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Saudi Journal of Biological Sciences Aug 2024Human Rotavirus (HRV) is the causative pathogen of severe acute enteric infections that cause mortality among children worldwide. This study focuses on developing a new...
Human Rotavirus (HRV) is the causative pathogen of severe acute enteric infections that cause mortality among children worldwide. This study focuses on developing a new and effective treatment for rotavirus infection using an extract from Saccharomyces cerevisiae, aiming to make this treatment easily accessible to everyone. 15 antigens and 26 antibodies were detected in serum and stool using ELISA. The titers of HRVq1, HRVq2, HRVC1, and HRVC2 on Vero cells were determined to be 1.2x10, 3.0x10, 4.2x10, and 7.5x10 (Plaque forming unit, PFU/ml) four days after infection, respectively. The HRVq1 isolate induced cytopathic effects, i.e., forming multinucleated, rounded, enlarged, and expanding gigantic cells. RT-PCR identified this isolate, and the accession number 2691714 was assigned to GeneBank. The molecular docking analysis revealed that nonstructural proteins (NSPs) NSP1, NSP2, NSP3, NSP4, NSP5, and NSP6 exhibited significant binding with RNA. NSP2 demonstrated the highest binding affinity and the lowest binding energy (-8.9 kcal/mol). This affinity was maintained via hydrophobic interactions and hydrogen bonds spanning in length from 1.12 Å to 3.11 Å. The ADMET and bioactivity predictions indicated that the yeast extract possessed ideal solubility, was nontoxic, and did not cause cancer. The inhibitory constant values predicted for the extract in the presence of HRV vital proteins varied from 5.32 to 7.45 mM, indicating its potential as a viable drug candidate. extract could be utilized as a dietary supplement to combat HRV as an alternative dietary supplement.
PubMed: 38946847
DOI: 10.1016/j.sjbs.2024.104031 -
Frontiers in Nutrition 2024The study highlighted the potential of sesame seed coat (SSC), typically discarded during sesame paste processing, as a valuable resource for valorization through...
The study highlighted the potential of sesame seed coat (SSC), typically discarded during sesame paste processing, as a valuable resource for valorization through extracting bioactive compounds. It examined the phenolic composition and antioxidant activity of SSC, and evaluated its antibacterial properties against foodborne pathogens such as O157:H7, and Typhimurium. Additionally, SSC underwent nanoemulsion coating, analyzed using dynamic light scattering and scanning electron microscopy, to enhance its application as a natural preservative. The research specifically focused on incorporating SSC nanoemulsion into milk to determine its effectiveness as a preservative. SSC demonstrated considerable antioxidant activity and phenolic content, with catechin identified as the predominant polyphenol. GC-MS analysis revealed seven major compounds, led by oleic acid. Notably, SSC effectively inhibited in broth at 100 mg/ml. The application of SSC and its nanoemulsion resulted in changes to bacterial morphology and a significant reduction in bacterial counts in milk, highlighting its potential as an effective natural antibacterial agent. The findings of this study highlight the potential use of SSC as a valuable by-product in the food industry, with significant implications for food preservation.
PubMed: 38946786
DOI: 10.3389/fnut.2024.1405708 -
The Pan African Medical Journal 2024as cholera, due to toxigenic bacteria Vibrio cholera (serogroups O1 and O139), is a major public health threat in Africa, the aim of this work was to investigate...
INTRODUCTION
as cholera, due to toxigenic bacteria Vibrio cholera (serogroups O1 and O139), is a major public health threat in Africa, the aim of this work was to investigate potentially pathogenic Vibrionaceae bacteria firstly from human stool samples, and secondly from various environmental water points of Saint-Louis city in Senegal.
METHODS
a hospital-based study was conducted between 2013 and 2015. Stool samples were taken and cultured from daily incoming patients or hospitalized for acute diarrhea at Saint-Louis´ regional hospital. For environment, a monthly longitudinal sampling from January to October 2016 was carried out at 10 sites in the city. We used total DNA extracted from APW (alkaline peptone water) broth solutions and on suspect bacterial colonies to run PCR Multiplex targeting specific DNA fragments to detect Vibrio genus and specific species. In case of positivity, a simplex PCR was performed to test for cholera toxins Ctx, and V. parahaemolyticus TRH and TDH.
RESULTS
for 43 patients screened, bacterial culture was positive in 6% of cases but no strain of V. cholerae or other Vibrio sp. was isolated. PCR on 90 APW solutions were positive for Vibrio sp.(n = 43), V. cholera(n = 27), V. mimicus(n = 16), V. parahaemolyticus(8), V. alginolyticus(n = 4), and V. vulnificus(n = 2). Unlike for those on suspected colonies which were positive for a majority of V. parahaemolyticus (n = 40) and V. cholerae non-O1 / O139 (n = 35). Six strains of V. parahaemolyticus carried TRH gene, 3 of which expressed simultaneously virulence TRH and TDH genes. For physicochemical parameters, all temperatures varied similarly according to a unimodal seasonality, as well as salinity.
CONCLUSION
despite the presence of natural populations of Vibrionaceae, even toxigenic ones, was noted in water environment, along with favorable habitat conditions that could play a role in transmission of Vibriosis in the Saint Louis population, we did not isolate any of them from patients screened at the hospital.
Topics: Humans; Senegal; Cholera; Feces; Polymerase Chain Reaction; Diarrhea; Water Microbiology; Vibrionaceae; Vibrio; DNA, Bacterial; Vibrio cholerae; Adult; Female; Male
PubMed: 38946740
DOI: 10.11604/pamj.2024.48.5.34685 -
Epilepsia Open Jul 2024Epilepsy is a suitable target for gene panel sequencing because a considerable portion of epilepsy is now explained by genetic components, especially in syndromic cases....
OBJECTIVE
Epilepsy is a suitable target for gene panel sequencing because a considerable portion of epilepsy is now explained by genetic components, especially in syndromic cases. However, previous gene panel studies on epilepsy have mostly focused on pediatric patients.
METHODS
We enrolled adult epilepsy patients meeting any of the following criteria: family history of epilepsy, seizure onset age ≤ 19 years, neuronal migration disorder, and seizure freedom not achieved by dual anti-seizure medications. We sequenced the exonic regions of 211 epilepsy genes in these patients. To confirm the pathogenicity of a novel MTOR truncating variant, we electroporated vectors with different MTOR variants into developing mouse brains.
RESULTS
A total of 92 probands and 4 affected relatives were tested, and the proportion of intellectual disability (ID) and/or developmental disability (DD) was 21.7%. As a result, twelve probands (13.0%) had pathogenic or likely pathogenic variants in the following genes or regions: DEPDC5, 15q12-q13 duplication (n = 2), SLC6A1, SYNGAP1, EEF1A2, LGI1, MTOR, KCNQ2, MEF2C, and TSC1 (n = 1). We confirmed the functional impact of a novel truncating mutation in the MTOR gene (c.7570C > T, p.Gln2524Ter) that disrupted neuronal migration in a mouse model. The diagnostic yield was higher in patients with ID/DD or childhood-onset seizures. We also identified additional candidate variants in 20 patients that could be reassessed by further studies.
SIGNIFICANCE
Our findings underscore the clinical utility of gene panel sequencing in adult epilepsy patients suspected of having genetic etiology, especially those with ID/DD or early-onset seizures. Gene panel sequencing could not only lead to genetic diagnosis in a substantial portion of adult epilepsy patients but also inform more precise therapeutic decisions based on their genetic background.
PLAIN LANGUAGE SUMMARY
This study demonstrated the effectiveness of gene panel sequencing in adults with epilepsy, revealing pathogenic or likely pathogenic variants in 13.0% of patients. Higher diagnostic yields were observed in those with neurodevelopmental disorders or childhood-onset seizures. Additionally, we have shown that expanding genetic studies into adult patients would uncover new types of pathogenic variants for epilepsy, contributing to the advancement of precision medicine for individuals with epilepsy. In conclusion, our results highlight the practical value of employing gene panel sequencing in adult epilepsy patients, particularly when genetic etiology is clinically suspected.
PubMed: 38946282
DOI: 10.1002/epi4.12993 -
Quantitative phosphoproteomics reveals molecular pathway network in wheat resistance to stripe rust.Stress Biology Jul 2024Protein phosphorylation plays an important role in immune signaling transduction in plant resistance to pathogens. Wheat stripe rust, caused by Puccinia striiformis f....
Protein phosphorylation plays an important role in immune signaling transduction in plant resistance to pathogens. Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), severely devastates wheat production. Nonetheless, the molecular mechanism of wheat resistance to stripe rust remains limited. In this study, quantitative phosphoproteomics was employed to investigate the protein phosphorylation changes in wheat challenged by Pst. A total of 1537 and 2470 differentially accumulated phosphoproteins (DAPs) were identified from four early infection stage (6, 12, 18 and 24 h post-inoculation) in incompatible and compatible wheat-Pst interactions respectively. KEGG analysis revealed that Oxidative Phosphorylation, Phosphatidylinositol Signaling, and MAPK signaling processes are distinctively enriched in incompatible interaction, while Biosynthesis of secondary metabolites and RNA degradation process were significantly enriched in compatible interactions. In particular, abundant changes in phosphorylation levels of chloroplast proteins were identified, suggesting the regulatory role of photosynthesis in wheat-Pst interaction, which is further emphasized by protein-protein interaction (PPI) network analysis. Motif-x analysis identified [xxxxSPxxxx] motif, likely phosphorylation sites for defensive response-related kinases, and a new [xxxxSSxxxx] motif significantly enriched in incompatible interaction. The results shed light on the early phosphorylation events contributing to wheat resistance against Pst. Moreover, our study demonstrated that the phosphorylation levels of Nucleoside diphosphate kinase TaNAPK1 are upregulated at 12 hpi with CYR23 and at 24 hpi with CYR31. Transient silencing of TaNAPK1 was able to attenuate wheat resistance to CYR23 and CYR31. Our study provides new insights into the mechanisms underlying Pst-wheat interactions and may provide database to find potential targets for the development of new resistant varieties.
PubMed: 38945963
DOI: 10.1007/s44154-024-00170-0 -
Experimental & Molecular Medicine Jul 2024Neutrophils are emerging as an important player in skeletal muscle injury and repair. Neutrophils accumulate in injured tissue, thus releasing inflammatory factors,... (Review)
Review
Neutrophils are emerging as an important player in skeletal muscle injury and repair. Neutrophils accumulate in injured tissue, thus releasing inflammatory factors, proteases and neutrophil extracellular traps (NETs) to clear muscle debris and pathogens when skeletal muscle is damaged. During the process of muscle repair, neutrophils can promote self-renewal and angiogenesis in satellite cells. When neutrophils are abnormally overactivated, neutrophils cause collagen deposition, functional impairment of satellite cells, and damage to the skeletal muscle vascular endothelium. Heterotopic ossification (HO) refers to abnormal bone formation in soft tissue. Skeletal muscle injury is one of the main causes of traumatic HO (tHO). Neutrophils play a pivotal role in activating BMPs and TGF-β signals, thus promoting the differentiation of mesenchymal stem cells and progenitor cells into osteoblasts or osteoclasts to facilitate HO. Furthermore, NETs are specifically localized at the site of HO, thereby accelerating the formation of HO. Additionally, the overactivation of neutrophils contributes to the disruption of immune homeostasis to trigger HO. An understanding of the diverse roles of neutrophils will not only provide more information on the pathogenesis of skeletal muscle injury for repair and HO but also provides a foundation for the development of more efficacious treatment modalities for HO.
PubMed: 38945957
DOI: 10.1038/s12276-024-01270-7 -
Experimental & Molecular Medicine Jul 2024Proinflammatory cytokines and chemokines play a crucial role in regulating the inflammatory response, which is essential for the proper functioning of our immune system.... (Review)
Review
Proinflammatory cytokines and chemokines play a crucial role in regulating the inflammatory response, which is essential for the proper functioning of our immune system. When infections or threats to the body's defense mechanisms are detected, the innate immune system takes the lead. However, an excessive inflammatory response can lead to the production of high concentrations of cytotoxic molecules, resulting in tissue damage. Inflammasomes are significant contributors to innate immunity, and one of the most extensively studied inflammasome complexes is NOD-like receptor 3 (NLRP3). NLRP3 has a wide range of recognition mechanisms that streamline immune activation and eliminate pathogens. These cytosolic multiprotein complexes are composed of effector, adaptor, and sensor proteins, which are crucial for identifying intracellular bacterial breakdown products and initiating an innate immune cascade. To understand the diverse behavior of NLRP3 activation and its significance in the development of lifestyle-related diseases, one must delve into the study of the immune response and apoptosis mediated by the release of proinflammatory cytokines. In this review, we briefly explore the immune response in the context of lifestyle associated disorders such as obesity, hyperlipidemia, diabetes, chronic respiratory disease, oral disease, and cardiovascular disease.
PubMed: 38945951
DOI: 10.1038/s12276-024-01261-8 -
Drug Discoveries & Therapeutics Jun 2024Synthesis of metal nanoparticles using plant extracts is environmentally friendly and of increasing interest. However, not all plant extracts can meet successfully on...
Synthesis of metal nanoparticles using plant extracts is environmentally friendly and of increasing interest. However, not all plant extracts can meet successfully on the synthesis. Therefore, searching for the high potential extracts that can reduce the metal salt precursor in the synthesis reaction is essential. The present study explores the synthesis of copper oxide nanoparticles (CuONPs) using Caesalpinia sappan heartwood extract. Phytochemical analysis and determination of the total phenolic content of the extract were performed before use as a reducing agent. Under the suitable synthesized condition, a color change in the color of the solutions to brown confirmed the formation of CuONPs. The obtained CuONPs were confirmed using ultraviolet-visible spectroscopy, photon correlation spectroscopy, X-ray diffraction, scanning electron microscope, energy dispersive X-ray, and Fourier transform infrared analysis. The synthesized CuONPs investigated for antioxidant, antiglycation, and antibacterial activities. CuONPs possessed antioxidant activities by quenching free radicals with an IC value of 63.35 µg/mL and reducing activity with an EC range of 3.19-10.27 mM/mg. CuONPs also inhibited the formation of advanced glycation end products in the bovine serum albumin/ribose model with an IC value of 17.05 µg/mL. In addition, CuONPs showed inhibition of human pathogens, including Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli, and prevention of biofilm formation and biofilm eradication, with maximum inhibition of approx. 75%. Our findings suggest that C. sappan extract can be used to obtain highly bioactive CuONPs for the development of certain medical devices and therapeutic agents.
PubMed: 38945877
DOI: 10.5582/ddt.2024.01030 -
Japanese Journal of Infectious Diseases Jun 2024The combination of the four regions of vacA with cagA, cagE, dupA genes and cagA-EPIYA motifs, was studied to find the most likely combination that can be used as a...
The combination of the four regions of vacA with cagA, cagE, dupA genes and cagA-EPIYA motifs, was studied to find the most likely combination that can be used as a disease determinant marker in Moroccan population. A total of 838 H. pylori positive obtained from consenting patients, that were previously analyzed by PCR to characterize vacA-s -m, -i regions, cagE status and cagA 3' region polymorphism, were used to characterize vacA-d region and to determine dupA gene status. The analysis shows the predominance of the less virulent combination (vacA(s2m2i2d2)dupA(-)cagE(-)cagA(-)), and shows that the risk of gastric cancer is 13.33 fold higher (1.06-166.37)) in patients infected by strains harboring vacA(s1m1i1d1)dupA(-)cagE(+)cagA(2EPIYA-C) compared to patients with gastritis without lesions and infected by H.pylori strains harboring vacA(s2m2i2d2)dupA(-)cagE(-)cagA(-). The infection with strains harboring vacA(s1m1i1d1)dupA(+)cagE(+)cagA(1EPIYAC) genotype combination represents a risk factor for gastric ulcer and duodenal ulcer (the Odds Ratio (95% CI) were 16 (1.09-234.24) and 6.54 (1.60-26.69) respectively) compared to patients with gastritis without lesions. These results suggest that the combination of the active form of vacA genotypes, dupA gene status and the number of EPIYA-C motif may be considered helpful markers to discriminate between several gastric diseases.
PubMed: 38945860
DOI: 10.7883/yoken.JJID.2024.061 -
Japanese Journal of Infectious Diseases Jun 2024Hand, foot and mouth disease (HFMD) was one of the most common infectious disease in the past few decades. After 2013, coxsackievirus A6 (CVA6) has replaced enterovirus...
Hand, foot and mouth disease (HFMD) was one of the most common infectious disease in the past few decades. After 2013, coxsackievirus A6 (CVA6) has replaced enterovirus 71 (EV-A71) and coxsackievirus A16 (CVA16), becoming the predominant pathogen responsible for HFMD in many areas in China. The objective of this study is to investigate the genetic characteristics and molecular epidemiology of CVA6 in Linyi from 2022 to 2023. A total of 965 HFMD cases were enrolled in this study and analyses based on VP1 nucleotide sequences were performed to determine the evolutionary trajectory of CVA6. In 2022, 281 (281/386, 72.8%) were positive for enterovirus (EVs), and 217 (217/281, 77.2%) were CVA6 positive. In 2023, 398 (398/579, 68.7%) samples were positive for EVs, and 243 (243/398, 61.1%) were CVA6 positive. Six sequences were selected from each year for the homology analysis. The results showed that 12 strains isolated in Linyi were far from the prototype strain (AY421764) and the first CVA6 strain reported in China (JQ364886). Phylogenetic analysis showed that the CVA6 strains isolated in Linyi all belonged to D3 subgenotype. CVA6 is emerging as a common pathogen causing HFMD in Linyi, and continuous surveillance of HFMD etiological agents is necessary.
PubMed: 38945859
DOI: 10.7883/yoken.JJID.2024.072