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1.
ACS Med Chem Lett ; 15(6): 892-898, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38894896

RESUMO

Two series of ten new 1,2,4-trisubstituted imidazolin-5-ones were synthesized and screened against MCF-7 breast cancer and A549 lung cancer cell lines to test their potential in vitro anticancer activity. The results revealed preferential activity of the tested compounds toward MCF-7 cell lines compared to A549 cell lines. The most promising ten compounds (3a, 3c, 3f, 3g, 3h, 3i, 3j, 6a, 6f, and 6i) were subjected to VEGFR-2 enzyme inhibitory activity testing to further explore their mechanism of action. The tested compounds showed remarkable enzyme inhibition in micromolar concentrations ranging from 0.07 to 0.36 µM, compared with Sorafenib and Sunitinib with IC50 values of 0.06 and 0.12 µM, respectively. The most promising candidate, 3j, was further evaluated for its cell cycle phases, apoptotic induction ability, as well as its antiproliferative activity and inhibitory potential for endothelial cell migration, analyzed by a cell scratch assay. Furthermore, in silico studies were also performed to identify and detect the stability of the binding poses.

2.
Cureus ; 16(3): e56485, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38638783

RESUMO

Background and objective The association between sibship composition and child body mass index (BMI) has not been investigated in any Arab/Middle Eastern populations. In light of this, this study aimed to examine the association of the number of siblings, number of older siblings, and number of younger siblings with child BMI z-score (BMIz) among preschoolers in the Kingdom of Saudi Arabia (KSA). Methods A total of 209 mothers and their children were recruited from preschools in Jeddah, KSA. Mothers reported their responses to the study questionnaire via telephone. Child anthropometry was objectively measured; BMIz was calculated based on age- and sex-specific World Health Organization (WHO) growth standards and reference data. We used hierarchical multiple linear regression to examine the association between sibship composition variables and child BMIz, independent of the effect of potential confounders, and to evaluate changes in model fit. Results The number of siblings was negatively associated with child BMIz [b = -0.18, 95% confidence interval (CI) = -0.35, -0.06, p<0.01, adjusted R2 = 0.16]. There was a negative association between the number of older siblings and child BMIz (b = -0.23, 95% CI = -0.38, -0.11, p<0.01, adjusted R2 = 0.21) as well as between the number of older sisters and child BMIz (b = -0.18, 95% CI = -0.52, -0.09, p<0.01, adjusted R2 = 0.19). However, there were no significant associations between the number of older brothers or the number of younger siblings and child BMIz. Conclusions Based on our findings, sibship composition was found to be associated with BMIz among a sample of preschoolers in KSA. More research is needed to further establish this association and to understand the underlying mechanism of the association of the greater number of older siblings and older sisters with lower BMIz.

3.
J Genet Eng Biotechnol ; 22(1): 100360, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38494244

RESUMO

BACKGROUND: Somatic embryogenesis offers a reliable method for cucumber (Cucumis sativus L.) regeneration and genetic enhancement against Fusarium wilt. This study aimed to establish a tailored somatic embryogenesis system for Egyptian cultivars, fostering genetic improvements and Fusarium wilt-resistance lines. RESULTS: Employing the Optimal Arbitrary Design (OAD) approach, we optimized the induction medium, initiating prolific embryogenic calli (53.3 %) at 1 mg/L 2,4-D. The cotyledonary leaf (CL) was the preferred explant, showing 60 % embryogenic callus development. Bieth Alpha exhibited higher responsiveness, generating âˆ¼ 18 somatic embryos per explant compared to Prince's âˆ¼ 10. Somatic embryogenesis system validation used quantitative RT-PCR, showing Cucumis sativus splicing factor 3B subunit (CUS1) and an embryogenesis marker gene expression exclusively within embryogenic calli and mainly during embryogenesis initiation. Evaluating fungal toxin filtrate concentrations for selecting embryogenic calli, the S2 selection (25 % filtrate, four subculture cycles) was chosen for somatic embryo development. To gauge the ramifications of selection at the genetic stratum, an in-depth analysis was executed. A cluster analysis grounded in ISSR banding patterns revealed a distinct separation between in vivo-cultivated plants of the two cultivars and regenerated plants devoid of pathogen filtrate treatment or those regenerated post-filtrate treatment. This segregation distinctly underscores the discernible genetic impact of the selection process. CONCLUSIONS: The highest embryogenic capacity (53.3%) was achieved in this study by optimizing the induction stage, which demonstrated the optimal concentrations of BA and 2,4-D for induced proembryonic masses. Moreover, consistent gene expression throughout both stages of embryogenesis suggests that our system unequivocally follows the somatic embryogenesis pathway.

4.
AIMS Microbiol ; 10(1): 148-160, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38525041

RESUMO

One of the most prevalent malignancies that significantly affects world health is colorectal cancer (CRC). While genetics are involved in a portion of CRC patients, most cases are sporadic. The microbiome composition could be a new source of tumor initiation and progression. This research was conducted to investigate the microbiota composition of CRC patients post colectomy at taxonomic and functional levels. Using a next-generation sequencing approach, using an Illumina Novaseq 6000, the fecal samples of 13 patients were analyzed and the obtained data was subjected to a bioinformatics analysis. The bacterial abundance and uniqueness varied in CRC patients alongside differences in bacterial counts between patients. Bacteroides fragilis, Bacteroides vulgatus, Escherichia coli, and Fusobacterium nucleatum were among the pro-cancerous microorganisms found. Concurrently, bacteria linked to CRC progression were detected that have been previously linked to metastasis and recurrence. At the same time, probiotic bacteria such as Bifidobacterium dentium, Bifidobacterium bifidum, and Akkermansia muciniphila increased in abundance after colectomies. Additionally, numerous pathways were deferentially enriched in CRC, which emerged from functional pathways based on bacterial shotgun data. CRC-specific microbiome signatures include an altered bacterial composition. Our research showed that microbial biomarkers could be more usefully employed to explore the link between gut microbiota and CRC using metagenomic techniques in the diagnosis, prognosis, and remission of CRC, thereby opening new avenues for CRC treatment.

5.
J Dairy Sci ; 107(7): 4714-4725, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38310961

RESUMO

In dairy cattle production, it is important to understand how inbreeding affects production, fertility, and health traits. However, there is still limited use of genomic information to estimate inbreeding, despite advancements in genotyping technologies. To address this gap, we investigated the effect of inbreeding on German Holstein dairy cattle using both pedigree-based and genomic-based inbreeding estimators. We employed one method based on pedigree information (Fped) together with 6 genomic-based methods, including 3 genome-wide complex trait analysis software estimators (Fhat1, Fhat2, Fhat3), VanRaden's first method (FVR1, with observed allele frequencies, and FVR0.5, when allele frequencies are set to 0.5), and one based on runs of homozygosity (Froh). Data from 24,489 cows with both phenotypes and genotypes were used, with a pedigree including 232,780 animals born between 1970 and 2018. We analyzed the effects of inbreeding depression on production, fertility, and health traits separately, using single-trait linear animal models as well as threshold models to account for the binary nature of the health traits. For the health traits, we transformed solutions from the liability scale to a probability scale for easier interpretation. Our results showed that the mean inbreeding coefficients from all estimators ranged from -0.003 to 0.243, with negative values observed for most genomic-based methods. We found out that a 1% increase in inbreeding caused a depression ranging from 25.94 kg (Fhat1) to 40.62 kg (Fhat3), 1.18 kg (Fhat2) to 1.70 kg (Fhat3), 0.90 kg (Fhat2) to 1.45 kg (Froh and Fhat3), 0.19 (Fped) to 0.34 d (Fhat3) for 305-d milk yield, fat, protein, and calving interval, respectively. The health traits showed very slight gradual changes when inbreeding was increased steadily from 0% to 50%, with digital dermatitis showing a rather contrasting trend to that of mastitis, which increased the more an animal was inbred. Overall, our study highlights the importance of considering both pedigree-based and genomic-based inbreeding estimators when assessing the impact on inbreeding, emphasizing that not all inbreeding is harmful.


Assuntos
Fertilidade , Genótipo , Endogamia , Fenótipo , Animais , Bovinos/genética , Fertilidade/genética , Feminino , Linhagem , Frequência do Gene
6.
Heliyon ; 10(2): e24343, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38298671

RESUMO

This work deals with the synthesis, structural characterization and applications of N-halamine glycinate functionalized silica-mesoporous silica coated ZnO-NPs/AC composite for water disinfection. Several nanocomposite materials were obtained: ZnO-NPs/AC, ZnO-NPs/AC@SiO2, ZnO-NPs/AC@SiO2@mSiO2, ZnO-NPs@SiO2@mSiO2-Gly and ZnO-NPs@SiO2@mSiO2-N-halamine-Gly. These nanocomposite materials were fully characterized via different physiochemical techniques including: FTIR, TGA, XPS, XRD, SEM, TEM and BET. XRD indicated a predominance of crystalline pattern of ZnO-NPs impregnated into activated carbon (AC) and their silica and m-mesoporous silica coating precursors. The FTIR spectra confirmed an immense combination between ZnO-NPs and AC of ZnO-NPs/AC nanocomposite as well as its interactions with coated silica precursors. SEM, TEM images illustrated that the fabricated ZnO-NPs/AC nanocomposites are well coated with silica-mesoporous silica functionalized N-halamine. The distinctive surface area has decreased from 800 m2/g for pristine AC to 772 m2/g for ZnO-NPs/AC and to 282 m2/g for ZnO-NPs/AC@SiO2 and to 139 m2/g for ZnO-NPs/AC@SiO2@mSiO2 and to 15.4 m2/g for ZnO-NPs@SiO2@mSiO2-N-Gly. All those nanocomposites showed good efficacy against all four bacterial species, with higher inhibition zones for the 2 g-positive bacteria than that of the 2 g-negative ones. The ZnO@SiO2@mSiO2-N-halamine-Gly exhibited the high zone inhibition against all tested bacteria except for E. Coli.

7.
Future Med Chem ; 16(4): 349-368, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38288554

RESUMO

Background: The search is ongoing for ideal anti-inflammatory and analgesic agents with promising potency and reasonable selectivity. Methods: New N1-substituted pyrazoles with or without an acetamide linkage were synthesized and evaluated for their anti-inflammatory and analgesic activities. COX inhibitory testing, molecular docking, molecular dynamics simulation and antiproliferative activity assessments were performed. Results: All compounds exhibited anti-inflammatory activity up to 90.40% inhibition. They also exhibited good analgesic activity with up to 100% protection. N1-benzensulfonamides 3d, 6c and 6h were preferentially selective agents toward COX-2. Compound 3d showed good cytotoxicity against MCF-7 and HTC116 cancer cell lines. Molecular modeling studies predicted the binding pattern of the most active compounds. Molecular dynamics confirmed the docking results. All compounds showed remarkable pharmacokinetic properties.


Assuntos
Anti-Inflamatórios , Pirazóis , Pirazóis/farmacologia , Pirazóis/química , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Anti-Inflamatórios/farmacologia , Analgésicos/farmacologia , Analgésicos/química , Ciclo-Oxigenase 2/metabolismo , Simulação de Dinâmica Molecular , Estrutura Molecular , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/química
8.
Int J Mol Sci ; 24(21)2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37958828

RESUMO

(1) Background: Hepatitis C virus (HCV) infection is endemic in Egypt, with the highest prevalence rate worldwide. Sofosbuvir (SOF) is a nucleos(t)ide analog that specifically inhibits HCV replication. This study aimed to explore the possible effects of the therapeutic dose of SOF on the mitochondrial biogenesis and functions of the liver, muscle, and ovarian tissues of young normal female rats. (2) Methods: This study was conducted on 20 female Wistar rats, classified into two groups, the control group and the exposed group; the latter was orally supplemented with 4 mg/kg/day of SOF for 3 months. (3) Results: The exposure to SOF impairs mitochondrial biogenesis via mitochondrial DNA copy number decline and suppressed mitochondrial biogenesis-regulated parameters at mRNA and protein levels. Also, SOF suppresses the DNA polymerase γ (POLG) expression, citrate synthase activity, and mitochondrial NADH dehydrogenase subunit-5 (ND5) content, which impairs mitochondrial functions. SOF increased lipid peroxidation and oxidative DNA damage markers and decreased tissue expression of nuclear factor erythroid 2-related factor 2 (Nfe2l2). (4) Conclusions: The present findings demonstrate the adverse effects of SOF on mitochondrial biogenesis and function in different tissues of young female rats, which mostly appeared in ovarian tissues.


Assuntos
Hepatite C Crônica , Hepatite C , Feminino , Ratos , Animais , Antivirais , Hepatite C Crônica/tratamento farmacológico , Biogênese de Organelas , Resultado do Tratamento , Ratos Wistar , Sofosbuvir/uso terapêutico , Hepatite C/tratamento farmacológico , Hepacivirus/genética , Quimioterapia Combinada , Genótipo
9.
Life Sci ; 335: 122252, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37935275

RESUMO

Attention deficit hyperactivity disorder (ADHD) has high incidence rate among children which may be due to excessive monosodium glutamate (MSG) consumption and social isolation (SI). AIM: We aimed to explore the relationships between MSG, SI, and ADHD development and to evaluate the neuroprotective potential of Punicalagin (PUN). METHODS: Eighty male rat pups randomly distributed into eight groups. Group I is the control, and Group II is socially engaged rats treated with PUN. Groups III to VII were exposed to ADHD-inducing factors: Group III to SI, Group IV to MSG, and Group V to both SI and MSG. Furthermore, Groups VI to VIII were the same Groups III to V but additionally received PUN treatment. KEY FINDINGS: Exposure to MSG and/or SI led to pronounced behavioral anomalies, histological changes and indicative of ADHD-like symptoms in rat pups which is accompanied by inhibition of the nuclear factor erythroid 2-related factor 2 (Nrf2)/Heme-oxygenase 1 (HO-1)/Glutathione (GSH) pathway, decline of the brain-derived neurotrophic factor (BDNF) expression and activation of the Toll-like receptor 4 (TLR4)/Nuclear factor kappa B (NF-kB)/NLR Family Pyrin Domain Containing 3 (NLRP3) pathway. This resulted in elevated inflammatory biomarker levels, neuronal apoptosis, and disrupted neurotransmitter equilibrium. Meanwhile, pretreatment with PUN protected against all the previous alterations. SIGNIFICANCE: We established compelling associations between MSG consumption, SI, and ADHD progression. Moreover, we proved that PUN is a promising neuroprotective agent against all risk factors of ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estresse Oxidativo , Humanos , Criança , Ratos , Animais , Masculino , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Glutamato de Sódio , Oxirredução , Glutationa/metabolismo , Isolamento Social , Fator 2 Relacionado a NF-E2/metabolismo
10.
Neurosurg Rev ; 46(1): 261, 2023 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-37779130

RESUMO

Epilepsy is a common condition that affects approximately 1% of the world's population, with about one-third being refractory epilepsy. Temporal lobe epilepsy is the most common type of drug-resistant epilepsy, and laser interstitial thermal therapy (LITT) is an innovative treatment. In this systematic review and meta-analysis, we aimed to summarize the current evidence on outcomes after LITT, including seizure freedom rate, complication rate, and neurocognitive outcome. PubMed and OVID Medline search engines were systematically searched for all indexed publications in the English language up to July15, 2023. The search was limited to human studies. Proportions and 95% confidence interval (CI) values were calculated for seizure, neurocognitive outcome, and complication rate. A total of 836 patients were included. Overall seizure outcomes, regardless of the pathology, included Engel I outcome in 56% (95% CI, 52.4-59.5%), Engel II outcome in 19.2% (95% CI, 15.4-23.6%), Engel III outcome in 17.3% (95% CI, 13.5-21.8%), and Engel IV outcome in 10.5% (95% CI 6.3-17%) of the patients. The overall decline in verbal and visual memory regardless of laterality was 24.2 (95% CI 8.6-52%) and 25.2% (8.3-55.8%). For naming, the decline was 13.4% (6.6-25.4%). The results of the pooled analysis in comparison with available data in the literature showed that seizure outcomes after LITT were slightly inferior to published data after temporal lobectomy. Data on cognitive outcomes after LITT are scarce and heterogeneous.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia do Lobo Temporal , Epilepsia , Terapia a Laser , Humanos , Epilepsia do Lobo Temporal/cirurgia , Resultado do Tratamento , Terapia a Laser/métodos , Convulsões/cirurgia , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia/cirurgia , Imageamento por Ressonância Magnética/métodos , Lasers
11.
Diagnostics (Basel) ; 13(20)2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37892067

RESUMO

Antibiotic resistance is a global public health concern, posing a significant threat to the effectiveness of antibiotics in treating bacterial infections. The accurate and timely detection of antibiotic-resistant bacteria is crucial for implementing appropriate treatment strategies and preventing the spread of resistant strains. This manuscript provides an overview of the current and emerging technologies used for the detection of antibiotic-resistant bacteria. We discuss traditional culture-based methods, molecular techniques, and innovative approaches, highlighting their advantages, limitations, and potential future applications. By understanding the strengths and limitations of these technologies, researchers and healthcare professionals can make informed decisions in combating antibiotic resistance and improving patient outcomes.

12.
J Biol Chem ; 299(11): 105303, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37777154

RESUMO

Mitochondrial fission protein 1 (FIS1) is conserved in all eukaryotes, yet its function in metazoans is thought divergent. Structure-based sequence alignments of FIS1 revealed a conserved, but noncanonical, three-residue insert in its first tetratricopeptide repeat (TPR) suggesting a conserved function. In vertebrates, this insert is serine (S45), lysine (K46), and tyrosine (Y47). To determine the biological role of the "SKY insert," three variants were tested in HCT116 cells for altered mitochondrial morphology and recruitment of fission mechanoenzyme DRP1 and mitophagic adaptor TBC1D15. Similar to ectopically expressed wildtype FIS1, substitution of the SKY insert with alanine (AAA) fragmented mitochondria into perinuclear clumps associated with increased mitochondrial DRP1. In contrast, deletion variants (either ∆SKY or ∆SKYD49G) elongated mitochondrial networks with reduced mitochondrial recruitment of DRP1, despite DRP1 coimmunoprecipitates being highly enriched with ΔSKY variants. Ectopic wildtype FIS1 drove co-expressed YFP-TBC1D15 entirely from the cytoplasm to mitochondria as punctate structures concomitant with enhanced mitochondrial DRP1 recruitment. YFP-TBC1D15 co-expressed with the AAA variant further enhanced mitochondrial DRP1 recruitment, indicating a gain of function. In contrast, YFP-TBC1D15 co-expressed with deletion variants impaired mitochondrial DRP1 and YFP-TBC1D15 recruitment; however, mitochondrial fragmentation was restored. These phenotypes were not due to misfolding or poor expression of FIS1 variants, although ∆SKYD49G induced conformational heterogeneity that is lost upon deletion of the regulatory Fis1 arm, indicating SKY-arm interactions. Collectively, these results support a unifying model whereby FIS1 activity is effectively governed by intramolecular interactions between its regulatory arm and a noncanonical TPR insert that is conserved across eukaryotes.


Assuntos
Proteínas de Membrana , Dinâmica Mitocondrial , Animais , Citoplasma/metabolismo , Dinaminas/genética , Dinaminas/metabolismo , Proteínas de Membrana/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Humanos , Linhagem Celular Tumoral
13.
Int J Mol Sci ; 24(18)2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37761983

RESUMO

Sofosbuvir (SOF), a nucleos(t)ide polymerase inhibitor, has been used during the past decade for mass treatment of viral hepatitis C in endemic countries like Egypt, increasing the exposure of women at childbearing age to SOF. This study investigated the long-lasting consequences of the pre-conceptional exposure of young female rats to SOF on the ovarian tissues of F1 offspring and explored the possible molecular mechanisms of these intergenerational effects at various levels. The study was conducted on young female rats that were divided into control group and SOF-exposed group at a dose of 4 mg/kg/day for three months. After that, pregnancy was induced in both groups by mating with healthy male rats. After delivery, the female neonates were followed for 4 months, and the ovarian tissues were collected to assess the studied parameters. Pre-conceptional exposure to SOF affected the ovarian functions of F1 offspring through modulation of estrogen receptors, ovarian Kiss1 and its receptor, increased lipid peroxidation marker, DNA oxidation marker, and redox-sensitive nuclear factor kappa B, and decreased nuclear erythroid-2-related factor 2, mitochondrial function, and biogenesis. SOF affected the ovarian function of the F1 offspring by inducing oxidative stress and inflammation, leading to the modulation of mitochondrial functions and biogenesis.


Assuntos
Hepatite C , Sofosbuvir , Gravidez , Animais , Ratos , Feminino , Humanos , Masculino , Sofosbuvir/farmacologia , Fertilização , Reprodução , Comunicação Celular
14.
Front Psychol ; 14: 1126687, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37593653

RESUMO

Evidence from previous work suggest that feeding practices during the first years of life may influence the development of eating behaviors later in childhood. Early feeding practices may also predict later maternal feeding behaviors. Mothers from an Arab/Middle Eastern background may adopt unique early feeding practices. The objective of this study was to examine the association of offering fruit juice and date syrup-milk mixture in a baby bottle during infancy with: 1) Child eating behaviors during preschool years; 2) Maternal indulgent feeding practices during preschool years. Mothers of preschoolers (n = 115) completed questions adopted from the Children's Eating Behavior Questionnaire (CEBQ), Child Feeding Questionnaire-Arabic (CFQ-A), as well as questions assessing early feeding practices and demographic characteristics. Unadjusted and adjusted logistic regression models were tested to examine the association of early feeding practices with child eating behaviors and maternal indulgent feeding behaviors. Odds ratios (ORs) and respective 95% confidence intervals (CI) were derived. Adjusting for covariates, children who were ever offered fruit juice in a baby bottle as infants were more likely to have high food responsiveness at preschool, compared to children who were not (OR = 2.93, 95% CI = 1.16, 7.42). Mothers who reported ever offering fruit juice in a baby bottle when their children were infants were more likely to adopt greater use of food as a reward when their children were at preschool (OR = 3.25, 95% CI = 1.22, 8.68). Early feeding practices are associated with child eating and maternal feeding behaviors later in childhood. Future longitudinal studies are needed to further establish these associations. Findings from this study can help inform community awareness and education programs to prevent maladaptive feeding practices and promote appropriate feeding strategies throughout childhood.

15.
BMC Microbiol ; 23(1): 238, 2023 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-37644393

RESUMO

BACKGROUND: Colorectal cancer (CRC) is a public health concern and the second most common disease worldwide. This is due to genetic coding and is influenced by environmental aspects, in which the gut microbiota plays a significant role. The purpose of this study was to compare the microbiota makeup of CRC patients with that of healthy control and to identify upregulated and downregulated proteins and metabolites in CRC patients. Using a next-generation sequencing approach, fecal samples of five females (4 CRC patients and one healthy control) were analyzed by BGI DNBSEQ-T7, Hong Kong, China. Furthermore, proteomics and metabolomics analysis were performed using LC-MS/MS technique. RESULTS: Dysbiosis of gut microbiota has been observed in patients with CRC, with an increase in microbiota diversity at all taxonomic levels relative to healthy control. Where, at the functional level the bacterial species participate in many different pathways among them de novo nucleotide synthesis and amino acids pathways were aberrantly upregulated in CRC patients. Proteomics and metabolomics profiles of CRC patients showed different proteins and metabolites, a total of 360 and 158 proteins and metabolites, respectively were highly expressed compared to healthy control with fold change ≥ 1.2. Among the highly expressed proteins were transketolase, sushi domain-containing protein, sulfide quinone oxidoreductase protein, AAA family ATPase protein, carbonic anhydrase, IgG Fc-binding protein, nucleoside diphosphate kinase protein, arylsulfatase, alkaline phosphatase protein, phosphoglycerate kinase, protein kinase domain-containing protein, non-specific serine/threonine protein kinase, Acyl-CoA synthetase and EF-hand domain-containing protein. Some of the differential metabolites, Taurine, Taurocholic acid, 7-ketodeoxycholic acid, Glycochenodeoxycholic acid, Glycocholic acid, and Taurochenodeoxycholic acid that belong to bile acids metabolites. CONCLUSIONS: Some bacterial species, proteins, and metabolites could be used as diagnostic biomarkers for CRC. Our study paves an insight into using multi-omics technology to address the relationship between gut microbiota and CRC.


Assuntos
Neoplasias Colorretais , Multiômica , Feminino , Humanos , Projetos Piloto , Cromatografia Líquida , Espectrometria de Massas em Tandem , Proteínas Quinases , Neoplasias Colorretais/genética
16.
Mol Med ; 29(1): 71, 2023 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-37280507

RESUMO

BACKGROUND: Hepatitis C virus (HCV) infection is a global public health problem and Egypt has the highest HCV prevalence worldwide. Hence, global efforts target to eliminate HCV by 2030. Sofosbuvir is a nucleotide analogue inhibitor of HCV polymerase essential for viral replication. Animal studies prove that Sofosbuvir metabolites cross the placenta and are excreted in the milk of nursing animals. We aimed to investigate the possible effects of preconception maternal exposure to Sofosbuvir on mitochondrial biogenesis in prenatal fetal liver, skeletal muscle, and placental tissues. METHODS: The study was conducted on 20 female albino rats divided into a control group receiving a placebo and an exposed group receiving 4 mg/kg orally/day for 3 months of Sofosbuvir. At the end of the treatment period, pregnancy was induced in both groups by mating with healthy male rats overnight. At gestational day 17, all pregnant female rats were sacrificed. Each fetus was dissected to obtain the fetal liver, skeletal muscle, and placental tissues. RESULTS: The results of our study indicated that the exposure of young female rats to Sofosbuvir affects pregnancy outcomes. Fetal liver and muscle showed lower mitochondrial DNA-copy number (mtDNA-CN) by about 24% and 29% respectively, peroxisome proliferator-activated receptor-gamma coactivator-1 alpha and its downstream targets; nuclear respiratory factor-1 and mitochondrial transcription factor A. While the placental tissues showed different patterns, particularly elevated in mtDNA-CN by about 43%. CONCLUSIONS: The study provides preliminary evidence of the detrimental effects of Sofosbuvir on the pregnancy outcomes of the exposed females and may impair the placental and fetal organs' development. These effects may be mediated through modulating mitochondrial homeostasis and functions.


Assuntos
Hepatite C , Sofosbuvir , Humanos , Feminino , Gravidez , Masculino , Ratos , Animais , Sofosbuvir/farmacologia , Sofosbuvir/uso terapêutico , Placenta/metabolismo , Exposição Materna/efeitos adversos , Biogênese de Organelas , DNA Mitocondrial/metabolismo , DNA Mitocondrial/farmacologia , Feto , Hepatite C/tratamento farmacológico , Hepatite C/metabolismo , Genótipo
17.
Vaccines (Basel) ; 11(6)2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37376459

RESUMO

Despite the effectiveness of current vaccines in reducing the spread and severity of SARS-CoV-2 infections, many people, including migrants, refugees, and foreign workers, are hesitant to be vaccinated. This systematic review and meta-analysis (SRMA) was conducted to determine the pooled prevalence estimate of the acceptance and hesitancy rates of the COVID-19 vaccine among these populations. A comprehensive search of the peer-reviewed literature indexed in PubMed, Scopus, Science Direct, and Web of Science databases was conducted. Initially, 797 potential records were identified, of which 19 articles met the inclusion criteria. A meta-analysis of proportions using data from 14 studies revealed that the overall acceptance rate of COVID vaccination among 29,152 subjects was 56.7% (95% CI: 44.9-68.5%), while the prevalence of vaccine hesitancy among 26,154 migrants reported in 12 studies was estimated to be 31.7% (95% CI: 44.9-68.5%). The acceptance rate for the COVID-19 vaccination first declined from 77.3% in 2020 to 52.9% in 2021 and then slightly increased to 56.1% in 2022. The most frequent factors influencing vaccine hesitancy were worries about vaccine efficacy and safety. Intensive vaccination campaigns should be implemented to raise vaccination awareness among migrants, which will increase the acceptance rate for the COVID-19 vaccine and result in herd immunity.

18.
Am J Speech Lang Pathol ; 32(4): 1770-1781, 2023 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-37257285

RESUMO

PURPOSE: Swallowing and taste share innervation pathways and are crucial to nutritive intake. Individuals vary in their perception of taste due to factors such as genetics; however, it is unclear to what extent genetic taste status influences swallowing physiology and function. The purpose of this review article is to provide background on genetic taste status, review the evidence on the association between genetic taste status and swallowing, and discuss research and clinical implications. METHOD: A comprehensive literature review was conducted using search terms related to swallowing and genetic taste status. Studies were included if they investigated the main effect of genetic taste status on swallowing or the interaction of genetic taste status with other variables. Studies were grouped by participant population (healthy participants or persons with a swallowing disorder), swallowing-related outcome measure, and method of genetic taste status measurement. RESULTS: The results were mixed, with five of 10 reviewed studies reporting a statistically significant main or interaction effect on swallowing. Most studies included healthy participants, with only one study investigating participants with dysphagia. Additionally, swallowing-related outcome measures and methods of determining genetic taste status varied greatly between studies conducted on separate cohorts. CONCLUSIONS: Few studies have incorporated genetic taste status as a variable in swallowing research, and results are mixed. Future research on sensation and swallowing should consider the potential effect of genetic taste status and follow standardized procedures for its determination. Despite the limited evidence, clinicians may consider how individual differences in perception shape swallowing outcomes.


Assuntos
Transtornos de Deglutição , Deglutição , Humanos , Deglutição/fisiologia , Paladar/genética , Percepção Gustatória/genética , Transtornos de Deglutição/genética , Voluntários Saudáveis
19.
Cureus ; 15(4): e37636, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37200671

RESUMO

Background and objective Hypothyroidism is extremely common and associated with far-reaching health consequences. The negative effects of hypothyroidism on patients' quality of life (QoL) are well-documented. It is said to be common in the countries of the Arabian Gulf, although it is often misdiagnosed and treated in an inconsistent manner. Hence, understanding how an illness like this affects a patient's life might help us enhance their QoL and get us closer to the healthcare transformation goals of Saudi Arabia's Vision 2030. Methodology This cross-sectional study was conducted in Riyadh, Saudi Arabia, between June 2022 and February 2023. A convenience non-probability sampling method was used. The WHO Quality of Life (WHOQOL)-BREF questionnaire in Arabic was used to compile the data. Data were collected using a standardized form, refined using Google Forms, and then documented in an Excel spreadsheet. The descriptive statistics were shown as means and standard deviations (SD). To assess the numerical data, a t-test was used, while the chi-square test was employed to examine the relationship between the qualitative factors. Results A total of 394 adults from the general population with hypothyroidism were surveyed, including 105 men and 289 women. Of them, 151 (38.3%) patients had not sought therapy for their hypothyroidism, while 243 (61.7%) patients had. When asked about the QoL, a significant segment (37.6%) of patients reported that it was high, and 29.7% reported being totally satisfied with their health. The WHOQOL-BREF domain scores revealed that environmental health had the highest value (24.04 ±4.62), followed by physical health (22.24 ±3.23), and then psychological health (18.08 ±2.82), and the lowest scores were reported for the rate of QoL and satisfaction with health (2.64 ±1.36 and 2.80 ±1.68), respectively. Each domain of the WHOQOL-BREF had its own set of variables that differed from one another in a statistically significant manner (p<0.001). Conclusions  Based on our findings, we recommend expert physician monitoring and implementing educational programs as well as placing a greater emphasis on patients' QoL in the management of hypothyroidism.

20.
Infect Dis Ther ; 12(5): 1217-1235, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37071349

RESUMO

INTRODUCTION: Gram-negative bacteria (GNB) have become prominent across healthcare and community settings due to factors including lack of effective infection control and prevention (ICP) and antimicrobial stewardship programs (ASPs), GNB developing antimicrobial resistance (AMR), and difficulty treating infections. This review summarizes available literature on healthcare-associated infections (HAIs) in Middle Eastern pediatric patients. METHODS: Literature searches were performed with PubMed and Embase databases. Articles not reporting data on GNB, HAIs, pediatric patients, and countries of interest were excluded. RESULTS: The searches resulted in 220 publications, of which 49 met the inclusion criteria and 1 additional study was identified manually. Among 19 studies across Egypt reporting GNB prevalence among pediatric patients, Klebsiella species/K. pneumoniae and Escherichia coli were typically the most common GNB infections; among studies reporting carbapenem resistance and multidrug resistance (MDR), rates reached 86% and 100%, respectively. Similarly, in Saudi Arabia, Klebsiella spp./K. pneumoniae and E. coli were the GNB most consistently associated with infections, and carbapenem resistance (up to 100%) and MDR (up to 75%) were frequently observed. In other Gulf Cooperation Council countries, including Kuwait, Oman, and Qatar, carbapenem resistance and MDR were also commonly reported. In Jordan and Lebanon, E. coli and Klebsiella spp./K. pneumoniae were the most common GNB isolates, and AMR rates reached 100%. DISCUSSION: This review indicated the prevalence of GNB-causing HAIs among pediatric patients in Middle Eastern countries, with studies varying in reporting GNB and AMR. Most publications reported antimicrobial susceptibility of isolated GNB strains, with high prevalence of extended-spectrum beta-lactamase-producing K. pneumoniae and E. coli isolates. A review of ASPs highlighted the lack of data available in the region. CONCLUSIONS: Enhanced implementation of ICP, ASPs, and AMR surveillance is necessary to better understand the widespread burden of antimicrobial-resistant GNB and to better manage GNB-associated HAIs across Middle Eastern countries.

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