Peanut allergy is majorly related to severe food induced allergic reactions.Several food including cow's milk,hen's eggs,soy,wheat,peanuts,tree nuts(walnuts,hazelnuts,almonds,cashews,pecans and pistachios),fis...Peanut allergy is majorly related to severe food induced allergic reactions.Several food including cow's milk,hen's eggs,soy,wheat,peanuts,tree nuts(walnuts,hazelnuts,almonds,cashews,pecans and pistachios),fish and shellfish are responsible for more than 90%of food allergies.Here,we provide promising insights using a large-scale data-driven analysis,comparing the mechanistic feature and biological relevance of different ingredients presents in peanuts,tree nuts(walnuts,almonds,cashews,pecans and pistachios)and soybean.Additionally,we have analysed the chemical compositions of peanuts in different processed form raw,boiled and dry-roasted.Using the data-driven approach we are able to generate new hypotheses to explain why nuclear receptors like the peroxisome proliferator-activated receptors(PPARs)and its isoform and their interaction with dietary lipids may have significant effect on allergic response.The results obtained from this study will direct future experimeantal and clinical studies to understand the role of dietary lipids and PPARisoforms to exert pro-inflammatory or anti-inflammatory functions on cells of the innate immunity and influence antigen presentation to the cells of the adaptive immunity.展开更多
Background: In 2019, the WHO estimated that over 296 million people were living with chronic hepatitis B virus (HBV) infection and over 820,000 deaths attributable to hepatitis B. Most people living with HBV are unawa...Background: In 2019, the WHO estimated that over 296 million people were living with chronic hepatitis B virus (HBV) infection and over 820,000 deaths attributable to hepatitis B. Most people living with HBV are unaware of their immune status and live in endemic areas. This is the case of Benin and Senegal, which have little data on the disease. Objective: This study aimed to provide epidemiological furthers on hepatitis B in Dakar and Cotonou according to WHO recommendations about “obtaining data for action”. Materials and Methods: Our study took place at the Medical Biology Laboratory of the Idrissa Pouye General Hospital (LBM-HOGIP) in Dakar, Senegal. Participants were selected at the LBM-HOGIP of Dakar or at the LBMs of the health centres of the Archdiocese of Cotonou respectively from November to December 2019 and February to March 2020. All participants were tested for hepatitis B virus antigen (HBsAg) using a microparticle chemiluminescence immunoassay assay. Other risk factors including blood transfusion, haemodialysis, tattooing, cultural or clan scarification, piercing, injecting drug use, unprotected sex and surgical procedures were also investigated. Informed consent was obtained from each participant. The study was approved by the ethics committees in Senegal and Benin. For the biological tests, Excel and IBM SPSS Statistics software were used for the analysis of the results. Results: A total of 470 participants were recruited including 234 in Cotonou and 236 in Dakar. The median age in Cotonou was 29 years with extremes of 10 and 65 years, and 38 years in Dakar with extremes of 6 and 93 years. The prevalence of HBsAg was 12.39% in Cotonou and 19.91% in Dakar. The most affected age groups were 20 - 29 in Dakar and 30 - 39 in Cotonou. Except for piercing, none of the other risk factors considered in our study were found to be associated with HBV transmission in our populations. Conclusion: Our study is hospital-based and revealed high prevalence of HBsAg. These prevalences were higher in men.展开更多
Objective: Despite the existence of several therapeutic strategies, the management of cervical cancer remains challenging. Our region has very little data on the interaction between the immune system and the clinical ...Objective: Despite the existence of several therapeutic strategies, the management of cervical cancer remains challenging. Our region has very little data on the interaction between the immune system and the clinical response to chemotherapy. This work examines plasma levels of galectin-3 (Gal-3) and percentages of activated T cells in patients with cervical cancer treated with chemotherapy and investigates if there is a relationship between the rates of these two elements. Methods: We compared data from 37 patients with cervical cancer undergoing chemotherapy and 42 controls with normal cervical cytology. Plasma Gal-3 concentrations were assessed by ELISA and expression of activation markers by T cells (CD69 and HLA-DR) was assessed by flow cytometry at three different time points during chemotherapy. Results: Our results showed that patients had a significantly higher concentration of Gal-3 compared to controls (4.025 vs. 1.340, p 0.001), similarly, they had a significantly high percentage of activated lymphocytes (2.610 vs. 0.731;p 0.0001). According to the response to treatment, patients with no response to treatment had a lower concentration of circulating Gal-3 but had approximately the same percentage of activated CD4 and CD8 lymphocytes as patients with a partial or total response. In addition, we found a positive correlation between the Gal-3 level and CD4 T cells expressing the activation marker CD69 (p 0.05;rho = 0.44). Conclusion: In conclusion, our results show that there would be a relationship between circulating galectin-3 and the percentage of peripheral CD4+</sup>CD69+</sup> cells in cervical cancer.展开更多
Background: According to WHO estimates, by 2022 over 296 million people are living with chronic hepatitis B virus (HBV) infection, and over 820,000 have died from complications. In sub-Saharan African countries such a...Background: According to WHO estimates, by 2022 over 296 million people are living with chronic hepatitis B virus (HBV) infection, and over 820,000 have died from complications. In sub-Saharan African countries such as Benin and Senegal, few research studies have addressed the issue of HBV immunization. Objective: The main objective of this study was to evaluate immunization against the hepatitis B virus in populations residing in Cotonou and Dakar by titrating anti-HBs antibodies (Ab) and detecting total anti-HBc immunoglobulins (Ig). Materials and Methods: This was a prospective, descriptive, analytical study of two West African populations recruited in Dakar at the Laboratory of Medical Biology (LBM) of the General Hospital Idrissa Pouye (HOGIP) and in Cotonou at the LBMs of the health centres of the Cotonou archdiocese. HBsAg-negative patients constituted our study population. The study took place in November-December 2019 for Dakar and February-March 2020 for Cotonou. Anti-HBs antibodies were tested and titrated. In the event of anti-HBs positivity, total anti-HBc was determined. A microparticle chemiluminescence immunoassay was used for marker determination. The detection threshold was 2.50 IU/L for anti-HBs. Excel and IBM SPSS Statistics software were used for data analysis. Subjects’ sociodemographic characteristics were collected using a questionnaire, as was knowledge of their vaccination status. The study was approved by the ethics committees in Benin and Senegal. Results: A total of 394 HBs antigen-negative participants were recruited: 205 in Cotonou and 189 in Dakar. The population was predominantly female, with 65.36% (N = 134) and 57.14% (N = 108) women in Cotonou and Dakar respectively. The median age of participants was 29 years in Cotonou, with extremes of 10 and 65 years, versus 39 years in Dakar, with extremes of 6 and 93 years. Some participants claimed to be unaware of their vaccination status: 33.17% in Cotonou and 56.61% in Dakar. The total prevalence of anti-HBs-positive subjects was 88.78% (N = 182) in Cotonou and 98.41% (N = 186) in Dakar. In Cotonou (N = 205), 35.61% (N = 73) of subjects had protective anti-HBs levels between 11.60 IU/L and 10,000 IU/L. In Dakar, 61.38% (N = 116) of subjects had protective HBV immunity, with anti-HBs titres ranging from 10.30 IU/L to 11357 IU/L. In Cotonou, 80.82% (N = 59) of immunized subjects (N = 73) had anti-HBC antibodies, compared with 84.48% (N = 98) of immunized individuals (N = 116) in the population recruited in Dakar, indicating immunization following HBV infection. Conclusion: Our study involved a predominantly female population, many of whom were unaware of their serological status. Vaccination policies and knowledge of the viral hepatitis B epidemic need to be strengthened.展开更多
Background: The persistence of the rapid spread of the COVID-19 pandemic is linked to the appearance of several variants of SARS-CoV2 with an impact on biological diagnosis, treatment and vaccination. The United State...Background: The persistence of the rapid spread of the COVID-19 pandemic is linked to the appearance of several variants of SARS-CoV2 with an impact on biological diagnosis, treatment and vaccination. The United States Food and Drug Administration (FDA) has granted several SARS-CoV-2 detection tests Emergency Use Authorization (EUA) for diagnosis and better epidemiological surveillance. Thus, multiple RT-PCR tests have been developed and brought to market in order to meet the urgent need for the diagnosis of COVID-19. However, comparative data between these tests in clinical laboratories are scarcely available to assess their performance. Objective: To compare two molecular methods for detecting SARS-CoV-2: the RT-PCR, Allplex™2019-nCoV tests on CFX96 Bio-Rad and the Abbott m2000sp/rt RealTime SARS-CoV-2. Materials and Methods: Nasopharyngeal and oropharyngeal swabs were taken from patients to diagnose SARS-CoV-2 infection. For each sample, we searched for the virus with two different RT-PCR tests: 1) first on Abbott m2000 SARS-CoV-2 targeting the N and RdRp genes, 2) then on Allplex™2019-nCoV Assay looking for the E, N and RdRp genes. Results: Percentages of the agreement were calculated. A total of 100 samples that tested negative and 90 positives on Abbott m2000 SARS-CoV-2 were retested on Allplex™2019-nCoV. Overall agreement was 74.74% on all samples. The specific agreement was 84% and 64.4% respectively for negative and positive samples with the RealTime SARS-CoV-2 test. A positive correlation (r<sup>2</sup> = 0.63;p Conclusion: Our results showed good overall agreement between RT-PCR, Allplex™2019-nCoV and Abbott RealTime SARS-CoV-2 tests in the diagnosis of COVID-19. As the concordance is low for small viremias, the RT-PCR Allplex™2019-nCoV Assay would be better indicated during the acute and symptomatic phase of the disease.展开更多
Periodontitis is caused by overactive osteoclast activity that results in the loss of periodontal supporting tissue and mesenchymal stem cells(MSCs)are essential for periodontal regeneration.However,the hypoxic period...Periodontitis is caused by overactive osteoclast activity that results in the loss of periodontal supporting tissue and mesenchymal stem cells(MSCs)are essential for periodontal regeneration.However,the hypoxic periodontal microenvironment during periodontitis induces the apoptosis of MSCs.Apoptotic bodies(ABs)are the major product of apoptotic cells and have been attracting increased attention as potential mediators for periodontitis treatment,thus we investigated the effects of ABs derived from MSCs on periodontitis.MSCs were derived from bone marrows of mice and were cultured under hypoxic conditions for 72 h,after which ABs were isolated from the culture supernatant using a multi-filtration system.The results demonstrate that ABs derived from MSCs inhibited osteoclast differentiation and alveolar bone resorption.miRNA array analysis showed that miR-223-3p is highly enriched in those ABs and is critical for their therapeutic effects.Targetscan and luciferase activity results confirmed that Itgb1 is targeted by miR-223-3p,which interferes with the function of osteoclasts.Additionally,DC-STAMP is a key regulator that mediates membrane infusion.ABs and pre-osteoclasts expressed high levels of DC-STAMP on their membranes,which mediates the engulfment of ABs by pre-osteoclasts.ABs with knock-down of DC-STAMP failed to be engulfed by pre-osteoclasts.Collectively,MSC-derived ABs are targeted to be engulfed by pre-osteoclasts via DC-STAMP,which rescued alveolar bone loss by transferring miR-223-3p to osteoclasts,which in turn led to the attenuation of their differentiation and bone resorption.These results suggest that MSC-derived ABs are promising therapeutic agents for the treatment of periodontitis.展开更多
Background: In recent years, head and neck cancers have become common worldwide, ranking sixth in incidence. In 2007, in France the incidence increased by 14,697 including 11,158 among men, which places them in fourth...Background: In recent years, head and neck cancers have become common worldwide, ranking sixth in incidence. In 2007, in France the incidence increased by 14,697 including 11,158 among men, which places them in fourth place. The same year, 32,268 patients were hospitalized for this pathology, but 95% are associated with alcohol and tobacco poisoning. Few data exist on these cancers in Africa and Senegal. In recent years, many studies have hypothesized that about 25% of head and neck cancers are associated with high-risk oncogenic human papillomaviruses (HPV) whose role in cervical cancer was already widely established. Objective: To know the prevalence and genotypes of HPV in head and neck cancers, particularly hypopharyngeal cancer. Material and method: This study was carried out on samples of biopsies of hypopharynx cancerous tissue (ulcerative-budding lesion) and healthy oropharyngeal tissue obtained from the ENT department of the Fann hospital, then sent to the Molecular Biology Unit of the Ouakam military hospital (HMO). The nucleic acids extraction was carried out using the standard method of the Zymo research kit “Quick-DNA<sup>TM</sup> Miniprep Plus kit” https://www.zymoresearch.com/. Molecular HPV detection and genotyping were performed by multiplex RT-PCR with the Seegene Anyplex<sup>TM</sup> II HPV28 kit Detection on a Biorad CFX96 automaton according to the manufacturer’s protocol for the simultaneous genotyping of 28 types of HPV including 19 at High Risk (HR) and 9 low risk (LR). Results: 156 patients were sampled, 61 Hypopharynx cancer biopsies and 95 healthy tissues. The median age of the general population was 36.5 years [12, 73];the median age of the population with hypopharyngeal cancer of 40 years. Of the general study population 24.36% (38/156) was infected with HPV. In populations with hypopharyngeal cancer, HPV prevalence was 19.67% (12/61), 17.84% (5/28) in men and 21.21% (7/33) in women. HPV6 was the most frequently encountered genotype in the cancer population. Multiple infections have also been noted in cancer patients: HPV6+HPV18, HPV6+HPV56. For patients without hypopharyngeal cancer, the HPV prevalence was 27.36% (26/95), 9.59% (7/73) in women and 89.36% (19/22) in men. Several types of HPV-HR genotypes (HPV18, HPV26, HPV69), and HPV-LR genotypes (HPV42, HPV43, HPV70, HPV6) have been detected in healthy patients but also cases of co-infections (HPV6+HPV69;HPV56+HPV44;HPV58+HPV18). Conclusion: Our results showed a higher prevalence of HPV in non-cancer patients compared to hypopharyngeal cancer patients. The genotypes (HPV 6, 18 and 56) were observed in the study population. Molecular genotyping does not show a significant involvement of HPV in hypopharyngeal cancer.展开更多
Background : SHARPIN (SHANK- associated RH domain interactor) is a component ofthe linear ubiquitination complex that regulates the NF- κB signaling pathway. To betterunderstand the function of SHARPIN, we sought to ...Background : SHARPIN (SHANK- associated RH domain interactor) is a component ofthe linear ubiquitination complex that regulates the NF- κB signaling pathway. To betterunderstand the function of SHARPIN, we sought to establish a novel geneticallyengineered Syrian hamster with SHARPIN disruption using the CRISPR/Cas9 system.Methods : A single- guide ribonucleic acid targeting exon 1 of SHARPIN gene was designedand constructed. The zygotes generated by cytoplasmic injection of the Cas9/gRNA ribonucleoprotein were transferred into pseudopregnant hamsters. Neonatalmutants were identified by genotyping. SHARPIN protein expression was detectedusing Western blotting assay. Splenic, mesenteric lymph nodes (MLNs), and thymicweights were measured, and organ coefficients were calculated. Histopathologicalexamination of the spleen, liver, lung, small intestine, and esophagus was performedindependently by a pathologist. The expression of lymphocytic markers and cytokineswas evaluated using reverse transcriptase- quantitative polymerase chain reaction.Results : All the offspring harbored germline- transmitted SHARPIN mutations.Compared with wild- type hamsters, SHARPIN protein was undetectable in SHARPIN −/−hamsters. Spleen enlargement and splenic coefficient elevation were spotted inSHARPIN −/− hamsters, with the descent of MLNs and thymuses. Further, eosinophilinfiltration and structural alteration in spleens, livers, lungs, small intestines, and esophagiwere obvious after the deletion of SHARPIN. Notably, the expression of CD94 and CD22 was downregulated in the spleens of knockout (KO) animals. Nonetheless,the expression of CCR3, CCL11, Il4 , and Il13 was upregulated in the esophagi. Theexpression of NF- κB and phosphorylation of NF- κB and IκB protein significantly diminishedin SHARPIN −/− animals.Conclusions : A novel SHARPIN KO hamster was successfully established using theCRISPR/Cas9 system. Abnormal development of secondary lymphoid organs andeosinophil infiltration in multiple organs reveal its potential in delineating SHARPINfunction and chronic inflammation.展开更多
Hand osteoarthritis is a common heterogeneous joint disorder with unclear molecular mechanisms and no disease-modifying drugs.In this study,we performed single-cell RNA sequencing analysis to compare the cellular comp...Hand osteoarthritis is a common heterogeneous joint disorder with unclear molecular mechanisms and no disease-modifying drugs.In this study,we performed single-cell RNA sequencing analysis to compare the cellular composition and subpopulationspecific gene expression between cartilage with macroscopically confirmed osteoarthritis(n=5)and cartilage without osteoarthritis(n=5)from the interphalangeal joints of five donors.Of 105142 cells,we identified 13 subpopulations,including a novel subpopulation with inflammation-modulating potential annotated as inflammatory chondrocytes.Fibrocartilage chondrocytes exhibited extensive alteration of gene expression patterns in osteoarthritic cartilage compared with nonosteoarthritic cartilage.Both inflammatory chondrocytes and fibrocartilage chondrocytes showed a trend toward increased numbers in osteoarthritic cartilage.In these two subpopulations from osteoarthritic cartilage,the ferroptosis pathway was enriched,and expression of iron overload-related genes,e.g.,FTH1,was elevated.To verify these findings,we conducted a Mendelian randomization study using UK Biobank and a population-based cross-sectional study using data collected from Xiangya Osteoarthritis Study.Genetic predisposition toward higher expression of FTH1 mRNA significantly increased the risk of hand osteoarthritis(odds ratio=1.07,95%confidence interval:1.02–1.11)among participants(n=332668)in UK Biobank.High levels of serum ferritin(encoded by FTH1),a biomarker of body iron overload,were significantly associated with a high prevalence of hand osteoarthritis among participants(n=1241)of Xiangya Osteoarthritis Study(P-for-trend=0.037).In conclusion,our findings indicate that inflammatory and fibrocartilage chondrocytes are key subpopulations and that ferroptosis may be a key pathway in hand osteoarthritis,providing new insights into the pathophysiology and potential therapeutic targets of hand osteoarthritis.展开更多
AIM: To determine the prevalence of several autoantibodies in chronic hepatitis C patients, and to find out whether the pattern of autoantibodies was associated with hepatitis C virus (HCV) genotypes.METHODS: Sera fro...AIM: To determine the prevalence of several autoantibodies in chronic hepatitis C patients, and to find out whether the pattern of autoantibodies was associated with hepatitis C virus (HCV) genotypes.METHODS: Sera from 90 consecutive patients with chronic hepatitis C were investigated on the presence of anti-nuclear (ANA), anti-mitochondrial (AMA), anti-smooth muscle (SMA),anti-liver-kidney microsomal type 1 (LKMA1), anti-parietal cell (PCA), anti-thyroid microsomal (TMA), and anti-reticulin (ARA) autoantibodies. The autoantibodies were identified by indirect immunofluorescence. HCV genotypes were determined by a restriction fragment length polymorphism analysis of the amplified 5' noncoding genome region.RESULTS: Forty-six (51.1%) patients were positive for at least one autoantibody. Various antibodies were presented as follows: ANA in 13 (14.4%) patients, SMA in 39 (43.3%),TMA in 2 (2.2%), and ARA in 1 (1.1%) patients. In 9 cases,sera were positive for two autoantibodies (ANA and SMA).AMA, PCA and LKMA1 were not detected in the observed sera. HCV genotypes were distributed as follows: 1b in 66 (73.3%) patients, 3a in 18 (20.0%), and 2a in 6 (6.7%)patients.CONCLUSION: A high prevalence of ANA and SMA can be found in chronic hepatitis C patients. Autoantibodies are present at low titre (1: 10) in most of the cases. Distribution of the autoantibodies show no differences in the sex groups and between patients infected with different HCV genotypes.展开更多
AIM:To determine the possibility of the development of dry eye disease(DED) as a result of persistent infection with Chlamydia trachomatis and Ureaplasma urealyticum in the conjunctiva of patients.METHODS: This study ...AIM:To determine the possibility of the development of dry eye disease(DED) as a result of persistent infection with Chlamydia trachomatis and Ureaplasma urealyticum in the conjunctiva of patients.METHODS: This study was conducted on 58 patients of age range 20-50 y,diagnosed with DED confirmed by Schirmer I test and tear breakup time.The non-dry eye control group included 27 subjects of the same age.Ocular specimens were collected as conjunctival scrapings and swabs divided into three groups: the first used for bacterial culture,the second and third taken to detect Chlamydia trachomatis and Ureaplasma urealyticum by direct fluorescent antibody(DFA) assay and polymerase chain reaction(PCR) method. RESULTS: Chlamydia trachomatis was detected in 65.5% and 76% of DED patients by DFA and PCR methods respectively.Ureaplasma urealyticum was found in 44.8% of DED infected patients using the PCR method.Both organisms were identified in only 37.9% of DED patients found to be infected.Control subjects had a 22%detection rate of Chlamydia trachomatis by DFA assay versus a 7% detection rate by PCR; while Ureaplasma urealyticum was detected in 3.7% of the controls by PCR method.The conjunctival culture revealed that gram positive microorganisms represented 75% of isolates with coagulase negative Staphylococci the most common(50%) followed by Staphylococcus aureus(20%),whereas gram negative microorganisms occurred in 25% of cases,isolating Moraxella spp.as the most frequent organism. CONCLUSION: Our results tend to point out that Chlamydia trachomatis and Ureaplasma urealyticum were detected in a moderate percentage of patients with DED,and could be a fair possibility for its development.PCR is more reliable in detecting Chlamydia trachomatis than DFA technique.The presence of isolated conjunctival bacterial microflora can be of some potential value.展开更多
Obesity is increasingly being recognized as a risk factor for a number of benign and malignant gastrointestinal conditions. However, literature on the underlying pathophysiological mechanisms is sparse and ambiguous. ...Obesity is increasingly being recognized as a risk factor for a number of benign and malignant gastrointestinal conditions. However, literature on the underlying pathophysiological mechanisms is sparse and ambiguous. There is compelling evidence that both overnutrition and undernutrition negatively interfere with the immune system. Overnutrition has been found to increase susceptibility to the development of inflammatory diseases, autoimmune diseases and cancer. In the regulation of immune and in? ammatory processes, white adipose tissue plays a critical role, not only as an energy store but also as an important endocrine organ. The obese state is characterised by a low-grade systemic in? ammation, mainly as a result of increased adipocytes as well as fat resident-and recruited-macrophage activity. In the past few years, various products of adipose tissue including adipokines and cytokines have been characterised and a number of pathways linking adipose tissue metabolism with the immune system have been identified. Activation of the innate immune system plays a major role in hepatic steatosis. Non-alcoholic fatty liver disease includes a wide spectrum of diseases, from pure steatosis to non-alcoholic steato-hepatitis in the absence of signif icant alcohol consumption. Although steatosis is considered a non-progressive disease, non-alcoholic steatohepatitis may deteriorate in advanced chronic liver diseases, cirrhosis, and hepatocellular carcinoma. An important parallel between obesityrelated pathology of adipose tissue and liver pertains to the emerging role of macrophages, and growing evidence suggests that Kupffer cells critically contribute to progression of non-alcoholic fatty liver disease. Moreover, a close link between specif ic immune activation and atherosclerosis has been well established, suggesting that fat can directly trigger immune responses. This review discusses the role of fat as "a matter of disturbance for the immune system" with a focus on hepatic steatosis.展开更多
Objective:Oral squamous-cell carcinoma(OSCC)accounts for >90% of oral cancers affecting adults mostly between the fourth to seventh decades of life.The most common OSCC treatment is concomitant chemoradiotherapy(CC...Objective:Oral squamous-cell carcinoma(OSCC)accounts for >90% of oral cancers affecting adults mostly between the fourth to seventh decades of life.The most common OSCC treatment is concomitant chemoradiotherapy(CCRT)having both locoregional and distant control,but CCRT has acute and chronic toxic effects on adjacent normal tissue.This study aimed to determine the side effects of CCRT on the oral mucosa and to characterize the clinicopathology of oral lesions in patients with OSCC.Methods:This descriptive,cross-sectional study was certified by the Ethical Review Committee(UHS/Education/126-12/2728)of the University of Health Sciences,Lahore,Pakistan.OSSC patients(n=81)with various histological subtypes,grades,and stages were recruited,and findings on their oral examination were recorded.These patients received 70,90,and 119 Gy of radiotherapy dosages in combination with the chemotherapy drugs cisplatin and 5-fluorouracil.Data were analyzed using SPSS 20.0.Results:The most common presentation of OSCC was a nonhealing ulcer(63%) involving tongue(55.6%).Clinical findings included mucositis(92.6%)and xerostomia of mild,moderate,and severe degrees in 11.1%,46.9%,and 35.8% cases,respectively.Ulcers(87.7%),palpable lymph nodes(64.2%),limited mouth opening(64.2%)and fistula(40.7%) were also observed.In females,the association of radiotherapy dosage with limited mouth opening,xerostomia,and histological grading was statistically significant(P<0.05).The association of chemotherapy drugs with xerostomia(P=0.003)was also statistically significant.Conclusions:CCRT induced mucositis,xerostomia,and trismus in patients with OSCC.展开更多
Gastric cancer(GC) is the fifth most common malignancy in the world. The major cause of GC is chronic infection with Helicobacter pylori(H. pylori). Infection with H. pylori leads to an active inflammatory microenviro...Gastric cancer(GC) is the fifth most common malignancy in the world. The major cause of GC is chronic infection with Helicobacter pylori(H. pylori). Infection with H. pylori leads to an active inflammatory microenvironment that is maintained by immune cells such as T cells, macrophages, natural killer cells, among other cells. Immune cell dysfunction allows the initiation and accumulation of mutations in GC cells, inducing aberrant proliferation and protection from apoptosis. Meanwhile, immune cells can secrete certain signals, including cytokines, and chemokines, to alter intracellular signaling pathways in GC cells. Thus, GC cells obtain the ability to metastasize to lymph nodes by undergoing the epithelial-mesenchymal transition(EMT), whereby epithelial cells lose their epithelial attributes and acquire a mesenchymal cell phenotype. Metastasis is a leading cause of death for GC patients, and the involved mechanisms are still under investigation. In this review, we summarize the current research on how the inflammatory environment affects GC initiation and metastasis via EMT.展开更多
The chemokine system consists of four different subclasses with over 50 chemokines and 19 receptors. Their functions in the immune system have been well elucidated and research during the last decades unveils their ne...The chemokine system consists of four different subclasses with over 50 chemokines and 19 receptors. Their functions in the immune system have been well elucidated and research during the last decades unveils their new roles in hepatocellular carcinoma(HCC). The chemokines and their receptors in the microenvironment influence the development of HCCby several aspects including:inflammation,effects on immune cells,angiogenesis,and direct effects on HCC cells. Regarding these aspects,pre-clinical research by targeting the chemokine system has yielded promising data,and these findings bring us new clues in the chemokine-based therapies for HCC.展开更多
AIM: Inflammatory bowel diseases (IBD) are multifactorial pathologies of unknown etiology. One susceptibility locus,IBD5, has been mapped to chromosome 5q31. We analyzed our Spanish cohorts of Crohn's disease (CD)...AIM: Inflammatory bowel diseases (IBD) are multifactorial pathologies of unknown etiology. One susceptibility locus,IBD5, has been mapped to chromosome 5q31. We analyzed our Spanish cohorts of Crohn's disease (CD)and ulcerative colitis (UC) patients to determine whether this locus is associated with IBD, and to ascertain the main clinical phenotype influenced by this risk factor. The kind of interaction, either genetic heterogeneity or epistasis, between this IBD5 susceptibility region and the NOD2/CARD15 gene mutations was studied as well.Finally, ve assessed whether this locus can predict response to infliximab therapy.METHODS: A case control study was performed with 274CD and 211 UC patients recruited from a single center and 511 healthy ethnically matched controls. Two polymorphisms were genotyped in the IBD5 locus and three in the CARD15/NOD2 gene.RESULTS: Our results evidence association only with CD especially with the fistulizing phenotype and in the absence of NOD2/CARD15 variants (mutant allele frequency in patients vscontrols: OR = 2.03, 95% CI = 1.35-3.06,P＜0.01). The frequency of the IBD5 homozygous mutant genotype significantly increased in CD patients lacking response to infliximab (RR = 3.88, 95% CI = 1.18-12.0,P＜0.05). UC patients overall do not show association with 5q31 polymorphisms, although a similar trend to the one observed in CD is found within the worse prognosis group.CONCLUSION: The IBD5 variants may enhance an individual carrier's risk for CD, mainly in the absence of the NOD2/CARD15 mutations and in fistulizing patients.The data presented suggest the potential role of the 5q31polymorphisms as markers of response to infiiximab.展开更多
AIM: To determine whether local antibiotic resistance involves P-glycoprotein (Pgp)-mediated active drug outpumping during Helicobacter pylori ( H pylori) infection treatment with classic antibiotic therapy. METHODS: ...AIM: To determine whether local antibiotic resistance involves P-glycoprotein (Pgp)-mediated active drug outpumping during Helicobacter pylori ( H pylori) infection treatment with classic antibiotic therapy. METHODS: Pgp activity was determined in gastric mucosa biopsy specimens obtained from 53 patients with pathohistologically verified gastritis and microbiologically confirmed H pylori infection, and compared with the Pgp activity in 12 control subjects with normal endoscopic findings. TheH pylori positive patients were treated with short-term 7-d therapy consisting of two antibiotics (amoxicillin and azithromycin/metronidazole and clarithromycin) and a proton pump inhibitor. Pgp activity was determined by flow cytometry in the test of rhodamine dye efflux and quantified as mean fluorescence ratio (RMF).RESULTS: Upon the first cycle,H pylori was successfully eradicated in 20 patients, whereas therapy was continued in 33 patients. In the course of antibiotic therapy, RMF increased (P＜0.05) and gastric cells showed higher rhodamine dye efflux. The mean pre-treatment RMF values were also higher (P＜0.0001) in patients with multiple therapeutic failure than in those with successful H pylorieradication and control subjects.CONCLUSION: Pgp might be one of the causes of therapy failure in patients with H pylori and antibiotic therapy could be chosen and followed up on the basis of the Pgp transporter local activity.展开更多
文摘Peanut allergy is majorly related to severe food induced allergic reactions.Several food including cow's milk,hen's eggs,soy,wheat,peanuts,tree nuts(walnuts,hazelnuts,almonds,cashews,pecans and pistachios),fish and shellfish are responsible for more than 90%of food allergies.Here,we provide promising insights using a large-scale data-driven analysis,comparing the mechanistic feature and biological relevance of different ingredients presents in peanuts,tree nuts(walnuts,almonds,cashews,pecans and pistachios)and soybean.Additionally,we have analysed the chemical compositions of peanuts in different processed form raw,boiled and dry-roasted.Using the data-driven approach we are able to generate new hypotheses to explain why nuclear receptors like the peroxisome proliferator-activated receptors(PPARs)and its isoform and their interaction with dietary lipids may have significant effect on allergic response.The results obtained from this study will direct future experimeantal and clinical studies to understand the role of dietary lipids and PPARisoforms to exert pro-inflammatory or anti-inflammatory functions on cells of the innate immunity and influence antigen presentation to the cells of the adaptive immunity.
文摘Background: In 2019, the WHO estimated that over 296 million people were living with chronic hepatitis B virus (HBV) infection and over 820,000 deaths attributable to hepatitis B. Most people living with HBV are unaware of their immune status and live in endemic areas. This is the case of Benin and Senegal, which have little data on the disease. Objective: This study aimed to provide epidemiological furthers on hepatitis B in Dakar and Cotonou according to WHO recommendations about “obtaining data for action”. Materials and Methods: Our study took place at the Medical Biology Laboratory of the Idrissa Pouye General Hospital (LBM-HOGIP) in Dakar, Senegal. Participants were selected at the LBM-HOGIP of Dakar or at the LBMs of the health centres of the Archdiocese of Cotonou respectively from November to December 2019 and February to March 2020. All participants were tested for hepatitis B virus antigen (HBsAg) using a microparticle chemiluminescence immunoassay assay. Other risk factors including blood transfusion, haemodialysis, tattooing, cultural or clan scarification, piercing, injecting drug use, unprotected sex and surgical procedures were also investigated. Informed consent was obtained from each participant. The study was approved by the ethics committees in Senegal and Benin. For the biological tests, Excel and IBM SPSS Statistics software were used for the analysis of the results. Results: A total of 470 participants were recruited including 234 in Cotonou and 236 in Dakar. The median age in Cotonou was 29 years with extremes of 10 and 65 years, and 38 years in Dakar with extremes of 6 and 93 years. The prevalence of HBsAg was 12.39% in Cotonou and 19.91% in Dakar. The most affected age groups were 20 - 29 in Dakar and 30 - 39 in Cotonou. Except for piercing, none of the other risk factors considered in our study were found to be associated with HBV transmission in our populations. Conclusion: Our study is hospital-based and revealed high prevalence of HBsAg. These prevalences were higher in men.
文摘Objective: Despite the existence of several therapeutic strategies, the management of cervical cancer remains challenging. Our region has very little data on the interaction between the immune system and the clinical response to chemotherapy. This work examines plasma levels of galectin-3 (Gal-3) and percentages of activated T cells in patients with cervical cancer treated with chemotherapy and investigates if there is a relationship between the rates of these two elements. Methods: We compared data from 37 patients with cervical cancer undergoing chemotherapy and 42 controls with normal cervical cytology. Plasma Gal-3 concentrations were assessed by ELISA and expression of activation markers by T cells (CD69 and HLA-DR) was assessed by flow cytometry at three different time points during chemotherapy. Results: Our results showed that patients had a significantly higher concentration of Gal-3 compared to controls (4.025 vs. 1.340, p 0.001), similarly, they had a significantly high percentage of activated lymphocytes (2.610 vs. 0.731;p 0.0001). According to the response to treatment, patients with no response to treatment had a lower concentration of circulating Gal-3 but had approximately the same percentage of activated CD4 and CD8 lymphocytes as patients with a partial or total response. In addition, we found a positive correlation between the Gal-3 level and CD4 T cells expressing the activation marker CD69 (p 0.05;rho = 0.44). Conclusion: In conclusion, our results show that there would be a relationship between circulating galectin-3 and the percentage of peripheral CD4+</sup>CD69+</sup> cells in cervical cancer.
文摘Background: According to WHO estimates, by 2022 over 296 million people are living with chronic hepatitis B virus (HBV) infection, and over 820,000 have died from complications. In sub-Saharan African countries such as Benin and Senegal, few research studies have addressed the issue of HBV immunization. Objective: The main objective of this study was to evaluate immunization against the hepatitis B virus in populations residing in Cotonou and Dakar by titrating anti-HBs antibodies (Ab) and detecting total anti-HBc immunoglobulins (Ig). Materials and Methods: This was a prospective, descriptive, analytical study of two West African populations recruited in Dakar at the Laboratory of Medical Biology (LBM) of the General Hospital Idrissa Pouye (HOGIP) and in Cotonou at the LBMs of the health centres of the Cotonou archdiocese. HBsAg-negative patients constituted our study population. The study took place in November-December 2019 for Dakar and February-March 2020 for Cotonou. Anti-HBs antibodies were tested and titrated. In the event of anti-HBs positivity, total anti-HBc was determined. A microparticle chemiluminescence immunoassay was used for marker determination. The detection threshold was 2.50 IU/L for anti-HBs. Excel and IBM SPSS Statistics software were used for data analysis. Subjects’ sociodemographic characteristics were collected using a questionnaire, as was knowledge of their vaccination status. The study was approved by the ethics committees in Benin and Senegal. Results: A total of 394 HBs antigen-negative participants were recruited: 205 in Cotonou and 189 in Dakar. The population was predominantly female, with 65.36% (N = 134) and 57.14% (N = 108) women in Cotonou and Dakar respectively. The median age of participants was 29 years in Cotonou, with extremes of 10 and 65 years, versus 39 years in Dakar, with extremes of 6 and 93 years. Some participants claimed to be unaware of their vaccination status: 33.17% in Cotonou and 56.61% in Dakar. The total prevalence of anti-HBs-positive subjects was 88.78% (N = 182) in Cotonou and 98.41% (N = 186) in Dakar. In Cotonou (N = 205), 35.61% (N = 73) of subjects had protective anti-HBs levels between 11.60 IU/L and 10,000 IU/L. In Dakar, 61.38% (N = 116) of subjects had protective HBV immunity, with anti-HBs titres ranging from 10.30 IU/L to 11357 IU/L. In Cotonou, 80.82% (N = 59) of immunized subjects (N = 73) had anti-HBC antibodies, compared with 84.48% (N = 98) of immunized individuals (N = 116) in the population recruited in Dakar, indicating immunization following HBV infection. Conclusion: Our study involved a predominantly female population, many of whom were unaware of their serological status. Vaccination policies and knowledge of the viral hepatitis B epidemic need to be strengthened.
文摘Background: The persistence of the rapid spread of the COVID-19 pandemic is linked to the appearance of several variants of SARS-CoV2 with an impact on biological diagnosis, treatment and vaccination. The United States Food and Drug Administration (FDA) has granted several SARS-CoV-2 detection tests Emergency Use Authorization (EUA) for diagnosis and better epidemiological surveillance. Thus, multiple RT-PCR tests have been developed and brought to market in order to meet the urgent need for the diagnosis of COVID-19. However, comparative data between these tests in clinical laboratories are scarcely available to assess their performance. Objective: To compare two molecular methods for detecting SARS-CoV-2: the RT-PCR, Allplex™2019-nCoV tests on CFX96 Bio-Rad and the Abbott m2000sp/rt RealTime SARS-CoV-2. Materials and Methods: Nasopharyngeal and oropharyngeal swabs were taken from patients to diagnose SARS-CoV-2 infection. For each sample, we searched for the virus with two different RT-PCR tests: 1) first on Abbott m2000 SARS-CoV-2 targeting the N and RdRp genes, 2) then on Allplex™2019-nCoV Assay looking for the E, N and RdRp genes. Results: Percentages of the agreement were calculated. A total of 100 samples that tested negative and 90 positives on Abbott m2000 SARS-CoV-2 were retested on Allplex™2019-nCoV. Overall agreement was 74.74% on all samples. The specific agreement was 84% and 64.4% respectively for negative and positive samples with the RealTime SARS-CoV-2 test. A positive correlation (r<sup>2</sup> = 0.63;p Conclusion: Our results showed good overall agreement between RT-PCR, Allplex™2019-nCoV and Abbott RealTime SARS-CoV-2 tests in the diagnosis of COVID-19. As the concordance is low for small viremias, the RT-PCR Allplex™2019-nCoV Assay would be better indicated during the acute and symptomatic phase of the disease.
基金grants from National Key R&D Program of China(Grant No.2022YFC2504200)the National Nature Science Foundation of China(81991504 and 81974149 to Y.L.+7 种基金82201052 to X.Y.L.)the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support(ZYLX202121 to Y.L.)the Innovation Research Team Project of Beijing Stomatological Hospital,Capital Medical University(CXTD202202)the Beijing Municipal Administration of Hospitals’Ascent Plan(DFL20181501 to Y.L.)the Beijing Municipal Administration of Hospitals’Youth Programme(QML20181501 to L.J.G.QML20231505 to X.Y.L.)the Beijing Stomatological Hospital,Capital Medical University Young Scientist Program(No.YSP202103 to X.Y.L.)the Innovation Foundation of Beijing Stomatological Hospital,Capital Medical University(21-09-18 to L.J.G.).
文摘Periodontitis is caused by overactive osteoclast activity that results in the loss of periodontal supporting tissue and mesenchymal stem cells(MSCs)are essential for periodontal regeneration.However,the hypoxic periodontal microenvironment during periodontitis induces the apoptosis of MSCs.Apoptotic bodies(ABs)are the major product of apoptotic cells and have been attracting increased attention as potential mediators for periodontitis treatment,thus we investigated the effects of ABs derived from MSCs on periodontitis.MSCs were derived from bone marrows of mice and were cultured under hypoxic conditions for 72 h,after which ABs were isolated from the culture supernatant using a multi-filtration system.The results demonstrate that ABs derived from MSCs inhibited osteoclast differentiation and alveolar bone resorption.miRNA array analysis showed that miR-223-3p is highly enriched in those ABs and is critical for their therapeutic effects.Targetscan and luciferase activity results confirmed that Itgb1 is targeted by miR-223-3p,which interferes with the function of osteoclasts.Additionally,DC-STAMP is a key regulator that mediates membrane infusion.ABs and pre-osteoclasts expressed high levels of DC-STAMP on their membranes,which mediates the engulfment of ABs by pre-osteoclasts.ABs with knock-down of DC-STAMP failed to be engulfed by pre-osteoclasts.Collectively,MSC-derived ABs are targeted to be engulfed by pre-osteoclasts via DC-STAMP,which rescued alveolar bone loss by transferring miR-223-3p to osteoclasts,which in turn led to the attenuation of their differentiation and bone resorption.These results suggest that MSC-derived ABs are promising therapeutic agents for the treatment of periodontitis.
文摘Background: In recent years, head and neck cancers have become common worldwide, ranking sixth in incidence. In 2007, in France the incidence increased by 14,697 including 11,158 among men, which places them in fourth place. The same year, 32,268 patients were hospitalized for this pathology, but 95% are associated with alcohol and tobacco poisoning. Few data exist on these cancers in Africa and Senegal. In recent years, many studies have hypothesized that about 25% of head and neck cancers are associated with high-risk oncogenic human papillomaviruses (HPV) whose role in cervical cancer was already widely established. Objective: To know the prevalence and genotypes of HPV in head and neck cancers, particularly hypopharyngeal cancer. Material and method: This study was carried out on samples of biopsies of hypopharynx cancerous tissue (ulcerative-budding lesion) and healthy oropharyngeal tissue obtained from the ENT department of the Fann hospital, then sent to the Molecular Biology Unit of the Ouakam military hospital (HMO). The nucleic acids extraction was carried out using the standard method of the Zymo research kit “Quick-DNA<sup>TM</sup> Miniprep Plus kit” https://www.zymoresearch.com/. Molecular HPV detection and genotyping were performed by multiplex RT-PCR with the Seegene Anyplex<sup>TM</sup> II HPV28 kit Detection on a Biorad CFX96 automaton according to the manufacturer’s protocol for the simultaneous genotyping of 28 types of HPV including 19 at High Risk (HR) and 9 low risk (LR). Results: 156 patients were sampled, 61 Hypopharynx cancer biopsies and 95 healthy tissues. The median age of the general population was 36.5 years [12, 73];the median age of the population with hypopharyngeal cancer of 40 years. Of the general study population 24.36% (38/156) was infected with HPV. In populations with hypopharyngeal cancer, HPV prevalence was 19.67% (12/61), 17.84% (5/28) in men and 21.21% (7/33) in women. HPV6 was the most frequently encountered genotype in the cancer population. Multiple infections have also been noted in cancer patients: HPV6+HPV18, HPV6+HPV56. For patients without hypopharyngeal cancer, the HPV prevalence was 27.36% (26/95), 9.59% (7/73) in women and 89.36% (19/22) in men. Several types of HPV-HR genotypes (HPV18, HPV26, HPV69), and HPV-LR genotypes (HPV42, HPV43, HPV70, HPV6) have been detected in healthy patients but also cases of co-infections (HPV6+HPV69;HPV56+HPV44;HPV58+HPV18). Conclusion: Our results showed a higher prevalence of HPV in non-cancer patients compared to hypopharyngeal cancer patients. The genotypes (HPV 6, 18 and 56) were observed in the study population. Molecular genotyping does not show a significant involvement of HPV in hypopharyngeal cancer.
基金Natural Science Foundation of Henan Province,Grant/Award Number:202300410259Henan Postdoctoral Science Foundation,Grant/Award Number:202001043China Postdoctoral Science Foundation,Grant/Award Number:2021T140184。
文摘Background : SHARPIN (SHANK- associated RH domain interactor) is a component ofthe linear ubiquitination complex that regulates the NF- κB signaling pathway. To betterunderstand the function of SHARPIN, we sought to establish a novel geneticallyengineered Syrian hamster with SHARPIN disruption using the CRISPR/Cas9 system.Methods : A single- guide ribonucleic acid targeting exon 1 of SHARPIN gene was designedand constructed. The zygotes generated by cytoplasmic injection of the Cas9/gRNA ribonucleoprotein were transferred into pseudopregnant hamsters. Neonatalmutants were identified by genotyping. SHARPIN protein expression was detectedusing Western blotting assay. Splenic, mesenteric lymph nodes (MLNs), and thymicweights were measured, and organ coefficients were calculated. Histopathologicalexamination of the spleen, liver, lung, small intestine, and esophagus was performedindependently by a pathologist. The expression of lymphocytic markers and cytokineswas evaluated using reverse transcriptase- quantitative polymerase chain reaction.Results : All the offspring harbored germline- transmitted SHARPIN mutations.Compared with wild- type hamsters, SHARPIN protein was undetectable in SHARPIN −/−hamsters. Spleen enlargement and splenic coefficient elevation were spotted inSHARPIN −/− hamsters, with the descent of MLNs and thymuses. Further, eosinophilinfiltration and structural alteration in spleens, livers, lungs, small intestines, and esophagiwere obvious after the deletion of SHARPIN. Notably, the expression of CD94 and CD22 was downregulated in the spleens of knockout (KO) animals. Nonetheless,the expression of CCR3, CCL11, Il4 , and Il13 was upregulated in the esophagi. Theexpression of NF- κB and phosphorylation of NF- κB and IκB protein significantly diminishedin SHARPIN −/− animals.Conclusions : A novel SHARPIN KO hamster was successfully established using theCRISPR/Cas9 system. Abnormal development of secondary lymphoid organs andeosinophil infiltration in multiple organs reveal its potential in delineating SHARPINfunction and chronic inflammation.
基金supported by the National Natural Science Foundation of China(81930071,82072502)the National Natural Science Foundation Regional Innovation and Development Joint Fund(U21A20352)+5 种基金the National Key Research and Development Project(2022YFC3601900,2022YFC2505500)the Project Program of National Clinical Research Center for Geriatric Disorders(Xiangya Hospital,2021LNJJ06,2022LNJJ07)the Natural Science Foundation of Hunan Province(2022JJ20100)the Key Research and Development Program of Hunan Province(2021SK2017)the Science and Technology Innovation Program of Hunan Province(2022RC3075)the Central South University Innovation-Driven Research Program(2023CXQD031)。
文摘Hand osteoarthritis is a common heterogeneous joint disorder with unclear molecular mechanisms and no disease-modifying drugs.In this study,we performed single-cell RNA sequencing analysis to compare the cellular composition and subpopulationspecific gene expression between cartilage with macroscopically confirmed osteoarthritis(n=5)and cartilage without osteoarthritis(n=5)from the interphalangeal joints of five donors.Of 105142 cells,we identified 13 subpopulations,including a novel subpopulation with inflammation-modulating potential annotated as inflammatory chondrocytes.Fibrocartilage chondrocytes exhibited extensive alteration of gene expression patterns in osteoarthritic cartilage compared with nonosteoarthritic cartilage.Both inflammatory chondrocytes and fibrocartilage chondrocytes showed a trend toward increased numbers in osteoarthritic cartilage.In these two subpopulations from osteoarthritic cartilage,the ferroptosis pathway was enriched,and expression of iron overload-related genes,e.g.,FTH1,was elevated.To verify these findings,we conducted a Mendelian randomization study using UK Biobank and a population-based cross-sectional study using data collected from Xiangya Osteoarthritis Study.Genetic predisposition toward higher expression of FTH1 mRNA significantly increased the risk of hand osteoarthritis(odds ratio=1.07,95%confidence interval:1.02–1.11)among participants(n=332668)in UK Biobank.High levels of serum ferritin(encoded by FTH1),a biomarker of body iron overload,were significantly associated with a high prevalence of hand osteoarthritis among participants(n=1241)of Xiangya Osteoarthritis Study(P-for-trend=0.037).In conclusion,our findings indicate that inflammatory and fibrocartilage chondrocytes are key subpopulations and that ferroptosis may be a key pathway in hand osteoarthritis,providing new insights into the pathophysiology and potential therapeutic targets of hand osteoarthritis.
文摘AIM: To determine the prevalence of several autoantibodies in chronic hepatitis C patients, and to find out whether the pattern of autoantibodies was associated with hepatitis C virus (HCV) genotypes.METHODS: Sera from 90 consecutive patients with chronic hepatitis C were investigated on the presence of anti-nuclear (ANA), anti-mitochondrial (AMA), anti-smooth muscle (SMA),anti-liver-kidney microsomal type 1 (LKMA1), anti-parietal cell (PCA), anti-thyroid microsomal (TMA), and anti-reticulin (ARA) autoantibodies. The autoantibodies were identified by indirect immunofluorescence. HCV genotypes were determined by a restriction fragment length polymorphism analysis of the amplified 5' noncoding genome region.RESULTS: Forty-six (51.1%) patients were positive for at least one autoantibody. Various antibodies were presented as follows: ANA in 13 (14.4%) patients, SMA in 39 (43.3%),TMA in 2 (2.2%), and ARA in 1 (1.1%) patients. In 9 cases,sera were positive for two autoantibodies (ANA and SMA).AMA, PCA and LKMA1 were not detected in the observed sera. HCV genotypes were distributed as follows: 1b in 66 (73.3%) patients, 3a in 18 (20.0%), and 2a in 6 (6.7%)patients.CONCLUSION: A high prevalence of ANA and SMA can be found in chronic hepatitis C patients. Autoantibodies are present at low titre (1: 10) in most of the cases. Distribution of the autoantibodies show no differences in the sex groups and between patients infected with different HCV genotypes.
文摘AIM:To determine the possibility of the development of dry eye disease(DED) as a result of persistent infection with Chlamydia trachomatis and Ureaplasma urealyticum in the conjunctiva of patients.METHODS: This study was conducted on 58 patients of age range 20-50 y,diagnosed with DED confirmed by Schirmer I test and tear breakup time.The non-dry eye control group included 27 subjects of the same age.Ocular specimens were collected as conjunctival scrapings and swabs divided into three groups: the first used for bacterial culture,the second and third taken to detect Chlamydia trachomatis and Ureaplasma urealyticum by direct fluorescent antibody(DFA) assay and polymerase chain reaction(PCR) method. RESULTS: Chlamydia trachomatis was detected in 65.5% and 76% of DED patients by DFA and PCR methods respectively.Ureaplasma urealyticum was found in 44.8% of DED infected patients using the PCR method.Both organisms were identified in only 37.9% of DED patients found to be infected.Control subjects had a 22%detection rate of Chlamydia trachomatis by DFA assay versus a 7% detection rate by PCR; while Ureaplasma urealyticum was detected in 3.7% of the controls by PCR method.The conjunctival culture revealed that gram positive microorganisms represented 75% of isolates with coagulase negative Staphylococci the most common(50%) followed by Staphylococcus aureus(20%),whereas gram negative microorganisms occurred in 25% of cases,isolating Moraxella spp.as the most frequent organism. CONCLUSION: Our results tend to point out that Chlamydia trachomatis and Ureaplasma urealyticum were detected in a moderate percentage of patients with DED,and could be a fair possibility for its development.PCR is more reliable in detecting Chlamydia trachomatis than DFA technique.The presence of isolated conjunctival bacterial microflora can be of some potential value.
文摘Obesity is increasingly being recognized as a risk factor for a number of benign and malignant gastrointestinal conditions. However, literature on the underlying pathophysiological mechanisms is sparse and ambiguous. There is compelling evidence that both overnutrition and undernutrition negatively interfere with the immune system. Overnutrition has been found to increase susceptibility to the development of inflammatory diseases, autoimmune diseases and cancer. In the regulation of immune and in? ammatory processes, white adipose tissue plays a critical role, not only as an energy store but also as an important endocrine organ. The obese state is characterised by a low-grade systemic in? ammation, mainly as a result of increased adipocytes as well as fat resident-and recruited-macrophage activity. In the past few years, various products of adipose tissue including adipokines and cytokines have been characterised and a number of pathways linking adipose tissue metabolism with the immune system have been identified. Activation of the innate immune system plays a major role in hepatic steatosis. Non-alcoholic fatty liver disease includes a wide spectrum of diseases, from pure steatosis to non-alcoholic steato-hepatitis in the absence of signif icant alcohol consumption. Although steatosis is considered a non-progressive disease, non-alcoholic steatohepatitis may deteriorate in advanced chronic liver diseases, cirrhosis, and hepatocellular carcinoma. An important parallel between obesityrelated pathology of adipose tissue and liver pertains to the emerging role of macrophages, and growing evidence suggests that Kupffer cells critically contribute to progression of non-alcoholic fatty liver disease. Moreover, a close link between specif ic immune activation and atherosclerosis has been well established, suggesting that fat can directly trigger immune responses. This review discusses the role of fat as "a matter of disturbance for the immune system" with a focus on hepatic steatosis.
文摘Objective:Oral squamous-cell carcinoma(OSCC)accounts for >90% of oral cancers affecting adults mostly between the fourth to seventh decades of life.The most common OSCC treatment is concomitant chemoradiotherapy(CCRT)having both locoregional and distant control,but CCRT has acute and chronic toxic effects on adjacent normal tissue.This study aimed to determine the side effects of CCRT on the oral mucosa and to characterize the clinicopathology of oral lesions in patients with OSCC.Methods:This descriptive,cross-sectional study was certified by the Ethical Review Committee(UHS/Education/126-12/2728)of the University of Health Sciences,Lahore,Pakistan.OSSC patients(n=81)with various histological subtypes,grades,and stages were recruited,and findings on their oral examination were recorded.These patients received 70,90,and 119 Gy of radiotherapy dosages in combination with the chemotherapy drugs cisplatin and 5-fluorouracil.Data were analyzed using SPSS 20.0.Results:The most common presentation of OSCC was a nonhealing ulcer(63%) involving tongue(55.6%).Clinical findings included mucositis(92.6%)and xerostomia of mild,moderate,and severe degrees in 11.1%,46.9%,and 35.8% cases,respectively.Ulcers(87.7%),palpable lymph nodes(64.2%),limited mouth opening(64.2%)and fistula(40.7%) were also observed.In females,the association of radiotherapy dosage with limited mouth opening,xerostomia,and histological grading was statistically significant(P<0.05).The association of chemotherapy drugs with xerostomia(P=0.003)was also statistically significant.Conclusions:CCRT induced mucositis,xerostomia,and trismus in patients with OSCC.
基金Supported by National Science Foundation of China,No.31471147
文摘Gastric cancer(GC) is the fifth most common malignancy in the world. The major cause of GC is chronic infection with Helicobacter pylori(H. pylori). Infection with H. pylori leads to an active inflammatory microenvironment that is maintained by immune cells such as T cells, macrophages, natural killer cells, among other cells. Immune cell dysfunction allows the initiation and accumulation of mutations in GC cells, inducing aberrant proliferation and protection from apoptosis. Meanwhile, immune cells can secrete certain signals, including cytokines, and chemokines, to alter intracellular signaling pathways in GC cells. Thus, GC cells obtain the ability to metastasize to lymph nodes by undergoing the epithelial-mesenchymal transition(EMT), whereby epithelial cells lose their epithelial attributes and acquire a mesenchymal cell phenotype. Metastasis is a leading cause of death for GC patients, and the involved mechanisms are still under investigation. In this review, we summarize the current research on how the inflammatory environment affects GC initiation and metastasis via EMT.
基金Supported by National Science Foundation of China,No.31471147
文摘The chemokine system consists of four different subclasses with over 50 chemokines and 19 receptors. Their functions in the immune system have been well elucidated and research during the last decades unveils their new roles in hepatocellular carcinoma(HCC). The chemokines and their receptors in the microenvironment influence the development of HCCby several aspects including:inflammation,effects on immune cells,angiogenesis,and direct effects on HCC cells. Regarding these aspects,pre-clinical research by targeting the chemokine system has yielded promising data,and these findings bring us new clues in the chemokine-based therapies for HCC.
基金Supported by grant from MCYT SAP 2003-08522. Elena Urcelay is recipient of a "Ramon y Cajal" contract of the MCYT. Alfonso Martinez is a recipient of a "Post-MIR" contract of the Spanish Health Ministry (01/F011)
文摘AIM: Inflammatory bowel diseases (IBD) are multifactorial pathologies of unknown etiology. One susceptibility locus,IBD5, has been mapped to chromosome 5q31. We analyzed our Spanish cohorts of Crohn's disease (CD)and ulcerative colitis (UC) patients to determine whether this locus is associated with IBD, and to ascertain the main clinical phenotype influenced by this risk factor. The kind of interaction, either genetic heterogeneity or epistasis, between this IBD5 susceptibility region and the NOD2/CARD15 gene mutations was studied as well.Finally, ve assessed whether this locus can predict response to infliximab therapy.METHODS: A case control study was performed with 274CD and 211 UC patients recruited from a single center and 511 healthy ethnically matched controls. Two polymorphisms were genotyped in the IBD5 locus and three in the CARD15/NOD2 gene.RESULTS: Our results evidence association only with CD especially with the fistulizing phenotype and in the absence of NOD2/CARD15 variants (mutant allele frequency in patients vscontrols: OR = 2.03, 95% CI = 1.35-3.06,P＜0.01). The frequency of the IBD5 homozygous mutant genotype significantly increased in CD patients lacking response to infliximab (RR = 3.88, 95% CI = 1.18-12.0,P＜0.05). UC patients overall do not show association with 5q31 polymorphisms, although a similar trend to the one observed in CD is found within the worse prognosis group.CONCLUSION: The IBD5 variants may enhance an individual carrier's risk for CD, mainly in the absence of the NOD2/CARD15 mutations and in fistulizing patients.The data presented suggest the potential role of the 5q31polymorphisms as markers of response to infiiximab.
基金Supported by Sveti Duh General Hospital, Zagreb, Croatia, approval, No. UR/P-10/1998
文摘AIM: To determine whether local antibiotic resistance involves P-glycoprotein (Pgp)-mediated active drug outpumping during Helicobacter pylori ( H pylori) infection treatment with classic antibiotic therapy. METHODS: Pgp activity was determined in gastric mucosa biopsy specimens obtained from 53 patients with pathohistologically verified gastritis and microbiologically confirmed H pylori infection, and compared with the Pgp activity in 12 control subjects with normal endoscopic findings. TheH pylori positive patients were treated with short-term 7-d therapy consisting of two antibiotics (amoxicillin and azithromycin/metronidazole and clarithromycin) and a proton pump inhibitor. Pgp activity was determined by flow cytometry in the test of rhodamine dye efflux and quantified as mean fluorescence ratio (RMF).RESULTS: Upon the first cycle,H pylori was successfully eradicated in 20 patients, whereas therapy was continued in 33 patients. In the course of antibiotic therapy, RMF increased (P＜0.05) and gastric cells showed higher rhodamine dye efflux. The mean pre-treatment RMF values were also higher (P＜0.0001) in patients with multiple therapeutic failure than in those with successful H pylorieradication and control subjects.CONCLUSION: Pgp might be one of the causes of therapy failure in patients with H pylori and antibiotic therapy could be chosen and followed up on the basis of the Pgp transporter local activity.
