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1.
Epigenomics ; 13(6): 465-480, 2021 03.
Article in English | MEDLINE | ID: mdl-33685230

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 is a positive-sense RNA virus, a causal agent of ongoing COVID-19 pandemic. ACE2R methylation across three CpG sites (cg04013915, cg08559914, cg03536816) determines the host cell's entry. It regulates ACE2 expression by controlling the SIRT1 and KDM5B activity. Further, it regulates Type I and III IFN response by modulating H3K27me3 and H3K4me3 histone mark. SARS-CoV-2 protein with bromodomain and protein E mimics bromodomain histones and evades from host immune response. The 2'-O MTases mimics the host's cap1 structure and plays a vital role in immune evasion through Hsp90-mediated epigenetic process to hijack the infected cells. Although the current review highlighted the critical epigenetic events associated with SARS-CoV-2 immune evasion, the detailed mechanism is yet to be elucidated.


Subject(s)
COVID-19/genetics , COVID-19/immunology , Epigenesis, Genetic , Immune Evasion , Angiotensin-Converting Enzyme 2/genetics , Antigen Presentation , DNA Methylation , HSP90 Heat-Shock Proteins/genetics , Histones , Humans , SARS-CoV-2/physiology , Virus Internalization
2.
Hemoglobin ; 45(6): 358-364, 2021 Nov.
Article in English | MEDLINE | ID: mdl-33393394

ABSTRACT

Sickle cell anemia is hallmarked by hemolysis, which releases hemoglobin (Hb) into the plasma promoting vaso-occlusive crisis (VOC). Haptoglobin (Hp) clears free Hb and decreases Hb-related pathophysiology in sickle cell anemia. There are two alleles (HP1 and HP2) and three genotypes (HP1-1, HP1-2 and HP2-2) of Hp with different frequencies in different populations. This study involved Hp level and genotype among normal and sickle cell anemia patients with varying severity of VOC. A total of 297 sickle cell anemia patients and 98 healthy controls were selected for the study. The sickle cell anemia patients were categorized as 'mild-phenotype' with no pain episodes and 'severe-phenotype' as having three or more acute pain episodes in the preceding 12 months. The Hp level was significantly lower (p < 0.001) in sickle cell patients anemia than controls; HP1-1 genotype had a higher Hp level compared to HP1-2 and HP2-2 (p < 0.05). Turkey-Kramer multiple comparison tests showed that mild and severe phenotypes have significant differences (p < 0.05) in Hb F%, Hb, platelet count, aspartate aminotransferase (AST), alanine aminotransferase (ALT), direct-bilirubin (Bil-D), total-bilirubin (Bil-T), lactate dehydrogenase (LDH) and Hp level. Pearson correlation revealed that Hp level has a positive (p < 0.05) correlation with Hb F%, Hb, packed cell volume (PCV) and serum urea; in contrast its level is negatively correlated with AST, ALT, Bil-T and LDH. A significantly higher frequency of HP2 allele and HP2-2 genotypes was found in severe phenotypes. In the studied population, it was found that higher HP2 frequency, low Hp level and more hemolysis favors the onset of VOC in sickle cell anemia.


Subject(s)
Anemia, Sickle Cell , Haptoglobins , Anemia, Sickle Cell/complications , Anemia, Sickle Cell/genetics , Bilirubin , Chromosomal Proteins, Non-Histone/genetics , Genotype , Haptoglobins/genetics , Hemoglobins/genetics , Hemolysis , Humans , India , L-Lactate Dehydrogenase
3.
Curr Pharm Biotechnol ; 21(14): 1412-1421, 2020.
Article in English | MEDLINE | ID: mdl-32386487

ABSTRACT

BACKGROUND: Floral has diversity and unique nature due to the complex structure and component. Alpinia is an important genus of the Zingiberaceae family having complex taxonomical diversity. The presence of many unique bioactive molecules makes this genus, a pharmaceutically important genus. They provide a wide range of medicinal properties, including traditional remedies to modern therapeutic applications. METHODS: Extracts of Alpinia mostly contain bioactive molecules and secondary metabolites such as polyphenolics, tannins, flavonoids and other therapeutically important compounds. These bioactive molecules are biologically active, treating against inflammation, cancer, arterial hypertension, and other deadly diseases. RESULTS: These bioactive molecules can act as natural enzyme inhibitors for some of the deadly diseases and can block the pathway for metabolic activities. In addition, these genera have played a major role in multidisciplinary studies of phytochemistry, ethnobotany, and pharmacological aspects in day-to-day life. CONCLUSION: Therefore, this review highlights the fewer known facts of the genus Alpinia in terms of bioactive molecules and its significant therapeutic applications to help in combating major diseases of humans.


Subject(s)
Alpinia/chemistry , Phytochemicals/pharmacology , Plant Extracts/pharmacology , Protective Agents/pharmacology , Alpinia/growth & development , Animals , Ethnobotany , Ethnopharmacology , Flowers/chemistry , Flowers/growth & development , Humans , Medicine, Ayurvedic , Medicine, Chinese Traditional , Phytochemicals/adverse effects , Phytochemicals/isolation & purification , Phytotherapy/methods , Plant Extracts/adverse effects , Plant Extracts/isolation & purification , Protective Agents/adverse effects , Protective Agents/isolation & purification
4.
Hemoglobin ; 43(2): 88-94, 2019 Mar.
Article in English | MEDLINE | ID: mdl-31290363

ABSTRACT

Vaso-occlusive crisis (VOC) occurs more frequently during stress in sickle cell disease patients. Epinephrine released during stress increases adhesion of sickled red blood cells (RBCs) to endothelium and to leukocytes, a process mediated through erythrocyte cyclic adenosine monophosphate (cAMP). Increased adhesion of sickled RBCs retards blood flow through the capillaries and promotes vaso-occlusion. Therefore, we examined the association of RBC-cAMP levels with frequency of acute pain episodes in sickle cell disease subjects. Using a case control study design, we measured RBC-cAMP levels, fetal hemoglobin (Hb F), α-thalassemia (α-thal) and other hematological parameters at baseline (sham treated) and after stimulation with epinephrine. The cases consisted of sickle cell disease subjects with three or more acute pain episodes in the last 12 months, and those without a single acute pain episode in the last 12 months were considered as controls. Significantly higher cAMP values were found in cases than the controls, in both sham treated (p < 0.001) and epinephrine treated RBCs (p < 0.001) by Wilcoxon Rank Sum test. However, significant association of cAMP values was observed both on univariate [odds ratio (OR): 4.8, 95% confidence interval (95% CI): 1.51-15.19, p < 0.008) and multivariate logistic regression analyses only in epinephrine treated (OR: 5.07, 95% CI: 1.53-16.82, p < 0.008) but not in sham-treated RBCs. In the covariates, Hb F consistently showed protective effects in univariate as well as in multivariate analyses. Frequent acute pain episodes are associated with higher cAMP levels than those with less frequent pain episodes, only after stimulation with epinephrine but not with baseline level.


Subject(s)
Acute Pain/etiology , Anemia, Sickle Cell/pathology , Cyclic AMP/analysis , Erythrocytes/chemistry , Adult , Anemia, Sickle Cell/complications , Case-Control Studies , Epinephrine/pharmacology , Female , Fetal Hemoglobin/pharmacology , Humans , India , Male
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