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1.
Crit Rev Biotechnol ; 44(2): 275-301, 2024 Mar.
Article in English | MEDLINE | ID: mdl-36683015

ABSTRACT

The hydrogels based on natural gums and chemically derivatized natural gums have great interest in pharmaceutical, food, cosmetics, and environmental remediation, due to their: economic viability, sustainability, nontoxicity, biodegradability, and biocompatibility. Since these natural gems are from plants, microorganisms, and seaweeds, they offer a great opportunity to chemically derivatize and modify into novel, innovative biomaterials as scaffolds for tissue engineering and drug delivery. Derivatization improves swelling properties, thereby developing interest in agriculture and separating technologies. This review highlights the work done over the past three and a half decades and the possibility of developing novel materials and technologies in a cost-effective and sustainable manner. This review has compiled various natural gums, their source, chemical composition, and chemically derivatized gums, various methods to synthesize hydrogel, and their applications in biomedical, food and agriculture, textile, cosmetics, water purification, remediation, and separation fields.


Subject(s)
Food Industry , Hydrogels , Hydrogels/chemistry , Biocompatible Materials , Tissue Engineering , Agriculture
2.
Microvasc Res ; 145: 104454, 2023 01.
Article in English | MEDLINE | ID: mdl-36347299

ABSTRACT

OBJECTIVE: Subclinical life style disease can cause endothelial dysfunction associated with perfusion abnormalities and reduced vascular compliance. Subclinical elevated beta type natriuretic peptide (BNP) has been associated with altered fluid shift from extra to intracellular space during acute hypoxia. Therefore we measured vascular response and BNP levels during acute hypoxia to study endothelial functions among healthy individuals. METHODS: Individuals were exposed to acute normobaric hypoxia of FiO2 = 0.15 for one hour in supine position and their pulmonary and systemic vascular response to hypoxia was compared. Individuals were divided into two groups based on either no response (Group 1) or rise in systolic pulmonary artery pressure to hypoxia (Group 2) and their BNP levels were compared. RESULTS: BNP was raised after hypoxia exposure in group 2 only from 18.52 ± 7 to 21.56 ± 10.82 picogram/ml, p < 0.05. Group 2 also showed an increase in mean arterial pressure and no fall in total body water in response to acute hypoxia indicating decreased endothelial function compared to Group 1. CONCLUSION: Rise in pulmonary artery pressure and BNP level in response to acute normobaric hypoxia indicates reduced endothelial function and can be used to screen subclinical lifestyle disease among healthy population.


Subject(s)
Hypoxia , Natriuretic Peptide, Brain , Humans , Hypoxia/diagnosis , Lung/blood supply , Vasodilator Agents , Life Style , Pulmonary Artery
3.
Clin Med (Lond) ; 23(Suppl 6): 24, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38182185
4.
Asian Pac J Cancer Prev ; 23(5): 1577-1586, 2022 May 01.
Article in English | MEDLINE | ID: mdl-35633541

ABSTRACT

OBJECTIVE: Cancer is a huge problem of disease globally. Today, the percentage of people die from cancer is more than a combination of various diseases. In females, most common types of malignancies that occur are breast and cervical. The present focus has been shifted on medicinal plants as a form of therapy and there is a constant need to identify new therapeutic agents. Choerospondias axillaris (C. axillaris), an underutilized fruit, has been used in the remedy of various diseases. In the present communication, we evaluated the molecular mechanism of C. axillaris methanol extract in regulating cell death in human breast cancer cells (MDA-MB-231). METHODS: Methanol extract of C. axillaris was prepared and compounds were screened by Gas chromatography-mass spectrometry. The effect of fruit extract was determined on MDA-MB-231 cells by MTT ((3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay and to analyse the molecular mechanism of human breast cancer cells after treating with fruit extract, protein profiling study was performed by two-dimensional gel electrophoresis. RESULTS: A total 9 differentially expressed proteins were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS/MS) analysis. Among 9 identified proteins, synphilin-1 protein was found to be significantly downregulated, validated by western blot and RT-qPCR analysis. Possible interacting partners of synphilin-1 (SNCAIP) were analyzed for their possible role in cancer by the in-silico method. CONCLUSION: Our data implicate that the presence of bioactive compound(s) in C. axillaris fruits might play an important role in inhibiting the proliferation of breast carcinoma cells and Synphilin-1 protein may play a role of apoptotic function.


Subject(s)
Anacardiaceae , Breast Neoplasms , Carrier Proteins , Nerve Tissue Proteins , Plant Extracts , alpha-Synuclein , Anacardiaceae/chemistry , Breast Neoplasms/drug therapy , Carrier Proteins/genetics , Cell Line, Tumor , Female , Fruit/chemistry , Humans , Methanol , Nerve Tissue Proteins/genetics , Plant Extracts/chemistry , Plant Extracts/pharmacology , Tandem Mass Spectrometry , alpha-Synuclein/genetics
5.
BMC Cancer ; 21(1): 962, 2021 Aug 27.
Article in English | MEDLINE | ID: mdl-34445986

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death in the world owing to limitations in its prognosis. The current prognosis approaches include radiological examination and detection of serum biomarkers, however, both have limited efficiency and are ineffective in early prognosis. Due to such limitations, we propose to use RNA-Seq data for evaluating putative higher accuracy biomarkers at the transcript level that could help in early prognosis. METHODS: To identify such potential transcript biomarkers, RNA-Seq data for healthy liver and various HCC cell models were subjected to five different machine learning algorithms: random forest, K-nearest neighbor, Naïve Bayes, support vector machine, and neural networks. Various metrics, namely sensitivity, specificity, MCC, informedness, and AUC-ROC (except for support vector machine) were evaluated. The algorithms that produced the highest values for all metrics were chosen to extract the top features that were subjected to recursive feature elimination. Through recursive feature elimination, the least number of features were obtained to differentiate between the healthy and HCC cell models. RESULTS: From the metrics used, it is demonstrated that the efficiency of the known protein biomarkers for HCC is comparatively lower than complete transcriptomics data. Among the different machine learning algorithms, random forest and support vector machine demonstrated the best performance. Using recursive feature elimination on top features of random forest and support vector machine three transcripts were selected that had an accuracy of 0.97 and kappa of 0.93. Of the three transcripts, two were protein coding (PARP2-202 and SPON2-203) and one was a non-coding transcript (CYREN-211). Lastly, we demonstrated that these three selected transcripts outperformed randomly taken three transcripts (15,000 combinations), hence were not chance findings, and could then be an interesting candidate for new HCC biomarker development. CONCLUSION: Using RNA-Seq data combined with machine learning approaches can aid in finding novel transcript biomarkers. The three biomarkers identified: PARP2-202, SPON2-203, and CYREN-211, presented the highest accuracy among all other transcripts in differentiating the healthy and HCC cell models. The machine learning pipeline developed in this study can be used for any RNA-Seq dataset to find novel transcript biomarkers. Code: www.github.com/rajinder4489/ML_biomarkers.


Subject(s)
Algorithms , Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Machine Learning , Neural Networks, Computer , RNA-Seq/methods , Bayes Theorem , Carcinoma, Hepatocellular/genetics , Humans , Liver Neoplasms/genetics
6.
Sci Rep ; 11(1): 11575, 2021 06 02.
Article in English | MEDLINE | ID: mdl-34078926

ABSTRACT

The renal proximal tubule is responsible for re-absorption of the majority of the glomerular filtrate and its proper function is necessary for whole-body homeostasis. Aging, certain diseases and chemical-induced toxicity are factors that contribute to proximal tubule injury and chronic kidney disease progression. To better understand these processes, it would be advantageous to generate renal tissues from human induced pluripotent stem cells (iPSC). Here, we report the differentiation and characterization of iPSC lines into proximal tubular-like cells (PTL). The protocol is a step wise exposure of small molecules and growth factors, including the GSK3 inhibitor (CHIR99021), the retinoic acid receptor activator (TTNPB), FGF9 and EGF, to drive iPSC to PTL via cell stages representing characteristics of early stages of renal development. Genome-wide RNA sequencing showed that PTL clustered within a kidney phenotype. PTL expressed proximal tubular-specific markers, including megalin (LRP2), showed a polarized phenotype, and were responsive to parathyroid hormone. PTL could take up albumin and exhibited ABCB1 transport activity. The phenotype was stable for up to 7 days and was maintained after passaging. This protocol will form the basis of an optimized strategy for molecular investigations using iPSC derived PTL.


Subject(s)
Induced Pluripotent Stem Cells/cytology , Kidney Tubules, Proximal/cytology , Biomarkers/metabolism , Cell Differentiation , Cells, Cultured , Humans , Sequence Analysis, RNA/methods
7.
Crit Rev Biotechnol ; 41(5): 767-791, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33530758

ABSTRACT

Globalization of the food trade requires precise and exact information about the origin, methods of production, transformation technologies, authentication, and the traceability of foodstuffs. New challenges in food supply chains such as deliberate fraudulent substitution, tampering or mislabeling of food and its ingredients or food packaging incapacitates the market and eventually the national economy. Currently, no proper standards have been established for the authentication of most of the food materials. However, in order to control food fraud, various robust and cost-effective technologies have been employed, like a spectrophotometer, GC-MS, HPLC, and DNA barcoding. Among these techniques, DNA barcoding is a biotechnology advantage with the principle of using 400-800 bp long standardized unique DNA sequences of mitochondrial (e.g. COI) or plastidial (e.g. rbcL) of nuclear origin (e.g. ITS) to analyze and classify the food commodities. This review covers several traded food commodities like legumes, seafood, oils, herbal products, spices, fruits, cereals, meat, and their unique barcodes which are critically analyzed to detect adulteration or fraud. DNA barcoding is a global initiative and it is being accepted as a global standard/marker for species identification or authentication. The research laboratories and industries should collaborate to realize its potential in setting standards for quality assurance, quality control, and food safety for different food products.


Subject(s)
DNA Barcoding, Taxonomic , Food Safety , Fruit , Meat , Quality Control
8.
Nanoscale Adv ; 3(10): 2679-2698, 2021 May 18.
Article in English | MEDLINE | ID: mdl-36134176

ABSTRACT

Gold nanoparticles (AuNPs) are highly compelling nanomaterials for biomedical studies due to their unique optical properties. By leveraging the versatile optical properties of different gold nanostructures, the performance of biosensing and biomedical imaging can be dramatically improved in terms of their sensitivity, specificity, speed, contrast, resolution and penetration depth. Here we review recent advances of optical biosensing and bioimaging techniques based on three major optical properties of AuNPs: surface plasmon resonance, surface enhanced Raman scattering and luminescence. We summarize the fabrication methods and optical properties of different types of AuNPs, highlight the emerging applications of these AuNPs for novel optical biosensors and biomedical imaging innovations, and discuss the future trends of AuNP-based optical biosensors and bioimaging as well as the challenges of implementing these techniques in preclinical and clinical investigations.

9.
Cell Stress Chaperones ; 26(2): 323-339, 2021 03.
Article in English | MEDLINE | ID: mdl-33210173

ABSTRACT

The present study aimed to investigate the differential response of oxidative (soleus) and glycolytic (gastrocnemius) muscles to heat-induced endoplasmic reticulum (ER) stress. It was hypothesized that due to compositional and functional differences, both muscles respond differently to acute heat stress. To address this, male Sprague Dawley rats (12/group) were subjected to thermoneutral (25 °C) or heat stress (42 °C) conditions for 1 h. Soleus and gastrocnemius muscles were removed for analysis post-exposure. A significant increase in body temperature and free radical generation was observed in both the muscles following heat exposure. This further caused a significant increase in protein carbonyl content, AOPP, and lipid peroxidation in heat-stressed muscles. These changes were more pronounced in heat-stressed soleus compared to the gastrocnemius muscle. Accumulation of unfolded, denatured proteins results in ER stress, causing activation of unfolded protein response (UPR) pathway. The expressions of UPR transducers were significantly higher in soleus as compared to the gastrocnemius muscle. A significant elevation in resting intracellular calcium ion was also observed in heat-stressed soleus muscle. Overloading of cells with misfolded proteins in soleus muscle activated ER-induced apoptosis as indicated by significant upregulation of C/EBP homologous protein and Caspase12. The study provides a detailed mechanistic representation of the differential response of muscles toward UPR under heat stress. Data suggests that soleus majorly being an oxidative muscle is more prone to heat stress-induced insult indicated by enhanced apoptosis. This study may aid in devising mitigation strategies to improve muscle performance under heat stress.


Subject(s)
Endoplasmic Reticulum Stress , Heat-Shock Response , Muscle, Skeletal/metabolism , Oxidative Stress , Animals , Apoptosis , Male , Muscle, Skeletal/cytology , Rats , Rats, Sprague-Dawley , Unfolded Protein Response
10.
Arch Toxicol ; 95(2): 573-589, 2021 02.
Article in English | MEDLINE | ID: mdl-33106934

ABSTRACT

The liver plays an important role in xenobiotic metabolism and represents a primary target for toxic substances. Many different in vitro cell models have been developed in the past decades. In this study, we used RNA-sequencing (RNA-Seq) to analyze the following human in vitro liver cell models in comparison to human liver tissue: cancer-derived cell lines (HepG2, HepaRG 3D), induced pluripotent stem cell-derived hepatocyte-like cells (iPSC-HLCs), cancerous human liver-derived assays (hPCLiS, human precision cut liver slices), non-cancerous human liver-derived assays (PHH, primary human hepatocytes) and 3D liver microtissues. First, using CellNet, we analyzed whether these liver in vitro cell models were indeed classified as liver, based on their baseline expression profile and gene regulatory networks (GRN). More comprehensive analyses using non-differentially expressed genes (non-DEGs) and differential transcript usage (DTU) were applied to assess the coverage for important liver pathways. Through different analyses, we noticed that 3D liver microtissues exhibited a high similarity with in vivo liver, in terms of CellNet (C/T score: 0.98), non-DEGs (10,363) and pathway coverage (highest for 19 out of 20 liver specific pathways shown) at the beginning of the incubation period (0 h) followed by a decrease during long-term incubation for 168 and 336 h. PHH also showed a high degree of similarity with human liver tissue and allowed stable conditions for a short-term cultivation period of 24 h. Using the same metrics, HepG2 cells illustrated the lowest similarity (C/T: 0.51, non-DEGs: 5623, and pathways coverage: least for 7 out of 20) with human liver tissue. The HepG2 are widely used in hepatotoxicity studies, however, due to their lower similarity, they should be used with caution. HepaRG models, iPSC-HLCs, and hPCLiS ranged clearly behind microtissues and PHH but showed higher similarity to human liver tissue than HepG2 cells. In conclusion, this study offers a resource of RNA-Seq data of several biological replicates of human liver cell models in vitro compared to human liver tissue.


Subject(s)
Computational Biology/methods , Hepatocytes/metabolism , Liver Neoplasms/metabolism , Liver/metabolism , Transcriptome , Cell Differentiation , Cell Line, Tumor , Cells, Cultured , Gene Expression Profiling , Gene Expression Regulation , Gene Regulatory Networks , Hep G2 Cells , High-Throughput Nucleotide Sequencing , Humans , In Vitro Techniques , Induced Pluripotent Stem Cells/metabolism , Models, Biological , RNA-Seq
11.
Bioinformatics ; 37(3): 375-381, 2021 04 20.
Article in English | MEDLINE | ID: mdl-32814975

ABSTRACT

SUMMARY: Typical RNA sequencing (RNA-Seq) analyses are performed either at the gene level by summing all reads from the same locus, assuming that all transcripts from a gene make a protein or at the transcript level, assuming that each transcript displays unique function. However, these assumptions are flawed, as a gene can code for different types of transcripts and different transcripts are capable of synthesizing similar, different or no protein. As a consequence, functional changes are not well illustrated by either gene or transcript analyses. We propose to improve RNA-Seq analyses by grouping the transcripts based on their similar functions. We developed FuSe to predict functional similarities using the primary and secondary structure of proteins. To estimate the likelihood of proteins with similar functions, FuSe computes two confidence scores: knowledge (KS) and discovery (DS) for protein pairs. Overlapping protein pairs exhibiting high confidence are grouped to form 'similar function protein groups' and expression is calculated for each functional group. The impact of using FuSe is demonstrated on in vitro cells exposed to paracetamol, which highlight genes responsible for cell adhesion and glycogen regulation which were earlier shown to be not differentially expressed with traditional analysis methods. AVAILABILITY AND IMPLEMENTATION: The source code is available at https://github.com/rajinder4489/FuSe. Data for APAP exposure are available in the BioStudies database (http://www.ebi.ac.uk/biostudies) under accession numbers S-HECA143, S-HECA(158) and S-HECA139. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Subject(s)
Proteins , Software , Gene Expression Profiling , RNA, Messenger/genetics , RNA-Seq , Sequence Analysis, RNA
12.
Sci Rep ; 10(1): 16714, 2020 10 07.
Article in English | MEDLINE | ID: mdl-33028897

ABSTRACT

Acrylamide (ACR) is a known neurotoxicant which crosses the blood-brain barrier, passes the placenta and has been detected in breast milk. Hence, early-life exposure to ACR could lead to developmental neurotoxicity. The aim of this study was to elucidate if non-cytotoxic concentrations of ACR alter neuronal differentiation by studying gene expression of markers significant for neurodevelopment in the human neuroblastoma SH-SY5Y cell model. Firstly, by using RNASeq we identified two relevant pathways that are activated during 9 days of retinoic acid (RA) induced differentiation i.e. RA receptor (RAR) activation and the cAMP response element-binding protein (CREB) signalling pathways. Next, by qPCR we showed that 1 and 70 µM ACR after 9 days exposure alter the expression of 13 out of 36 genes in the RAR activation pathway and 18 out of 47 in the CREB signalling pathway. Furthermore, the expression of established neuronal markers i.e. BDNF, STXBP2, STX3, TGFB1 and CHAT were down-regulated. Decreased protein expression of BDNF and altered ratio of phosphorylated CREB to total CREB were confirmed by western blot. Our results reveal that micromolar concentrations of ACR sustain proliferation, decrease neurite outgrowth and interfere with signalling pathways involved in neuronal differentiation in the SH-SY5Y cell model.


Subject(s)
Acrylamide/pharmacology , Cell Differentiation/drug effects , Cyclic AMP Response Element-Binding Protein/metabolism , Neurons/drug effects , Signal Transduction/drug effects , Tretinoin/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Humans , Neuroblastoma/metabolism , Neuronal Outgrowth/drug effects , Neurons/metabolism
13.
Life Sci ; 260: 118408, 2020 Nov 01.
Article in English | MEDLINE | ID: mdl-32926931

ABSTRACT

AIMS: Baseline elevated B-type Natriuretic Peptide (BNP) has been found in high altitude pulmonary edema susceptible population. Exaggerated pulmonary vascular response to hypoxia may be related to endothelial dysfunction in hypoxia susceptible. We hypothesize that baseline BNP levels can predict hypoxia susceptibility in healthy individuals. MAIN METHODS: The pulmonary vascular response to hypoxia was compared in 35 male healthy individuals divided into two groups based on BNP levels (Group 1 ≤ 15 and Group 2 > 15 pg/ml). Acute normobaric hypoxia was administered to both the groups, to confirm hypoxia susceptibility in Group 2. KEY FINDINGS: Unlike Group 1, Group 2 had elevated post hypoxia BNP levels (26 vs 33.5 pg/ml, p = 0.002) while pulmonary artery pressure was comparable. A negative correlation with tissue oxygen consumption (delta pO2) and compartmental fluid shift was seen in Group 1 only. Endothelial dysfunction in Group 2 resulted in reduced vascular compliance leading to elevation of mean blood pressure on acute hypoxia exposure. BNP showed a positive correlation with endothelial dysfunction in Group 2 and has been linked to pre-diabetic disorder (HbA1c 6 ± 0.44%) and may additionally represent a lower cross-sectional area of vascular bed related to vascular remodeling mediated by chronic hypoxia. SIGNIFICANCE: Hypoxia susceptibility in healthy individuals may be related to endothelial dysfunction that limits vascular compliance during hypoxic stress. BNP level showed positive correlation with HbA1c (r = 0.49, p = 0.04) and negative correlation with delta pO2 (r = -0.52, p = 0.04) can predict reduced microvascular compliance due to endothelial dysfunction contributing to hypoxia susceptibility in healthy individuals. BNP levels≤15 pg/ml at sea level is indicative of hypoxia resistance.


Subject(s)
Altitude , Endothelium, Vascular/physiopathology , Hypoxia/physiopathology , Lung/physiopathology , Natriuretic Peptide, Brain/metabolism , Pulmonary Artery/physiopathology , Pulmonary Edema/physiopathology , Adult , Female , Humans , Male , Respiratory Function Tests
15.
Biotechnol J ; 15(5): e1900279, 2020 May.
Article in English | MEDLINE | ID: mdl-32045505

ABSTRACT

One of the major challenges for scientists and engineers today is to develop technologies for the improvement of human health in both developed and developing countries. However, the need for cost-effective, high-performance diagnostic techniques is very crucial for providing accessible, affordable, and high-quality healthcare devices. In this context, microfluidic-based devices (MFDs) offer powerful platforms for automation and integration of complex tasks onto a single chip. The distinct advantage of MFDs lies in precise control of the sample quantities and flow rate of samples and reagents that enable quantification and detection of analytes with high resolution and sensitivity. With these excellent properties, microfluidics (MFs) have been used for various applications in healthcare, along with other biological and medical areas. This review focuses on the emerging demands of MFs in different fields such as biomedical diagnostics, environmental analysis, food and agriculture research, etc., in the last three or so years. It also aims to reveal new opportunities in these areas and future prospects of commercial MFDs.


Subject(s)
Biosensing Techniques/instrumentation , Microfluidic Analytical Techniques/instrumentation , Equipment Design , Food Industry , Humans , Lab-On-A-Chip Devices , Point-of-Care Testing
16.
Curr Pharm Biotechnol ; 21(7): 596-604, 2020.
Article in English | MEDLINE | ID: mdl-31820687

ABSTRACT

BACKGROUND: Rheumatoid Arthritis (RA) is an autoimmune, systemic disease mainly affecting joints. Presently, there is no specific treatment/ drug available for curing RA except few supportive medicines. Therefore, the focus has been shifted to medicinal plants for the treatment of such diseases. Choerospondias axillaris commonly known as Lupsi/Lapsi and has been reported to have several properties for the treatment of various diseases. OBJECTIVE: The present study has been conducted to explore the anti-inflammatory effects of Choerospondias axillaris fruit extract on Synoviocytes (FLS) and Collagen-Induced Arthritis (CIA) rat model. METHODS: Methanolic extract of the Choerospondias axillaris fruit was used for determining phytochemical, antioxidant and anti-inflammatory properties. Antioxidant activity of Choerospondias axillaris fruit was determined by free radicals scavenging assays and bioactive compounds were identified via LC-MS/MS analysis. Anti-inflammatory effect was investigated in RA and Osteo Arthritis (OA) primary cells and also in Collagen Induced Arthritis (CIA) rat models. Further, the medicinal properties of anti-inflammatory bioactive compounds were supported by docking studies. RESULTS: In-vitro and in-vivo studies showed significant decrease in the levels of inflammatory cytokines. Docking analysis revealed that quercetin inhibits TNF-α having -9.1 kcal/mol binding energy and 10.13 µM inhibitory constant. Quercetin also inhibits IL-6 having -6.6 kcal/mol binding energy and 21.9 µM inhibitory constant. CONCLUSION: Observed results suggest that the underutilized fruit Choerospondias axillaris can be used to reduce the inflammation of inflammatory diseases like RA.


Subject(s)
Anacardiaceae/chemistry , Anti-Inflammatory Agents/pharmacology , Arthritis, Experimental/drug therapy , Fruit/chemistry , Plant Extracts/pharmacology , Synoviocytes/drug effects , Animals , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/therapeutic use , Antioxidants/metabolism , Arthritis, Experimental/immunology , Cells, Cultured , Cytokines/metabolism , Female , Humans , Inflammation , Methanol/chemistry , Molecular Docking Simulation , Plant Extracts/isolation & purification , Plant Extracts/therapeutic use , Primary Cell Culture , Rats , Rats, Wistar , Synoviocytes/immunology , Synoviocytes/metabolism
17.
Sci Rep ; 9(1): 10975, 2019 07 29.
Article in English | MEDLINE | ID: mdl-31358833

ABSTRACT

High Altitude Pulmonary Edema (HAPE) is a threatening disorder caused due to acute exposure to high altitude above 3000 m. Apart from multiple factors involved, the genetic factors also play an important function in the pathogenesis of HAPE. This study aims to evaluate the role of mtDNA polymorphism and their association with haplogroup in understanding the etiology of HAPE. In this study, all the HAPE susceptible and acclimatized control subjects could be classified into nine haplogroups pertaining mostly to Macrohaplogroup M and U. The frequency of haplogroup M was significantly higher in HAPE susceptibles whereas the haplogroup M33a2'3 was found only in HAPE susceptibles. The variant G4491A and A4944G of MT-ND2, A14002G of MT-ND5, and C8562T of MT-ATP8, were definition site of haplogroup M33a2'3. The frequency of A10398G of MT-ND3, A8701G of MT-ATP6 and C14766T of MT-CYB genes were significantly higher in HAPE susceptibles. mtDNA copy number also plays a significant synergistic role in HAPE susceptibility. Our findings suggests that variants in MT-ND2 and MT-ND5 were predicted to confer decreased protein stability in HAPE susceptibles and in particular, highly conserved variants G4491A, A4944G and A14002G associated with haplogroup M33a2'3 may be the primary cause of susceptibility to HAPE in Indian male lowlanders.


Subject(s)
Altitude Sickness/genetics , DNA, Mitochondrial/genetics , Genetic Predisposition to Disease , Hypertension, Pulmonary/genetics , Genes, Mitochondrial , Haplotypes , Humans , India , Male , Mitochondria/genetics , Polymorphism, Single Nucleotide
18.
Sci Rep ; 7(1): 14892, 2017 11 02.
Article in English | MEDLINE | ID: mdl-29097771

ABSTRACT

HAPE susceptible (HAPE-S, had HAPE episode in past) subjects may have subclinical cardio-pulmonary dysfunction. We compared the results of pulmonary function tests in 25 healthy HAPE-S non-mountaineers and 19 matched HAPE resistant (HAPE-R, no HAPE episode in past). Acute normobaric hypoxia (FIo2 0.12) was administered at sea level to confirm hypoxia intolerance in HAPE-S. Unlike HAPE-R, HAPE-S subjects had elevated baseline and post-hypoxia systolic pulmonary arterial pressures (20.9 ± 3 vs 27.3 ± 5 mm Hg during normoxia and 26.2 ± 6 vs 45.44 ± 10 mm Hg during hypoxia, HAPE-R vs HAPE-S). Forced vital capacity (FVC) and single breath alveolar volume (SBVA) were significantly lower in HAPE-S compared to HAPE-R (FVC: 4.33 ± 0.5 vs 4.6 ± 0.4; SBVA: 5.17 ± 1 vs 5.6 ± 1 Lt; HAPE-S vs HAPE-R). Two subgroups with abnormal pulmonary function could be identified within HAPE-S; HAPE-S1 (n = 4) showed DLCO>140% of predicted, suggestive of asthma and HAPE-S2 (n = 12) showed restrictive pattern. Each of these patterns have previously been linked to early small airway disease and may additionally represent a lower cross-sectional area of the pulmonary vascular bed, related to lower lung volumes. HAPE susceptibility in healthy non-mountaineers may be related to sub-clinical pulmonary pathology that limits compensatory rise in ventilation and pulmonary circulation during hypoxic stress.


Subject(s)
Altitude Sickness/etiology , Altitude Sickness/physiopathology , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/physiopathology , Lung/physiopathology , Adult , Altitude , Arterial Pressure , Disease Susceptibility , Humans , Hypoxia/complications , Hypoxia/physiopathology , Lung/blood supply , Male , Pulmonary Artery/physiopathology , Respiratory Function Tests
19.
Neuroscience ; 358: 79-92, 2017 09 01.
Article in English | MEDLINE | ID: mdl-28663093

ABSTRACT

Heat Stress (HS) induces diverse pathophysiological changes, which include brain ischemia, oxidative stress and neuronal damage. The present study was undertaken with the objective to ascertain whether neuroinflammation in Hypothalamus (HTH) caused under HS affects monoamine levels and hence, its physiological role in thermoregulation. Rats were exposed to HS in a heat simulation environmental chamber (Ambient temperature, Ta=45±0.5°C and Relative Humidity, RH=30±10%) with real-time measurement of core temperature (Tc) and skin temperature (Ts). Animals were divided into two subgroups: Moderate HS (MHS) (Tc=40°C) and Severe HS (SHS)/Heat stroke (Tc=42°C). Rats with MHS showed an increase in Mean Arterial Pressure (MAP) and Heart Rate (HR) while fall in MAP and rise in HR was observed in rats with SHS. In addition, oxidative stress and an increase in pyknotic neurons were observed in HTH. High levels of Adrenocorticotropic-hormone (ACTH), Epinephrine (EPI), Norepinephrine (NE) and Dopamine (DA) in the systemic circulation and progressive increase in EPI and DA levels in HTH were recorded after the thermal insult. Moreover, a substantial increase in Glutamate (Glu) level was observed in HTH as well as in systemic circulation of heat stroke rats. We found a rise in NE whereas a fall in Serotonin (5-HT) level in HTH at MHS, without perturbing inflammatory mediators. However, rats with SHS exhibited significant elevations in NF-kB, IL-1ß, COX2, GFAP and Iba1 protein expression in HTH. In conclusion, the data suggest that SHS induces neuroinflammation in HTH, which is associated with monoamines and Glu imbalances, leading to thermoregulatory disruption.


Subject(s)
Biogenic Monoamines/metabolism , Body Temperature/physiology , Encephalitis , Hot Temperature/adverse effects , Zearalenone/analogs & derivatives , Adrenocorticotropic Hormone/metabolism , Analysis of Variance , Animals , Blood Pressure/physiology , Corticotropin-Releasing Hormone/metabolism , Cyclooxygenase 2/metabolism , Encephalitis/etiology , Encephalitis/pathology , Encephalitis/physiopathology , Glial Fibrillary Acidic Protein/metabolism , Heart Rate/physiology , Male , NF-kappa B/metabolism , Oxidative Stress/physiology , Random Allocation , Rats , Rats, Sprague-Dawley , Zearalenone/metabolism
20.
Crit Rev Biotechnol ; 37(8): 959-973, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28423942

ABSTRACT

Natural plant-based gums and their derivatives are widely utilized in food industries, however, their applications as edible coatings to extend fresh fruits and vegetable shelf-life has been explored recently. These natural polymeric polysaccharides have many advantages as compared to synthetic polymers, because they are biodegradable, nontoxic, economical and easily available in the environment. Natural gums can also be semi synthetically modified to produce derivatives, which can easily compete with the synthetic preservatives available on the food market. In this review, the recent developments in the use of natural gums and their derivatives as edible coatings have been explored and discussed.


Subject(s)
Plants/chemistry , Food Industry , Food Packaging , Food Preservation , Fruit
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