ABSTRACT
Epilepsy, affecting approximately 1% of the global population, manifests as recurring seizures and is heavily influenced by genetic factors. Recent advancements in genetic technologies have revolutionized our understanding of epilepsy's genetic landscape. Key studies, such as the discovery of mutations in ion channels (e.g., SCN1A and SCN2A), neurotransmitter receptors (e.g., GABRA1), and synaptic proteins (e.g., SYNGAP1, KCNQ2), have illuminated critical pathways underlying epilepsy susceptibility and pathogenesis. Genome-wide association studies (GWAS) have identified specific genetic variations linked to epilepsy risk, such as variants near SCN1A and PCDH7, enhancing diagnostic accuracy and enabling personalized treatment strategies. Moreover, epigenetic mechanisms, including DNA methylation (e.g., MBD5), histone modifications (e.g., HDACs), and non-coding RNAs (e.g., miR-134), play pivotal roles in altering gene expression and synaptic plasticity, contributing to epileptogenesis. These discoveries offer promising avenues for therapeutic interventions aimed at improving outcomes for epilepsy patients. Genetic testing has become essential in clinical practice, facilitating precise diagnosis and tailored management approaches based on individual genetic profiles. Furthermore, insights into epigenetic regulation suggest novel therapeutic targets for developing more effective epilepsy treatments. In summary, this review highlights significant progress in understanding the genetic and epigenetic foundations of epilepsy. By integrating findings from key studies and specifying genes involved in epigenetic modifications, we underscore the potential for advanced therapeutic strategies in this complex neurological disorder, emphasizing the importance of personalized medicine approaches in epilepsy management.
Subject(s)
Epilepsy , Genetic Predisposition to Disease , Humans , Epilepsy/genetics , Epilepsy/diagnosis , Epilepsy/therapy , Genetic Predisposition to Disease/genetics , Genome-Wide Association Study , Epigenesis, Genetic/genetics , Animals , Genetic Testing/methodsABSTRACT
The gut microbiome (GM) has been identified as a crucial factor in the development and progression of various diseases, including cancer. In the case of prostate cancer, commensal bacteria and other microbes are found to be associated with its development. Recent studies have demonstrated that the human GM, including Bacteroides, Streptococcus, Bacteroides massiliensis, Faecalibacterium prausnitzii, Eubacterium rectale, and Mycoplasma genitalium, are involved in prostate cancer development through both direct and indirect interactions. However, the pathogenic mechanisms of these interactions are yet to be fully understood. Moreover, the microbiota influences systemic hormone levels and contributes to prostate cancer pathogenesis. Currently, it has been shown that supplementation of prebiotics or probiotics can modify the composition of GM and prevent the onset of prostate cancer. The microbiota can also affect drug metabolism and toxicity, which may improve the response to cancer treatment. The composition of the microbiome is crucial for therapeutic efficacy and a potential target for modulating treatment response. However, their clinical application is still limited. Additionally, GM-based cancer therapies face limitations due to the complexity and diversity of microbial composition, and the lack of standardized protocols for manipulating gut microbiota, such as optimal probiotic selection, treatment duration, and administration timing, hindering widespread use. Therefore, this review provides a comprehensive exploration of the GM's involvement in prostate cancer pathogenesis. We delve into the underlying mechanisms and discuss their potential implications for both therapeutic and diagnostic approaches in managing prostate cancer. Through this analysis, we offer valuable insights into the pivotal role of the microbiome in prostate cancer and its promising application in future clinical settings.
ABSTRACT
In recent years, there has been a global increase in cases of male infertility. There are about 30 million cases of male infertility worldwide and male reproductive health is showing rapid decline in last few decades. It is now recognized as a potential risk factor for developing certain types of cancer, particularly genitourinary malignancies like testicular and prostate cancer. Male infertility is considered a potential indicator of overall health and an early biomarker for cancer. Cases of unexplained male factor infertility have high levels of oxidative stress and oxidative DNA damage and this induces both denovo germ line mutations and epimutations due to build up of 8-hydroxy 2 deoxygunaosine abase which is highly mutagenic and also induces hypomethylation and genomic instability. Consequently, there is growing evidence to explore the various factors contributing to an increased cancer risk. Currently, the available prognostic and predictive biomarkers associated with semen characteristics and cancer risk are limited but gaining significant attention in clinical research for the diagnosis and treatment of elevated cancer risk in the individual and in offspring. The male germ cell being transcriptionally and translationally inert has a highly truncated repair mechanism and has minimal antioxidants and thus most vulnerable to oxidative injury due to environmental factors and unhealthy lifestyle and social habits. Therefore, advancing our understanding requires a thorough evaluation of the pathophysiologic mechanisms at the DNA, RNA, protein, and metabolite levels to identify key biomarkers that may underlie the pathogenesis of male infertility and associated cancer. Advanced methodologies such as genomics, epigenetics, proteomics, transcriptomics, and metabolomics stand at the forefront of cutting-edge approaches for discovering novel biomarkers, spanning from infertility to associated cancer types. Henceforth, in this review, we aim to assess the role and potential of recently identified predictive and prognostic biomarkers, offering insights into the success of assisted reproductive technologies, causes of azoospermia and idiopathic infertility, the impact of integrated holistic approach and lifestyle modifications, and the monitoring of cancer susceptibility, initiation and progression. Comprehending these biomarkers is crucial for providing comprehensive counselling to infertile men and cancer patients, along with their families.
Subject(s)
Infertility, Male , Humans , Male , Infertility, Male/genetics , Infertility, Male/diagnosis , Prognosis , Biomarkers, Tumor/genetics , Neoplasms/genetics , Neoplasms/diagnosis , Risk Factors , Biomarkers/metabolismABSTRACT
Helminth parasites modulate the host immune system to ensure a long-lasting asymptomatic form of infection generally, mediated by the secretion of immunomodulatory molecules and one such molecule is a homologue of human host cytokine, Macrophage migratory Inhibitory Factor (hMIF). In this study, we sought to understand the role of homologue of hMIF from the lymphatic filarial parasite, Wuchereria bancrofti (Wba-MIF2), in the immunomodulation of the Streptozotocin (STZ)-induced Type1 Diabetes Mellitus (T1DM) animal model. Full-length recombinant Wba-MIF2 was expressed and found to have both oxidoreductase and tautomerase activities. Wba-MIF2 recombinant protein was treated to STZ induced T1DM animals, and after 5 weeks pro-inflammatory (IL-1, IL-2, IL-6, TNF-α, IFN-γ) and anti-inflammatory (IL-4, IL-10) cytokines and gene expressions were determined in sera samples and spleen respectively. Pro-inflammatory and anti-inflammatory cytokine levels were significantly (p<0.05) up-regulated and down-regulated respectively, in the STZ-T1DM animals, as compared to treated groups. Histopathology showed macrophage infiltration and greater damage of islets of beta cells in the pancreatic tissue of STZ-T1DM animals, than Wba-MIF2 treated STZ-T1DM animals. The present study clearly showed the potential of Wba-MIF2 as an immunomodulatory molecule, which could modulate the host immune system in the STZ-T1DM mice model from a pro-inflammatory to anti-inflammatory milieu.
Subject(s)
Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 1 , Filarioidea , Macrophage Migration-Inhibitory Factors , Parasites , Humans , Animals , Mice , Wuchereria bancrofti , Macrophage Migration-Inhibitory Factors/genetics , Macrophage Migration-Inhibitory Factors/metabolism , Parasites/metabolism , Streptozocin , Immunologic Factors , Diabetes Mellitus, Experimental/genetics , Anti-Inflammatory Agents , Intramolecular OxidoreductasesABSTRACT
Glaucoma stands as a leading global cause of blindness, affecting millions. It entails optic nerve damage and vision loss, categorized into open-angle and closed-angle glaucoma with subtypes like POAG, ACG, XFG, PCG, PDG, and developmental glaucoma. The pathophysiological and genetic factors behind glaucoma remain partially understood, with past studies linking intraocular pressure (IOP) levels to retinal ganglion cell death. Open-angle glaucoma involves elevated resistance to aqueous outflow via the trabecular meshwork, while angle-closure glaucoma typically sees drainage pathways obstructed by the iris. Genes have been identified for POAG, ACG, XFG, PCG, PDG, and developmental glaucoma, allowing for early-onset detection and the emergence of gene therapy as an effective treatment. Nevertheless, diagnostic and treatment options have their constraints, necessitating large-scale, well-designed studies to deepen our grasp of genetics' role in glaucoma's pathogenesis. This review delves into glaucoma's risk factors, pathophysiology, genetics, diagnosis, and available treatment options, including gene therapy. Additionally, it suggests alternative therapies like yoga and meditation as adjunct treatments for glaucoma prevention. Overall, this review advances our comprehension of the pathophysiology and genetic associations of glaucoma while highlighting the potential of gene therapy as a treatment avenue. Further research is imperative to fully elucidate the genetic mechanisms underpinning glaucoma and to devise effective treatments.
Subject(s)
Glaucoma, Open-Angle , Glaucoma , Humans , Glaucoma/diagnosis , Glaucoma/genetics , Glaucoma/therapy , Trabecular Meshwork/metabolism , Optic Nerve/pathology , Intraocular Pressure/geneticsABSTRACT
BACKGROUND: As per estimates by WHO in 2021 almost half of the world's population was at risk of malaria and > 0.6 million deaths were attributed to malaria. Therefore, the present study was aimed to explore the antimalarial activity of extracts derived from the leaves of the plant Anacardium occidentale L., which has been used traditionally for the treatment of malaria. Different extracts of A. occidentale leaves were prepared and tested for their inhibitory activity against recombinant P. falciparum transketolase (rPfTK) enzyme, in vitro. Further, growth inhibitory activity against cultivated blood stage P. falciparum parasites (3D7 strain), was studied using SYBR Green fluorescence-based in vitro assays. Acute toxicity of the hydro alcoholic extracts of leaves of A. occidentale (HELA) at different concentrations was evaluated on mice and Zebra fish embryos. HELA showed 75.45 ± 0.35% inhibitory activity against the recombinant PfTk and 99.31 ± 0.08% growth inhibition against intra-erythrocytic stages of P. falciparum at the maximum concentration (50 µg/ml) with IC50 of 4.17 ± 0.22 µg/ml. The toxicity test results showed that the heartbeat, somite formation, tail detachment and hatching of embryos were not affected when Zebra fish embryos were treated with 0.1 to 10 µg/ml of the extract. However, at higher concentrations of the extract, at 48 h (1000 µg/ml) and 96 h (100 µg/ml and 1000 µg/ml, respectively) there was no heartbeat in the fish embryos. In the acute oral toxicity tests performed on mice, the extract showed no toxicity up to 300 mg/kg body weight in mice. CONCLUSION: The hydro-alcoholic extract of leaves of A. occidentale L. showed potent antimalarial activity against blood stage P. falciparum. Based on the observed inhibitory activity on the transketolase enzyme of P. falciparum it is likely that this enzyme is the target for the development of bioactive molecules present in the plant extracts. The promising anti-malarial activity of purified compounds from leaves of A. occidentale needs to be further explored for development of new anti-malarial therapy.
Subject(s)
Anacardium , Antimalarials , Malaria, Falciparum , Malaria , Animals , Mice , Antimalarials/toxicity , Plasmodium falciparum , Transketolase/therapeutic use , Zebrafish , Malaria/drug therapy , Malaria/parasitology , Malaria, Falciparum/drug therapy , Plant Extracts/pharmacologyABSTRACT
Dengue and chikungunya are two important mosquito-borne infections which are known to occur extensively in tropical and subtropical areas. Presently, there is no treatment for these viral diseases. In vitro antiviral screening of 25 extracts prepared from the plants of Vitex negundo, Plumeria alba, Ancistrocladus heyneanus, Bacopa monnieri, Anacardium occidentale, Cucurbita maxima, Simarouba glauca, and Embelia ribes using different solvents and four purified compounds (anacardic acid, chloroquinone, glaucarubinone, and methyl gallate) were carried out for their anti-dengue virus (DENV) and anti-chikungunya virus (CHIKV) activities. Maximum nontoxic concentrations of the chloroform, methanol, ethyl acetate, petroleum ether, dichloromethane, and hydroalcoholic extracts of eight plants were used. The antiviral activity was assessed by focus-forming unit assay, quantitative real-time RT-PCR, and immunofluorescence assays. Extracts from Plumeria alba, Ancistrocladus heyneanus, Bacopa monnieri, and Cucurbita maxima showed both anti-DENV and CHIKV activity while extract from Vitex negundo showed only anti-DENV activity. Among the purified compounds, anacardic acid, chloroquinone and methyl gallate showed anti-dengue activity while only methyl gallate had anti-chikungunya activity. The present study had identified the plant extracts with anti-dengue and anti-chikungunya activities, and these extracts can be further characterized for finding effective phytopharmaceutical drugs against dengue and chikungunya.
Subject(s)
Chikungunya Fever , Chikungunya virus , Dengue Virus , Dengue , Plants, Medicinal , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Chikungunya Fever/drug therapy , Dengue/drug therapy , Plant Extracts/pharmacology , Plant Extracts/therapeutic useABSTRACT
Different types of thiosemicarbazone derivatives were designed and tested for their Drug-Like Molecular (DLM) nature by using Lipinski and Veber rules. Subsequently, compounds with DLM properties were synthesized and characterized by spectral methods. In vitro antimalarial activity studies of the synthesized thiosemicarbazone derivatives have been carried out against Plasmodium falciparum, 3D7 strain using fluorescence assay method and found that the compounds, (E)-2-(1-(4-fluorophenyl)ethylidene)hydrazine-1-carbothioamide (6), (E)-2-(1-(3-bromophenyl) ethylidene) hydrazine-1-carbothioamide (15) and (E)-2-(3,4,5-trimethoxybenzylidene) hydrazine-1-carbothioamide (29) showed notable antimalarial activity with EC50 values of 13.54⯵M, 15.83⯵M and 14.52⯵M respectively.