Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.194
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-33523027

RESUMO

BACKGROUND: It is known that small for gestational age (SGA) babies may be at an increased risk of cardiovascular diseases during adulthood. There is paucity of literature regarding comparative cardiac functions of SGA and appropriate for gestational age (AGA) babies in neonatal period. The present study was conceived to compare the cardiac function of term small and appropriate for gestational age (AGA) babies through a relatively novel echocardiographic index in early neonatal period. OBJECTIVES: To compare values of myocardial performance index (MPI) index (MPI = IVCT + IVRT/ET) at 48-72 hours of age among AGA and SGA babies. METHODS: Morphological and anthropometric assessment of serially born term babies was done at time of birth to recruit hundred each of AGA and SGA babies. Tissue Doppler Imaging (TDI) was done between 48-72 hours for each enrolled baby to assess both right and left ventricle MPI in each group. RESULTS: Mean±SD values for right ventricular MPI in AGA and SGA groups were 0.268 + 0.007 and 0.30 + 0.026 respectively (p <  0.001). Mean±SD values for left ventricular MPI in AGA and SGA groups were 0.25 + 0.012 and 0.30 + 0.017 respectively (p <  0.001). There was significant negative correlation between MPI values for either ventricles and the birth weight (spearmen's rho of -0.66) (p <  0.001). Mean±SD values for LVET in AGA and SGA group were 0.304 + 0.026 and 0.266 + 0.032 respectively (p <  0.001). CONCLUSION: MPI had a higher absolute value in the SGA babies as compared to AGA babies. These observations point towards suboptimal cardiac performance among SGA babies as compared to AGA babies on the basis of myocardial performance index.

2.
Cell Biochem Biophys ; 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33555556

RESUMO

Epimerase-deficiency galactosemia (EDG) is caused by mutations in the UDP-galactose 4'-epimerase enzyme, encoded by gene GALE. Catalyzing the last reaction in the Leloir pathway, UDP-galactose-4-epimerase catalyzes the interconversion of UDP-galactose and UDP-glucose. This study aimed to use in-depth computational strategies to prioritize the pathogenic missense mutations in GALE protein and investigate the systemic behavior, conformational spaces, atomic motions, and cross-correlation matrix of the GALE protein. We searched four databases (dbSNP, ClinVar, UniProt, and HGMD) and major biological literature databases (PubMed, Science Direct, and Google Scholar), for missense mutations that are associated with EDG patients, our search yielded 190 missense mutations. We applied a systematic computational prediction pipeline, including pathogenicity, stability, biochemical, conservational, protein residue contacts, and structural analysis, to predict the pathogenicity of these mutations. We found three mutations (p.K161N, p.R239W, and p.G302D) with a severe phenotype in patients with EDG that correlated with our computational prediction analysis; thus, they were selected for further structural and simulation analyses to compute the flexibility and stability of the mutant GALE proteins. The three mutants were subjected to molecular dynamics simulation (MDS) with native protein for 200 ns using GROMACS. The MDS demonstrated that these mutations affected the beta-sheets and helical region that are responsible for the catalytic activity; subsequently, affects the stability and flexibility of the mutant proteins along with a decrease and more deviations in compactness when compared to that of a native. Also, three mutations created major variations in the combined atomic motions of the catalytic and C-terminal regions. The network analysis of the residues in the native and three mutant protein structures showed disturbed residue contacts occurred owing to the missense mutations. Our findings help to understand the structural behavior of a protein owing to mutation and are intended to serve as a platform for prioritizing mutations, which could be potential targets for drug discovery and development of targeted therapeutics.

3.
Adv Protein Chem Struct Biol ; 123: 241-273, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33485486

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a rare yet crucial persistent lung disorder that actuates scarring of lung tissues, which makes breathing difficult. Smoking, environmental pollution, and certain viral infections could initiate lung scarring. However, the molecular mechanism involved in IPF remains elusive. To develop an efficient therapeutic arsenal against IPF, it is vital to understand the pathology and deviations in biochemical pathways that lead to disorder. In this study, we availed network analysis and other computational pipelines to delineate the prominent membrane proteins as diagnostic biomarkers and therapeutic targets for IPF. This study yielded a significant role of glycosaminoglycan binding, endothelin, and GABA-B receptor signaling pathway in IPF pathogenesis. Furthermore, ADCY8, CRH, FGB, GPR17, MCHR1, NMUR1, and SAA1 genes were found to be immensely involved with IPF, and the enrichment pathway analysis suggests that most of the pathways were corresponding to membrane transport and signal transduction functionalities. This analysis could help in better understanding the molecular mechanism behind IPF to develop an efficient therapeutic target or biomarkers for IPF.

4.
Adv Protein Chem Struct Biol ; 123: 49-71, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33485488

RESUMO

Membrane proteins are the most common types of cancer that are active in the prognosis. Membrane proteins are a distinguishing characteristic of a cancer cell. In tumor cell therapy, the overexpressed membrane proteins are becoming ever more relevant. The 3-kinase (PI3K)/AKT phosphatidylinositol pathway is downstream triggered by different extracellular signals, and this signaling pathway activation impacts a variety of proliferation of the cellular processes like cell growth and surviving. Frequent PI3K/AKT dysregulation in human cancer has rendered proteins of this pathway desirable for diagnostic markers. Members of the ERBB family-like ERBB2 and ERBB3 activate intracellular signaling pathways such as PI3K/AKT. The mutations in these proteins dysfunctions the proteins in the downstream. Considering this importance, we have developed a computational pipeline to identify the mutation position with a highest number of mutations and to screen them for pathogenicity, stability, conservation, and structural changes using PredictSNP, iStable, ConSurf, and GROMACS simulation software respectively. Further, a virtual screening approach was initiated to find the most similar non-toxic lead compound, which could be an alternative to the currently used lapatinib. To conclude, protein-ligand dynamics were undertaken to study the actions of native and mutants with the lapatinib and the lead compound. From the overall analysis, we identified position 755 with leucine in the native condition is prone to frequent mutations. The leucine at 755th position is more prone to mutate as serine and tryptophan. Further from the computational analysis, we identified that the mutation L755S is more significant than the L755W mutation. We have witnessed CID140590176 be a potential lead compound with no toxicity. The behavior of the lead compound has shown more compactness with an increased number of intermolecular hydrogen bonds in the ERBB2 with L755S. This lead compound can be further taken for experimental validations, and we believe that this lead compound could be a potent ERBB2 inhibitor.

5.
Int J Mol Sci ; 21(23)2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33260951

RESUMO

Aspirin, synthesized and marketed in 1897 by Bayer, is one of the most widely used drugs in the world. It has a well-recognized role in decreasing inflammation, pain and fever, and in the prevention of thrombotic cardiovascular diseases. Its anti-inflammatory and cardio-protective actions have been well studied and occur through inhibition of cyclooxygenases (COX). Interestingly, a vast amount of epidemiological, preclinical and clinical studies have revealed aspirin as a promising chemopreventive agent, particularly against colorectal cancers (CRC); however, the primary mechanism by which it decreases the occurrences of CRC has still not been established. Numerous mechanisms have been proposed for aspirin's chemopreventive properties among which the inhibition of COX enzymes has been widely discussed. Despite the wide attention COX-inhibition has received as the most probable mechanism of cancer prevention by aspirin, it is clear that aspirin targets many other proteins and pathways, suggesting that these extra-COX targets may also be equally important in preventing CRC. In this review, we discuss the COX-dependent and -independent pathways described in literature for aspirin's anti-cancer effects and highlight the strengths and limitations of the proposed mechanisms. Additionally, we emphasize the potential role of the metabolites of aspirin and salicylic acid (generated in the gut through microbial biotransformation) in contributing to aspirin's chemopreventive actions. We suggest that the preferential chemopreventive effect of aspirin against CRC may be related to direct exposure of aspirin/salicylic acid or its metabolites to the colorectal tissues. Future investigations should shed light on the role of aspirin, its metabolites and the role of the gut microbiota in cancer prevention against CRC.

6.
Protein Pept Lett ; 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33319654

RESUMO

Large numbers of bioactive peptides with potential applications in protecting against human diseases have been identified from plant sources. In this review, we summarized recent progress in the research of plant-derived bioactive peptides, encompassing their production, biological effects, and mechanisms. This review focuses on antioxidant, antimicrobial, antidiabetic, and anticancer peptides, giving special attention to evidence derived from cellular and animal models. Studies investigating peptides with known sequences and well-characterized peptidic fractions or protein hydrolysates will be discussed. The use of molecular docking tools to elucidate inter-molecular interactions between bioactive peptides and target proteins is highlighted. In conclusion, the accumulating evidence from in silico, in vitro and in vivo studies to date supports the envisioned applications of plant peptides as natural antioxidants as well as health-promoting agents. Notwithstanding, much work is still required before the envisioned applications of plant peptides can be realized. To this end, future researches for addressing current gaps were proposed.

7.
Indian Heart J ; 72(6): 477-481, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33357634

RESUMO

AIM: Ensuring adherence to guideline-directed medical therapy (GDMT) is an effective strategy to reduce mortality and readmission rates for heart failure (HF). Use of a checklist is one of the best tools to ensure GDMT. The aim was to develop a consensus document with a robust checklist for stabilized acute decompensated HF patients with reduced ejection fraction. While there are multiple checklists available, an India-specific checklist that is easy to fill and validated by regional and national subject matter experts (SMEs) is required. METHODOLOGY: A total of 25 Cardiology SMEs who consented to participate from India discussed data from literature, current evidence, international guidelines and practical experiences in two national and four regional meetings. RESULTS: Recommendations included HF management, treatment optimization, and patient education. The checklist should be filled at four time points- (a) transition from intensive care unit to ward, (b) at discharge, (c) 1st follow-up and (d) subsequent follow-up. The checklist is the responsibility of the consultant or the treating physician which can be delegated to a junior resident or a trained HF nurse. CONCLUSION: This checklist will ensure GDMT, simplify transition of care and can be used by all doctors across India. Institutions, associations, and societies should recommend this checklist for adaptability in public and private hospital. Hospital administrations should roll out policy for adoption of checklist by ensuring patient files have the checklist at the time of discharge and encourage practice of filling it diligently during follow-up visits.

8.
Eur Rev Med Pharmacol Sci ; 24(23): 12593-12608, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33336780

RESUMO

The coronavirus disease 2019 (COVID-19) is declared as an international emergency in 2020. Its prevalence and fatality rate are rapidly increasing but the medication options are still limited for this perilous disease. The emergent outbreak of COVID-19 triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps propagating globally. The present scenario has emphasized the requirement for therapeutic opportunities to relive and overcome this latest pandemic. Despite the fact, the deteriorating developments of COVID-19, there is no drug certified to have considerable effects in the medical treatment for COVID-19 patients. The COVID-19 pandemic requests for the rapid testing of new treatment approaches. Based on the evidence, hydroxychloroquine is the first medicine opted for the treatment of disease. Umifenovir, remdesivir, and fevipiravir are deemed the most hopeful antiviral agent by improving the health of infected patients. The dexamethasone is a first known steroid medicine that can save the lives of seriously ill patients, and it is shown in a randomized clinical trial by the United Kingdom that it reduced the death rate in COVID-19 patients. The current review recapitulates the existing evidence of possible therapeutic drugs, peptides, humanized antibodies, convulsant plasma, and vaccination that has revealed potential in fighting COVID-19 infections. Many randomized and controlled clinical trials are taking place to further validate these agent's safety and effectiveness in curing COVID-19.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , /tratamento farmacológico , /terapia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Amidas/uso terapêutico , Antibacterianos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , Antiparasitários/uso terapêutico , Canabinoides/uso terapêutico , Cloroquina/uso terapêutico , Inativadores do Complemento/uso terapêutico , Dexametasona/uso terapêutico , Combinação de Medicamentos , Inibidores Enzimáticos/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Imunização Passiva , Indóis/uso terapêutico , Interferons/uso terapêutico , Ivermectina/uso terapêutico , Lopinavir/uso terapêutico , Pirazinas/uso terapêutico , Ritonavir/uso terapêutico , Teicoplanina/uso terapêutico , Tetraciclinas/uso terapêutico , Tiazóis/uso terapêutico
9.
J Fish Dis ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33169393

RESUMO

Prophenoloxidase (proPO) is very important to protect the invertebrates from microbial infections. Our previous studies revealed that proPO was up-regulated in WSSV-injected Macrobrachium rosenbergii and is responsible for protecting M. rosenbergii from WSSV. In order to prove this mechanism, an attempt was made in the present study to silence the proPO gene in freshwater prawn by injection of dsRNA-proPO followed by WSSV challenge. Two partial fragments of proPO with the size of 251 and 331 bp were used to synthesize dsRNA using LITMUS38i vector and E. coli. The bacterially synthesized dsRNA-proPO was used to silence proPO gene to determine its involvement in developing resistance in prawn against WSSV. In proPO gene-silenced prawn, 100% mortality was observed after WSSV challenge whereas no mortality was observed in prawn injected with WSSV alone. The WSSV infection in gene-silenced prawn was confirmed by PCR, and its propagation was quantified by ELISA and real-time PCR at different time intervals. Real-time PCR assay revealed a significant reduction in the expression of proPO gene in WSSV-challenged proPO-silenced prawn when compared to normal prawn. Level of proPO was reduced significantly in the haemolymph of proPO-silenced prawn when compared to prawn injected with PBS.

10.
Phys Chem Chem Phys ; 22(42): 24516-24525, 2020 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-33090146

RESUMO

Self-oscillating chemical reactions are dynamical reaction-diffusion systems that show immense potential in the design of synthetic soft materials with biomimetic functionalities. The Belousov-Zhabotinsky (BZ) reaction is one such reaction, where the periodic change in the redox state of the metal ion catalyst drives the rhythmic chemical oscillations. Inspired by the exceptional properties of graphene, specifically its catalytic activity for redox reactions, we investigate the effect of graphene-based nanocomposites on the dynamics of the BZ reaction. In particular, we synthesized catalytic mats by decorating ceria nanoparticles (CeNPs) on graphene-based nanosheets, thereby creating 0D-2D heterostructures and subsequently, incorporate these catalytic mats into the BZ reaction. Our investigations reveal that CeNP decorated nanocomposites significantly enhance the oscillating frequency of the BZ reaction, not only compared to the traditional solution-based catalysts but also compared to the bare graphene-based nanosheets. From our experiments at various temperatures and concentrations, together with modelling and simulations, we determine the apparent rate constant for different CeNP decorated graphene nanocomposites. Ultimately, we determine the apparent rate and estimate various kinetic parameters, including activation energy and reaction order. In short, we demonstrate that CeNP decorated nanomats are excellent catalysts and elucidate that the kinetics of the BZ reaction can be simulated using the Oregonator model with our kinetic parameters. We envisage that our findings can be utilized to harness multiscale interactions to design a variety of multifunctional stimuli responsive materials.

11.
J Family Med Prim Care ; 9(7): 3623-3629, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33102340

RESUMO

Background: Effective and efficient use of technological advances will ease public health interventions and also help in reaching a larger population. Geographic Information System (GIS) and Foldscope are two such technologies, which have promising utilities in public health. Identifying intestinal parasitic infections early through feasible technologies will help in their effective management. With this objective, this study was conducted to assess the prevalence of intestinal parasitic infections among school children in southern districts of Karnataka, India. Methods: This cross-sectional study was conducted among randomly selected 10 urban, 10 rural, and 5 tribal schools of southern districts of Karnataka. A total of 1052 children studying in these schools were selected. Stool samples were collected and examined under Foldscope for parasitic infestation. The schools where children with worm infestations present were plotted in the GIS map. Findings: Among 1052 children included in this study, 139 (13.2%) were found to have an intestinal parasitic infestation. Among these children, 24.6% were in the age group of 5-9 years, 12.2% were males, and 14.4% were females. Urban students had higher odds (2.765) of parasitic infections compared to rural students. Mean age, height, and weight were significantly lesser among subjects with a worm infestation. Interpretation: Utility of Foldscope and GIS was found to be feasible and effective in the detection and mapping of parasitic infestations. The prevalence of parasitic infestation was found to be high among urban school children. Age, weight, height, and urban residence were found to be the major predictors of outcome.

12.
Mol Genet Metab Rep ; 25: 100645, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32995289

RESUMO

Propionic Acidemia (PA) is an inborn error of metabolism caused by variants in the PCCA or PCCB genes, leading to mitochondrial accumulation of propionyl-CoA and its by-products. Here, we report a 2 year-old Egyptian boy with PA who was born to consanguineous parents. Biochemical analysis was performed using tandem mass spectrometry (MS/MS) on the patient's dried blood spots (DBS) followed by urine examination of amino acids using gas chromatography/mass spectrometry (GC/MS). Molecular genetic analysis was carried out using whole-exome sequencing (WES). The PCCA gene sequencing revealed a novel homozygous missense variant affecting the locus (chr13:100962160) of exon 16 of the PCCA gene, resulting in the substitution of the amino acid arginine with proline at site 476 (p.Arg476Pro). Computational analysis revealed that the novel variant might be pathogenic and attributed to decrease the stability and also has an effect on the biotin carboxylase c-terminal domain of the propionyl carboxylase enzyme. The physicochemical properties analysis using NCBI amino acid explorer study revealed restrictions in the side chain and loss of hydrogen bonds due to the variant. On the structural level, the loss of beta-sheet was observed due to the variant proline, which has further led to the loss of surrounding interactions. This loss of beta-sheet and the surrounding interactions might serve the purpose of the structural stability changes. The current study demonstrates that a combination of whole-exome sequencing (WES) and computational analysis are potent tools for validation of diagnosis and classification of disease-causing variants.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32986686

RESUMO

Pulmonary interstitial emphysema (PIE) is a severe complication of mechanical ventilation in preterm infants. Selective bronchial intubation is a rarely used treatment strategy, as it is challenging, especially left main stem bronchial intubation. We report our experience in an infant at 24 weeks gestation with bedside left main stem bronchial intubation using flexible fiberoptic bronchoscopy. We also describe in detail the procedural details involved in the selective left main stem bronchial intubation including the helpful technique of gently bending the tip of the endotracheal tube to create "memory" to better direct the tube into the left main-stem bronchus while using the flexible fiberoptic bronchoscope. A review of the literature regarding selective bronchial intubation in newborn infants is presented. This case report and literature review suggest that bedside left main stem bronchial intubation using a flexible fiberoptic bronchoscope is a viable option to successfully manage even the most unstable extreme premature infant with unilateral right lung cystic PIE. This may potentially prevent a rare but necessary invasive surgical procedure like lobectomy or even death.

14.
Artigo em Inglês | MEDLINE | ID: mdl-32986687

RESUMO

Renal cystic diseases are a clinically and genetically diverse group of renal diseases that can manifest in utero, infancy, or throughout childhood and adulthood. These diseases may be unilateral or bilateral with a single cyst or multiple cysts, or with increased echogenicity of the renal cortex without macroscopic cysts. Certain cystic renal diseases are life-threatening, with many developing chronic kidney and hepatic disease if not recognized early enough. Therefore, due to the prevalence and life-altering complications of this specific group of diseases in vulnerable populations, it is crucial for clinicians and healthcare providers to have an overall understanding of cystic diseases and how to pre-emptively detect and manage these conditions. In this review, we discuss in detail the epidemiology, genetics and pathophysiology, diagnosis, presentation, and management of numerous genetic and sporadic renal cystic diseases, such as polycystic kidney disease, multicystic dysplastic kidney, and calyceal diverticula, with an emphasis on prenatal care and pregnancy counseling.

15.
Talanta ; 220: 121439, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32928440

RESUMO

N-acetyl-ß-d-glucosaminidase (NAGase) is an established indicative biomarker released upon damage or necrosis of tubular epithelial cells in both humans and animals, indicating severe nephrological disorders and bovine mastitis (BM), respectively. The latter is the most common and costly disease in dairy cattle associated with production losses, elevated somatic cell counts and deteriorated health status. Herein, we report on a reflective based assay for early diagnosis of BM through the analysis of NAGase inherent content found in whole milk samples using a miniaturized optical transducer. Gelatin functionalized porous Si Fabry-Pérot interferometers are employed for monitoring the lysosomal activity in various stages of the inflammation (healthy, subclinical and clinical). The enzymatic reaction products precipitate and accumulate within the porous nanostructure, thus alter the average refractive index monitored using reflectometric interference spectroscopy. The optical assay is calibrated within the clinically relevant concentrations of BM while presenting a dynamic range of 1.04-16.7 µM min-1 and the detection limit of 0.49 µM min-1. The specific optical performance of the biosensor correlates with a gold standard laboratory-based approach, in which escalated somatic cell counts reveal augmented NAGase levels and thus severe pathogenesis. Overall, our study provides new opportunities to develop a convenient bio-diagnostic sensing system for BM detection and classification by addressing the limitations of conventional practices.

16.
Br Dent J ; 229(5): 268-269, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32917994
17.
Diabetes Metab Syndr ; 14(5): 1327-1332, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32755831

RESUMO

BACKGROUND AND AIMS: Associated with severe complications and morbidity, Diabetes Mellitus is a significant public health burden. The need for regular monitoring and adherence to treatment and lifestyle changes have a high impact on the quality of life of the patients. This study attempts to assess the effect of smartphone-based lifestyle modification intervention in the quality of life of patients with type 2 Diabetes through a randomized filed trial. METHODS: A randomized field trial was performed among the patients attending the outpatient department of a tertiary care hospital in Mysuru city. A mobile application named DIAGURU, mainly focusing on the lifestyle modification and medication management was used for a period of 6 months from April 2019 to September 2019 by 150 patients in the intervention group while another 150 participants served as controls. The quality of life was assessed using the WHO QOL BREF questionnaire at the beginning of the study and after six months. RESULTS: The change in the quality of life in a positive direction was significantly higher in the intervention group compared to the non-intervention group after six months. The differences in the change in scores of quality of life of participants recruited in intervention and non-intervention groups were statistically significant in all the four domains after the intervention with a p value < 0.001. CONCLUSION: The evidence generated in this study suggest that such technological approaches can be used as a public health measure to improve the quality of life of patients with type 2 Diabetes Mellitus.

18.
Ann Maxillofac Surg ; 10(1): 108-113, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32855925

RESUMO

Aim: The present study is designed to evaluate and compare the ability of serratiopeptidase and dexamethasone to control edema following the surgical removal of mandibular third molar. Materials and Methods: Two drugs, dexamethasone and serratiopeptidase, were compared for its efficacy in reducing the postoperative swelling. A total of 100 patients requiring the surgical removal of impacted mandibular third molar were randomly divided into two groups, consisting of 50 patients each. One group was administered 1 mg dexamethasone, one-half h preoperatively and every 8th hourly for 3 days postoperatively. The other group was given 10 mg serratiopeptidase every 8th hourly for 3 days postoperatively. The swelling was measured on 1st, 2nd, 5th, and 7th postoperative days. The results of this study showed that serratiopeptidase was effective in reducing swelling from 2nd to 5th postoperative day, and dexamethasone was effective in reducing swelling from 1st to 2nd postoperative day, further, it also reduced the swelling from 2nd to 5th postoperative day. Results: There was highly significant difference in the facial measurement between serratiopeptidase and dexamethasone group on postoperative day 2 (the mean difference was 62.5 with P < 0.001) and statistically significant difference on postoperative day 1, day 5, and day 7 (P < 0.01). Conclusion: It can be concluded that serratiopeptidase, a proteolytic enzyme and dexamethasone, a long-acting corticosteroid was effective in reducing the swelling, but dexamethasone was more effective than serratiopeptidase in reducing the swelling.

19.
Placenta ; 97: 79-88, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32792069

RESUMO

INTRODUCTION: We use an in-vitro human fetal membrane (FM) explant-based model to study inflammation-induced FM weakening, a prerequisite for PPROM. In this system, GMCSF is a critical intermediate, both necessary and sufficient for TNFα and thrombin induced FM weakening. α-Lipoic-acid (LA) blocks TNFα and thrombin, as well as GMCSF-induced weakening. Recently, we reported LA concomitantly blocks GMCSF-induction of MMPs 2, 9 and 10 and inhibition of TIMPs 1-3. The aim of this study was to show that LA blocks GMCSF-induced increases in additional proteases and reductions in additional protease inhibitors. METHODS: FM fragments were cultured±LA and then±GMCSF. In other experiments, weak versus strong, fresh FM were cultured without additions. Fragments were strength tested and media analyzed by multiplex protein ELISA for proteases and protease inhibitors. RESULTS: GMCSF induced FM weakening and concomitantly increased several Proteases (Cathepsin-S, Proteinase-3, Elastase-2) and decreased several protease inhibitors (NGAL, Cystatin-C, HE4 and Thrombospondin1). LA inhibited GMCSF-induced FM weakening and all enzymatic changes. Untreated weaker versus stronger regions of fresh FM showed comparable differences in proteases and protease inhibitor patterns to GMCSF-stimulated versus controls. CONCLUSION: LA blocks GMCSF-induced human FM weakening and associated protease increases and inhibitor decreases. The GMCSF-induced spectrum of protease/protease-inhibitor changes is similar to that in the natural weak FM fragments. In concert with previously reported GMCSF-induced changes in MMPs & TIMPs, these other protease and protease-inhibitor changes presumably facilitate FM weakening and rupture. LA blocks these GMCSF effects and therefore may be a useful agent to prevent PPROM.

20.
Front Genet ; 11: 734, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760426

RESUMO

Background and Aims: Familial hypercholesterolemia (FH) is one of the major risk factor for the progression of atherosclerosis and coronary artery disease. This study focused on identifying the dysregulated molecular pathways and core genes that are differentially regulated in FH and to identify the possible genetic factors and potential underlying mechanisms that increase the risk to atherosclerosis in patients with FH. Methods: The Affymetrix microarray dataset (GSE13985) from the GEO database and the GEO2R statistical tool were used to identify the differentially expressed genes (DEGs) from the white blood cells (WBCs) of five heterozygous FH patients and five healthy controls. The interaction between the DEGs was identified by applying the STRING tool and visualized using Cytoscape software. MCODE was used to determine the gene cluster in the interactive networks. The identified DEGs were subjected to the DAVID v6.8 webserver and ClueGo/CluePedia for functional annotation, such as gene ontology (GO) and enriched molecular pathway analysis of DEGs. Results: We investigated the top 250 significant DEGs (p-value < 0.05; fold two change ≥ 1 or ≤ -1). The GO analysis of DEGs with significant differences revealed that they are involved in critical biological processes and molecular pathways, such as myeloid cell differentiation, peptidyl-lysine modification, signaling pathway of MyD88-dependent Toll-like receptor, and cell-cell adhesion. The analysis of enriched KEGG pathways revealed the association of the DEGs in ubiquitin-mediated proteolysis and cardiac muscle contraction. The genes involved in the molecular pathways were shown to be differentially regulated by either activating or inhibiting the genes that are essential for the canonical signaling pathways. Our study identified seven core genes (UQCR11, UBE2N, ADD1, TLN1, IRAK3, LY96, and MAP3K1) that are strongly linked to FH and lead to a higher risk of atherosclerosis. Conclusion: We identified seven core genes that represent potential molecular biomarkers for the diagnosis of atherosclerosis and might serve as a platform for developing therapeutics against both FH and atherosclerosis. However, functional studies are further needed to validate their role in the pathogenesis of FH and atherosclerosis.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA