14 research outputs found
Identification of new key genes and their association with breast cancer occurrence and poor survival using in silico and in vitro methods
Breast cancer is one of the most prevalent types of cancer diagnosed globally and continues to have a significant impact on the global number of cancer deaths. Despite all efforts of epidemiological and experimental research, therapeutic concepts in cancer are still unsatisfactory. Gene expression datasets are widely used to discover the new biomarkers and molecular therapeutic targets in diseases. In the present study, we analyzed four datasets using R packages with accession number GSE29044, GSE42568, GSE89116, and GSE109169 retrieved from NCBI-GEO and differential expressed genes (DEGs) were identified. Proteinâprotein interaction (PPI) network was constructed to screen the key genes. Subsequently, the GO function and KEGG pathways were analyzed to determine the biological function of key genes. Expression profile of key genes was validated in MCF-7 and MDA-MB-231 human breast cancer cell lines using qRT-PCR. Overall expression level and stage wise expression pattern of key genes was determined by GEPIA. The bc-GenExMiner was used to compare expression level of genes among groups of patients with respect to age factor. OncoLnc was used to analyze the effect of expression levels of LAMA2, TIMP4, and TMTC1 on the survival of breast cancer patients. We identified nine key genes, of which COL11A1, MMP11, and COL10A1 were found up-regulated and PCOLCE2, LAMA2, TMTC1, ADAMTS5, TIMP4, and RSPO3 were found down-regulated. Similar expression pattern of seven among nine genes (except ADAMTS5 and RSPO3) was observed in MCF-7 and MDA-MB-231 cells. Further, we found that LAMA2, TMTC1, and TIMP4 were significantly expressed among different age groups of patients. LAMA2 and TIMP4 were found significantly associated and TMTC1 was found less correlated with breast cancer occurrence. We found that the expression level of LAMA2, TIMP4, and TMTC1 was abnormal in all TCGA tumors and significantly associated with poor survival.Indian Council of Medical Research | Ref. BMI/11/(35)/2020MICINN | Ref. RYC-2017-2289
Identification of potential therapeutic targets for COVID-19 through a structural-based similarity approach between SARS-CoV-2 and its human host proteins
Background: The COVID-19 pandemic caused by SARS-CoV-2 has led to millions of deaths worldwide, and vaccination efficacy has been decreasing with each lineage, necessitating the need for alternative antiviral therapies. Predicting hostâvirus proteinâprotein interactions (HV-PPIs) is essential for identifying potential host-targeting drug targets against SARS-CoV-2 infection.Objective: This study aims to identify therapeutic target proteins in humans that could act as virusâhost-targeting drug targets against SARS-CoV-2 and study their interaction against antiviral inhibitors.Methods: A structure-based similarity approach was used to predict human proteins similar to SARS-CoV-2 (âhCoV-2â), followed by identifying PPIs between hCoV-2 and its target human proteins. Overlapping genes were identified between the protein-coding genes of the target and COVID-19-infected patientâs mRNA expression data. Pathway and Gene Ontology (GO) term analyses, the construction of PPI networks, and the detection of hub gene modules were performed. Structure-based virtual screening with antiviral compounds was performed to identify potential hits against target gene-encoded protein.Results: This study predicted 19,051 unique target human proteins that interact with hCoV-2, and compared to the microarray dataset, 1,120 target and infected group differentially expressed genes (TIG-DEGs) were identified. The significant pathway and GO enrichment analyses revealed the involvement of these genes in several biological processes and molecular functions. PPI network analysis identified a significant hub gene with maximum neighboring partners. Virtual screening analysis identified three potential antiviral compounds against the target gene-encoded protein.Conclusion: This study provides potential targets for host-targeting drug development against SARS-CoV-2 infection, and further experimental validation of the target protein is required for pharmaceutical intervention
Effect of hospitalization on rest-activity rhythm and quality of life of cancer patients
549-558Rest-activity rhythm and quality of life
(QoL) in three cohorts, namely (1) cancer in-patients, (2) out-patients, and
(3) control subjects were studied. The patients of the former two groups  were chosen randomly from the Regional Cancer
Center, Raipur, India.
All patients received chemotherapy for 3-4 consecutive days. The in-patients
remained hospitalized for the entire period of chemotherapy plus one day post
treatment. The out-patients, unlike the in-patients, went to their homes daily
after treatment. Rest-activity rhythm of the patients was monitored  using Actical.
Quality of life (QoL) and psychological status of patients were assessed using
EORTC QLQ-C30 and Hospital Anxiety & Depression Scale, respectively. Each
subject exhibited significant circadian rhythm in rest-activity. The average
values for Mesor, amplitude, peak activity, <span style="mso-bidi-font-style:
italic">autocorrelation coefficient and dichotomy index of all three
groups varied significantly between one group to the other in the following
order: in-patient < out-patient < control. Further, quality of life,
measured from responses on functional and symptom scales, was better off in
cancer out-patients compared to the in-patients. It is concluded that
hospitalization alters rest-activity rhythm parameters markedly and
deteriorates QoL in cancer patients. Nevertheless, further extensive
investigation is desirable to support the above speculation and to ascertain if
hospitalization produces similar effects on patients suffering from diseases
other than cancer.
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Unraveling epigenetic interplay between inflammation, thrombosis, and immune-related disorders through a network meta-analysis
Inflammation and thrombosis are two distinct yet interdependent physiological processes. The inflammation results in the activation of the coagulation system that directs the immune system and its activation, resulting in the initiation of the pathophysiology of thrombosis, a process termed immune-thrombosis. Still, the shared underlying molecular mechanism related to the immune system and coagulation has not yet been explored extensively. Inspired to answer this, we carried out a comprehensive gene expression meta-analysis using publicly available datasets of four diseases, including venous thrombosis (VT), Systemic lupus erythematosus (SLE), Rheumatoid arthritis (RA), and Inflammatory Bowel Disease (IBD). A total of 609 DEGs shared by all four datasets were identified based on the combined effect (ES) approach. The pathway enrichment analysis of the DEGs showed enrichment of various epigenetic pathways such as histone modifying enzymes, post-translational protein modification, chromatin organization, chromatin modifying enzymes, HATs acetylate proteins. Network-based protein-protein interaction analysis showed epigenetic enzyme coding genes dominating among the top hub genes. The miRNA interacting partner of the top 10 hub genes was determined. The predomination of epitranscriptomics regulation opens a layout for the meta-analysis of miRNA datasets of the same four diseases. We identified 30 DEmiRs shared by these diseases. There were 9 common DEmiRs selected from the list of miRNA interacting partners of top 10 hub genes and shared significant DEmiRs from microRNAs dataset acquisition. These common DEmiRs were found to regulate genes involved in epigenetic modulation and indicate a promising epigenetic aspect that needs to be explored for future molecular studies in the context of immunothrombosis and inflammatory disease
Dim Light at Night Induced Neurodegeneration and Ameliorative Effect of Curcumin
It is a well-known fact that following a proper routine light/dark or diurnal rhythm controls almost all biological processes. With the introduction of modern lighting and artificial illumination systems, continuous exposure to light at night may lead to the disruption of diurnal rhythm. However, the effect of light during the night on brain anatomy, physiology, and human body functions is less explored and poorly understood. In this study, we have evaluated the effect of exposure to dim light (5 lux) at night (dLAN) on Swiss Albino mice over a duration of three consecutive weeks. Results have revealed that exposure to dLAN led to an impairment of cognitive and non-cognitive behaviour, oxidative stress–mediated elevation of lipid peroxidation, and reduction of superoxide dismutase and catalase activity. It also led to the downregulation of hippocampal proteins (BDNF, Synapsin II and DCX) at both protein and mRNA level. Additionally, there was downregulation of CREB and SIRT1 mRNAs and neurodegeneration-associated miRNA21a-5p and miRNA34a-5p. The pyramidal and cortical neurons started showing pyknotic and chromatolysis characteristics. However, a dose of curcumin administered to the mice positively modulated these parameters in our experimental animals. We proposed the modulatory role of curcumin in addressing the deleterious effects of dLAN