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SARS-CoV-2 (severe acute respiratory syndrome) is highly infectious and causes severe acute respiratory distress syndrome (SARD), immune suppression, and multi-organ failure. For SARS-CoV-2, only supportive treatment options are available, such as oxygen supportive therapy, ventilator support, antibiotics for secondary infections, mineral and fluid treatment, and a significant subset of repurposed effective drugs. Viral targeted inhibitors are the most suitable molecules, such as ACE2 (angiotensin-converting enzyme-2) and RBD (receptor-binding domain) protein-based inhibitors, inhibitors of host proteases, inhibitors of viral proteases 3CLpro (3C-like proteinase) and PLpro (papain-like protease), inhibitors of replicative enzymes, inhibitors of viral attachment of SARS-CoV-2 to the ACE2 receptor and TMPRSS2 (transmembrane serine proteinase 2), inhibitors of HR1 (Heptad Repeat 1)-HR2 (Heptad Repeat 2) interaction at the S2 protein of the coronavirus, etc. Targeting the cathepsin L proteinase, peptide analogues, monoclonal antibodies, and protein chimaeras as RBD inhibitors interferes with the spike protein's ability to fuse to the membrane. Targeting the cathepsin L proteinase, peptide analogues, monoclonal antibodies, and protein chimaeras as RBD inhibitors interferes with the spike protein's ability to fuse to the membrane. Even with the tremendous progress made, creating effective drugs remains difficult. To develop COVID-19 treatment alternatives, clinical studies are examining a variety of therapy categories, including antibodies, antivirals, cell-based therapy, repurposed diagnostic medicines, and more. In this article, we discuss recent clinical updates on SARS-CoV-2 infection, clinical characteristics, diagnosis, immunopathology, the new emergence of variant, SARS-CoV-2, various approaches to drug development and treatment options. The development of therapies has been complicated by the global occurrence of many SARS-CoV-2 mutations. Discussion of this manuscript will provide new insight into drug pathophysiology and drug development.
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The latest breakthrough towards the adequate and decisive methods of gene editing tools provided by CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeat/CRISPR Associated System), has been repurposed into a tool for genetically engineering eukaryotic cells and now considered as the major innovation in gene-related disorders. Nanotechnology has provided an alternate way to overcome the conventional problems where methods to deliver therapeutic agents have failed. The use of nanotechnology has the potential to safe-side the CRISPR/Cas9 components delivery by using customized polymeric nanoparticles for safety and efficacy. The pairing of two (CRISPR/Cas9 and nanotechnology) has the potential for opening new avenues in therapeutic use. In this review, we will discuss the most recent advances in developing nanoparticle-based CRISPR/Cas9 gene editing cargo delivery with a focus on several polymeric nanoparticles including fabrication proposals to combat microbial infections.
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Infecciones Bacterianas/genética , Infecciones Bacterianas/terapia , Sistemas CRISPR-Cas/genética , Sistemas de Liberación de Medicamentos , Edición Génica/métodos , Nanopartículas/administración & dosificación , Polímeros/administración & dosificación , Humanos , NanomedicinaRESUMEN
Recent developments in the nucleic acid editing technologies have provided a powerful tool to precisely engineer the genome and epigenome for studying many aspects of immune cell differentiation and development as well as several immune mediated diseases (IMDs) including autoimmunity and cancer. Here, we discuss the recent technological achievements of the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-based RNA-guided genome and epigenome editing toolkit and provide an insight into how CRISPR/Cas9 (CRISPR Associated Protein 9) toolbox could be used to examine genetic and epigenetic mechanisms underlying IMDs. In addition, we will review the progress in CRISPR/Cas9-based genome-wide genome and epigenome screens in various cell types including immune cells. Finally, we will discuss the potential of CRISPR/Cas9 in defining the molecular function of disease associated SNPs overlapping gene regulatory elements.
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Sistemas CRISPR-Cas/genética , Epigénesis Genética/genética , Ingeniería Genética , Enfermedades del Sistema Inmune/tratamiento farmacológico , Enfermedades del Sistema Inmune/genética , Animales , HumanosRESUMEN
Among all PRT enzymes of purine salvage pathway in Leishmania, XPRT (Xanthine phosphoribosyl transferase) is unique in its substrate specificity and their non-existence in human. It is an interesting protein not only for drug designing but also to understand the molecular determinants of its substrate specificity. Analysis of the 3D model of L. donovani XPRT (Ld-XPRT) revealed that Ile 209, Glu 215 and Tyr 208 may be responsible for the altered substrate specificity of Ld-XPRT. Comparisons with it's nearest homologue in humans, revealed significant differences between the two. A 28 residue long unique motif was identified in Ld-XPRT, which showed highest fluctuation upon substrate binding during MD simulations. In kinetic analysis, Ld-XPRT could phosphoribosylate xanthine, hypoxanthine and guanine with Km values of 7.27, 8.13, 8.48µM and kcat values of 2.24, 1.82, 1.19min-1 respectively. Out of 159 compounds from docking studies, six compounds were characterized further by fluorescence spectroscopy, CD spectroscopy and enzyme inhibition studies. Fluorescence quenching experiment was performed to study the binding of inhibitors with Ld-XPRT and dissociation constants were calculated. Four compounds are bi-substrate analogues and show competitive inhibition with both the substrates (Xanthine and PRPP) of Ld-XPRT. The CD spectral analysis revealed that the binding of inhibitors to Ld-XPRT induce change in its tertiary structure, where as its secondary structure pattern remains unchanged. Two Ld-XPRT inhibitors (dGDP and cGMP), which also have ability to inhibit Leishmanial HGPRT, are predicted as potential drug candidates as it can inhibit both the important enzymes of the purine salvage pathway.
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Leishmania donovani/enzimología , Pentosiltransferasa/metabolismo , Proteínas Protozoarias/metabolismo , Xantina/metabolismo , Secuencia de Aminoácidos , Biocatálisis/efectos de los fármacos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/metabolismo , Inhibidores Enzimáticos/farmacología , Guanina/química , Guanina/metabolismo , Humanos , Hipoxantina/química , Hipoxantina/metabolismo , Cinética , Leishmania donovani/genética , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Pentosiltransferasa/clasificación , Pentosiltransferasa/genética , Filogenia , Proteínas Protozoarias/química , Proteínas Protozoarias/genética , Homología de Secuencia de Aminoácido , Especificidad por Sustrato , Xantina/químicaRESUMEN
BACKGROUND & OBJECTIVES: The epidemiology of dengue fever (DF) is complex in the Indian subcontinent as all the four serotypes are circulating. This study reports observations on dengue cases from a virus diagnostic laboratory of a north Indian tertiary care hospital catering to areas in and around Lucknow, Uttar Pradesh. METHODS: Serum samples were obtained from suspected cases of dengue referred to the virus diagnostic laboratory during 2011 to 2013, and detailed history was taken on a pre-structured datasheet. All samples were tested for anti-dengue virus (DV) IgM antibodies and DV-non structural protein 1 antigen (NS1Ag) by ELISA. NS1Ag positive samples were tested further by conventional RT-PCR for DV-RNA detection and serotyping. RESULTS: Of the 4019 suspected patients of dengue, 886 (22%) showed laboratory evidence of dengue virus infection. Of these, 19, 17 and 27 per cent were positive in 2011, 2012 and 2013, respectively. Children and adults were similarly affected by dengue in all the three years. Males were more commonly affected than females. The predominant DV serotype detected was DV-2, DV-1 and DV-3 in 2011, 2012 and 2013, respectively. DV-4 serotype was not detected. About half the cases positive for DV infection, showed symptoms of dengue with warning signs/ severe dengue. A distinct seasonality with increase in number of dengue cases in the post monsoon period was seen. INTERPRETATION & CONCLUSIONS: Change in circulating serotype of dengue virus; a distinct adult dengue involvement; and a remarkable number of cases presenting with severe dengue manifestations are the main findings of this study.
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Anticuerpos Antivirales/sangre , Virus del Dengue/aislamiento & purificación , Dengue/epidemiología , Inmunoglobulina M/sangre , Adolescente , Adulto , Anticuerpos Antivirales/inmunología , Niño , Preescolar , Dengue/sangre , Dengue/virología , Virus del Dengue/inmunología , Virus del Dengue/patogenicidad , Femenino , Humanos , Inmunoglobulina M/inmunología , India , Masculino , Estaciones del Año , SerotipificaciónRESUMEN
Lactation is an important physiological process in dairy animals. During lactation, up to 85% of the body glucose is directed toward the mammary glands for milk synthesis. Studies related to lactation physiology are generally carried out on mammary biopsies, which may adversely affect animal health. In the present study, milk enriched MEC were used to study the expression pattern of GLUT1 and apoptotic genes (BAX and BCL2) across different stages of lactation in riverine buffalo in relation to milk yield. MEC were enriched from milk using cytokeratin-8 antibodies coated magnetic beads. Total RNA isolated from enriched MEC showed significant correlation (r(2) = 0.92 ± 0.02) with the milk yield at different stages of lactation. GLUT1 expression pattern correlated with the milk yield as highest GLUT1 expression (4.68 ± 0.79) was observed during peak-lactation (90 days post-parturition), whereas low GLUT1 expression (1.01 ± 0.1, 15 d; 0.71 ± 0.03, 30 d) was observed during early lactation. The BAX/BCL2 ratio was high (1.02 ± 0.2, 15 d; 0.94 ± 0.06, 30 d) during the early phase of lactation, indicating high rate of apoptosis, whereas low BAX/BCL2 ratio (0.25 ± 0.03, 60 d; 0.42 ± 0.04, 90 d) was observed during mid-lactation coinciding with the increase in RNA concentration and milk yield. Highest BAX/BCL2 ratio (1.41 ± 0.3, 120 d; 4.02 ± 0.6, 240 d) was observed during late lactation i.e., 240 days, which was also reflected as decline in milk yield and RNA concentration. Also, BAX/BCL2 ratio in milk enriched MEC was in accordance with RNA concentration in MEC and milk yield at different phases of lactation. Our study showed that expression pattern of genes under study (GLUT1, BAX, and BCL2) in milk enriched MEC correlated well with important physiological properties such as milk yield in buffalo.
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Células Epiteliales/metabolismo , Transportador de Glucosa de Tipo 1/genética , Lactancia/genética , Leche/química , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteína X Asociada a bcl-2/genética , Animales , Búfalos , Femenino , Perfilación de la Expresión Génica , Transportador de Glucosa de Tipo 1/análisis , Transportador de Glucosa de Tipo 1/metabolismo , Lactancia/metabolismo , Leche/citología , Leche/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , ARN Mensajero/análisis , ARN Mensajero/genética , Proteína X Asociada a bcl-2/análisis , Proteína X Asociada a bcl-2/metabolismoRESUMEN
BACKGROUND: Type 2 diabetes mellitus (T2DM) is a metabolic disease of impaired glucose utilization. Uncontrolled high sugar levels lead to advanced glycation end products (AGEs), which affects several metabolic pathways by its receptor of advanced glycation end products (RAGE) and causes diabetic complication. MiRNAs are small RNA molecules which regulate genes linked to diabetes and affect AGEs pathogenesis, and target tissues, influencing health and disease processes. AIM: To explore miRNA roles in T2DM's metabolic pathways for potential therapeutic and diagnostic advancements in diabetes complications. METHODS: We systematically searched the electronic database PubMed using keywords. We included free, full-length research articles that evaluate the role of miRNAs in T2DM and its complications, focusing on genetic and molecular disease mechanisms. After assessing the full-length papers of the shortlisted articles, we included 12 research articles. RESULTS: Several types of miRNAs are linked in metabolic pathways which are affected by AGE/RAGE axis in T2DM and its complications. miR-96-5p, miR-7-5p, miR-132, has_circ_0071106, miR-143, miR-21, miR-145-5p, and more are associated with various aspects of T2DM, including disease risk, diagnostic markers, complications, and gene regulation. CONCLUSION: Targeting the AGE/RAGE axis, with a focus on miRNA regulation, holds promise for managing T2DM and its complications. MiRNAs have therapeutic potential as they can influence the metabolic pathways affected by AGEs and RAGE, potentially reducing inflammation, oxidative stress, and vascular complications. Additionally, miRNAs may serve as early diagnostic biomarkers for T2DM. Further research in this area may lead to innovative therapeutic strategies for diabetes and its associated complications.
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Lectins are sugar interacting proteins which bind specific glycans reversibly and have ubiquitous presence in all forms of life. They have diverse biological functions such as cell signaling, molecular recognition, etc. C-type lectins (CTL) are a group of proteins from the lectin family which have been studied extensively in animals and are reported to be involved in immune functions, carcinogenesis, cell signaling, etc. The carbohydrate recognition domain (CRD) in CTL has a highly variable protein sequence and proteins carrying this domain are also referred to as C-type lectin domain containing proteins (CTLD). Because of this low sequence homology, identification of CTLD from hypothetical proteins in the sequenced genomes using homology based programs has limitations. Machine learning (ML) tools use characteristic features to identify homologous sequences and it has been used to develop a tool for identification of CTLD. Initially 500 sequences of well annotated CTLD and 500 sequences of non CTLD were used in developing the machine learning model. The classifier program Linear SVC from sci kit library of python was used and characteristic features in CTLD sequences like dipeptide and tripeptide composition were used as training attributes in various classifiers. A precision, recall and multiple correlation coefficient (MCC) value of 0.92, 0.91 and 0.82 respectively were obtained when tested on external test set. On fine tuning of the parameters like kernel, C value, gamma, degree and increasing number of non CTLD sequences there was improvement in precision, recall and MCC and the corresponding values were 0.99, 0.99 and 0.96. New CTLD have also been identified in the hypothetical segment of human genome using the trained model. The tool is available on our local server for interested users.
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Lectinas Tipo C , Aprendizaje Automático , Lectinas Tipo C/química , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Humanos , Dominios ProteicosRESUMEN
BACKGROUND: Type 2 diabetes (T2D) is a metabolic disease of impaired glucose utilization and a major cause of cardiovascular disease (CVD). The pathogenesis of both diseases shares common risk factors and mechanisms, and both are significant contributors to global morbidity and mortality. Supplements of natural products for T2D mellitus (T2DM) and CVD can be seen as a potential preventive and effective therapeutic strategy. AIM: To critically evaluate the therapeutic potential of natural products in T2D and coronary artery disease (CAD). METHODS: By using specific keywords, we strategically searched the PubMed database. Randomized controlled trials (RCTs) were searched as the primary focus that examined the effect of natural products on glycemic control, oxidative stress, and antioxidant levels. We focused on outcomes such as low blood glucose levels, adjustment on markers of oxidative stress and antioxidants. After screening full-length papers, we included 9 RCTs in our review that met our inclusion criteria. RESULTS: In the literature search on the database, we found that various natural products like plant secondary metabolites play a diverse role in the management of CAD. American ginseng, sesame oil and cocoa flavanols proved effective in lowering blood glucose levels and controlling blood pressure, which are key factors in managing T2DM and CVD. In diabetic patients Melissa officinalis effectively reduce inflammation and shows diabetes prevention. Both fish oil and flaxseed oil reduced insulin levels and inflammatory markers, suggesting benefits for both conditions. The lipid profile and endothelial function were enhanced by Nigella sativa oil and Terminalia chebula, which is significant for the management of cardiovascular risk factors in T2DM. Additionally Bilberry extract also showed promise for improving glycemic control in patients with T2DM. CONCLUSION: The high level of antioxidant, anti-inflammatory, and anti-angiogenic properties found in natural products makes them promising therapeutic options for the management of CAD, with the potential benefit of lowering the risk of CAD.
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Computational algorithms and tools have retrenched the drug discovery and development timeline. The applicability of computational approaches has gained immense relevance owing to the dramatic surge in the structural information of biomacromolecules and their heteromolecular complexes. Computational methods are now extensively used in identifying new protein targets, druggability assessment, pharmacophore mapping, molecular docking, the virtual screening of lead molecules, bioactivity prediction, molecular dynamics of protein-ligand complexes, affinity prediction, and for designing better ligands. Herein, we provide an overview of salient components of recently reported computational drug-discovery workflows that includes algorithms, tools, and databases for protein target identification and optimized ligand selection.
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Allium sativum agglutinin (ASA) is an important lectin isolated from garlic bulbs and has shown promising therapeutic potential in earlier reports. It has a bulb-type lectin domain, and members of this protein family have been investigated for anti-cancer, antimicrobial and other effects. In our earlier study, we have reported ASA as an anti-cancer agent, and in the present study, we have evaluated it for its antifungal and antimicrobial effects. The effects of ASA on the opportunistic pathogens in humans Candida auris and Candida glabrata fungal strains have been evaluated, and efforts are made to evaluate the mechanistic basis of these antifungal effects. The antifungal activity of ASA on different strains of C. glabrata and C. auris was found with MIC50 concentration range of 30-70 µg/ml. Fungal growth was significantly suppressed upon treatment with ASA at MIC50 and 2MIC50. Hydrogen peroxide production was detected after ASA treatment in fungal cells and cell morphology, and integrity was affected when analysed through FE-SEM. Further, the anti-biofilm effect of ASA was investigated against Candida and three bacterial strains (Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae), and promising results were obtained with maximal effect in case of K. pneumoniae among the bacterial strains. These results can form the basis for the development of ASA as antimicrobial agent.
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Antiinfecciosos , Ajo , Humanos , Antifúngicos/farmacología , Lectinas , Antiinfecciosos/farmacología , Candida , Antioxidantes/farmacología , Pruebas de Sensibilidad MicrobianaRESUMEN
Triple-negative breast cancer (TNBC) is a more aggressive type of breast cancer due to its heterogeneity and complex molecular mechanisms. TNBC has a high risk for metastasis, and it is difficult to manage clinical conditions of the patients. Various investigations are being conducted to overcome these challenges using RNA, DNA, and proteins for early diagnosis and treatment. Recently, long non-coding RNAs (lncRNAs) have emerged as a novel target to treat the multistep process of TNBC. LncRNAs regulate epigenetic expression levels, cell proliferation and apoptosis, and tumour invasiveness and metastasis. Thus, lncRNA-based early diagnosis and treatment options could be helpful, especially for patients with severe TNBC. lncRNAs are expressed in a highly specific manner in cells and tissues and are involved in TNBC progression and development. lncRNAs could be used as sensitive and specific targets for diagnosis, treatment, and monitoring of patients with TNBC. Therefore, the exploration of novel diagnostic and prognostic biomarkers is of extreme importance. Here, we discuss the molecular advances on lncRNA regulation of TNBC and lncRNA-based early diagnosis, treatment, and drug resistance.
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ARN Largo no Codificante , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/patología , ARN Largo no Codificante/genética , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , ApoptosisRESUMEN
BACKGROUND: Severe acute malnutrition (SAM) is a significant public health problem in developing countries, including India, where a significant proportion of children suffer from malnutrition. OBJECTIVE: This research aims to investigate the factors contributing to severe acute malnutrition (SAM). Additionally, the study seeks to explore the relationship between micronutrient levels and pro-inflammatory cytokines in SAM children with and without clinical complications. Furthermore, the effectiveness of antibiotic treatment in SAM children without complications is evaluated. METHODS: The study involved three groups comprising 66 subjects each: a healthy control group, SAM children with complications, and SAM children without complications. Blood samples were collected, and various analyses were conducted, including biochemical, hematological, micronutrient, and pro-inflammatory marker quantification. The data were analyzed using SPSS version 22.0. RESULTS: The results indicate that the levels of IL-6, CRP, and TNF-α were significantly higher in the SAM group with complications compared to both the control group and the SAM group without complications. Zinc and copper levels were significantly lower in both SAM groups compared to the control group, and a negative correlation was observed between zinc levels and inflammatory markers. The study also assessed the efficacy of antibiotic treatment in SAM children without complications by comparing their weight, height, weight-for-height, and weight-for-age at baseline and after a 15-day follow-up period. Significant improvements in these parameters were observed in both the group receiving antibiotic treatment and the group not receiving antibiotic treatment. CONCLUSION: The findings suggest that a combination of antibiotic treatment and nutritional support can lead to significant clinical improvements in SAM children without complications. This study has important implications for the management and treatment of SAM in India and other developing countries.
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Micronutrientes , Desnutrición Aguda Severa , Niño , Humanos , Lactante , Citocinas , Centros de Atención Terciaria , Desnutrición Aguda Severa/terapia , Antibacterianos/uso terapéutico , ZincRESUMEN
Based on recent research, the non-coding genome is essential for controlling genes and genetic programming during development, as well as for health and cardiovascular diseases (CVDs). The microRNAs (miRNAs), lncRNAs (long ncRNAs), and circRNAs (circular RNAs) with significant regulatory and structural roles make up approximately 99% of the human genome, which does not contain proteins. Non-coding RNAs (ncRNA) have been discovered to be essential novel regulators of cardiovascular risk factors and cellular processes, making them significant prospects for advanced diagnostics and prognosis evaluation. Cases of CVDs are rising due to limitations in the current therapeutic approach; most of the treatment options are based on the coding transcripts that encode proteins. Recently, various investigations have shown the role of nc-RNA in the early diagnosis and treatment of CVDs. Furthermore, the development of novel diagnoses and treatments based on miRNAs, lncRNAs, and circRNAs could be more helpful in the clinical management of patients with CVDs. CVDs are classified into various types of heart diseases, including cardiac hypertrophy (CH), heart failure (HF), rheumatic heart disease (RHD), acute coronary syndrome (ACS), myocardial infarction (MI), atherosclerosis (AS), myocardial fibrosis (MF), arrhythmia (ARR), and pulmonary arterial hypertension (PAH). Here, we discuss the biological and clinical importance of miRNAs, lncRNAs, and circRNAs and their expression profiles and manipulation of non-coding transcripts in CVDs, which will deliver an in-depth knowledge of the role of ncRNAs in CVDs for progressing new clinical diagnosis and treatment.
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Enfermedades Cardiovasculares , MicroARNs , ARN Largo no Codificante , Humanos , MicroARNs/genética , MicroARNs/uso terapéutico , ARN Largo no Codificante/genética , ARN Largo no Codificante/uso terapéutico , ARN Circular/genética , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/tratamiento farmacológico , Relevancia Clínica , ARN no TraducidoRESUMEN
BACKGROUND: Coronary artery disease (CAD) is a major cause of death worldwide, and India contributes to about one-fifth of total CAD deaths. The development of CAD has been linked to the accumulation of Nε-carboxymethyl-lysine (CML) in heart muscle, which correlates with fibrosis. AIM: To assess the impact of CML and inflammatory markers on the biochemical and cardiovascular characteristics of CAD patients with and without diabetes. METHODS: We enrolled 200 consecutive CAD patients who were undergoing coronary angiography and categorized them into two groups based on their serum glycosylated hemoglobin (HbA1c) levels (group I: HbA1c ≥ 6.5; group II: HbA1c < 6.5). We analyzed the levels of lipoproteins, plasma HbA1c levels, CML, interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and nitric oxide. RESULTS: Group I (81 males and 19 females) patients had a mean age of 54.2 ± 10.2 years, with a mean diabetes duration of 4.9 ± 2.2 years. Group II (89 males and 11 females) patients had a mean age of 53.2 ± 10.3 years. Group I had more severe CAD, with a higher percentage of patients with single vessel disease and greater stenosis severity in the left anterior descending coronary artery compared to group II. Group I also exhibited a larger left atrium diameter. Group I patients exhibited significantly higher levels of CML, TNF-α, and IL-6 and lower levels of nitric oxide as compared with group II patients. Additionally, CML showed a significant positive correlation with IL-6 (r = 0.596, P = 0.001) and TNF-α (r = 0.337, P = 0.001) and a negative correlation with nitric oxide (r=-4.16, P = 0.001). Odds ratio analysis revealed that patients with CML in the third quartile (264.43-364.31 ng/mL) were significantly associated with diabetic CAD at unadjusted and adjusted levels with covariates. CONCLUSION: CML and inflammatory markers may play a significant role in the development of CAD, particularly in diabetic individuals, and may serve as potential biomarkers for the prediction of CAD in both diabetic and non-diabetic patients.
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We have previously reported the purification and preliminary X-ray characterization of a hemagglutinin from the seeds of Jatropha curcas and, with the detailed sequencing information available now, we find that it is similar to a 2S albumin allergen isolated from the same source. Through a search of Jatropha genome database (http://www.kazusa.or.jp/jatropha/), we map it to the sequence id JcCA0234191 (now referred to as Jcr4S00619.70 in the new version, release 4.5) which has a conserved alpha amylase inhibitor/seed storage protein domain found in the 2S albumin allergens. The putative sequence of the small and large chains of the protein is assigned and the total mass of the two subunits matches with the intact mass 10 kDa determined through MALDI. The protein retains hemagglutination activity between pH 6-9 and up to 60 °C on heat treatment and its hemagglutination activity is inhibited by sialic acid and fetuin. Bioinformatics studies show that the isolated protein sequence clusters in close association with a 2S albumin from Ricinus communis in phylogeny analysis and has a conservation of the characteristic four disulfide linkage pattern. Hemagglutinins and lectins are known to have allergenic effects through their interaction with immunoglobulin E and histamine release and earlier studies have shown that this interaction can be inhibited by lectin-specific sugars. We hope this report bridges the plant allergens and hemagglutinins further for exploring possible mediation of allergenic activity through sialic acid and complex sugar interactions and generates further interest in the area.
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Albuminas 2S de Plantas/química , Alérgenos/química , Carbohidratos/farmacología , Hemaglutininas/química , Jatropha/química , Albuminas 2S de Plantas/antagonistas & inhibidores , Albuminas 2S de Plantas/inmunología , Pruebas de Aglutinación , Alérgenos/inmunología , Alérgenos/metabolismo , Secuencia de Aminoácidos , Animales , Fetuínas/farmacología , Hemaglutininas/inmunología , Concentración de Iones de Hidrógeno , Datos de Secuencia Molecular , Peso Molecular , Ácido N-Acetilneuramínico/farmacología , Filogenia , Conformación Proteica , Conejos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , TemperaturaRESUMEN
BACKGROUND & OBJECTIVES: Dengue virus (DV) infection has emerged as a major health problem in north India. Here, we report the annual trend of dengue virus infection as seen in Lucknow, Uttar Pradesh, during 2008-2010. METHODS: Blood samples from clinically suspected cases of dengue virus infection were collected and history was taken on structured clinical data sheet. All samples were tested for dengue IgM by antibody capture ELISA. Selected samples were tested by conventional RT-PCR for dengue virus RNA. Weather information was continuously recorded from website of world weather information service . RESULTS: There was a gradual increase in number of dengue fever cases with increased occurrence in 2010. Cases referred in January - December 2008 were 398 (54.5% anti DV IgM positive), in January - December 2009 were 599 (51.9% anti DV IgM positive) and in January - December 2010 were 1602 (64.9% anti DV IgM positive). Serotypes circulating in years 2008, 2009 and 2010 were DV-2 & DV-3, DV -1, 2 & 3 and DV-1 and DV-2 respectively. There is no statistical significant correlation between weather data and increasing dengue positive cases. INTERPRETATION & CONCLUSIONS: Increased cases of dengue fever were seen in 2010, which was not correlated with any change in environmental factors. A change in circulating serotypes was noted.
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Dengue/epidemiología , Virus del Dengue/genética , Virus del Dengue/inmunología , Virus del Dengue/aislamiento & purificación , Ensayo de Inmunoadsorción Enzimática , Hospitales , Humanos , Inmunoglobulina M/sangre , India/epidemiología , ARN Viral/sangre , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Detection of multiple viruses is important for global analysis of gene or protein content and expression, opening up new prospects in terms of molecular and physiological systems for pathogenic diagnosis. Early diagnosis is crucial for disease treatment and control as it reduces inappropriate use of antiviral therapy and focuses surveillance activity. This requires the ability to detect and accurately diagnose infection at or close to the source/outbreak with minimum delay and the need for specific, accessible point-of-care diagnosis able to distinguish causative viruses and their subtypes. None of the available viral diagnostic assays combine a point-of-care format with the complex capability to identify a large range of human and animal viruses. Microarray detection provides a useful, labor-saving tool for detection of multiple viruses with several advantages, such as convenience and prevention of cross-contamination of polymerase chain reaction (PCR) products, which is of foremost importance in such applications. Recently, real-time PCR assays with the ability to confirm the amplification product and quantitate the target concentration have been developed. Furthermore, nucleotide sequence analysis of amplification products has facilitated epidemiological studies of infectious disease outbreaks and monitoring of treatment outcomes for infections, in particular for viruses that mutate at high frequency. This review discusses applications of microarray technology as a potential new tool for detection and identification of acute encephalitis-causing viruses in human serum, plasma, and cell cultures.
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Encefalitis Viral/virología , Flavivirus/genética , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Enfermedad Aguda , Análisis de Varianza , Bases de Datos Genéticas , Encefalitis Viral/diagnóstico , Flavivirus/aislamiento & purificación , Perfilación de la Expresión Génica/métodos , Humanos , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
BACKGROUND: Garlic (Allium sativum) from the family Amaryllidaceae is widely used in culinary and is reported to have potential anticancer, anti-diabetic, antimicrobial, and cardioprotective activities. Allium sativum agglutinin (ASA) is a bulb-type lectin (BTL) domaincontaining lectin isolated from garlic and has been studied for its various biological functions. Previous studies have reported the anti-cancer effects of ASA on histiocytic lymphoma (U937), promyelocytic leukemia (HL60), and oral cancer (KB). METHODS: In this study, we have purified and characterized ASA and evaluated it for its anticancer effects on other cancer cell lines. MTT assay and FACS analysis was done to corroborate the anticancer findings against cervical (HeLa) and lung cancer (A549) cell lines. RESULTS: IC50 value of 37 µg/ml in HeLa and a weak activity (26.4 ± 1.9% cellular inhibition at 100µg/ml treatment) in A549 were found in the MTT assay. FACS analysis further corroborated these findings and showed the apoptotic effects of ASA in these cell lines. CONCLUSION: Anticancer activity for members of bulb-type lectin (BTL) domain-containing lectins has been widely reported, and we hope that our study forms a basis for the development of ASA as a therapeutic agent.
Asunto(s)
Productos Biológicos , Ajo , Aglutininas/farmacología , Antioxidantes , Ajo/metabolismo , Lectinas , Lectinas de Plantas/metabolismo , Lectinas de Plantas/farmacologíaRESUMEN
Breast cancer (BC) is caused by epigenetic modifications and genetic heterogeneity and exhibits various histological feature. HER2+ (Human epidermal growth factor receptor 2) is a more aggressive type of breast cancer, diagnosis and prognosis are difficult for HER2+ BC. Anti-HER2+ inhibitors have been effectively used for patient treatment. High mortality rate is reported in HER2+ BC, due to availability of limited therapeutic options. Despite advances in systemic medications to treat metastatic breast cancer (MBC), HER2-positive MBC is still challenging for patients and treating clinicians. The clinical characteristics of the disease have changed after treatment with HER2-targeted therapy. Various types of Tyrosine kinase inhibitors (TKIs) have been developed to treat patients with HER2+ BC including afatinib, lapatinib, neratinib, tucatinib, and pyrotinib, have been developed as HER2-targeted therapies. The antibody-drug conjugates adotrastuzumab, emtansine, famtrastuzumab, and deruxtecan, as well as the anti-HER2 monoclonal antibody pertuzumab are used in both early-stage and metastatic situations, either alone or in conjunction with chemotherapy and other HER2-targeting therapies. The emergence of drug resistance in anti-HER2 therapies has been observed. To overcome drug resistance and limited efficacy in current treatment options, nano formulations can be used in patients with HER2+ BC treatment. Anti-HER2 ligands can be used in various nano formulations to target HER2 receptors. Here we will discuss, targeted TKIs in patients with HER2+ BC, clinical studies of HER2+ targeted TKIs, mechanisms of resistance to HER2-directed therapies with new implications of TKIs in HER2+ MBC (metastatic breast cancer) and anti-HER2 ligand in various nano formulations to target HER2 receptors.