Pub Date : 2024-10-30DOI: 10.1016/j.genrep.2024.102073
Aynaz Ghojoghi , Ali Zarei Mahmoudabadi , Sadegh Khodavaisy , Eisa Nazar , Mahnaz Fatahinia
Candida albicans is a diploid yeast that, under certain conditions, can cause oral or oropharyngeal infections, particularly in immunocompromised individuals. Recent molecular investigations have classified genotypes A, B, and C for Candida albicans, along with genotype D for Candida dubliniensis. This study aimed to identify the different genotypes of the C. albicans complex in drug abusers in Iran. Oral swabs were collected from drug abusers and cultured on CHROMagar Candida. A 21-plex PCR method was employed for the detection of isolates, and the Candida 25S rDNA gene was amplified using primer pairs CA-INT-L and CA-INT-R for ABC genotyping of C. albicans. Out of the 245 substance abusers screened, 151 individuals (61.63 %) were found to harbor the C. albicans complex. The most common genotype among patients was genotype D (39.1 %), followed by genotype A (31.12 %), genotype B (9.93 %), and genotype C (5.29 %). Additionally, 14.56 % of patients had a mixed genotype. Notably, significant differences in genotype distribution were observed in relation to age, underlying diseases, and marital status (P < 0.05). This study highlights the significance of molecular genotyping in understanding the epidemiology of C. albicans and C. dubliniensis in at-risk groups.
{"title":"Unveiling the genotypic diversity of Candida albicans and Candida dubliniensis in the oral cavities of drug abusers in Ahvaz, Iran","authors":"Aynaz Ghojoghi , Ali Zarei Mahmoudabadi , Sadegh Khodavaisy , Eisa Nazar , Mahnaz Fatahinia","doi":"10.1016/j.genrep.2024.102073","DOIUrl":"10.1016/j.genrep.2024.102073","url":null,"abstract":"<div><div><em>Candida albicans</em> is a diploid yeast that, under certain conditions, can cause oral or oropharyngeal infections, particularly in immunocompromised individuals. Recent molecular investigations have classified genotypes A, B, and C for <em>Candida albicans</em>, along with genotype D for <em>Candida dubliniensis</em>. This study aimed to identify the different genotypes of the <em>C. albicans</em> complex in drug abusers in Iran. Oral swabs were collected from drug abusers and cultured on CHROMagar <em>Candida</em>. A 21-plex PCR method was employed for the detection of isolates, and the <em>Candida</em> 25S rDNA gene was amplified using primer pairs CA-INT-L and CA-INT-R for ABC genotyping of <em>C. albicans</em>. Out of the 245 substance abusers screened, 151 individuals (61.63 %) were found to harbor the <em>C. albicans</em> complex. The most common genotype among patients was genotype D (39.1 %), followed by genotype A (31.12 %), genotype B (9.93 %), and genotype C (5.29 %). Additionally, 14.56 % of patients had a mixed genotype. Notably, significant differences in genotype distribution were observed in relation to age, underlying diseases, and marital status (<em>P</em> < 0.05). This study highlights the significance of molecular genotyping in understanding the epidemiology of <em>C. albicans</em> and <em>C. dubliniensis</em> in at-risk groups.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102073"},"PeriodicalIF":1.0,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-30DOI: 10.1016/j.genrep.2024.102075
Anqi Chen , Chaoneng Ji , Chengtao Li , Suhua Zhang
Background
Animal models are commonly utilized by the pharmaceutical industry to evaluate new drugs; however, the results of these studies are not always applicable to humans due to differences between the genetic backgrounds.
Methods
Since liver plays a prominent role in drug metabolism, we evaluated the expression profiles of human, mouse, rat, and rhesus monkey liver tissues. The differentially expressed genes were identified in different genders, strains, and species.
Results
The primates had fewer differences compared to the rodents, suggesting rhesus monkey could be a preferred model organism. Although the human HGFR (MET), a putative AAV3 receptor, together with its ligand HGF, showed no significant expression differences to the mammal models, the ligand-receptor (HGF/MET) ratio difference between the human (HGF/MET = 0.56) and the mice (HGF/MET = 0.12) might result in the transduction failure of murine hepatocytes using the AAV3 vectors. Our results also showed ACE2 expression was not detected in the human liver, while low expression levels were observed in other species, suggesting that the liver might not be the main target of SARS-CoV2.
Conclusion
In summary, even though all model organisms have limitations, non-human primates or humanized animals are indispensable during drug development before proceeding to clinical trials.
{"title":"Comparing liver RNA-seq analysis of human, rhesus monkey, mouse and rat","authors":"Anqi Chen , Chaoneng Ji , Chengtao Li , Suhua Zhang","doi":"10.1016/j.genrep.2024.102075","DOIUrl":"10.1016/j.genrep.2024.102075","url":null,"abstract":"<div><h3>Background</h3><div>Animal models are commonly utilized by the pharmaceutical industry to evaluate new drugs; however, the results of these studies are not always applicable to humans due to differences between the genetic backgrounds.</div></div><div><h3>Methods</h3><div>Since liver plays a prominent role in drug metabolism, we evaluated the expression profiles of human, mouse, rat, and rhesus monkey liver tissues. The differentially expressed genes were identified in different genders, strains, and species.</div></div><div><h3>Results</h3><div>The primates had fewer differences compared to the rodents, suggesting rhesus monkey could be a preferred model organism. Although the human HGFR (MET), a putative AAV3 receptor, together with its ligand HGF, showed no significant expression differences to the mammal models, the ligand-receptor (HGF/MET) ratio difference between the human (HGF/MET = 0.56) and the mice (HGF/MET = 0.12) might result in the transduction failure of murine hepatocytes using the AAV3 vectors. Our results also showed ACE2 expression was not detected in the human liver, while low expression levels were observed in other species, suggesting that the liver might not be the main target of SARS-CoV2.</div></div><div><h3>Conclusion</h3><div>In summary, even though all model organisms have limitations, non-human primates or humanized animals are indispensable during drug development before proceeding to clinical trials.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102075"},"PeriodicalIF":1.0,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142573480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-29DOI: 10.1016/j.genrep.2024.102067
Sanjukta Dasgupta
Background
Idiopathic pulmonary fibrosis (IPF) is characterized by progressive fibrosis in the lung parenchyma. Given the fact that IPF patients are at significant risk of developing lung cancer (LC), the overlapping gene signatures between IPF and LC need to be explored.
Methods
Two datasets (GSE79544 and GSE103888) were procured from the Gene Expression Omnibus repository and used to determine the overlapping genes between IPF and LC. Next, the prediction ability of these genes in differentiating the diseased group from controls was explored using two machine learning (ML) models (random forest and k-nearest neighbor). Potential drugs targeting the candidate genes were identified, and advanced structural analysis was conducted to determine the binding affinity between the candidate drug and target receptor.
Result
A total of ten common genes (CCL13, CXCL2, MALT1, MARCKS, PLA2G7, SEMA6B, SFTPB, SPARC, SPP1, and TLCD2) are differentially expressed in IPF and LC as compared to the controls. PLA2G7 demonstrated promising potential in differentiating between IPF, LC, and controls. The increased expression correlated with poor survival in patients with LC. The expression of PLA2G7 indicated a similar trend in the validation dataset. Darapladib, a selective inhibitor that belongs to toxicity class 4 and lethal dose50 value of 800 mg/kg exhibited maximum potential in targeting PLA2G7 with a binding affinity score of −9.2 kcal/mol (chain A) and −9.3 kcal/mol (chain B), respectively.
Conclusion
The present study is the first of its kind that combines in-silico and ML algorithms to identify the gene signatures and promising drugs for treating the progression of LC in patients with IPF.
{"title":"Identification and molecular modelling of potential drugs targeting the genes involved in the progression of lung cancer in patients with idiopathic pulmonary fibrosis","authors":"Sanjukta Dasgupta","doi":"10.1016/j.genrep.2024.102067","DOIUrl":"10.1016/j.genrep.2024.102067","url":null,"abstract":"<div><h3>Background</h3><div>Idiopathic pulmonary fibrosis (IPF) is characterized by progressive fibrosis in the lung parenchyma. Given the fact that IPF patients are at significant risk of developing lung cancer (LC), the overlapping gene signatures between IPF and LC need to be explored.</div></div><div><h3>Methods</h3><div>Two datasets (GSE79544 and GSE103888) were procured from the Gene Expression Omnibus repository and used to determine the overlapping genes between IPF and LC. Next, the prediction ability of these genes in differentiating the diseased group from controls was explored using two machine learning (ML) models (random forest and k-nearest neighbor). Potential drugs targeting the candidate genes were identified, and advanced structural analysis was conducted to determine the binding affinity between the candidate drug and target receptor.</div></div><div><h3>Result</h3><div>A total of ten common genes (<em>CCL13</em>, <em>CXCL2</em>, <em>MALT1</em>, <em>MARCKS</em>, <em>PLA2G7</em>, <em>SEMA6B</em>, <em>SFTPB</em>, <em>SPARC</em>, <em>SPP1</em>, and <em>TLCD2</em>) are differentially expressed in IPF and LC as compared to the controls. <em>PLA2G7</em> demonstrated promising potential in differentiating between IPF, LC, and controls. The increased expression correlated with poor survival in patients with LC. The expression of <em>PLA2G7</em> indicated a similar trend in the validation dataset. Darapladib, a selective inhibitor that belongs to toxicity class 4 and lethal dose50 value of 800 mg/kg exhibited maximum potential in targeting <em>PLA2G7</em> with a binding affinity score of −9.2 kcal/mol (chain A) and −9.3 kcal/mol (chain B), respectively.</div></div><div><h3>Conclusion</h3><div>The present study is the first of its kind that combines in-silico and ML algorithms to identify the gene signatures and promising drugs for treating the progression of LC in patients with IPF.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102067"},"PeriodicalIF":1.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142573010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-29DOI: 10.1016/j.genrep.2024.102071
Astrid S. Espinoza García , Rosa L. Díaz Chávez , Elia H. Valdés Miramontes , Isela Parra Rojas , Zyanya Reyes Castillo
Purpose
Obesity develops as a result of the interplay between obesogenic environment and the individual's eating behaviors. Genetic variants in genes coding for neuropeptides involved in metabolic regulation, such as ghrelin (GHRL) and leptin (LEP) have been associated to development of obesity and its role on appetite regulation has also been suggested. The purpose of this exploratory study was to evaluate the association of genetic variants at GHRL (rs27647, rs696217) and LEP (rs7799039) with body composition parameters as well as food approach and food avoidance appetitive traits in young adults from western Mexico.
Methods
255 young adults were included. Body composition parameters were measured by bioelectrical bioimpedance, and appetitive traits were assessed via Adult Eating Behavior Questionnaire (AEBQ). Genotyping of rs27647, rs696217 and rs7799039 variants was performed using PCR-RFLP techniques.
Results and conclusion
Median age for both sexes were 20 (19–21) years, mean body fat percentage was 36.1 ± 7.8 for women, and for men 23.7 ± 7.4. The evaluated genetic variants were not associated to body composition parameters, however GG genotype of the rs696217 variant in GHRL was associated to higher scores on food approach appetitive traits (enjoyment of food p < 0.01 and food responsiveness p < 0.0009). In addition, the GG genotype of rs7799039 variant in LEP was associated to higher scores in food avoidance appetitive traits (emotional undereating p < 0.004 and food fussiness p < 0.001). Our results suggest an association between genetic variants in GHRL and LEP genes with appetitive traits in Mexican young adults, showing an indirect genetic link with obesity, through eating behaviors modulation.
{"title":"Genetic variants in ghrelin (rs27647, rs696217) and leptin (rs7799039) are not associated with body composition parameters but are related to appetitive traits in Mexican young adults","authors":"Astrid S. Espinoza García , Rosa L. Díaz Chávez , Elia H. Valdés Miramontes , Isela Parra Rojas , Zyanya Reyes Castillo","doi":"10.1016/j.genrep.2024.102071","DOIUrl":"10.1016/j.genrep.2024.102071","url":null,"abstract":"<div><h3>Purpose</h3><div>Obesity develops as a result of the interplay between obesogenic environment and the individual's eating behaviors. Genetic variants in genes coding for neuropeptides involved in metabolic regulation, such as ghrelin (<em>GHRL</em>) and leptin (<em>LEP</em>) have been associated to development of obesity and its role on appetite regulation has also been suggested. The purpose of this exploratory study was to evaluate the association of genetic variants at <em>GHRL</em> (rs27647, rs696217) and <em>LEP</em> (rs7799039) with body composition parameters as well as food approach and food avoidance appetitive traits in young adults from western Mexico.</div></div><div><h3>Methods</h3><div>255 young adults were included. Body composition parameters were measured by bioelectrical bioimpedance, and appetitive traits were assessed via Adult Eating Behavior Questionnaire (AEBQ). Genotyping of rs27647, rs696217 and rs7799039 variants was performed using PCR-RFLP techniques.</div></div><div><h3>Results and conclusion</h3><div>Median age for both sexes were 20 (19–21) years, mean body fat percentage was 36.1 ± 7.8 for women, and for men 23.7 ± 7.4. The evaluated genetic variants were not associated to body composition parameters, however GG genotype of the rs696217 variant in <em>GHRL</em> was associated to higher scores on food approach appetitive traits (enjoyment of food <em>p</em> < 0.01 and food responsiveness <em>p</em> < 0.0009). In addition, the GG genotype of rs7799039 variant in <em>LEP</em> was associated to higher scores in food avoidance appetitive traits (emotional undereating <em>p</em> < 0.004 and food fussiness <em>p</em> < 0.001). Our results suggest an association between genetic variants in <em>GHRL</em> and <em>LEP</em> genes with appetitive traits in Mexican young adults, showing an indirect genetic link with obesity, through eating behaviors modulation.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102071"},"PeriodicalIF":1.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142573011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-28DOI: 10.1016/j.genrep.2024.102068
Razieh Farkhondeh , Seyedeh Zahra Hasanpour , Mohsen Hamidpour , Mehdi Allah Bakhshian , Seyedeh Ommolbanin Ghasemian , Majid Gholami-Ahangaran
Introduction
The interaction between Bone marrow (BM) microenvironment and acute myeloblastic leukemia (AML) cells is an essential event in the development of leukemia.
Material and methods
In this study investigated the expression of fibroblastic growth factor 2 (FGF2), chemokine (CC motif) ligand 3 (CCL-3), thrombopoietin (TPO) and connective tissue growth factor (CTGF) in 60 newly diagnosed AML patients and 60 healthy volunteers. BM and peripheral blood samples were collected from patients and healthy individuals and the expression of genes was assessed using qRT-PCR. The obtained data were analyzed using t-test, one-way ANOVA and Pearson correlation coefficient.
Results
The results showed that while the expression of CCL-3 and FGF2 was upregulated, the expression of TPO was downregulated in AML patients as compared with the control group. We also failed to find any difference in the expression of CTGF between patients and healthy individuals. Moreover, we found that there was no association between gene expression and the age and gender of AML patients. Only the expression of CTGF had a negative correlation with the percentage of blasts in AML patients. A positive significant correlation between FGF2 and CCL-3, FGF2 and TPO, FGF2 and CTGF as well as CCL-3 and TPO were detected.
Conclusions
This study proposed that the expression of growth factors and cytokines could be used as a prognostic factor. However, to gain better insight into the precise role of these factors, further studies at larger statistical population are required.
{"title":"The expression of CCL-3, FGF2, TPO and CTGF in newly diagnosed acute myeloblastic leukemia (AML)","authors":"Razieh Farkhondeh , Seyedeh Zahra Hasanpour , Mohsen Hamidpour , Mehdi Allah Bakhshian , Seyedeh Ommolbanin Ghasemian , Majid Gholami-Ahangaran","doi":"10.1016/j.genrep.2024.102068","DOIUrl":"10.1016/j.genrep.2024.102068","url":null,"abstract":"<div><h3>Introduction</h3><div>The interaction between Bone marrow (BM) microenvironment and acute myeloblastic leukemia (AML) cells is an essential event in the development of leukemia.</div></div><div><h3>Material and methods</h3><div>In this study investigated the expression of fibroblastic growth factor 2 (FGF2), chemokine (C<img>C motif) ligand 3 (CCL-3), thrombopoietin (TPO) and connective tissue growth factor (CTGF) in 60 newly diagnosed AML patients and 60 healthy volunteers. BM and peripheral blood samples were collected from patients and healthy individuals and the expression of genes was assessed using qRT-PCR. The obtained data were analyzed using <em>t</em>-test, one-way ANOVA and Pearson correlation coefficient.</div></div><div><h3>Results</h3><div>The results showed that while the expression of CCL-3 and FGF2 was upregulated, the expression of TPO was downregulated in AML patients as compared with the control group. We also failed to find any difference in the expression of CTGF between patients and healthy individuals. Moreover, we found that there was no association between gene expression and the age and gender of AML patients. Only the expression of CTGF had a negative correlation with the percentage of blasts in AML patients. A positive significant correlation between FGF2 and CCL-3, FGF2 and TPO, FGF2 and CTGF as well as CCL-3 and TPO were detected.</div></div><div><h3>Conclusions</h3><div>This study proposed that the expression of growth factors and cytokines could be used as a prognostic factor. However, to gain better insight into the precise role of these factors, further studies at larger statistical population are required.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102068"},"PeriodicalIF":1.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-28DOI: 10.1016/j.genrep.2024.102070
Chayna Singha Mahapatra , Aruna Kuniyal , Gaurav Sharma , Shyma K. Latheef , Amit Kumar , Pronab Dhar
Porcine circovirus 1(PCV-1) is an inherent contaminant in all cells of porcine origin, including cell lines. Porcine Kidney 15 (PK-15) cells are one such cell line which are widely being used for the propagation of different porcine viruses and development of cell culture vaccines for pigs. PCV1 is a single-stranded DNA virus that remain in circular form with a high copy number inside the host cell. The presence of PCV1virus in PK-15 cells may affect the yield of porcine viruses and other vaccine strains like Classical Swine Fever Virus (CSFV) propagated in these cells. Hence the present study was conducted to explore the promising CRISPR/Cas9 tool in cleaving PCV-1 DNA from PK-15 cells, followed by the evaluation of these cells for producing CSF vaccine virus with better yield. PK-15 cells were subjected to CRISPR/Cas9 mediated cleavage with a cocktail of guide RNAs (sgRNAs) to cleave PCV-1 DNA. A significant reduction of PCV-1 DNA in the transfected cells was observed in droplet digital PCR and real-time PCR; indicating successful targeting of PCV-1 DNA by the chosen sgRNAs. Further, the PCV-1 cleaved PK-15 cells were infected with CSFV and found to have a better yield of harvested virus. Based on the present study, it can be suggested that knocking out of PCV-1 DNA from PK-15 cells offers a promising platform for generating contaminant free cell lines and vaccine development with higher yield.
{"title":"CRISPR/Cas mediated disruption of the Porcine Circovirus-1 gene present in PK-15 cells using sgRNA cocktail","authors":"Chayna Singha Mahapatra , Aruna Kuniyal , Gaurav Sharma , Shyma K. Latheef , Amit Kumar , Pronab Dhar","doi":"10.1016/j.genrep.2024.102070","DOIUrl":"10.1016/j.genrep.2024.102070","url":null,"abstract":"<div><div>Porcine circovirus 1(PCV-1) is an inherent contaminant in all cells of porcine origin, including cell lines. Porcine Kidney 15 (PK-15) cells are one such cell line which are widely being used for the propagation of different porcine viruses and development of cell culture vaccines for pigs. PCV1 is a single-stranded DNA virus that remain in circular form with a high copy number inside the host cell. The presence of PCV1virus in PK-15 cells may affect the yield of porcine viruses and other vaccine strains like Classical Swine Fever Virus (CSFV) propagated in these cells. Hence the present study was conducted to explore the promising CRISPR/Cas9 tool in cleaving PCV-1 DNA from PK-15 cells, followed by the evaluation of these cells for producing CSF vaccine virus with better yield. PK-15 cells were subjected to CRISPR/Cas9 mediated cleavage with a cocktail of guide RNAs (sgRNAs) to cleave PCV-1 DNA. A significant reduction of PCV-1 DNA in the transfected cells was observed in droplet digital PCR and real-time PCR; indicating successful targeting of PCV-1 DNA by the chosen sgRNAs. Further, the PCV-1 cleaved PK-15 cells were infected with CSFV and found to have a better yield of harvested virus. Based on the present study, it can be suggested that knocking out of PCV-1 DNA from PK-15 cells offers a promising platform for generating contaminant free cell lines and vaccine development with higher yield.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102070"},"PeriodicalIF":1.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142573479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-28DOI: 10.1016/j.genrep.2024.102069
Omer Abid Kathum , Saafa Abd.Al-kahdum , Umniah Abd-Al-Naser Saleh Hadi , Sarah Kamil Abood , Shaimaa Y. Abdulfattah
Background
It had been established that; influenza A viral infection is connected in a big range with stimulation of many cellular kinases which either being necessary for viral live cycle or as a kind of antagonistic response against this attack hoping to stop the viral invasion. This induction includes many cellular mediator's response. Among them; induction of Retinoic Inducible Genes I (RIG I) which is classified as the precursor of interferon β activation thereby the activation of another mediator like IRF3.
The objective of this study is to identify and establish a new and natural antiviral active compound which might help in enhancing the cellular immunity against influenza A virus thereby attenuating its ability to invade living cells.
Methods
In this work, variety of concentration of Alluim sativum (AS) or garlic plant extract; 12.5, 25, 50 μg/ml were tested on MDCKII or A549 cell as an in vitro experimental work to examine its ability to abort the replication of Influenza A/Puerto Rico/8/34 H1N1 (IAV PR8) strain depending on many techniques like, viral plaque assay, gene expression by real time PCR (rt PCR), luciferase assay and immunofluorescent stating.
Results
Our data explained that there was weak replication ability as explained in viral replication titer by plaque assay whether after 8 hours post infection using 0.1 MOI or even after 24 hours post infection using 0.01 MOI of influenza A PR8, this finding was propped with a prosaic expression of some viral protein genes like NS1, NP. the immunofluorescent staining also supported those data via the weak localization of NS1 protein during the treatment with garlic extract and that’s normally is connected with high induction of cellular gene expression representing by RIG I, IRF3 mediator and Interferon β genes necessary for induction of type I interferon caused by treatment with garlic extract.
Conclusion
Allium sativum plant extract sequestered influenza A virus PR8 replication significantly especially, at concentration of 50 μg/ ml which is the best concentration that can act against the virus due to acute induction of cellular proteins represented by RIG I pathogen recognizer and other proteins that interferes with activation of interferon then preventing the viral competition with cellular immunity to invade the cells.
In another word, the garlic extract is a direct inducer for RIG I and other mediators important for activation of type I interferon pathway as an immune response to prevent viral attack.
背景已经证实，甲型流感病毒感染在很大程度上与许多细胞激酶的刺激有关，这些激酶或者是病毒生命周期所必需的，或者是对这种攻击的一种拮抗反应，希望阻止病毒入侵。这种诱导包括许多细胞介质反应。本研究的目的是鉴定和建立一种新的天然抗病毒活性化合物，它可能有助于增强细胞对甲型流感病毒的免疫力，从而削弱其入侵活细胞的能力。5, 25, 50 μg/ml 在 MDCKII 或 A549 细胞上进行体外实验，通过病毒斑块检测、实时 PCR（rt PCR）基因表达、荧光素酶检测和免疫荧光检测等多种技术，检测其终止甲型流感/波多黎各/8/34 H1N1（IAV PR8）病毒株复制的能力。结果我们的数据表明，无论是在感染后 8 小时（使用 0.1 MOI），还是在感染后 24 小时（使用 0.01 MOI），病毒复制滴度的斑块检测都表明病毒复制能力很弱。免疫荧光染色也通过大蒜提取物处理过程中 NS1 蛋白的弱定位支持了这些数据，这通常与大蒜提取物处理过程中诱导 I 型干扰素所需的 RIG I、IRF3 mediator 和 Interferon β 基因对细胞基因表达的高诱导有关。结论大蒜提取物能显著抑制甲型流感病毒 PR8 的复制，特别是在 50 μg/ ml 的浓度下，该浓度是抗病毒的最佳浓度，这是因为大蒜提取物能急性诱导以 RIG I 病原体识别器为代表的细胞蛋白和其他蛋白，从而干扰干扰素的激活，阻止病毒与细胞免疫竞争入侵细胞。换句话说，大蒜提取物是 RIG I 和其他介质的直接诱导剂，这些介质对激活 I 型干扰素通路非常重要，是防止病毒攻击的一种免疫反应。
{"title":"Genetical and cellular induction of interferon genes via the treatment with (Allium sativum) garlic extract against recombinant influenza A/Puerto Rico/8/34 H1N PR8 infection","authors":"Omer Abid Kathum , Saafa Abd.Al-kahdum , Umniah Abd-Al-Naser Saleh Hadi , Sarah Kamil Abood , Shaimaa Y. Abdulfattah","doi":"10.1016/j.genrep.2024.102069","DOIUrl":"10.1016/j.genrep.2024.102069","url":null,"abstract":"<div><h3>Background</h3><div>It had been established that; influenza A viral infection is connected in a big range with stimulation of many cellular kinases which either being necessary for viral live cycle or as a kind of antagonistic response against this attack hoping to stop the viral invasion. This induction includes many cellular mediator's response. Among them; induction of Retinoic Inducible Genes I (RIG I) which is classified as the precursor of interferon β activation thereby the activation of another mediator like IRF3.</div><div>The objective of this study is to identify and establish a new and natural antiviral active compound which might help in enhancing the cellular immunity against influenza A virus thereby attenuating its ability to invade living cells.</div></div><div><h3>Methods</h3><div>In this work, variety of concentration of Alluim sativum (AS) or garlic plant extract; 12.5, 25, 50 μg/ml were tested on MDCKII or A549 cell as an in vitro experimental work to examine its ability to abort the replication of Influenza A/Puerto Rico/8/34 H1N1 (IAV PR8) strain depending on many techniques like, viral plaque assay, gene expression by real time PCR (rt PCR), luciferase assay and immunofluorescent stating.</div></div><div><h3>Results</h3><div>Our data explained that there was weak replication ability as explained in viral replication titer by plaque assay whether after 8 hours post infection using 0.1 MOI or even after 24 hours post infection using 0.01 MOI of influenza A PR8, this finding was propped with a prosaic expression of some viral protein genes like NS1, NP. the immunofluorescent staining also supported those data via the weak localization of NS1 protein during the treatment with garlic extract and that’s normally is connected with high induction of cellular gene expression representing by RIG I, IRF3 mediator and Interferon β genes necessary for induction of type I interferon caused by treatment with garlic extract.</div></div><div><h3>Conclusion</h3><div>Allium sativum plant extract sequestered influenza A virus PR8 replication significantly especially, at concentration of 50 μg/ ml which is the best concentration that can act against the virus due to acute induction of cellular proteins represented by RIG I pathogen recognizer and other proteins that interferes with activation of interferon then preventing the viral competition with cellular immunity to invade the cells.</div><div>In another word, the garlic extract is a direct inducer for RIG I and other mediators important for activation of type I interferon pathway as an immune response to prevent viral attack.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102069"},"PeriodicalIF":1.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142587269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chronic Myeloid Leukemia (CML) is a myeloproliferative disorder characterized by the Philadelphia chromosome (Ph) resulting from the reciprocal translocation t(9;22)(q34;q11). Sex chromosomal abnormalities are found rarely in CML patients.
Materials and methods
Conventional and molecular cytogenetic analysis (Fluorescent In Situ Hybridization (FISH)) were performed to reveal the presence of Ph and additional chromosomal abnormalities (ACA).
Results
Three patients with abnormalities within sex chromosomes, one Klinefelter syndrome (KS) patient and two cases with LOY (Loss of Y) diagnosed with CML CP were included in the study. All three patients initially responded to the targeted therapy, became resistant to their treatment course and switched to 2nd line therapies. In the 15th month, the KS patient abruptly turned into BC and showed clonal evolution with four karyotypic patterns. According to Mitelman databases, this is the first KS-CML patient who showed three major route abnormalities, +8, i(17) and + der(22) in a single clone. Survival analysis showed one patient with LOY chromosome expired on the 48th month of diagnosis.
Conclusion
The application of cytogenetic techniques in identifying the constitutional abnormality of KS, ACA at initial CML diagnosis, revealing of extra Ph during the treatment course and clonal evolution in BC (Blast Crisis) assist the proper monitoring of disease transformation and serves as a major diagnostic tool for CML patients thereby switching the treatment protocols. A systematic stratification of patients according to the chromosomal abnormalities is needed in CML patients.
{"title":"Impact of sex chromosome abnormalities in male chronic myeloid leukemia patients","authors":"Mahitha Mohanan Sreelatha , Narayanan Geetha , Vineetha Radhakrishnan Chandraprabha , Preethi Gopinath , Akhila Raj Thampirajan Vimala Devi , Geetha Raj John Anitha , Amritha Padmakumar , Devipriya Padmakumar , Hariharan Sreedharan","doi":"10.1016/j.genrep.2024.102066","DOIUrl":"10.1016/j.genrep.2024.102066","url":null,"abstract":"<div><h3>Introduction</h3><div>Chronic Myeloid Leukemia (CML) is a myeloproliferative disorder characterized by the Philadelphia chromosome (Ph) resulting from the reciprocal translocation t(9;22)(q34;q11). Sex chromosomal abnormalities are found rarely in CML patients.</div></div><div><h3>Materials and methods</h3><div>Conventional and molecular cytogenetic analysis (Fluorescent <em>In Situ</em> Hybridization (FISH)) were performed to reveal the presence of Ph and additional chromosomal abnormalities (ACA).</div></div><div><h3>Results</h3><div>Three patients with abnormalities within sex chromosomes, one Klinefelter syndrome (KS) patient and two cases with LOY (Loss of Y) diagnosed with CML CP were included in the study. All three patients initially responded to the targeted therapy, became resistant to their treatment course and switched to 2nd line therapies. In the 15th month, the KS patient abruptly turned into BC and showed clonal evolution with four karyotypic patterns. According to Mitelman databases, this is the first KS-CML patient who showed three major route abnormalities, +8, i(17) and + der(22) in a single clone. Survival analysis showed one patient with LOY chromosome expired on the 48th month of diagnosis.</div></div><div><h3>Conclusion</h3><div>The application of cytogenetic techniques in identifying the constitutional abnormality of KS, ACA at initial CML diagnosis, revealing of extra Ph during the treatment course and clonal evolution in BC (Blast Crisis) assist the proper monitoring of disease transformation and serves as a major diagnostic tool for CML patients thereby switching the treatment protocols. A systematic stratification of patients according to the chromosomal abnormalities is needed in CML patients.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102066"},"PeriodicalIF":1.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142573478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-17DOI: 10.1016/j.genrep.2024.102063
Yoshiyuki Suzuki, Masaya Yaeshiro, Daiki Uehara
Rotavirus alphagastroenteritidis (RVA), a pathogen causing acute gastroenteritis in young birds and mammals, possesses a genome of 11 segmented double-stranded RNAs, each of which is classified into genotypes. RVA has been divided into the avian and mammalian clusters as well as the basal group. Although the avian and mammalian clusters were considered to have evolved independently, genomic segment encoding viral protein 4 (VP4) of pheasant strain with genotype P[37] appeared to be transferred from mammalian cluster strain through reassortment. Here prototype sequences for all genotypes P[1]-P[58] of VP4 segment except for P[53] and P[54] retrieved from the International Nucleotide Sequence Database were analyzed to examine the possibility that P[37] was a product of intra-segmental recombinations between avian and mammalian cluster strains. In the sliding window analysis, different regions of P[37] appeared to have different relative similarities to avian and mammalian cluster strains. Using recombination detection programs, two regions of P[37] were identified to be derived from mammalian cluster strains and integrated into the background of avian cluster strain. These results were confirmed by phylogenetic analyses. Thus, even when genomic segments are not entirely compatible between strains, only compatible parts may be transferred through intra-segmental recombinations in RVA.
{"title":"Intra-segmental recombinations between avian and mammalian VP4 genotypes in Rotavirus alphagastroenteritidis","authors":"Yoshiyuki Suzuki, Masaya Yaeshiro, Daiki Uehara","doi":"10.1016/j.genrep.2024.102063","DOIUrl":"10.1016/j.genrep.2024.102063","url":null,"abstract":"<div><div><em>Rotavirus alphagastroenteritidis</em> (RVA), a pathogen causing acute gastroenteritis in young birds and mammals, possesses a genome of 11 segmented double-stranded RNAs, each of which is classified into genotypes. RVA has been divided into the avian and mammalian clusters as well as the basal group. Although the avian and mammalian clusters were considered to have evolved independently, genomic segment encoding viral protein 4 (VP4) of pheasant strain with genotype P[37] appeared to be transferred from mammalian cluster strain through reassortment. Here prototype sequences for all genotypes P[1]-P[58] of VP4 segment except for P[53] and P[54] retrieved from the International Nucleotide Sequence Database were analyzed to examine the possibility that P[37] was a product of intra-segmental recombinations between avian and mammalian cluster strains. In the sliding window analysis, different regions of P[37] appeared to have different relative similarities to avian and mammalian cluster strains. Using recombination detection programs, two regions of P[37] were identified to be derived from mammalian cluster strains and integrated into the background of avian cluster strain. These results were confirmed by phylogenetic analyses. Thus, even when genomic segments are not entirely compatible between strains, only compatible parts may be transferred through intra-segmental recombinations in RVA.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102063"},"PeriodicalIF":1.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142537373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.1016/j.genrep.2024.102065
Lubna Razaq , Fakhur Uddin , Sanum Ali , Shahzad Ali , Rizwana Kausar , Muhammad Sohail
Extended-spectrum-β-lactamase (ESBL)-producing Enterobacterales, especially Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, are highly prevalent in various parts of the world. However, the prevalence of ESBL variants in Enterobacterales from hospital-acquired (HA) and community-acquired (CA) urinary tract infections (UTI) had been infrequently reported in developing countries. This study analyzed the presence of ESBL-producing Enterobacterales, their resistance patterns, and ESBL variants. Of the 279 urine samples, 144 (51.6 %) were obtained from patients with CA-UTI and 135 (48.4 %) were obtained from patients with HA-UTI. From these samples, 145 and 135 Enterobacterales strains were isolated from the CA and HA-UTI groups, respectively. E. coli was the predominant (202/280; 72.2 %), followed by K. pneumoniae (53/280; 18.9 %) and P. mirabilis (25/280; 8.9 %). ESBL producers were higher (131/218; 60.09 %) in the HA-UTI isolates. Overall, blaSHV (48.2 %) was the predominant gene, followed by blaTEM (44 %), whereas blaCTX-M was rarely detected (7.79 %) in the CA and HA-UTI isolates. blaSHV-212, blaSHV-229, blaTEM-103, and blaTEM-104 were common among the isolates. The coexistence of blaTEM and blaSHV was also observed. This study highlights a different ESBL pattern among uropathogens that can aid in updating infectious disease control and antimicrobial stewardship guidelines.
{"title":"Extended-spectrum β-lactamase variants in Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis from community- and hospital-acquired urinary tract infections","authors":"Lubna Razaq , Fakhur Uddin , Sanum Ali , Shahzad Ali , Rizwana Kausar , Muhammad Sohail","doi":"10.1016/j.genrep.2024.102065","DOIUrl":"10.1016/j.genrep.2024.102065","url":null,"abstract":"<div><div>Extended-spectrum-β-lactamase (ESBL)-producing Enterobacterales, especially <em>Escherichia coli</em>, <em>Klebsiella pneumoniae</em>, and <em>Proteus mirabilis</em>, are highly prevalent in various parts of the world. However, the prevalence of ESBL variants in Enterobacterales from hospital-acquired (HA) and community-acquired (CA) urinary tract infections (UTI) had been infrequently reported in developing countries. This study analyzed the presence of ESBL-producing Enterobacterales, their resistance patterns, and ESBL variants. Of the 279 urine samples, 144 (51.6 %) were obtained from patients with CA-UTI and 135 (48.4 %) were obtained from patients with HA-UTI. From these samples, 145 and 135 Enterobacterales strains were isolated from the CA and HA-UTI groups, respectively. <em>E. coli</em> was the predominant (202/280; 72.2 %), followed by <em>K. pneumoniae</em> (53/280; 18.9 %) and <em>P. mirabilis</em> (25/280; 8.9 %). ESBL producers were higher (131/218; 60.09 %) in the HA-UTI isolates. Overall, <em>bla</em><sub>SHV</sub> (48.2 %) was the predominant gene, followed by <em>bla</em><sub>TEM</sub> (44 %), whereas <em>bla</em><sub>CTX-M</sub> was rarely detected (7.79 %) in the CA and HA-UTI isolates. <em>bla</em><sub>SHV</sub>-212, <em>bla</em><sub>SHV-229</sub>, <em>bla</em><sub>TEM</sub>-<sub>103</sub>, and <em>bla</em><sub>TEM</sub>-<sub>104</sub> were common among the isolates. The coexistence of <em>bla</em><sub>TEM</sub> and <em>bla</em><sub><em>S</em>HV</sub> was also observed. This study highlights a different ESBL pattern among uropathogens that can aid in updating infectious disease control and antimicrobial stewardship guidelines.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102065"},"PeriodicalIF":1.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142537374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号