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1.
BMC Plant Biol ; 23(1): 581, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37985970

RESUMO

BACKGROUND: Choy Sum (Brassica rapa ssp. chinensis var. parachinensis), grown in a controlled environment, is vulnerable to changes in indoor light quality and displays distinct photo-morphogenesis responses. The scarcity of Choy Sum germplasm for indoor cultivation necessitates the development of new cultivars. Hence, this study attempted to develop mutants through chemical mutagenesis and select low-light-tolerant mutants by using abiotic stress tolerance indices. RESULTS: A mutant population of Choy Sum created using 1.5% ethyl methane sulfonate (EMS) at 4 h was manually pollinated to obtain the M2 generation. 154 mutants with reduced hypocotyl length were initially isolated from 3600 M2 seedlings screened under low light (R: FR = 0.5). Five mutants that showed reduced plant height at mature stages were selected and screened directly for shade tolerance in the M3 generation. Principal component analysis based on phenotypic data distinguished the M3 mutants from the wild type. Abiotic stress tolerance indices such as relative stress index (RSI), stress tolerance index (STI), geometric mean productivity (GMP), yield stability index (YSI), and stress resistance index (SRI) showed significant (P < 0.05), and positive associations with leaf yield under shade. M3-12-2 was selected as a shade-tolerant mutant based on high values of STI, YSI, and SRI with low values for tolerance (TOL) and stress susceptibility index (SSI). CONCLUSIONS: The results demonstrate that mutation breeding can be used to create dominant mutants in Choy Sum. Furthermore, we show that screening for low light and selection based on abiotic tolerance indices allowed the identification of mutants with high resilience under shade. This method should apply to developing new cultivars in other crop plants that can be suitable for controlled environments with stable yield performance.


Assuntos
Brassica , Brassica/genética , Metanossulfonato de Etila , Melhoramento Vegetal , Mutagênese , Estresse Fisiológico/genética
2.
Mol Brain ; 16(1): 75, 2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37924159

RESUMO

Non-familial Alzheimer's disease (AD) occurring before 65 years of age is commonly referred to as early-onset Alzheimer's disease (EOAD) and constitutes ~ 5-6% of all AD cases (Mendez et al. in Continuum 25:34-51, 2019). While EOAD exhibits the same clinicopathological changes such as amyloid plaques, neurofibrillary tangles (NFTs), brain atrophy, and cognitive decline (Sirkis et al. in Mol Psychiatry 27:2674-88, 2022; Caldwell et al. in Mol Brain 15:83, 2022) as observed in the more prevalent late-onset AD (LOAD), EOAD patients tend to have more severe cognitive deficits, including visuospatial, language, and executive dysfunction (Sirkis et al. in Mol Psychiatry 27:2674-88, 2022). Patient-derived induced pluripotent stem cells (iPSCs) have been used to model and study penetrative, familial AD (FAD) mutations in APP, PSEN1, and PSEN2 (Valdes et al. in Research Square 1-30, 2022; Caldwell et al. in Sci Adv 6:1-16, 2020) but have been seldom used for sporadic forms of AD that display more heterogeneous disease mechanisms. In this study, we sought to characterize iPSC-derived neurons from EOAD patients via RNA sequencing. A modest difference in expression profiles between EOAD patients and non-demented control (NDC) subjects resulted in a limited number of differentially expressed genes (DEGs). Based on this analysis, we provide evidence that iPSC-derived neuron model systems, likely due to the loss of EOAD-associated epigenetic signatures arising from iPSC reprogramming, may not be ideal models for studying sporadic AD.


Assuntos
Doença de Alzheimer , Células-Tronco Pluripotentes Induzidas , Humanos , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Células-Tronco Pluripotentes Induzidas/patologia , Mutação/genética , Neurônios/patologia
3.
J Alzheimers Dis Rep ; 7(1): 957-972, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37849634

RESUMO

Background: While Alzheimer's disease (AD) pathology is associated with altered brain structure, it is not clear whether gene expression changes mirror the onset and evolution of pathology in distinct brain regions. Deciphering the mechanisms which cause the differential manifestation of the disease across different regions has the potential to help early diagnosis. Objective: We aimed to identify common and unique endotypes and their regulation in tangle-free neurons in sporadic AD (SAD) across six brain regions: entorhinal cortex (EC), hippocampus (HC), medial temporal gyrus (MTG), posterior cingulate (PC), superior frontal gyrus (SFG), and visual cortex (VCX). Methods: To decipher the states of tangle-free neurons across different brain regions in human subjects afflicted with AD, we performed analysis of the neural transcriptome. We explored changes in differential gene expression, functional and transcription factor target enrichment, and co-expression gene module detection analysis to discern disease-state transcriptomic variances and characterize endotypes. Additionally, we compared our results to tangled AD neuron microarray-based study and the Allen Brain Atlas. Results: We identified impaired neuron function in EC, MTG, PC, and VCX resulting from REST activation and reversal of mature neurons to a precursor-like state in EC, MTG, and SFG linked to SOX2 activation. Additionally, decreased neuron function and increased dedifferentiation were linked to the activation of SUZ12. Energetic deficit connected to NRF1 inactivation was found in HC, PC, and VCX. Conclusions: Our findings suggest that SAD manifestation varies in scale and severity in different brain regions. We identify endotypes, such as energetic shortfalls, impaired neuronal function, and dedifferentiation.

5.
Indian J Anaesth ; 67(3): 256-261, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37250511

RESUMO

Background and Aims: Ultrasound-guided central venous (CV) cannulation is the standard of care for inserting CV catheter in the right internal jugular vein (RIJV). However, mechanical complications can still occur. The primary objective of this study was to compare the incidence of posterior vessel wall puncture (PVWP) using conventional needle holding technique with pen holding method of needle holding technique for IJV cannulation. Secondary objectives were comparison of other mechanical complications, access time and ease of the procedure. Methods: This prospective, randomised parallel-group study included 90 patients. Patients requiring ultrasound-guided RIJV cannulation under general anaesthesia were randomised into two groups P (n = 45) and C (n = 45). In group C, the RIJV was cannulated using the conventional needle holding technique. In group P, the pen holding method of needle holding technique was used. Incidence of PVWP, complications (arterial puncture, haematoma) number of attempts for successful cannulation, time to insertion of guidewire and performer's ease were compared. The data were analysed using Statistical Package for the Social Sciences (SPSS version 24.0). A P value less than 0.05 was considered statistically significant. Results: In our study, there was no significant difference in incidence of PVWP and complications between the two groups. Number of attempts and time for successful guidewire insertion were comparable. Ease of the procedure was scored a median of 10 in both the groups. Conclusion: There was no significant difference in the incidence of PVWP between the two techniques in this study, necessitating further evaluation of this novel technique.

6.
J Biosci ; 472022.
Artigo em Inglês | MEDLINE | ID: mdl-36476775

RESUMO

In type 2 diabetes mellitus (T2DM) patients, chronic hyperglycemia and inflammation underlie susceptibility to tuberculosis (TB) and result in poor TB control. Here, an integrative pathway-based approach is used to investigate perturbed pathways in T2DM patients that render susceptibility to TB. We obtained 36 genes implicated in type 2 diabetes-associated tuberculosis (T2DMTB) from the literature. Gene expression analysis on T2DM patient data (GSE26168) showed that DEFA1 is differentially expressed at Padj <0.05. The human host TB susceptibility genes TNFRSF10A, MSRA, GPR148, SLC37A3, PXK, PROK2, REV3L, PGM1, HIST3H2A, PLAC4, LETM2, and EMP2 and hsa-miR-146a microRNA were also differentially expressed at Padj <0.05. We included all these genes and added the remaining 28 genes from the T2DMTB set and the remaining differentially expressed genes at Padj <0.05 in STRING and obtained a well-connected network with high confidence score (≥0.7). Further, we extracted the KEGG pathways at FDR <0.05 and retained only the diabetes and TB pathways. The network was simulated with BioNSi using gene expression data. It is evident from BioNSi analysis that the NF-kappa B and Toll-like receptor pathways are commonly perturbed with high ranking in multiple gene expression datasets of type 2 diabetes versus healthy controls. The other pathways, necroptosis pathway and FoxO signalling pathway, appear perturbed with high ranking in different gene expression datasets. These pathways likely underlie susceptibility to TB in T2DM patients.


Assuntos
Diabetes Mellitus Tipo 2 , Tuberculose , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Tuberculose/genética , DNA Polimerase Dirigida por DNA , Proteínas de Ligação a DNA , Glicoproteínas de Membrana
7.
Mol Brain ; 15(1): 83, 2022 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-36224601

RESUMO

Alzheimer's disease (AD) manifested before age 65 is commonly referred to as early-onset AD (EOAD) (Reitz et al. Neurol Genet. 2020;6:e512). While the majority (> 90%) of EOAD cases are not caused by autosomal-dominant mutations in PSEN1, PSEN2, and APP, they do have a higher heritability (92-100%) than sporadic late-onset AD (LOAD, 70%) (Wingo et al. Arch Neurol. 2012;69:59-64, Fulton-Howard et al. Neurobiol Aging. 2021;99:101.e1-101.e9). Although the endpoint clinicopathological changes, i.e., Aß plaques, tau tangles, and cognitive decline, are common across EOAD and LOAD, the disease progression is highly heterogeneous (Neff et al. Sci Adv Am Assoc Adv Sci. 2021;7:eabb5398). This heterogeneity, leading to temporally distinct age at onset (AAO) and stages of cognitive decline, may be caused by myriad combinations of distinct disease-associated molecular mechanisms. We and others have used transcriptome profiling in AD patient-derived neuron models of autosomal-dominant EOAD and sporadic LOAD to identify disease endotypes (Caldwell et al. Sci Adv Am Assoc Adv Sci. 2020;6:eaba5933, Mertens et al. Cell Stem Cell. 2021;28:1533-1548.e6, Caldwell et al. Alzheimers Demen. 2022). Further, analyses of large postmortem brain cohorts demonstrate that only one-third of AD patients show hallmark disease endotypes like increased inflammation and decreased synaptic signaling (Neff et al. Sci Adv Am Assoc Adv Sci. 2021;7:eabb5398). Areas of the brain less affected by AD pathology at early disease stages-such as the primary visual cortex-exhibit similar transcriptomic dysregulation as those regions traditionally affected and, therefore, may offer a view into the molecular mechanisms of AD without the associated inflammatory changes and gliosis induced by pathology (Haroutunian et al. Neurobiol Aging. 2009;30:561-73). To this end, we analyzed AD patient samples from the primary visual cortex (19 EOAD, 20 LOAD) using transcriptomic signatures to identify patient clusters and disease endotypes. Interestingly, although the clusters showed distinct combinations and severity of endotypes, each patient cluster contained both EOAD and LOAD cases, suggesting that AAO may not directly correlate with the identity and severity of AD endotypes.


Assuntos
Doença de Alzheimer , Idade de Início , Idoso , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Encéfalo/patologia , Perfilação da Expressão Gênica , Humanos , Transcriptoma/genética
8.
Comput Biol Chem ; 101: 107772, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36155273

RESUMO

Antimicrobial resistance (AMR), a top threat to global health, challenges preventive and treatment strategies of infections. AMR strains of microbial pathogens arise through multiple mechanisms. The underlying "antibiotic resistance genes" (ARGs) spread through various species by lateral gene transfer thereby causing global dissemination. Human methods also augment this process through inappropriate use, non-compliance to treatment schedule, and environmental waste. Worldwide significant efforts are being invested to discover novel therapeutic solutions for tackling resistant pathogens. Diverse therapeutic strategies have evolved over recent years. In this work we have developed a comprehensive knowledgebase by collecting alternative antimicrobial therapeutic strategies from literature data. Therapeutic strategies against bacteria, virus, fungus and parasites were extracted from PubMed literature using text mining. We have used a subjective (sentimental) approach for data mining new strategies, resulting in broad coverage of novel entities and subsequently add objective data like entity name (including IUPAC), potency, and safety information. The extracted data was organized in a freely accessible web platform, KOMBAT. The KOMBAT comprises 1104 Chemical compounds, 220 of newly identified antimicrobial peptides, 42 bacteriophages, 242 phytochemicals, 106 nanocomposites, and 94 novel entities for phototherapy. Entities tested and evaluated on AMR pathogens are included. We envision that this database will be useful for developing future therapeutics against AMR pathogens. The database can be accessed through http://kombat.igib.res.in/.


Assuntos
Anti-Infecciosos , Farmacorresistência Bacteriana , Humanos , Antibacterianos/farmacologia , Bactérias , Anti-Infecciosos/farmacologia , Bases de Conhecimento
9.
Monoclon Antib Immunodiagn Immunother ; 41(5): 243-254, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35939284

RESUMO

Increasing fungal infections in immunocompromised hosts are a growing concern for global public health. Along with treatments, preventive measures are required. The emergence of reverse vaccinology has opened avenues for using genomic and proteomic data from pathogens in the design of vaccines. In this work, we present a comprehensive collection of various computational tools and databases with potential to aid in vaccine development. The ongoing pandemic has directed attention toward the increasing number of mucormycosis infections in COVID-19 patients. As a case study, we developed a computational pipeline for assisting vaccine development for mucormycosis. We obtained 6 proteins from 29,447 sequences from UniProtKB as potential vaccine candidates against mucormycosis, fulfilling multiple criteria. These criteria included potential characteristics, namely adhesin properties, surface or extracellular localization, antigenicity, no similarity to any human proteins, nonallergenicity, stability in vitro, and expression in fungal cells. These six proteins were predicted to have B cell and T cell epitopes, proinflammatory inducing peptides, and orthologs in several mucormycosis-causing species. These data could aid in vaccine development against mucormycosis for at-risk individuals.


Assuntos
COVID-19 , Mucormicose , Humanos , Vacinologia , Proteômica , Anticorpos Monoclonais , Epitopos de Linfócito T/genética , Computadores , Biologia Computacional
10.
Struct Chem ; 33(6): 2169-2177, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36039155

RESUMO

The COVID-19 pandemic has immensely impacted global health causing colossal damage. The recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has increased the quest to explore phytochemicals as treatment options. We summarize phytochemicals with activity against various coronaviruses including SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). We compiled 705 phytochemical compounds through text mining of 893 PubMed articles. The physicochemical properties including molecular weight, lipophilicity, and the number of hydrogen bond donors and acceptors were determined from the structures of these compounds. A structure-based evaluation of these properties with respect to drug likeness showed that most compounds have a positive score of drug likeness. QSAR analysis showed that 5 descriptors, namely polar surface area, relative polar surface area, number of hydrogen bond donors, solubility, and lipophilicity, are significantly related to IC50. We envisage that these phytochemicals could be further explored for developing new potential therapeutic molecules for COVID-19. Supplementary Information: The online version contains supplementary material available at 10.1007/s11224-022-02035-6.

11.
Exp Mol Med ; 54(6): 777-787, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35672450

RESUMO

At high altitude Andean region, hypoxia-induced excessive erythrocytosis (EE) is the defining feature of Monge's disease or chronic mountain sickness (CMS). At the same altitude, resides a population that has developed adaptive mechanism(s) to constrain this hypoxic response (non-CMS). In this study, we utilized an in vitro induced pluripotent stem cell model system to study both populations using genomic and molecular approaches. Our whole genome analysis of the two groups identified differential SNPs between the CMS and non-CMS subjects in the ARID1B region. Under hypoxia, the expression levels of ARID1B significantly increased in the non-CMS cells but decreased in the CMS cells. At the molecular level, ARID1B knockdown (KD) in non-CMS cells increased the levels of the transcriptional regulator GATA1 by 3-fold and RBC levels by 100-fold under hypoxia. ARID1B KD in non-CMS cells led to increased proliferation and EPO sensitivity by lowering p53 levels and decreasing apoptosis through GATA1 mediation. Interestingly, under hypoxia ARID1B showed an epigenetic role, altering the chromatin states of erythroid genes. Indeed, combined Real-time PCR and ATAC-Seq results showed that ARID1B modulates the expression of GATA1 and p53 and chromatin accessibility at GATA1/p53 target genes. We conclude that ARID1B is a novel erythroid regulator under hypoxia that controls various aspects of erythropoiesis in high-altitude dwellers.


Assuntos
Doença da Altitude , Proteínas de Ligação a DNA , Fatores de Transcrição , Doença da Altitude/genética , Doença da Altitude/metabolismo , Cromatina/genética , Cromatina/metabolismo , Doença Crônica , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Eritropoese/genética , Humanos , Hipóxia/genética , Hipóxia/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteína Supressora de Tumor p53/genética
12.
Proteins ; 90(11): 1944-1964, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35620856

RESUMO

Nuclear factor kappa B (NF-κB) signaling is the master regulator of inflammatory pathways; therefore, its regulation has been the subject of investigation since last two decades. Multiple models have been published that describes the dynamics of NF-κB activity by stimulated activation and feedback loops. However, there is also paramount evidence of the critical role of posttranslational modifications (PTMs) in the regulation of NF-κB pathway. With the premise that PTMs present alternate routes for activation or repression of the NF-κB pathway, we have developed a model including all PTMs known so far describing the system behavior. We present a pathway network model consisting of 171 proteins forming 315 molecular species and consisting of 482 reactions that describe the NF-κB activity regulation in totality. The overexpression or knockdown of interacting molecular partners that regulate NF-κB transcriptional activity by PTMs is used to infer the dynamics of NF-κB activity and offers qualitative agreement between model predictions and the experimental results heuristically. Finally, we have demonstrated an instance of NF-κB constitutive activation through positive upregulation of cytokines (the stimuli) and IKK complex (NF-κB activator), the characteristic features in several cancer types and metabolic disorders, and its reversal by employing combinatorial activation of PPARG, PIAS3, and P50-homodimer. For the first time, we have presented a NF-κB model that includes transcriptional regulation by PTMs and presented a theoretical strategy for the reversal of NF-κB constitutive activation. The presented model would be important in understanding the NF-κB system, and the described method can be used for other pathways as well.


Assuntos
Quinase I-kappa B , NF-kappa B , Citocinas , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , PPAR gama , Transdução de Sinais
13.
J Minim Access Surg ; 18(2): 320-323, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35046172

RESUMO

Intraoperative injuries to the ureter can occur in complicated colorectal and gynaecologic procedures in minimal access surgery. The majority of these go unrecognised at the time of the operation, which can be disastrous to the patient. The routine use of ureteric stents is controversial, with some studies showing that stents only enable detection of ureteric injury but do not prevent it. Fluorescent image-guided surgery with indocyanine green (ICG) to visualise the ureter is a relatively new technique. We report our method of visualisation of the ureter in two patients undergoing laparoscopic anterior resection and Hartmann procedure, respectively. After induction of anaesthesia, retrograde catheterisation of both ureters was performed by the urologist. 2.5 mg ICG was injected into each catheter at the start of the procedure. Both ureters were visualised very well throughout the procedure with no post-operative complications. This technique using ICG adds visual cues to make up for the loss of tactile feedback, making it a safe strategy to prevent intraoperative ureteric injury.

14.
Gigascience ; 122022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-37983749

RESUMO

BACKGROUND: Biomedical research often involves contextual integration of multimodal and multiomic data in search of mechanisms for improved diagnosis, treatment, and monitoring. Researchers need to access information from diverse sources, comprising data in various and sometimes incongruent formats. The downstream processing of the data to decipher mechanisms by reconstructing networks and developing quantitative models warrants considerable effort. RESULTS: MetGENE is a knowledge-based, gene-centric data aggregator that hierarchically retrieves information about the gene(s), their related pathway(s), reaction(s), metabolite(s), and metabolomic studies from standard data repositories under one dashboard to enable ease of access through centralization of relevant information. We note that MetGENE focuses only on those genes that encode for proteins directly associated with metabolites. All other gene-metabolite associations are beyond the current scope of MetGENE. Further, the information can be contextualized by filtering by species, anatomy (tissue), and condition (disease or phenotype). CONCLUSIONS: MetGENE is an open-source tool that aggregates metabolite information for a given gene(s) and presents them in different computable formats (e.g., JSON) for further integration with other omics studies. MetGENE is available at https://bdcw.org/MetGENE/index.php.


Assuntos
Metabolômica , Proteínas , Fenótipo , Armazenamento e Recuperação da Informação
15.
Anesth Essays Res ; 16(3): 412-415, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36620120

RESUMO

Background: Limited studies are available for assessing the optimal pillow height for sniffing position to obtain the best glottic view during laryngoscopy and intubation in the Indian population. Aims: This study was designed to evaluate laryngoscopic view and intubation conditions in sniffing position using three different pillow heights (without a pillow, 4 cm, and 7 cm) during direct laryngoscopy. Settings and Design: This prospective analytical study was done in a tertiary care teaching institute. Materials and Methods: In 60 patients, direct laryngoscopy was performed in the sniffing position first without a pillow (0 cm), followed by a 4-cm pillow, and then a 7-cm pillow to assess the glottic view after administration of anesthesia. The laryngoscopic views were graded using the percentage of glottic opening (POGO) score and Cormack and Lehane (CL) grade. The pillow with the best laryngoscopic view was subsequently used to intubate the patient. Intubation difficulty was assessed by the Intubation Difficulty Score (IDS). The patient was followed up for 24 h postoperatively to evaluate postoperative complications due to intubation. Statistical Analysis: The categorical data were expressed in frequency and percentages and analyzed using the Chi-square test. Results: With a 4-cm pillow, there are a lower CL grade and a higher POGO score compared to views without a pillow and a 7-cm pillow which was statistically significant. There is a significantly lesser IDS score with a 4-cm pillow. Conclusions: The sniffing position with a 4-cm pillow provides a better laryngoscopic view and improved intubation condition than without a pillow and a 7-cm pillow in the study population.

16.
J Biomol Struct Dyn ; 40(22): 12118-12134, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34486935

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a colossal loss to human health and lives and has deeply impacted socio-economic growth. Remarkable efforts have been made by the scientific community in containing the virus by successful development of vaccines and diagnostic kits. Initiatives towards drug repurposing and discovery have also been undertaken. In this study, we compiled the known natural anti-viral compounds using text mining of the literature and examined them against four major structural proteins of SARS-CoV-2, namely, spike (S) protein, nucleocapsid (N) protein, membrane (M) protein and envelope (E) protein. Following computational approaches, we identified fangchinoline and versicolactone C as the compounds to exhibit strong binding to the target proteins and causing structural deformation of three structural proteins (N, S and M). We recommend the inhibitory effects of these compounds from our study should be experimentally validated against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Fatores de Transcrição , Antivirais/farmacologia , Mineração de Dados , Simulação de Acoplamento Molecular , Inibidores de Proteases , Simulação de Dinâmica Molecular
17.
Front Cell Dev Biol ; 9: 702974, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34595164

RESUMO

Endothelial cells (ECs) form the inner lining of blood vessels and are central to sensing chemical perturbations that can lead to oxidative stress. The degree of stress is correlated with divergent phenotypes such as quiescence, cell death, or senescence. Each possible cell fate is relevant for a different aspect of endothelial function, and hence, the regulation of cell fate decisions is critically important in maintaining vascular health. This study examined the oxidative stress response (OSR) in human ECs at the boundary of cell survival and death through longitudinal measurements, including cellular, gene expression, and perturbation measurements. 0.5 mM hydrogen peroxide (HP) produced significant oxidative stress, placed the cell at this junction, and provided a model to study the effectors of cell fate. The use of systematic perturbations and high-throughput measurements provide insights into multiple regimes of the stress response. Using a systems approach, we decipher molecular mechanisms across these regimes. Significantly, our study shows that heme oxygenase-1 (HMOX1) acts as a gatekeeper of cell fate decisions. Specifically, HP treatment of HMOX1 knockdown cells reversed the gene expression of about 51% of 2,892 differentially expressed genes when treated with HP alone, affecting a variety of cellular processes, including anti-oxidant response, inflammation, DNA injury and repair, cell cycle and growth, mitochondrial stress, metabolic stress, and autophagy. Further analysis revealed that these switched genes were highly enriched in three spatial locations viz., cell surface, mitochondria, and nucleus. In particular, it revealed the novel roles of HMOX1 on cell surface receptors EGFR and IGFR, mitochondrial ETCs (MTND3, MTATP6), and epigenetic regulation through chromatin modifiers (KDM6A, RBBP5, and PPM1D) and long non-coding RNA (lncRNAs) in orchestrating the cell fate at the boundary of cell survival and death. These novel aspects suggest that HMOX1 can influence transcriptional and epigenetic modulations to orchestrate OSR affecting cell fate decisions.

19.
Indian J Anaesth ; 65(5): 398-403, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34211198

RESUMO

BACKGROUND AND AIMS: Erector spinae plane block (ESPB) has been found effective in providing postoperative analgesia following a myriad of surgeries. This study was designed to evaluate the effectiveness of ultrasonography (USG) guided erector spinae plane block to provide postoperative analgesia following percutaneous nephrolithotomy (PCNL). METHODS: This was a prospective, double-blinded, randomised parallel-group study conducted in patients undergoing PCNL. Patients in Group C (n = 33) received subcutaneous infiltration of 20 mL of 0.25% bupivacaine at the incision site and Group B (n = 33) received USG guided ESPB with 20 mL of 0.25% bupivacaine postoperatively. Numeric rating scale (NRS) scores were assessed at intervals of 30 min, 60 min, then hourly for six h, followed by four-hourly up to 24 h. The primary objective of the study was to compare postoperative pain relief using the NRS score between the two groups. Secondary objectives were to compare the analgesic requirement and to assess the incidence of complications. Normally distributed data were expressed as mean and standard deviation and analysed using Student's t-test. Data following non-normal distribution were expressed as median and interquartile range and analysed using Mann- Whitney U-test. For categorical data, the Chi-square test was used. RESULTS: NRS scores were lower in Group B than Group C. There was significant prolongation in time for first analgesia in Group B (12 h) compared to Group C (30 min). There was a significant reduction in total tramadol consumption at 24 h postoperatively in the ESPB group. CONCLUSION: Ultrasound-guided ESPB is an efficacious analgesic technique with an opioid-sparing effect following PCNL.

20.
Research (Wash D C) ; 2021: 2173642, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33655212

RESUMO

Small-sized droplets/aerosol transmission is one of the factors responsible for the spread of COVID-19, in addition to large droplets and surface contamination (fomites). While large droplets and surface contamination can be relatively easier to deal with (i.e., using mask and proper hygiene measures), aerosol presents a different challenge due to their ability to remain airborne for a long time. This calls for mitigation solutions that can rapidly eliminate the airborne aerosol. Pre-COVID-19, air ionizers have been touted as effective tools to eliminate small particulates. In this work, we sought to evaluate the efficacy of a novel plant-based ionizer in eliminating aerosol. It was found that factors such as the ion concentration, humidity, and ventilation can drastically affect the efficacy of aerosol removal. The aerosol removal rate was quantified in terms of ACH (air changes per hour) and CADR- (clean air delivery rate-) equivalent unit, with ACH as high as 12 and CADR as high as 141 ft3/minute being achieved by a plant-based ionizer in a small isolated room. This work provides an important and timely guidance on the effective deployment of ionizers in minimizing the risk of COVID-19 spread via airborne aerosol, especially in a poorly-ventilated environment.

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