Identification of hub genes and potential networks by centrality network analysis of PCR amplified Fusarium oxysporum f. sp. lycopersici EF1α gene.

BACKGROUND: Fusarium wilt is a devastating soil-borne fungal disease of tomato across the world. Conventional method of disease prevention including usage of common pesticides and methods like soil solarisation are usually ineffective in the treatment of this disease. Therefore, there is an urgent need to identify virulence related genes in the pathogen which can be targeted for fungicide development. RESULTS: Pathogenicity testing and phylogenetic classification of the pathogen used in this study confirmed it as Fusarium oxysporum f. sp. lycopersici (Fol) strain. A recent discovery indicates that EF1α, a protein with conserved structural similarity across several fungal genera, has a role in the pathogenicity of Magnaporthe oryzae, the rice blast fungus. Therefore, in this study we have done structural and functional classification of EF1α to understand its role in pathogenicity of Fol. The protein model of Fol EF1α was created using the template crystal structure of the yeast elongation factor complex EEF1A:EEF1BA which showed maximum similarity with the target protein. Using the STRING online database, the interactive information among the hub genes of EF1α was identified and the protein-protein interaction network was recognized using the Cytoscape software. On combining the results of functional analysis, MCODE, CytoNCA and CytoHubba 4 hub genes including Fol EF1α were selected for further investigation. The three interactors of Fol EF1α showed maximum similarity with homologous proteins found in Neurospora crassa complexed with the known fungicide, cycloheximide. Through the sequence similarity and PDB database analysis, homologs of Fol EF1α were found: EEF1A:EEF1BA in complex with GDPNP in yeast and EF1α in complex with GDP in Sulfolobus solfataricus. The STITCH database analysis suggested that EF1α and its other interacting partners interact with guanosine diphosphate (GDPNP) and guanosine triphosphate (GTP). CONCLUSIONS: Our study offers a framework for recognition of several hub genes network in Fusarium wilt that can be used as novel targets for fungicide development. The involvement of EF1α in nucleocytoplasmic transport pathway suggests that it plays role in GTP binding and thus apart from its use as a biomarker, it may be further exploited as an effective target for fungicide development. Since, the three other proteins that were found to be tightly associated Fol EF1α have shown maximum similarity with homologous proteins of Neurospora crassa that form complex with fungicide- Cycloheximide. Therefore, we suggest that cycloheximide can also be used against Fusarium wilt disease in tomato. The active site cavity of Fol EF1α can also be determined for computational screening of fungicides using the homologous proteins observed in yeast and Sulfolobus solfataricus. On this basis, we also suggest that the other closely associated genes that have been identified through STITCH analysis, they can also be targeted for fungicide development.

An updated view of bacterial endophytes as antimicrobial agents against plant and human pathogens.

Bacterial endophytes are a crucial component of the phytomicrobiome, playing an essential role in agriculture and industries. Endophytes are a rich source of bioactive compounds, serving as natural antibiotics that can be effective in combating antibiotic resistance in pathogens. These bacteria interact with host plants through various processes such as quorum sensing, chemotaxis, antibiosis, and enzymatic activity. The current paper focuses on how plants benefit extensively from endophytic bacteria and their symbiotic relationship in which the microbes enhance plant growth, nitrogen fixation, increase nutrient uptake, improve defense mechanisms, and act as antimicrobial agents against pathogens. Moreover, it highlights some of the bioactive compounds produced by endophytes.

Impact of Epley's Manoeuvre on Quality of Life in Patients with Posterior Semicircular Canal Benign Paroxysmal Positional Vertigo: A Pre- and Post-Treatment Analysis.

Benign paroxysmal positional vertigo (BPPV) is a common vestibular disorder, predominantly affecting the posterior semicircular canal (PSC), and significantly impacts the quality of life (QoL) of patients. This study assesses the effectiveness of Epley's manoeuvre in improving QoL in patients with PSC-BPPV. This prospective analytical study, conducted at a tertiary care centre from January 2021 to December 2022, included 93 adult patients diagnosed with PSC-BPPV via the Dix-Hallpike test. Participants were evaluated using the dizziness handicap inventory (DHI) and visual vertigo analogue score (VAS) at baseline and on days 3, 10, and 30 post-treatments with Epley's manoeuvre. Data analysis focused on changes in DHI and VAS scores to assess the impact of treatment. The cohort comprised 58.1% males and 41.9% females, with a significant majority over 50 years of age. Notably, 90% of patients reported improvement by the first follow-up. Both DHI and VAS scores showed a statistically significant decrease over the follow-up period (p < 0.05), indicating a reduction in perceived dizziness and visual vertigo symptoms post-treatment. Epley's manoeuvre effectively improves the QoL in patients with PSC-BPPV, as evidenced by significant reductions in DHI and VAS scores. This study contributes to the evidence supporting Epley's manoeuvre as a key intervention in PSC-BPPV treatment, emphasizing its role in enhancing patient outcomes in clinical practice.

Enhancing BPPV Treatment Outcomes: A Comparative Study of the Epley Maneuver with and without the Dizzy-Fix Training Device.

INTRODUCTION: This study evaluates the effectiveness of combining the Epley Maneuver with the Dizzy-Fix Training Device in treating Benign Paroxysmal Positional Vertigo (BPPV), aiming to enhance treatment outcomes and patient satisfaction. METHODS: In this randomized controlled trial, 50 patients diagnosed with posterior canal BPPV were allocated into two groups: one receiving the traditional Epley Maneuver and the other undergoing the Epley Maneuver supplemented with the Dizzy-Fix Training Device. Key measures included the proportion of symptom-free patients at one month, changes in the Visual Analogue Scale (VAS) and Dizziness Handicap Inventory (DHI) scores, the recurrence rate within one month, and patient satisfaction. RESULTS: The Dizzy-Fix group achieved a significantly higher symptom resolution rate by day 7 (90% vs. 60%) and reported greater patient satisfaction (4.5/5 vs. 3.8/5) compared to the Epley Maneuver alone group. Additionally, this group exhibited a more substantial decrease in DHI scores (from an average of 30 to 5) and a lower recurrence rate (10% vs. 40%) within the first month post-treatment. CONCLUSION: Incorporating the Dizzy-Fix Training Device with the Epley Maneuver significantly improves the management of BPPV, evidenced by faster symptom resolution, enhanced patient satisfaction, and reduced symptom recurrence. These findings underscore the value of integrating real-time visual feedback technologies in vestibular rehabilitation, promising better patient outcomes, and advancing the quality of care in BPPV treatment.

Dietary mung bean as promising food for human health: gut microbiota modulation and insight into factors, regulation, mechanisms and therapeutics-an update.

Plant-based functional foods have gained wider attention in current scenario with mung bean harboring several bioactive compounds with promising gut health benefits and pharmacological importance. Consumption of mung bean has a positive impact on beneficial gut microbes and microbial metabolite production. The effects of dietary mung bean on gut microbial homeostasis and the management of gut-related diseases along with the possible mechanism of action, have been highlighted through this review paving a way for a promising role of dietary mung bean as a functional food in the management of gut-related diseases for example mung bean peptides can help not only in treating prediabetes but also delaying the aging process by targeting the intestinal microflora. In addition, expanding our knowledge of how diets affect host health and disease, including the effects of mung bean dietary components on gut microbiota-derived metabolites, will eventually allow for the development of tailored diets and nutrients.

Tongue orthotopic xenografts to study fusion-negative rhabdomyosarcoma invasion and metastasis in live animals.

PAX3/7 fusion-negative rhabdomyosarcoma (FN-RMS) is a childhood mesodermal lineage malignancy with a poor prognosis for metastatic or relapsed cases. Limited understanding of advanced FN-RMS is partially attributed to the absence of sequential invasion and dissemination events and the challenge in studying cell behavior, using, for example, non-invasive intravital microscopy (IVM), in currently used xenograft models. Here, we developed an orthotopic tongue xenograft model of FN-RMS to study cell behavior and the molecular basis of invasion and metastasis using IVM. FN-RMS cells are retained in the tongue and invade locally into muscle mysial spaces and vascular lumen, with evidence of hematogenous dissemination to the lungs and lymphatic dissemination to lymph nodes. Using IVM of tongue xenografts reveals shifts in cellular phenotype, migration to blood and lymphatic vessels, and lymphatic intravasation. Insight from this model into tumor invasion and metastasis at the tissue, cellular, and subcellular level can guide new therapeutic avenues for advanced FN-RMS.

Microbiota-brain axis: Exploring the role of gut microbiota in psychiatric disorders - A comprehensive review.

Mental illness is a hidden epidemic in modern science that has gradually spread worldwide. According to estimates from the World Health Organization (WHO), approximately 10% of the world's population suffers from various mental diseases each year. Worldwide, financial and health burdens on society are increasing annually. Therefore, understanding the different factors that can influence mental illness is required to formulate novel and effective treatments and interventions to combat mental illness. Gut microbiota, consisting of diverse microbial communities residing in the gastrointestinal tract, exert profound effects on the central nervous system through the gut-brain axis. The gut-brain axis serves as a conduit for bidirectional communication between the two systems, enabling the gut microbiota to affect emotional and cognitive functions. Dysbiosis, or an imbalance in the gut microbiota, is associated with an increased susceptibility to mental health disorders and psychiatric illnesses. Gut microbiota is one of the most diverse and abundant groups of microbes that have been found to interact with the central nervous system and play important physiological functions in the human gut, thus greatly affecting the development of mental illnesses. The interaction between gut microbiota and mental health-related illnesses is a multifaceted and promising field of study. This review explores the mechanisms by which gut microbiota influences mental health, encompassing the modulation of neurotransmitter production, neuroinflammation, and integrity of the gut barrier. In addition, it emphasizes a thorough understanding of how the gut microbiome affects various psychiatric conditions.

Heavy metals toxicity on epigenetic modifications in the pathogenesis of Alzheimer's disease (AD).

Alzheimer's disease (AD) is a progressive decline in cognitive ability and behavior which eventually disrupts daily activities. AD has no cure and the progression rate varies unlikely. Among various causative factors, heavy metals are reported to be a significant hazard in AD pathogenesis. Metal-induced neurodegeneration has been focused globally with thorough research to unravel the mechanistic insights in AD. Recently, heavy metals suggested to play an important role in epigenetic alterations which might provide evidential results on AD pathology. Epigenetic modifications are known to play towards novel therapeutic approaches in treating AD. Though many studies focus on epigenetics and heavy metal implications in AD, there is a lack of research on heavy metal influence on epigenetic toxicity in neurological disorders. The current review aims to elucidate the plausible role of cadmium (Cd), iron (Fe), arsenic (As), copper (Cu), and lithium (Li) metals on epigenetic factors and the increase in amyloid beta and tau phosphorylation in AD. Also, the review discusses the common methods of heavy metal detection to implicate in AD pathogenesis. Hence, from this review, we can extend the need for future research on identifying the mechanistic behavior of heavy metals on epigenetic toxicity and to develop diagnostic and therapeutic markers in AD.

Molecular insights and promise of oncolytic virus based immunotherapy.

Discovering a therapeutic that can counteract the aggressiveness of this disease's mechanism is crucial for improving survival rates for cancer patients and for better understanding the most different types of cancer. In recent years, using these viruses as an anticancer therapy has been thought to be successful. They mostly work by directly destroying cancer cells, activating the immune system to fight cancer, and expressing exogenous effector genes. For the treatment of tumors, oncolytic viruses (OVs), which can be modified to reproduce only in tumor tissues and lyse them while preserving the healthy non-neoplastic host cells and reinstating antitumor immunity which present a novel immunotherapeutic strategy. OVs can exist naturally or be created in a lab by altering existing viruses. These changes heralded the beginning of a new era of less harmful virus-based cancer therapy. We discuss three different types of oncolytic viruses that have already received regulatory approval to treat cancer as well as clinical research using oncolytic adenoviruses. The primary therapeutic applications, mechanism of action of oncolytic virus updates, future views of this therapy will be covered in this chapter.

Artificial intelligence and machine learning algorithms in the detection of heavy metals in water and wastewater: Methodological and ethical challenges.

Heavy metals (HMs) enter waterbodies through various means, which, when exceeding a threshold limit, cause toxic effects both on the environment and in humans upon entering their systems. Recent times have seen an increase in such HM influx incident rates. This requires an instant response in this regard to review the challenges in the available classical methods for HM detection and removal. As well as provide an opportunity to explore the applications of artificial intelligence (AI) and machine learning (ML) for the identification and further redemption of water and wastewater from the HMs. This review of research focuses on such applications in conjunction with the available in-silico models producing worldwide data for HM levels. Furthermore, the effect of HMs on various disease progressions has been provided, along with a brief account of prediction models analysing the health impact of HM intoxication. Also discussing the ethical and other challenges associated with the use of AI and ML in this field is the futuristic approach intended to follow, opening a wide scope of possibilities for improvement in wastewater treatment methodologies.

Synbiotics as potent functional food: recent updates on therapeutic potential and mechanistic insight.

Synbiotics are the specific mixtures of prebiotics with probiotics intended to give health benefits to the host by stabilizing and supporting the gut microbiota.The prebiotic substance used in the synbiotics selectively favors the growth and metabolite production of probiotics. Gut microbiome dysbiosis may lead to generation and progression of various chronic diseases. Synbiotics act synergistically to modulate the gut ecosystem for improvement of metabolic health of the host. Probiotics have been found promising against various diseases being safer, effective, as an alternative or combinatorial therapy. Specific combinations of probiotics with suitable prebiotic substrate as synbiotics, may be the more effective therapeutic agents that can provide all benefits of probiotics as well as prebiotics. Though, effective combinations, dosage, mechanism of action, safety, cost effectiveness and other clinical investigations are required to be established along with other relevant aspects. Synbiotics have the potential to be functional food of importance in future. Present review summarizes the mechanistic overview of synbiotics related to gut microbiota, therapeutic potential and promising health benefits for human illnesses according to the available literature. In present scenario, synbiotics are more promising future alternatives as therapeutics to maintain healthy microbiota inside the host gut which directly affects the onset or development ofrelated disorders or diseases.

Biochemical changes, antioxidative profile, and efficacy of the bio-stimulant in plant defense response against Sclerotinia sclerotiorum in common bean (Phasaeolus vulgaris L.).

Sclerotinia sclerotiorum, is a highly destructive pathogen with widespread impact on common bean (Phasaeolus vulgaris L.) worldwide. In this work, we investigated the efficacy of microbial consortia in bolstering host defense against sclerotinia rot. Specifically, we evaluated the performance of a microbial consortia comprising of Trichoderma erinaceum (T51) and Trichoderma viride (T52) (referred to as the T4 treatment) in terms of biochemical parameters, alleviation of the ROS induced cellular toxicity, membrane integrity (measured as MDA content), nutrient profiling, and the host defense-related antioxidative enzyme activities. Our findings demonstrate a notable enhancement in thiamine content, exhibiting 1.887 and 1.513-fold higher in the T4 compared to the un-inoculated control and the T1 treatment (only S. sclerotiorum treated). Similarly, the total proline content exhibited 3.46 and 1.24-fold higher and the total phenol content was 4.083 and 2.625-fold higher in the T4 compared to the un-inoculated control and the T1 treatment, respectively. Likewise, a general trend was found for other antioxidative and non-oxidative enzyme activities. However, results found were approximately similar in T2 treatment (bioprimed with T51) or T3 treatments (bioprimed with T52). Further, host defense attribute (survival rate) under the pathogen challenged condition was maximum in the T4 (15.55 % disease incidence) compared to others. Therefore, bio priming with consortia could be useful in reducing the economic losses incited by S. sclerotiorum in common beans.

Does gut brain axis has an impact on Parkinson's disease (PD)?

Parkinson's Disease (PD) is becoming a growing global concern by being the second most prevalent disease next to Alzheimer's Disease (AD). Henceforth new exploration is needed in search of new aspects towards the disease mechanism and origin. Evidence from recent studies has clearly stated the role of Gut Microbiota (GM) in the maintenance of the brain and as a root cause of various diseases and disorders including other neurological conditions. In the case of PD, with an unknown etiology, the GM is said to have a larger impact on the disease pathophysiology. Although GM and its metabolites are crucial for maintaining the normal physiology of the host, it is an undeniable fact that there is an influence of GM in the pathophysiology of PD. As such the Enteroendocrine Cells (EECs) in the epithelium of the intestine are one of the significant regulators of the gut-brain axis and act as a communication mediator between the gut and the brain. The communication is established via the molecules of neuroendocrine which are said to have a crucial part in neurological diseases such as AD, PD, and other psychiatry-related disorders. This review is focused on understanding the proper role of GM and EECs in PD. Here, we also focus on some of the metabolites and compounds that can interact with the PD genes causing various dysfunctions in the cell and facilitating the disease conditions using bioinformatical tools. Various mechanisms concerning EECs and PD, their identification, the latest studies, and available current therapies have also been discussed.

Association of Biochemical Parameters and Screening for Mutations in the MCU Gene in Alzheimer's Disease Patients.

The most prevalent form of dementia, Alzheimer's disease (AD) is a chronic illness that is on the rise among the geriatric population. Even though research into its biochemical, genetic, and cytogenetic pathways has advanced, its aetiology is still unclear and complex. In this study, we recruited sixty-eight participants diagnosed with AD where the cytogenetic, biochemical parameters and genetic mutations were analysed. Our results revealed chromosomal aberrations such as aneuploidies in the peripheral blood of Alzheimer's disease patients. Biochemical parameters revealed no statistical significance in the study though a pattern could be observed in the serum levels. Further few novel mutations at the c.21 C > T, c.56G > A were observed in the MCU gene of mitochondrial calcium uniporter. All these findings reveal the need for a larger cohort study to gain a better and more detailed understanding of the aetiology of Alzheimer's disease.

A cooperativity between virus and bacteria during respiratory infections.

Respiratory tract infections remain the leading cause of morbidity and mortality worldwide. The burden is further increased by polymicrobial infection or viral and bacterial co-infection, often exacerbating the existing condition. Way back in 1918, high morbidity due to secondary pneumonia caused by bacterial infection was known, and a similar phenomenon was observed during the recent COVID-19 pandemic in which secondary bacterial infection worsens the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) condition. It has been observed that viruses paved the way for subsequent bacterial infection; similarly, bacteria have also been found to aid in viral infection. Viruses elevate bacterial infection by impairing the host's immune response, disrupting epithelial barrier integrity, expression of surface receptors and adhesion proteins, direct binding of virus to bacteria, altering nutritional immunity, and effecting the bacterial biofilm. Similarly, the bacteria enhance viral infection by altering the host's immune response, up-regulation of adhesion proteins, and activation of viral proteins. During co-infection, respiratory bacterial and viral pathogens were found to adapt and co-exist in the airways of their survival and to benefit from each other, i.e., there is a cooperative existence between the two. This review comprehensively reviews the mechanisms involved in the synergistic/cooperativity relationship between viruses and bacteria and their interaction in clinically relevant respiratory infections.

Hepatoprotective effects of natural drugs: Current trends, scope, relevance and future perspectives.

BACKGROUND: The liver is a well-known player in the metabolism and removal of drugs. Drug metabolizing enzymes in the liver detoxify drugs and xenobiotics, ultimately leading to the acquisition of homeostasis. However, liver toxicity and cell damage are not only related to the nature and dosage of a particular drug but are also influenced by other factors such as aging, immune status, environmental contaminants, microbial metabolites, gender, obesity, and expression of individual genes Furthermore, factors such as drugs, alcohol, and environmental contaminants could induce oxidative stress, thereby impairing the regenerative potential of the liver and causing several diseases. Persons suffering from other ailments and those with comorbidities are found to be more prone to drug-induced toxicities. Moreover, drug composition and drug-drug interactions could further aggravate the risk of drug-induced hepatotoxicity. A plethora of mechanisms are responsible for initiating liver cell damage and further aggravating liver cell injury, followed by impairment of homeostasis, ultimately leading to the generation of reactive oxygen species, immune-suppression, and oxidative stress. OBJECTIVE: To summarize the potential of phytochemicals and natural bioactive compounds to treat hepatotoxicity and other liver diseases. STUDY DESIGN: A deductive qualitative content analysis approach was employed to assess the overall outcomes of the research and review articles pertaining to hepatoprotection induced by natural drugs, along with analysis of the interventions. METHODS: An extensive literature search of bibliographic databases, including Web of Science, PUBMED, SCOPUS, GOOGLE SCHOLAR, etc., was carried out to understand the role of hepatoprotective effects of natural drugs. RESULTS: Bioactive natural products, including curcumin, resveratrol, etc., have been seen as neutralizing agents against the side effects induced by the drugs. Moreover, these natural products are dietary and are readily available; thus, could be supplemented along with drugs to reduce toxicity to cells. Probiotics, prebiotics, and synbiotics have shown promise of improving overall liver functioning, and these should be evaluated more extensively for their hepatoprotective potential. Therefore, selecting an appropriate natural product or a bioactive compound that is free of toxicity and offers a reliable solution for drug-induced liver toxicity is quintessential. CONCLUSIONS: The current review highlights the role of natural bioactive products in neutralizing drug-induced hepatotoxicity. Efforts have been made to delineate the possible underlying mechanism associated with the neutralization process.

Outpatient Clinical Markers for Laryngopharyngeal Reflux Disease: A Correlational Study.

Laryngopharyngeal reflux disease (LPRD) is the result of retrograde flow of gastric contents to the laryngopharynx which comes in contact with tissues of the upper aerodigestive tract. Due to ill defined criteria for diagnosis & followup, LPRD patients are underdiagnosed & undertreated. Reflux Symptom Index (RSI) and the Reflux Finding Score (RFS) are two clinical methods which can be utilised especially in the outpatient setup. This study was done with the aim to assess various laryngoscopic findings in patients with LPRD diagnosed symptomatically and examine the correlation between the RSI & RFS by comparing these two indices. This prospective analytical study was conducted at a tertiary care centre in Bangalore in the Department of ENT for a period of 24 months between Dec 2020 to Dec 2022. The study included patients aged 18 to 60 years diagnosed with LPRD based on symptoms as per RSI score (> 13). RSI & RFS were assessed on diagnosis and patients were followed up for 1, 3 & 6 months for assessment. Total 96 patients were enrolled, with mean age of be 42.49 ± 11.33 years. Prevalence was found to be more in females (61.5%). The most common symptom according to RSI was frequent throat clearing & globus sensation (sensation of something sticking in throat) and most common finding according to RFS was erythema/hyperemia. The mean score of RSI and RFI was found to reduce with treatment at different intervals in follow-up visits. There was a significant strength of association between the RSI and RFS at baseline, 1st month, 3rd month and 6th month of follow-up (r = 0.568, r = 0.684, r = 0.774, r = 0.736 respectively) (p < 0.001).The RFS and RSI showed statistically significant strong relationships between total scores and sign and symptom characteristics. On follow-up, there was a significant reduction in the RSI which was also correlated with a reduction in RFS.

Mung bean as a potent emerging functional food having anticancer therapeutic potential: Mechanistic insight and recent updates.

Cancer is still a major challenge for humans. In recent years, researchers have focused on plant-based metabolites as a safe, efficient, alternative or combinatorial, as well as cost-effective preventive strategy against carcinogenesis. Mung bean is an important nutritious legume, and known for providing various health benefits due to various bioactive phytochemicals and easily digestible proteins. Regular intake of mung bean helps to regulate metabolism by affecting the growth and survival of good microbes in the host gut. Mung bean has also been reported to have anti-inflammatory, antioxidant, antiproliferative, and immunomodulatory properties. These properties may possess the preventive potential of mung bean against carcinogenesis. Bibliographic databases for peer-reviewed research literature were searched through a structured conceptual approach using focused review questions on mung beans, anticancer, therapeutics, and functional foods along with inclusion/exclusion criteria. For the appraisal of the quality of retrieved articles, standard tools were employed. A deductive qualitative content analysis methodology further led us to analyze outcomes of the research and review articles. The present review provides recent updates on the anticancer potential of mung bean and the possible mechanism of action thereof to prevent carcinogenesis and metastasis. Extensive research on the active metabolites and mechanisms of action is required to establish the anticancer potential of mung bean. Keeping the above facts in view, mung bean should be investigated for its bioactive compounds, to be considered as functional food of the future.