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1.
Mol Biol Rep ; 50(11): 9575-9585, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37776413

RESUMO

Colorectal cancer (CRC) is a serious global health concern, with a high incidence and mortality rate. Although there have been advancements in the early detection and treatment of CRC, therapy resistance is common. MicroRNAs (miRNAs), a type of small non-coding RNA that regulates gene expression, are key players in the initiation and progression of CRC. Recently, there has been growing attention to the complex interplay of miRNAs in cancer development. miRNAs are powerful RNA molecules that regulate gene expression and have been implicated in various physiological and pathological processes, including carcinogenesis. By identifying current challenges and limitations of treatment strategies and suggesting future research directions, this review aims to contribute to ongoing efforts to enhance CRC diagnosis and treatment. It also provides a comprehensive overview of the role miRNAs play in CRC carcinogenesis and explores the potential of miRNA-based therapies as a treatment option. Importantly, this review highlights the exciting potential of targeted modulation of miRNA function as a therapeutic approach for CRC.


Assuntos
Neoplasias Colorretais , MicroRNAs , Humanos , MicroRNAs/metabolismo , Neoplasias Colorretais/terapia , Neoplasias Colorretais/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica/genética , Carcinogênese/genética , Previsões , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Redes Reguladoras de Genes/genética
2.
Future Oncol ; 19(35): 2369-2382, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37970643

RESUMO

Colorectal cancer (CRC) is a significant contributor to cancer mortality worldwide, and the presence of cancer stem cells (CSC) represents a major challenge for achieving effective treatment. miRNAs have emerged as critical regulators of gene expression, and recent studies have highlighted their role in regulating stemness and therapeutic resistance in CRC stem cells. This review highlights the mechanisms of CSC development, therapy resistance and the potential of miRNAs as therapeutic targets for CRC. It emphasizes the promise of miRNAs as a novel approach to CRC treatment and calls for further research to explore effective miRNA-based therapies and strategies for delivering miRNAs to CSCs in vivo.


Assuntos
Neoplasias Colorretais , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Colorretais/terapia , Neoplasias Colorretais/tratamento farmacológico , Células-Tronco Neoplásicas/metabolismo , Regulação Neoplásica da Expressão Gênica
3.
Anim Biotechnol ; 34(8): 3729-3738, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37226739

RESUMO

Pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS), peptidoglycan (PGN), Polyinosinic-polycytidylic acid (poly I:C), and CpG Oligodeoxynucleotides (ODN) are recognized by Toll-like receptors (TLR). This study aimed to investigate the effect of diverse PAMPs on the transcription of TLR signaling pathway genes in goat blood. Whole blood was collected from 3 female BoerXSpanish goats and treated with the following PAMPs: 10 µg/ml LPS, PGN, CpG ODN (2216), CpG ODN (2006), and 12.5 µg/ml Poly I:C. Blood-treated PBS served as a control. The expression of 84 genes in the human TLR signaling pathway RT2 PCR Array (Qiagen) was evaluated using real-time PCR. Treatment with PBS affected the expression of 74 genes, Poly I:C affected the expression of 40 genes, t ODN 2006 affected the expression of 50 genes, ODN 2216 affected the expression of 52 genes, LPS affected the expression of 49 genes, while PGN affected the expression of 49 genes. Our results show that PAMPs modulated and increased the expression of genes in the TLR signaling pathway. These results highlight important insights into how the host responds to different pathogens and may help design adjuvants for therapeutics and vaccines that target different.


Assuntos
Lipopolissacarídeos , Moléculas com Motivos Associados a Patógenos , Feminino , Animais , Humanos , Lipopolissacarídeos/farmacologia , Cabras/genética , Cabras/metabolismo , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismo , Transdução de Sinais/genética , Poli I
4.
Int J Mol Sci ; 22(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34360812

RESUMO

This review provides insight into the importance of understanding NETosis in cows, sheep, and goats in light of the importance to their health, welfare and use as animal models. Neutrophils are essential to innate immunity, pathogen infection, and inflammatory diseases. The relevance of NETosis as a conserved innate immune response mechanism and the translational implications for public health are presented. Increased understanding of NETosis in ruminants will contribute to the prediction of pathologies and design of strategic interventions targeting NETs. This will help to control pathogens such as coronaviruses and inflammatory diseases such as mastitis that impact all mammals, including humans. Definition of unique attributes of NETosis in ruminants, in comparison to what has been observed in humans, has significant translational implications for one health and global food security, and thus warrants further study.


Assuntos
Armadilhas Extracelulares/imunologia , Imunidade Inata , Neutrófilos/imunologia , Ruminantes/imunologia , Animais , Humanos , Neutrófilos/citologia
5.
BMC Pregnancy Childbirth ; 20(1): 266, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375724

RESUMO

BACKGROUND: Candida is the leading cause of vaginitis, and 75% of women have at least one episode of infection in their lives, with pregnancy being a predisposing factor. If left untreated, vulvovaginal candidiasis (VVC) can lead to chorioamnionitis with subsequent abortion, prematurity and congenital infection of the neonate. We aimed to determine the prevalence of VVC, identify the recent and most frequently occurring species of Candida in pregnant women, and determine the most effective antifungal drug of choice for treatment. METHOD: A prospective cross-sectional study in which 176 high vaginal swab samples of consented pregnant women visiting the antenatal clinic from February 2018 to April 2018 were subjected to direct gram smear and culture for Candida isolation. Candida isolates were identified using a germ tube test and HiCrome Candida differential agar. Candida isolates were then subjected to a disk diffusion method using fluconazole (25 µg), nystatin (100 units), and voriconazole (1 µg) on Mueller-Hinton agar supplemented with 2% (w/v) glucose and 0.5 µg/ml methylene blue dye to determine the susceptibility pattern as per the guidelines of the Clinical Laboratory Standard Institute (CLSI). Chi-square analysis was used to ascertain the significant association of participants' sociodemographics and clinical presentations to VVC. A univariate logistic regression model was used to identify potential risk factors of VVC. RESULTS: The prevalence of VVC among our study participants was 30.7%. Non-albicans Candida (NAC) and Candida albicans had a prevalence of 74.1 and 25.9%, respectively. Candida glabrata was the most common species, followed by Candida albicans, Candida krusei, and Candida parapsilosis. 50.0, 18.5 and 3.7% of Candida species were susceptible to voriconazole, fluconazole and nystatin, respectively, whereas 37.0, 48.1 and 9.3% of Candida species were resistant to voriconazole, fluconazole and nystatin, respectively. The majority of isolates were susceptible dose dependent to all three antifungal agents, with voriconazole being the most efficacious antifungal agent. There was no significant association between participants' socio-demographic information and clinical presentations to VVC. CONCLUSION: The prevalence of VVC was high in the study area. C. glabrata was found to be the most common cause of VVC among the pregnant women attending antenatal clinics, in the Ho Municipality region of Ghana. The majority of the Candida isolates were susceptible and resistant to voriconazole and fluconazole, respectively.


Assuntos
Candidíase Vulvovaginal/epidemiologia , Complicações na Gravidez/epidemiologia , Adolescente , Adulto , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida/classificação , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Candida albicans/efeitos dos fármacos , Candida albicans/isolamento & purificação , Candida glabrata/efeitos dos fármacos , Candida glabrata/isolamento & purificação , Candida parapsilosis/efeitos dos fármacos , Candida parapsilosis/isolamento & purificação , Candidíase Vulvovaginal/tratamento farmacológico , Candidíase Vulvovaginal/microbiologia , Estudos Transversais , Feminino , Fluconazol/farmacologia , Fluconazol/uso terapêutico , Gana/epidemiologia , Humanos , Testes de Sensibilidade Microbiana , Pichia/efeitos dos fármacos , Pichia/isolamento & purificação , Gravidez , Complicações na Gravidez/microbiologia , Gestantes , Prevalência , Estudos Prospectivos , Esfregaço Vaginal , Voriconazol/farmacologia , Voriconazol/uso terapêutico , Adulto Jovem
6.
J Dairy Res ; 86(4): 394-398, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31727186

RESUMO

The work described in this research communication aimed to investigate whether rumen-protected methionine (Met) supplementation during the periparturient period would affect the expression of galectins in blood-derived neutrophils, and secretion of galectins, IL (interleukin)-1ß, IL-6, myeloperoxidase (MPO), and glucose in plasma. Because supplementation of rumen-protected Met would alleviate inflammation and oxidative stress during the peripartal period, we hypothesized that enhancing Met supply would benefit the innate immune response at least in part by altering the expression of galectin genes associated with neutrophil activity and inflammation. Galectins (Gal) have an immuno-modulating effect acting like cell-surface receptors whose activation often results in signaling cascades stimulating cells such as neutrophils. This study revealed an association between Met supplementation and galectin expression and secretion. This implies that galectin expression and secretion can be modulated by Met supplementation. Further studies are needed to evaluate the regulation of galectin gene expression for therapeutic and dietary intervention in the peripartal cow.


Assuntos
Bovinos/sangue , Suplementos Nutricionais , Galectinas/metabolismo , Metionina/farmacologia , Rúmen , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta/veterinária , Feminino , Galectinas/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação , Fenômenos Fisiológicos da Nutrição Materna , Metionina/administração & dosagem , Neutrófilos/metabolismo , Período Periparto/metabolismo
7.
Pharm Biol ; 54(8): 1354-63, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26449896

RESUMO

CONTEXT: Polyscias fruticosa (L.) Harms (Araliaceae) is used as a traditional remedy for asthma in Ghana. OBJECTIVE: The objective of this study is to establish the anti-asthmatic property and a possible mode of activity of an ethanol leaf extract of P. fruticosa (PFE). MATERIALS AND METHODS: The time (min) for pre-convulsive dyspnea, and time for recovery, after sensitization with 150 µg OVA and induction of bronchospasm with 1% acetylcholine or histamine in normal, and 100, 250, and 500 mg/kg PFE-treated Dunkin Hartley guinea pigs, were recorded. Atropine (0.1 mg), mepyramine (0.1 mg), and PFE (1 mg) effect on a contractile response of 2.0 × 10(-2) µg/ml acetylcholine and 5.8 × 10(-2) µg/ml histamine on the isolated guinea pig ileum was investigated. Cytological and histological studies were conducted using guinea pig peritoneal mast cells and mesenteric cells, respectively, to establish PFE effect on compound 48/80-induced mast cell degranulation. RESULTS: PFE (100-500 mg/kg) prolonged the onset of pre-convulsive dyspnea by 76.1-180.2% (p ≤ 0.01-0.001), and decreased recovery time by 71.9-78.5% (p ≤ 0.01-0.001). It also enhanced percentage protection against histamine-induced bronchospasm by 15.8-80.1-fold (p ≤ 0.05-0.01), and decreased percentage recovery time 2.5-3.3-fold (p ≤ 0.05-0.01). PFE significantly inhibited (60.4 ± 8.3%) contractile responses of histamine and produced significant inhibition (56-79%: p ≤ 0.001) of mast cell degranulation. CONCLUSION: PFE has anti-asthmatic, antihistaminic, and mast cell stabilization effect making it useful in traditional asthma management.


Assuntos
Antiasmáticos/farmacologia , Asma/prevenção & controle , Hiper-Reatividade Brônquica/prevenção & controle , Broncoconstrição/efeitos dos fármacos , Dispneia/prevenção & controle , Etanol/química , Pulmão/efeitos dos fármacos , Extratos Vegetais/farmacologia , Solventes/química , Animais , Antiasmáticos/isolamento & purificação , Araliaceae/química , Asma/induzido quimicamente , Asma/imunologia , Asma/fisiopatologia , Hiper-Reatividade Brônquica/induzido quimicamente , Hiper-Reatividade Brônquica/imunologia , Hiper-Reatividade Brônquica/fisiopatologia , Broncodilatadores/farmacologia , Degranulação Celular/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Dispneia/fisiopatologia , Cobaias , Antagonistas dos Receptores Histamínicos/farmacologia , Pulmão/imunologia , Pulmão/fisiopatologia , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Fitoterapia , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Plantas Medicinais
8.
S Afr J Infect Dis ; 39(1): 553, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962372

RESUMO

Background: Approximately 20 to 120 million women of reproductive age worldwide are thought to be affected by female genital schistosomiasis (FGS). It is a preventable manifestation of schistosomiasis in adolescent girls and women, which remains underreported, underdiagnosed, or misdiagnosed, and largely untreated. Objective: This study aimed to map evidence on the knowledge and management of FGS from 1950 to 2022 in sub-Saharan Africa. Method: The Arksey and O'Malley and Levac et al. framework suggestions and a guideline from Joanna Briggs Institute will be employed. Search for literature will be in PubMed, Scopus, Cochrane, Web of Science, MEDLINE via PubMed, and Google Scholar from 1950 to 2022 for useful published research articles using key phrases or search terms and grey literature with limitations for studies conducted in sub-Saharan Africa. Two reviewers will screen the articles. Kappa coefficients by Cohen statistics will be computed for inter-screener agreement, and the selected articles will be evaluated using Mixed Method Appraisal Tool (MMAT). Results: The researchers will map and explore the evidence of the knowledge and management of FGS in the subregion. The years of publications, countries of study, and settings will be reported, and the identified research gaps will be reported. Conclusion: The researchers anticipate that this study will determine and map the evidence on the knowledge and management of FGS in sub-Saharan Africa; identify knowledge and management gaps, and direct future research. Contribution: This study will add to the literature on FGS and direct future research regarding the knowledge and management of FGS.

9.
Vet Sci ; 11(2)2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38393075

RESUMO

Fenugreek seeds (FSs) are a natural source of bioactive compounds that may modulate the immune system and gut microbiota in broilers. This study examined the effects of dietary fenugreek seed powder on immune-related gene expression and cecal microbiota composition in broilers. A total of 144 broiler chickens were randomly allocated to three dietary groups, CON (0 g/kg FS, FS5 (5 g/kg FS) and FS10 (10 g/kg FS), each with 6 replicates of 8 birds. Ileum tissues and cecal contents were collected on day 42 for the mRNA expression of inflammation and antimicrobial defense-related genes and cecal microbiome diversity, respectively. The results indicated that fenugreek seeds downregulated mRNA-level inflammation and antimicrobial defense-related genes: IL6, IL8L2, CASP6, PTGS2, IRF7, AvBD9, AvBD10, and AvBD11. Moreover, fenugreek seeds altered the cecal microbial community by increasing the population of Firmicutes and decreasing the population of Actinobacteriota, Gemmatimonadota and Verrucomicrobiota at the phylum level and increasing Alistipes, Bacteriodes and Prevotellaceae at the genera level. These findings suggest that fenugreek seeds have a positive impact on the immunological profile and microbiome of broiler chickens, possibly through the interplay of the immune system and the gut microbiome.

10.
Poult Sci ; 103(10): 104130, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39121644

RESUMO

Intensive broiler production systems face challenges like enteric diseases, impacting global food security. Strategies to enhance broiler immunity and gut health, particularly amidst antibiotic growth promoter restrictions, are crucial. The present study investigated the combined effects of fenugreek seeds (FS) and Bacillus-based direct-fed microbials (DFM) on immune-related gene expression in the ileum and alteration of microbial population in the cecum of broiler. The study involved 160 Ross 308 broiler chicks, which were divided into four groups consisting of 5 replicates, each containing eight birds. The chicks were grown for a period of 42 d, during which they had ad libitum access to feed and water. Dietary treatments were: Control (basal diet), FS5 (basal + 5g/kg fenugreek seeds), FS5DFM (basal + 5g/kg fenugreek seeds + 0.1g/kg Bacillus-based DFM), and DFM (basal + 0.1g/kg Bacillus-based DFM). Ileum tissue and cecal contents were collected on d 42 for gene expression and gut microbiome analysis. Ileal gene expression analysis revealed the downregulation of IL-6, IL-8L2, CASP6, PTGS2, and IRF7 in both FSs and DFMs groups compared to the control, suggesting individual immunomodulatory effects. However, avian ß-defensin genes exhibited complex regulation, highlighting the need for further investigation. Cecal microbiome diversity remained stable, with subtle shifts in specific taxa influenced by FSs and DFMs. Interestingly, the combination of the FSs and DFMs uniquely impacted specific taxa, including Clostridiales vadin BB60. These findings suggest that both FSs and DFMs demonstrated potential for improving broiler immunity through inflammation reduction. The combination of FSs and DFMs offers a synergistic effect in immune modulation and specific microbial modulation, warranting further investigation with pathogen challenge models for comprehensive understanding.


Assuntos
Ração Animal , Bacillus , Ceco , Galinhas , Dieta , Microbioma Gastrointestinal , Probióticos , Trigonella , Animais , Galinhas/imunologia , Galinhas/microbiologia , Trigonella/química , Ração Animal/análise , Dieta/veterinária , Microbioma Gastrointestinal/efeitos dos fármacos , Ceco/microbiologia , Probióticos/farmacologia , Probióticos/administração & dosagem , Bacillus/química , Sementes/química , Suplementos Nutricionais/análise , Íleo/microbiologia , Íleo/imunologia , Distribuição Aleatória , Masculino , Expressão Gênica/efeitos dos fármacos , Extratos Vegetais
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