Pesticides impacts on human health and the environment with their mechanisms of action and possible countermeasures.

Pesticides are chemical constituents used to prevent or control pests, including insects, rodents, fungi, weeds, and other unwanted organisms. Despite their advantages in crop production and disease management, the use of pesticides poses significant hazards to the environment and public health. Pesticide elements have now perpetually entered our atmosphere and subsequently contaminated water, food, and soil, leading to health threats ranging from acute to chronic toxicities. Pesticides can cause acute toxicity if a high dose is inhaled, ingested, or comes into contact with the skin or eyes, while prolonged or recurrent exposure to pesticides leads to chronic toxicity. Pesticides produce different types of toxicity, for instance, neurotoxicity, mutagenicity, carcinogenicity, teratogenicity, and endocrine disruption. The toxicity of a pesticide formulation may depend on the specific active ingredient and the presence of synergistic or inert compounds that can enhance or modify its toxicity. Safety concerns are the need of the hour to control contemporary pesticide-induced health hazards. The effectiveness and implementation of the current legislature in providing ample protection for human health and the environment are key concerns. This review explored a comprehensive summary of pesticides regarding their updated impacts on human health and advanced safety concerns with legislation. Implementing regulations, proper training, and education can help mitigate the negative impacts of pesticide use and promote safer and more sustainable agricultural practices.

Deciphering the Enigma of Neuron-Glial Interactions in Neurological Disorders.

Innate lymphocytes, including microglial cells, astrocytes, and oligodendrocytes, play a crucial role in initiating neuroinflammatory reactions inside the central nervous system (CNS). The prime focus of this paper is on the involvement and interplay of neurons and glial cells in neurological disorders such as Alzheimer's Disease (AD), Autism Spectrum Disorder (ASD), epilepsy, and multiple sclerosis (MS). In this review, we explore the specific contributions of microglia and astrocytes and analyzes multiple pathways implicated in neuroinflammation and disturbances in excitatory and inhibitory processes. Firstly, we elucidate the mechanisms through which toxic protein accumulation in AD results in synaptic dysfunction and deregulation of the immune system and examines the roles of microglia, astrocytes, and hereditary factors in the pathogenesis of the disease. Secondly, we focus on ASD and the involvement of glial cells in the development of the nervous system and the formation of connections between neurons and investigates the genetic connections associated with these processes. Lastly, we also address the participation of glial cells in epilepsy and MS, providing insights into their pivotal functions in both conditions. We also tried to give an overview of seven different pathways like toll-like receptor signalling pathway, MyD88-dependent and independent pathway, etc and its relevance in the context with these neurological disorders. In this review, we also explore the role of activated glial cells in AD, ASD, epilepsy, and MS which lead to neuroinflammation. Even we focus on excitatory and inhibitory imbalance in all four neurological disorders as imbalance affect the proper functioning of neuronal circuits. Finally, this review concludes that there is necessity for additional investigation on glial cells and their involvement in neurological illnesses.

Knowledge, acceptance, motivators and barriers of booster dose of COVID-19 vaccination among dental patients: A cross-sectional study.

Given the lingering threat of COVID infection, questions are being raised if coronavirus disease 2019 (COVID-19) vaccine needs annual or regular boosters to maintain high levels of immunity against both the original virus and variants. This study was designed to evaluate the knowledge, acceptance, motivators and barriers of the booster dose of COVID-19 vaccine among the dental patients of District Lucknow, India. A total of 297 respondents were selected by a convenience sampling method in this cross-sectional study from various dental clinics. An anonymous, self-administered, closed-ended questionnaire was used. Overall 37.7% respondents reported to have taken all 3 doses and 57.9% had taken single/double doses. Correct information about booster doses shows a significant association with the number of doses taken. The majority had information about the availability of the Pfizer booster vaccine (69.0%). About 58% of participants had information about the technology used in booster doses. The hesitancy for booster doses and the development of natural immunity by infection show significant associations with the number of doses taken. Only 18.2% patients had hesitation about the booster dose and most of them 78.8% recommended others to take the booster vaccine as soon as possible. The majority assumed that previous COVID-19 vaccines can help them get immune (21.5%) followed by not much research has been done on the booster vaccines (15.5%) and their chronic diseases warn them against the booster dose administration (12.5%). Nearly 18.2% of respondents had hesitation about booster dose and less than one third of the respondents trusted a government source for information about booster dose of COVID vaccine. Nearly 36 % did not know that the booster dose of COVID vaccine is available at health centers. Dental health professionals and policymakers should implement and support strategies to ensure people are vaccinated for COVID-19 booster doses.

Ganoderma lucidum: Novel Insight into Hepatoprotective Potential with Mechanisms of Action.

Ganoderma lucidum (G. lucidum) has been widely used for its health benefits as an edible and traditional medicinal mushroom for thousands of years in Asian countries. It is currently used as a nutraceutical and functional food owing to its major bioactive compounds, polysaccharides and triterpenoids. G. lucidum exhibits a broad range of hepatoprotective impacts in various liver disorders, such as hepatic cancer, nonalcoholic fatty liver disease (NAFLD), alcohol-induced liver disease, hepatitis B, hepatic fibrosis, and liver injury induced by carbon tetrachloride (CCl4) and α-amanitin. G. lucidum protects the liver through a broad range of mechanisms that include the modulation of liver Phase I and II enzymes, the suppression of ß-glucuronidase, antifibrotic and antiviral actions, the regulation of the production of nitric oxide (NO), the maintenance of hepatocellular calcium homeostasis, immunomodulatory activity, and scavenging free radicals. G. lucidum could signify an encouraging approach for the management of various chronic hepatopathies, and its potential mechanisms make it a distinctive agent when used alone or with other drugs and applied as a functional food, nutraceutical supplement, or adjuvant to modern medicine. This review summarizes the hepatoprotective properties of G. lucidum with its various mechanisms of action on different liver ailments. Biologically active substances derived from G. lucidum are still being studied for their potential benefits in treating different liver ailments.

In-silico approaches for identification of compounds inhibiting SARS-CoV-2 3CL protease.

The world has witnessed of many pandemic waves of SARS-CoV-2. However, the incidence of SARS-CoV-2 infection has now declined but the novel variant and responsible cases has been observed globally. Most of the world population has received the vaccinations, but the immune response against COVID-19 is not long-lasting, which may cause new outbreaks. A highly efficient pharmaceutical molecule is desperately needed in these circumstances. In the present study, a potent natural compound that could inhibit the 3CL protease protein of SARS-CoV-2 was found with computationally intensive search. This research approach is based on physics-based principles and a machine-learning approach. Deep learning design was applied to the library of natural compounds to rank the potential candidates. This procedure screened 32,484 compounds, and the top five hits based on estimated pIC50 were selected for molecular docking and modeling. This work identified two hit compounds, CMP4 and CMP2, which exhibited strong interaction with the 3CL protease using molecular docking and simulation. These two compounds demonstrated potential interaction with the catalytic residues His41 and Cys154 of the 3CL protease. Their calculated binding free energies to MMGBSA were compared to those of the native 3CL protease inhibitor. Using steered molecular dynamics, the dissociation strength of these complexes was sequentially determined. In conclusion, CMP4 demonstrated strong comparative performance with native inhibitors and was identified as a promising hit candidate. This compound can be applied in-vitro experiment for the validation of its inhibitory activity. Additionally, these methods can be used to identify new binding sites on the enzyme and to design new compounds that target these sites.

Awareness and Perceptions of the Impact of Tonsillectomy on the Level of Immunity and Autoimmune Diseases among the Adult Population in Abha City, Kingdom of Saudi Arabia.

The widespread misconception that tonsillectomy leads to a decrease in immunity may lead to fear and avoidance of the operation. This can result in a deterioration of the situation, such as sleep-related breathing issues, frequent infections, and an increase in complications. The current research was conducted to assess the awareness and perception with respect to the impact of tonsillectomy on the immune system and to assess the awareness and perception of the relationship between autoimmune diseases and tonsillectomy. This 6-month descriptive cross-sectional online questionnaire survey was conducted among individuals who were 18 years and above living in Abha city, Saudi Arabia. Out of the 800 study subjects, 104 (13%) had undergone tonsillectomy. Statistically significant associations were found between age group, education, income, and occupation among those who had undergone tonsillectomy. Multivariate logistic regression analysis showed that ages 18-30 years and 31-40 years (OR: 2.36, 95% CI: 1.18-4.71, and OR: 1.46, 95% CI: 0.53-3.97) and education levels of high school, bachelors, and above (OR: 8.30, 95% CI: 3.05-22.58 and OR: 10.89, 95% CI: 4.23-28.05) were found to be associated with tonsillectomy status of the subjects. On the contrary, income levels of 5000-9000 and >9000 (OR: 0.65, 95% CI: 0.36-1.17 and OR: 0.78, 95%CI: 0.42-1.42) and male gender (OR: 0.79, 95% CI: 0.52-1.19) were found to be associated with non-tonsillectomy status of subjects. Almost 36% of study subjects thought that tonsillectomy affects immunity. Only 18% of study subjects thought that there is a relationship between tonsillectomy and autoimmune diseases. About one-third of the respondents had received this information from community members and social media. A small number of study subjects relied on public awareness programs. Therefore, social media can play a vital role in the community to remove misconceptions regarding tonsillectomy and its effect on immunity and autoimmune disease. Further educational interventional studies are required to see the correction to the public perception of tonsillectomy and its effect on immunity and autoimmune diseases.

Preparedness for the Dengue Epidemic: Vaccine as a Viable Approach.

Dengue fever is one of the significant fatal mosquito-borne viral diseases and is considered to be a worldwide problem. Aedes mosquito is responsible for transmitting various serotypes of dengue viruses to humans. Dengue incidence has developed prominently throughout the world in the last ten years. The exact number of dengue cases is underestimated, whereas plenty of cases are misdiagnosed as alternative febrile sicknesses. There is an estimation that about 390 million dengue cases occur annually. Dengue fever encompasses a wide range of clinical presentations, usually with undefinable clinical progression and outcome. The diagnosis of dengue depends on serology tests, molecular diagnostic methods, and antigen detection tests. The therapeutic approach relies completely on supplemental drugs, which is far from the real approach. Vaccines for dengue disease are in various stages of development. The commercial formulation Dengvaxia (CYD-TDV) is accessible and developed by Sanofi Pasteur. The vaccine candidate Dengvaxia was inefficient in liberating a stabilized immune reaction toward different serotypes (1-4) of dengue fever. Numerous promising vaccine candidates are now being developed in preclinical and clinical stages even though different serotypes of DENV exist that worsen the situation for a vaccine to be equally effective for all serotypes. Thus, the development of an efficient dengue fever vaccine candidate requires time. Effective dengue fever management can be a multidisciplinary challenge, involving international cooperation from diverse perspectives and expertise to resolve this global concern.

Use of gold nanoparticle-silibinin conjugates: A novel approach against lung cancer cells.

Lung cancer presents one of the most challenging carcinomas with meager 5-year survival rates (less than 20%), high metastasis and high recurrence due to chemo- and radio- resistance. An alternative or complementation to existing prognosis modalities is the use of phytochemicals such as silibinin, which targets essential cytokines, angiogenic factors and transcription factors for a profound anti-tumor effect. However, the problems of low solubility in an aqueous physiological environment, poor penetration, high metabolism and rapid systemic clearance limit the therapeutic use of silibinin. Conjugation of gold nanoparticles (GNPs) with silibinin may overcome the above challenges along with distinct advantages of biocompatibility, optical properties for monitoring and causation of cytotoxicity in cancer cells. The current study thus aims to develop silibinin conjugated gold nanoparticles (Sb-GNPs) with pH responsive release in the cancer microenvironment, optimizing several parameters for its higher activity and further evaluate the nanoplatform for their efficacy in inducing cell death in vitro against A549 lung cancer cells. GNPs was synthesized using trisodium citrate dihydrate as the reducing agent and further used for the conjugation of silibinin. The synthesized GNPs were found to be monodispersed and spherical in shape. The silibinin was successfully conjugated with gold nanoparticles and long-term stability of GNPs and Sb-GNPs nanoconjugates in suspension phase was confirmed by FTIR and DLS. Anticancer properties of Sb-GNPs were confirmed by different assay using MTT, Trypan blue dye exclusion assay and cell cycle analysis assay. After conjugation of silibinin with GNPs, the efficacy of silibinin increased 4-5 times in killing the cancer cells. This is the first report on using silibinin gold nanoconjugate system for lung cancer therapy with promising future applications.

Role of bioactive compounds in the treatment of hepatitis: A review.

Hepatitis causes liver infection leading to inflammation that is swelling of the liver. They are of various types and detrimental to human beings. Natural products have recently been used to develop antiviral drugs against severe viral infections like viral hepatitis. They are usually extracted from herbs or plants and animals. The naturally derived compounds have demonstrated significant antiviral effects against the hepatitis virus and they interfere with different stages of the life cycle of the virus, viral release, replication, and its host-specific interactions. Antiviral activities have been demonstrated by natural products such as phenylpropanoids, flavonoids, xanthones, anthraquinones, terpenoids, alkaloids, aromatics, etc., against hepatitis B and hepatitis C viruses. The recent studies conducted to understand the viral hepatitis life cycle, more effective naturally derived drugs are being produced with a promising future for the treatment of the infection. This review emphasizes the current strategies for treating hepatitis, their shortcomings, the properties of natural products and their numerous types, clinical trials, and future prospects as potential drugs.

Investigation on Antimicrobial, Antioxidant, and Anti-cancerous activity of Agaricus bisporus derived ß-Glucan particles against cervical cancer cell line.

Cervical cancer is one of the leading causes of death among women. Due to incomplete knowledge and hidden symptoms, it is not easily diagnosable. After the diagnosis of cervical cancer at an advanced stage, treatment such as chemotherapy and radiation therapy become too much costly along with having many side effects such as hair loss, loss of appetite, nausea, tiredness, etc. ß-Glucan does a novel polysaccharide has many immunomodulatory properties. In our research, we have tested the efficacy of Agaricus bisporus derived ß-Glucan particles (ADGPs) as an antimicrobial, antioxidant and anticancer agent against the cervical cancer HeLa cells. Prepared particles were quantified for carbohydrate content by anthrone test and further HPTLC analysis to confirm the polysaccharide nature and 1,3 glycosidic linkages of ß-Glucan. ADGPs were found to have efficient antimicrobial activity against various fungal and bacterial tested strains. DPPH assay confirmed the antioxidant activity of ADGPs. Cell viability was assessed against the cervical cancer cell line by using the MTT and IC50 was found at 54µg/ml. Furthermore, ß-Glucan was found to induce a significant amount of ROS, leading to the apoptosis of cells. The same was also assessed with the help of Propidium Iodide (PI) staining. With the help of JC-1 staining, ß-Glucan was found to disrupt the Mitochondrial Membrane Potential (MMP), ultimately resulting in the cancer cell HeLa death. Based on our experimental findings, we found that ADGPs can be proven as an efficient therapy for cervical cancer treatment and work as an antimicrobial and antioxidant agent.

COVID-19 and SARS-CoV-2 Variants: Current Challenges and Health Concern.

The ongoing coronavirus disease 2019 (COVID-19) outbreak in Wuhan, China, was triggered and unfolded quickly throughout the globe by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The new virus, transmitted primarily through inhalation or contact with infected droplets, seems very contagious and pathogenic, with an incubation period varying from 2 to 14 days. The epidemic is an ongoing public health problem that challenges the present global health system. A worldwide social and economic stress has been observed. The transitional source of origin and its transport to humans is unknown, but speedy human transportation has been accepted extensively. The typical clinical symptoms of COVID-19 are almost like colds. With case fatality rates varying from 2 to 3 percent, a small number of patients may experience serious health problems or even die. To date, there is a limited number of antiviral agents or vaccines for the treatment of COVID-19. The occurrence and pathogenicity of COVID-19 infection are outlined and comparatively analyzed, given the outbreak's urgency. The recent developments in diagnostics, treatment, and marketed vaccine are discussed to deal with this viral outbreak. Now the scientist is concerned about the appearance of several variants over the globe and the efficacy of the vaccine against these variants. There is a need for consistent monitoring of the virus epidemiology and surveillance of the ongoing variant and related disease severity.

Association of Helicobacter pylori Infection and Host Cytokine Gene Polymorphism with Gastric Cancer.

The global cancer burden of new cases of various types rose with millions of death in 2018. Based on the data extracted by GLOBOCAN 2018, gastric cancer (GC) is the third leading cause of mortality related to cancer across the globe. Carcinogenic or oncogenic infections associated with Helicobacter pylori (Hp) are regarded as one of the essential risk factors for GC development. It contributes to the increased production of cytokines that cause inflammation prior to their growth in the host cells. Hp infections and specific types of polymorphisms within the host cells encoding cytokines are significant contributors to the host's increased susceptibility in terms of the development of GC. Against the backdrop of such an observation is that only a small portion of the cells infected can become malignant. The diversities are a consequence of the differences in the pathogenic pathway of the Hp, susceptibility of the host, environmental conditions, and interplay between these factors. It is evident that hosts carrying cytokine genes with high inflammatory levels and polymorphism tend to exhibit an increased risk of development of GC, with special emphasis being placed on the host cytokines gene polymorphisms.

Microbial Nano-Factories: Synthesis and Biomedical Applications.

In the recent times, nanomaterials have emerged in the field of biology, medicine, electronics, and agriculture due to their immense applications. Owing to their nanoscale sizes, they present large surface/volume ratio, characteristic structures, and similar dimensions to biomolecules resulting in unique properties for biomedical applications. The chemical and physical methods to synthesize nanoparticles have their own limitations which can be overcome using biological methods for the synthesis. Moreover, through the biogenic synthesis route, the usage of microorganisms has offered a reliable, sustainable, safe, and environmental friendly technique for nanosynthesis. Bacterial, algal, fungal, and yeast cells are known to transport metals from their environment and convert them to elemental nanoparticle forms which are either accumulated or secreted. Additionally, robust nanocarriers have also been developed using viruses. In order to prevent aggregation and promote stabilization of the nanoparticles, capping agents are often secreted during biosynthesis. Microbial nanoparticles find biomedical applications in rapid diagnostics, imaging, biopharmaceuticals, drug delivery systems, antimicrobials, biomaterials for tissue regeneration as well as biosensors. The major challenges in therapeutic applications of microbial nanoparticles include biocompatibility, bioavailability, stability, degradation in the gastro-intestinal tract, and immune response. Thus, the current review article is focused on the microbe-mediated synthesis of various nanoparticles, the different microbial strains explored for such synthesis along with their current and future biomedical applications.

Oncolytic viruses in the treatment of cancer: a review of current strategies.

Oncolytic viruses are live, replication-competent viruses that replicate selectively in tumor cells leading to the destruction of the tumor cells. Tumor-selective replicating viruses offer appealing advantages over conventional cancer therapy and are promising a new approach for the treatment of human cancer. The development of virotherapeutics is based on several strategies. Virotherapy is not a new concept, but recent technical advances in the genetic modification of oncolytic viruses have improved their tumor specificity, leading to the development of new weapons for the war against cancer. Clinical trials with oncolytic viruses demonstrate the safety and feasibility of an effective virotherapeutic approach. Strategies to overcome potential obstacles and challenges to virotherapy are currently being explored. Systemic administrations of oncolytic viruses will successfully extend novel treatment against a range of tumors. Combination therapy has shown some encouraging antitumor responses by eliciting strong immunity against established cancer.

Transgenic tobacco plant expressing environmental E. coli merA gene for enhanced volatilization of ionic mercury.

The practicability of transgenic tobacco engineered to express bacterial native mercuric reductase (MerA), responsible for the transport of Hg2+ ions into cell and their reduction to elemental mercury (Hg0), without any codon modification for phytoremediation of mercury pollution was evaluated. Transgenic tobacco plants reduce mercury ions to the metallic form; take up metallic mercury through their roots; and evolve less toxic elemental mercury. Transformed tobacco produced a large amount of merA protein in leaves and showed a relatively high resistant phenotype to HgCl2 than wild-type. Results suggests that the integrated merA gene, encoding mercuric reductase, a key enzyme of bacterial mer operon, is stably integrated into tobacco genome, and translated to active MerA which catalyzed the bioconversion of toxic Hg2+ to least toxic elemental Hg0, and suggest that MerA is capable of reducing the Hg2+, probably via NADPH as an electron donor. The transgenic tobacco expressing merA volatilized significantly more mercury than wild-type plants. This is first time we are reporting the expression of bacterial native merA gene via the nuclear genome of Nicotiana tabacum and enhanced mercury volatilization from tobacco transgenics. The study clearly indicates that transgenic tobacco plants are reasonable candidates for the remediation of mercury contaminated areas.

Molecular studies of E. coli mercuric reductase gene (merA) and its impact on human health.

Bacterial plasmids encode resistance systems for toxic metal ions including Hg2+ functioning by energy-dependent efflux of toxic ions. The inducible mercury resistance (mer) operon encodes both a mercuric ion uptake and a detoxification enzymes. In Gram-negative bacteria especially in E. coli, a periplasmic protein, MerP, an inner- membrane transport protein, MerT, and a cytoplasmic enzyme, mercuric reductase (the MerA protein), are responsible for the transport of mercuric ions into cell and their reduction to elemental mercury, Hg0. Phytoremediation involves the use of plants to extract, detoxify and/or sequester environmental pollutants from soil and water. Transgenic plants cleave mercury ions from methyl-mercury complexes; reduce mercury ions to the metallic form; take up metallic mercury through their roots; and evolve less toxic elemental mercury. PCR were performed to detect 1695 bp of mercuric reductase gene (merA), which is mainly responsible for the conversion of mercuric (Hg+2) and mercurous (Hg+1) ions into non-toxic elemental mercury. PCR products of putative merA genes from environmental E. coli strains were purified and cloned into a plant expression vector pRT100. The construct will be transformed in calli of Nicotiana plants.