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1.
Microbiol Res ; 285: 127758, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38781787

ABSTRACT

The role of the plant innate immune system in the defense and symbiosis processes becomes integral in a complex network of interactions between plants and fungi. An understanding of the molecular characterization of the plant innate immune system is crucial because it constitutes plants' self-defense shield against harmful fungi, while creating mutualistic relationships with beneficial fungi. Due to the plant-induced awareness and their complexity of interaction with fungi, sufficient assessment of the participation of the plant innate immune system in ecological balance, agriculture, and maintenance of an infinite ecosystem is mandatory. Given the current global challenge, such as the surge of plant-infectious diseases, and pursuit of sustainable forms of agriculture; it is imperative to understand the molecular language of communication between plants and fungi. That knowledge can be practically used in diverse areas, e.g., in agriculture, new tactics may be sought after to try new methods that boost crop receptiveness against fungal pathogens and reduce the dependence on chemical management. Also, it could boost sustainable agricultural practices via enhancing mycorrhizal interactions that promote nutrient absorption and optimum cropping with limited exposure of environmental contamination. Moreover, this review offers insights that go beyond agriculture and can be manipulated to boost plant conservation, environmental restoration, and quality understanding of host-pathogen interactions. Consequently, this specific review paper has offered a comprehensive view of the complex plant innate immune-based responses with fungi and the mechanisms in which they interact.


Subject(s)
Fungi , Host-Pathogen Interactions , Immunity, Innate , Plant Diseases , Plant Immunity , Plants , Symbiosis , Fungi/immunology , Plants/immunology , Plants/microbiology , Plant Diseases/microbiology , Plant Diseases/immunology , Host-Pathogen Interactions/immunology , Symbiosis/immunology , Agriculture , Mycorrhizae/physiology , Ecosystem
2.
J Biomol Struct Dyn ; 42(10): 5402-5414, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38764132

ABSTRACT

RNA-dependent RNA polymerase (RdRp) is considered a potential drug target for dengue virus (DENV) inhibition and has attracted attention in antiviral drug discovery. Here, we screened 121 natural compounds from Litsea cubeba against DENV RdRp using various approaches of computer-based drug discovery. Notably, we identified four potential compounds (Ushinsunine, Cassameridine, (+)-Epiexcelsin, (-)-Phanostenine) with good binding scores and allosteric interactions with the target protein. Moreover, molecular dynamics simulation studies were done to check the conformational stability of the complexes under given conditions. Additionally, we performed post-simulation analysis to find the stability of potential drugs in the target protein. The findings suggest Litsea cubeba-derived phytomolecules as a therapeutic solution to control DENV infection.Communicated by Ramaswamy H. Sarma.


Subject(s)
Antiviral Agents , Dengue Virus , Litsea , Molecular Docking Simulation , Molecular Dynamics Simulation , Phytochemicals , RNA-Dependent RNA Polymerase , Dengue Virus/drug effects , Dengue Virus/enzymology , RNA-Dependent RNA Polymerase/antagonists & inhibitors , RNA-Dependent RNA Polymerase/chemistry , RNA-Dependent RNA Polymerase/metabolism , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Phytochemicals/pharmacology , Phytochemicals/chemistry , Allosteric Regulation/drug effects , Litsea/chemistry , Protein Binding
3.
Aging Dis ; 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38607741

ABSTRACT

The diagnosis, treatment, and management of dementia provide significant challenges due to its chronic cognitive impairment. The complexity of this condition is further highlighted by the impact of gene-environment interactions. A recent strategy combines advanced genomics and precision medicine methods to explore the complex genetic foundations of dementia. Utilizing the most recent research in the field of neurogenetics, the importance of precise genetic data in explaining the variation seen in dementia patients can be investigated. Gene-environment interactions are important because they influence genetic susceptibilities and aid in the development and progression of dementia. Modified to each patient's genetic profile, precision medicine has the potential to detect groups at risk and make previously unheard-of predictions about the course of diseases. Precision medicine techniques have the potential to completely transform treatment and diagnosis methods. Targeted medications that target genetic abnormalities will probably appear, providing the possibility for more efficient and customized medical interventions. Investigating the relationship between genes and the environment may lead to preventive measures that would enable people to change their surroundings and minimize the risk of dementia, leading to the improved lifestyle of affected people. This paper provides a comprehensive overview of the genomic insights into dementia, emphasizing the pivotal role of precision medicine, and gene-environment interactions.

5.
Mol Biotechnol ; 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38512426

ABSTRACT

Breast cancer is considered a significant health concern worldwide, with genetic predisposition playing a critical role in its etiology. Single nucleotide polymorphisms (SNPs), particularly those within the 3' untranslated regions (3'UTRs) of target genes, are emerging as key factors in breast cancer susceptibility. Specifically, miRNAs have been recognized as possible novel approach for biomarkers discovery for both prognosis and diagnosis due to their direct association with cancer progression. Regional disparities in breast cancer incidence underscore the need for precise interventions, considering socio-cultural and economic factors. This review explores into the differential effects of SNP-miRNA interactions on breast cancer risk, emphasizing both risk-enhancing and protective associations across diverse populations. Furthermore, it explores the clinical implications of these findings, highlighting the potential of personalized approaches in breast cancer management. Additionally, it reviews the evolving therapeutic prospect of microRNAs (miRNAs), extending beyond cancer therapeutics to encompass various diseases, indicative of their versatility as therapeutic agents.

6.
Front Oral Health ; 4: 1246873, 2023.
Article in English | MEDLINE | ID: mdl-37859687

ABSTRACT

Oral cancer, particularly oral squamous cell carcinoma (OSCC), is a prevalent malignancy having a significant fatality rate worldwide. Despite advancements in conventional treatment modalities, the overall survival rate for OSCC remains low. Therefore, there is a critical need to explore alternative therapeutic approaches that can improve patient outcomes. This review focuses on the potential of dietary factors and plant extracts as chemopreventive agents in treating oral cancer. These compounds possess diverse biological functions encompassing a range of attributes, such as antioxidative, anti-inflammatory, and anticancer capabilities. By targeting multiple cellular pathways involved in carcinogenesis, they possess the capacity to hinder tumor growth and development, promote programmed cell death, and impede the progression of oral cancer. Signaling pathways targeted by natural compounds that have been included in this review include Akt/mTOR/NF-κB signaling, Hippo-Tafazzin signaling pathway, notch signaling pathway, mitochondrial pathway, and Sonic Hedgehog pathway.

7.
Luminescence ; 38(7): 1405-1415, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36929030

ABSTRACT

This study involves the single-step, mass-scale productive synthesis, photoconduction, and luminescence characteristics of pure and cerium rare-earth-ion-doped ZnO (CZO) nanophosphors with different Ce concentrations (Ce: 0, 2, 4, 6, and 8 wt.%) synthesized using the solid-state reaction method. The synthesized nanophosphors were characterized for their structural, morphological, optical, and photoconductivity (PC) properties using X-ray diffraction (XRD), field-effect scanning electron microscopy (FE-SEM), energy dispersive spectroscopy, Fourier-transform infrared (FT-IR), photoluminescence (PL), and PC measurements. The sharp diffraction peaks of XRD results exhibit the formation of crystalline hexagonal wurtzite ZnO nanostructures. The decrease in diffraction peak intensities of CZO with an increase in Ce concentrations signifies the deterioration of the ZnO crystal. FE-SEM images exhibit the good crystalline quality of nanophosphors composed of spherical- and elongated-shaped nanoparticles that are distributed consistently on the surface. The energy dispersive X-ray pattern of the 4 wt.% Ce-doped ZnO (CZO4 ) sample confirms the doping of Ce in ZnO. The presence of chemical bonds and functional groups corresponds to transmittance peaks established using FT-IR spectroscopy. Deconvoluted PL spectra show two major emission peaks, one in the UV region, which is near-band-edge, and the other in the visible region ranging from ~456 to 561 nm. In PC studies, current-voltage (I-V) and current-time (I-T) characteristics, that is, rise/decayin current under dark as well as UV light conditions, are also investigated. Efficient photoconduction is observed in CZO samples. The obtained results indicate the suitability to luminescent and photosensor applications.


Subject(s)
Nanostructures , Zinc Oxide , Zinc Oxide/chemistry , Luminescence , Spectroscopy, Fourier Transform Infrared , Ultraviolet Rays , Nanostructures/chemistry , X-Ray Diffraction
8.
Biology (Basel) ; 12(2)2023 Feb 06.
Article in English | MEDLINE | ID: mdl-36829533

ABSTRACT

Each cell in a multicellular organism has its own phenotype despite sharing the same genome. Epigenetics is a somatic, heritable pattern of gene expression or cellular phenotype mediated by structural changes in chromatin that occur without altering the DNA sequence. Epigenetic modification is an important factor in determining the level and timing of gene expression in response to endogenous and exogenous stimuli. There is also growing evidence concerning the interaction between epigenetics and metabolism. Accordingly, several enzymes that consume vital metabolites as substrates or cofactors are used during the catalysis of epigenetic modification. Therefore, altered metabolism might lead to diseases and pathogenesis, including endocrine disorders and cancer. In addition, it has been demonstrated that epigenetic modification influences the endocrine system and immune response-related pathways. In this regard, epigenetic modification may impact the levels of hormones that are important in regulating growth, development, reproduction, energy balance, and metabolism. Altering the function of the endocrine system has negative health consequences. Furthermore, endocrine disruptors (EDC) have a significant impact on the endocrine system, causing the abnormal functioning of hormones and their receptors, resulting in various diseases and disorders. Overall, this review focuses on the impact of epigenetics on the endocrine system and its interaction with metabolism.

9.
Naunyn Schmiedebergs Arch Pharmacol ; 396(4): 649-657, 2023 04.
Article in English | MEDLINE | ID: mdl-36441265

ABSTRACT

Cervical cancer is one of the leading causes of women's mortality in developing countries. The prevalence of cervical cancer is higher in developing countries like India and continents like Africa. Hyper-methylation of tumor suppressor genes through human papillomavirus (HPV) infection is known to be one of the major causes of cervical cancer. The promoter hypermethylation of the cell adhesion molecule 1 (CADM1) and suppressor of cytokine signalling (SOCS1) genes due to DNMT1 overexpression leads to their epigenetic silencing followed by gene repression causing cervical cancer. In silico study on the inhibition effect of capsaicin on DNMT1 was simulated by different servers. The binding energy was observed to be -7.8 kcal/mol. In vitro studies on the effect of capsaicin on aberrant methylation of CADM1 and SOCS1 were performed on the adenocarcinoma cervical cancer cell line, HeLa. The IC50 of capsaicin was observed to be 160 µM through crystal violet assay. DNA methylation of the CADM1 and SOCS1 was analyzed by methylation-specific PCR along with their reversal using capsaicin (20 µM) by treating the cells for 72 h and 6 days. In silico results suggested that capsaicin has an inhibitory effect on DNMT1, which regulates DNA methylation leading to the hypermethylation of CADM1 and SOCS1 genes. The in vitro studies suggested that hypermethylation leads to the inhibition of CADM1 and SOCS1 expression, which could be reversed using capsaicin with visible changes in methylation-specific and unmethylation-specific bands in MS-PCR, respectively. The present study shows the reversal of methylation of CADM1 and SOCS1 after 72 h which showed a further increase in case of 6 days of treatment using 20 µM capsaicin, which makes capsaicin a potent candidate for causing demethylation of CADM1 and SOCS1 genes that may lead to the reactivation of the downregulated gene.


Subject(s)
Uterine Cervical Neoplasms , Humans , Female , Cell Adhesion Molecule-1/genetics , Cell Adhesion Molecule-1/metabolism , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology , Capsaicin/pharmacology , DNA Methylation , Suppressor of Cytokine Signaling Proteins/genetics , HeLa Cells , Demethylation , Cell Line, Tumor , Suppressor of Cytokine Signaling 1 Protein/genetics , Suppressor of Cytokine Signaling 1 Protein/metabolism
10.
Viruses ; 14(12)2022 11 30.
Article in English | MEDLINE | ID: mdl-36560690

ABSTRACT

The Japanese encephalitis virus (JEV) is the most common cause of neurodegenerative disease in Southeast Asia and the Western Pacific region; approximately 1.15 billion people are at risk, and thousands suffer from permanent neurological disorders across Asian countries, with 10-15 thousand people dying each year. JEV crosses the blood-brain barrier (BBB) and forms a complex with receptors on the surface of neurons. GRP78, Src, TLR7, caveolin-1, and dopamine receptor D2 are involved in JEV binding and entry into the neurons, and these receptors also play a role in carcinogenic activity in cells. JEV binds to GRP78, a member of the HSP70 overexpressed on malignant cells to enter neurons, indicating a higher chance of JEV infection in cancer patients. However, JEV enters human brain microvascular endothelial cells via an endocytic pathway mediated by caveolae and the ezrin protein and also targets dopamine-rich areas for infection of the midbrain via altering dopamine levels. In addition, JEV complexed with CLEC5A receptor of macrophage cells is involved in the breakdown of the BBB and central nervous system (CNS) inflammation. CLEC5A-mediated infection is also responsible for the influx of cytokines into the CNS. In this review, we discuss the neuronal and macrophage surface receptors involved in neuronal death.


Subject(s)
Encephalitis Virus, Japanese , Encephalitis Viruses, Japanese , Encephalitis, Japanese , Neurodegenerative Diseases , Humans , Encephalitis Virus, Japanese/physiology , Endothelial Cells/metabolism , Endoplasmic Reticulum Chaperone BiP , Dopamine , Neurodegenerative Diseases/pathology , Central Nervous System , Encephalitis Viruses, Japanese/metabolism , Receptors, Cell Surface , Lectins, C-Type/metabolism
11.
Front Genet ; 13: 886487, 2022.
Article in English | MEDLINE | ID: mdl-36212140

ABSTRACT

Epigenetic modifications are inherited differences in cellular phenotypes, such as cell gene expression alterations, that occur during somatic cell divisions (also, in rare circumstances, in germ line transmission), but no alterations to the DNA sequence are involved. Histone alterations, polycomb/trithorax associated proteins, short non-coding or short RNAs, long non-coding RNAs (lncRNAs), & DNA methylation are just a few biological processes involved in epigenetic events. These various modifications are intricately linked. The transcriptional potential of genes is closely conditioned by epigenetic control, which is crucial in normal growth and development. Epigenetic mechanisms transmit genomic adaptation to an environment, resulting in a specific phenotype. The purpose of this systematic review is to glance at the roles of Estrogen signalling, polycomb/trithorax associated proteins, DNA methylation in breast cancer progression, as well as epigenetic mechanisms in breast cancer therapy, with an emphasis on functionality, regulatory factors, therapeutic value, and future challenges.

13.
Curr Issues Mol Biol ; 44(10): 4584-4615, 2022 Sep 30.
Article in English | MEDLINE | ID: mdl-36286029

ABSTRACT

Alzheimer's disease (AD) is a deadly brain degenerative disorder that leads to brain shrinkage and dementia. AD is manifested with hyperphosphorylated tau protein levels and amyloid beta (Aß) peptide buildup in the hippocampus and cortex regions of the brain. The nervous tissue of AD patients also contains fungal proteins and DNA which are linked to bacterial infections, suggesting that polymicrobial infections also occur in the brains of those with AD. Both immunohistochemistry and next-generation sequencing (NGS) techniques were employed to assess fungal and bacterial infections in the brain tissue of AD patients and non-AD controls, with the most prevalent fungus genera detected in AD patients being Alternaria, Botrytis, Candida, and Malassezia. Interestingly, Fusarium was the most common genus detected in the control group. Both AD patients and controls were also detectable for Proteobacteria, followed by Firmicutes, Actinobacteria, and Bacteroides for bacterial infection. At the family level, Burkholderiaceae and Staphylococcaceae exhibited higher levels in the brains of those with AD than the brains of the control group. Accordingly, there is thought to be a viscous cycle of uncontrolled neuroinflammation and neurodegeneration in the brain, caused by agents such as the herpes simplex virus type 1 (HSV1), Chlamydophilapneumonia, and Spirochetes, and the presence of apolipoprotein E4 (APOE4), which is associated with an increased proinflammatory response in the immune system. Systemic proinflammatory cytokines are produced by microorganisms such as Cytomegalovirus, Helicobacter pylori, and those related to periodontal infections. These can then cross the blood-brain barrier (BBB) and lead to the onset of dementia. Here, we reviewed the relationship between the etiology of AD and microorganisms (such as bacterial pathogens, Herpesviridae viruses, and periodontal pathogens) according to the evidence available to understand the pathogenesis of AD. These findings might guide a targeted anti-inflammatory therapeutic approach to AD.

14.
Brain Sci ; 12(6)2022 Jun 12.
Article in English | MEDLINE | ID: mdl-35741655

ABSTRACT

Calcium homeostasis modulator 1 (CALHM1) is a protein responsible for causing Alzheimer's disease. In the absence of an experimentally designed protein molecule, homology modelling was performed. Through homology modelling, different CALHM1 models were generated and validated through Rampage. To carry out further in silico studies, through molecular docking and molecular dynamics simulation experiments, various flavonoids and alkaloids from Bauhinia variegata were utilised as inhibitors to target the protein (CALHM1). The sequence of CALHM1 was retrieved from UniProt and the secondary structure prediction of CALHM1 was done through CFSSP, GOR4, and SOPMA methods. The structure was identified through LOMETS, MUSTER, and MODELLER and finally, the structures were validated through Rampage. Bauhinia variegata plant was used to check the interaction of alkaloids and flavonoids against CALHM1. The protein and protein-ligand complex were also validated through molecular dynamics simulations studies. The model generated through MODELLER software with 6VAM A was used because this model predicted the best results in the Ramachandran plot. Further molecular docking was performed, quercetin was found to be the most appropriate candidate for the protein molecule with the minimum binding energy of -12.45 kcal/mol and their ADME properties were analysed through Molsoft and Molinspiration. Molecular dynamics simulations showed that CALHM1 and CALHM1-quercetin complex became stable at 2500 ps. It may be seen through the study that quercetin may act as a good inhibitor for treatment. With the help of an in silico study, it was easier to analyse the 3D structure of the protein, which may be scrutinized for the best-predicted model. Quercetin may work as a good inhibitor for treating Alzheimer's disease, according to in silico research using molecular docking and molecular dynamics simulations, and future in vitro and in vivo analysis may confirm its effectiveness.

15.
Preprint in English | bioRxiv | ID: ppbiorxiv-496021

ABSTRACT

The immunity acquired after natural infection or vaccinations against SARS-CoV-2 tend to wane with time. Vaccine effectiveness also varies with the variant of infection. Here, we compared the protective efficacy of COVAXIN(R) following 2 and 3 dose immunizations against the Delta variant and also studied the efficacy of COVAXIN(R) against Omicron variants in a Syrian hamster model. The antibody response, clinical observations, viral load reduction and lung disease severity after virus challenge were studied. Protective response in terms of the reduction in lung viral load and lung lesions were observed in both the 2 dose as well as 3 doses COVAXIN(R) immunized group when compared to placebo group following the Delta variant challenge. In spite of the comparable neutralizing antibody response against the homologous vaccine strain in both the 2 dose and 3 dose immunized groups, considerable reduction in the lung disease severity was observed in the 3 dose immunized group post Delta variant challenge indicating the involvement of cell mediated immune response also in protection. In the vaccine efficacy study against the Omicron variants i.e., BA.1 and BA.2, lesser virus shedding, lung viral load and lung disease severity were observed in the immunized groups in comparison to the placebo groups. The present study shows that administration of COVAXIN(R) booster dose will enhance the vaccine effectiveness against the Delta variant infection and give protection against the Omicron variants BA.1.1 and BA.2.

16.
Biology (Basel) ; 11(2)2022 Jan 28.
Article in English | MEDLINE | ID: mdl-35205079

ABSTRACT

Alzheimer's disease (AD) rate is accelerating with the increasing aging of the world's population. The World Health Organization (WHO) stated AD as a global health priority. According to the WHO report, around 82 million people in 2030 and 152 million in 2050 will develop dementia (AD contributes 60% to 70% of cases), considering the current scenario. AD is the most common neurodegenerative disease, intensifying impairments in cognition, behavior, and memory. Histopathological AD variations include extracellular senile plaques' formation, tangling of intracellular neurofibrils, and synaptic and neuronal loss in the brain. Multiple evidence directly indicates that oxidative stress participates in an early phase of AD before cytopathology. Moreover, oxidative stress is induced by almost all misfolded protein lumps like α-synuclein, amyloid-ß, and others. Oxidative stress plays a crucial role in activating and causing various cell signaling pathways that result in lesion formations of toxic substances, which foster the development of the disease. Antioxidants are widely preferred to combat oxidative stress, and those derived from natural sources, which are often incorporated into dietary habits, can play an important role in delaying the onset as well as reducing the progression of AD. However, this approach has not been extensively explored yet. Moreover, there has been growing evidence that a combination of antioxidants in conjugation with a nutrient-rich diet might be more effective in tackling AD pathogenesis. Thus, considering the above-stated fact, this comprehensive review aims to elaborate the basics of AD and antioxidants, including the vitality of antioxidants in AD. Moreover, this review may help researchers to develop effectively and potentially improved antioxidant therapeutic strategies for this disease as it also deals with the clinical trials in the stated field.

17.
Preprint in English | bioRxiv | ID: ppbiorxiv-477013

ABSTRACT

SARS-CoV-2 Omicron variant is rampantly spreading across the globe. Animal models are useful in understanding the disease characteristics as well as properties of emerging SARS-CoV-2 variants. We assessed the pathogenicity and immune response generated by BA.1 sub-lineage of SARS-CoV-2 Omicron variant with R346K mutation in 5 to 6-week old Syrian hamsters. Virus shedding, organ viral load, lung disease and immune response generated were sequentially assessed. The disease characteristics of Omicron were found to be similar to that of other SARS-CoV-2 variants of concerns in hamsters like high viral replication in the respiratory tract and interstitial pneumonia. The infected hamsters demonstrated lesser body weight gain in comparison to the uninfected control hamsters. Viral RNA could be detected in nasal washes and respiratory organs (nasal turbinate, trachea, bronchi and lungs) till 10 and 14 days respectively. The clearance of the virus was observed from nasal washes and lungs by day 7. Neutralizing antibody response against Omicron variant was detected from day 5 with rising antibody titers till 14 days. However, the cross-neutralization titre of the sera against other variants showed severe reduction ie., 7 fold reduction against Alpha and no titers against B.1, Beta and Delta. This preliminary data shows that Omicron variant infection can produce moderate to severe lung disease and the neutralizing antibodies produced in response to Omicron variant infection shows poor neutralizing ability against other co-circulating SARS-CoV-2 variants like Delta which necessitates caution as it may lead to increased cases of reinfection.

18.
Preprint in English | medRxiv | ID: ppmedrxiv-21267278

ABSTRACT

BackgroundWe report here a Nipah virus (NiV) outbreak in Kozhikode district of Kerala state, India which had caused fatal encephalitis in an adolescent male and the outbreak response which led to the successful containment of the disease and the related investigations. MethodsQuantitative real-time RT-PCR, ELISA based antibody detection and whole genome sequencing were performed to confirm the Nipah virus infection. Contacts of the index case were traced and isolated based on risk categorization. Bats from the areas near the epicenter of the outbreak were sampled for throat swabs, rectal swabs and blood samples for Nipah virus screening by real time RT-PCR and anti-Nipah virus bat IgG ELISA. Plaque reduction neutralization test was performed for the detection of neutralizing antibodies. ResultsNipah viral RNA and anti-NiV IgG antibodies were detected in the serum of the index case. Rapid establishment of an onsite NiV diagnostic facility and contact tracing helped in quick containment of the outbreak. NiV sequences retrieved from the clinical specimen of the index case formed a sub-cluster with the earlier reported Nipah I genotype sequences from India with more than 95% similarity. Anti-NiV IgG positivity could be detected in 21% of Pteropus medius and 37.73% of Rousettus leschenaultia. Neutralizing antibodies against NiV could be detected in P.medius. ConclusionsStringent surveillance and awareness campaigns needs to be implemented in the area to reduce human-bat interactions and minimize spill over events which can lead to sporadic outbreaks of NiV.

19.
Preprint in English | bioRxiv | ID: ppbiorxiv-442760

ABSTRACT

BackgroundThe recent emergence of new SARS-CoV-2 lineage B.1.617 in India has been associated with a surge in the number of daily infections. This variant has combination of specific mutations L452R, E484Q and P681R reported to possibly enhance the transmissibility with likelihood of escaping the immunity. We investigated the viral load and pathogenic potential of B.1.617.1 in Syrian golden hamsters. MethodsTwo groups of Syrian golden hamsters (9 each) were inoculated intranasally with SARS CoV-2 isolates, B.1 (D614G) and B.1.617.1 respectively. The animals were monitored daily for the clinical signs and body weight. The necropsy of three hamsters each was performed on 3, 5- and 7-days post-infection (DPI). Throat swab (TS), nasal wash (NW) and organ samples (lungs, nasal turbinate, trachea) were collected and screened using SARS-CoV-2 specific Real-time RT-PCR. ResultsThe hamsters infected with B.1.617.1 demonstrated increased body weight loss compared to B.1 variant. The highest viral load was observed in nasal turbinate and lung specimens of animals infected with B.1.167.1 on 3 DPI. Neutralizing antibody (NAb) and IgG response in hamsters of both the groups were observed from 5 and 7 DPI respectively. However, higher neutralizing antibody titers were observed against B.1.167.1. Gross pathology showed pronounced lung lesions and hemorrhage with B.1.671 compared to B.1. ConclusionsB.1617.1 and B.1 variant varied greatly in their infectiousness, pathogenesis in hamster model. This study demonstrates higher pathogenicity in hamsters evident with reduced body weight, higher viral load in lungs and pronounced lung lesions as compared to B.1 variant. SummaryB.1.617.1 is the new SARS-CoV-2 lineage that emerged in India. Maximal body weight loss and higher viral load in hamsters infected with B.1.617.1. It caused pronounced lung lesions in hamsters compared to B.1 variant which demonstrates the pathogenic potential of B.1.617.1.

20.
Asian Pac J Cancer Prev ; 22(3): 977-982, 2021 Mar 01.
Article in English | MEDLINE | ID: mdl-33773564

ABSTRACT

BACKGROUND: LATS1 (Large Tumor Suppressor, isoform 1) is a gene that forms a complex with the cyclin-dependent kinase, CDK1, and regulates cell cycle progression. Genetic modifications lead to a loss in the activity of LATS1 gene. OSCC is the most commonly emerging cancer caused by genetic as well as epigenetic changes. Epigenetics changes vary from one population to another because these are influenced by dietary factors and environmental factors.  Tobacco chewing and smoking has been reported as major risk factors in OSCC. No report was found in the previous literature showing promoter hypermethylation of LATS1 gene. METHODS: A total of 50 OSCC patients and 20 normal individuals were recruited in this study. Blood samples (50) from OSCC patients and blood samples (20) from healthy individuals as controls were used in the present study. Isolation of genomic DNA was carried out from blood using the standard phenol-chloroform extraction. Further Isolated DNA was modified with sodium bisulfite using the agarose bead method and finally, the methylation studies of LATS1 gene were carried out using Methylation-Specific PCR (MSP-PCR). RESULTS: 19 out of 50 patients (38.0%) were found to be methylated for LATS1 gene.; a statistically significant result was obtained (p -value= < 0.05) with an odds ratio of 0.37 in cases compared to controls. The status of methylation of LATS1 genes was also found to be statistically significantly associated with smokers and tobacco chewers (p-value = < 0.05). The methylation of LATS1 gene showed a significant risk of developing OSCC in patients. CONCLUSION: These results suggest that the LATS1 gene may provide a better alternative as a diagnostic biomarker. This is the first report on the promoter hypermethylation of LATS1 gene in OSCC patients among the North Indian population.
.


Subject(s)
DNA Methylation , Mouth Neoplasms/genetics , Promoter Regions, Genetic/genetics , Protein Serine-Threonine Kinases/genetics , Squamous Cell Carcinoma of Head and Neck/genetics , Case-Control Studies , Humans , India , Tobacco Smoking/genetics , Tobacco Use/genetics , Tobacco, Smokeless
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