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1.
Clin Neuropsychol ; : 1-15, 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39096060

RESUMO

OBJECTIVE: The values of a field are reflected in the science it publishes. The goal of this study was to present a historical analysis of the extent to which the field of clinical neuropsychology publishes journals with titles that address culture in the context of brain function and behavior between 2010 and 2020. METHODS: Titles from articles published in 13 neuropsychology journals from 2010-2020 were collected and coded with regard to culture and multicultural content. The aims of the study were to (1) determine how often cultural or multicultural topics were represented in journal titles, (2) determine if cultural or multicultural content in neuropsychology journal publication titles increased over time, and (3) to explore other neuropsychological content that was most and least likely to appear in publications pertaining to culture or multicultural issues. RESULTS: Results indicated that titles for publications in clinical neuropsychology journals with content relevant to cultural or multicultural neuropsychology represented 1.1% to 13.4% of titles across the 13 journals. The number of cultural/multicultural titles increased over time. The number of cultural/multicultural titles per journal was not significantly correlated with the journal impact factor. Normative data were addressed significantly more often in cultural/multicultural titles versus non-cultural/multicultural titles, whereas psychiatric issues were addressed significantly less often. CONCLUSIONS: There are many actions that clinical neuropsychologists can take to increase the field's attention to the effects of culture on brain function and behavior. It is vital to update our data from 2021 to the present, given the substantial increase in awareness of social justice issues that occurred since 2020.

2.
Artigo em Inglês | MEDLINE | ID: mdl-39167171

RESUMO

Liver diseases represent a formidable global health threat. Hesperidin, a flavonoid found in citrus fruits, is the source of diosmin (DS). The in vivo and in vitro investigations of the pharmacological effects of DS reveal that it exhibits tremendous beneficial effects, such as fighting against inflammation, oxidative stress, and fibrosis. These effects have been noticed in various disease models, emphasizing the potential therapeutic value of DS in tackling diverse pathological conditions. Interestingly, DS has promising liver-defense capabilities against a range of hepatic illnesses, such as radiation-induced hepatic injury, liver ischemia/reperfusion injury, alcoholic hepatic disease, nonalcoholic fatty liver disease (NAFLD), and hepatocellular carcinoma (HCC). Furthermore, DS demonstrates potential hepatoprotective effects against environmental toxins, such as heavy metals. DS activates PPAR-γ and Nrf2, leading to antioxidant effects that reduce oxidative stress. Moreover, DS suppresses NF-κB, NLRP3, MAPK activities, and cytokine production (TNF-α and IL-1ß), resulting in inflammation suppression. These anti-inflammatory effects are attributed to the activation of PPAR-γ and Nrf2, which are NF-κB inhibitors. This review aims to comprehensively discuss the hepatoprotective capacity of DS, elucidating the underlying mechanisms and identifying several research avenues that warrant further exploration to ascertain the prospective clinical advantages of DS intake as a viable strategy for the treatment of hepatic illnesses.

3.
J Parasit Dis ; 48(3): 551-569, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39145357

RESUMO

Schistosomiasis is a neglected tropical disease with considerable morbidity. The lone effective drug, praziquantel (PZQ), is showing emergence of drug resistance hence, searching for new supportive treatment is crucial. This study aimed to evaluate the efficacy of mucus and nucleoproteins (NPs) extracted from Biomphalaria alexandrina (B. alexandrina) snails on miracidia, cercariae and Schistosoma mansoni (S. mansoni) adults in vitro and assess their experimental in vivo effect through parasitological, histopathological, and biochemical parameters. The in vivo study included 90 male Swiss albino mice. Mice were grouped into 9 groups; G1-G5 were infected and treated with; GI: PZQ, GII: mucus, GIII: combined PZQ and mucus, GIV: NPs, GV: combined PZQ and NPs. Control groups; C1: Non infected non treated (negative control), C2: Infected non treated (positive control), C3: Non infected mucus treated and C4: Non infected NPs treated. The in vitro study proved that the mucus had a better lethal effect on cercariae than miracidia, while NPs had better lethal effect on miracidia. The mucus lethal effect on adults surpassed the NPs as 100% and 60%, respectively. The in vivo study proved that the combined NPs or mucus with PZQ added to the effect of individual PZQ resulting in 100% total worm burden (TWB) reduction. As regard oxidative stress markers, the lowest level of nitric oxide (NO) was shown with combined PZQ and NPs. While, the highest glutathione (GSH) level was produced by individual PZQ. The study concluded that mucus and NPs of B. alexandrina had cercaricidal, miracidicidal and anti-schistosomal effect in vitro and that their combination could be considered a contribution to PZQ potentiality in vivo.

4.
BioTech (Basel) ; 13(3)2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-39051339

RESUMO

Rutin, a flavonoid phytochemical compound, plays a vital role in human health. It is used in treating capillary fragility and has anti-Alzheimer, anti-inflammatory, and antioxidant effects. In this study, Ti-Mo-Ni-O nanotubes (NTs) were used, for the first time, in an unprecedented plant biotechnology application, wherein in vitro Philodendron shoots (Philodendron erubescens) known as "Imperial Red" were targeted for rutin accumulation. The antioxidant responses and the accumulation of rutin were evaluated in treated Philodendron erubescens (P. erubescens) shoots using 5.0 mg/L of Ti-Mo-Ni-O NTs. The total phenolic content and total flavonoid content were estimated, and an ABTS+ assay, FRAP assay, and iron metal chelation assay were performed. The application of Ti-Mo-Ni-O NTs enhanced the rutin content considerably from 0.02 mg/g to 2.96 mg/g for dry-weight shootlet extracts. Therefore, the use of Ti-Mo-Ni-O NTs is proposed to be a superior alternative to elevate the rutin content. The aim of the current study is to target P. erubescens shoots grown in vitro for the accumulation of rutin compounds using Ti-Mo-Ni-O NT powder, to determine the quantitative and qualitative accumulation of rutin via HPLC-DAD analysis, and to estimate the antioxidant activity of P. erubescens shoot extract. This study presents a novel methodology for utilizing nano-biotechnology in the synthesis of plant secondary metabolites.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38956882

RESUMO

The current research aimed to assess the effects of dietary macadamia oil (MO) on carcass traits, growth performance, physio-biochemical components, immune function, thyroid hormones and inflammation markers of growing rabbits. A total of 96 growing rabbits were randomly distributed into four treatments, with 24 rabbits in each group. The rabbits were fed a basal diet (control group) or a diet supplemented with MO at 0.5 (MO0.5), 1 (MO1.0) and 2 (MO2.0) mL/kg of diet for eight weeks. The daily body weight gain and feed conversion ratio showed a quadratic improvement with increasing levels of MO, and the optimal dose was 1.25 mL/kg of diet. Increasing levels of MO also had a quadratic effect on hepatic and renal functions. Dose-response curves revealed that the optimal doses of MO were 1.50, 1.75 and 1.25 mL/kg of diet for total bilirubin, gamma-glutamyl transferase, and creatinine respectively. A quadratic relationship was observed between the increased levels of MO and tumour necrosis factor-α (p = 0.038), interleukin-6 (p = 0.014) and immunoglobulins (p = 0.016 and IgM p = 0.026). Additionally, a linear relationship was observed between the increment in MO levels and both nitric oxide (p = 0.040) and interleukin-4 (p = 0.001). The activities of superoxide dismutase and glutathione peroxidase showed a linear increase with increasing dietary MO content, while xanthine oxidase showed a linear decrease. Total antioxidant capacity showed quadratic improvement (p = 0.035) with the dietary treatment, with the optimal dose observed at 1.25 mL/kg of diet. The inclusion of MO in the diet had a linear effect on the activity of thyroxine (p = 0.001). Therefore, supplementation of MO at a dose of 1 or 1.5 mL/kg of diet in growing rabbits' diets can improve growth and carcass traits, sustain thyroid function by supporting immunity, and reduce oxidative/inflammation pathways.

6.
Int Immunopharmacol ; 139: 112774, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39067398

RESUMO

Repetitive traumatic brain injury (RTBI) is acknowledged as a silent overlooked public health crisis, with an incomplete understanding of its pathomechanistic signaling pathways. Mounting evidence suggests the involvement of thrombin and its receptor, the protease-activated receptor (PAR)1, in the development of secondary injury in TBI; however, the consequences of PAR1 modulation and its impact on ferroptosis-redox signaling, and NLRP3 inflammasome activation in RTBI, remain unclear. Further, the utilitarian function of PAR1 as a therapeutic target in RTBI has not been elucidated. To study this crosstalk, RTBI was induced in Wistar rats by daily weight drops on the right frontal region for five days. Three groups were included: normal control, untreated RTBI, and RTBI+SCH79797 (a PAR1 inhibitor administered post-trauma at 25 µg/kg/day). The concomitant treatment of PAR1 antagonism improved altered behavior function, cortical histoarchitecture, and neuronal cell survival. Moreover, the receptor blockade downregulated mRNA expression of PAR1 but upregulatedthat of the neuroprotective receptor PPAR-γ. The anti-inflammatory impact of SCH79797 was signified by the low immune expression/levels of NF-κB p65,TNF-α, IL-1ß, and IL-18. Consequently, the PAR1 blocker hindered the formation of inflammasome components NLRP3, ASC, and activated caspase-1. Ultimately, SCH79797 treatment abated ferroptosis-dependent iron redox signaling through the activation of the antioxidant Nrf2/HO-1 axis and its subsequent antioxidant machinery (GPX4, SOD) to limit lipid peroxidation, iron accumulation, and transferrin serum increment. Collectively, SCH79797 offered putative preventive mechanisms against secondary RTBI consequences in rats by impeding ferroptosis and NLRP3 inflammasome through activating the PPAR-γ/Nrf2 antioxidant cue.


Assuntos
Lesões Encefálicas Traumáticas , Ferroptose , Inflamassomos , Fator 2 Relacionado a NF-E2 , Proteína 3 que Contém Domínio de Pirina da Família NLR , PPAR gama , Ratos Wistar , Receptor PAR-1 , Transdução de Sinais , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , PPAR gama/metabolismo , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/imunologia , Lesões Encefálicas Traumáticas/patologia , Inflamassomos/metabolismo , Ferroptose/efeitos dos fármacos , Masculino , Ratos , Transdução de Sinais/efeitos dos fármacos , Receptor PAR-1/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Heme Oxigenase (Desciclizante)/genética , Modelos Animais de Doenças
7.
Life Sci ; 351: 122813, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38857655

RESUMO

The cytoplasmic oligomer NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome has been implicated in most inflammatory and autoimmune diseases. Here, we highlight the significance of NLRP3 in diverse renal disorders, demonstrating its activation in macrophages and non-immune tubular epithelial and mesangial cells in response to various stimuli. This activation leads to the release of pro-inflammatory cytokines, contributing to the development of acute kidney injury (AKI), chronic renal injury, or fibrosis. In AKI, NLRP3 inflammasome activation and pyroptotic renal tubular cell death is driven by contrast and chemotherapeutic agents, sepsis, and rhabdomyolysis. Nevertheless, inflammasome is provoked in disorders such as crystal and diabetic nephropathy, obesity-related renal fibrosis, lupus nephritis, and hypertension-induced renal damage that induce chronic kidney injury and/or fibrosis. The mechanisms by which the inflammatory NLRP3/ Apoptosis-associated Speck-like protein containing a Caspase recruitment domain (ASC)/caspase-1/interleukin (IL)-1ß & IL-18 pathway can turn on renal fibrosis is also comprehended. This review further outlines the involvement of dopamine and its associated G protein-coupled receptors (GPCRs), including D1-like (D1, D5) and D2-like (D2-D4) subtypes, in regulating this inflammation-linked renal dysfunction pathway. Hence, we identify D-related receptors as promising targets for renal disease management by inhibiting the functionality of the NLRP3 inflammasome.


Assuntos
Inflamassomos , Nefropatias , Proteína 3 que Contém Domínio de Pirina da Família NLR , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Animais , Nefropatias/metabolismo , Nefropatias/patologia , Nefropatias/etiologia , Rim/patologia , Rim/metabolismo , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia
8.
BMC Vet Res ; 20(1): 262, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890656

RESUMO

BACKGROUND: In recent years, anthropogenic activities have released heavy metals and polluted the aquatic environment. This study investigated the ability of the silica-stabilized magnetite (Si-M) nanocomposite materials to dispose of lead nitrate (Pb(NO3)2) toxicity in Nile tilapia and African catfish. RESULTS: Preliminary toxicity tests were conducted and determined the median lethal concentration (LC50) of lead nitrate (Pb(NO3)2) to Nile tilapia and African catfish to be 5 mg/l. The sublethal concentration, equivalent to 1/20 of the 96-hour LC50 Pb(NO3)2, was selected for our experiment. Fish of each species were divided into four duplicated groups. The first group served as the control negative group, while the second group (Pb group) was exposed to 0.25 mg/l Pb(NO3)2 (1/20 of the 96-hour LC50). The third group (Si-MNPs) was exposed to silica-stabilized magnetite nanoparticles at a concentration of 1 mg/l, and the fourth group (Pb + Si-MNPs) was exposed simultaneously to Pb(NO3)2 and Si-MNPs at the same concentrations as the second and third groups. Throughout the experimental period, no mortalities or abnormal clinical observations were recorded in any of the treated groups, except for melanosis and abnormal nervous behavior observed in some fish in the Pb group. After three weeks of sublethal exposure, we analyzed hepatorenal indices, oxidative stress parameters, and genotoxicity. Values of alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), urea, and creatinine were significantly higher in the Pb-intoxicated groups compared to the control and Pb + Si-MNPs groups in both fish species. Oxidative stress parameters showed a significant decrease in reduced glutathione (GSH) concentration, along with a significant increase in malondialdehyde (MDA) and protein carbonyl content (PCC) concentrations, as well as DNA fragmentation percentage in the Pb group. However, these values were nearly restored to control levels in the Pb + Si-MNPs groups. High lead accumulation was observed in the liver and gills of the Pb group, with the least accumulation in the muscles of tilapia and catfish in the Pb + Si-MNPs group. Histopathological analysis of tissue samples from Pb-exposed groups of tilapia and catfish revealed brain vacuolation, gill fusion, hyperplasia, and marked hepatocellular and renal necrosis, contrasting with Pb + Si-MNP group, which appeared to have an apparently normal tissue structure. CONCLUSIONS: Our results demonstrate that Si-MNPs are safe and effective aqueous additives in reducing the toxic effects of Pb (NO3)2 on fish tissue through the lead-chelating ability of Si-MNPs in water before being absorbed by fish.


Assuntos
Peixes-Gato , Ciclídeos , Chumbo , Fígado , Nitratos , Estresse Oxidativo , Dióxido de Silício , Poluentes Químicos da Água , Animais , Chumbo/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Dióxido de Silício/química , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Poluentes Químicos da Água/toxicidade , Nanocompostos/química , Nanocompostos/toxicidade , Quelantes/farmacologia , Rim/efeitos dos fármacos , Rim/patologia , Bioacumulação , Brânquias/efeitos dos fármacos , Brânquias/patologia , Dano ao DNA/efeitos dos fármacos
9.
Arch Pharm (Weinheim) ; : e2400331, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38943437

RESUMO

Considering the emergence of new anticancer drugs, in this review we emphasized and highlighted the recent reports and advances related to sulfamate-incorporating compounds with potential anticancer activity during the last 5 years (2020-2024). Additionally, we discussed their structure-activity relationship, clarifying their potent bioactivity as anticancer agents. Sulfamate derivatives hold promise as effective therapeutic candidates against cancer. By targeting biological targets associated with the development of cancer, such as steroid sulfatases (STS), carbonic anhydrases (CAs), microtubules, NEDD8-activating enzyme, small ubiquitin-like modifiers (SUMO)-activating enzyme (SAE), cyclin-dependent kinases (CDKs), breast cancer susceptibility gene 1 (BRCA1), and so on, this can furnish small molecules as anticancer lead candidates serving the drug discovery field. For example, compound 2, an STS inhibitor, demonstrated superior activity compared to its reference, irosustat, by fivefold. In addition, compound 21, an SAE, is under phase I clinical trials. Continued research into sulfamate derivatives holds potential for the development of novel therapeutic agents targeting various diseases.

10.
Eur J Med Chem ; 274: 116557, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38850857

RESUMO

Design and synthesis of novel 4-carboxamidopyrido[3,2-b]pyridine derivatives as novel rigid analogues of sorafenib are reported herein. The target compounds showed potent antiproliferative activities against a panel of NCI-60 cancer cell lines as well as hepatocellular carcinoma cell line. Compounds 8g and 9f were among the most promising derivatives in terms of effectiveness and safety. Therefore, they were further examined to demonstrate their ability to induce apoptosis and alter cell cycle progression in hepatocellular carcinoma cells. The most potent compounds were tested against a panel of kinases that indicated their selectivity against FMS kinase. Compounds 8g and 8h showed the most potent activities against FMS kinase with IC50 values of 21.5 and 73.9 nM, respectively. The two compounds were also tested in NanoBRET assay to investigate their ability to inhibit FMS kinase in cells (IC50 = 563 nM (8g) and 1347 nM (8h) vs. IC50 = 1654 nM for sorafenib). Furthermore, compounds 8g and 8h possess potent inhibitory activities against macrophages when investigated in bone marrow-derived macrophages (BMDM) assay (IC50 = 56 nM and 167 nM, respectively, 164 nM for sorafenib). The safety and selectivity of these compounds were confirmed when tested against normal cell lines. Their safety profile was further confirmed using hERG assay. In silico studies were carried out to investigate their binding modes in the active site of FMS kinase, and to develop a QSAR model for these new motifs.


Assuntos
Antineoplásicos , Proliferação de Células , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores de Proteínas Quinases , Piridinas , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Piridinas/farmacologia , Piridinas/química , Piridinas/síntese química , Proliferação de Células/efeitos dos fármacos , Relação Estrutura-Atividade , Estrutura Molecular , Apoptose/efeitos dos fármacos , Relação Dose-Resposta a Droga , Linhagem Celular Tumoral , Animais , Simulação de Acoplamento Molecular , Camundongos
11.
Arch Acad Emerg Med ; 12(1): e35, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38721447

RESUMO

Introduction: Proton pump inhibitors (PPI) are a commonly prescribed medication, but recent evidence suggests that their long-term use may lead to several adverse events. To address this issue, our study aims to assess patient awareness and pharmacist practices in educating patients about the potential risks associated with prolonged PPI use. Methods: Two questionnaires were developed by researchers and administered in the United Arab Emirates from June to August 2021 to gather insights from patients and pharmacists about the use of PPIs, their knowledge of potential side effects, and their experiences and attitudes toward receiving education about PPI side effects. The patients' knowledge was evaluated based on their cumulative correct answers to questions related to PPI's long-term adverse effects including increased fracture risk and hypocalcemia, vitamin B12 deficiency, hypomagnesemia, and the caution of abrupt withdrawal. All statistical analyses were conducted using SPSS 25.0 software. Results: Overall, 348 participants with a median age of 40 years participated in the survey, among them, 91 (26.14%) used various forms of PPI with 38% of users taking PPI as over-the-counter drugs. Patients had low knowledge about PPI side effects and their proper discontinuation with a median knowledge score of 0 (Interquartile range: 0-2) and only 22.2% of patients were familiar with at least three out of five asked harms. Those with lower knowledge were more likely to be Emirati compared to other nations (p=0.004) and aged over 30 years compared to their younger counterparts (p = 0.016). Few patients have obtained the relevant information from their physicians (25%) or pharmacists (7%). Inquiring 136 pharmacists, it was shown that the most common education was concerning vitamin B12 deficiency (62.5%) followed by fracture risk (58.09%) yet less than half (48%) of pharmacists instructed patients about the potential risk of hypomagnesemia. Almost all pharmacists (99%) agreed that there is a requirement for additional education on the possible harmful consequences of PPIs. Conclusion: The present study has established that a considerable proportion of PPI users in the UAE lack the necessary awareness about the potential adverse effects of PPI despite their extensive use in this country. The current pharmacist practice is inefficient for inculcating the potential harms of chronic PPI use and they are required to optimize their efforts to educate patients and bridge the knowledge gaps.

12.
Mol Biol Rep ; 51(1): 660, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750264

RESUMO

BACKGROUND: Cadmium (Cd) is a heavy metal with extremely harmful toxic effects on the brain. Quetiapine (QTP) has unique neuroprotective effects with anti-inflammatory and antioxidant actions. However, its neuroprotective effect against Cd-induced neurotoxicity has not been previously studied. METHODS: QTP was administered in 10 and 20 mg/kg doses, while Cd was given in a dose of 6.5 mg/kg. RESULTS: In our study, QTP dose-dependently attenuated neuronal injury by downregulating p-tau and ß-amyloid. QTP potently attenuates histological abrasions induced by Cd. QTP counteracted oxidative injury by decreasing neuronal MDA and increased GSH levels mediated by downregulating Keap1 and upregulating Nrf2 and HO-1. QTP mitigated inflammation by decreasing MPO and NO2 and neuronal cytokines TNF-α and IL-1ß and upregulating IL-10 levels mediated by NF-κB downregulation. Additionally, QTP counteracted Cd-induced pyroptosis by downregulating caspase-1, ASC, and NLRP3 protein levels. CONCLUSION: In conclusion, QTP mitigates neurotoxicity induced by Cd through suppression of inflammation, pyroptosis, and oxidative stress by controlling the NF-κB, Keap1/Nrf2, and pyroptosis signals.


Assuntos
Cádmio , Inflamação , Estresse Oxidativo , Piroptose , Fumarato de Quetiapina , Estresse Oxidativo/efeitos dos fármacos , Piroptose/efeitos dos fármacos , Animais , Cádmio/toxicidade , Fumarato de Quetiapina/farmacologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Camundongos , Fármacos Neuroprotetores/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/metabolismo , Antioxidantes/farmacologia , Anti-Inflamatórios/farmacologia , NF-kappa B/metabolismo
13.
Int J Biol Macromol ; 271(Pt 1): 132502, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38768915

RESUMO

A series of sulfonate and sulfamate derivatives bearing benzofuran or benzothiophene scaffold exhibited potent inhibitory effect on urease enzyme. Most of the derivatives exhibited significantly higher potency than thiourea, the standard inhibitor. Compound 1s was identified as the most potent urease inhibitor with an IC50 value of 0.42 ± 0.08 µM, which is 53-fold more potent than thiourea, positive control (IC50 = 22.3 ± 0.031 µM). The docking results further revealed the binding interactions towards the urease active site. Phenotypic screening revealed that compounds 1c, 1d, 1e, 1f, 1j, 1n, and 1t exhibit high potency against H. pylori with MIC values ranging from 0.00625 to 0.05 mM and IC50 values ranging from 0.0031 to 0.0095 mM, much more potent than the positive control, acetohydroxamic acid (MIC and IC50 values were 12.5 and 7.38 mM, respectively). Additional studies were performed to investigate the toxicity of these compounds against the gastric epithelial cell line (AGS) and their selectivity profile against E. coli, and five Lactobacillus species representative of the gut microflora. Permeability characteristics of the most promising derivatives were investigated in Caco-2 cell line. The results indicate that the compounds could be targeted in the GIT only without systemic side effects.


Assuntos
Antibacterianos , Benzofuranos , Inibidores Enzimáticos , Helicobacter pylori , Simulação de Acoplamento Molecular , Ácidos Sulfônicos , Tiofenos , Urease , Urease/antagonistas & inibidores , Urease/metabolismo , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/enzimologia , Ácidos Sulfônicos/química , Ácidos Sulfônicos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Benzofuranos/química , Benzofuranos/farmacologia , Humanos , Tiofenos/química , Tiofenos/farmacologia , Desenho de Fármacos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade , Descoberta de Drogas
14.
Poult Sci ; 103(7): 103771, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38749109

RESUMO

This work aimed to investigate the effects of dietary frankincense oil and ginger on the growth efficiency of growing Japanese quail, including live body weight, body weight gain, feed intake, feed conversion ratio, carcass traits, and physical characteristics of the meat. In total, 150 unsexed Japanese quail chicks that were 7 d old were utilized in the experiment. The chicks were randomly divided into 5 groups. Each group was divided into 3 replicates with ten birds in a completely randomized design. Group 1 received a basal diet without supplements and was used as a control group. Groups 2 and 3 received basal diets with 250 and 500 mg of ginger per kg of diet, respectively. Groups 4 and 5 received basal diets with 200 and 400 mg of frankincense oil per kg of diet, respectively. Results showed that BW of chicks received 500 mg of ginger and the 2 levels of frankincense oil at 5 wk of age, and 250 mg of ginger and 400 mg of frankincense oil at 6 wk significantly increased. BWG was significantly increased by using 500 mg of ginger and 2 levels of frankincense oil at 1 to 3 wk, 250 mg of ginger and 400 mg of frankincense oil at 3 to 6 wk, and 1 to 6 wk of age, in comparison with the control group. Treatments insignificantly influenced feed intake (FI), and feed conversion ratio (FCR) was improved considerably by using 250 mg of ginger and 400 mg of frankincense at 3 to 6 wk and 1 to 6 wk of age, respectively. Gizzard% was notably reduced with 200 mg of frankincense oil. The pH value of meat was significantly increased by having 2 levels of ginger. Still, water holding capacity and tenderness significantly decreased owing to 500 mg of ginger and 400 mg of frankincense oil. We can conclude that adding ginger and frankincense oil to Japanese quail diets may be beneficial.


Assuntos
Ração Animal , Coturnix , Dieta , Suplementos Nutricionais , Carne , Zingiber officinale , Animais , Zingiber officinale/química , Ração Animal/análise , Dieta/veterinária , Suplementos Nutricionais/análise , Coturnix/crescimento & desenvolvimento , Coturnix/fisiologia , Carne/análise , Distribuição Aleatória , Masculino , Franquincenso/administração & dosagem , Franquincenso/química , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Óleos de Plantas/administração & dosagem , Óleos de Plantas/farmacologia
15.
RSC Adv ; 14(24): 17295, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38812962

RESUMO

Expression of concern for 'Antibacterial and antibiofilm activities of silver-decorated zinc ferrite nanoparticles synthesized by a gamma irradiation-coupled sol-gel method against some pathogenic bacteria from medical operating room surfaces' by M. I. A. Abdel Maksoud et al., RSC Adv., 2021, 11, 28361-28374, https://doi.org/10.1039/D1RA04785J.

16.
Int Immunopharmacol ; 136: 112335, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38815349

RESUMO

Chlorpyrifos (CPF) is a widely used organophosphate insecticide in agriculture and homes. Exposure to organophosphates is associated with neurotoxicity. Fluoxetine (FLX) is a selective serotonin reuptake inhibitor (SSRI) that is widely prescribed for depression and anxiety disorders. Studies have shown that FLX has neuroprotective, anti-inflammatory, antioxidant, and antiapoptotic effects. The molecular mechanisms underlying FLX are not fully understood. This work aimed to investigate the potential neuroprotective effect of FLX on CPF-induced neurotoxicity and the underlying molecular mechanisms involved. Thirty-two rats were randomly divided into four groups: (I) the vehicle control group; (II) the FLX-treated group (10 mg/kg/day for 28 days, p.o); (III) the CPF-treated group (10 mg/kg for 28 days); and (IV) the FLX+CPF group. FLX attenuated CPF-induced neuronal injury, as evidenced by a significant decrease in Aß and p-Tau levels and attenuation of cerebral and hippocampal histological abrasion injury induced by CPF. FLX ameliorated neuronal oxidative stress, effectively reduced MDA production, and restored SOD and GSH levels through the coactivation of the PPARγ and SIRT1 proteins. FLX counteracted the neuronal inflammation induced by CPF by decreasing MPO, NO, TNF-α, IL-1ß, and IL-6 levels by suppressing NF-κB and JAK1/STAT3 activation. The antioxidant and anti-inflammatory properties of FLX help to prevent CPF-induced neuronal intoxication.


Assuntos
Clorpirifos , Fluoxetina , Janus Quinase 1 , NF-kappa B , Fármacos Neuroprotetores , PPAR gama , Fator de Transcrição STAT3 , Transdução de Sinais , Sirtuína 1 , Animais , Fator de Transcrição STAT3/metabolismo , Sirtuína 1/metabolismo , NF-kappa B/metabolismo , PPAR gama/metabolismo , Janus Quinase 1/metabolismo , Masculino , Fluoxetina/farmacologia , Fluoxetina/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Clorpirifos/toxicidade , Ratos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Neurônios/efeitos dos fármacos , Neurônios/patologia , Estresse Oxidativo/efeitos dos fármacos , Inseticidas/toxicidade , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Ratos Sprague-Dawley , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/patologia
17.
Artigo em Inglês | MEDLINE | ID: mdl-38695909

RESUMO

Lignans are biologically active compounds widely distributed, recognized, and identified in seeds, fruits, and vegetables. Lignans have several intriguing bioactivities, including anti-inflammatory, antioxidant, and anticancer activities. Nrf2 controls the expression of many cytoprotective genes. Activation of Nrf2 is a promising therapeutic approach for treating and preventing diseases resulting from oxidative injury and inflammation. Lignans have been demonstrated to stimulate Nrf2 signaling in a variety of in vitro and experimental animal models. The review summarizes the findings of fourteen lignans (Schisandrin A, Schisandrin B, Schisandrian C, Magnolol, Honokiol, Sesamin, Sesamol, Sauchinone, Pinoresinol, Phyllanthin, Nectandrin B, Isoeucommin A, Arctigenin, Lariciresinol) as antioxidative and anti-inflammatory agents, affirming how Nrf2 activation affects their pharmacological effects. Therefore, lignans may offer therapeutic candidates for the treatment and prevention of various diseases and may contribute to the development of effective Nrf2 modulators.

18.
Int Immunopharmacol ; 132: 112011, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38581991

RESUMO

Liver cancer (LC) is the sixth most common disease and the third most common cause of cancer-related mortality. The WHO predicts that more than 1 million deaths will occur from LC by 2030. Hepatocellular carcinoma (HCC) is a common form of primary LC. Today, the management of LC involves multiple disciplines, and multimodal therapy is typically selected on an individual basis, considering the intricate interactions between the patient's overall health, the stage of the tumor, and the degree of underlying liver disease. Currently, the treatment of cancers, including LC, has undergone a paradigm shift in the last ten years because of immuno-oncology. To treat HCC, immune therapy approaches have been developed to enhance or cause the body's natural immune response to specifically target tumor cells. In this context, immune checkpoint pathway inhibitors, engineered cytokines, adoptive cell therapy, immune cells modified with chimeric antigen receptors, and therapeutic cancer vaccines have advanced to clinical trials and offered new hope to cancer patients. The outcomes of these treatments are encouraging. Additionally, treatment using stem cells is a new approach for restoring deteriorated tissues because of their strong differentiation potential and capacity to release cytokines that encourage cell division and the formation of blood vessels. Although there is no proof that stem cell therapy works for many types of cancer, preclinical research on stem cells has shown promise in treating HCC. This review provides a recent update regarding the impact of immunotherapy and stem cells in HCC and promising outcomes.


Assuntos
Carcinoma Hepatocelular , Imunoterapia , Neoplasias Hepáticas , Transplante de Células-Tronco , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/imunologia , Imunoterapia/métodos , Animais , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/imunologia
19.
Life Sci ; 347: 122642, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38641047

RESUMO

Drug repurposing involves the investigation of existing drugs for new indications. It offers a great opportunity to quickly identify a new drug candidate at a lower cost than novel discovery and development. Despite the importance and potential role of drug repurposing, there is no specific definition that healthcare providers and the World Health Organization credit. Unfortunately, many similar and interchangeable concepts are being used in the literature, making it difficult to collect and analyze uniform data on repurposed drugs. This research was conducted based on understanding general criteria for drug repurposing, concentrating on liver diseases. Many drugs have been investigated for their effect on liver diseases even though they were originally approved (or on their way to being approved) for other diseases. Some of the hypotheses for drug repurposing were first captured from the literature and then processed further to test the hypothesis. Recently, with the revolution in bioinformatics techniques, scientists have started to use drug libraries and computer systems that can analyze hundreds of drugs to give a short list of candidates to be analyzed pharmacologically. However, this study revealed that drug repurposing is a potential aid that may help deal with liver diseases. It provides available or under-investigated drugs that could help treat hepatitis, liver cirrhosis, Wilson disease, liver cancer, and fatty liver. However, many further studies are needed to ensure the efficacy of these drugs on a large scale.


Assuntos
Reposicionamento de Medicamentos , Hepatopatias , Reposicionamento de Medicamentos/métodos , Humanos , Hepatopatias/tratamento farmacológico , Biologia Computacional/métodos , Descoberta de Drogas/métodos
20.
Cureus ; 16(1): e52015, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38344500

RESUMO

BACKGROUND AND AIM: Surgical site infections (SSIs) are one of the significant complications detected after surgical procedures. Recent studies have highlighted the antimicrobial, wound-healing, and immunological properties of vitamin D. Therefore, this study examined the association between levels of preoperative vitamin D and SSI occurrence in Saudi Arabia. METHODS: We conducted this retrospective observational study among patients who underwent surgery at King Faisal Medical Complex, Saudi Arabia. We included data from patients who underwent surgery between January 2021 and October 2023 in the study. If vitamin D concentrations were not measured at admission, patients were excluded from the final analysis. The researchers performed statistical analysis using the computer program Statistical Package for Social Sciences (SPSS), version 26.0 (IBM Corp., Armonk, NY). The significant level was considered when the p-value was less than 0.05. RESULTS: The study included 130 patients with a mean (SD) age of 26.98 (9.3) years. Most patients were females (n = 92, 70.8%), had diabetes mellitus disease (n = 121, 93.1%), had a vitamin D deficiency (<30 ng/dl) (n = 106, 81.5%), and underwent cesarean section (n = 80, 61.5%). The mean (SD) vitamin D level among patients was 19.9 (9.7) ng/dl, and the mean (SD) hemoglobin level was almost normal (12.30 (2.1) g/dl). Out of 40.8% (n = 53) of patients, the most detected pathogenic bacteria was Escherichia coli, followed by Staphylococcus aureus (n = 11, 44%, and n = 7, 25%, respectively). Furthermore, vitamin D deficiency significantly impacted positive SSI; patients with insufficient levels had a higher infection rate compared to those with sufficient levels (n = 58, 54.7% vs. n = 7, 29.2%, p-value = 0.024). A longer surgery duration did not increase the risk of SSI (p-value = 0.047). Patients with class 3 wounds were more prone to SSI than those with class 2 wounds (n = 12, 100% vs. n = 53, 44.9%, p-value<0.001). CONCLUSION: This study provides important evidence supporting the relationship between vitamin D deficiency and SSI incidence. Patients with lower levels of vitamin D reported a higher incidence of SSIs. Healthcare providers should pay attention to the high prevalence of vitamin D deficiency among patients undergoing surgery. Screening for vitamin D deficiency and implementing convenient interventions to optimize vitamin D levels could help reduce the incidence of SSIs. Further research with larger sample sizes, more diverse populations, and different surgery types is necessary to validate these findings and explore additional factors influencing SSI development.

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