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1.
Artigo em Inglês | MEDLINE | ID: mdl-34488604

RESUMO

BACKGROUND: Conyza bonariensis is known to have anti-cancer properties. OBJECTIVE: The study investigated the in vitro pro-apoptotic properties of Conyza bonariensis (C. bonariensis) towards human lymphoblastic leukemia Jurkat cells. METHODS: C. bonariensis are extracted with non-polar solvent by maceration. MTS cell viability assay was employed to determine the cytotoxic activity of the extract towards human leukemia Jurket cells and normal Peripheral Blood Mononuclear Cells (PBMCs) cells. The phytochemical composition of the extract was chemically characterized using HPLC. Flow cytometric studies (FACS) were conducted to explore the pro-apoptotic potential of the extract. Western blot studies were employed to identify the molecular targets involved in the induction of apoptosis. RESULTS: The n-hexane extract showed selective cytotoxic activity towards Jurkat cells. FACS analysis indicated that the extract induced early and late apoptosis in Jurkat cells. Western blot studies revealed that the extract down-regulated the expression of DNMT1, SIRT1, and UHRF1 with a simultaneous up-regulation of the expression of p73 and caspases-3 proteins. HPLC characterization of the extract revealed the presence of phenolic compounds. CONCLUSION: Overall these findings demonstrate that the anticancer effects of a Conyza bonariensis extract towards human lymphoblastic leukemiais due to the modulation of the activity of multiple oncogenic and tumor suppressor proteins and that its phenolic content is involved are proposed to be responsible for these activities.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34476688

RESUMO

Parkinson's disease is a progressive neurodegenerative disorder that affects mostly elderly people above the age of 60. Previously, we have reported that the ethoxylated chalcone derivative (E)-1-(4-ethoxyphenyl)-3-(fluorophenyl)prop-2-en-1-one (E7) showed potent, reversible, and competitive MAO-B inhibition with an IC50 value of 0.053 µm. The present study aims to investigate the anti-Parkinson activity of compound E7 in a haloperidol-induced animal model of mice. The disease was induced with haloperidol (1 mg/kg, intraperitoneal route) once daily for 21 days. E7 was given at dose levels of 10, 20, and 30 mg/kg/day for 21 days, consecutively. Behavioural tests were carried out during and at the end of the study. Biochemical analyses such as oxidative stress biomarkers and neurotransmitters were quantified on the brain homogenate at the end of the study. Behavioural results showed that there is a marked improvement in locomotor activity and motor coordination in the treatment group. Oxidative stress biomarkers such as SOD, CAT, and GSH levels were increased dose-dependently with a maximum at 30 mg/kg, whereas the dose-dependent decrease (30 mg/kg) in the MDA and nitrite levels were observed in the treatment groups. Levels of neurotransmitters, such as dopamine, serotonin, and noradrenaline, were increased in the treatment groups while dopamine and noradrenaline levels were more than in the standard treated group. MAO-B level was also decreased dose dependently in the treatment group in comparison with the control group. Based on the findings, it was concluded that the E7 compound exhibited anti-Parkinson activity which was more evident at 30 mg/kg oral dose as evaluated by the haloperidol-induced animal model of mice.

3.
Int J Mycobacteriol ; 10(2): 129-135, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34558463

RESUMO

Background: The emergence of drug-resistant tuberculosis (DRTB) has continued to pose a threat to public health in sub-Saharan Africa and globally. Despite the high burden of tuberculosis (TB) in Nigeria, there are paucity of data on the safety and efficacy of newer agents and repurposed drugs used in the treatment of DRTB. Methods: This prospective cohort study was conducted at a regional DRTB treatment center in Kano, Northwestern Nigeria. Descriptive statistics, Mann-Whitney U-test, and Chi-square or Fisher's exact test were used to analyze the data as appropriate. Results: The median age of the patients was 32 years (interquartile range 26-42 years). Of the 39 patients, 34 (87.18%) were males. The majority of the patients came from the rural areas 25 (64.10%). By 10 months of initiation of combination therapy, 25 (64.10%) of the patients were alive, culture negative and on treatment while 14 (35.90%) of the patients have died. Out of the 39 patients in the cohort, 26 (66.67%) patients had at least one serious adverse event. The most common serious adverse events were hematological disorders (13 [35.14%] of 37 events) and neurological disorders (11 [29.73%] of 37 events). Peripheral neuropathy (P < 0.0001), anemia (P = 0.029), and skin reaction (P = 0.021) occurred more frequently among linezolid interrupters. Conclusions: In conclusion linezolid-based combination therapy, with linezolid at a dose of 600mg daily is associated with satisfactory culture conversion rate by 10 months of therapy. However, linezolid may be associated with peripheral neuropathy that may warrant interruption of the drug.

4.
Life Sci ; 285: 119994, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34592236

RESUMO

AIM OF THE STUDY: Breast cancer is caused by abnormal growth of the cells and progressed due to the over-expression of estrogen (ER) and progesterone (PR). The current study was designed to evaluate the anti-tumor activity of 2,4,6 tris-methyphenylamino1,3,5-triazine compound (MPAT) in N-nitroso, N-methyl urea (NMU)-induced mammary gland cancer. METHODS: Molecular docking and in-vitro studies were conducted before the in-vivo analysis. Female Albino rats were divided into 5 groups (n = 6). Group I received Carboxymethylcellulose (CMC) (1 mL/100 g). Group II (diseased group) received NMU 50 mg/kg. Group III (standard group) received tamoxifen (5 mg/kg). Group IV-V received MPAT at doses of 30 and 60 mg/kg respectively. All groups received NMU intraperitoneally except the control group at 3 weeks intervals for 12 weeks. After 12 weeks of NMU dosing, MPAT was given for 15 consecutive days. Biochemical, oxidative stress markers, hormonal profile, and inflammatory mediators were analyzed. KEY FINDINGS: MPAT showed significant interaction with the selected targets in docking studies. An over-expression of ER and PR was observed in NMU-treated rats which were restored significantly after MPAT administration. Nitrite and MDA levels were high in the diseased group and MPAT treatment attenuated the oxidative damage after treatment. Antioxidants such as superoxide dismutase (SOD), Catalase (CAT), total sulfhydryl (TSH), glutathione (GSH), and Lactate dehydrogenase (LDH) values were low in NMU-treated rats. SIGNIFICANCE: This study concluded that MPAT can be used as an anticancer agent due to its significant effects on down-regulating the hormonal profile and oxidative stress markers.

5.
Environ Monit Assess ; 193(10): 649, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34523031

RESUMO

The present study aims to assess the recent changes and trends in the extreme climate indices in the Kashmir basin using the observational records from 1980 to 2016. The extreme climate indices were computed using the ClimPACT2 software and a total of 39 indices were selected for the analysis having particular utility to various sectors like agriculture, water resources, energy consumption, and human health. Besides adopting the station scale analysis, regional averages were computed for each index. In terms of the mean climatology, an increase has been observed in the annual mean temperature with a magnitude of 0.024 °C/year. Further, differential warming patterns have been observed in the mean maximum and minimum temperatures with mean maximum temperature revealing higher increases than mean minimum temperature. On the other hand, the annual precipitation shows a decrease over most of the region, and the decreases are more pronouncing in the higher altitudes. The trend analysis of the extreme indices reveals that in consonance with the rising temperature there has been an increase in the warm temperatures and decrease in the cold temperatures across the Kashmir basin. Furthermore, our analysis suggests a decrease in the extreme precipitation events. The drought indices viz., Standardised Precipitation Index (SPI), and Standardised Precipitation Evapotranspiration Index (SPEI) manifest decreasing trends with the tendency towards drier regimes implying the need for better water resource management in the region under changing climate.


Assuntos
Mudança Climática , Monitoramento Ambiental , Secas , Humanos , Meteorologia , Temperatura
6.
Oxid Med Cell Longev ; 2021: 3268136, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34336089

RESUMO

Genistein is an isoflavone first isolated from the brooming plant Dyer's Genista tinctoria L. and is widely distributed in the Fabaceae family. As an isoflavone, mammalian genistein exerts estrogen-like functions. Several biological effects of genistein have been reported in preclinical studies, such as the antioxidant, anti-inflammatory, antibacterial, and antiviral activities, the effects of angiogenesis and estrogen, and the pharmacological activities on diabetes and lipid metabolism. The purpose of this review is to provide up-to-date evidence of preclinical pharmacological activities with mechanisms of action, bioavailability, and clinical evidence of genistein. The literature was researched using the most important keyword "genistein" from the PubMed, Science, and Google Scholar databases, and the taxonomy was validated using The Plant List. Data were also collected from specialized books and other online resources. The main positive effects of genistein refer to the protection against cardiovascular diseases and to the decrease of the incidence of some types of cancer, especially breast cancer. Although the mechanism of protection against cancer involves several aspects of genistein metabolism, the researchers attribute this effect to the similarity between the structure of soy genistein and that of estrogen. This structural similarity allows genistein to displace estrogen from cellular receptors, thus blocking their hormonal activity. The pharmacological activities resulting from the experimental studies of this review support the traditional uses of genistein, but in the future, further investigations are needed on the efficacy, safety, and use of nanotechnologies to increase bioavailability and therapeutic efficacy.

7.
PLoS One ; 16(8): e0255189, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34415906

RESUMO

BACKGROUND & AIM: Hepatitis B and C infections are global issues that are associated with a massive financial burden in developing countries where vertical transmission is the major mode and remains high. This cross-sectional study was designed to investigate the seroepidemiology and associated risk factors of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among 375 pregnant women attending antenatal care health facilities at Bacha Khan Medical Complex (BKMC) Shahmansoor and District Head Quarter (DHQ) Hospital Swabi, Khyber Pakhtunkhwa, Pakistan. METHODOLOGY: From a total of 375 pregnant women selected using systematic random sampling from both hospitals, 10 ml of blood samples were collected and alienated serum was examined for indicators identification through the Immuno-Chromatographic Test (ICT) and 3rd Generation Enzyme-Linked Immunosorbent Assay (ELISA). A pre-structured questionnaire was used to collect the socio-demographic data and possible risk factors. The data was analyzed via SPSS 23.0 statistical software. A chi-square analysis was performed to determine the association between variables. P-value < 0.05 was set statistically significant. RESULTS: The overall frequency of HBV and HCV among 375 pregnant women involved in the study was 3.7% and 2.1% respectively. None of the pregnant women were co-infected with HBV and HCV. Dental extraction (P = 0.001) and blood transfusion (P = 0.0005) were significantly allied with HBV infection while surgical procedure (P = 0.0001) was significantly associated with HCV infection. Moreover the sociodemographic characteristics: residential status (P = 0.017) and educational level (P = 0.048) were found significant risk factors of HBsAg and maternal age (P = 0.033) of anti-HCV, respectively. CONCLUSION & RECOMMENDATION: HBV and HCV infections are intermediary endemic in the study area. A higher prevalence of HBV was detected among pregnant mothers with a history of dental extraction, history of blood transfusion, resident to the urban area and low educational level. The age and surgical procedures were the potential risk factors found significantly associated with HCV positivity among pregnant mothers in our setup. Future negotiations to control vertical transmission should include routine antenatal screening for these infections early in pregnancy and the requirement of efficient preventive tools including the birth dose of the hepatitis B vaccine in combination with hepatitis B immune globulins to the neonate.

8.
Sci Rep ; 11(1): 15023, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34294747

RESUMO

Hepatitis C virus (HCV), a small, single-stranded RNA virus with a 9.6 kb genome, is one of the most common causes of liver diseases. Sequencing of the 5' untranslated region (UTR) is usually used for HCV genotyping, but it is less important in numerous subtypes due to its scarce sequence variations. This study aimed to identify genotypes using the 5' UTR of HCV from cirrhotic patients of Khyber Pakhtunkhwa (KP). Serum RNA samples (44) were screened by real time PCR to determine the HCV viral load. Nested PCR was performed to identify cDNA and the 5' UTR. The HCV 5' UTR was sequenced using the Sanger method. MEGA-7 software was used to analyze evolutionary relatedness. After 5' UTR sequencing, 26 samples (59%) were identified as genotype 3, and 2 samples (6%) were identified as genotypes 1, 2 and 4. The most predominant genotype was 3a, and genotype 4 was rarely reported in the phylogenetic tree. Analysis of the HCV 5' UTR is an efficient alternative method for confirmation of various genotypes. Phylogenetic analysis showed that genotype 3 was dominant in the area of KP, Pakistan.

9.
Pak J Pharm Sci ; 34(2(Supplementary)): 737-745, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34275809

RESUMO

Present study is aimed to investigate the hepatoprotective and hematopoietic effect of Typha elephantina leaves aqueous (T.E.AQ), extract in paracetamol (PCM) intoxicated rabbits. Experimental animals were divided into various groups. The blood was taken on day 7th (W1=Week 1), day 14th (W2 = week 2) and day 21st (W3 = week 3) of treatments and was analyzed for all hematological and serum biochemical markers. PCM administration caused marked increase in the levels of serum biochemical and hematological parameters. The leaves of T.E.AQ extract at dose rate 300mg/kg body weight significantly (P<0.05) reduced the elevated levels of serum biochemical and hematological indices towards normal values on third week (day 21st) of treatment while treatment in the first two weeks revealed non-significant effects even at all doses of extract. The levels of glutathione (GSH) and radical scavenging activity (RSA) were reduced and thiobarbituric acid reactive substances (TBARS) levels was high in the PCM feed animals. Administration of (T.E.AQ) extract at high dose (300mg/kg) significantly regulated and normalized these antioxidant values. The antioxidant capacity of (TE.AQ) extract, showed increase inhibition against various extract concentrations on the basis of percent scavenging of (DPPH) free radical. The histological sections of liver further supported the hepatoprotective activity of extract.

10.
Eur J Pharmacol ; 907: 174305, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34224698

RESUMO

Gastric cancer (G.C) is one of the most lethal cancer types worldwide. Current treatment requires surgery along with chemotherapy, which causes obstacles for speedy recovery. The discovery of novel drugs is needed for better treatment of G.C with minimum side effects. Latcripin-7A (LP-7A) is a newly discovered peptide extracted from Lentinula edodes. It is recently studied for its anti-cancer activity. In this study, LP-7A was modeled using a phyre2 server. Anti-proliferation effects of LP-7A on G.C cells were examined via CCK-8, colony formation, and morphology assay. Apoptosis of LP-7A treated G.C cells was evaluated via Hoechst Stain, western blot and flow cytometry. Autophagy was assessed via acridine orange staining and western blot. The cell cycle was assessed via flow cytometry assay and western blot. Pathway was studied via western blot and STRING database. Anti-migratory effects of LP-7A treated G.C cells were analyzed via wound healing, western blot, and migration and invasion assay. LP-7A effectively inhibited the growth of G.C cells by inhibiting the PI3K/Akt/mTOR pathway. G.C cells treated with LP-7A arrested the cell cycle at the G1 phase, contributing to the inhibition of migration and invasion. Furthermore, LP-7A induced apoptosis and autophagy in gastric cancer cells. These results indicated that LP-7A is a promising anti-cancer agent. It affected the proliferation and growth of G.C cells (SGC-7901 and BGC-823) by inducing apoptosis, autophagy, and inhibiting cell cycle at the G1 phase in G.C cells.

11.
Chaos Solitons Fractals ; : 110952, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33967407

RESUMO

A novel coronavirus disease (COVID-19) appeared in Wuhan, China in December 2019 and spread around the world at a rapid pace, taking the form of pandemic. There was an urgent need to look for the remedy and control this deadly disease. A new strain of coronavirus called Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was considered to be responsible for COVID-19. Novel coronavirus (SARS-CoV-2) belongs to the family of coronaviruses crowned with homotrimeric class 1 fusion spike protein (or S protein) on their surfaces. COVID-19 attacks primarily at our throat and lungs epithelial cells. In COVID-19, a stronger adaptive immune response against SARS-CoV-2 can lead to longer recovery time and leads to several complications. In this paper, we propose a mathematical model for examining the consequence of adaptive immune responses to the viral mutation to control disease transmission. We consider three populations, namely, the uninfected epithelial cells, infected cells, and the SARS-CoV-2 virus. We also take into account combination drug therapy on the dynamics of COVID-19 and its effect. We present a fractional-order model representing COVID-19/SARS-CoV-2 infection of epithelial cells. The main aim of our study is to explore the effect of adaptive immune response using fractional order operator to monitor the influence of memory on the cell-biological aspects. Also, we have studied the outcome of an antiviral drug on the system to obstruct the contact between epithelial cells and SARS-CoV-2 to restrict the COVID-19 disease. Numerical simulations have been done to illustrate our analytical findings.

12.
Neurochem Res ; 46(7): 1814-1829, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33877499

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with decline in memory and cognitive impairments. Phosphodiesterase IV (PDE4) protein, an intracellular cAMP levels regulator, when inhibited act as potent neuroprotective agents by virtue of ceasing the activity of Pro-inflammatory mediators. The complexity of AD etiology has ever since compelled the researchers to discover multifunctional compounds to combat the AD and neurodegeneration. The aim of this study was to probe into role of drotaverine a PDE4 inhibitor in the management of AD. Albino mice were divided into seven groups (n = 10). Group 1 control group received carboxy methyl cellulose (CMC 1 mL/kg), group II diseased group treated with streptozotocin (STZ 3 mg/kg) by intracerebroventricular (ICV) route, group III administered standard drug Piracetam 200 mg/kg and groups IV-VII were given drotaverine (10, 20, 40, and 80 mg/kg i/p respectively). Groups II-VII were given STZ (3 mg/kg, ICV) on 1st and 3rd day of treatment to induce AD. All the groups were given their respective treatments for 23 days. Improvement in learning and memory was evaluated by using behavioral tests like open field test, elevated plus maze test, Morris water maze test and passive avoidance test. Furthermore, brain levels of biochemical markers of oxidative stress, neurotransmitters, ß-amyloid and tau protein were also measured. Drotaverine showed statistically significant dose dependent improvement in behavioral and biochemical markers of AD: the maximum response was achieved at a dose level of 80 mg/kg. The Study concluded that drotaverine ameliorates cognitive impairment and as well as exhibited modulated the brain levels of neurotransmitters.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Nootrópicos/uso terapêutico , Papaverina/análogos & derivados , Inibidores da Fosfodiesterase 4/uso terapêutico , Acetilcolinesterase/metabolismo , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/metabolismo , Animais , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Feminino , Aprendizagem/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Camundongos , Simulação de Acoplamento Molecular , Teste do Labirinto Aquático de Morris/efeitos dos fármacos , Neurotransmissores/metabolismo , Nootrópicos/metabolismo , Teste de Campo Aberto/efeitos dos fármacos , Papaverina/metabolismo , Papaverina/uso terapêutico , Inibidores da Fosfodiesterase 4/metabolismo , Ligação Proteica , Estreptozocina
13.
Artigo em Inglês | MEDLINE | ID: mdl-33806383

RESUMO

Heat stress provokes thermal discomfort to people living in semiarid and arid climates. This study evaluates thermal discomfort levels, building design concepts, and some heat mitigation strategies in low-income neighborhoods of Faisalabad, Pakistan. The outdoor and indoor weather data are collected from April to August 2016 using a weather station installed ad hoc in urban settings, and the 52 houses of the five low-income participating communities living in congested and less environment-friendly areas of Faisalabad. The discomfort index values, related to the building design concepts, including (i) house orientation to sunlight and (ii) house ventilation, are calculated from outdoor and indoor dry-bulb and wet-bulb temperatures. Our results show that although June was the hottest month of summer 2016, based on the monthly mean temperature of the Faisalabad region, the month of May produced the highest discomfort levels, which were higher in houses exposed to sunlight and without ventilation. The study also identifies some popular heat mitigation strategies adopted by the five participating low-income communities during various heat-related health complaints. The strategies are gender-biased and have medical, cultural/customary backgrounds. For example, about 52% of the males and 28% of the females drank more water during dehydration, diarrhea, and eye infection. Over 11% and 19% of the males and females, respectively, moved to cooler places during fever. About 43% of the males and 51% of the females took water showers and rested to combat flu (runny nose), headache, and nosebleed. The people did not know how to cure muscular fatigue, skin allergy (from a type of Milia), and mild temperature. Planting trees in an area and developing open parks with greenery and thick canopy trees can be beneficial for neighborhoods resembling those evaluated in this study.


Assuntos
Transtornos de Estresse por Calor , Cidades , Feminino , Temperatura Alta , Humanos , Masculino , Paquistão , Temperatura
14.
Metab Brain Dis ; 36(6): 1231-1251, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33759084

RESUMO

Cucurbita pepo is used as a vegetable in Pakistan and its seeds are also rich in tocopherol. Data showed the pivotal role of tocopherol in the treatment of Parkinson's disease (PD). The current study was designed to probe into the antiparkinson activity of methanolic extract of C. pepo (MECP) seeds in the haloperidol-induced Parkinson rat model. Behavioral studies showed improvement in motor functions. The increase in catalase, superoxide dismutase, glutathione levels whereas the decreases in the malondialdehyde and nitrite levels were noted in a dose-dependent manner. Acetylcholine-esterase (AchE) activity was increased. Molecular docking results revealed significant binding interaction of selected phytoconstituents within an active site of target protein AchE (PDB ID: 4EY7). Furthermore, α-synuclein was up regulated with down regulation of TNF-α and IL-1ß in the qRT-PCR study. Subsequently, ADMET results on the basis of structure to activity predictions in terms of pharmacokinetics and toxicity estimations show that selected phytochemicals exhibited moderately acceptable properties. These properties add knowledge towards the structural features which could improve the bioavailability of selected phytochemicals before moving towards the initial phase of the drug development. Our integrated drug discovery scheme concluded that C. pepo seeds could ameliorate symptoms of PD and may prove a lead remedy for the treatment of PD.

15.
J Food Biochem ; 45(4): e13677, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33709527

RESUMO

This study aimed to appraise the anti-Parkinson's potential of rhinacanthin-C (RC). RC (5, 10, and 20 mg/kg) was orally administered for 25 days in albino mice to treat haloperidol-induced parkinsonism (1 mg/kg). RC significantly (p < .05) improved the motor symptoms in block, bar, rotarod, and balance beam walking tests in treated mice. RC reduced the cataleptic effect dose-dependently. The RC therapy notably (p < .001) enhanced reduced glutathione, catalase, and superoxide dismutase levels while decreased malondialdehyde and nitrite levels in the tissue homogenates of the treated mice. The RC therapy significantly (p < .01-.001) restored the dopamine, norepinephrine, and serotonin levels in the brain tissue of treated mice as co-evidenced from brain histology. RC did not adversely affect complete blood count, and liver and kidney function tests. Taken together, these results have shown that RC is effective in treating motor and non-motor symptoms of Parkinson's disease. PRACTICAL APPLICATIONS: Rhinacanthus nasutus is a medicinally rich plant that has folklore use in several ailments. The plant possessed multiple pharmacological activities due to the presence of naphthoquinones. The major compound of this plant rhinacanthin-C was used in the present study to evaluate it's anti-Parkinson's activity. The results provide scientific evidence of the anti-Parkinson's potential of rhinacanthin-C that support the use of R. nasutus leaves in the prevention and treatment of Parkinson's disorder.


Assuntos
Acanthaceae , Naftoquinonas , Transtornos Parkinsonianos , Animais , Haloperidol/toxicidade , Camundongos , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/tratamento farmacológico
16.
NPJ Precis Oncol ; 5(1): 20, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33742100

RESUMO

E74-like ETS transcription factor 5 (ELF5) is involved in a wide spectrum of biological processes, e.g., mammogenesis and tumor progression. We have identified a list of p300-interacting proteins in human breast cancer cells. Among these, ELF5 was found to interact with p300 via acetylation, and the potential acetylation sites were identified as K130, K134, K143, K197, K228, and K245. Furthermore, an ELF5-specific deacetylase, SIRT6, was also identified. Acetylation of ELF5 promoted its ubiquitination and degradation, but was also essential for its antiproliferative effect against breast cancer, as overexpression of wild-type ELF5 and sustained acetylation-mimicking ELF5 mutant could inhibit the expression of its target gene CCND1. Taken together, the results demonstrated a novel regulation of ELF5 as well as shedding light on its important role in modulation of breast cancer progression.

17.
Artif Cells Nanomed Biotechnol ; 49(1): 194-203, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33629627

RESUMO

This study deals with facile and rapid synthesis of silver nanoparticles (AgNPs) and Gold nanoparticles (AuNPs) using Mentha longifolia leaves extracts (MLE). The synthesized AgNPs and AuNPs were characterized by UV-visible spectroscopy (UV-Vis), Fourier transformed infra-red spectroscopy (FT-IR), atomic force microscopy (AFM) and transmission electron microscopy (TEM) techniques. The phytochemical analysis showed the presence of bioactive secondary metabolites, which are involved in the synthesis of nanoparticles (NPs). The surface plasmon resonance (SPR) observed at 435 and 550 nm, confirmed the green synthesis of AgNPs and AuNPs, respectively. The TEM images showed poly dispersed and round oval shapes of Ag and Au NPs with an average particles size of 10.23 ± 2 nm and 13.45 ± 2 nm, respectively. TEM results are in close agreements with that of AFM analysis. The FT-IR spectroscopy revealed the presence of OH, -NH2 and C = O groups, which involved in the synthesis of NPs. The MLE and their AgNPs and AuNP exhibited good in vitro antibacterial and anti-oxidant activities. Moreover, MLE and NPs also showed in vivo analgesic activities in mice, and excellent sedative properties in open field test paradigm.


Assuntos
Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Mentha/química , Nanopartículas Metálicas/química , Methanomicrobiaceae/química , Extratos Vegetais/química , Prata/química , Animais , Materiais Biocompatíveis/síntese química , Técnicas de Química Sintética , Ouro , Química Verde , Camundongos
18.
Sci Rep ; 11(1): 2866, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536517

RESUMO

In the present work, silver nanoparticles were prepared by using the extract of Camellia Sinensis. The extract contains phytochemicals which are mainly polyphenols acting as the natural reducing and stabilizing agents leading to the formation of uniformly dispersed and stabilized silver nanoparticles. The synthesis of silver nanoparticles was significantly influenced by the impact of the pH, as well as temperature conditions. It was found that at pH 5 and 25 °C, nanoparticles of different morphologies (spherical, polygonal, capsule) and sizes were formed. However, with the increase in temperature from 25 °C to 65 °C but at the same pH, these particles started attaining the spherical shape of different sizes owing to an increase in the reduction rate. Furthermore, for the reaction of the mixture at 65 °C, an increase in pH from 5 to 11 led to an increase in the monodispersity of spherically shaped nanoparticles, attributed to the hydroxide ions facilitated reduction. The prepared nanoparticles were investigated for their antibacterial activity using Nathan's Agar Well-Diffusion method. It was found that AgNPs prepared at pH 9 and 65 °C demonstrated strong antibacterial activity against gram-negative Escherichia coli in contrast to gram-positive Staphylococcus aureus. In reference to the cytotoxic potency, the prepared AgNPs showed clear cytotoxicity for HeLa cells and showcased a close relationship between activity and concentration as evidenced by the decrease in the percentage (100 to 30%) of metabolically active cells up to 25 µM-75 µM concentration of silver nanoparticles.

19.
Metab Brain Dis ; 36(5): 889-900, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33570733

RESUMO

Alzheimer's disease affects daily routine due to loss of memory and decline in cognition. In vitro data showed acetylcholine esterase inhibition activity of Malva neglecta but no in vivo evidence is available. The current study aims to investigate the anti-Alzheimer's activity of Malva neglecta methanolic extract in the AlCl3-induced Alzheimer disease rats' model. Thirty Wistar rats were divided into six groups and respective doses were given orally for 21 days. Behavioural observations were recorded and biochemical analysis was performed on brain homogenate. Improvement in memory and cognition was noted in treated rats as compared to disease control. A dose-dependent decrease (0.530 ± 0.009 at 200 mg/kg, 0.212 ± 0.007 at 400 mg/kg, 0.173 ± 0.005 at 600 mg/kg) in AChE activity was noted in the treatment groups with reference to disease control value (1.572 ± 0.013). This decrease in AChE activity is linked with an increase in acetylcholine in the brain which plays a key role in retaining memory. Oxidative stress biomarkers; GSH (66.77 ± 0.01 at 600 mg/kg), SOD (26.60 ± 0.10 at 600 mg/kg), CAT (21.46 ± 0.01 at 600 mg/kg) levels were increased with a decrease in MDA (103.33 ±0.49 at 600 mg/kg) level in a dose-dependently manner in the treatment groups as compared to disease control respective values. It is concluded that Malva neglecta could ameliorate Alzheimer's symptoms possibly by decreasing AChE activity and oxidative stress.

20.
Neurochem Res ; 46(4): 905-920, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33486698

RESUMO

Alzheimer's disease (AD) is age-dependent neurological disorder with progressive loss of cognition and memory. This multifactorial disease is characterized by intracellular neurofibrillary tangles, beta amyloid plaques, neuroinflammation, and increased oxidative stress. The increased cellular manifestations of these markers play a critical role in neurodegeneration and pathogenesis of AD. Therefore, reducing neurodegeneration by decreasing one or more of these markers may provide a potential therapeutic roadmap for the treatment of AD. AD causes a devastating loss of cognition with no conclusive and effective treatment. Many synthetic compound containing isoxazolone nucleus have been reported as neuroprotective agents. The aim of this study was to explore the anti-Alzheimer's potential of a newly synthesized 3,4,5-trimethoxy isoxazolone derivative (TMI) that attenuated the beta amyloid (Aß1-42) and tau protein levels in streptozotocin (STZ) induced Alzheimer's disease mouse model. Molecular analysis revealed increased beta amyloid (Aß1-42) protein levels, increased tau protein levels, increased cellular oxidative stress and reduced antioxidant enzymes in STZ exposed mice brains. Furthermore, ELISA and PCR were used to validate the expression of Aß1-42. Pre-treatment with TMI significantly improved the memory and cognitive behavior along with ameliorated levels of Aß1-42 proteins. TMI treated mice further showed marked increase in GSH, CAT, SOD levels while decreased levels of acetylcholinesterase inhibitors (AChEI's) and MDA intermediate. The multidimensional nature of isoxazolone derivatives and its versatile affinity towards various targets highpoint its multistep targeting nature. These results indicated the neuroprotective potential of TMI which may be considered for the treatment of neurodegenerative disease specifically in AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Isoxazóis/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Acetilcolinesterase/metabolismo , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Avaliação Pré-Clínica de Medicamentos , Teste de Labirinto em Cruz Elevado , Feminino , Isoxazóis/metabolismo , Masculino , Camundongos , Simulação de Acoplamento Molecular , Fármacos Neuroprotetores/metabolismo , Teste de Campo Aberto/efeitos dos fármacos , Fragmentos de Peptídeos/metabolismo , Ligação Proteica , Estreptozocina , Proteínas tau/metabolismo
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