In memory of Dr. Azar Andami, an eminent researcher and scholar at the Pasteur Institute of Iran

This paper focuses on the remarkable contributions and achievements of Dr.Azar Andami(1926–1984),a renowned physician and specialist at the Pasteur Institute of Iran.Dr.Andami conducted extensive research on infectious diseases,particularly cholera,utilizing her knowledge in medicine,bacteriology,and laboratory sciences.She played a crucial role in the mass production of the cholera vaccine at the Pasteur Institute of Iran and in controlling the spread of communicable diseases both locally and globally.This paper aims to highlight her remarkable works and accomplishments.

Hepatitis B Virus (HBV) Infection in Patients at Pasteur Institute of Dakar in Senegal from 2016 to 2020: Prevalence and Seroprotection Level

Hepatitis B virus (HBV) infection is highly endemic in Senegal. Vaccination of all children against HBV was introduced in 1999 and included in Expanded Programme on Immunisation in 2005. The aim of this study was to assess the prevalence and immune status against HBV in patients received at Pasteur Institut in Dakar, Senegal. Methods: Between January 2016 and December 2020, patients aged between 1 and 96 years received laboratory were included in the study. Serum samples were analysed for HBV serology (HBs antigen: HBsAg, HBs antibody: HBsAb and HBc antibody: HBcAb) using ARCHITECT? analyser. Patients with anti-HBs antibody levels (HBsAb ≥ 10 IU/l) were considered seroprotected against HBV. Results: A total of 5629 patients were analysed with a mean age of 39 years and extremes from 1 to 96 years. The most represented age group was 31 - 45 years with 38.4%. HBsAg was present in 520 patients (9.2%) and was signed by sex and age group. Anti-HBc antibodies were found in 52.7% of patients and 1603 (28.48%) had isolated anti-HBs antibodies reflecting proportion of people vaccinated at the time of the study. However, 2143 patients (41.9%) had no seroprotection (HBsAb 10 IU/L) and 640 (12.6%) had strong seroprotection defined as HBsAb > 1000 IU/L. Conclusion: Our results show a significant presence of virus in Senegalese population and low vaccination coverage, especially in adults. Evaluation of HBsAb levels and provision of HBV booster shots should be considered for children in Senegal.

Post-transcriptional mechanisms controlling neurogenesis and direct neuronal reprogramming

Neurogenesis is a tightly regulated process in time and space both in the developing embryo and in adult neurogenic niches.A drastic change in the transcriptome and proteome of radial glial cells or neural stem cells towards the neuronal state is achieved due to sophisticated mechanisms of epigenetic,transcriptional,and post-transcriptional regulation.Understanding these neurogenic mechanisms is of major importance,not only for shedding light on very complex and crucial developmental processes,but also for the identification of putative reprogramming factors,that harbor hierarchically central regulatory roles in the course of neurogenesis and bare thus the capacity to drive direct reprogramming towards the neuronal fate.The major transcriptional programs that orchestrate the neurogenic process have been the focus of research for many years and key neurogenic transcription factors,as well as repressor complexes,have been identified and employed in direct reprogramming protocols to convert non-neuronal cells,into functional neurons.The post-transcriptional regulation of gene expression during nervous system development has emerged as another important and intricate regulatory layer,strongly contributing to the complexity of the mechanisms controlling neurogenesis and neuronal function.In particular,recent advances are highlighting the importance of specific RNA binding proteins that control major steps of mRNA life cycle during neurogenesis,such as alternative splicing,polyadenylation,stability,and translation.Apart from the RNA binding proteins,microRNAs,a class of small non-coding RNAs that block the translation of their target mRNAs,have also been shown to play crucial roles in all the stages of the neurogenic process,from neural stem/progenitor cell proliferation,neuronal differentiation and migration,to functional maturation.Here,we provide an overview of the most prominent post-transcriptional mechanisms mediated by RNA binding proteins and microRNAs during the neurogenic process,giving particular emphasis on the interplay of specific RNA binding proteins with neurogenic microRNAs.Taking under consideration that the molecular mechanisms of neurogenesis exert high similarity to the ones driving direct neuronal reprogramming,we also discuss the current advances in in vitro and in vivo direct neuronal reprogramming approaches that have employed microRNAs or RNA binding proteins as reprogramming factors,highlighting the so far known mechanisms of their reprogramming action.

Phenotypic Detection of Enterobacterales Strains Susceptible of Producing OXA-48 Carbapenemase

Background: Nowadays, emergence of Carbapenemase-Producing Enterobacterales (CPE) throughout the world has become a public health problem, especially in countries with limited resources. In recent years, CPE of type OXA-48 (Ambler class D) have been identified in Dakar. The aim of this study was to evaluate the phenotypic detection of OXA-48 CPE using a temocillin disc (30 μg). Methodology: A retrospective study was carried out at Medical Biology Laboratory of Pasteur Institute in Dakar on Ertapenem-Resistant Enterobacterales (ERE) strains isolated from 2015 to 2017. These strains were then tested with a 30 μg temocillin disc. Any strain resistant to temocillin (inhibition diameter Results: Forty-one ERE isolated during the study period were tested, of which 34 (82.9%) were OXA-48 based on phenotypic detection using temocillin disc and confirmed by PCR (100%). OXA-48 CPE strains detected were composed of Klebsiella pneumoniae (n = 14;41.2%), Enterobacter cloacae (n = 8;23.5%), Escherichia coli (n = 7, 20.5%), Citrobacter freundii (n = 3;8.8%), Cronobacter sakazakii (n = 1;3%) and Morganella morganii (n = 1;3%). Conclusion: Temocillin resistance has a good positive predictive value for detecting OXA-48 CPE by phenotypic method, confirmed by PCR. Temocillin is therefore a good marker for detection of OXA-48 CPE except Hafnia alvei.

Fatal cases in pediatric patients after post-exposure prophylaxis for rabies:A report of two cases

Rationale:Rabies is a zoonotic disease with a high mortality,primarily transmitted through the bite of infected mammals,particularly dogs and cats.Despite being a well-known disease since ancient times,it continues to cause a significant number of human deaths worldwide,with approximately 65000 fatalities reported annually.Patient concerns:We present two fatal cases of rabies in a 12-year-old immigrant boy and a 7-year-old boy.The first case was subject to a 24-hour delay in receiving appropriate medical attention and rabies preventive measures due to the lack of awareness among emergency hospital staff,leading to the administration of wound dressing only.The second case received timely rabies immunoglobulin administration;however,there was a 4-day delay in administering the fourth dose of the rabies vaccine,despite presenting evident symptoms of rabies.Diagnosis:Postmortem examination of brain samples from both patients confirmed the presence of rabies virus.Interventions:Post-exposure prophylaxis for rabies.Outcomes:Both patients were admitted to the hospital after the manifestation of rabies-related symptoms,with the 12-year-old child seeking medical care 47 days after the animal bite and the 7-year-old child seeking medical care 58 days after the exposure.Finally,the first patient died after 27 days and the second patient died after 40 days of hospitalization.Lessons:There is an urgent need for heightened awareness and education among both healthcare professionals and the public regarding the urgency of seeking immediate medical attention after potential rabies exposure.Timely recognition and initiation of post-exposure prophylaxis are pivotal in preventing the progression of the disease.Strengthening surveillance and reporting systems,coupled with continuous training for healthcare professionals,can contribute to early detection and management of rabies cases.

Dissemination of Resistance Integrons and Genes Coding for Blse and Cabapenemases in the Urban Drainage Network in Cote d’Ivoire

Antibiotic resistance has become a major threat to human health worldwide. Environment, particularly the water environment, has long been overlooked as a player in the antibiotic resistance cycle, although its role remains unclear. These can provide an ideal setting for the acquisition and dissemination of antibiotic resistance, as they are frequently affected by anthropogenic activities. The objective of this study was to establish a diffusion map of resistance integrons used as genetic markers of resistance associated with antibiotic resistance conferring genes (ARGs). Total DNA extracts from non-cultivable bacterial communities were used for the analyses. These communities were obtained from wastewater samples from 14 sites upstream and downstream of drainage channels or effluents in the cities of Abidjan, Bouaké, and Yamoussoukro. The results obtained correspond to the number of positives among the treated samples (n = 39). Among the genetic markers of dissemination, class 1 integrons were the most evident in 94.8% of samples in Abidjan (93.3%), Bouaké (100%) and Yamoussoukro (91.6%). Class 2 integrons and class 3 integrons were found respectively in 41% and 51% of all samples. Genes coding for β-lactamases and blaTEM was identified in almost all samples at a rate of 97.4%. A co-presence of the three genes blaTEM, blaSHV and blaCTX-M is also remarkable in the sites of the city of Yamoussoukro. Among the genes coding for carbapenemases, only blaKPC 17.94%, blaNDM 30.76% and blaOXA48 38.46% were detected in the samples.

Targeted anti-tumor synergistic effects of Myc decoy oligodeoxynucleotides-loaded selenium nanostructure combined with chemoradiotherapy on LNCaP prostate cancer cells

In the present study,we investigated the synergistic effects of targeted methotrexate-selenium nanostructure containing Myc decoy oligodeoxynucleotides along with X-irradiation exposure as a combination therapy on LNCaP prostate cancer cells.Myc decoy ODNs were designed based on the promoter of Bcl-2 gene and analyzed by molecular docking and molecular dynamics assays.ODNs were loaded on the synthesized Se@BSA@Chi-MTX nanostructure.The physicochemical characteristics of nanostructures were determined by FTIR,DLS,UV-vis,TEM,EDX,in vitro release,and hemolysis tests.Subsequently,the cytotoxicity properties of them with and without X-irradiation were investigated by uptake,MTT,cell cycle,apoptosis,and scratch assays on the LNCaP cell line.The results of DLS and TEM showed negative charge(−9 mV)and nanometer size(40 nm)for Se@BSA@Chi-DEC-MTX NPs,respectively.The results of FTIR,UV-vis,and EDX showed the proper interaction of different parts and the correct synthesis of nanoparticles.The results of hemolysis showed the hemocompatibility of this nanoparticle in concentrations less than 6 mg/mL.The ODNs release from the nanostructures showed a pH-dependent manner,and the release rate was 15%higher in acidic pH.The targeted Se@BSA@Chi-labeled ODN-MTX NPs were efficiently taken up by LNCaP cells by targeting the prostate-specific membrane antigen(PSMA).The significant synergistic effects of nanostructure(containing MTX drug)treatment along with X-irradiation showed cell growth inhibition,apoptosis induction(~57%),cell cycle arrest(G2/M phase),and migration inhibition(up to 90%)compared to the control.The results suggested that the Se@BSA@Chi-DEC-MTX NPs can potentially suppress the cell growth of LNCaP cells.This nanostructure system can be a promising approach for targeted drug delivery and chemoradiotherapy in prostate cancer treatment.

Prevalence and Factors Associated with Positivity of Antinuclear Antibodies (ANA) Patterns, Native Anti-DNA and Extractable Nuclear Antigens (ENA) Antibodies: Experience from a Laboratory in Dakar

Background: Diagnosis of autoimmune diseases (AID) is challenging, due to overlapping features with other non-immune disorders. Anti-nuclear antibodies (ANA) are sensitive screening tests but anti-deoxyribonucleic acid-antibody (anti-DNA), and anti-extractable nuclear antigens (anti-ENA) are specific for AIDs. We aimed to look at ANA patterns in our patients and correlated them with anti-ENA for proper interpretation and better patient management cost-effectively. Methods: A retrospective study was conducted over 1 year from January to December 2022 who were tested for ANA at biology medical laboratory of Pasteur Institute of Dakar. Anti-ENA and anti-DNA results were also analyzed for ANA-positive patients. Statistical analysis was performed using STATA 14.0, p Results: 216 patients were analyzed. Women predominated at 79.2% and mean age was 48 years [CI 95%, 46 - 50], with extremes of 10 and 89. Most represented age group was [41 - 60] with 38%. ANA was positive in 27 (12.5%) of patients, 59.2% of whom were strongly positive (titer of 1/1000, 1/3200 or 1/6400). The most common pattern was nuclear speckled, which was found in 77.8% of samples. Anti-ENA and anti-DNA positivity in ANA-positive patients was found respectively in 63% (17/27) and 1.4% (3/27) of the samples analyzed. Most commonly identified anti-ENA was anti-Sm 29.6%, anti-SSA 29.6%, anti-Ro-52 25.9%, anti-RNP 18.5% and anti-SSB 14.8% which was associated with speckled pattern. Association results indicated a significant relationship between both tests and between ANA titer in the anti-ENA- and ANA-positive patients (p 0.001). Conclusions: ANA, Anti-ENA and anti-DNA antibodies are essential for AIDS diagnosis. However, the testing repertoire should follow an algorithm comprising of clinical features, followed by ANA results with nuclear, mitotic, and cytoplasmic patterns, anti-ENA, and anti-DNA for a more meaningful, and cost-effective diagnostic approach.

Immunovirological Profile of HIV1 Infection in Children and Adolescents Followed at the Bangui Pediatric University Hospital

History: Pediatric management of HIV infection in children in the Central African Republic began in 2004 with the use of fractionated adult antiretrovirals and Cotrimoxazole. It has evolved over the years with the use of pediatric forms, oral suspensions and dispersible tablets. The transition to Dolutegravir took place in 2020. The active file of our patients will grow from 78 to over 1900 today. Follow-up examinations are carried out to assess adherence to treatment. Objective: To determine the immunovirological profile and factors associated with treatment failure during follow-up of children on ART at the Bangui pediatric university hospital. Patients and Method: This was a cross-sectional, analytical study from May 30 to December 02, 2022. The study sample was drawn from a cohort of HIV-1-infected children followed up at the Bangui pediatric university hospital and on ART for three semesters who met the selection criteria. Results: The prevalence of treatment failure varied from one semester to the next. Thus, the prevalence of therapeutic failure was 20% in the first semester, 10% in the second semester and 7% in the third semester. The prevalence of virological failure was 10.28% in the first half of the year, 6.91% in the second half and 4.98% in the third. Secondly, immunological failure was 0.48% in the first half of the year, 0.32% in the second 0.64% in the third half. Finally, clinical failure was 8.82% in the first half, 4.82% in the second half, 1.92% in the third half. Socio-demographic and clinical factors associated with treatment failure were male gender (p 1000 copies/ml (p Conclusion: The occurrence of treatment failures in children is a major problem, especially in our resource-limited countries, given the challenges facing antiretroviral therapy. It is therefore necessary to carry out a study on resistance genotyping in order to propose correct management protocols, as the future of treatment programs depends on it.

Bacteriological Profile of Infections Encountered in a Pneumology Service in a Moderate-Income Country [Pneumology Department of CHU Cocody (Côte d’Ivoire)]

Introduction: Infections represent a real public health problem aggravating the morbidity and mortality of hospitalized patients. Methods: This was a retrospective study with descriptive purposes over a period of 05 years, in the Pneumology Department of the University Hospital of Cocody. Results: The average age in our population was 42 years. We observed a male predo- minance of 64.5%, with a sex ratio of 1.8. Medical history was dominated by HIV infection (23.5%), followed by tuberculosis (15.6%). Concerning lifestyle, smoking was found in 38% of cases. Symptoms progressed chronically in 80% of cases. An infectious syndrome was found in 75% of cases. Microbial culture was positive in 42% of cases. Pseudomonas aeruginosa and Klebsiella pneumoniae were encountered in 26.4% of cases each, followed by Echerichia coli in 10.4% of cases. Klebsiella pneumoniae in the first three years topped the list, but gradually. Pseudomonas aeruginosa maintained its leadership over the last three years. Pseudomonas aeruginosa isolates expressed a resistance rate of 9.8% to ceftazidime and 8.1% to imipenem;to aztreonam (36%), ticarcillin (33.3%) and levofloxacin. These strains were susceptible to fosfomycin (100%), mero- penem (96.6%) and amikacin (96%). For isolated strains of Entero- bacteria- ceae, resistance was observed about ticarcillin (83.3%) and amoxicillin clavula- nic acid (71.2%). Streptococcaceae showed resistance to tetracycline (69.2%) and erythromycin (50%). Over the years there has been an increase in re- sistance to amoxicillin-clavulanic acid ceftriaxone. The death rate was 14%. Conclusion: The bacterial profile of infections is dominated by germs respon- sible for nosocomial infection with significant mortality.

Vaginal Carriage of Group B Streptococcus in Pregnant Women in Rural Areas in Senegal

Vaginal carriage of Group B Streptococcus (GBS) is a maternal and child health issue. Our objective was to determine the prevalence of GBS carriage;identify the factors associated with this carriage and determine the antibiotic sensitivity of the isolated strains. We conducted a cross-sectional and prospective study in rural Senegal (in the health district of Sokone). Socio-demographic, clinical and gynaeco-obstetrical data were collected. Vaginal swabs were taken by the midwives on specific settings in order to test for GBS and other High Risk Vaginal Bacteria (HRVB). Antibiotic susceptibility testing was done according to the recommendations of the CA SFM/EUCAST 2020. In total, 100 pregnant women were targeted and 97 pregnant women were included. Their age ranged from 18 to 40 years with 64.9% (63/97) of participants belonging to the “20 - 30” age group. The overall prevalence of Group B Streptococcus carriage was 15.5% (15/97). However, the proportion of women with at least one high risk infectious bacteria was 29.89% (29/97). No statistically significant differences were found between GBS carriage and the potential factors studied. However, the study also looked for the presence of other high-risk bacteria and coinfections were indeed found between GBS and E. coli and Staphylococcus aureus. Antibiotic susceptibility testing shows that GBS strains were fully susceptible to penicillin G, erythromycin, clindamycin, chloramphenicol, rifampicin and vancomycin. Sensitivities to norfloxacin and gentamycin were 73.3% and 86.7% respectively. In contrast, high resistance to tetracycline (86.7%) was observed. GBS carriage remains a major public health issue because of its consequences for the mother and the newborn. Correct screening and proper monitoring of strain susceptibility remain one of the most effective means of patient management and care.

Epidemiological Facies of Human Rabies Deaths in Côte d’Ivoire from 2016 to 2022

Introduction: Rabies is a highly fatal viral disease outside the post-exposure prophylaxis (PEP). Data from previous studies and reports from the rabies center show that cases of death from human rabies are regularly reported, despite training measures for health workers, awareness-raising and communities, and the availability of vaccines. Objectives: The aim of this study was to analyse the determinants of human rabies deaths in Côte d’Ivoire from 2016 to 2022. Method: A retrospective cross-sectional qualitative study was carried out from January to August 2023 on all the records of patients who died of human rabies at the Treichville Rabies Center from 2016 to 2022. An analysis of the rabies center’s annual activity reports from 2016 to 2022 was also carried out in order to complete the information gathered from the files. Results: The socio-demographic characteristics showed that out of 148 deaths, children accounted for 47.97% (71) and 66.22% (98) of rabies deaths were male, with an M/F sex ratio of 1.96. In terms of clinical characteristics, in 97.30% (144) of cases, the deceased had presented with furious rabies, and analysis by the Pasteur Institute of Côte d’Ivoire laboratory confirmed 101 cases (92.66%) of human rabies. Geographical distribution showed that cases of human rabies were recorded in 56 health district, and 64% (94) of the deceased lived in rural areas. The main causes of the occurrence of rabies were essentially non-use of post-exposure prophylaxis (PEP) and missed vaccination due to ignorance. Conclusion: In view of these results, control strategies and interventions need to be adapted to the epidemiological characteristics of the disease, using a community-based approach with a view to eliminating dog-transmitted rabies by 2030.

Risk Factors for COVID-19 Related Death during the First Three Waves of the Pandemic in an Epidemic Treatment Center at Dakar, Senegal

Introduction-Objective: COVID-19 is a highly transmissible but often mild viral infection. However, some patients can present severe COVID-19 and subsequently die. The aim of the present study was to assess the risk factors for COVID-19 related death during the first three waves of the disease at the Epidemic Treatment Center (ETC) of Dakar Principal Hospital (DPH). Method: We conducted a descriptive and analytical perspective survival study from April 4, 2020 to September 25, 2021, including adult patients with COVID-19, hospitalized at the ETC of DPH. Log Rank test and multivariate Cox model were performed to identify risk factors for death. Results: We included 556 COVID-19 patients with mean age of 57 ± 17 years and a male-to-female ratio of 1.26. The number of deaths during one month of follow-up was 41, representing a cumulative risk of 7.4%. The log Rank test showed that being from the third wave (p = 0.0056), advanced age (p = 0.00098), presence of at least one comorbidity (p = 0.034), High blood pressure (p = 0.024), d-dimer level ≥ 1000 IU/L (p Conclusion: Our study showed that elderly and third-wave of COVID-19 patients were more at risk to die. Knowledge of risk factors for COVID-19 related death could improve the prognosis of these patients.

Capacity Development of National Reference Centers (NRC) to Face the Challenges of Emerging Infections in Côte d’Ivoire

Background: Some national and international strategies for the detection and prevention of emerging infectious diseases have been established across sectors. The capacity to carry out these tasks varies from country to country, and that remains largely undervalued. The Pasteur Institute of C?te d’Ivoire has created and implemented the capacity of national reference centers to fight against emerging and other infectious diseases. Objective: Show on the one hand the strategies used to develop the National Reference Centers and the IPCI and on the other hand the results obtained by performing these strategies. Method: Datas collection by documentary analysis (published scientific articles and grey literature) was done on Google Scholar, PUBMED and institutional reference documents. The documentary research was carried out to have a better understanding of strategies used to create and develop the NRCs in microbiology of communicable diseases. Results: Seven integrated strategies were launched: 1-training and workforce development;2-investigation of epidemics or public health events;3-strengthening laboratory epidemiological research;4-strengthening surveillance systems;5-improving communication with partners and stakeholders;6-building national and international collaborations;and 7-strengthening technical and technological platforms. In two decades, the number of researchers has risen from 10 in 2004 to ninety (90) in 2021, with 12 senior researchers and 32 junior researchers. A number of health service staff had attended a qualifying training course, 27 investigations into outbreaks and other public health events had been carried out, 18 short-term research projects had been launched, major surveillance programs and epidemiological research efforts on vector-borne, food-borne and nosocomial infections had begun, and several scientific manuscripts had been published or were edited in the writting press. Conclusion: The Ivorian experience shows that, with concerted effort, considerable progress can be made in the development and implementation of an infectious disease control program.

双曲钩端螺旋体溶血素基因tlyA的克隆、表达及初步功能鉴定

目的研究双曲钩端螺旋体(简称双曲钩体)是否含有溶血素基因,并鉴定其溶血活性。方法对双曲钩体LEBIa2503基因编码产物进行结构域预测、序列比对后,PCR扩增目的片断,克隆到原核表达载体pET28b(+),转化宿主细胞,并诱导表达产物进行初步功能鉴定。同时,以RT-PCR检测LEBIa2503的转录情况。另外,也对双曲钩体菌体本身有无溶血活性进行检测。结果双曲钩体LEBIa2503基因与问号钩体tlyA溶血素基因在蛋白水平上有相同的结构域,属于直系同源基因(orthologues gene)。原核表达的重组融合蛋白在羊血平板上出现β-溶血环。以RT-PCR的方法能检测到在双曲钩体中有LEBIa2503基因的转录,但双曲钩体菌体本身则检测不到溶血活性。结论未发现双曲钩体有溶血活性,但其含有溶血素基因tlyA,并且在普通培养环境下能被转录,这对进一步研究其内在机制奠定了基础,并对探索致病性问号钩体致病机制提供了一定线索。

1988年上海甲型肝炎暴发流行可能重叠ECHO13型病毒感染

继从毛蚶直接观察和分离到甲型肝炎(下称甲肝)病毒、并且证实1988年初上海甲肝暴发流行确系食用污染毛蚶所致后,我们又意外地发现,在所分离的5株甲肝病毒(毛蚶2株,急性期病人粪便3株)培养物中,还存在可致MRC-5株人二倍体细胞和PLC/PRF/5系人肝癌细胞产生细胞病变的ECHO 13型病毒。继之用原始毛蚶再分离,经RIA及核酸探针分子杂交等方法检测,也证实了上述结果。对该毛蚶产地人群血清学回顾性调查也支持上述可能。甲肝暴发流行重叠ECHO 13型病毒感染,尚未见报道.

New insights of Helicobacter pylori host-pathogen interactions: The triangle of virulence factors, epigenetic modifications and non-coding RNAs

Helicobacter pylori(H. pylori) is a model organism for understanding host-pathogen interactions and infection-mediated carcinogenesis. Gastric cancer and H. pylori colonization indicates the strong correlation. The progression and exacerbation of H. pylori infection are influenced by some factors of pathogen and host. Several virulence factors involved in the proper adherence and attenuation of immune defense to contribute the risk of emerging gastric cancer, therefore analysis of them is very important. H. pylori also modulates inflammatory and autophagy process to intensify its pathogenicity. From the host regard, different genetic factors particularly affect the development of gastric cancer. Indeed, epigenetic modifications, Micro RNA and long non-coding RNA received more attention. Generally, various factors related to pathogen and host that modulate gastric cancer development in response to H. pylori need more attention due to develop an efficacious therapeutic intervention. Therefore, this paper will present a brief overview of host-pathogen interaction especially emphases on bacterial virulence factors, interruption of host cellular signaling, the role of epigenetic modifications and non-coding RNAs.

AZF microdeletions and partial deletions of AZFc region on the Y chromosome in Moroccan men

Aim： To evaluate for the first time the frequency of Y chromosome microdeletions and the occurrence of the partial deletions of AZFc region in Moroccan men, and to discuss the clinical significance of AZF deletions. Methods： We screened Y chromosome microdeletions and partial deletions of the AZFc region of a consecutive group of infertile men （n = 149） and controls （100 fertile men, 76 normospermic men）. AZFa, AZFb, AZFc and partial deletions of the AZFc region were analyzed by polymerase chain reaction （PCR） according to established protocols. Results： Among the 127 infertile men screened for microdeletion, four subjects were found to have microdeletions： two AZFc deletions and two AZFb＋AZFc deletions. All the deletions were found only in azoospermic subjects （4/48, 8.33%）. The overall AZFc deletion frequency was low （4/127, 3.15%）. AZF microdeletions were not observed in either oligoasthenoteratozoospermia （OATS） or the control. Partial deletions of AZFc （gr/gr） were observed in a total of 7 of the 149 infertile men （4.70%） and 7 partial AZFc deletions （gr/gr） were found in the control group （7/176, 3.98%）. In addition, two b2/b3 deletions were identified in two azoospermic subjects （2/149, 1.34%） but not in the control group. Conclusion： Our results suggest that the frequency of Y chromosome AZF microdeletions is elevated in individuals with severe spermatogenic failure and that gr/gr deletions are not associated with spermatogenic failure.

The interferon inducing pathways and the hepatitis C virus

The innate immune response is triggered by a variety of pathogens, including viruses, and requires rapid induction of typeⅠ?interferons (IFN), such as IFNβ and IFNα. IFN induction occurs when specific pathogen motifs bind to specific cellular receptors. In non-professional immune, virally-infected cells, IFN induction is essentially initiated after the binding of dsRNA structures to TLR3 receptors or to intracytosolic RNA helicases, such as RIG-Ⅰ/MDA5. This leads to the recruitment of specific adaptors, such as TRIF for TLR3 and the mitochondrial-associated IPS-1/VISA/MAVS/CARDIF adapter protein for the RNA helicases, and the ultimate recruitment of kinases, such as MAPKs, the canonical IKK complex and the TBK1/IKKε kinases, which activate the transcription factors ATF-2/ c-jun, NF-κB and IRF3, respectively. The coordinated action of these transcription factors leads to induction of IFN and of pro-inflammatory cytokines and to the establishment of the innate immune response. HCV can cleave both the adapters TRIF and IPS-1/VISA/MAVS/ CARDIF through the action of its NS3/4A protease. This provokes abrogation of the induction of the IFN and cytokine pathways and favours viral propagation and presumably HCV chronic infection.

New animal models for hepatitis C viral infection and pathogenesis studies

Hepatitis C virus (HCV) is a major cause of chronic live disease, cirrhosis and hepatocellular carcinoma (HCC) In man, the pathobiological changes associated wit HCV infection have been attributed to both the immun system and direct viral cytopathic effects. Until now, th lack of simple culture systems to infect and propagat the virus has hampered progress in understandin the viral life cycle and pathogenesis of HCV infection including the molecular mechanisms implicated in HCV induced HCC. This clearly demonstrates the need t develop small animal models for the study of HCV associated pathogenesis. This review describes an discusses the development of new HCV animal models t study viral infection and investigate the direct effects o viral protein expression on liver disease.