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1.
Poult Sci ; 103(9): 103981, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38981360

RESUMO

This work was designed to assess the impact of varying zeolite concentrations in diet and litter to enhance broiler's growth performance, immunity, and litter quality. A complete random arrangement was used for distributing 525 unsexed "Cobb 500" broiler chicks into seven treatments (75 chick / treatment), each treatment divided into 3 replicates (25 chicks / replicate). The 1st group (control one) received the recommended basal diet. Zeolite has been introduced to the basal diet (ZD) of the second, third, and fourth groups at concentrations of 5, 10, and 15 g/kg, respectively. The 5th, 6th and 7th groups used zeolite mixed with litter (ZL) at 0.5, 1, and 1.5 kg/m2 of litter, respectively. Due to the obtained results, adding zeolite with levels 15 g/kg of diet and 1.5 kg/1 m2 of litter, a significant improvement occurred in live body weight (LBW), body weight gain (BWG), feed intake (FI), feed conversion ratio (FCR) and European production efficiency factor (EPEF). Also, transaminase enzymes (ALT and AST), creatinine, white blood cells (WBCs) and different Immunoglobulins were significantly increased with different zeolite levels, except urea concentrations which showed reduced due to different zeolite treatments. In addition, spleen relative weight hasn't been affected by zeolite treatments, even though thymus and bursa relative weights had been affected significantly. Moreover, the antibodies' production to Newcastle disease virus (NDV) and Avian influenza virus (AIV) had increased significantly with adding zeolite with levels 10 g/kg of diet and 1.5 kg/1m2 of litter. Litter quality traits (NH3 concentration, pH values, and Moisture content) were improved with zeolite addition. So, zeolite could be employed in both feed and litter of broilers to maximize their production, immunity and improve farm's climate.

2.
Exp Appl Acarol ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967736

RESUMO

Equine piroplasmosis is not fully understood regarding pathogenicity, prophylaxis, host immune response expression, and specific vectors. Accurately identifying the parasite vector is crucial for developing an effective control plan for a particular infection. This study focused on morphologically identifying two Hyalomma species (H. anatolicum and H. marginatum) and one Rhipicephalus annulatus (R. annulatus) at the species level. The identification process was followed by phylogenetic analysis using the neighbor-joining method based on the cytochrome oxidase subunit 1 (COXI) gene as a specific vector for Theileria equi (T. equi) in horses. T. equi was diagnosed morphologically and molecularly from infected blood samples and crushed tick species using conventional PCR. Subsequently, phylogenetic analysis based on the amplification of the 18 S rRNA gene was conducted. The obtained sequence data were evaluated and registered in GenBank under accession numbers OR064161, OR067911, OR187727, and OR068139, representing the three tick species and the isolated T. equi, respectively. The study demonstrated that T. equi infection leads to immune system suppression by significantly increasing the levels of oxidative stress markers (CAT, GPx, MDA, and SOD) (P ≤ 0.0001), with this elevation being directly proportional to parasitemia levels in infected blood cells. Furthermore, a correlation was observed between parasitemia levels and the expression of immune response infection genes (IFN-gamma, TGF-ß1, and IL-1ß cytokines) in infected horses compared to non-infected equine. Common macroscopic symptoms indicating T. equi infection in horses include intermittent fever, enlarged lymph nodes (LN), and tick infestation.

3.
Plants (Basel) ; 13(12)2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38931028

RESUMO

Salinity stress poses a significant threat to crop productivity worldwide, necessitating effective mitigation strategies. This study investigated the phytochemical composition and potential of grape seed extract (GSE) to mitigate salinity stress effects on faba bean plants. GC-MS analysis revealed several bioactive components in GSE, predominantly fatty acids. GSE was rich in essential nutrients and possessed a high antioxidant capacity. After 14 days of germination, GSE was applied as a foliar spray at different concentrations (0, 2, 4, 6, and 8 g/L) to mitigate the negative effects of salt stress (150 mM NaCl) on faba bean plants. Foliar application of 2-8 g/L GSE significantly enhanced growth parameters such as shoot length, root length, fresh weight, and dry weight of salt-stressed bean plants compared to the control. The Fv/Fm ratio, indicating photosynthetic activity, also improved with GSE treatment under salinity stress compared to the control. GSE effectively alleviated the oxidative stress induced by salinity, reducing malondialdehyde, hydrogen peroxide, praline, and glycine betaine levels. Total soluble proteins, amino acids, and sugars were enhanced in GSE-treated, salt-stressed plants. GSE treatment under salinity stress modulated the total antioxidant capacity, antioxidant responses, and enzyme activities such as peroxidase, ascorbate peroxidase, and polyphenol oxidase compared to salt-stressed plants. Gene expression analysis revealed GSE (6 g/L) upregulated photosynthesis (chlorophyll a/b-binding protein of LHCII type 1-like (Lhcb1) and ribulose bisphosphate carboxylase large chain-like (RbcL)) and carbohydrate metabolism (cell wall invertase I (CWINV1) genes) while downregulating stress response genes (ornithine aminotransferase (OAT) and ethylene-responsive transcription factor 1 (ERF1)) in salt-stressed bean plants. The study demonstrates GSE's usefulness in mitigating salinity stress effects on bean plants by modulating growth, physiology, and gene expression patterns, highlighting its potential as a natural approach to enhance salt tolerance.

4.
BMC Microbiol ; 24(1): 225, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926687

RESUMO

BACKGROUND: The incidence of hospital-acquired infections in extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) has been increasing worldwide and is frequently associated with an increase in mortality and morbidity rates. The aim of this study was to characterize clinical XDR-PA isolates recovered during six months at three different hospitals in Egypt. RESULTS: Seventy hospital-acquired clinical isolates of P. aeruginosa were classified into multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant (PDR), according to their antimicrobial resistance profile. In addition, the possession of genes associated with mobile genetic elements and genes encoding antimicrobial resistance determinants among isolates were detected using polymerase chain reaction. As a result, a significant percentage of the isolates (75.7%) were XDR, while 18.5% were MDR, however only 5.7% of the isolates were non-MDR. The phenotypic detection of carbapenemases, extended-spectrum ß-lactamases (ESBLs) and metallo ß-lactamase (MBL) enzymes showed that 73.6% of XDR-PA isolates were carbapenemases producers, whereas 75.5% and 88.7% of XDR-PA isolates produced ESBLs and MBL respectively. In addition, PCR screening showed that oxa gene was the most frequently detected gene of carbapenemases (91.4%), while aac(6')-lb gene was mostly detected (84.3%) among the screened aminoglycosides-resistance genes. Furthermore, the molecular detection of the colistin resistance gene showed that 12.9% of isolates harbored mcr-1 gene. Concerning mobile genetic element markers (intI, traA, tnp513, and merA), intI was the highest detected gene as it was amplified in 67 isolates (95.7%). Finally, phylogenetic and molecular typing of the isolates via ERIC-PCR analysis revealed 10 different ERIC fingerprints. CONCLUSION: The present study revealed a high prevalence of XDR-PA in hospital settings which were resistant to a variety of antibiotics due to several mechanisms. In addition, 98% of the XDR-PA clinical isolates contained at least one gene associated with movable genetic elements, which could have aided the evolution of these XDR-PA strains. To reduce spread of drug resistance, judicious use of antimicrobial agents and strict infection control measures are therefore essential.


Assuntos
Antibacterianos , Infecção Hospitalar , Farmacorresistência Bacteriana Múltipla , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas , Pseudomonas aeruginosa , beta-Lactamases , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Humanos , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/epidemiologia , Farmacorresistência Bacteriana Múltipla/genética , Infecção Hospitalar/microbiologia , Infecção Hospitalar/epidemiologia , Egito/epidemiologia , beta-Lactamases/genética , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Hospitais/estatística & dados numéricos , Sequências Repetitivas Dispersas/genética , Reação em Cadeia da Polimerase
5.
PLoS One ; 19(6): e0303702, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38833454

RESUMO

Nile tilapia (Oreochromis niloticus) is valued in aquaculture because of its quick development and ability to thrive in various environments. Myxosporeans are among the fish parasites that affect fish productivity, as they impact fish growth and reproduction, resulting in large fish deaths in farms and hatcheries. This study has been focused on morpho-molecular identification for the myxosporean parasites infecting Nile tilapia from three governorates in Egypt and assessment of gene expression of different cytokines (Interleukin-1ßeta (IL-1ß), major histocompatibility complex class II (MHC-II), and clusters of differentiation 4 (CD-4) and 8 (CD-8)) in tissues. Additionally, this work aimed to correlate the developed histopathological alterations and inflammatory reactions in gills with immunohistochemical expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-α). Finally, the infected fish's cortisol levels and blood glucose were assessed. Results of BLAST sequence analysis of the 18S rRNA for the collected protozoans confirmed Myxobolus agolus, M. brachysporus, M. tilapiae, and Henneguya species. The molecular characterization of the immunological status of gills revealed marked upregulation of different inflammatory cytokines in the gills of infected fish. There was a significantly increased serum cortisol and glucose level in infected fish compared with control, non-infected ones. Severe histopathological alterations were observed in the infected fish gills, associated with increased expression of iNOS and TNF-α and related to myxosporean infection. The present study provides new insights into oxidative stress biomarkers in Nile tilapia infected with Myxosporeans and elucidates the gill's immune status changes as a portal of entry for protozoa that contribute to tissue damage.


Assuntos
Ciclídeos , Doenças dos Peixes , Brânquias , Myxozoa , Doenças Parasitárias em Animais , Animais , Brânquias/parasitologia , Brânquias/patologia , Brânquias/imunologia , Ciclídeos/parasitologia , Ciclídeos/imunologia , Ciclídeos/genética , Doenças dos Peixes/parasitologia , Doenças dos Peixes/imunologia , Doenças Parasitárias em Animais/parasitologia , Doenças Parasitárias em Animais/imunologia , Doenças Parasitárias em Animais/patologia , Myxozoa/fisiologia , Biomarcadores , Imuno-Histoquímica , Citocinas/metabolismo , Egito , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo II/genética
6.
Front Public Health ; 12: 1411724, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38873295

RESUMO

Introduction: Low energy availability (LEA) is a state of inadequate energy reserves that results from a negative energy balance. This condition can lead to severe health risks such as amenorrhea and osteoporosis. Various causes for LEA, such as eating disorders and exercise addiction, have been reported in the literature. However, data in Saudi Arabia are lacking. This cross-sectional study measures the prevalence of LEA, eating disorders, and exercise addiction among adult females in Saudi Arabia and identifies possible associated risk factors. Methods: The sample comprised 119 female athletes who filled out an online survey adapted from the LEA in Females Questionnaire, the Eating Disorder Examination Questionnaire, and the Exercise Addiction Inventory. Results: Participants showed a high prevalence of LEA (66.4%), eating disorder (33.6%), and exercise addiction (10.1%), confirming the association between normal weight and LEA in females living in Saudi Arabia (p < 0.00). Discussion and conclusion: With an increasing number of females in the country interested in following a healthy lifestyle, there is a need to raise the awareness of the population on the issues of LEA, eating disorders, and exercise addiction and their effects on the body by developing educational programs about energy intake and healthy physical activity routines.


Assuntos
Atletas , Exercício Físico , Transtornos da Alimentação e da Ingestão de Alimentos , Humanos , Feminino , Arábia Saudita/epidemiologia , Estudos Transversais , Atletas/estatística & dados numéricos , Adulto , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Inquéritos e Questionários , Prevalência , Fatores de Risco , Adulto Jovem , Ingestão de Energia , Adolescente , Comportamento Aditivo/epidemiologia
7.
BMC Med Educ ; 24(1): 661, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877491

RESUMO

BACKGROUND: Systematic biases in group decision making (i.e., group biases) may result in suboptimal decisions and potentially harm patients. It is not well known how impaired group decision making in patient care may affect medical training. This study aimed to explore medical residents' experiences and perspectives regarding impaired group decision making and the role of group biases in medical decision making. METHODS: This study used a qualitative approach with thematic analysis underpinned by a social constructionist epistemology. Semi-structured interviews of medical residents were conducted at a single internal medicine residency program. Residents were initially asked about their experiences with suboptimal medical decision making as a group or team. Then, questions were targeted to several group biases (groupthink, social loafing, escalation of commitment). Interviews were transcribed and transferred to a qualitative data analysis software. Thematic analysis was conducted to generate major themes within the dataset. RESULTS: Sixteen interviews with residents revealed five major themes: (1) hierarchical influence on group decision making; (2) group decision making under pressure; (3) post-call challenges in decision making; (4) interactions between teamwork and decision making; and (5) personal and cultural influences in group decision making. Subthemes were also identified for each major theme. Most residents were able to recognize groupthink in their past experiences working with medical teams. Residents perceived social loafing or escalation of commitment as less relevant for medical team decision making. CONCLUSIONS: Our findings provide unique insights into the complexities of group decision making processes in teaching hospitals. Team hierarchy significantly influenced residents' experiences with group decision making-most group decisions were attributed to consultants or senior team members, while lower ranking team members contributed less and perceived fewer opportunities to engage in group decisions. Other factors such as time constraints on decision making, perceived pressures from other staff members, and challenges associated with post-call days were identified as important barriers to optimal group decision making in patient care. Future studies may build upon these findings to enhance our understanding of medical team decision making and develop strategies to improve group decisions, ultimately leading to higher quality patient care and training.


Assuntos
Internato e Residência , Pesquisa Qualitativa , Humanos , Feminino , Masculino , Processos Grupais , Tomada de Decisão Clínica , Adulto , Atitude do Pessoal de Saúde , Medicina Interna/educação , Entrevistas como Assunto , Tomada de Decisões
9.
Viral Immunol ; 37(4): 186-193, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38717821

RESUMO

Coronavirus disease 2019 (COVID-19) represented an international health risk. Variants of the interferon-induced transmembrane protein-3 (IFITM3) gene can increase the risk of developing severe viral infections. This cross-sectional study investigated the association between IFITM3 rs12252A>G single nucleotide polymorphism (SNP) and COVID-19 severity and mortality in 100 Egyptian patients. All participants were subjected to serum interleukin-6 (IL-6) determination by ELISA and IFITM3 rs12252 genotyping by real-time polymerase chain reaction. Of all participants, 85.0% had the IFITM3 rs12252 homozygous AA genotype, whereas 15.0% had the heterozygous AG genotype. None of our participants had the homozygous GG genotype. The IFITM3 rs12252A allele was found in 92.5% and the G allele in only 7.5%. There was no significant association (p > 0.05) between the IFITM3 rs12252 SNP and COVID-19 severity, intensive care unit (ICU) admission, or IL-6 serum levels. The heterozygous AG genotype frequency showed a significant increase among participants who died (32.0%) compared with those who had been cured (9.3%). The mutant G allele was associated with patients' death. Its frequency among cured participants was 8.5%, whereas in those who died was 24.2% (p = 0.024) with 3.429 odds ratio [95% confidence interval: 1.1-10.4]. In conclusion, this study revealed a significant association between the G allele variant of IFITM3 rs12252 and COVID-19 mortality. However, results were unable to establish a significant link between rs12252 polymorphism, disease severity, ICU admission, or serum IL-6 levels.


Assuntos
COVID-19 , Proteínas de Membrana , Proteínas de Ligação a RNA , SARS-CoV-2 , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Alelos , COVID-19/mortalidade , COVID-19/genética , Estudos Transversais , Egito , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Interleucina-6/sangue , Interleucina-6/genética , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , Proteínas de Ligação a RNA/genética , SARS-CoV-2/patogenicidade , Índice de Gravidade de Doença
10.
Drug Dev Res ; 85(4): e22197, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38751223

RESUMO

Although various approaches exist for treating cancer, chemotherapy continues to hold a prominent role in the management of this disease. Besides, microtubules serve as a vital component of the cellular skeleton, playing a pivotal role in the process of cell division making it an attractive target for cancer treatment. Hence, the scope of this work was adapted to design and synthesize new anti-tubulin tetrabromophthalimide hybrids (3-17) with colchicine binding site (CBS) inhibitory potential. The conducted in vitro studies showed that compound 16 displayed the lowest IC50 values (11.46 µM) at the FaDu cancer cell lines, whereas compound 17 exhibited the lowest IC50 value (13.62 µM) at the PC3 cancer cell line. However, compound 7b exhibited the lowest IC50 value (11.45 µM) at the MDA-MB-468 cancer cell line. Moreover, compound 17 was observed to be the superior antitumor candidate against all three tested cancer cell lines (MDA-MB-468, PC3, and FaDu) with IC50 values of 17.22, 13.15, and 13.62 µM, respectively. In addition, compound 17 showed a well-established upregulation of apoptotic markers (Caspases 3, 7, 8, and 9, Bax, and P53). Moreover, compound 17 induced downregulation of the antiapoptotic markers (MMP2, MMP9, and BCL-2). Furthermore, the colchicine binding site inhibition assay showed that compounds 15a and 17 exhibited particularly significant inhibitory potentials, with IC50 values of 23.07 and 4.25 µM, respectively, compared to colchicine, which had an IC50 value of 3.89 µM. Additionally, cell cycle analysis was conducted, showing that compound 17 could prompt cell cycle arrest at both the G0-G1 and G2-M phases. On the other hand, a molecular docking approach was applied to investigate the binding interactions of the examined candidates compared to colchicine towards CBS of the ß-tubulin subunit. Thus, the synthesized tetrabromophthalimide hybrids can be regarded as outstanding anticancer candidates with significant apoptotic activity.


Assuntos
Antineoplásicos , Apoptose , Desenho de Fármacos , Ftalimidas , Moduladores de Tubulina , Humanos , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Simulação de Acoplamento Molecular , Ftalimidas/síntese química , Ftalimidas/farmacologia , Relação Estrutura-Atividade , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/síntese química , Moduladores de Tubulina/farmacologia
11.
World J Hepatol ; 16(5): 784-790, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38818291

RESUMO

BACKGROUND: Among patients with cirrhosis and pre-malignant or early malignant mucosal lesions, surgical intervention carries a much higher bleeding risk. When such lesions are discovered, endoscopic submucosal dissection (ESD) may offer curative therapy with lower risks than surgery and improved outcomes compared to traditional endoscopic resection. AIM: To evaluate the outcomes of ESD in patients with cirrhosis. METHODS: Patients with cirrhosis undergoing ESD between July 2015 and August 2022 were retrospectively matched in 1:2 fashion to controls based on lesion location, size, and anticoagulation use. Procedural outcomes were compared between groups. RESULTS: A total of 64 Lesions from 59 patients were included (16 cirrhosis, 43 control). There were no differences in patient or lesion characteristics between groups. En bloc and curative resection was achieved in 84.21%, 78.94% of the cirrhosis group and 88.89%, 68.89% of controls, respectively, with no significant differences. Cirrhotic patients had significantly higher rates of intra-procedural coagulation grasper use for control of bleeding (47.37% vs 20%; P = 0.02). There were otherwise no significant differences in adverse event rates. In the 29 patients with follow up, we found higher rates of recurrence in the cirrhosis group compared to controls (40% vs 5.26%; P = 0.019), however this effect did not persist on multivariable analysis controlling for known confounders. CONCLUSION: ESD may be safe and effective in patients with cirrhosis. Most procedure related outcomes were not significantly different between groups. Intra-procedural bleeding requiring use of the coagulation grasper use was expectedly higher in the cirrhosis group given the known effects of liver disease on hemostasis.

12.
Res Vet Sci ; 172: 105239, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38583195

RESUMO

Improperly cooked fish, carrying active metacercariae (MCs), can pose a significant risk for transmitting fish-borne zoonotic trematodes (FBZTs) to human consumers. This study aimed to enhance our understanding of FBZTs by conducting a comprehensive cross-sectional analysis involving various fish species, such as Nile tilapia (Oreochromis niloticus), African catfish (Clarias gariepinus), and red-belly tilapia (Tilapia zillii). These fish specimens were collected from distinct Egyptian governorates, specifically Giza, Kafr al-Shaykh, and Fayoum. The recovered flukes from experimentally infected domestic pigeons were identified as Prohemistomum vivax, Haplorchis pumilio, and Pygidiopsis genata based on morphological features. Furthermore, the identity of the retrieved adult flukes was confirmed using three species-specific primers for PCR amplification and sequencing analysis of the ITS rDNA region and have been deposited in GenBank with the following accession numbers: P. vivax (OR291421.1 and OR291422.1), P. genata (OP099561.1), and H. pumilio (OM439581.1-OP090510.1). Quantitative real-time PCR targeting the immunological genes Tumor Necrosis Factor-alpha (TNF-alpha) and Interleukin-1 (IL-1Β) was employed to compare the cellular immune response between infected with EMCs and uninfected O. niloticus. The results indicated a significant increase in TNF- and IL-1Β levels in FBZTs-infected vs un-infected fishes. Importantly, the presence of adult flukes and EMCs led to substantial histological alterations in both experimentally infected pigeons and naturally infected fish tissues. These changes included the necrosis of fish muscle bundles and a pronounced inflammatory reaction with muscular necrosis in the digestive tracts of experimentally infected pigeons.


Assuntos
Doenças dos Peixes , Infecções por Trematódeos , Animais , Estudos Transversais , Doenças dos Peixes/parasitologia , Doenças dos Peixes/imunologia , Infecções por Trematódeos/veterinária , Infecções por Trematódeos/parasitologia , Infecções por Trematódeos/imunologia , Zoonoses/parasitologia , Metacercárias , Ciclídeos/parasitologia , Ciclídeos/imunologia , Egito , Água Doce , Peixes-Gato/parasitologia , Tilápia/parasitologia , Trematódeos
13.
J Microencapsul ; 41(4): 255-268, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38647544

RESUMO

The aim is to investigate the possible pulmonary protective effect of vanillic acid (VA) in liposome-TPGS nanoparticles, to overcome VA's poor bioavailability. VA was successfully extracted. Liposomes were prepared using thin film hydration. Central composite design was adopted for optimisation of liposomes to get the maximum entrapment efficiency (EE%) and the minimum mean diameter, where the liposomes were further modified with TPGS, and tested for PDI, zeta-potential, and in-vitro drug release. In-vivo study on mice with LPS-acute pulmonary toxicity was tested. TPGS-modified VA-liposomes showed EE% of 69.35 ± 1.23%, PS of 201.7 ± 3.23 nm, PDI of 0.19 ± 0.02, and zeta-potential of -32.2 ± 0.32 mv. A sustained drug release of the TPGS-modified VA-liposomes was observed compared to standard VA, and a pulmonary-protective effect through decreasing miR-217 expression with subsequent anti-inflammatory effect through suppression of MAPK and PI3K/NF-κB pathways was also demonstrated in the current study. TPGS-modified VA-liposomes showed an enhanced bioavailability and a sustained drug release with promising pulmonary protective effects against acute pulmonary injury diseases.


Assuntos
Lipossomos , MicroRNAs , NF-kappa B , Ácido Vanílico , Vitamina E , Animais , NF-kappa B/metabolismo , Ácido Vanílico/farmacologia , Ácido Vanílico/análogos & derivados , Vitamina E/química , Vitamina E/farmacologia , Vitamina E/análogos & derivados , Camundongos , Transdução de Sinais/efeitos dos fármacos , Masculino , Pulmão/efeitos dos fármacos
14.
Science ; 384(6694): eadf5489, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38662826

RESUMO

Tubulin, one of the most abundant cytoskeletal building blocks, has numerous isotypes in metazoans encoded by different conserved genes. Whether these distinct isotypes form cell type- and context-specific microtubule structures is poorly understood. Based on a cohort of 12 patients with primary ciliary dyskinesia as well as mouse mutants, we identified and characterized variants in the TUBB4B isotype that specifically perturbed centriole and cilium biogenesis. Distinct TUBB4B variants differentially affected microtubule dynamics and cilia formation in a dominant-negative manner. Structure-function studies revealed that different TUBB4B variants disrupted distinct tubulin interfaces, thereby enabling stratification of patients into three classes of ciliopathic diseases. These findings show that specific tubulin isotypes have distinct and nonredundant subcellular functions and establish a link between tubulinopathies and ciliopathies.


Assuntos
Axonema , Centríolos , Cílios , Transtornos da Motilidade Ciliar , Tubulina (Proteína) , Animais , Humanos , Camundongos , Axonema/metabolismo , Centríolos/metabolismo , Cílios/metabolismo , Transtornos da Motilidade Ciliar/genética , Transtornos da Motilidade Ciliar/metabolismo , Mutação , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Masculino , Feminino , Camundongos Knockout
15.
J Breast Imaging ; 6(3): 304-310, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38630578

RESUMO

OBJECTIVE: To identify structure, benefits, and shortcomings of a multi-institutional virtual visiting professorship (VVP) program from 2020 to 2022, 2 years after inception and after gradual resumption of an in-person, prepandemic academic environment. METHODS: An IRB-exempt, 70-question survey about structure, benefits, and shortcomings of the VVP program was distributed to its participants (14 breast imaging departments across the U.S.), using the snowball sampling technique. RESULTS: A total of 72 responses were received; 54.2% (32/59) radiologists >5 years of experience, 18.6% (11/59) radiologists <5 years of experience, 15.3% (9/59) residents, and 8.5% (5/59) fellows. Radiologists' attendance increased from 8% (5/59) to 53% (31/59) over 2 years, with 69% (41/59) of respondents supporting continued participation. The most important factors for attendance were expanding breast imaging knowledge (86.4% [51/59]) and the virtual format (76.2% [45/59]). The number of presented lectures increased from 1 to 3 lectures in 43.7% (7/16) of programs in year 1 and from 4 to 9 lectures in 50% (8/16) of programs in year 2. The greatest professional benefits were collaborations on publications for organizers (56.3% [9/16]) and building academic portfolios for presenters (50% [7/14]). For trainees, attending the program increased their knowledge (64.3% [9/14]) and enthusiasm for breast imaging (50% [7/14]). CONCLUSION: The VVP program facilitated scholarly collaboration among breast imaging radiologists, promoted academic portfolios for junior faculty, and increased enthusiasm for breast imaging for trainees. These accomplishments extended beyond the COVID-19 pandemic, as evidenced by the growth of the program after resumption of an in-person academic environment. Future expansion to other programs would benefit more practicing radiologists.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Inquéritos e Questionários , Feminino , Docentes de Medicina , Estados Unidos , Radiologia/educação , Pandemias , SARS-CoV-2 , Educação a Distância/métodos
16.
Bioorg Chem ; 147: 107332, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38581966

RESUMO

Activin receptor­like kinase-5 (ALK5) is an outstanding member of the transforming growth factor-ß (TGF-ß) family. (TGF-ß) signaling pathway integrates pleiotropic proteins that regulate various cellular processes such as growth, proliferation, and differentiation. Dysregulation within the signaling pathway can cause variety of diseases, such as fibrosis, cardiovascular disease, and especially cancer, rendering ALK5 a potential drug target. Hence, various small molecules have been designed and synthesized as potent ALK5 inhibitors. In this review, we shed light on the current ATP-competitive inhibitors of ALK5 through diverse heterocyclic based scaffolds that are in clinical or pre-clinical phases of development. Moreover, we focused on the binding interactions of the compounds to the ATP binding site and the structure-activity relationship (SAR) of each scaffold, revealing new scopes for designing novel candidates with enhanced selectivity and metabolic profiles.


Assuntos
Descoberta de Drogas , Inibidores de Proteínas Quinases , Receptor do Fator de Crescimento Transformador beta Tipo I , Humanos , Relação Estrutura-Atividade , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/síntese química , Receptor do Fator de Crescimento Transformador beta Tipo I/antagonistas & inibidores , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Estrutura Molecular , Animais
17.
BMC Vet Res ; 20(1): 129, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561778

RESUMO

BACKGROUND: Vibriosis is one of the most serious bacterial diseases and causes high morbidity and mortality among cultured sea breams. This study was undertaken to track the surveillance of Vibrio infection and its correlation to environmental factors. A total of 115 gilthead sea breams were collected seasonally from a private earthen pond fish farm in the Shatta area of Damietta, Egypt from September 2022 to July 2023. Physicochemical parameters of water were analyzed, and heavy metal levels were measured. The fish samples were subjected to clinical, bacteriological, Enterobacterial Repetitive Intergenic Consensus (ERIC) fingerprinting, and hematoxylin and Eosin histopathological staining. RESULTS: The results revealed significant variations in the water quality parameters over different seasons, in addition to an increase in heavy metals. Naturally infected fish showed external signs and postmortem lesions that were relevant to bacterial infection. Two dominant Vibrio subspecies of bacteria were identified: V. alginolyticus (205 isolates) and V. fluvialis (87 isolates). PCR confirmed the presence of V. alginolyticus using the species-specific primer collagenase at 737 bp. The highest prevalence of V. alginolyticus was detected during the summer season (57.72%), and the lowest prevalence was observed in autumn (39.75%). The correlation analysis revealed a positive relationship between V. alginolyticus and water temperature (r = 0.69). On the other hand, V. fluvialis showed a high prevalence during the autumn season (25.30%) and the lowest prevalence during the summer season (10.56%), where it was negatively correlated with water temperatures (r =-0.03). ERIC fingerprinting showed genetic variation within the Vibrio isolates. Antimicrobial susceptibility testing revealed sensitivity to ciprofloxacin and doxycycline, and resistance to amoxicillin and erythromycin. The multiple antibiotic resistance (MAR) index values for V. alginolyticus and V. fluvialis ranged from 0.3 to 0.7, with a multi-drug resistance pattern to at least three antibiotics. Histopathological alterations in the affected tissues revealed marked hemorrhage, vascular congestion, and hemosiderosis infiltration. CONCLUSION: This study provides insights into the potential propagation of waterborne diseases and antibiotic resistance in the environment. Ensuring that the environment does not serve as a reservoir for virulent and contagious Vibrio species is a critical concern for regional aquaculture industries. Therefore, we recommend implementing environmental context-specific monitoring and surveillance tools for microbial resistance.


Assuntos
Dourada , Vibrioses , Vibrio , Animais , Dourada/microbiologia , Prevalência , Egito/epidemiologia , Farmacorresistência Bacteriana , Vibrio/genética , Antibacterianos/farmacologia , Vibrioses/veterinária , Variação Genética
18.
Gastrointest Endosc ; 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38467200

RESUMO

BACKGROUND AND AIMS: Post-operative stricture is serious common adverse event following extensive endoscopic submucosal dissection (ESD) in the esophagus. The self-assembling peptide (SA) gel has been shown to promote tissue healing and re-epithelialization. We aimed to evaluate the effect of the SAP gel for esophageal stricture prevention after ESD. METHODS: Multicenter prospective study of patients who underwent esophageal ESD followed by SAP gel application between March 2022 to December 2023. Patients were included if ESD mucosal defect involved ≥ 50% of the circumference of the esophagus. High-risk cases were defined as mucosal defects ≥75% of the circumference. Stricture was defined as the inability to pass an endoscope ≥8.9 mm in diameter or a narrow-caliber lumen in a patient with symptoms. RESULTS: A total of 43 patients (median age 71 years; 81.4% men) underwent ESD (median resected specimen size 50 mm) during the study period. SAP gel (median 3 mL) was successfully applied in all cases (median time 4 minutes). In aggregate, stricture occurred in 20.9% (9/43) of the cases. Stricture developed in 30.8% of the high-risk cases: 80% (4/5) after circumferential ESD and 19% (4/21) in those with defects ≥75% but <100% of the circumference. All cases of stricture resolved with endoscopic treatment. Three cases (6.9%) of postoperative bleeding occurred and were adequately managed endoscopically. CONCLUSION: We demonstrate that SAP gel application was easy, quick, and associated with a relatively low stricture rate comparable to other prophylactic methods. Additional comparative studies are needed to corroborate these preliminary findings.

19.
BMC Mol Cell Biol ; 25(1): 5, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438917

RESUMO

BACKGROUND: Combination therapies in cancer treatment have demonstrated synergistic or additive outcomes while also reducing the development of drug resistance compared to monotherapy. This study explores the potential of combining the chemotherapeutic agent Paclitaxel (PTX) with Sulforaphane (SFN), a natural compound primarily found in cruciferous vegetables, to enhance treatment efficacy in prostate cancer. METHODS: Two prostate cancer cell lines, PC-3 and LNCaP, were treated with varying concentrations of PTX, SFN, and their combination. Cell viability was assessed using the thiazolyl blue tetrazolium bromide (MTT) assay to determine the EC50 values. Western blot analysis was conducted to evaluate the expression of Bax, Bcl2, and Caspase-3 activation proteins in response to individual and combined treatments of PTX and SFN. Fluorescent microscopy was employed to observe morphological changes indicative of apoptotic stress in cell nuclei. Flow cytometry analysis was utilized to assess alterations in cell cycle phases, such as redistribution and arrest. Statistical analyses, including Student's t-tests and one-way analysis of variance with Tukey's correction, were performed to determine significant differences between mono- and combination treatments. RESULTS: The impact of PTX, SFN, and their combination on cell viability reduction was evaluated in a dose-dependent manner. The combined treatment enhanced PTX's effects and decreased the EC50 values of both drugs compared to individual treatments. PTX and SFN treatments differentially regulated the expression of Bax and Bcl2 proteins in PC-3 and LNCaP cell lines, favoring apoptosis over cell survival. Our data indicated that combination therapy significantly increased Bax protein expression and the Bax/Bcl2 ratio compared to PTX or SFN alone. Flow cytometry analysis revealed alterations in cell cycle phases, including S-phase arrest and an increased population of apoptotic cells. Notably, the combination treatments did not have a discernible impact on necrotic cells. Signs of apoptotic cell death were confirmed through Caspase-3 cleavage, and morphological changes in cell nuclei were assessed via western blot and fluorescent microscopy. CONCLUSION: This combination therapy of PTX and SFN has the potential to improve prostate cancer treatment by minimizing side effects while maintaining efficacy. Mechanistic investigations revealed that SFN enhances PTX efficacy by promoting apoptosis, activating caspase-3, inducing nuclear morphology changes, modulating the cell cycle, and altering Bax and Bcl2 protein expression. These findings offer valuable insights into the synergistic effects of PTX and SFN, supporting the optimization of combination therapy and providing efficient therapeutic strategies in preclinical research.


Assuntos
Apoptose , Isotiocianatos , Neoplasias da Próstata , Sulfóxidos , Masculino , Humanos , Proteína X Associada a bcl-2 , Caspase 3 , Neoplasias da Próstata/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2
20.
J Educ Health Promot ; 13: 36, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38545308

RESUMO

BACKGROUND: Enrolling in medical school launches a more demanding and stressful way of life for newly admitted students. Some students will struggle academically and will ultimately drop out from medical school. The study aims to understand the perspectives that dropped-out students have and their opinion regarding possible preventative solutions. MATERIALS AND METHODS: This study uses a mixed-method approach. The results of students' examinations in the first 2 years of admission (within four academic years from 2016 until 2020) were collected from the medical school records. A questionnaire was developed to investigate the causes of early attrition during the study period. All dropped-out students who were admitted were included in this study. RESULTS: The study included 479 admitted students, 349 (72.9%) were females; 152 (31.7%) students dropped out in the premedical program (first two years); 104 (68.4%) of the dropped-out students were females. Thirty-five (23%) students responded to the questionnaire. Twenty-eight (80%) respondents believed that their low academic performance and leaving medical school was primarily related to psychological problems, 19 (54%) of respondents reported leaving for social reasons, and lack of self-organization in 13 (37.1%) respondents. Human anatomy was recorded as the most difficult course in the first year by 21 (63.6%) students. CONCLUSIONS: The cause of attrition is often multifactorial and complex. Psychological problems are one of the important factors in students with low academic performance and dropping out of the students. Some difficult courses in the curriculum may affect the students' academic performance leading to their attrition.

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