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1.
PLoS One ; 18(11): e0267784, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37939081

RESUMEN

BACKGROUND: One of the important aftereffects of rapid global development is international mobility, which has placed the health of migrant workers as a key public health issue. A less-developed country, Nepal, with political instability and a significant lack of employment, could not remain untouched by this phenomenon of migration. Our goal was to identify and determine the predictors of anxiety, depression, and psychological wellbeing among Nepalese migrant workers in Gulf countries (United Arab Emirates, Saudi Arabia, Qatar, Oman, Kuwait, Bahrain) and Malaysia. METHODS: A descriptive cross-sectional study was used to collect information from 502 Nepalese migrant workers in the arrival section of Tribhuvan International Airport from May to June 2019 using purposive sampling. Workers with a minimum work experience of 6 months and above were included in the study. A structured questionnaire with socio-demographic items was used along with the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and WHO (five) wellbeing scale for measuring the subjective psychological wellbeing and screening for depression. RESULTS: The mean age of the respondents was 32.97 years. Majority (41.8%) of the respondents had work experience in Qatar and 63.7% had work experience of 1-5 years. The results suggested that 14.4% had mild to severe depression while 4.4% had a moderate level of anxiety. The WHO5 wellbeing index score suggested that 14.1% of the respondents had a score below 13, which is suggestive of poor psychological wellbeing. Further, the country of work (p = 0.043), sleeping hours (p = 0.001), occupation (p = 0.044), working hours (p = 0.000), water intake (p = 0.010) and anxiety level (p = 0.000) were found to be significantly associated with depression score. Similarly, sleeping hours (p = 0.022), occupation (p = 0.016), working hours (p = 0.000), water intake (p = 0.010), and anxiety level (0.000) were significantly associated with the WHO5 wellbeing score. CONCLUSIONS: Nepalese migrant workers in the Gulf countries (United Arab Emirates, Saudi Arabia, Qatar, Oman, Kuwait, Bahrain) and Malaysia bear an important burden of psychological morbidities. This highlights the need to prioritize the migrant worker's mental health by Nepal as well as Gulf countries and Malaysia.


Asunto(s)
Migrantes , Humanos , Adulto , Nepal/epidemiología , Malasia/epidemiología , Estudios Transversales , Qatar , Kuwait , Omán , Arabia Saudita , Bahrein , Emiratos Árabes Unidos , Morbilidad
2.
Analyst ; 148(18): 4513-4524, 2023 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-37580982

RESUMEN

Copper is one of the most important transition metals in our body for various physiological functions. An imbalance in the homeostasis of copper in our body can lead to various neurological disorders such as Alzheimer's disease, Parkinson's, and Menkes disease. As a result, there is a need for the detection of excess copper present in the environment and the human system. In this work, we have designed a quinoline-based fluorescent/colorimetric probe (QHS) for rapid and selective detection of copper ions via quenching of fluorescence/color change from yellow to peach which is visible to the naked eye. The probe displayed high selectivity towards copper(II), i.e., Cu(II) in the presence of different metal analytes in water samples. The sensing mechanism of the probe was confirmed by NMR, HRMS, IR spectroscopy, and SEM. The detection limit of Cu(II) ions was found to be 0.493 µM which is lower than the tolerable limit of copper (20 µM) in drinking water as per the EPA. The probe was also utilized for the visualization of Cu(II) in cell lines. The probe was also demonstrated for its application in real-time detection of aqueous samples using portable paper strips.


Asunto(s)
Colorimetría , Cobre , Humanos , Cobre/química , Colorimetría/métodos , Colorantes Fluorescentes/química , Agua/química , Iones
3.
J Indian Soc Pedod Prev Dent ; 41(1): 70-75, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37282415

RESUMEN

Aim: The aim of the study was to compare the antimicrobial efficacy of sodium hypochlorite (NaOCl), Saline, and Er, Cr:YSGG laser-assisted disinfection through microbiological analysis in root canal treatment of primary molars. Materials and Methods: Forty-five primary teeth were selected for this study as per the inclusion and exclusion criteria in the age group of 4-8 years and then randomly allocated to Three Groups A, B, and C. In Group A, during root canal treatment, irrigation was done using NaOCl, in Group B, laser-assisted disinfection was done using Er, Cr:YSGG laser, and in Group C, saline was used as an irrigating agent. This was followed by obtaining pre- and postirrigation samples from the canals for microbiological investigation in all the groups. Data analysis was performed using Statistical Package for the Social Science-21 (SPSS-21). Results: NaOCl was more effective against aerobic bacteria while Er, Cr:YSGG laser was more effective against anaerobic bacteria when used for disinfection in root canal treatment. There was a significant difference among the three groups (P > 0.05). Conclusion: The study showed that NaOCl and Er, Cr:YSGG laser have antimicrobial effects when used for disinfection in root canal treatment of primary teeth. Moreover, the study also shows that Er, Cr:YSGG laser may be used as a valuable tool for laser-assisted disinfection in root canal treatment of primary teeth.


Asunto(s)
Antiinfecciosos , Láseres de Estado Sólido , Humanos , Preescolar , Niño , Hipoclorito de Sodio/farmacología , Desinfección , Láseres de Estado Sólido/uso terapéutico , Cavidad Pulpar/microbiología , Enterococcus faecalis , Irrigantes del Conducto Radicular/farmacología , Irrigantes del Conducto Radicular/uso terapéutico , Diente Molar , Preparación del Conducto Radicular
4.
Curr HIV Res ; 21(3): 149-159, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37221692

RESUMEN

Viruses belong to the class of micro-organisms that are well known for causing infections in the human body. Antiviral medications are given out to prevent the spread of disease-causing viruses. When the viruses are actively reproducing, these agents have their greatest impact. It is particularly challenging to develop virus-specific medications since viruses share the majority of the metabolic functions of the host cell. In the continuous search for better antiviral agents, the United States Food and Drug Administration (USFDA) approved a new drug named Evotaz on January 29, 2015 for the treatment of human immunodeficiency virus (HIV). Evotaz is a combined once-daily fixed drug, containing Atazanavir, an HIV protease inhibitor, and cobicistat, an inhibitor of the human liver cytochrome P450 (CYP) enzyme. The medication is created such that it can kill viruses by concurrently inhibiting protease and CYP enzymes. The medicine is still being studied for a number of criteria, but its usefulness in children under the age of 12 is currently unknown. The preclinical and clinical characteristics of Evotaz, as well as its safety and efficacy profiles and a comparison of the novel drug with antiviral medications presently available in the market, are the main topics of this review paper.


Asunto(s)
Fármacos Anti-VIH , Antiinfecciosos , Infecciones por VIH , Inhibidores de la Proteasa del VIH , VIH-1 , Niño , Humanos , Fármacos Anti-VIH/farmacología , Antivirales/farmacología , Sulfato de Atazanavir/farmacología , Cobicistat , Sistema Enzimático del Citocromo P-450 , Interacciones Farmacológicas , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/metabolismo , Inhibidores de la Proteasa del VIH/farmacología , Inhibidores de Proteasas/farmacología , Estados Unidos
5.
Anal Chim Acta ; 1239: 340727, 2023 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-36628772

RESUMEN

The highly sensitive, selective, easy-to-prepare, aqueous media based on two novel probes 2-(pyren-1-yl)imidazo[1,2-a]pyridine (IMP-Py) and (2-(pyren-1-yl)imidazo[1,2-a]pyridin-3-yl)methanol (IMP-Py-OH) are synthesized for the detection of toxic chemical warfare nerve agent mimic diethylcyanochlorophosphonate (DCNP). Both probes are found effective in the detection of DCNP but comparatively, IMP-Py shows better properties in terms of instantaneous response, specificity, selectivity and a low detection limit of 16.9 nM. A significant enhancement of fluorescence intensity of IMP-Py due to aggregation-induced emission enhancement (AIEE) and photoinduced electron transfer (PET) phenomenon was inhibited due to phosphorylation of the hydroxy group of IMP-Py-OH in presence of DCNP has been observed. Taking the advantages of good sensitivity and fast response, probe IMP-Py has been fabricated into a viable paper strips portable product, tested for its potential for the detection of DCNP in tap water as well as with its vapor and response is visible under a UV lamp of 365 nm wavelength.


Asunto(s)
Sustancias para la Guerra Química , Colorantes Fluorescentes , Colorantes Fluorescentes/química , Organofosfatos/química , Sustancias para la Guerra Química/análisis , Agua , Tomografía de Emisión de Positrones
6.
Nat Prod Res ; 37(15): 2575-2582, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35382651

RESUMEN

To combat the shortage of single agro-residue and overcome the problem of seasonal availability, it is beneficial to use mixture of lignocellulosic biomasses. In the present study, efforts were made to use mixed lignocellulosic biomass for production of bioethanol, along with microbial lipids and lactic acid. Upon enzymatic hydrolysis of mixed biomass at varied proportions it was observed that mixture of paddy straw and jute in the ratio 3:1 resulted in best sugar yield (41.50 g/L) at 10% substrate loading. Ethanolic fermentation of mixed substrate hydrolysate by thermotolerant yeast, Saccharomyces cerevisiae JRC6 resulted in 8.39 g/L of ethanol. To maintain sustainability and economic impact, oleaginous yeast (Trichosporon mycotoxinivorans S2) and lactic acid bacteria (Lactobacillus plantarum LP-9) were used for lipid production (14.5 g/L) and lactic acid production (11.08 g/L), respectively. Therefore, this study explored the potential of mixed lignocellulosic biomass to be exploited for production of various value-added products.


Asunto(s)
Ácido Láctico , Saccharomyces cerevisiae , Etanol , Fermentación , Lípidos , Biomasa , Hidrólisis
7.
Curr Top Med Chem ; 23(2): 98-113, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36503471

RESUMEN

Pyridoxine and its derivatives, pyridoxamine, and pyridoxal have been recognized for more than 70 years and are known for regulating cellular biology and metabolism. During the past few decades, the anti-oxidant and anti-inflammatory properties of pyridoxine and its vitamers were explored. However, an interesting turnabout was observed in pyridoxine chemical modification in the last two decades. The various important pathophysiological aspects of pyridoxine and its derivatives on several cellular systems have been discovered by researchers. Recent findings have shown that many diseases, like cancer, diabetes, hypertension, tuberculosis, epilepsy, and neurodegenerative diseases are linked to the alteration of pyridoxine. Herein, our main focus is to review the importance of pyridoxine and its derivatives obtained by various chemical modifications, in various disease areas and to recognize important directions for future research.


Asunto(s)
Piridoxal , Piridoxina , Piridoxal/metabolismo , Piridoxamina , Piridoxina/farmacología , Piridoxina/metabolismo
8.
Drug Chem Toxicol ; : 1-16, 2022 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-36514993

RESUMEN

A series of uncharged salicylaldehyde oximes were synthesized and evaluated for the reactivation of organophosphorus (OP) nerve agents simulants Diethylchlorophosphonate (DCP) & Diethylcyanophosphonate (DCNP) and pesticides (paraoxon & malaoxon) inhibited electric eel Acetylcholinesterase (AChE). The computational software Swiss ADME and molinspiration were used to unfold the probability of drug-likeness properties of the oximes derivatives. Substituted aromatic oximes with diethylamino or bromo group with free hydroxyl group ortho to oxime moiety were found efficient to regenerate the enzymatic activity in in-vitro AChE assay. The alkylation of the ortho hydroxyl group of derivatives led to the loss of reactivation potential. The derivatives with a hydroxyl group and without oxime group and vice versa did not show significant reactivation potency against tested OP toxicants. Further, we also evaluated the reactivation potential of these selected molecules on the rat brain homogenate against different OPs inhibited ChE and found maximum reactivation potency of oxime 2e. The in-vitro results were further validated by molecular docking and dynamic studies which showed that the hydroxyl group interacted with serine amino acids in the catalytic anionic site of AChE enzyme and was stable up to 200 ns consequently providing proper orientation to oxime moiety for reactivating the OP inhibited enzyme. It has thus been proved by the structure-activity relationship of oximes derivatives that hydroxyl group ortho to oxime is essential for reactivating OP inhibited electric eel AChE. Amongst the twenty-one oximes derivatives, 2e was found to be most active in regenerating the paraoxon, malaoxon, DCP and DCNP inhibited AChE enzyme.

9.
Crit Rev Anal Chem ; : 1-18, 2022 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-36562726

RESUMEN

Different classes of Imidazopyridine i.e., Imidazo[1,2-a]pyridine, Imidazo[1,5-a] pyridine, Imidazo[4,5-b]pyridine, have shown versatile applications in various fields. In this review, we have concisely presented the usefulness of the fluorescent property of imidazopyridine in different fields such as imaging tools, optoelectronics, metal ion detection, etc. Fluorescence mechanisms such as excited state intramolecular proton transfer, photoinduced electron transfer, fluorescence resonance energy transfer, intramolecular charge transfer, etc. are incorporated in the designed fluorophore to make it for fluorescent applications. It has been widely employed for metal ion detection, where selective metal ion detection is possible with triazole-attached imidazopyridine, ß-carboline imidazopyridine hybrid, quinoline conjugated imidazopyridine, and many more. Also, other popular applications involve organic light emitting diodes and cell imaging. This review shed a light on recent development in this area especially focusing on the optical properties of the molecules with their usage which would be helpful in designing application-based new imidazopyridine derivatives.

10.
J Obstet Gynaecol India ; 72(Suppl 2): 425-428, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36457446

RESUMEN

Case Summary: A 27 years old female presented to gynae OPD with foul smelling discharge per vaginum off and on for a year and was given treatment for PID (Pelvic inflammatory disease) and cervicitis. Pap smear was taken and was reported unsatisfactory due to inflammation. Colposcopy was planned later due to her bothersome complaints and suspicious looking cervix. A white worm popped out of cervix while doing colposcopy which turned out to be Trichuris trichiura. Deworming was done for the patient and her family members. Patient reported again with similar complaints and this time colposcopy and guided biopsy was done that showed Tubercular Granulomatous cervicitis hence, she was put on category I ATT (Anti-tubercular treatment) that relieved her symptoms and improved cervical findings. Conclusion: People living in tropical and subtropical areas are at highest risk of infection by T. trichiura. This is the first case of T. trichiura in ectopic location and first case of a live worm found in female genital tract. Previous studies have shown that helminthic infection can reactivate latent TB and aggravate the disease expression.

11.
Spectrochim Acta A Mol Biomol Spectrosc ; 282: 121633, 2022 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-35932602

RESUMEN

A fused heterocyclic ESIPT imidazo[1,2-a]pyridine-based probes for colorimetric and fluorometric detection of nerve agents simulant sarin (DCP) and tabun (DCNP) are reported. The probes (5b, 6a & 6b) were found to be highly sensitive and selective for the detection of DCNP and DCP at a micromolar concentration within seconds with no observed interference from other various types of analytes. The LOD for 6b towards DCP was found to be 0.6 µM with a linear range from 0 to 8 µM. The low-cost portable cellulose paper strip fabricated with probe 6b for real-time detection of DCP in the gas phase and spiked water has been developed. The paper strip product was found effective in detecting the presence of DCP in water and vapor state with substantial color changes which could be easily observed by the naked eye and under a handheld UV lamp at a wavelength of 365 nm.


Asunto(s)
Agentes Nerviosos , Colorimetría , Colorantes Fluorescentes/análisis , Agentes Nerviosos/análisis , Piridinas , Agua
12.
PLoS One ; 17(4): e0267362, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35482671

RESUMEN

15-40% of non-small cell lung cancer (NSCLC) patients harbor epidermal growth factor receptor (EGFR)-sensitizing mutations. Tyrosine kinase inhibitors (TKIs) provide significant clinical benefit in this population, yet all patients will ultimately progress. Liquid biopsy can reliably identify somatic tumor-associated EGFR mutations in plasma. This study aimed to assess the feasibility and value of the quantitative assessment of EGFR driver mutations in plasma in EGFR-mutated NSCLC patients treated with EGFR-TKIs as a tool to evaluate therapeutic response to TKIs and monitor for disease progression. The study included 136 patients with tissue biopsy-confirmed EGFR-sensitizing, mutation-positive lung adenocarcinoma with plasma collected prior to TKI treatment and at least two post-initiation TKI treatment/follow-up blood samples. Plasma samples were tested with the cobas® EGFR Mutation Test v2 (cobas EGFR Test), and semi-quantitative index (SQI) values for each identified mutation were reported by the assay software. The most common baseline EGFR mutations detected in tissue were L858R (53.7%) and exon 19 deletion (39.7%). Plasma cell-free DNA analysis detected EGFR mutations in 74% of the baseline samples. Objective response rate by RECIST 1.1 was achieved in 72% of patients, while 93% had a molecular response (defined as disappearance of the EGFR mutation from plasma). 83% of patients had molecular progression (MP; 1.5X SQI increase or new T790M mutation), and 82% who had a clinical response had clinical progression. On average, MP occurred 42 days prior to clinical progression. Patients who progressed while on first-line TKI showed MP of the original EGFR-sensitizing mutations prior to the emergence of a T790M mutation, which was detected in 27% of the EGFR plasma-positive patients. Longitudinal monitoring of EGFR mutational load in plasma is feasible and can predict both response and clinical progression in EGFR-mutated NSCLC patients treated with EGFR-TKIs, as well as detect treatment-emergent EGFR mutations.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Receptores ErbB , Humanos , Biopsia Líquida , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Mutación , Inhibidores de Proteínas Quinasas/uso terapéutico
13.
Curr Drug Targets ; 23(9): 933-953, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35346005

RESUMEN

Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative disorder that may account for approximately 60-70% of cases of dementia worldwide. AD is characterized by impaired behavioural and cognitive functions, including memory, language, conception, attentiveness, judgment, and reasoning problems. The two important hallmarks of AD are the appearance of plaques and tangles of amyloid-beta (Aß) and tau proteins, respectively, in the brain based on the etiology of the disease, including cholinergic impairment, metal dyshomeostasis, oxidative stress, and degradation of neurotransmitters. Currently, the used medication only provides alleviation of symptoms but is not effective in curing the disease, which creates the need to develop new molecules to treat AD. Heterocyclic compounds have proven their ability to be developed as drugs for the treatment of various diseases. The five-membered heterocyclic compound triazole has received foremost fascination for the discovery of new drugs due to the possibility of structural variation. Moreover, it has proved its significance in various drug categories. This review mainly summarizes the recent advancements in the development of novel 1,2,3-triazole and 1,2,4-triazole-based molecules in the drug discovery process for targeting various AD targets such as phosphodiesterase 1 (PDE1) inhibitors, apoptosis signal-regulating kinase 1 (ASK1) inhibitors, somatostatin receptor subtype-4 (SSTR4) agonist, several other druggable targets, molecular modelling studies, as well as various methodologies for the synthesis of triazoles containing molecules such as click reaction, Pellizzari reaction, and Einhorn- Brunner reaction.


Asunto(s)
Enfermedad de Alzheimer , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Humanos , Estrés Oxidativo , Triazoles/farmacología , Triazoles/uso terapéutico
14.
JAMA Netw Open ; 5(2): e2146798, 2022 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-35171263

RESUMEN

Importance: The incidence of infection during SARS-CoV-2 viral waves, the factors associated with infection, and the durability of antibody responses to infection among Canadian adults remain undocumented. Objective: To assess the cumulative incidence of SARS-CoV-2 infection during the first 2 viral waves in Canada by measuring seropositivity among adults. Design, Setting, and Participants: The Action to Beat Coronavirus study conducted 2 rounds of an online survey about COVID-19 experience and analyzed immunoglobulin G levels based on participant-collected dried blood spots (DBS) to assess the cumulative incidence of SARS-CoV-2 infection during the first and second viral waves in Canada. A sample of 19 994 Canadian adults (aged ≥18 years) was recruited from established members of the Angus Reid Forum, a public polling organization. The study comprised 2 phases (phase 1 from May 1 to September 30, 2020, and phase 2 from December 1, 2020, to March 31, 2021) that generally corresponded to the first (April 1 to July 31, 2020) and second (October 1, 2020, to March 1, 2021) viral waves. Main Outcomes and Measures: SARS-CoV-2 immunoglobulin G seropositivity (using a chemiluminescence assay) by major geographic and demographic variables and correlation with COVID-19 symptom reporting. Results: Among 19 994 adults who completed the online questionnaire in phase 1, the mean (SD) age was 50.9 (15.4) years, and 10 522 participants (51.9%) were female; 2948 participants (14.5%) had self-identified racial and ethnic minority group status, and 1578 participants (8.2%) were self-identified Indigenous Canadians. Among participants in phase 1, 8967 had DBS testing. In phase 2, 14 621 adults completed online questionnaires, and 7102 of those had DBS testing. Of 19 994 adults who completed the online survey in phase 1, fewer had an educational level of some college or less (4747 individuals [33.1%]) compared with the general population in Canada (45.0%). Survey respondents were otherwise representative of the general population, including in prevalence of known risk factors associated with SARS-CoV-2 infection. The cumulative incidence of SARS-CoV-2 infection among unvaccinated adults increased from 1.9% in phase 1 to 6.5% in phase 2. The seropositivity pattern was demographically and geographically heterogeneous during phase 1 but more homogeneous by phase 2 (with a cumulative incidence ranging from 6.4% to 7.0% in most regions). The exception was the Atlantic region, in which cumulative incidence reached only 3.3% (odds ratio [OR] vs Ontario, 0.46; 95% CI, 0.21-1.02). A total of 47 of 188 adults (25.3%) reporting COVID-19 symptoms during phase 2 were seropositive, and the OR of seropositivity for COVID-19 symptoms was 6.15 (95% CI, 2.02-18.69). In phase 2, 94 of 444 seropositive adults (22.2%) reported having no symptoms. Of 134 seropositive adults in phase 1 who were retested in phase 2, 111 individuals (81.8%) remained seropositive. Participants who had a history of diabetes (OR, 0.58; 95% CI, 0.38-0.90) had lower odds of having detectable antibodies in phase 2. Conclusions and Relevance: The Action to Beat Coronavirus study found that the incidence of SARS-CoV-2 infection in Canada was modest until March 2021, and this incidence was lower than the levels of population immunity required to substantially reduce transmission of the virus. Ongoing vaccination efforts remain central to reducing viral transmission and mortality. Assessment of future infection-induced and vaccine-induced immunity is practicable through the use of serial online surveys and participant-collected DBS.


Asunto(s)
Prueba Serológica para COVID-19/estadística & datos numéricos , COVID-19/epidemiología , Inmunoglobulina G/sangre , Adolescente , Adulto , Anciano , COVID-19/inmunología , Canadá/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pandemias , SARS-CoV-2 , Encuestas y Cuestionarios
15.
Med Chem ; 18(2): 273-287, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-33563155

RESUMEN

AIM: To synthesize and evaluate the fused heterocyclic imidazo[1,2-a]pyridine based oxime as a reactivator against paraoxon inhibited acetylcholinesterase. BACKGROUND: Organophosphorus compounds (OPs) include parathion, malathion, chlorpyrifos, monocrotophos, and diazinon, which are commonly used in agriculture for enhancing agricultural productivity via killing crop-damaging pests. However, people may get exposed to OPs pesticides unintentionally/intentionally via ingestion, inhalation, or dermal. The current treatment regimen includes reactivator such as mono or bis-pyridinium oximes along with anticholinergic and anticonvulsant drugs that are recommended for the treatment of OP poisoning. Unfortunately, the drawback of the existing reactivator is the permanent charge present on the pyridinium, making them inefficient to cross the blood-brain barrier (BBB) and reactivate OP-inhibited central nervous system (CNS) acetylcholinesterase. Therefore, there is a need of a reactivator that could cross the BBB and reactivate the OP inhibited acetylcholinesterase. OBJECTIVE: The objectives of the study were synthesis, molecular docking, BSA binding, and in-vitro estimation of oximes of various substituted imidazo [1,2-a]pyridine against paraoxon inhibited acetylcholinesterase. METHODS: The reactivators were synthesized in three steps and characterized using various spectroscopic techniques. The molecular docking study was performed on 2WHP and 3ZLV PDB using the Glide-XP software. The acid dissociation constant (pKa) of oximes was calculated experimentally, and the drug-likeness properties of the oximes were calculated in silico using Molinspiration and Swiss ADME software. The binding of oximes with bovine serum albumin (BSA) was also investigated using a Fluorescence spectrophotometer. The reactivation potential of the oximes was determined by in vitro enzymatic assay. RESULTS: The In-silico study inferred that the synthesized molecules fulfilled the parameters required for a successful CNS drug candidate. Furthermore, in-vitro enzymatic assay indicated reasonable reactivation potential of the oximes against paraoxon-inhibited AChE. The binding of oximes with bovine serum albumin (BSA) revealed that there was a static quenching of intrinsic fluorescence of BSA by the oxime. The binding constant value and number of binding sites were found to be 0.24 x 104 mol-1 and 1, respectively. CONCLUSION: The results of the study concluded that this scaffold could be used for further designing of more efficient uncharged reactivators.


Asunto(s)
Acetilcolinesterasa , Reactivadores de la Colinesterasa , Reactivadores de la Colinesterasa/farmacología , Humanos , Imidazoles , Simulación del Acoplamiento Molecular , Oximas/farmacología , Paraoxon/toxicidad , Piridinas , Albúmina Sérica Bovina
16.
3 Biotech ; 11(11): 462, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34745813

RESUMEN

Due to growing consumer preference towards natural ingredients in food products, the production of flavors by microbial biotransformation of agrowastes provides an eco-friendly, cost-effective and sustainable pathway for biovanillin production. In the present study, biovanillin was produced by microbial biotransformation of ferulic acid (FA) using Streptomyces sp. ssr-198. The strain was able to grow in glucose medium supplemented with 1 g/L FA and produce 20.91 ± 1.11 mg/L vanillin within 96 h, along with 5.78 ± 0.13 mg/L vanillic acid in 144 h. Estimation of enzymes involved in FA degradation detected maximum feruloyl-CoA synthetase activity (1.21 ± 0.03 U/mg protein) at 96 h and maximum vanillin dehydrogenase activity (0.31 ± 0.008 U/mg protein) at 168 h, with small amounts of ferulic acid esterase activity (0.13 ± 0.002 U/mg protein) in the fermentation medium. Further, the glucose deficient production medium supplemented with 3 g/L of ferulic acid when inoculated with Streptomyces sp. ssr-198 (6% wet weight) produced maximum vanillin (685 ± 20.11 mg/L) within 72 h at 37 °C under agitation (150 rpm) and declined thereafter. Furthermore, in a one-pot experiment, wherein crude ferulic acid esterase (700 IU/g of substrate) from Enterococcus lactis SR1 was added into 10% w/v wheat bran (natural source of ferulic acid) based medium and was inoculated with 1% w/v of Streptomyces sp. ssr-198 resulted in maximum vanillin production (1.02 ± 0.02 mg/g of substrate) within 60 h of incubation. The study provides an insight into synergistic effect of using FAE of E. lactis SR1 and Streptomyces sp. ssr-198 for bioproduction of biovanillin using agro residues. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-03006-0.

17.
Top Curr Chem (Cham) ; 379(5): 33, 2021 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-34346011

RESUMEN

Organophosphorus (OP) compounds are typically a broad class of compounds that possess various uses such as insecticides, pesticides, etc. One of the most evil utilizations of these compounds is as chemical warfare agents, which pose a greater threat than biological weapons because of their ease of access. OP compounds are highly toxic compounds that cause irreversible inhibition of enzyme acetylcholinesterase, which is essential for hydrolysis of neurotransmitter acetylcholine, leading to series of neurological disorders and even death. Due to the extensive use of these organophosphorus compounds in agriculture, there is an increase in the environmental burden of these toxic chemicals, with severe environmental consequences. Hence, the rapid and sensitive, selective, real-time detection of OP compounds is very much required in terms of environmental protection, health, and survival. Several techniques have been developed over a few decades to easily detect them, but still, numerous challenges and problems remain to be solved. Major advancement has been observed in the development of sensors using the spectroscopic technique over recent years because of the advantages offered over other techniques, which we focus on in the presented review.


Asunto(s)
Agentes Nerviosos/química , Compuestos Organofosforados/química , Plaguicidas/química , Acetilcolinesterasa/química , Acetilcolinesterasa/metabolismo , Carbocianinas/química , Transporte de Electrón , Colorantes Fluorescentes/química , Humanos , Microscopía Fluorescente , Agentes Nerviosos/metabolismo , Compuestos Organofosforados/metabolismo , Plaguicidas/metabolismo , Espectrometría de Fluorescencia
18.
Asia Pac J Oncol Nurs ; 8(2): 115-131, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33688560

RESUMEN

Interventions delivered to cancer patients along with their caregiver as a unit of care indicates dyadic intervention. With the shift of care to home, dyadic interventions are being popular among cancer care. This review aims to identify the dyadic interventions targeting quality of life (QOL) of cancer patient. The current review examined different dyadic interventions for cancer patients from January 2009 to January 2020. PubMed, Psych-info, and CINAHL databases were searched, and 27 studies were included in the review. There were different dyadic interventions for cancer patients including skill based, psychosocial (psycho-educational, educational, counseling), yoga, mindfulness, coping, dance, writing, training along with education, and counseling. Interventions were different in mode of delivery, duration, and delivery personnel. Interventions had improved some aspects of QOL among cancer patients as well as caregivers. Although some aspects of QOL were improved, precise dose and use of different approaches together could be integrated to develop further interventions. Further intervention based on strong theoretical framework guided by the standard protocol is recommended.

19.
Sci Rep ; 11(1): 4068, 2021 02 18.
Artículo en Inglés | MEDLINE | ID: mdl-33603022

RESUMEN

Monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA), a lipophilic chelator has been evaluated for its potential use as an antidote in arsenic poisoning. The pharmacokinetics and pharmacodynamics properties of a drug could be understood via study its mechanism of interaction with bovine serum albumin protein (BSA). Therefore, the interaction between MiADMSA with BSA was investigated using various spectroscopic techniques and computational methods. Linear quenching of BSA intrinsic fluorescence intensity with the increasing concentration of MiADMSA was observed in the fluorescence study. Furthermore, synchronous results revealed that MiADMSA slightly changed the conformation of BSA. The binding constant value of the BSA-MiADMSA complex was found 1.60 × 104 M-1 at 298 K. The value of thermodynamic parameters ΔG, ΔH, and ΔS described that the process is spontaneous, endothermic, and hydrophobic forces are involved in the interaction of MiADMSA with BSA. Competitive site marker experiments showed that MiADMSA binds to site-II of BSA. Conformational changes of BSA with the interaction of MiADMSA were apparent by CD, UV-Visible, FT-IR, and 3D fluorescence spectroscopy. To strengthen the experimental findings we have also performed a theoretical study on the BSA-MiADMSA complex. Two sites were identified with docking score of - 6.642 kcal/mol at site IIa and - 3.80 kcal/mol for site IIb via molecular docking study. Molecular dynamics simulation study inferred the stability of the BSA-MiADMSA complex which was analyzed in a long simulation run. The experimental and computational studies have shown the effective binding of MiADMSA with BSA which is essential for the transportation and elimination of a drug from the body.


Asunto(s)
Albúmina Sérica Bovina/metabolismo , Succímero/análogos & derivados , Sitios de Unión , Dicroismo Circular , Fluorescencia , Simulación del Acoplamiento Molecular/métodos , Estructura Terciaria de Proteína , Albúmina Sérica Bovina/química , Espectroscopía Infrarroja por Transformada de Fourier , Succímero/química , Succímero/metabolismo
20.
Mini Rev Med Chem ; 21(12): 1527-1540, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33371834

RESUMEN

Memory remains an obligatory regime of the human brain, and impaired memory causes serious obstacles in our everyday life. Alzheimer's disease (AD) is one such neurodegenerative disease which mostly affects the elderly population, above the age of 60; marked by cognitive impairment of memory. Besides the known targets of AD against the several etiologies known to date, the zone of epigenetics has recently evolved as an ingenious field in AD. Epigenetic modifications do not affect DNA sequence but only long-term gene expression. Considering the complex multifactorial nature of AD, we herein discuss the various epigenetic targets which might give rise to potential therapeutic approaches. We reviewed the possible epigenetic targets for AD-like HDAC, Sirtuins, glial cells, miRNA and epigenetic modifications like DNA methylation. A deeper insight into these target areas can surely evolve AD diagnosis and therapeutics.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Epigénesis Genética/efectos de los fármacos , Terapia Molecular Dirigida , Animales , Humanos
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