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1.
Sci Rep ; 14(1): 8933, 2024 04 18.
Article En | MEDLINE | ID: mdl-38637659

Plasma metabolomics holds potential for precision medicine, but limited information is available to compare the performance of such methods across multiple cohorts. We compared plasma metabolite profiles after an overnight fast in 11,309 participants of five population-based Swedish cohorts (50-80 years, 52% women). Metabolite profiles were uniformly generated at a core laboratory (Metabolon Inc.) with untargeted liquid chromatography mass spectrometry and a comprehensive reference library. Analysis of a second sample obtained one year later was conducted in a subset. Of 1629 detected metabolites, 1074 (66%) were detected in all cohorts while only 10% were unique to one cohort, most of which were xenobiotics or uncharacterized. The major classes were lipids (28%), xenobiotics (22%), amino acids (14%), and uncharacterized (19%). The most abundant plasma metabolome components were the major dietary fatty acids and amino acids, glucose, lactate and creatinine. Most metabolites displayed a log-normal distribution. Temporal variability was generally similar to clinical chemistry analytes but more pronounced for xenobiotics. Extensive metabolite-metabolite correlations were observed but mainly restricted to within each class. Metabolites were broadly associated with clinical factors, particularly body mass index, sex and renal function. Collectively, our findings inform the conduct and interpretation of metabolite association and precision medicine studies.


Metabolome , Metabolomics , Humans , Female , Male , Metabolomics/methods , Plasma/metabolism , Amino Acids/metabolism , Sweden
2.
J Thromb Thrombolysis ; 57(4): 699-709, 2024 Apr.
Article En | MEDLINE | ID: mdl-38393674

Venous thrombosis (VT) is a complex multi-factorial disease and a major health concern worldwide. Its clinical implications include deep vein thrombosis (DVT) and pulmonary embolism (PE). VT pathogenesis involves intricate interplay of various coagulants and anti-coagulants. Growing evidences from epidemiological studies have shown that many non-coding microRNAs play significant regulatory role in VT pathogenesis by modulating expressions of large number of gene involved in blood coagulation. Present study aimed to investigate the effect of human micro RNA (hsa-miR)-320a antagonist on thrombus formation in VT. Surgery was performed on Sprague-Dawley (SD) rats, wherein the inferior vena cava (IVC) was ligated to introduce DVT. Animals were divided into four groups (n = 5 in each group); Sham controls (Sham), IVC ligated-DVT (DVT), IVC ligated-DVT + transfection reagent (DVT-NC) and IVC ligated-DVT + miR320a antagonist (DVT-miR-320a antagonist). IVC was dissected after 6 h and 24 h of surgery to estimate thrombus weight and coagulatory parameters such as levels of D-dimer, clotting time and bleeding time. Also, ELISA based biochemical assays were formed to assess toxicity of miRNA antagonist in animals. Our experimental analysis demonstrated that there was a marked reduction in size of thrombus in hsa-miR-320a antagonist treated animals, both at 6 h and 24 h. There was a marked reduction in D-dimer levels in hsa-miR-320a antagonist treated animals. Also, blood clotting time was delayed and bleeding time was increased significantly in hsa-miR-320a antagonist treated rats compared to the non-treated and Sham rats. There was no sign of toxicity in treated group compared to control animals. Hsa-miR-320a antagonist could be promising therapeutic target for management of VT.


MicroRNAs , Venous Thrombosis , Animals , Rats , MicroRNAs/antagonists & inhibitors , MicroRNAs/genetics , Pulmonary Embolism , Rats, Sprague-Dawley , Venous Thrombosis/complications , Venous Thrombosis/genetics
3.
Heliyon ; 9(2): e13388, 2023 Feb.
Article En | MEDLINE | ID: mdl-36743852

Outbreak of COVID-19 pandemic in December 2019 affected millions of people globally. After substantial research, several biomarkers for COVID-19 have been validated however no specific and reliable biomarker for the prognosis of patients with COVID-19 infection exists. Present study was designed to identify specific biomarkers to predict COVID-19 severity and tool for formulating treatment. A small cohort of subjects (n = 43) were enrolled and categorized in four study groups; Dead (n = 16), Severe (n = 10) and Moderate (n = 7) patients and healthy controls (n = 10). Small RNA sequencing was done on Illumina platform after isolation of microRNA from peripheral blood. Differential expression (DE) of miRNA (patients groups compared to control) revealed 118 down-regulated and 103 up-regulated known miRNAs with fold change (FC) expression ≥2 folds and p ≤ 0.05. DE miRNAs were then subjected to functional enrichment and network analysis. Bioinformatic analysis resulted in 31 miRNAs (24 Down-regulated; 7 up-regulated) significantly associated with COVID-19 having AUC>0.8 obtained from ROC curve. Seventeen out of 31 DE miRNAs have been linked to COVID-19 in previous studies. Three miRNAs, hsa-miR-147b-5p and hsa-miR-107 (down-regulated) and hsa-miR-1299 (up-regulated) showed significant unique DE in Dead patients. Another set of 4 miRNAs, hsa-miR-224-5p (down-regulated) and hsa-miR-4659b-3p, hsa-miR-495-3p and hsa-miR-335-3p were differentially up-regulated uniquely in Severe patients. Members of three miRNA families, hsa-miR-20, hsa-miR-32 and hsa-miR-548 were significantly down-regulated in all patients group in comparison to healthy controls. Thus a distinct miRNA expression profile was observed in Dead, Severe and Moderate COVID-19 patients. Present study suggests a panel of miRNAs which identified in COVID-19 patients and could be utilized as potential diagnostic biomarkers for predicting COVID-19 severity.

4.
Sci Rep ; 13(1): 2370, 2023 02 09.
Article En | MEDLINE | ID: mdl-36759533

The study was aimed to evaluate the performance of a newly developed spectroscopy-based non-invasive and noncontact device (SAMIRA) for the simultaneous measurement of hemoglobin, bilirubin and oxygen saturation as an alternative to the invasive biochemical method of blood sampling. The accuracy of the device was assessed in 4318 neonates having incidences of either anemia, jaundice, or hypoxia. Transcutaneous bilirubin, hemoglobin and blood saturation values were obtained by the newly developed instrument which was corroborated with the biochemical blood tests by expert clinicians. The instrument is trained using Artificial Neural Network Analysis to increase the acceptability of the data. The artificial intelligence incorporated within the instrument determines the disease condition of the neonate. The Pearson's correlation coefficient, r was found to be 0.987 for hemoglobin estimation and 0.988 for bilirubin and blood gas saturation respectively. The bias and the limits of agreement for the measurement of all the three parameters were within the clinically acceptance limit.


Bilirubin , Hemoglobins , Oxygen Saturation , Oxygen , Point-of-Care Systems , Spectrum Analysis , Humans , Infant, Newborn , Artificial Intelligence , Bilirubin/blood , Hemoglobins/analysis , Oxygen/blood , Spectrum Analysis/instrumentation , Spectrum Analysis/methods , Optical Imaging/instrumentation , Optical Imaging/methods
5.
Crit Rev Clin Lab Sci ; 60(2): 153-170, 2023 03.
Article En | MEDLINE | ID: mdl-36420874

The two common progressive lung diseases, asthma and chronic obstructive pulmonary disease (COPD), are the leading causes of morbidity and mortality worldwide. Asthma-COPD overlap, referred to as ACO, is another complex pulmonary disease that manifests itself with features of both asthma and COPD. The disease has no clear diagnostic or therapeutic guidelines, thereby making both diagnosis and treatment challenging. Though a number of studies on ACO have been documented, gaps in knowledge regarding the pathophysiologic mechanism of this disorder exist. Addressing this issue is an urgent need for improved diagnostic and therapeutic management of the disease. Metabolomics, an increasingly popular technique, reveals the pathogenesis of complex diseases and holds promise in biomarker discovery. This comprehensive narrative review, comprising 99 original research articles in the last five years (2017-2022), summarizes the scientific advances in terms of metabolic alterations in patients with asthma, COPD, and ACO. The analytical tools, nuclear magnetic resonance (NMR), gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-mass spectrometry (LC-MS), commonly used to study the expression of the metabolome, are discussed. Challenges frequently encountered during metabolite identification and quality assessment are highlighted. Bridging the gap between phenotype and metabotype is envisioned in the future.


Asthma , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/metabolism , Asthma/diagnosis , Asthma/drug therapy , Asthma/metabolism , Metabolomics/methods , Metabolome , Chromatography, Liquid/methods
6.
J Family Med Prim Care ; 12(12): 3024-3027, 2023 Dec.
Article En | MEDLINE | ID: mdl-38361851

A woman's health should reach beyond the narrow perspective of maternal and reproductive health and should encompass physical as well as mental health across the life cycle. The focus should be shifted to a broader, social, legal, and economic factors rather than just immersing on lifestyle and individual factors. Recognition of mental health issues among women, education, training, and interventions at various levels would contribute to the improvement of mental health issues among women.

7.
Indian J Med Ethics ; VIII(4): 341-342, 2023.
Article En | MEDLINE | ID: mdl-38374679

In the twenty-first century, there is still a taboo on frank discussion of menstruation in Indian society, particularly with men. This inadvertently widens the gender/equity gap in families and in society. Even men in the healthcare sector are uncomfortable talking about this because the societal norms often overpower professional knowledge. Indian society needs to move forward and normalise menstruation in the perceptions of boys and men in all settings. We highlight below some salient points on the orientation of men regarding menstruation.


Health Knowledge, Attitudes, Practice , Menstruation , Male , Female , Humans , Taboo , India
8.
J Family Med Prim Care ; 11(8): 4661-4666, 2022 Aug.
Article En | MEDLINE | ID: mdl-36352935

Background: Childhood pneumonia is one of the leading causes of mortality among under-five children. It is responsible for 15% of all deaths of children U5, killing 808,694 children in 2017 (1). Traditional visual inspection and manual count method is used to detect and classify fast-breathing, a key indicator of Pneumonia. In response to UNICEF's call for a reliable diagnostic tool, Philips was the first to respond with the Children's Automatic Respiratory Monitor for measuring fast breathing objectively. Aim: UNICEF and Philips Foundation initiated a field study to test the acceptability, usability and efficacy of the Automatic Respiratory Monitor in Determining Fast Breathing in low resource setting environments. Settings and Design: Philips Foundation partnered up with the Directorate of Medical Education in West Bengal, India to conduct the field study amongst community healthcare workers and beneficiaries in a rural district of West Bengal. In collaboration with North Bengal Medical College & Hospital, a community-based study was conducted in a tribal tea garden of Naxalbari block. Methods and Material: Acceptability and usability of the device was assessed through structtured interviews and dialogues with community health workers (CHWs), caregivers and local healthcare practitioners. Efficacy of the device was represented by the inter-rater agreement between the traditional visual inspection and manual count method and the device reading. Statistical Analysis Used: A descriptive community based mixed method study was conducted. Satisfaction among community healthcare workers (CHWs) and beneficiaries was found to be promising across all study parameters. Results and Conclusions: The paper captures the study methods, statistical analysis of the data, the conclusions, areas of further research and recommends community-wide use of the device in objectively measuring fast breathing among children under the age of five years.

10.
Heliyon ; 8(11): e11536, 2022 Nov.
Article En | MEDLINE | ID: mdl-36387492

Background: Present study aimed to identify DNA polymorphisms (variants) which can modulate the risk of COVID-19 infection progression to severe condition. TaqMan based SNP genotyping assay was performed for 11 single nucleotide polymorphisms (SNPs) in pro-coagulant and anti-coagulant genes. Methodology: A total of 33 COVID-19 patients, including dead, severe and moderately infected individuals were compared to 35 healthy controls. Both alleles in the SNP were labelled with two different fluorescent dyes (FAM and VIC) during assay formulation. DNA of study subjects were mixed with SNP assay and TaqMan master mix on 96 well PCR plate according to manufacturer's protocol and RT-PCR was performed. Allelic discrimination assay gave clear results for presence of specific allele in each sample. Three SNPs were located in the pro-coagulant genes, another three involved in blood clot dissolution while rest five were in the genes encoding natural anti-coagulants. COVID-19 infected patients were further sub-divided into three groups, deceased (n = 16), severe (n = 10) and moderately infected (n = 7). Results: SNP genotyping showed significant differences between COVID-19 patients and controls in two SNPs, rs6133 in Selectin-P (SELP) and rs5361 in Selectin-E (SELE) gene. Also, rs2020921 and rs8176592, in clot dissolution genes, tissue Plasminogen activator (tPA) and tissue factor pathway inhibitor (TFPI) respectively showed significant genotypic and allelic difference in patients of COVID-19 compared to healthy controls. Further three SNPs rs2227589, rs757583846, and rs121918476 in natural anti-coagulant genes anti-thrombin III (ATIII), protein C (PROC), and protein S (PROS) respectively showed statistically significant difference between the study groups. Conclusion: Our findings indicate that gene variants, those involved in coagulation and anti-coagulation may play a major role in determining individual susceptibility to COVID-19.

11.
J Family Med Prim Care ; 11(7): 3628-3632, 2022 Jul.
Article En | MEDLINE | ID: mdl-36387639

Background: COVID-19 pandemic is a unique public health challenge causing unprecedented disruptions in normalcy. Low-and-middle-income countries need more context-relevant approaches since a majority of the world population lives here. Pandemic response in India was graded, and routine healthcare came to a screeching halt. COVID 19 Screening clinic was initiated with the intent to screen suspects and provide needful care after required consultation. It imparted preventive health education and addressed relevant queries, alleviating stress in the process. The second wave hit hard despite vaccination. Objectives: To determine the pattern of patients attending, to conduct SWOT analysis for an insight into clinic functioning and to generate a database for further simulation were primary objectives. Methods: Descriptive cross-sectional hospital-based secondary data analysis was conducted in North Bengal medical college and hospital (NBMCH) for three months with the help of preformed proforma, interview guide and available records. An exit interview was conducted. Willing participants were enrolled. Verbal consent and Institutional Ethics Clearance were taken. Results: An induction program was held every two months by the Department of Medicine, NBMCH. The clinic recorded 60,427 cases from 23rd March 2020 to 28th February 2021. The majority were males, Hindus and from rural areas of the Darjeeling district. 60.4% were symptomatic. Total cases quarantined, tested and admitted were 39.8%, 74.9% and 34.7%, respectively. However, unlike before, from September, 80.1% of the cases were symptomatic, and the majority came only for testing as national lockdown had ceased. SWOT Analysis revealed Strength as being able to operate 24*7 with coordination among all tiers of health care workers. Select seniors helped in its smooth conduction. The Weakness identified was clinic location beside the emergency, creating confusion.

12.
Appl Microbiol Biotechnol ; 106(19-20): 6397-6412, 2022 Oct.
Article En | MEDLINE | ID: mdl-36107215

Aristolochia, belonging to the family Aristolochiaceae, has immense ecological significance due to its large size and huge geographic distribution. In the context of dealing with a genus with a huge number of species like Aristolochia, these markers come in handy to precisely identify a particular species and enumerate the genetic diversity. Also, certain species of Aristolochia are economically important due to the presence of secondary metabolites and vast use in traditional and modern medicine. But, the presence of profitable biochemical constituents in Aristolochia is very low and the breeding process of the plant is highly dependable on pollinators. Hence, identifying different biotechnological approaches to fasten the reproductive cycle of Aristolochia and increase the secondary metabolites is of great interest to the researchers. In this study, a comprehensive review has been established on different types of morphological/anatomical markers (starch grains with "Maltese cross"), phytochemical markers (aristolochic acid, triterpenoid, aristolactam etc.) and genetic markers (ISSR, SSR, DNA bar-coding) for various Aristolochia spp. We have also discussed the applications of different biotechnological tools in Aristolochia spp. which include discrete approaches to promote in vitro germination, in vitro shooting, root induction, somatic embryogenesis, synthetic seed production, acclimatization and hardening and sustainable production of secondary metabolites. In a nutshell, the present review is a first of kind approach to comprehensively demonstrate the genetic diversity studies and biotechnological aspects in Aristolochia spp. KEY POINTS: • Insights into the in vitro propagation of Aristolochia spp. • In vitro production and optimization of secondary metabolites. • Assessment of genetic diversity by molecular markers.


Aristolochia , Triterpenes , Aristolochia/chemistry , Aristolochia/genetics , Genetic Markers , Genetic Variation , Starch
13.
Adv Ther ; 39(9): 4094-4113, 2022 09.
Article En | MEDLINE | ID: mdl-35788961

INTRODUCTION: Sarcopenic obesity (SO) represents the confluence of two epidemics-an aging population and an increasing rate of obesity. The two diseases may act synergistically, and SO may significantly affect morbidity and mortality. However, the burden is not defined to drive the policy changes. Hence the present study was done to estimate the prevalence and predictors of SO in India. METHODS: We did a secondary data analysis of the 72,250 older adults who participated in the first wave of the Longitudinal Aging Study in India (2017-18). Possible sarcopenia was defined as per the guidelines by the Asian Working Group for Sarcopenia (AWGS) criteria. The modified criterion of overweight and obesity for Asian adults was used to categorize obesity. Presence of both sarcopenia and obesity depicted SO. Weighted analysis was done to estimate the prevalence of SO, and multinomial bivariate logistics regression was used to identify the predictors of SO. RESULTS: The overall prevalence of obesity, sarcopenia, and SO was 27.1%, 41.9%, and 8.7%, respectively. The mean age, weight, body mass index (BMI), and blood pressure of adults with SO were significantly higher compared to others. Higher age, urban residence, west and south regions of India, consumption of tobacco or alcohol, no physical activity, and presence of diabetes contribute to SO. CONCLUSION: The burden of SO seems to be less but amounts to a massive number in an aging country. We stress increased screening of the geriatric age group and advocate increased physical activity and dietary modifications to realize the concept of healthy aging.


Sarcopenia , Aged , Aging/physiology , Body Mass Index , Data Analysis , Humans , Obesity/complications , Prevalence , Sarcopenia/epidemiology
14.
Pathobiology ; 89(6): 407-417, 2022.
Article En | MEDLINE | ID: mdl-35344951

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a novel viral disease that spread as a global pandemic in 2020 by infecting millions of people across the world. Its clinical prognosis is dependent on various coagulatory parameters since thrombotic events are frequently associated with infection severity. METHODS: A total of 383 COVID-19 patients enrolled in Rajiv Gandhi Super Specialty Hospital, Delhi, India, were included in the present retrospective study. Patients were divided into three categories, severe (n = 141), moderate (n = 138), and mild (n = 104) based on infection severity. Various thrombotic parameters and anticoagulant levels were measured in 70 patients and further analyzed. RESULTS: Coagulopathy is seen in COVID-19 patients (n = 70) with a significant increase in fibrinogen, D-dimer levels, and prothrombin time in patients with severe and moderate disease compared to patients with a mild infection. Approximately, 70% of patients with severe and moderate disease demonstrated fibrinogen levels higher than the standard reference range. 60.41% of patients with severe disease showed significantly higher D-dimer levels. Thrombotic parameters were notably elevated in the nonsurvivors group compared to COVID-19 survivors. Nearly, 91% of patients with severe infection had anticoagulant protein S levels below the reference range. CONCLUSION: COVID-19 infection severely impacts the blood coagulation cascade, which might lead to the manifestation of severe symptoms and increased mortality in patients.


COVID-19 , Thrombosis , Humans , COVID-19/complications , SARS-CoV-2 , Retrospective Studies , Thrombosis/etiology , Anticoagulants/therapeutic use , Fibrinogen
15.
Bioelectrochemistry ; 143: 107971, 2022 Feb.
Article En | MEDLINE | ID: mdl-34666224

Chronic obstructive pulmonary disease (COPD) and asthma are the two most common obstructive lung diseases which affects millions worldwide and impose an enormous burden on global healthcare. The overlapping features shared by these two diseases often make differential diagnosis difficult to achieve, leading to misdiagnosis of these patients. Both asthma and COPD are associated with chronic inflammation of the airways which is perpetuated by the interplay between immunological mediators. The crucial role played by these mediators make them attractive targets for disease diagnosis. The present study investigates the immunological mediator profile in these patients as compared with controls. Further, a potential biomarker for the development of a sensing platform is identified. Multiplexed analysis of 8 commonly studied immunological markers (IL-4, IL-5, IL-6, IL-13, TGF-ß, IFN-γ, MCP-1 and NGAL) in serum showed distinct dysregulation pattern, with IL-13 showing the highest potential for differential diagnosis. An impedimetric self-assembled monolayer (SAM) based sensor for detecting IL-13 is developed to distinguish between asthma and COPD. The device shows reliable output with high accuracy and sensitivity towards the detection of IL-13.


Interleukin-13
16.
Mol Omics ; 18(2): 101-111, 2022 02 21.
Article En | MEDLINE | ID: mdl-34881764

Hypersensitivity pneumonitis (HP) is an immune-mediated granulomatous interstitial lung disease (ILD) that results from repeated inhalation of certain antigens. Despite major advances in research, pathophysiology of the disease remains poorly understood. The present study combines metabolomic and transcriptomic data to determine alterations in HP subjects as compared with healthy controls. Metabolic signatures were identified in serum, exhaled breath condensate (EBC) and bronchoalveolar lavage fluid (BALF) of HP patients using proton nuclear magnetic resonance (NMR) metabolomics. The expression of three metabolites, i.e., lactate, pyruvate, and proline, was found to be significantly altered in all three biofluids. The potential of differential diagnosis based on these three metabolites was investigated by including a group of patients with sarcoidosis, which is another type of granulomatous ILD. In addition, differentially expressed transcriptomic fingerprints in blood samples were identified by analyzing a Gene Expression Omnibus (GEO) database. The transcriptomics analysis of these microarray-based data revealed 59 genes to be significantly dysregulated in patients with HP. Over representation analysis of the metabolites and genes of interest was performed using IMPaLA (Integrated Molecular Pathway Level Analysis) version 12. Integrated analysis of serum metabolite signatures and blood gene expression suggests dysregulation of PI3K-AKT signaling and TCA cycle pathways in these patients. This preliminary study is a step towards better understanding of the pathogenesis of HP by identification of differentially expressed metabolites and transcriptomic fingerprints. These molecular signatures may be explored as diagnostic markers for differentiating HP from other lung diseases.


Alveolitis, Extrinsic Allergic , Transcriptome , Alveolitis, Extrinsic Allergic/diagnosis , Alveolitis, Extrinsic Allergic/genetics , Humans , Magnetic Resonance Spectroscopy , Metabolomics , Phosphatidylinositol 3-Kinases , Transcriptome/genetics
17.
Metabolomics ; 17(10): 94, 2021 10 01.
Article En | MEDLINE | ID: mdl-34599402

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) associated pulmonary hypertension (COPD-PH), one of the most prevalent forms of PH, is a major burden on the healthcare system. Although PH in COPD is usually of mild-to-moderate severity, its presence is associated with shorter survival, more frequent exacerbations and worse clinical outcomes. The pathophysiologic mechanisms responsible for PH development in COPD patients remain unclear. It is envisioned that a better understanding of the underlying mechanism will help in diagnosis and future treatment strategies. OBJECTIVES: The present study aims to determine metabolomic alterations in COPD-PH patients as compared to healthy controls. Additionally, to ensure that the dysregulated metabolites arise due to the presence of PH per se, an independent COPD cohort is included for comparison purposes. METHODS: Paired serum and exhaled breath condensate (EBC) samples were collected from male patients with COPD-PH (n = 60) in accordance with the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines. Age, sex and BMI matched healthy controls (n = 57) and COPD patients (n = 59) were recruited for comparison purposes. All samples were characterized using 1H nuclear magnetic resonance (NMR) spectroscopy. RESULTS: Fifteen serum and 9 EBC metabolites were found to be significantly altered in COPD-PH patients as compared to healthy controls. Lactate and pyruvate were dysregulated in both the biofluids and were further correlated with echocardiographic systolic pulmonary artery pressure (sPAP). Multivariate analysis showed distinct class separation between COPD-PH and COPD. CONCLUSIONS: The findings of this study indicate an increased energy demand in patients with COPD-PH. Furthermore, both lactate and pyruvate correlate with sPAP, indicating their importance in the clinical course of the disease.


Hypertension, Pulmonary , Pulmonary Disease, Chronic Obstructive , Breath Tests , Humans , Lactates , Male , Pyruvates
18.
Sci Rep ; 11(1): 16664, 2021 08 17.
Article En | MEDLINE | ID: mdl-34404870

Asthma-chronic obstructive pulmonary disease (COPD) overlap, termed as ACO, is a complex heterogeneous disease characterised by persistent airflow limitation, which manifests features of both asthma and COPD. These patients have a worse prognosis, in terms of more frequent and severe exacerbations, more frequent symptoms, worse quality of life, increased comorbidities and a faster lung function decline. In absence of clear diagnostic or therapeutic guidelines, ACO presents as a challenge to clinicians. The present study aims to investigate whether ACO patients have a distinct exhaled breath condensate (EBC) metabolic profile in comparison to asthma and COPD. A total of 132 age and BMI matched male smokers were recruited in the exploratory phase which consisted of (i) controls = 33 (ii) asthma = 34 (iii) COPD = 30 and (iv) ACO = 35. Using nuclear magnetic resonance (NMR) metabolomics, 8 metabolites (fatty acid, propionate, isopropanol, lactate, acetone, valine, methanol and formate) were identified to be significantly dysregulated in ACO subjects when compared to both, asthma and COPD. The expression of these dysregulated metabolites were further validated in a fresh patient cohort consisting of (i) asthma = 32 (ii) COPD = 32 and (iii) ACO = 40, which exhibited a similar expression pattern. Multivariate receiver operating characteristic (ROC) curves generated using these metabolites provided a robust ACO classification model. The findings were also integrated with previously identified serum metabolites and inflammatory markers to develop a robust predictive model for differentiation of ACO. Our findings suggest that NMR metabolomics of EBC holds potential as a platform to identify robust, non-invasive biomarkers for differentiating ACO from asthma and COPD.


Asthma/metabolism , Metabolome , Pulmonary Disease, Chronic Obstructive/metabolism , Smoking/metabolism , Adult , Asthma/diagnosis , Breath Tests , Humans , Male , Metabolomics , Middle Aged , Prognosis , Pulmonary Disease, Chronic Obstructive/diagnosis , Smokers
19.
Microb Pathog ; 158: 105008, 2021 Sep.
Article En | MEDLINE | ID: mdl-34087389

Coronavirus disease 2019 (COVID-19) transmits from person to person mainly through respiratory droplets and coughing. Infection severity ranges from asymptomatic and mild infection to those with moderate and severe symptoms which may lead to multiple organ failure and mortality. Infection severity largely depends on individual's immune response, age and co-morbidities. Present study categorized COVID-19 infected patients based on their infection severity and linked COVID-19 severity with age, gender and ABO blood group types. Clinical details of 383 COVID-19 patients were collected from Rajiv Gandhi Super Specialty hospital (RGSSH), India; divided into three groups; mild, moderate and severe patients, based on their symptoms. Present analysis revealed that age plays major role in infection severity, as the symptoms are more severe in patients above 45 years. Infection rate was higher in males compared to females. Most patients with A(+ve) and B(+ve) blood group were severely affected compared to those of blood group type O(+ve) and AB(+ve). O(+ve) blood group was least represented in severe patients. Present findings could be helpful in generating awareness amongst the population regarding susceptibility towards the COVID-19 infection. This supportive information would help clinicians and health workers to propose new strategies and tactical solution against COVID-19 infection.


ABO Blood-Group System , COVID-19 , Comorbidity , Female , Humans , India/epidemiology , Male , Middle Aged , SARS-CoV-2
20.
Mol Cell Biochem ; 476(3): 1489-1504, 2021 Mar.
Article En | MEDLINE | ID: mdl-33398665

Integrins are a group of transmembrane glycoprotein receptors that are responsible for platelet activation through bidirectional signalling. These receptors have left their footprints in various cellular events and have intrigued many groups of scientists that have led to some significant discoveries. A lot of the recent understanding of haemostasis has been possible due to the integrins filling the gaps in between several cellular mechanism. Apart from this, other important functions carried out by integrins are growth and maturation of cardiomyocytes, mechano-transduction, and interaction with actin cytoskeleton. The signalling cascade for integrin activation involves certain intracellular interacting proteins, which initiates the step-by-step activation procedure through 'inside-out' signalling. The signalling cascade gets activated through 'outside-in' signalling with the involvement of agonists such as ADP, Fibronectin, Vitronectin, and so on. This is a crucial step for the downstream processes of platelet spreading, followed by aggregation, clot progression and finally thrombus formation. Researchers throughout the world have shown direct relation of integrins with CVD and cardiac remodelling. The present review aims to summarize the information available so far on the involvement of integrins in thrombosis and its relationship to DVT. This information could be a bedrock of hidden answers to several questions on pathogenesis of deep vein thrombosis.


Integrins/metabolism , Thrombosis/metabolism , Venous Thrombosis/metabolism , Actin Cytoskeleton/metabolism , Animals , Blood Platelets/metabolism , Cytoskeletal Proteins/metabolism , Cytoskeleton/metabolism , Disease Models, Animal , Heart/physiology , Hemostasis , Ligands , Mice , Mice, Transgenic , Myocardium/metabolism , Platelet Aggregation , Platelet Glycoprotein GPIIb-IIIa Complex/metabolism , Signal Transduction , Talin/metabolism , rap GTP-Binding Proteins/metabolism
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