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1.
Chemosphere ; 254: 126857, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32353810

RESUMO

The present study reveals the distribution of terrestrial radionuclides (226Ra, 232Th and 40K) and heavy metals (Cr, Ni, Cu, Zn, Pb, Co) from soil samples of Una, Hamirpur and Kangra districts of Himachal Pradesh (India). The 226Ra, 232Th, 40K activity concentration in the studied region has been varied from 8 to 3593 Bq kg-1; 21-370 Bq kg-116; 62-7130 Bq kg-1 respectively. High disequilibrium factor (238U/226Ra) depicts that uranium constantly migrates from clay oxidizing zone and getting precipitated with enrichment towards south. An attempt has been made to correlate the distribution of these radionuclides and heavy metals with geology and rock type formation of Siwalik region. The concentration of Pb, Zn and Co was found higher than Indian average background value. Multiple radiological and pollution indices have been estimated for proper risk analysis in the studied region. The annual effective dose in studied region is lower than the recommended limit of 1.0 mSv a-1. The obtained geo-accumulation index and enrichment factor indicated that the sites located in the Hamirpur and Kangra regions were moderately contaminated with Pb and Co. The Nemerow pollution index and contamination security index suggested that almost 45% sites were slightly to moderately polluted. The non-carcinogenic and carcinogenic risks for both children and adults were within acceptable limits.

2.
J Opioid Manag ; 16(3): 219-222, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32421843

RESUMO

Pain management in advanced cancer patients using opioids like morphine is challenging due to presence of predisposing factors like renal insufficiency, hepatic insufficiency, hypoproteinemia, hypoalbuminemia, and anemia that can easily precipitate inadvertent toxic effects. We report a case morphine toxicity in an elderly patient of lung cancer with concomitant presence of chronic obstructive pulmonary disease (COPD) and recent onset renal impairment. Opioid analgesic overdose is a lethal but at the same time, a preventable and treatable condition. We managed the case using naloxone infusion. However, we emphasize early anticipation and recognition of predisposing factors followed by timely intervention to manage this life-threatening condition.

3.
J Biomol Struct Dyn ; : 1-14, 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32362235

RESUMO

The current outbreak of a novel coronavirus, named as SARS-CoV-2 causing COVID-19 occurred in 2019, is in dire need of finding potential therapeutic agents. Recently, ongoing viral epidemic due to coronavirus (SARS-CoV-2) primarily affected mainland China that now threatened to spread to populations in most countries of the world. In spite of this, there is currently no antiviral drug/ vaccine available against coronavirus infection, COVID-19. In the present study, computer-aided drug design-based screening to find out promising inhibitors against the coronavirus (SARS-CoV-2) leads to infection, COVID-19. The lead therapeutic molecule was investigated through docking and molecular dynamics simulations. In this, binding affinity of noscapines(23B)-protease of SARS-CoV-2 complex was evaluated through MD simulations at different temperatures. Our research group has established that noscapine is a chemotherapeutic agent for the treatment of drug resistant cancers; however, noscapine was also being used as anti-malarial, anti-stroke and cough-suppressant. This study suggests for the first time that noscapine exerts its antiviral effects by inhibiting viral protein synthesis.

4.
J Pak Med Assoc ; 70(5): 878-883, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32400746

RESUMO

OBJECTIVE: To calculate frequency of worsening renal failure (WRF) in patients with acute decompensated heart failure (ADHF), to evaluate predictors of WRF and to assess its effect on in-hospital and 12 month adverse outcomes. METHODS: A single center observational prospective study was conducted on consecutive patients admitted with ADHF from Sept 2016 - February 2017. Follow-up was done for 12 months post discharge. Data were obtained from electronic medical records and telephonic calls. Early adverse outcome was composite of hospital mortality, prolonged length of stay (LOS) >4days or new need for haemodialysis. Intermediate term adverse event was composite of 12 months all-cause mortality or re-hospitalization. RESULTS: Total of 247 ADHF patients were admitted. Mean age was 67.6±33.4 years. Males were 163 (65.9%). WRF was found in 57 (23.1%) patients. Predictors of WRF were age>70years, furosemide dose>400mg and admission eGFR <60ml/min. The odds of composite in-hospital outcomes were four times higher in WRF compared to stable renal function (38.6% versus 13.2%, (p<0.01) but were mainly driven by prolonged LOS (4.2 vs. 2.2 days respectively). Follow up was available for 230(97%). Intermediate term outcome was not different between two groups on log rank test. CONCLUSIONS: WRF is a significant problem in ADHF, is common in elderly patients, with baseline impaired renal function and is associated with high requirement of diuretics and prolonged hospital stay. Composite of mortality or HF hospitalization at 12 months was not different between the two groups.

5.
Ecotoxicol Environ Saf ; 200: 110730, 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32464439

RESUMO

Monitoring of oxidative stress caused by a wide range of reactive oxygen species (ROS) is essential to have an idea about the fitness and growth of photosynthetic organisms. The imaging-based oxidative stress measurement in cyanobacteria using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) dye has the limitation of small sample size as the only selected number of cells are analyzed to measure the ROS levels. Here, we developed a method for oxidative stress measurement by DCFH-DA and flow cytometer (FCM) using unicellular Synechococcus elongatus PCC 7942 and filamentous Fremyella diplosiphon BK14 cyanobacteria. F. diplosiphon BK14 inherently possess high levels of ROS and showed higher sensitivity to hydrogen peroxide treatment in comparison to S. elongatus PCC 7942. We successfully measured oxidative stress in glutaredoxin lacking strain (Δgrx3) of S. elongatus PCC 7942, and wild-type Synechocystis sp. PCC 6803 using FCM based method. Importantly, ROS were not detected in these two strains of cyanobacteria by fluorescence microscope-based method due to their small spherical morphology. Δgrx3 strain showed high ROS levels in comparison to its wild-type strain. Treatment of abiotic factors such as high PAR in wild-type and Δgrx3 strains of S. elongatus PCC 7942, low PAR or low PAR + UVR in wild-type S. elongatus PCC 7942, and high PAR or high PAR + NaCl in Synechocystis sp. PCC 6803 increased oxidative stress. In summary, the FCM based method can measure ROS levels produced due to physiological conditions associated with genetic changes or abiotic stress in a large population of cells regardless of their morphology. Therefore, the present study shows the usefulness of the method in monitoring the health of organisms in a large scale cultivation system.

7.
Genomics ; 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32360910

RESUMO

CancerEnD is an integrated resource developed for annotating 8524 unique expressed enhancers, associated genes, somatic mutations and copy number variations of 8063 cancer samples from 18 cancer types of TCGA. Somatic mutation data was taken from the COSMIC repository. To delineate the relationship of change in copy number of enhancer elements with the prognosis of cancer patients, survival analysis was done using the survival package in R. We identified 1762 overall survival associated enhancers, which can be used for prognostic purposes of cancer patients in a tissue-specific manner. CancerEnD (https://webs.iiitd.edu.in/raghava/cancerend/) is developed on a user-friendly responsive template, that enables searching, browsing and downloading of the annotated enhancer elements in terms of gene expression, copy number variation and survival association. We hope it provides a promising avenue for researchers to facilitate the understanding of enhancer deregulation in tumorigenesis, and to identify new biomarkers for therapy and disease-diagnosis.

8.
J Fluoresc ; 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32418161

RESUMO

An adept, rapid and novel water-soluble glutathione functionalized CdS quantum dots (GSH@CdS QDs) were fabricated using green pathway for sensing of heavy metal contamination prevalent in industrial wastewater. GSH@CdS QDs were facilely synthesized in an aqueous phase reaction and were effectively characterized using FT-IR, XRD, FESEM, HRTEM and EDX techniques. The distinct fluorescence characteristics of GSH@CdS QDs were explored and the QDs showed selective sensitivity towards mercury ions with a low limit of detection of 0.54 nM under optimal conditions. The detailed interaction between GSH@CdS QDs and Hg2+ and the probable fluorescence quenching mechanism were established in this study. In comparison to already reported fluorescent probes, GSH@CdS QDs showed high sensitivity, biocompatibility, long fluorescence stability and convenient removal of mercury ions. Graphical Abstract Facile green route for the fabrication of glutathione capped CdS quantum dots for fluorescence-based detection of toxic Hg2+ ions.

9.
Development ; 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32345744

RESUMO

Precise guided pollen tube growth by the female gametophyte is a pre-requisite for successful sexual reproduction in flowering plants. Cysteine-rich proteins (CRPs) secreted from the embryo sac are known pollen tube attractants perceived by pollen tube receptor-like kinases (RLK's). How pre-mRNA splicing facilitates this cell-to-cell communication is not understood. Here, we report novel function of Pre-mRNA PROCESSING factor 8 paralogs, PRP8A and PRP8B, as regulators of pollen tube attraction. Double mutant prp8a prp8b ovules cannot attract pollen tubes, and prp8a prp8b pollen tubes fail in sensing ovules attraction signals. Only 3% of ovule-expressed genes were misregulated in prp8a prp8b Combination of RNA-seq and MYB98/LURE1.2-YFP reporter revealed the expression of MYB98, LUREs and 49 other CRPs were downregulated suggesting loss of synergid cell fate. Differential Exon usage (DEU) and Intron-retention (IR) analysis revealed autoregulation of PPR8A/PRP8B splicing. In vivo, PRP8A coimmunoprecipitates with splicing enhancer AtSF3A1, suggesting involvement of PRP8A in 3'-splice site selection. Our data hint that PRP8A/PRP8B module exhibit spliceosome-autoregulation to facilitate pollen tube attraction via transcriptional regulation of MYB98, CRPs and LURE pollen tube attractants.

10.
Int J Pharm ; 581: 119291, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32259638

RESUMO

Ketamine in sub-anaesthetic doses is an analgesic adjuvant with a morphine-sparing effect. Co-administration of a strong opioid with an analgesic adjuvant such as ketamine is a potential treatment option, especially for patients with cancer-related pain. A limitation of ketamine is its short in vivo elimination half-life. Hence, our aim was to develop biocompatible and biodegradable ketamine-loaded poly(ethylene glycol) (PEG)-block-poly(lactic-co-glycolic acid) (PLGA) nanoparticles for sustained release. Ketamine-encapsulated single polymer PEG-PLGA nanoparticles and double polymer PEG-PLGA/shellac (SH) nanoparticles with a high drug loading of 41.8% (drug weight/the total weight of drug-loaded nanoparticles) were prepared using a new sequential nanoprecipitation method. These drug-loaded nanoparticles exhibited a sustained-release profile for up to 21 days in vitro and for more than 5 days after intravenous injection in mice. Our study demonstrates that high drug loading and a sustained release profile can be achieved with ketamine-loaded PEG-PLGA nanoparticles prepared using this new nanoprecipitation method.

11.
Ecotoxicol Environ Saf ; 198: 110645, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-32344266

RESUMO

Finding a sound ecological-based approach for the removal of petroleum hydrocarbons (PHCs) from petroleum oily sludge (POS) generated in oil refinery plants is still a challenge. This study investigated the removal of total petroleum hydrocarbons (TPHs) using bioaugmentated composting (BC) by hydrocarbon-degrading bacteria (HDB) and vermicomposting (VC) by Eisenia fetida, individually and in combination (BCVC). After isolating two native bacterial strains from POS prepared from an oil refinery plant in Iran, the degradation capability of their consortium was initially assessed in mineral Bushnell-Haas medium (MBHM). Then, the biodegradation rates of POS in the BC, VC, and BCVC treatments containing different concentrations of TPHs (5, 10, and 20 g/kg) were determined by measuring TPHs before and after the biodegradation. The results showed that the consortium degraded 20-62% of TPHs contents of Kerosene (1-5%) in the MBHM after 7 days. After 12 weeks, the TPHs removal percentages in the BC, VC, and BCVC treatments were respectively found to be 81-83, 31-49, and 85-91 indicating the synergistic effect of bacteria and worms in bioremediation of POS. The PHCs biodegradation in the BC, VC, and BCVC experiments was fitted to 1st order model kinetics. The results of toxicity tests indicated that the values of the no observed lethal concentration (NOLC) and median lethal concentration (LC50) of TPHs were 2-5 and 14.64 g/kg, respectively after 28 days of earthworm exposure. Morphological impairments such as swelling, coiling, and curling were observed when TPHs concentration was even lower than NOLC. The study verified the effectiveness of vermicomposting bioaugmentated with the indigenous bacterial consortium for POS bioremediation.

12.
Biochimie ; 174: 74-83, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32304771

RESUMO

EDA2R is a member of the large family of tumor necrosis factor receptor (TNFR). Previous studies suggested that EDA2R expression might be increased in the kidneys of diabetic mice. However, its mRNA and protein expression in kidneys were not analyzed; moreover, its role in the development of diabetic kidney disease was not explored. Here we analyzed the mRNA and protein expressions of EDA2R in diabetic kidneys and examined its role in the podocyte injury in high glucose milieu. By analysis with real-time PCR, Western blotting, we found that both the mRNA and protein levels of EDA2R were increased in the kidneys of diabetic mice. Immunohistochemical studies revealed that EDA2R expression was enhanced in both glomerular and tubular cells of diabetic mice and humans. In vitro studies, high glucose increased EDA2R expression in cultured human podocytes. Overexpression of EDA2R in podocytes promoted podocyte apoptosis and decreased nephrin expression. Moreover, ED2AR increased ROS generation in podocytes, while inhibiting ROS generation attenuates EDA2R-mediated podocyte injury. In addition, EDA2R silencing partially suppressed high glucose-induced ROS generation, apoptosis, and nephrin decrease. Our study demonstrated that high glucose increases EDA2R expression in kidney cells and that EDA2R induces podocyte apoptosis and dedifferentiation in high glucose milieu partially through enhanced ROS generation.

13.
Int J Biol Macromol ; 156: 598-607, 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32305370

RESUMO

There is ongoing quest to look for alternate sustainable and renewable biopolymers which can address the existing environmental issues. Bacterial cellulose could be one such option. Several organisms have been reported to produce bacterial cellulose. Among this, acetic acid bacteria (AAB) are reported to be one of the major producers of bacterial cellulose. Recently, we have identified an Acetobacter pasteurianus RSV-4 and reported to produce high tensile strength bacterial cellulose. In order to globally understand its genetic structure, a draft genome sequence of Acetobacter pasteurianus RSV-4 was performed in the present study. The assembled genome had 101 contigs contributing to a total length of 3.8 Mbp. Predicted coding DNA sequences were 3311, of which approximately 70% were assigned the functions. Genome level phylogenetic analysis revealed that RSV-4 belongs to A. pasteurianus. Glycolysis was found to be incomplete in the genome analysis of RSV-4, while the genes/enzymes involved in pentose-phosphate pathway were present. The final draft genome sequence lacked bacterial cellulose synthase (bcs) operon. However, the presence of operon was evident in raw genomic sequences by Sanger sequencing. Therefore, presence of bcs operon in Acetobacter pasteurianus RSV-4 has documented its potential for bacterial cellulose production.

14.
16.
Toxicol Ind Health ; 36(2): 110-118, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32279653

RESUMO

Anilofos is an organophosphate compound and is used extensively as a preemergence and early postemergence herbicide for the management of sedges, annual grasses, and some broad-leaved weeds in rice fields. The present study was aimed to assess the mutagenic potential of anilofos after sub-chronic exposure in Swiss albino mice. For this, a combined approach employing micronucleus (MN), chromosomal aberration (CA) studies and sperm-head abnormalities (SHAs) was used. Three dose levels of 1%, 2%, and 4% of maximum tolerated dose (MTD) (235 mg/kg b.wt.), that is, 2.35, 4.7 and 9.4 mg/kg b.wt., respectively, were administered orally daily for 90 days. A higher incidence of micronucleated erythrocytes (polychromatic erythrocytes + normochromatic erythrocytes), significant increase in CA frequency, and significant decrease in the ratio of polychromatic/normochromatic erythrocytes (P/N) ratio were observed at the 4.7 and 9.4 mg/kg b.wt. dose levels. A significant increase in SHA was observed in all treatment groups (2.35, 4.7, and 9.4 mg/kg b.wt.) from the control group. In conclusion, anilofos exposure of 2% and 4% of MTD caused a higher rate of micronucleated erythrocytes, increased frequency of CA, increase in SHA, and lower P/N ratio, and pesticide exposure of 1% of MTD only resulted in higher SHAs. Thus, anilofos was found to have mutagenic potential in mice when administered daily orally at dose rate of 4.7 and 9.4 mg/kg b.wt. for 90 days.

18.
PLoS Pathog ; 16(4): e1008408, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32251450

RESUMO

Candida bloodstream infection, i.e. candidemia, is the most frequently encountered life-threatening fungal infection worldwide, with mortality rates up to almost 50%. In the majority of candidemia cases, Candida albicans is responsible. Worryingly, a global increase in the number of patients who are susceptible to infection (e.g. immunocompromised patients), has led to a rise in the incidence of candidemia in the last few decades. Therefore, a better understanding of the anti-Candida host response is essential to overcome this poor prognosis and to lower disease incidence. Here, we integrated genome-wide association studies with bulk and single-cell transcriptomic analyses of immune cells stimulated with Candida albicans to further our understanding of the anti-Candida host response. We show that differential expression analysis upon Candida stimulation in single-cell expression data can reveal the important cell types involved in the host response against Candida. This confirmed the known major role of monocytes, but more interestingly, also uncovered an important role for NK cells. Moreover, combining the power of bulk RNA-seq with the high resolution of single-cell RNA-seq data led to the identification of 27 Candida-response QTLs and revealed the cell types potentially involved herein. Integration of these response QTLs with a GWAS on candidemia susceptibility uncovered a potential new role for LY86 in candidemia susceptibility. Finally, experimental follow-up confirmed that LY86 knockdown results in reduced monocyte migration towards the chemokine MCP-1, thereby implying that this reduced migration may underlie the increased susceptibility to candidemia. Altogether, our integrative systems genetics approach identifies previously unknown mechanisms underlying the immune response to Candida infection.

19.
Indian J Cancer ; 57(1): 93-97, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32129300

RESUMO

Scrambler therapy (ST) is a novel noninvasive modality for treatment of chronic neuropathic and cancer pain using 5 artificial neurons. The principle with Scrambler Therapy is that synthetic "non-pain" information is transmitted by C fiber surface receptors. Chemotherapy-induced peripheral neuropathy can markedly deteriorate patient's quality of life and can also negatively affect compliance with the anticancer treatment. Chronic neuropathic pain presents a therapeutic challenge if resistant to pharmacological management opioids and other types of treatments. We have described here successful use of scrambler therapy in three cases of chemotherapy-induced peripheral neuropathy.

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