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1.
Pharmaceutics ; 16(6)2024 May 29.
Article in English | MEDLINE | ID: mdl-38931856

ABSTRACT

Combining immune checkpoint inhibitors, specifically nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4), holds substantial promise in revolutionizing cancer treatment. This review explores the transformative impact of these combinations, emphasizing their potential for enhancing therapeutic outcomes across various cancers. Immune checkpoint proteins, such as PD1 and CTLA4, play a pivotal role in modulating immune responses. Blocking these checkpoints unleashes anticancer activity, and the synergy observed when combining multiple checkpoint inhibitors underscores their potential for enhanced efficacy. Nivolumab and ipilimumab harness the host's immune system to target cancer cells, presenting a powerful approach to prevent tumor development. Despite their efficacy, immune checkpoint inhibitors are accompanied by a distinct set of adverse effects, particularly immune-related adverse effects affecting various organs. Understanding these challenges is crucial for optimizing treatment strategies and ensuring patient well-being. Ongoing clinical trials are actively exploring the combination of checkpoint inhibitory therapies, aiming to decipher their synergistic effects and efficacy against diverse cancer types. This review discusses the mechanisms, adverse effects, and various clinical trials involving nivolumab and ipilimumab across different cancers, emphasizing their transformative impact on cancer treatment.

2.
Front Genet ; 13: 880440, 2022.
Article in English | MEDLINE | ID: mdl-36479247

ABSTRACT

Data integration with phenotypes such as gene expression, pathways or function, and protein-protein interactions data has proven to be a highly promising technique for improving human complex diseases, particularly cancer patient outcome prediction. Hepatocellular carcinoma is one of the most prevalent cancers, and the most common cause is chronic HBV and HCV infection, which is linked to the majority of cases, and HBV and HCV play a role in multistep carcinogenesis progression. We examined the list of known hepatocellular carcinoma biomarkers with the publicly available expression profile dataset of hepatocellular carcinoma infected with HCV from day 1 to day 10 in this study. The study covers an overexpression pattern for the selected biomarkers in clinical hepatocellular carcinoma patients, a combined investigation of these biomarkers with the gathered temporal dataset, temporal expression profiling changes, and temporal pathway enrichment following HCV infection. Following a temporal analysis, it was discovered that the early stages of HCV infection tend to be more harmful in terms of expression shifting patterns, and that there is no significant change after that, followed by a set of genes that are consistently altered. PI3K, cAMP, TGF, TNF, Rap1, NF-kB, Apoptosis, Longevity regulating pathway, signaling pathways regulating pluripotency of stem cells, Cytokine-cytokine receptor interaction, p53 signaling, Wnt signaling, Toll-like receptor signaling, and Hippo signaling pathways are just a few of the most commonly enriched pathways. The majority of these pathways are well-known for their roles in the immune system, infection and inflammation, and human illnesses like cancer. We also find that ADCY8, MYC, PTK2, CTNNB1, TP53, RB1, PRKCA, TCF7L2, PAK1, ITPR2, CYP3A4, UGT1A6, GCK, and FGFR2/3 appear to be among the prominent genes based on the networks of genes and pathways based on the copy number alterations, mutations, and structural variants study.

3.
Cells ; 11(24)2022 12 19.
Article in English | MEDLINE | ID: mdl-36552885

ABSTRACT

To understand complex diseases, high-throughput data are generated at large and multiple levels. However, extracting meaningful information from large datasets for comprehensive understanding of cell phenotypes and disease pathophysiology remains a major challenge. Despite tremendous advances in understanding molecular mechanisms of cancer and its progression, current knowledge appears discrete and fragmented. In order to render this wealth of data more integrated and thus informative, we have developed a GECIP toolbox to investigate the crosstalk and the responsible genes'/proteins' connectivity of enriched pathways from gene expression data. To implement this toolbox, we used mainly gene expression datasets of prostate cancer, and the three datasets were GSE17951, GSE8218, and GSE1431. The raw samples were processed for normalization, prediction of differentially expressed genes, and the prediction of enriched pathways for the differentially expressed genes. The enriched pathways have been processed for crosstalk degree calculations for which number connections per gene, the frequency of genes in the pathways, sharing frequency, and the connectivity have been used. For network prediction, protein-protein interaction network database FunCoup2.0 was used, and cytoscape software was used for the network visualization. In our results, we found that there were enriched pathways 27, 45, and 22 for GSE17951, GSE8218, and GSE1431, respectively, and 11 pathways in common between all of them. From the crosstalk results, we observe that focal adhesion and PI3K pathways, both experimentally proven central for cellular output upon perturbation of numerous individual/distinct signaling pathways, displayed highest crosstalk degree. Moreover, we also observe that there were more critical pathways which appear to be highly significant, and these pathways are HIF1a, hippo, AMPK, and Ras. In terms of the pathways' components, GSK3B, YWHAE, HIF1A, ATP1A3, and PRKCA are shared between the aforementioned pathways and have higher connectivity with the pathways and the other pathway components. Finally, we conclude that the focal adhesion and PI3K pathways are the most critical pathways, and since for many other pathways, high-rank enrichment did not translate to high crosstalk degree, the global impact of one pathway on others appears distinct from enrichment.


Subject(s)
Phosphatidylinositol 3-Kinases , Prostatic Neoplasms , Humans , Male , Phosphatidylinositol 3-Kinases/genetics , Gene Expression Profiling/methods , Prostatic Neoplasms/genetics , Protein Interaction Maps/genetics , Computer Simulation , Sodium-Potassium-Exchanging ATPase/genetics
4.
Life (Basel) ; 12(12)2022 Dec 02.
Article in English | MEDLINE | ID: mdl-36556376

ABSTRACT

Defects in signaling pathways are the root cause of many disorders. These malformations come in a wide variety of types, and their causes are also very diverse. Some of these flaws can be brought on by pathogenic organisms and viruses, many of which can obstruct signaling processes. Other illnesses are linked to malfunctions in the way that cell signaling pathways work. When thinking about how errors in signaling pathways might cause disease, the idea of signalosome remodeling is helpful. The signalosome may be conveniently divided into two types of defects: phenotypic remodeling and genotypic remodeling. The majority of significant illnesses that affect people, including high blood pressure, heart disease, diabetes, and many types of mental illness, appear to be caused by minute phenotypic changes in signaling pathways. Such phenotypic remodeling modifies cell behavior and subverts normal cellular processes, resulting in illness. There has not been much progress in creating efficient therapies since it has been challenging to definitively confirm this connection between signalosome remodeling and illness. The considerable redundancy included into cell signaling systems presents several potential for developing novel treatments for various disease conditions. One of the most important pathways, NF-κB, controls several aspects of innate and adaptive immune responses, is a key modulator of inflammatory reactions, and has been widely studied both from experimental and theoretical perspectives. NF-κB contributes to the control of inflammasomes and stimulates the expression of a number of pro-inflammatory genes, including those that produce cytokines and chemokines. Additionally, NF-κB is essential for controlling innate immune cells and inflammatory T cells' survival, activation, and differentiation. As a result, aberrant NF-κB activation plays a role in the pathogenesis of several inflammatory illnesses. The activation and function of NF-κB in relation to inflammatory illnesses was covered here, and the advancement of treatment approaches based on NF-κB inhibition will be highlighted. This review presents the temporal behavior of NF-κB and its potential relevance in different human diseases which will be helpful not only for theoretical but also for experimental perspectives.

6.
Int J Mol Sci ; 23(19)2022 Sep 20.
Article in English | MEDLINE | ID: mdl-36232319

ABSTRACT

The creation of novel anticancer treatments for a variety of human illnesses, including different malignancies and dangerous microbes, also potentially depends on nanoparticles including silver. Recently, it has been successful to biologically synthesize metal nanoparticles using plant extracts. The natural flavonoid 3,3', 4', 5,5', and 7 hexahydroxyflavon (myricetin) has anticancer properties. There is not much known about the regulatory effects of myricetin on the possible cell fate-determination mechanisms (such as apoptosis/proliferation) in colorectal cancer. Because the majority of investigations related to the anticancer activity of myricetin have dominantly focused on the enhancement of tumor cell uncontrolled growth (i.e., apoptosis). Thus, we have decided to explore the potential myricetin interactors and the associated biological functions by using an in-silico approach. Then, we focused on the main goal of the work which involved the synthesis of silver nanoparticles and the labeling of myricetin with it. The synthesized silver nanoparticles were examined using UV-visible spectroscopy, dynamic light scattering spectroscopy, Fourier transform infrared spectroscopy, and scanning electron microscopy. In this study, we have investigated the effects of myricetin on colorectal cancer where numerous techniques were used to show myricetin's effect on colon cancer cells. Transmission Electron Microscopy was employed to monitor morphological changes. Furthermore, we have combined the results of the colorectal cancer gene expression dataset with those of the myricetin interactors and pathways. Based on the results, we conclude that myricetin is able to efficiently kill human colorectal cancer cell lines. Since, it shares important biological roles and possible route components and this myricetin may be a promising herbal treatment for colorectal cancer as per an in-silico analysis of the TCGA dataset.


Subject(s)
Antineoplastic Agents , Metal Nanoparticles , Neoplasms , Anti-Bacterial Agents/pharmacology , Antineoplastic Agents/chemistry , Flavonoids/pharmacology , Humans , Metal Nanoparticles/chemistry , Plant Extracts/pharmacology , Silver/chemistry , Spectroscopy, Fourier Transform Infrared
7.
Front Oncol ; 12: 914032, 2022.
Article in English | MEDLINE | ID: mdl-35936719

ABSTRACT

MAP/microtubule affinity-regulating kinase 4 (MARK4) is associated with various biological functions, including neuronal migration, cell polarity, microtubule dynamics, apoptosis, and cell cycle regulation, specifically in the G1/S checkpoint, cell signaling, and differentiation. It plays a critical role in different types of cancers. Hepatocellular carcinoma (HCC) is the one of the most common forms of liver cancer caused due to mutations, epigenetic aberrations, and altered gene expression patterns. Here, we have applied an integrated network biology approach to see the potential links of MARK4 in HCC, and subsequently identified potential herbal drugs. This work focuses on the naturally-derived compounds from medicinal plants and their properties, making them targets for potential anti-hepatocellular treatments. We further analyzed the HCC mutated genes from the TCGA database by using cBioPortal and mapped out the MARK4 targets among the mutated list. MARK4 and Mimosin, Quercetin, and Resveratrol could potentially interact with critical cancer-associated proteins. A set of the hepatocellular carcinoma altered genes is directly the part of infection, inflammation, immune systems, and cancer pathways. Finally, we conclude that among all these drugs, Gingerol and Fisetin appear to be the highly promising drugs against MARK4-based targets, followed by Quercetin, Resveratrol, and Apigenin.

8.
Biomedicines ; 10(5)2022 May 06.
Article in English | MEDLINE | ID: mdl-35625813

ABSTRACT

Because of their medicinal characteristics, effectiveness, and importance, plant-derived flavonoids have been a possible subject of research for many years, particularly in the last decade. Plants contain a huge number of flavonoids, and Diosmin, a flavone glycoside, is one of them. Numerous in-vitro and in-vivo studies have validated Diosmin's extensive range of biological capabilities which present antioxidative, antihyperglycemic, anti-inflammatory, antimutagenic, and antiulcer properties. We have presented this review work because of the greater biological properties and influences of Diosmin. We have provided a brief overview of Diosmin, its pharmacology, major biological properties, such as anti-cancer, anti-diabetic, antibacterial, anticardiovascular, liver protection, and neuroprotection, therapeutic approach, potential Diosmin targets, and pathways that are known to be associated with it.

9.
Sci Rep ; 12(1): 7240, 2022 05 04.
Article in English | MEDLINE | ID: mdl-35508649

ABSTRACT

Cancer is among the highly complex disease and renal cell carcinoma is the sixth-leading cause of cancer death. In order to understand complex diseases such as cancer, diabetes and kidney diseases, high-throughput data are generated at large scale and it has helped in the research and diagnostic advancement. However, to unravel the meaningful information from such large datasets for comprehensive and minute understanding of cell phenotypes and disease pathophysiology remains a trivial challenge and also the molecular events leading to disease onset and progression are not well understood. With this goal, we have collected gene expression datasets from publicly available dataset which are for two different stages (I and II) for renal cell carcinoma and furthermore, the TCGA and cBioPortal database have been utilized for clinical relevance understanding. In this work, we have applied computational approach to unravel the differentially expressed genes, their networks for the enriched pathways. Based on our results, we conclude that among the most dominantly altered pathways for renal cell carcinoma, are PI3K-Akt, Foxo, endocytosis, MAPK, Tight junction, cytokine-cytokine receptor interaction pathways and the major source of alteration for these pathways are MAP3K13, CHAF1A, FDX1, ARHGAP26, ITGBL1, C10orf118, MTO1, LAMP2, STAMBP, DLC1, NSMAF, YY1, TPGS2, SCARB2, PRSS23, SYNJ1, CNPPD1, PPP2R5E. In terms of clinical significance, there are large number of differentially expressed genes which appears to be playing critical roles in survival.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Biomarkers, Tumor/genetics , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Computational Biology , Critical Pathways , Female , GTPase-Activating Proteins/metabolism , Gene Expression Profiling/methods , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , Humans , Integrin beta1 , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Male , Phosphatidylinositol 3-Kinases/metabolism , Protein Phosphatase 2/metabolism , Tumor Suppressor Proteins/genetics
10.
Comb Chem High Throughput Screen ; 25(14): 2452-2462, 2022.
Article in English | MEDLINE | ID: mdl-34348612

ABSTRACT

BACKGROUND: Coronavirus is an enclosed positive-sense RNA virus with club-like spikes extending from its surface. It is most typically associated with acute respiratory infections in humans, but its capacity to infect many host species and cause multiple illnesses makes it a complicated pathogen. The frequent encounters between wild animals and humans are a typical cause of infection. The zoonotic infections SARS-CoV and MERS-CoV are among the most common causes of serious respiratory illnesses in humans. AIM: The main goal of this research was to look at gene expression profiles in human samples that were either infected with coronavirus or were not, and compare the varied expression patterns and their functional implications. METHODS: The previously researched samples were acquired from a public database for this purpose, and the study was conducted, which included gene expression analysis, pathway analysis, and network-level comprehension. The results for differentially expressed genes, enriched pathways, and networks for prospective genes and gene sets are presented in the analysis. In terms of COVID-19 gene expression and its relationship to type 2 diabetes. RESULTS: We see a lot of genes that have different gene expression patterns than normal for coronavirus infection, but in terms of pathways, it appears that there are only a few sets of functions that are affected by altered gene expression, and they are related to infection, inflammation, and the immune system. CONCLUSION: Based on our study, we conclude that the potential genes which are affected due to infection are NFKBIA, MYC, FOXO3, BIRC3, ICAM1, IL8, CXCL1/2/5, GADD45A, RELB, SGK1, AREG, BBC3, DDIT3/4, EGR1, MTHFD2, and SESN2 and the functional changes are mainly associated with these pathways: TNF, cytokine, NF-kB, TLR, TCR, BCR, Foxo, and TGF signaling pathways are among them and there are additional pathways such as hippo signaling, apoptosis, estrogen signaling, regulating pluropotency of stem cells, ErbB, Wnt, p53, cAMP, MAPK, PI3K-AKT, oxidative phosphorylation, protein processing in endoplasmic reticulum, prolactin signaling, adipocytokine, neurotrophine signaling, and longevity regulating pathways. SMARCD3, PARL, GLIPR1, STAT2, PMAIP1, GP1BA, and TOX genes and PI3K-Akt, focal adhesion, Foxo, phagosome, adrenergic, osteoclast differentiation, platelet activation, insulin, cytokine- cytokine interaction, apoptosis, ECM, JAK-STAT, and oxytocin signaling appear as the linkage between COVID-19 and Type-2 diabetes.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Immune System , Animals , Humans , COVID-19/genetics , COVID-19/immunology , Cytokines , Diabetes Mellitus, Type 2/genetics , Gene Expression Profiling , Prospective Studies
11.
Life (Basel) ; 13(1)2022 Dec 22.
Article in English | MEDLINE | ID: mdl-36675976

ABSTRACT

The function of noncoding sequence variations at ZNF143 binding sites in breast cancer cells is currently not well understood. Distal elements and promoters, also known as cis-regulatory elements, control the expression of genes. They may be identified by functional genomic techniques and sequence conservation, and they frequently show cell- and tissue-type specificity. The creation, destruction, or modulation of TF binding and function may be influenced by genetic modifications at TF binding sites that affect the binding affinity. Therefore, noncoding mutations that affect the ZNF143 binding site may be able to alter the expression of some genes in breast cancer. In order to understand the relationship among ZNF143, gene expression patterns, and noncoding mutations, we adopted an integrative strategy in this study and paid close attention to putative immunological signaling pathways. The immune system-related pathways ErbB, HIF1a, NF-kB, FoxO, JAK-STAT, Wnt, Notch, cell cycle, PI3K-AKT, RAP1, calcium signaling, cell junctions and adhesion, actin cytoskeleton regulation, and cancer pathways are among those that may be significant, according to the overall analysis.

12.
Front Cell Infect Microbiol ; 11: 707905, 2021.
Article in English | MEDLINE | ID: mdl-34778101

ABSTRACT

Infectious diseases are the disorders caused by organisms such as bacteria, viruses, fungi, or parasites. Although many of them are permentantly hazardous, a number of them live in and on our bodies and they are normally harmless or even helpful. Under certain circumstances, some organisms may cause diseases and these infectious diseases may be passed directly from person to person or via intermediate vectors including insects and other animals. Dengue virus and Streptococcus pneumoniae are the critical and common sources of infectious diseases. So, it is critical to understand the gene expression profiling and their inferred functions in comparison to the normal and virus infected conditions. Here, we have analyzed the gene expression profiling for dengue hemorrhagic fever, dengue fever, and normal human dataset. Similar to it, streptococcus pneumoniae infectious data were analyzed and both the outcomes were compared. Our study leads to the conclusion that the dengue hemorrhagic fever arises in result to potential change in the gene expression pattern, and the inferred functions obviously belong to the immune system, but also there are some additional potential pathways which are critical signaling pathways. In the case of pneumoniae infection, 19 pathways were enriched, almost all these pathways are associated with the immune system and 17 of the enriched pathways were common with dengue infection except platelet activation and antigen processing and presentation. In terms of the comparative study between dengue virus and Streptococcus pneumoniae infection, we conclude that cell adhesion molecules (CAMs), MAPK signaling pathway, natural killer cell mediated cytotoxicity, regulation of actin cytoskeleton, and cytokine-cytokine receptor interaction are commonly enriched in all the three cases of dengue infection and Streptococcus pneumoniae infection, focal adhesion was enriched between classical dengue fever - dengue hemorrhagic fever, dengue hemorrhagic fever-normal samples, and SP, and antigen processing and presentation and Leukocyte transendothelial migration were enriched in classical dengue fever -normal samples, dengue hemorrhagic fever-normal samples, and Streptococcus pneumoniae infection.


Subject(s)
Dengue , Pneumococcal Infections , Animals , Gene Expression Profiling , Humans , Killer Cells, Natural , Microarray Analysis
13.
Sci Rep ; 11(1): 19576, 2021 10 01.
Article in English | MEDLINE | ID: mdl-34599215

ABSTRACT

There are a few biological functions or phenomenon which are universally associated with majority of the cancers and hypoxia and immune systems are among them. Hypoxia often occurs in most of the cancers which helps the cells in adapting different responses with respect to the normal cells which may be the activation of signaling pathways which regulate proliferation, angiogenesis, and cell death. Similar to it, immune signaling pathways are known to play critical roles in cancers. Moreover, there are a number of genes which are known to be associated with these hypoxia and immune system and appear to direct affect the tumor growth and propagations. Cancer is among the leading cause of death and oral cancer is the tenth-leading cause due to cancer death. In this study, we were mainly interested to understand the impact of alteration in the expression of hypoxia and immune system-related genes and their contribution to head and neck squamous cell carcinoma. Moreover, we have collected the genes associated with hypoxia and immune system from the literatures. In this work, we have performed meta-analysis of the gene and microRNA expression and mutational datasets obtained from public database for different grades of tumor in case of oral cancer. Based on our results, we conclude that the critical pathways which dominantly enriched are associated with metabolism, cell cycle, immune system and based on the survival analysis of the hypoxic genes, we observe that the potential genes associated with head and neck squamous cell carcinoma and its progression are STC2, PGK1, P4HA1, HK1, SPIB, ANXA5, SERPINE1, HGF, PFKM, TGFB1, L1CAM, ELK4, EHF, and CDK2.


Subject(s)
Disease Susceptibility , Hypoxia/metabolism , Immune System/immunology , Immune System/metabolism , Mouth Neoplasms/etiology , Mouth Neoplasms/metabolism , Signal Transduction , Computational Biology/methods , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Hypoxia/genetics , MicroRNAs , Mouth Neoplasms/pathology , Mutation , RNA Interference , RNA, Messenger
14.
Front Endocrinol (Lausanne) ; 12: 641888, 2021.
Article in English | MEDLINE | ID: mdl-33927693

ABSTRACT

Type-2 diabetes and obesity are among the leading human diseases and highly complex in terms of diagnostic and therapeutic approaches and are among the most frequent and highly complex and heterogeneous in nature. Based on epidemiological evidence, it is known that the patients suffering from obesity are considered to be at a significantly higher risk of type-2 diabetes. There are several pieces of evidence that support the hypothesis that these diseases interlinked and obesity may aggravate the risk(s) of type-2 diabetes. Multi-level unwanted alterations such as (epi-) genetic alterations, changes at the transcriptional level, and altered signaling pathways (receptor, cytoplasmic, and nuclear level) are the major sources that promote several complex diseases, and such a heterogeneous level of complexity is considered as a major barrier in the development of therapeutics. With so many known challenges, it is critical to understand the relationships and the shared causes between type-2 diabetes and obesity, and these are difficult to unravel and understand. For this purpose, we have selected publicly available datasets of gene expression for obesity and type-2 diabetes, have unraveled the genes and the pathways associated with the immune system, and have also focused on the T-cell signaling pathway and its components. We have applied a simplified computational approach to understanding differential gene expression and patterns and the enriched pathways for obesity and type-2 diabetes. Furthermore, we have also analyzed genes by using network-level understanding. In the analysis, we observe that there are fewer genes that are commonly differentially expressed while a comparatively higher number of pathways are shared between them. There are only 4 pathways that are associated with the immune system in case of obesity and 10 immune-associated pathways in case of type-2 diabetes, and, among them, only 2 pathways are commonly altered. Furthermore, we have presented SPNS1, PTPN6, CD247, FOS, and PIK3R5 as the overexpressed genes, which are the direct components of TCR signaling.


Subject(s)
Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/immunology , Insulin Resistance , Insulin/metabolism , Obesity/complications , Adult , Animals , Computer Simulation , Diabetes Mellitus, Type 2/complications , Female , Gene Expression Profiling , Gene Expression Regulation , Humans , Immune System , Middle Aged , Obesity/genetics , Obesity/immunology , Receptors, Antigen, T-Cell/metabolism , Signal Transduction , Subcutaneous Fat/metabolism
15.
Curr Pharm Des ; 26(41): 5293-5299, 2020.
Article in English | MEDLINE | ID: mdl-33155901

ABSTRACT

BACKGROUND: Dengue virus is a potential source of propagating dengue hemorrhagic fever. This virus leads to dengue hemorrhagic fever/dengue shock syndrome, benign syndrome, and severe syndrome and due to its infection, there occurs alterations at multiple levels such as gene expression and pathway levels. So, it is critical to understand the pathogenesis of dengue infection in terms of gene expression and the associated functions. METHODS: For this purpose, here, we have analyzed the temporal gene expression profiling for the dengue hemorrhagic fever dataset at 12, 24, and 48 hours. RESULTS: The outcome appears that the dengue hemorrhagic fever evolves differently at different time periods or stages. CONCLUSION: The change in the gene expression pattern increases exponentially from 12 hours to 48 hours and the number of altered functions (pathways) also increases. Wnt, apoptosis, and transcription signaling are among the critical pathways which are dominantly altered. In the initial phase (first 12 hours), only two pathways are altered due to dengue infection, while in the next 12 hours, eight pathways are altered, and finally, in the next 24 hours, 11 pathways are altered and most of these 11 pathways are very critical in terms of biological pathways and functions.


Subject(s)
Dengue Virus , Dengue , Causality , Dengue/genetics , Gene Expression Profiling , Humans
16.
Comb Chem High Throughput Screen ; 23(8): 788-796, 2020.
Article in English | MEDLINE | ID: mdl-32338213

ABSTRACT

AIM AND OBJECTIVE: Nipah virus (NiV) is a zoonotic virus of the paramyxovirus family that sporadically breaks out from livestock and spreads in humans through breathing resulting in an indication of encephalitis syndrome. In the current study, T cell epitopes with the NiV W protein antigens were predicted. MATERIALS AND METHODS: Modelling of unavailable 3D structure of W protein followed by docking studies of respective Human MHC - class I and MHC - class II alleles predicted was carried out for the highest binding rates. In the computational analysis, epitopes were assessed for immunogenicity, conservation, and toxicity analysis. T - cell-based vaccine development against NiV was screened for eight epitopes of Indian - Asian origin. RESULTS: Two epitopes, SPVIAEHYY and LVNDGLNII, have been screened and selected for further docking study based on toxicity and conservancy analyses. These epitopes showed a significant score of -1.19 kcal/mol and 0.15 kcal/mol with HLA- B*35:03 and HLA- DRB1 * 07:03, respectively by using allele - Class I and Class II from AutoDock. These two peptides predicted by the reverse vaccinology approach are likely to induce immune response mediated by T - cells. CONCLUSION: Simulation using GROMACS has revealed that LVNDGLNII epitope forms a more stable complex with HLA molecule and will be useful in developing the epitope-based Nipah virus vaccine.


Subject(s)
Epitopes, T-Lymphocyte/chemistry , Nipah Virus/immunology , Vaccination/methods , Amino Acid Sequence , Computational Biology , Epitopes, T-Lymphocyte/immunology , Humans , Molecular Docking Simulation , Peptides/chemistry , Peptides/metabolism , Protein Binding , Thermodynamics , Viral Proteins/chemistry , Viral Proteins/metabolism
17.
BMC Genomics ; 21(1): 161, 2020 Feb 14.
Article in English | MEDLINE | ID: mdl-32059637

ABSTRACT

BACKGROUND: Exploration of the bioactive components of bovine milk has gained global interest due to their potential applications in human nutrition and health promotion. Despite advances in proteomics profiling, limited studies have been carried out to fully characterize the bovine milk proteome. This study explored the milk proteome of Jersey and Kashmiri cattle at day 90 of lactation using high-resolution mass spectrometry based quantitative proteomics nano-scale LC-MS/Q-TOF technique. Data are available via ProteomeXchange with identifier PXD017412. RESULTS: Proteins from whey were fractionated by precipitation into high and low abundant proteins. A total of 81 high-abundant and 99 low-abundant proteins were significantly differentially expressed between Kashmiri and Jersey cattle, clearly differentiating the two breeds at the proteome level. Among the top differentiating proteins, the Kashmiri cattle milk proteome was characterised by increased concentrations of immune-related proteins (apelin, acid glycoprotein, CD14 antigen), neonatal developmental protein (probetacellulin), xenobiotic metabolising enzyme (flavin monooxygenase 3 (FMO3), GLYCAM1 and HSP90AA1 (chaperone) while the Jersey milk proteome presented higher concentrations of enzyme modulators (SERPINA1, RAC1, serine peptidase inhibitor) and hydrolases (LTF, LPL, CYM, PNLIPRP2). Pathway analysis in Kashmiri cattle revealed enrichment of key pathways involved in the regulation of mammary gland development like Wnt signalling pathway, EGF receptor signalling pathway and FGF signalling pathway while a pathway (T-cell activation pathway) associated with immune system regulation was significantly enriched in Jersey cattle. Most importantly, the high-abundant FMO3 enzyme with an observed 17-fold higher expression in Kashmiri cattle milk seems to be a characteristic feature of the breed. The presence of this (FMO3) bioactive peptide/enzyme in Kashmiri cattle could be economically advantageous for milk products from Kashmiri cattle. CONCLUSION: In conclusion, this is the first study to provide insights not only into the milk proteome differences between Kashmiri and Jersey cattle but also provides potential directions for application of specific milk proteins from Kashmiri cattle in special milk preparations like infant formula.


Subject(s)
Food Quality , Immune System/metabolism , Immunomodulation , Milk Proteins/metabolism , Proteome , Proteomics , Animals , Cattle , Chromatography, Liquid , Computational Biology/methods , Food Analysis , Gene Ontology , Proteomics/methods , Tandem Mass Spectrometry
18.
Int J Biol Macromol ; 143: 11-29, 2020 Jan 15.
Article in English | MEDLINE | ID: mdl-31811847

ABSTRACT

Fucoidan, a macromolecule, a type of polysaccharide and contains high percentage of fucose and sulfate ester groups and other compounds in low percentage. In the last decades, a number of interesting biological activities have been studied so fucoidan has been major focus of interest for exploring new drugs against the leading human diseases. It is known in relation to biological pathways and function that it activates the pathways which mediate apoptosis. Using LC-MS and interdisciplincary approach, we developed our goal to elucidate the potential difference between the crude and pure fucoidan and the interaction of fucoidan with potential signaling molecules STAT4 and IL12RB2. Based on our analysis, we conclude that there is major difference between crude and pure fucoidan in terms of identified metabolites and their functional relevance. It leads to the conclusion that there are 18 functions which are common between crude and pure fucoidans, 47 functions pure fucoidan specific, and 84 functions crude fucoidan specific which leads to the conclusion that even the fucoidans obtained from the same organism behave functionally completely different between the processing states (with/without processing) while docking study with STAT4 and IL12RB2 display very strong binding between fucoidan and both these signaling molecules.


Subject(s)
Chromatography, Liquid , Molecular Docking Simulation , Molecular Dynamics Simulation , Polysaccharides/chemistry , Tandem Mass Spectrometry , Chromatography, Liquid/methods , Humans , Metabolomics/methods , Models, Molecular , Molecular Conformation , Polysaccharides/metabolism , Structure-Activity Relationship , Tandem Mass Spectrometry/methods
19.
Int. arch. otorhinolaryngol. (Impr.) ; 23(3): 354-359, July-Sept. 2019. tab, graf
Article in English | LILACS | ID: biblio-1040017

ABSTRACT

Abstract Introduction Schwannomas are benign, solitary, encapsulated tumors that may originate at any site of the peripheral nervous system, with the exception of the olfactory and optic nerves. Schwannomas of the base of tongue are very rare, and only sporadic cases are documented. The tongue base represents a challenge for surgeons. Carbon dioxide (CO2) laser might provide an effective surgical option for such lesions because of the easy access to the lesion, the bloodless surgical field and optimum epithelization of wounds. Objective We present an unusual case of pedunculated schwannoma of the tongue base treated via transoral CO2-assisted excision. We also provide a review of the available literature, in English language, on humans. Data synthesis The authors searched the PubMed database and Google up to July 2018. The following search terms were applied: tongue and lingual, combined with schwannoma and neurilemmoma. Titles and abstracts were screened, and, then, only supraglottic (hypopharyngeal) tongue base masses were considered. Fourteen articles were included in this review, reporting 17 cases. The age of the patients ranged from 9 to 39 years, affecting predominantly females. Dysphagia and lump sensations were the most common presenting symptoms, and the mean follow-up period range was 1.5 to 60 months (mean = 13 months). There was no evidence of recurrence in any of the cases. Conclusion We could conclude that tongue base schwannomas are rare. Transoral complete excision of the tumor is the treatment of choice. CO2 laser surgery is a minimally invasive treatment option that has been performed in few reports with no recurrence and with favorable outcomes.


Subject(s)
Humans , Male , Female , Child , Adolescent , Adult , Middle Aged , Aged , Tongue Neoplasms/surgery , Carbon Dioxide/therapeutic use , Laser Therapy/methods , Neurilemmoma/surgery , Tomography, X-Ray Computed , Diagnosis, Differential , Neurilemmoma/diagnosis , Neurilemmoma/pathology
20.
Int Arch Otorhinolaryngol ; 23(3): e354-e359, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31360258

ABSTRACT

Introduction Schwannomas are benign, solitary, encapsulated tumors that may originate at any site of the peripheral nervous system, with the exception of the olfactory and optic nerves. Schwannomas of the base of tongue are very rare, and only sporadic cases are documented. The tongue base represents a challenge for surgeons. Carbon dioxide (CO 2 ) laser might provide an effective surgical option for such lesions because of the easy access to the lesion, the bloodless surgical field and optimum epithelization of wounds. Objective We present an unusual case of pedunculated schwannoma of the tongue base treated via transoral CO 2 -assisted excision. We also provide a review of the available literature, in English language, on humans. Data synthesis The authors searched the PubMed database and Google up to July 2018. The following search terms were applied: tongue and lingual, combined with schwannoma and neurilemmoma . Titles and abstracts were screened, and, then, only supraglottic (hypopharyngeal) tongue base masses were considered. Fourteen articles were included in this review, reporting 17 cases. The age of the patients ranged from 9 to 39 years, affecting predominantly females. Dysphagia and lump sensations were the most common presenting symptoms, and the mean follow-up period range was 1.5 to 60 months (mean = 13 months). There was no evidence of recurrence in any of the cases. Conclusion We could conclude that tongue base schwannomas are rare. Transoral complete excision of the tumor is the treatment of choice. CO 2 laser surgery is a minimally invasive treatment option that has been performed in few reports with no recurrence and with favorable outcomes.

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