RESUMO
Adipocytes play a crucial role in the metabolism of lipids and sugars. Their response varies depending on the circumstances or other factors influenced by physiological and metabolic stresses. People living with HIV (PLWH) experience different effects of HIV and highly active antiretroviral therapy (HAART) on their body fat. Some patients respond well to antiretroviral therapy (ART), while others taking similar regimens do not. The genetic makeup of patients has been strongly linked to the variable responses to HAART among PLWH. The cause of HIV-associated lipodystrophy syndrome (HALS) is not well understood, but it may be influenced by genetic variations in the host. The metabolism of lipid effectively modulates plasma triglyceride and high-density lipoprotein cholesterol levels in PLWH. Genes related to drug metabolism and transport play an important role in the transportation and metabolism of ART drugs. Genetic variation in metabolizing enzyme genes of antiretroviral drugs, lipid transport and transcription factor-related genes could interfere with fat storage and metabolism, contributing to the development of HALS. Hence we examined the impact of genes associated with transport, metabolism and various transcription factors in metabolic complications, and their impact on HALS. A study using databases such as PubMed, EMBASE and Google Scholar was conducted to understand the impact of these genes on metabolic complications and HALS. The present article discuss the changes in the expression and regulation of genes and their involvement in the lipid metabolism, lipolysis and lipogenesis pathways. Moreover, alteration of the drug transporter, metabolizing enzyme and various transcription factors can lead to HALS. Single-nucleotide polymorphisms in genes that play an essential role in drug metabolism and drug and lipid transportation may also contribute to individual differences in the emergence of metabolic and morphological alterations during HAART treatment.
Assuntos
Infecções por HIV , Síndrome de Lipodistrofia Associada ao HIV , Humanos , Síndrome de Lipodistrofia Associada ao HIV/genética , Síndrome de Lipodistrofia Associada ao HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Proteínas de Membrana Transportadoras , Lipídeos , Genes Reguladores , Fatores de Transcrição/metabolismo , Variação GenéticaRESUMO
Cytokines affect lipid and glucose metabolism and also alter the body's habitus. They play a role in the development of lipodystrophy syndrome. Adipocytes secrete the pro-inflammatory cytokines IL-1, TNF-α and IL-6. The plasma cytokine concentration is associated with the percentage and distribution of fat tissue in the body. The metabolic disturbances are strongly associated with increased levels of pro-inflammatory cytokines (IL-1, IL-6 and TNF-α). Plasma levels of cytokines such as TNF-α, IL-6 and leptin were found to be increased while plasma resistin levels were found to be variable in patients suffering from obesity and type II diabetes mellitus. Until now, limited information has been available on the polymorphism of cytokine and adipokine genes in patients of HIV-associated lipodystrophy (HIVLD), which can contribute to individual variations in susceptibility to metabolic diseases, especially to HIVLD. Hence, we studied the association of cytokine and adipokine gene polymorphisms in various diseases and their impact on HIVLD. We carry out an extensive search using several databases, including PubMed, EMBASE and Google Scholar. The distribution of cytokine and adipokine gene polymorphisms and their expression levels varied among various populations. We examined the variants of cytokine and adipokine genes, which can contribute to individual variations in susceptibility to metabolic diseases, especially to HIVLD. In the current review, we present a brief account of the risk factors of HIVLD, the pathogenesis of HIVLD and the polymorphism of cytokine and adipokine genes in various diseases with special reference to their impact on HIVLD.
Assuntos
Diabetes Mellitus Tipo 2 , Síndrome de Lipodistrofia Associada ao HIV , Lipodistrofia , Humanos , Citocinas/genética , Citocinas/metabolismo , Adipocinas/genética , Síndrome de Lipodistrofia Associada ao HIV/genética , Síndrome de Lipodistrofia Associada ao HIV/patologia , Fator de Necrose Tumoral alfa , Interleucina-6 , Interleucina-1RESUMO
Last two decades have witnessed several global infectious outbreaks. Among these, coronavirus is identified as a prime culprit ranging from its involvement in severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) to COVID-19. These infections involved in huge healthcare and economic cost incurred globally. Every time, coronavirus improved its infection ability and surprised the medical practitioners and researchers. Currently, COVID-19 is also causing numerous infections and stalled global activities. Global efforts are underway to identify potential viral targets for management of these outbreaks, but significant progress in prevention of these outbreaks is not yet achieved. We explored host-pathogen protein-protein interactions of MERS, SARS and COVID-19, and identified host targets common among all recent coronavirus outbreaks. Further, we tried to understand their potential for management of coronavirus. The common proteins involved in coronavirus host-pathogen interactions indicate their indispensable role in the pathogenesis and therefore targeting these proteins can give strategies to prevent current and future coronavirus outbreaks. Viral variability necessitates development of new therapeutic modalities for every outbreak, in contrast targeting necessary human proteins required by all coronaviruses can provide us a clue to prevent current and future coronavirus outbreaks. We found that targeting FURIN and TMPRSS2 can provide good results due to their common involvement in current and previous outbreaks. We also listed some known molecules against these two targets for their potential drug repurposing evaluation. Although, several recent studies undergoing with targeting these proteins for management of coronavirus, but safety evaluation and risk assessment must be given prime importance while targeting human proteins.
Assuntos
COVID-19/epidemiologia , COVID-19/virologia , Surtos de Doenças , Interações Hospedeiro-Patógeno , SARS-CoV-2/metabolismo , Furina/metabolismo , Humanos , Mapas de Interação de Proteínas , Serina Endopeptidases/metabolismoRESUMO
A number of articles have discussed the potential of microbiota in oncogenesis. Several of these have evaluated the modulation of microbiota and its influence on cancer development. Even in recent past, a plethora of studies have gathered in order to understand the difference in microbiota population among different cancer and normal individuals. Although in majority of studies, microbiota mediated oncogenesis has been primarily attributed to the inflammatory mechanisms, there are several other ways through which microbiota can influence oncogenesis. These relatively less discussed aspects including the hormonal modulation through estrobolome and endobolome, production of cyclomodulins, and lateral gene transfer need more attention of scientific community. We prepared this article to discuss the role of microbiota in oncogenesis in order to provide concise information on these relatively less discussed microbiota mediated oncogenesis mechanisms.
Assuntos
Microbiota , Neoplasias , Humanos , Carcinogênese , Microbiota/genética , Interações entre Hospedeiro e MicrorganismosRESUMO
COVID-19 caused a global catastrophe with a large number of cases making it one of the major pandemics of the human history. The clinical presentations of the disease are continuously challenging healthcare workers with the variation of pandemic waves and viral variants. Recently, SARS-CoV2 patients have shown increased occurrence of invasive pulmonary aspergillosis infection even in the absence of traditional risk factors. The mechanism of COVID-19-associated aspergillosis is not completely understood and therefore, we performed this system biological study in order to identify mechanistic implications of aspergillosis susceptibility in COVID-19 patients and the important targets associated with this disease. We performed host-pathogen interaction (HPI) analysis of SARS-CoV2, and most common COVID-19-associated aspergillosis pathogen, Aspergillus fumigatus, using in silico approaches. The known host-pathogen interactions data of SARS-CoV2 was obtained from BIOGRID database. In addition, A. fumigatus host-pathogen interactions were predicted through homology modeling. The human targets interacting with both pathogens were separately analyzed for their involvement in aspergillosis. The aspergillosis human targets were screened from DisGeNet and GeneCards. The aspergillosis targets involved in both HPI were further analyzed for functional overrepresentation analysis using PANTHER. The results indicate that both pathogens interact with a number of aspergillosis targets and altogether they recruit more aspergillosis targets in host-pathogen interaction than alone. Common aspergillosis targets involved in HPI with both SARS-CoV2 and A. fumigatus can indicate strategies for the management of both conditions by modulating these common disease targets.
Assuntos
Aspergilose , COVID-19 , Humanos , Aspergillus fumigatus , RNA Viral , SARS-CoV-2 , Interações Hospedeiro-PatógenoRESUMO
MOTIVATION: The outbreak of COVID-2019 initiated at Wuhan, China has become a global threat by rapid transmission and severe fatalities. Recent studies have uncovered whole genome sequence of SARS-CoV-2 (causing COVID-2019). In addition, lung metagenomic studies on infected patients revealed overrepresented Prevotella spp. producing certain proteins in abundance. We performed host-pathogen protein-protein interaction analysis between SARS-CoV-2 and overrepresented Prevotella proteins with human proteome. We also performed functional overrepresentation analysis of interacting proteins to understand their role in COVID-2019 severity. RESULTS: It was found that overexpressed Prevotella proteins can promote viral infection. As per the results, Prevotella proteins, but not viral proteins, are involved in multiple interactions with NF-kB, which is involved in increasing clinical severity of COVID-2019. Prevotella may have role in COVID-2019 outbreak and should be given importance for understanding disease mechanisms and improving treatment outcomes. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Assuntos
Proteínas de Bactérias/imunologia , Infecções por Coronavirus/complicações , Interações Hospedeiro-Patógeno , Pneumonia Viral/complicações , Prevotella , Mapeamento de Interação de Proteínas , Infecções por Bacteroidaceae/complicações , Betacoronavirus , COVID-19 , China , Humanos , NF-kappa B , Pandemias , SARS-CoV-2RESUMO
BACKGROUND: Several studies have linked chronic typhoid infection with gallbladder carcinoma without completely understood mechanism. This study was performed in order to understand role of Salmonella in gallbladder cancer etiology. METHODS: Known Salmonella host-pathogen interactions were screened from database in addition to known gallbladder carcinoma targets. Host-pathogen interaction map of S. enterica was prepared and screened for interactions with gallbladder carcinoma targets. Further functional overrepresentation analysis was performed to understand the role of human targets involved in Salmonella host-pathogen interactions in gallbladder carcinoma. RESULTS: Salmonella interact with several human proteins involved in gallbladder carcinoma. MAPK and RAC1 are the most important human proteins based on node degree value among all GBC associated interactors identified in current data search. Functional over-representation analysis reveals that Salmonella can induce adenocarcinoma which constitutes 85% of gallbladder cancer. CONCLUSION: Though, the role of MAPK/ERK and PI3K/AKT/mTOR pathway is already suggested for Salmonella mediated gallbladder cancer, but current data based approach indicate several new insight for exploration of the role of Salmonella in gallbladder cancer etiology. The results indicate about several other processes including CREB/SP-1 and BSG(CD147) signaling, that must be given consideration for understanding the role of Salmonella in gallbladder cancer.
Assuntos
Neoplasias da Vesícula Biliar , Salmonella enterica , Interações Hospedeiro-Patógeno , Humanos , Proteínas Quinases Ativadas por Mitógeno , Salmonella , Proteínas rac1 de Ligação ao GTPRESUMO
BACKGROUND: Long period of SARS-CoV-2 infection has been associated with psychiatric and cognitive disorders in adolescents and children. SARS-CoV-2 remains dormant in the CNS leading to neurological complications. The wide expression of ACE2 in the brain raises concern for its involvement in SARS-CoV-2 infection. Though, the mechanistic insights about blood-brain barriers (BBB) crossing by SARS-CoV-2 and further brain infection are still not clear. Moreover, the mechanism behind dormant SARS-CoV-2 infections leading to chronic neurological disorders needs to be unveiled. There is an urgent need to find out the risk factor involved in COVID-19-associated neurological disease. Therefore, the role of immune-associated genes in the pathogenesis of COVID-19 associated neurological diseases is presented which could contribute to finding associated genetic risk factors. METHOD: The search utilizing multiple databases, specifically, EMBASE, PubMed (Medline), and Google Scholar was performed. Moreover, the literature survey on the involvement of COVID-19, neuropathogenesis, and its consequences was done. DESCRIPTION: Persistent inflammatory stimuli may promote the progression of neurodegenerative diseases. An increased expression level of cytokine, chemokine, and decreased expression level of immune cells has been associated with the COVID-19 patient. Cytokine storm was observed in severe COVID-19 patients. The nature of SARS-CoV-2 infection can be neuroinflammatory. Genes of immune response could be associated with neurodegenerative diseases. CONCLUSION: The present review will provide a useful framework and help in understanding COVID-19-associated neuropathogenesis. Experimental studies on immune-associated genes in COVID-19 patients with neurological manifestations could be helpful to establish its neuropathogenesis.
Assuntos
COVID-19 , Doenças Neurodegenerativas , Adolescente , Encéfalo , Citocinas , Humanos , SARS-CoV-2RESUMO
BACKGROUND: A carboxypeptidase protein called ACE2 is found in many organs. ACE2 protein can play a pivotal role to regulate the pathological changes of several diseases including COVID-19. TMPRSS2 gene is expressed in many human tissues and plays a critical role in spreading the infection of the viruses including coronavirus and progression of prostate cancer, and hence could be used as a potential drug target. There are limited reports on occurrence of genetic polymorphism of ACE2 and TMPRSS2 in general population, expressions in pathological conditions, and its impact on COVID-19 disease. Hence we comprehended the occurrence of ACE2, TMPRSS2 polymorphism in general population, expression in various diseases and its impact on COVID-19 disease. METHOD: We utilized multiple databases, PubMed (Medline), EMBASE and Google Scholar for literature search. DESCRIPTION: ACE2 polymorphisms have significant linkages with various diseases, including severity of SARS-CoV-2 infection. Genetic variations of these genes contribute to individual's genetic susceptibility to viral infection and its subsequent clearance. The diversity and variations in the population distribution of these genes, might greatly influence and in turn reflect into the observed population and gender differences of the severity and clinical outcomes of SARS-CoV-2 infection. CONCLUSION: There are diversities in distribution of ACE2 and TMPRSS2 polymorphisms among different populations. Analyzing the genetic variants and expression of ACE2 and TMPRSS2 genes, in a population may provide the genetic marker for susceptibility or resistance against the coronavirus infection, which might be useful for identifying the susceptible population groups for targeted interventions and for making relevant public health policy decisions.
Assuntos
Enzima de Conversão de Angiotensina 2/genética , COVID-19/genética , Serina Endopeptidases/genética , COVID-19/enzimologia , COVID-19/virologia , Bases de Dados Factuais , Expressão Gênica , Predisposição Genética para Doença , Genética Populacional , Humanos , Polimorfismo Genético , SARS-CoV-2/isolamento & purificaçãoRESUMO
Microbial pathogenesis involves several aspects of host-pathogen interactions, including microbial proteins targeting host subcellular compartments and subsequent effects on host physiology. Such studies are supported by experimental data, but recent detection of bacterial proteins localization through computational eukaryotic subcellular protein targeting prediction tools has also come into practice. We evaluated inter-kingdom prediction certainty of these tools. The bacterial proteins experimentally known to target host subcellular compartments were predicted with eukaryotic subcellular targeting prediction tools, and prediction certainty was assessed. The results indicate that these tools alone are not sufficient for inter-kingdom protein targeting prediction. The correct prediction of pathogen's protein subcellular targeting depends on several factors, including presence of localization signal, transmembrane domain and molecular weight, etc., in addition to approach for subcellular targeting prediction. The detection of protein targeting in endomembrane system is comparatively difficult, as the proteins in this location are channelized to different compartments. In addition, the high specificity of training data set also creates low inter-kingdom prediction accuracy. Current data can help to suggest strategy for correct prediction of bacterial protein's subcellular localization in host cell.
Assuntos
Proteínas de Bactérias/análise , Biologia Computacional/métodos , Interações Hospedeiro-Patógeno , Modelos Biológicos , Proteoma/análise , Animais , Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Membrana Celular/metabolismo , Citoplasma/metabolismo , Bases de Dados de Proteínas , Humanos , Proteoma/metabolismo , Software , Frações SubcelularesRESUMO
Recent past years have witnessed the development of several artificial enzymes, using different materials to mimic natural enzymes with respect to their structure and functions. The nanozymes are nanomaterials possessing similar characteristics to the natural enzymes and have emerged recently as an innovative class of artificial enzymes. The nanozymes have got remarkable attention from the researchers and notable developments have been achieved owing to their unique properties compared with natural enzymes and classic artificial enzymes. In this regard, several nanomaterials have been scrutinized so far to mimic different natural enzymes for wider applications ranging from imaging, sensing, water treatment, pollutant removal, and therapeutics. The applications of nanozymes in biomedicine research are fast-growing and various nanozymes have been implicated in diagnostic medicine, targeted cancer therapy. Such abilities make them an appropriate alternative for the development of affordable, sustainable and safe diagnostic as well as therapeutic agents.
Assuntos
Materiais Biomiméticos/química , Técnicas Biossensoriais , Enzimas/química , Nanoestruturas/químicaRESUMO
Squamous cell carcinoma (SCC) is the most common cancer worldwide. The treatment of locally advanced disease generally requires various combinations of radiotherapy, surgery, and systemic therapy. Despite aggressive multimodal treatment, most of the patients relapse. Identification of molecules that sustain cancer cell growth and survival has made molecular targeting a feasible therapeutic strategy. Survivin is a member of the Inhibitor of Apoptosis Protein (IAP) family, which is overexpressed in most of the malignancies including SCC and totally absent in most of the normal tissues. This feature makes survivin an ideal target for cancer therapy. It orchestrates several important mechanisms to support cancer cell survival including inhibition of apoptosis and regulation of cell division. Overexpression of survivin in tumors is also associated with poor prognosis, aggressive tumor behavior, resistance to therapy, and high tumor recurrence. Various strategies have been developed to target survivin expression in cancer cells, and their effects on apoptosis induction and tumor growth attenuation have been demonstrated. In this review, we discuss recent advances in therapeutic potential of survivin in cancer treatment.
Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Proteínas Inibidoras de Apoptose/efeitos dos fármacos , Antineoplásicos/farmacologia , Apoptose , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/fisiopatologia , Proliferação de Células , Humanos , SurvivinaRESUMO
Cobalt oxide nanoparticles (Co3O4-NPs) were synthesized using simple urea-based thermal decomposition method. Phase purity and particle size of as-synthesized nanoparticles were characterized through X-ray diffraction pattern (XRD) and transmission electron microscopy. Through XRD morphology of the Co3O4-NPs was found to be variable in size with range of 36 nm. In our present study, we explored the potential cytotoxic and antibacterial effects of Co3O4-NPs in human colorectal types of cancerous cells (HT29 and SW620) and also nine Gram-positive and Gram-negative bacteria. Co3O4-NPs showed promising anticancer activity against HT29 and SW620 cells with IC50 value of 2.26 and 394.5 µg/mL, respectively. However, no significant effect of Co3O4-NPs was observed against bacterial strains. Furthermore, a detailed study has been carried out to investigate the possible mechanism of cell death in HT29 cancer cell line through the analysis of expression level of anti-apoptotic Bcl2 and BclxL markers. Western blot analysis results suggested significant role of Co3O4-NPs exposure in cell death due to apoptosis.
Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Bactérias/efeitos dos fármacos , Cobalto/farmacologia , Nanopartículas Metálicas , Óxidos/farmacologia , Antibacterianos/química , Antineoplásicos/química , Bioensaio , Western Blotting , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cobalto/química , Relação Dose-Resposta a Droga , Humanos , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Transmissão , Óxidos/químicaRESUMO
Eighteen N-(4-aryl/cyclohexyl)-2-(pyridine-4-yl carbonyl) hydrazinecarbothioamide derivatives were synthesized, evaluated against ten clinical isolates of Candida spp. and compared with itraconazole. Introduction of p-chloro (2c), p-iodo (2q), m-chloro (2l) and o-nitro (2r) substitution at phenyl ring of thiosemicarbazide enhanced the anti-Candida activity. Compound (2c) bearing p-cholorophenyl ring was found to be the most effective against Candida albicans ATCC 66027, Candida spp. 12810 (blood) and Candida spp. 178 (HVS) with MIC value of 0.09-0.78 µg/mL, whereas itraconazole exhibits the inhibitory activity with MIC value of 0.04-1.56 µg/mL against all tested strains. There is a correlation between anti-Candidal activity and p-chloro substitution at phenyl ring of thiosemicarbazide. All synthesized compounds were investigated for their potential cytotoxicity against non cancer cell line MCF-10A. The active compounds 2c, 2r and 2a were further investigated for their cytotoxic effects on three cancer cell lines; HT1080 (skin), HepG2 (liver) and A549 (lung). The active compounds showed minimal cytotoxic activity against non cancer cell line and all three cancer cell lines. Moreover, compound 2c displaying better activity against C. albicans ATCC66027 and Candida spp. [blood] compared to reference drug (itraconazole), represents a good lead for the development of newer, potent and broad spectrum anti-Candidal agents.
Assuntos
Antifúngicos/síntese química , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Hidrazinas/química , Piridinas/química , Tioamidas/química , Antifúngicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Farmacorresistência Fúngica , Células Hep G2 , Humanos , Testes de Sensibilidade Microbiana , Conformação Molecular , Tioamidas/síntese química , Tioamidas/farmacologiaRESUMO
The growing interest of the scientific community in the study of probiotics has gathered valuable data about its beneficial effects for multiple clinical conditions. This data also provides evidence for the functions and properties of probiotics and how they contribute to health benefits by influencing normal microbiota. Lactobacillus is an important genus which has long been utilized in the food industry and is also found as normal oral, intestinal and vaginal microbiota. Lactobacillus has shown multiple health benefits but its relative importance as a probiotic is majorly explored for gastrointestinal health. Healthy vaginal microbiota typically harbors Lactobacillus spp. providing several health benefits for female reproductive health, but there is more data required in order to compare the relative benefits with probiotic Lactobacillus added through either natural food sources or with standard probiotics supplements. The present article discusses the current status of knowledge about vaginal Lactobacillus as a probiotic and also compares the potential of probiotics from natural sources and through supplements along with recent approaches in this area.
RESUMO
Microbial communities coexisting with humans are collectively known as microbiome. It influences almost every aspect of an individual's body function. Microbiome is idiosyncratic for body condition and its alteration is indicative for several abnormalities. This article discusses about recent ideas for developing microbiology based cancer indicators using alterations in microbiome. It is noteworthy that large exploratory studies are required to identify cancer indicator microorganisms from complex and diverse microbiome constituents. This complexity also warrants that these markers should be used in conjunction with other routine cancer indicators. The present article concludes that such studies can spur development of novel microbiome based cancer diagnostics.
Assuntos
Metagenoma , Neoplasias/microbiologia , Animais , Transformação Celular Neoplásica , Humanos , Neoplasias/diagnóstico , Neoplasias/imunologiaRESUMO
Infections associated with cancer are a major scourge and cause of substantial morbidity and mortality in cancer patients. The aim of present study was to appraise the in vitro activity of anticancer agent vincristine and antifungal fluconazole alone and in combination against Candida spp. Results were interpreted in terms of fractional inhibitory concentration index (FICI). Antifungal activity of fluconazole showed marked synergism when used in combination with vincristine, with FICI ranging from 0.25-0.5 against different Candida spp. Although, the use of vincristine with fluconazole is always disputed due to its side effects including decreased peristalsis, but the present research can help to perform suitability analysis of fluconazole use in life threatening invasive candidiasis associated with cancer patients. In addition, the synergism in antifungal activity after using with vincristine also warrants further research in the direction of minimizing adverse reaction associated with combined use of fluconazole and vincristine.
Assuntos
Antifúngicos/farmacologia , Antineoplásicos/farmacologia , Candida/efeitos dos fármacos , Fluconazol/farmacologia , Vincristina/farmacologia , Candida/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Quimioterapia Combinada , Testes de Sensibilidade MicrobianaRESUMO
Tuberculosis (TB) among patients with human immunodeficiency virus (HIV) is a major global health burden and contributes to a high mortality rate due to HIV-mediated immunosuppression and subsequent susceptibility to TB. It is imperative to understand the pathogenesis of the association between HIV and TB for therapeutic innovation and preventive medicine. In the present study, we employed transcriptomic and bioinformatic analyses of differential gene expression data obtained from Gene Expression Omnibus (GEO) of the National Center for Biotechnology Information. The expression data of Mycobacterium tuberculosis-infected macrophages and blood samples from TB patients (GSE54992, GSE52819, and GSE19435) and blood samples from HIV patients (GSE30310) were accessed for identification of differentially expressed genes (DEGs). Data from 20 healthy subjects and 19 patients with TB and 16 healthy subjects and 16 patients with HIV were analyzed. We report here the DEGs shared by HIV and TB infection. Moreover, HIV and TB host-pathogen interaction data were collected from BIOGRID, v 4.4.210, for identifying significantly modulated genes' targets and their interactions with the host. Host targets, including PLSCR1 (phospholipid scramblase 1), STAT1 (signal transducer and activator of transcription-1 alpha/beta), FBXO6 (F-box only protein 6), ITGAL (integrin alpha-L), and APP (amyloid beta precursor protein), are commonly modulated in both diseases. The function of these targets was screened from and reconciled with the literature to understand their role in the pathogenesis of HIV and TB. Overall, the study results suggest that these targets may potentially be important contributors to the pathogenesis of this comorbidity. Further experimental work is needed for evaluating these new observations, with a view to future therapeutic innovation for patients with HIV and TB.
Assuntos
Infecções por HIV , Mycobacterium tuberculosis , Tuberculose , Humanos , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/uso terapêutico , HIV/genética , Infecções por HIV/genética , Mycobacterium tuberculosis/genética , Transcriptoma/genética , Tuberculose/tratamento farmacológicoRESUMO
L-Asparaginase is an enzyme used in the treatment of acute lymphoblastic leukemia and other related malignancies. Its further use includes reduction of asparagine concentration in food products, which may lead to formation of acrylamide. Currently bacterial asparaginase is produced at industrial scale, but the enzyme isolated from bacterial origin is often associated with adverse reactions. These side effects require development of asparaginase from alternative sources. In the present study, Penicillium digitatum was explored for the production of extracellular L-asparaginase using modified Czapek-Dox media. The enzyme was purified about 60.95-fold and then kinetic study showed that the Km value of the enzyme was 1 × 10â»5 M. The optimum pH and temperature for the enzyme were 7.0 and 30°C, respectively. The optimum incubation period for L-asparaginase was 15 min. This work concludes that this enzyme can be a suitable candidate due to its strong kinetic properties, and further research can usher into development of asparaginase formulation from fungal origin with less adverse effects.
Assuntos
Asparaginase/isolamento & purificação , Proteínas Fúngicas/isolamento & purificação , Penicillium/enzimologia , Asparaginase/química , Asparagina/química , Meios de Cultura/química , Ativação Enzimática , Ensaios Enzimáticos , Proteínas Fúngicas/química , Concentração de Íons de Hidrogênio , Cinética , Temperatura , Fatores de TempoRESUMO
The lack of precise molecular signatures limits the early diagnosis of non-small cell lung cancer (NSCLC). The present study used gene expression data and interaction networks to develop a highly accurate model with the least absolute shrinkage and selection operator (LASSO) for predicting NSCLC. The differentially expressed genes (DEGs) were identified in NSCLC compared with normal tissues using TCGA and GTEx data. A biological network was constructed using DEGs, and the top 20 upregulated and 20 downregulated hub genes were identified. These hub genes were used to identify signature genes with penalized logistic regression using the LASSO to predict NSCLC. Our model's development involved the following steps: (i) the dataset was divided into 80% for training (TR) and 20% for testing (TD1); (ii) a LASSO logistic regression analysis was performed on the TR with 10-fold cross-validation and identified a combination of 17 genes as NSCLC predictors, which were used further for development of the LASSO model. The model's performance was assessed on the TD1 dataset and achieved an accuracy and an area under the curve of the receiver operating characteristics (AUC-ROC) of 0.986 and 0.998, respectively. Furthermore, the performance of the LASSO model was evaluated using three independent NSCLC test datasets (GSE18842, GSE27262, GSE19804) and achieved high accuracy, with an AUC-ROC of >0.99, >0.99, and 0.95, respectively. Based on this study, a web application called NSCLCpred was developed to predict NSCLC.