNs and caused the longitudinal growth of plant. Also, ultimately reduce environmental risk from nematicide pollution.