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1.
Discov Nano ; 19(1): 123, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39105979

RESUMO

Resin cement integrated with zein-incorporated magnesium oxide nanoparticles has previously been found to inhibit oral microbes and decrease bacterial biofilm. However, the bond strength and surface features of this biomaterial have yet to be investigated. The objective of this study was to evaluate the shear bond strength, mode of fracture, and surface roughness of resin cement modified with zein-incorporated magnesium oxide nanoparticles. Characterization of the cement was performed by X-ray diffraction, field emission scanning electron microscopy, and Fourier transform infrared spectroscopy. 126 human teeth were divided into 3 groups and cemented to lithium disilicate ceramic using resin cement with zein-incorporated magnesium oxide nanoparticles at concentrations of 0%, 1%, and 2% (n = 42). 21 samples of each group were subjected to the shear bond strength test, while the other 21 underwent thermocycling for 10,000 cycles before the test, after which all samples were evaluated for the mode of fracture. To assess surface roughness, resin cement disks were analyzed by a profilometer before and after undergoing thermocycling for 10,000 cycles. The shear bond strength of the cement with 1% and 2% nanoparticles was significantly higher than the control before thermocycling. The mode of fracture was found to be mainly adhesive with all groups, with the unmodified cement presenting the highest cohesive failure. There was no significant difference in surface roughness between the groups before or after thermocycling. The addition of zein-incorporated magnesium oxide nanoparticles to resin cement improved or maintained the shear bond strength and surface roughness of the resin cement.

2.
Infect Dis Rep ; 16(4): 770-782, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39195010

RESUMO

OBJECTIVE: This cross-sectional-survey-based study aimed to investigate the severity of side-effects from Coronavirus disease (COVID-19) mRNA (Pfizer, Moderna), viral vector DNA (Oxford-AstraZeneca, J&J/Janssen), inactivated virus (Sinopharm, Sinovac), and other vaccines among healthcare workers (HCWs) in Saudi Arabia, focusing on their impact on work attendance. METHODS: A total of 894 HCWs residing in Saudi Arabia participated in this study from March 2023 to May 2023. Participants completed an online questionnaire assessing demographic information, vaccination status, comorbidities, vaccine side-effects, and missed work information after vaccination. Descriptive statistics and chi-square tests were used for data analysis. RESULTS: The majority of participants were female (83.7%) and aged 25-34 years (42.8%). Most participants were predominantly vaccinated with mRNA vaccines. Common side-effects included pain at the injection site, fatigue, fever, and chills. However, no significant association was found between vaccine type, side-effects, and work absenteeism. While demographic factors such as age and healthcare profession did not influence work absenteeism, variations were observed among different racial groups. CONCLUSION: COVID-19 vaccination among HCWs in Saudi Arabia is associated with common side-effects, but their impact on work attendance is not significant. Understanding these implications can inform strategies to support the healthcare workforce and mitigate the impact on patient care and staffing during the ongoing COVID-19 pandemic.

3.
Mol Biol Cell ; : mbcE24050216, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39167497

RESUMO

The regulation of maternal mRNAs is essential for proper oogenesis, the production of viable gametes, and to avoid birth defects and infertility. Many oogenic RNA-binding proteins have been identified with roles in mRNA metabolism, some of which localize to dynamic ribonucleoprotein granules and others that appear dispersed. Here, we use a combination of in vitro condensation assays and the in vivo C. elegans oogenesis model to characterize the properties of the conserved KH-domain MEX-3 protein and to identify novel regulators of MEX-3 and three other translational regulators. We demonstrate that MEX-3 undergoes phase separation and appears to have intrinsic gel-like properties in vitro. We also identify novel roles for the CCT chaperonin and actin in preventing ectopic RNA-binding protein condensates in maturing oocytes that appear to be independent of MEX-3 folding. The CCT chaperonin and actin also oppose the expansion of ER sheets that may promote ectopic condensation of RNA-binding proteins. These novel regulators of condensation are also required for the translational repression of maternal mRNA which is essential for oocyte quality and fertility. The identification of this regulatory network may also have implications for understanding the role of hMex3 phase transitions in cancer.

4.
Poult Sci ; 103(9): 103880, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39094436

RESUMO

Antibiotic overuse in poultry feeds has disastrous implications; consequently, long-term alternatives must be developed. As a result, the current study aims to assess the impact of Aspergillus niger filtrate (ANF) high in organic acids grown on agro-industrial residue of faba bean (AIRFB) on quail diet, as well as their influence on bird productivity, digestion, carcass yield, blood chemistry, and intestinal microbiota. A total of 240 Japanese quails (aged 7 d) were used in this study, divided equally among 5 experimental groups with 48 quails each. Group 1 (G1) received a basal diet without any ANF, group 2 (G2) received a basal diet supplemented with 0.5 mL ANF/kg diet, group 3 (G3) received a basal diet supplemented with 1.0 mL ANF/kg diet, group 4 (G4) received a basal diet supplemented with 1.5 mL ANF/kg diet, and group 5 (G5) received a basal diet supplemented with 2 mL ANF/kg diet. The performance parameters were monitored at 1 to 3, 3 to 5, and 1 to 5 wk. Adding ANF increased body weight at 3 and 5 wk, as well as body weight gain at 1 to 3, 3 to 5, and 1 to 5 wk, compared to the control diet. The ANF fed quails had the highest feed conversion ratio compared to the control group. The addition of ANF to the quail diet had no effect on the weight of the carcass, gizzard, heart, liver, giblets, or dressing; however, it did lower triglycerides, low-density lipoprotein, and very low-density lipoprotein while increasing high-density lipoprotein levels. The quail groups that received ANF had enhanced immunological indices such as IgG, IgM, IgA, and lysozymes. It also increased the levels of superoxide dismutase and total antioxidant contents, as well as catalase, and digestive enzymes such as protease, amylase, and lipase. However, it lowered the blood MDA levels compared to control. It has been demonstrated that the total gut microbiota, Escherichia coli, total coliforms, and the population of Salmonella are all reduced in ANF-fed quails. Histological examination of ANF quails' liver and intestinal sections revealed normal hepatic parenchyma, typical leaf-like intestinal villi, and comparatively short and frequently free lumina. In conclusion, Japanese quail showed improvements in performance, digestive enzymes, antioxidant indices, immunity, and capacity to reduce intestinal pathogenic bacteria after consuming diet supplemented with ANF.


Assuntos
Ração Animal , Antioxidantes , Coturnix , Dieta , Suplementos Nutricionais , Microbioma Gastrointestinal , Vicia faba , Animais , Coturnix/fisiologia , Ração Animal/análise , Dieta/veterinária , Suplementos Nutricionais/análise , Vicia faba/química , Antioxidantes/metabolismo , Fermentação , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Aspergillus niger , Análise Química do Sangue/veterinária , Masculino , Distribuição Aleatória
5.
Poult Sci ; 103(10): 104089, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-39142030

RESUMO

Avian chlamydiosis is a serious avian infection that carries a significant zoonotic danger to the poultry industry. The respiratory co-infections caused by the low pathogenic avian influenza virus H9N2 (LPAIV H9N2) also cause significant financial losses in the poultry industry. The purpose of this study was to examine the pathogenicity of Chlamydophila psittaci, and LPAIV H9N2 individually and in combination in broiler chickens, as well as to determine whether or not aqueous neem (Azadirachta indica) leaf extract is effective against infections caused by these pathogens. Therefore, 120 broiler cobb chicks were equally divided into 4 groups (30 birds each) with triplicates with 10 birds. Broilers in group 1 (G1) were infected with only C. psittaci, broilers in group 2 (G2) were infected with only LPAIV H9N2, broilers in group 3 (G3) were infected with C. psittaci and LPAIV H9N2, and broilers in group 4 (G4) remained not challenged and non-treated with any therapeutic or preventive treatment (negative control). At 21 d postinfection (dpi), birds in G1, G2, and G3 were divided into 3 subgroups of 10 birds each: subgroup (A) remained infected and untreated (positive control), subgroup (B) infected and received oxytetracycline for 5 consecutive d, and subgroup (C) infected and received 8% aqueous neem leaf extract for 5 consecutive d. The multiplication of C. psittaci in birds in G1, in various tissues was evaluated using Giemsa staining and the data showed that multiplication was much higher in the lung, spleen, and liver from 6 h to 21 dpi, but low in the heart from 8 to 21 dpi. During simultaneous co-infection in G3, the birds developed significant clinical symptoms and postmortem lesions (PM). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect viral shedding from oropharyngeal and cloacal swabs between 2 dpi and 8 dpi, with cycle threshold (CT) values ranging from 22 to 24. In contrast, bacterial shedding began 6 h after infection and continued until 21 dpi, with CT values ranging from 23 to 26. Administration of an aqueous neem leaf extract at an 8% concentration (Group C) resulted in a numerical rise in average body weight across all treatment groups in the third and fourth week, as well as a reduction in LPAIV H9N2 and C. psittaci replication in the respiratory and gut of treated birds compared to those treated with oxytetracycline (Group B). Overall, respiratory co-infections pose a considerable risk to the poultry business, which is a big threat. To control C. psittaci and LPAIV H9N2 in broiler chickens, oral supplementation of 8% aqueous neem leaf extract is recommended. This treatment improves the birds' performance, as evidenced by an increase in their average body weight. In addition, the application of 8% aqueous neem leaf extract lowers C. psittaci replication within tissues and diminishes LPAIV H9N2 shedding.

6.
Bioorg Chem ; 152: 107760, 2024 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-39197383

RESUMO

A novel series of thiazole derivatives with pyrazole scaffold 16a-l as hybrid rosiglitazone/celecoxib analogs was designed, synthesized and tested for its PPAR-γ activation, α-glucosidase, α-amylase and COX-2 inhibitory activities. Regarding the anti-diabetic activity, all compounds were assessed in vitro against PPAR-γ activation, α-glucosidase and α-amylase inhibition in addition to in vivo hypoglycemic activity (one day and 15 days studies). Compounds 16b, 16c, 16e and 16 k showed good PPAR-γ activation (activation % ≈ 72-79 %) compared to that of the reference drug rosiglitazone (74 %). In addition, the same derivatives 16b, 16c, 16e and 16 k showed the highest inhibitory activities against α-glucosidase (IC50 = 0.158, 0.314, 0.305, 0.128 µM, respectively) and against α-amylase (IC50 = 32.46, 23.21, 7.74, 35.85 µM, respectively) compared to the reference drug acarbose (IC50 = 0.161 and 31.46 µM for α-glucosidase and α-amylase, respectively). The most active derivatives 16b, 16c, 16e and 16 k also revealed good in vivo hypoglycemic effect comparable to that of rosiglitazone. In addition, compounds 16b and 16c had the best COX-2 selectivity index (S.I. = 18.7, 31.7, respectively) compared to celecoxib (S.I. = 10.3). In vivo anti-inflammatory activity of the target derivatives 16b, 16c, 16e and 16 k supported the results of in vitro screening as the derivatives 16b and 16c (ED50 = 8.2 and 24 mg/kg, respectively) were more potent than celecoxib (ED50 = 30 mg/kg). In silico docking, ADME, toxicity, and molecular dynamic studies were carried out to explain the interactions of the most active anti-diabetic and anti-inflammatory compounds 16b, 16c, 16e and 16 k with the target enzymes in addition to their physiochemical parameters.

7.
Curr Alzheimer Res ; 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39136502

RESUMO

BACKGROUND: Alzheimer's disease (AD) affects approximately 50 million people globally and is expected to triple by 2050. Arctiin is a lignan found in the Arctium lappa L. plant. Arctiin possesses anti-proliferative, antioxidative and anti-adipogenic. OBJECTIVES: We aimed to explore the potential therapeutic effects of Arctiin on rats with AD by evaluating the expression of TLR4, NLRP3, STAT3, TGF-ß, cyclin D1, and CDK2. METHODS: AD was induced in rats by administering 70 mg/kg of aluminum chloride through intraperitoneal injection daily for six weeks. After inducing AD, some rats were treated with 25 mg/kg of Arctiin daily for three weeks through oral gavage. Furthermore, to examine the brain tissue structure, hippocampal sections were stained with hematoxylin/eosin and anti-TLR4 antibodies. The collected samples were analyzed for gene expression and protein levels of TLR4, NLRP3, STAT3, TGF-ß, cyclin D1, and CDK2. RESULTS: In behavioral tests, rats showed a significant improvement in their behavior when treated with Arctiin. Microimages stained with hematoxylin/eosin showed that Arctiin helped to improve the structure and cohesion of the hippocampus, which was previously impaired by AD. Furthermore, Arctiin reduced the expression of TLR4, NLRP3, STAT3, TGF-ß, cyclin D1, and CDK2. CONCLUSION: Arctiin can enhance rats' behavior and structure of the hippocampus in AD rats. This is achieved through its ability to reduce the expression of both TLR4 and NLRP3, hence inhibiting the inflammasome pathway. Furthermore, Arctiin can improve tissue fibrosis by regulating STAT3 and TGF-ß. Lastly, it can block the cell cycle proteins cyclin D1 and CDK2.

8.
J Environ Manage ; 367: 122018, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39111007

RESUMO

Climate change has a significant impact on dissolved oxygen (DO) concentrations, particularly in coastal inlets where numerous human activities occur. Due to the various water quality (WQ), hydrological, and climatic parameters that influence this phenomenon, predicting and modeling DO variation is a challenging process. Accordingly, this study introduces an innovative Deep Learning Neural Network (DLNN) methodology to model and predict DO concentrations for the Egyptian Rashid coastal inlet, leveraging field-recorded WQ and hydroclimatic datasets. Initially, statistical and exploratory data analyses are performed to provide a thorough understanding of the relationship between DO fluctuations and associated WQ and hydroclimatic stressors. As an initial step towards developing an effective DO predictive model, conventional Machine Learning (ML) approaches such as Gaussian Process Regression (GPR), Support Vector Regression (SVR), and Decision Tree Regressor (DTR) are employed. Subsequently, a DLNN approach is utilized to validate the prediction capabilities of the investigated conventional ML approaches. Finally, a sensitivity analysis is conducted to evaluate the impact of WQ and hydroclimatic parameters on predicted DO. The outcomes demonstrate that DLNN significantly improves DO prediction accuracy by 4% compared to the best-performing ML approach, achieving a Correlation Coefficient of 0.95 with a root mean square error (RMSE) of 0.42 mg/l. Solar radiation (SR), pH, water levels (WL), and atmospheric pressure (P) emerge as the most significant hydroclimatic parameters influencing DO fluctuations. Ultimately, the developed models could serve as effective indicators for coastal authorities to monitor DO changes resulting from accelerated climate change along the Egyptian coast.


Assuntos
Mudança Climática , Aprendizado Profundo , Oxigênio , Oxigênio/química , Oxigênio/análise , Redes Neurais de Computação , Qualidade da Água , Monitoramento Ambiental/métodos
9.
Bioorg Chem ; 150: 107622, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38996545

RESUMO

Novel thieno[2,3-d]pyrimidine analogues were designed, synthesized and evaluated for anti-proliferative activity against HepG-2, PC-3 and MCF-7 cancer cell lines. In addition, WI-38 normal cell line was used to explore the safety of all the tested compounds. Compounds 2 (IC50 = 4.29 µM HePG-2, 10.84 µM MCF-7), 6 (IC50 = 14.86 µM HePG-2, 8.04 µM PC-3 and 12.90 µM MCF-7) and 17 (IC50 = 9.98 µM HePG-2, 33.66 µM PC-3 and 14.62 µM MCF-7) were the most promising candidates on the tested cancer cells with high selective toxicity-sparing normal cells. A further mechanistic evaluation revealed promising kinase inhibitory activity, where compound 2 inhibited VEGFR-2 and AKT at IC50 = 0.161 and 1.06 µM, respectively, Furthermore, derivative 6 inhibited VEGFR-2 and AKT at IC50 = 0.487 and 0.364 µM, respectively, while compound 17 showed IC50 = 0.164 and 0.452 µM, respectively. Moreover, compounds 2, 6 resulted in G1 phase cell cycle arrest while candidate 17 arrest cell cycle at G2/M phase. Similar to the apoptosis results, compound 17 showed the highest autophagic induction among the evaluated derivatives. Finally, docking studies were conducted to assess the binding patterns of these active derivatives. The results showed that the binding patterns inside the active sites of both the VEGFR-2 and AKT-1 (allosteric pocket) crystal structures were identical to the reference ligands.


Assuntos
Antineoplásicos , Apoptose , Autofagia , Proliferação de Células , Relação Dose-Resposta a Droga , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores de Proteínas Quinases , Proteínas Proto-Oncogênicas c-akt , Pirimidinas , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Humanos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Pirimidinas/farmacologia , Pirimidinas/síntese química , Pirimidinas/química , Apoptose/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Autofagia/efeitos dos fármacos , Relação Estrutura-Atividade , Proliferação de Células/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Estrutura Molecular , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Simulação de Acoplamento Molecular , Linhagem Celular Tumoral
10.
An Acad Bras Cienc ; 96(3): e20230646, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39046020

RESUMO

This work investigated the antioxidant and hepatoprotective activities of lemongrass extract and its effects on rat hepatotoxicity. The lemongrass extract (LGE) contains bioactive components such as phenolic acids, flavonoid components, vitamin C, fibers, and tannins. The LGE had high phenolic content (397 mg/100g) and flavonoids (164 mg/100g), influencing its antioxidant activity of 91.25%. Additionally, it inhibited 81% of breast cancer, also, inhibited the growth of pathogenic bacteria and Candida at a concentration of 20-40 µg/mL. Additionally, it inhibited SARS-Cov-2 by 75%; however, increasing the activity of Cas-3. Quercetin-3-rhamnoside was the main phenolic compound in the HPLC profile; the phenolic compounds may be attributable to the beneficial effects of LGE. In this study, the CCl4-challenged rats delivered two levels of LGE (100 and 300 mg/kg BW). LGE reduced ALT, AST, creatinine and urea by 50 and 37%, respectively. Generally, LGE mitigated the oxidative stress induced by CCl4, which is evident in the histology of liver and kidney tissues, where significant improvement, with no cytoplasmic degradation in undamaged liver hepatocytes, improved kidney performance and shape. It can be concluded that polyphenolic-rich LGE can mitigate the oxidative stress induced by CCl4 and other parameters while enhancing kidney and liver performance.


Assuntos
Antioxidantes , Antivirais , Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas , Extratos Vegetais , Folhas de Planta , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Antioxidantes/farmacologia , Ratos , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Antivirais/farmacologia , Folhas de Planta/química , Masculino , Ratos Wistar , Anti-Infecciosos/farmacologia , Fígado/efeitos dos fármacos , Fígado/patologia
11.
J Dent ; 149: 105271, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39069250

RESUMO

INTRODUCTION: Zein-incorporated magnesium oxide nanoparticles (zMgO NPs) can influence the mechanical properties of dental materials. However, the effect of this addition on the mechanical properties of resin composite has yet to be investigated. The objective of this study was to add various concentrations of zMgO NPs to conventional, flowable, and bulk-fill composite and assess the effect on the compressive strength, flexural strength, and microhardness. METHODOLOGY: 150 samples each of conventional composite, flowable composite, and bulk-fill composite (n = 450) were enhanced with concentrations of zMgO NPs at 0 %, 0.3 %, 0.5 %, 1 %, and 2 % (n = 30). 10 samples of each group were randomly allotted to the compressive strength, flexural strength, or hardness test. Characterization of the specimens was performed by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, and transmission electron microscopy. Two-way ANOVA test was used to compare between groups, and one-way ANOVA followed by Tukey's test was done at p = 0.05 to determine significance. RESULTS: Characterization yielded a uniform distribution of nanoparticles in the matrix and the formation of a new hybrid composite that maintained its properties. Composite of all types enhanced with 0.3 % and 0.5 % zMgO NPs demonstrated a statistically significant increase in compressive strength, flexural strength, and hardness when compared to the control (p < 0.05). The bulk-fill composite with zMgO NPs concentrations of all groups demonstrated a statistically significant increase (p < 0.05) in hardness when compared to the control. CONCLUSION: The modified composites' compressive strength, flexural strength, and hardness improved or remained consistent. CLINICAL SIGNIFICANCE: An improved dental resin composite will enhance the quality of care and patient experience. The augmented strength and hardness of resin composite is desirable in prolonging the durability of the restoration.

12.
Int Dent J ; 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39079838

RESUMO

INTRODUCTION: Zein-incorporated magnesium oxide nanoparticles (zMgO NPs) were found to be effective against the bacteria S. mutans, S. aureus, E. faecalis and C. albicans, and can impart this antimicrobial effect on the resin composite it is integrated with. However, the effect of different light curing systems on the mechanical properties of this novel biomaterial has yet to be investigated. The objective of this study was to assess the effect of light-emitting diode (LED) and quarts-tungsten halogen (QTH) light curing systems on the compressive strength, flexural strength, and microhardness of bulk-fill resin composite modified with zMgO NPs. METHODOLOGY: A Teflon mold was used to fabricate 180 bulk-fill composite samples with concentrations of zMgO NPs at 0%, 0.3% and 0.5% (n = 60). Samples of each group were allocated to light curing by LED or QTH, after which 10 samples of each group were allotted to a mechanical test. Characterization of the specimens was performed by X-ray diffraction, field emission scanning electron microscopy and Fourier transform infrared spectroscopy. Two-way ANOVA and Tukey's post-hoc test was conducted at P = .05 to determine significance. RESULTS: The characterization revealed a uniform distribution of nanoparticles in the matrix and the formation of a new hybrid composite that maintained its properties. The compressive strength of the 0.3% zMgO composite for the QTH group significantly increased, while the remaining groups underwent no significant change. There was no significant difference among the groups for the flexural strength and microhardness tests. CONCLUSION: The modified composites' compressive strength, flexural strength, and microhardness improved or remained consistent. Long-term clinical studies can further substantiate the enhanced resin composite. CLINICAL RELEVANCE: The modified composite will exhibit similar or improved mechanical properties whether an LED or QTH light cure device is used. The addition of an antimicrobial effect to bulk-fill resin composite will aid in the prevention of secondary caries.

13.
bioRxiv ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-39005301

RESUMO

The regulation of maternal mRNAs is essential for proper oogenesis, the production of viable gametes, and to avoid birth defects and infertility. Many oogenic RNA-binding proteins have been identified with roles in mRNA metabolism, some of which localize to dynamic ribonucleoprotein granules and others that appear dispersed. Here, we use a combination of in vitro condensation assays and the in vivo C. elegans oogenesis model to determine the intrinsic properties of the conserved KH-domain MEX-3 protein and to identify novel regulators of MEX-3 and the Lsm protein, CAR-1. We demonstrate that MEX-3 undergoes liquid-liquid phase separation and appears to have intrinsic gel-like properties in vitro . We also identify novel roles for the CCT chaperonin and actin in preventing ectopic RNA-binding protein condensates in maturing oocytes that appear to be independent of MEX-3 folding. CCT and actin also oppose the expansion of ER sheets that may promote ectopic condensation of RNA-binding proteins that are associated with de-repression of maternal mRNA. This regulatory network is essential to preserve oocyte quality, prevent infertility, and may have implications for understanding the role of hMex3 phase transitions in cancer. Significance statement: The molecular mechanisms that regulate phase transitions of oogenic RNA-binding proteins are critical to elucidate but are not fully understood.We identify novel regulators of RNA-binding protein phase transitions in maturing oocytes that are required to maintain translational repression of maternal mRNAs and oocyte quality.This study is the first to elucidate a regulatory network involving the CCT chaperonin, actin, and the ER for phase transitions of RNA-binding proteins during oogenesis. Our findings for the conserved MEX-3 protein may also be applicable to better understanding the role of hMex3 phase transitions in cancer.

14.
Mar Pollut Bull ; 206: 116613, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39053258

RESUMO

Pesticide contamination has become a global concern. Pesticides can sorb onto suspended particles and deposit into the sedimentary layers of aquatic environments, resulting in ecosystem degradation, pollution, and diseases. Pesticides impact the behavior of aquatic environments by contaminating organic matter in water, which serves as the primary food source for aquatic food webs. Pesticide residues can increase ammonium, nitrite, nitrate, and sulfate in aquatic systems; thus, threatening ecological environment and human health. Several physical, chemical, and biological methodologies have been implemented to effectively remove pesticide traces from aquatic environments. The present review highlights the potential consequences of pesticide exposure on fish and humans, focusing on the (epi)genetic alterations affecting growth, behavior, and immune system. Mitigation strategies (e.g., bioremediation) to prevent/minimize the detrimental impacts of pesticides are also discussed. This review aims to shed light on the awareness in reducing the risk of water pollution for safe and sustainable pesticide management.


Assuntos
Praguicidas , Poluentes Químicos da Água , Praguicidas/análise , Poluentes Químicos da Água/análise , Humanos , Animais , Ecossistema , Monitoramento Ambiental , Peixes
15.
Ecotoxicol Environ Saf ; 282: 116726, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39047360

RESUMO

Acid rain and invasive plants have quintessential adverse impacts on terrestrial ecosystems. As an environmentally safe method for disposal of invasive plants, we tested the effect of biochar produced from these plants in altering soil deterioration under acid rain as compared with lime. Given the impacts of the feedstock type and soil properties on the response of soil to the added biochar, we hypothesized that the microbial community and functions would respond differently to the charred invasive plants under acid rain. A pot experiment was conducted to examine the response of soil microbiomes and functions to the biochar produced from Blackjack (Biden Pilosa), Wedelia (Wedelia trilobata), and Bitter vine (Mikania micrantha Kunth), or quicklime (CaO) at a rate of 1 % (w/w) under acid rain. Like soil pH, the nutrient contents (nitrogen, phosphorus, and potassium), calcium, and cation exchange capacity (CEC) were important as dominant edaphic factors affecting soil microbial community and functionality. In this respect, lime decreased nutrients availability, driven by 11-fold, 44 %, and 2-fold increments in calcium content, pH, and C/N ratio. Meanwhile, biochar improved nutrients availability under acid rain owing to maintaining a neutral pH (∼6.5), increasing calcium (by only 2-fold), and improving CEC, water repellency, and aggregation while decreasing the C/N ratio and aluminum content. Unlike biochar, lime decreased the relative abundance of Nitrosomonadaceae (the dominant ammonia-oxidizing bacteria) while augmenting the relative abundance of some fungal pathogens such as Spizellomycetaceae and Sporormiaceae. Given the highest nitrogen and dissolved organic carbon content than other biochar types, Wedelia-biochar resulted in the greatest relative abundance of Nitrosomonadaceae; thus, the microbial carbon and nitrogen biomasses were maximized. This study outlined the responses of the soil biogeochemical properties and the related microbial community structure and functionality to the biochar produced from invasive plants under acid rain. This study suggests that biochar can replace lime to ameliorate the effects of acid rain on soil physical, chemical and biological properties.


Assuntos
Chuva Ácida , Compostos de Cálcio , Carvão Vegetal , Espécies Introduzidas , Microbiologia do Solo , Solo , Carvão Vegetal/química , Carvão Vegetal/farmacologia , Compostos de Cálcio/farmacologia , Solo/química , Microbiota/efeitos dos fármacos , Óxidos , Wedelia , Concentração de Íons de Hidrogênio , Nitrogênio/análise , Ecossistema , Fósforo/análise
16.
Int J Biol Macromol ; 277(Pt 3): 134223, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39084416

RESUMO

Polyphenols, including phenolics, alkaloids, and terpenes, are secondary metabolites that are commonly found in fruits, vegetables, and beverages, such as tea, coffee, wine, chocolate, and beer. These compounds have gained considerable attention and market demand because of their potential health benefits. However, their application is limited due to their low absorption rates and reduced tissue distribution efficiency. Engineering polyphenol-protein complexes or conjugates can enhance the antioxidant properties, bioavailability, and stability of polyphenols and improve digestive enzyme hydrolysis, target-specific delivery, and overall biological functions. Complex polyphenols, such as melanin, tannins, and ellagitannins, can promote gut microbiota balance, bolster antioxidant defense, and improve overall human health. Despite these benefits, the safety of polyphenol complexes must be thoroughly evaluated before their use as functional food additives or supplements. This review provides a detailed overview of the types of macromolecular polyphenols, their chemical composition, and their role in food enrichment. The mechanisms by which complex polyphenols act as antioxidative, anti-inflammatory, and anticancer agents have also been discussed.

17.
Biomolecules ; 14(7)2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39062575

RESUMO

Congenital heart disease (CHD) is the most common birth defect, requiring invasive surgery often before a child's first birthday. Current materials used during CHD surgery lack the ability to grow, remodel, and regenerate. To solve those limitations, 3D bioprinting is an emerging tool with the capability to create tailored constructs based on patients' own imaging data with the ability to grow and remodel once implanted in children with CHD. It has the potential to integrate multiple bioinks with several cell types and biomolecules within 3D-bioprinted constructs that exhibit good structural fidelity, stability, and mechanical integrity. This review gives an overview of CHD and recent advancements in 3D bioprinting technologies with potential use in the treatment of CHD. Moreover, the selection of appropriate biomaterials based on their chemical, physical, and biological properties that are further manipulated to suit their application are also discussed. An introduction to bioink formulations composed of various biomaterials with emphasis on multiple cell types and biomolecules is briefly overviewed. Vasculogenesis and angiogenesis of prefabricated 3D-bioprinted structures and novel 4D printing technology are also summarized. Finally, we discuss several restrictions and our perspective on future directions in 3D bioprinting technologies in the treatment of CHD.


Assuntos
Materiais Biocompatíveis , Bioimpressão , Cardiopatias Congênitas , Hidrogéis , Impressão Tridimensional , Engenharia Tecidual , Humanos , Cardiopatias Congênitas/terapia , Bioimpressão/métodos , Hidrogéis/química , Engenharia Tecidual/métodos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , Alicerces Teciduais/química , Animais
18.
Drug Dev Res ; 85(4): e22217, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38845214

RESUMO

As a hybrid weapon, two novel series of pyrazoles, 16a-f and 17a-f, targeting both COX-2 and ACE-1-N-domain, were created and their anti-inflammatory, anti-hypertensive, and anti-fibrotic properties were evaluated. In vitro, 17b and 17f showed COX-2 selectivity (SI = 534.22 and 491.90, respectively) compared to celecoxib (SI = 326.66) and NF-κB (IC50 1.87 and 2.03 µM, respectively). 17b (IC50 0.078 µM) and 17 f (IC50 0.094 µM) inhibited ACE-1 comparable to perindopril (PER) (IC50 0.048 µM). In vivo, 17b decreased systolic blood pressure by 18.6%, 17b and 17f increased serum NO levels by 345.8%, and 183.2%, respectively, increased eNOS expression by 0.97 and 0.52 folds, respectively and reduced NF-κB-p65 and P38-MAPK expression by -0.62, -0.22, -0.53, and -0.24 folds, respectively compared to  l-NAME (-0.34, -0.45 folds decline in NF-κB-p65 and P38-MAPK, respectively). 17b reduced ANG-II expression which significantly reversed the cardiac histological changes induced by L-NAME.


Assuntos
Inibidores da Enzima Conversora de Angiotensina , Anti-Inflamatórios , Anti-Hipertensivos , Inibidores de Ciclo-Oxigenase 2 , Pirazóis , Tetrazóis , Pirazóis/farmacologia , Pirazóis/química , Animais , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/química , Anti-Hipertensivos/síntese química , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/química , Inibidores da Enzima Conversora de Angiotensina/síntese química , Tetrazóis/farmacologia , Tetrazóis/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/síntese química , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/química , Ratos , Desenho de Fármacos , Masculino , Antifibróticos/farmacologia , Antifibróticos/química , Ciclo-Oxigenase 2/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Humanos , Peptidil Dipeptidase A/metabolismo
19.
Bioorg Chem ; 150: 107566, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38896936

RESUMO

In the current study, novel pyrazolo[3,4-d]pyrimidine derivatives 5a-h were designed and synthesized as targeted anti-cancer agents through dual CDK2/GSK-3ß inhibition. The designed compounds demonstrated moderate to potent activity on the evaluated cancer cell lines (MCF-7 and T-47D). Compounds 5c and 5 g showed the most promising cytotoxic activity against the tested cell lines surpassing that of the used reference standard; staurosporine. On the other hand, both compounds showed good safety and tolerability on normal fibroblast cell line (MCR5). The final compounds 5c and 5 g showed a promising dual CDK2/GSK-3ß inhibitory activity with IC50 of 0.244 and 0.128 µM, respectively, against CDK2, and IC50 of 0.317 and 0.160 µM, respectively, against GSK-3ß. Investigating the effect of compounds 5c and 5 g on CDK2 and GSK-3ß downstream cascades showed that they reduced the relative cellular content of phosphorylated RB1 and ß-catenin compared to that in the untreated MCF-7 cells. Moreover, compounds 5c and 5 g showed a reasonable selective inhibition against the target kinases CDK2/GSK-3ß in comparison to a set of seven off-target kinases. Furthermore, the most potent compound 5 g caused cell cycle arrest at the S phase in MCF-7 cells preventing the cells' progression to G2/M phase inducing cell apoptosis. Molecular docking studies showed that the final pyrazolo[3,4-d]pyrimidine derivatives have analogous binding modes in the target kinases interacting with the hinge region key amino acids. Molecular dynamics simulations confirmed the predicted binding mode by molecular docking. Moreover, in silico predictions indicated their favorable physicochemical and pharmacokinetic properties in addition to their promising cytotoxic activity.


Assuntos
Antineoplásicos , Proliferação de Células , Quinase 2 Dependente de Ciclina , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Glicogênio Sintase Quinase 3 beta , Simulação de Acoplamento Molecular , Inibidores de Proteínas Quinases , Pirazóis , Pirimidinas , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Glicogênio Sintase Quinase 3 beta/metabolismo , Quinase 2 Dependente de Ciclina/antagonistas & inibidores , Quinase 2 Dependente de Ciclina/metabolismo , Pirimidinas/química , Pirimidinas/farmacologia , Pirimidinas/síntese química , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Pirazóis/química , Pirazóis/farmacologia , Pirazóis/síntese química , Relação Estrutura-Atividade , Proliferação de Células/efeitos dos fármacos , Estrutura Molecular , Relação Dose-Resposta a Droga , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos
20.
Front Immunol ; 15: 1277074, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38915405

RESUMO

Garlic (Allium sativum L.) is a widely abundant spice, known for its aroma and pungent flavor. It contains several bioactive compounds and offers a wide range of health benefits to humans, including those pertaining to nutrition, physiology, and medicine. Therefore, garlic is considered as one of the most effective disease-preventive diets. Many in vitro and in vivo studies have reported the sulfur-containing compounds, allicin and ajoene, for their effective anticancer, anti-diabetic, anti-inflammatory, antioxidant, antimicrobial, immune-boosting, and cardioprotective properties. As a rich natural source of bioactive compounds, including polysaccharides, saponins, tannins, linalool, geraniol, phellandrene, ß-phellandrene, ajoene, alliin, S-allyl-mercapto cysteine, and ß-phellandrene, garlic has many therapeutic applications and may play a role in drug development against various human diseases. In the current review, garlic and its major bioactive components along with their biological function and mechanisms of action for their role in disease prevention and therapy are discussed.


Assuntos
Alho , Alho/química , Humanos , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Compostos Fitoquímicos/uso terapêutico , Compostos Fitoquímicos/farmacologia , Ácidos Sulfínicos/uso terapêutico , Ácidos Sulfínicos/farmacologia , Dissulfetos
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