Increased V-ATPase activity can lead to chemo-resistance in oral squamous cell carcinoma via autophagy induction: new insights.

Oral squamous cell carcinoma (OSCC) is a cancer type with a high rate of recurrence and a poor prognosis. Tumor chemo-resistance remains an issue for OSCC patients despite the availability of multimodal therapy options, which causes an increase in tumor invasiveness. Vacuolar ATPase (V-ATPase), appears to be one of the most significant molecules implicated in MDR in tumors like OSCC. It is primarily responsible for controlling the acidity in the solid tumors' microenvironment, which interferes with the absorption of chemotherapeutic medications. However, the exact cellular and molecular mechanisms V-ATPase plays in OSCC chemo-resistance have not been understood. Uncovering these mechanisms can contribute to combating OSCC chemo-resistance and poor prognosis. Hence, in this review, we suggest that one of these underlying mechanisms is autophagy induced by V-ATPase which can potentially contribute to OSCC chemo-resistance. Finally, specialized autophagy and V-ATPase inhibitors may be beneficial as an approach to reduce drug resistance to anticancer therapies in addition to serving as coadjuvants in antitumor treatments. Also, V-ATPase could be a prognostic factor for OSCC patients. However, in the future, more investigations are required to demonstrate these suggestions and hypotheses.

Autophagy induced by Helicobacter Pylori infection can lead to gastric cancer dormancy, metastasis, and recurrence: new insights.

According to the findings of recent research, Helicobacter Pylori (H. pylori) infection is not only the primary cause of gastric cancer (GC), but it is also linked to the spread and invasion of GC through a number of processes and factors that contribute to virulence. In this study, we discussed that H. pylori infection can increase autophagy in GC tumor cells, leading to poor prognosis in such patients. Until now, the main concerns have been focused on H. pylori's role in GC development. According to our hypothesis, however, H. pylori infection may also lead to GC dormancy, metastasis, and recurrence by stimulating autophagy. Therefore, understanding how H. pylori possess these processes through its virulence factors and various microRNAs can open new windows for providing new prevention and/or therapeutic approaches to combat GC dormancy, metastasis, and recurrence which can occur in GC patients with H. pylori infection with targeting autophagy and eradicating H. pylori infection.

Quinolone resistance and biofilm formation capability of uropathogenic Escherichia coli isolates from an Iranian inpatients' population.

BACKGROUND: Uropathogenic Escherichia coli (UPEC) is a major pathogen of the urinary tract infection (UTI), and biofilm formation is crucial as it facilitates the colonization in the urinary tract. We aimed to investigate the antibiotic susceptibility pattern, biofilm formation capability, distribution of quinolone resistance genes, and phylogenetic groups among UPEC isolates from an Iranian inpatients' community. METHODS AND RESULTS: A collection of 126 UPEC obtained from hospitalized patients with symptomatic UTI at 3 teaching hospitals during 2016 were included. Antibiogram of all isolates against quinolone and fluoroquinolones was performed using the disk diffusion method. Phylogenetic groups and qnr A, B, and S genes were assessed by PCR. Susceptibility pattern showed that more than 50% and 81% of the isolates were resistant to fluoroquinolones and quinolones, correspondingly. The frequency of qnrS and qnrB genes was 22% and 13.5%, correspondingly. Our result indicated no significant association between the presence of fluoroquinolone genes and antibiotic resistance to them. The frequent common phylogroup was B2 (84.1%), followed by D (10.3%), A (3.2%) and B1 (2.4%) groups. Indeed, 80.2% of the isolates were biofilm producers, so that 42.1%, 16.7% and 21.4% of them were classified as weak, moderate and strong producers, respectively. CONCLUSIONS: Our results showed considerable fluoroquinolone and quinolone resistance among UPEC along with a remarkable rate of biofilm-producing isolates from symptomatic hospitalized patients, making them a serious health concern in the region. This survey highlights the need for awareness on quinolone resistance and careful prescription of them by physicians.

Non-coding RNAs in gynecologic cancer.

The term "gynecologic cancer" pertains to neoplasms impacting the reproductive tissues and organs of women encompassing the endometrium, vagina, cervix, uterus, vulva, and ovaries. The progression of gynecologic cancer is linked to various molecular mechanisms. Historically, cancer research primarily focused on protein-coding genes. However, recent years have unveiled the involvement of non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs (LncRNAs), and circular RNAs, in modulating cellular functions within gynecological cancer. Substantial evidence suggests that ncRNAs may wield a dual role in gynecological cancer, acting as either oncogenic or tumor-suppressive agents. Numerous clinical trials are presently investigating the roles of ncRNAs as biomarkers and therapeutic agents. These endeavors may introduce a fresh perspective on the diagnosis and treatment of gynecological cancer. In this overview, we highlight some of the ncRNAs associated with gynecological cancers.

The first report of Enterobacter gergoviae carrying bla NDM-1 in Iran.

OBJECTIVES: Prompt detection of extended-spectrum ß-lactamases (ESBL) and carbapenemase-producing enterobacteriaceae is crucial for infection prevention and control strategies. The present study aimed to characterize the ESBL and carbapenemase genes among Enterobacter isolates from an Iranian inpatient population. MATERIALS AND METHODS: A total of 96 Enterobacter isolates obtained from inpatients between June 2016 and March 2017, were identified by the conventional microbiological methods and diagnostic kits. Antimicrobial susceptibility pattern was performed using the disk diffusion method. The ESBL and carbapenemase genes were screened using polymerase chain reaction (PCR). RESULTS: All clinical isolates of Enterobacter were classified as E. gergoviae (52, 54.2%), E. aerogenes (34, 35.4%), E. cloacae (7, 7.3%), Cronobacter (E). sakazakii (3, 3.1%). The highest and lowest antimicrobial resistance rates were observed against ampicillin (93.8%) and imipenem (21.9%). High prevalence of multi-drug resistance (MDR=96.9%) was substantial. Of the 96 Enterobacter isolates, 35 (36.5%) and 28 (29.2%) were phenotypically ESBL-positive and non-susceptible carbapenem, respectively. Overall, the frequency of evaluated genes was as follows: blaCTX-M =25 (26%), blaTEM =30 (31.3%), blaSHV =12 (12.5%), blaIMP =3 (3.1%), blaVIM =0 (0%), blaNDM =8 (8.3%), and blaKPC =0 (0%). CONCLUSION: In this study, we report for the first time the presence of E. gergoviae harboring blaNDM from an Iranian population. Regarding the increase of MDR Enterobacter spp. in our region, strict hygiene rules will be needed to control the quick spread of ESBL and carbapenemase-producing Enterobacter isolates in healthcare facilities of developing countries.

Production of egg yolk antibody (IgY) against shiga-like toxin (stx) and evaluation of its prophylaxis potency in mice.

OBJECTIVE: Enterohemorrhagic Escherichia coli (E. coli O157: H7) is an enteric pathogen, transmitted through contaminated water and food. Pathogenic factors include bacterial adhesion, invasion of intestinal epithelial and epithelium cells. The pathogenicity of EHEC is due to the production of Shiga-like toxin (Stx). This toxin binds to the ribosome and inhibits the synthesis of proteins. EHEC causes hemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS). The EHEC treatment with antibiotics leads to resistance. The best way to solve this problem is to use specific antibodies and prophylaxis. Egg yolk antibody (IgY) is a suitable method for prophylaxis. Hence, the aim of this study was to investigate the production of IgY against Stx toxin and its prophylaxis. RESULT: The produced antibodies were confirmed by SDS-PAGE and ELISA. IgY was obtained at a concentration of about 5 mg/ml (30 mg of each egg) and a purity of more than 90%. Toxin and antibody challenge was performed in mice. The obtained IgY was able to neutralize the effect of Stx at 2 mg/mice. CONCLUSION: This challenge showed that an antibody produced with an acceptable percentage was able to neutralize the effect of Stx.

The Prevalence of Bacteriospermia in Infertile Men and Association with Semen Quality in Southwestern Iran.

INTRODUCTION: Infertility considered as a social and public health issue and estimated that most of these infertile couples are residents of developing countries. Infectious diseases including the history of Sexually Transmitted Infections (STIs) may impact on male reproductive function. Therefore, the present study aimed to investigate the prevalence of bacterial contaminants of semen and probable association with sperm quality of infertile men in Iranian population. METHODS: The study population consisted of 200 infertile men and 150 fertile men attending an infertility Center in southwestern Iran during the study period in 2015. The assessment of sperm parameters was according to the World Health Organization (WHO) guidelines. The presumptive pathogens were identified using standard microbiology tests and confirmed by specific PCR primers. RESULTS: The prevalence of bacteriospermia in the semen of the infertile group was significantly higher than that in the fertile group (48% vs. 26.7%, P <0.001). The microbiological analysis of samples showed that the most abundant species of bacteria in semen of infertile men were Chlamydia trachomatis (12.5%) followed by Neisseria gonorrhoeae (11%). On the other hand, in the control group, Lactobacillus spp. (17.3%) was the most isolated pathogen. Results showed that the presence of N. gonorrhoeae, C. trachomatis, Mycoplasma genitalium, Haemophilus, and Klebsiella was significantly associated with sperm abnormality. CONCLUSIONS: Based on our findings, it seems that bacteriospermia is associated with alterations in the properties of semen which may lead to a decrease in the fertilization potential of sperm. Therefore, immediate and appropriate treatment is necessary before investigating every other possible cause of infertility.

Burden of Clostridium (Clostridioides) difficile Infection among Patients in Western Asia: A Systematic Review and Meta-Analysis.

BACKGROUND: Clostridium difficile is the most common causes of hospital-acquired diarrhea affecting particularly hospitalized patients globally. This organism has re-emerged in recent years with significant morbidity and mortality. The present study aimed to estimate the burden of C. difficile infection (CDI) and to acquire information on the overall rates of community- and hospital-acquired CDI in western Asia. METHODS: A systematic literature search was performed to identify articles published from the eight Persian Gulf countries in western Asia including Iran, Iraq, Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates in the electronic databases within Jan of 2000 to Dec of 2017. Then, 20 publications which met our inclusion criteria were selected for data extraction and analysis by Comprehensive Meta-Analysis Software. RESULTS: Twenty studies reported the prevalence of toxigenic strains of C. difficile among patients from Persian Gulf countries, of these the pooled prevalence of CDI was 9% (95% CI: 6.5%-12.5%). Totally, 8 studies showed the prevalence of hospital-acquired CDI, from those studies the prevalence of CDI was estimated 8.4% (95% CI: 4.9%-14.1%). Moreover, 7 studies reported the prevalence of community-acquired CDI, from those studies the prevalence of CDI was estimated 1.8% (95% CI: 1.2%-2.9%). CONCLUSION: The prevalence of CDI in western Asia is lower than southern and eastern region. Moreover, the lower prevalence of community-acquired CDI compared to hospital-acquired CDI, indicate that the source of infection in western Asia is more likely in the hospitals.

Prevalence of quinolone-resistant uropathogenic Escherichia coli in a tertiary care hospital in south Iran.

Background: Quinolones are a family of synthetic antimicrobial agents with a broad antibacterial activity commonly used as a suitable therapy in patients with urinary tract infection (UTI). In the present study, we aimed to evaluate the prevalence of quinolones resistance and the presence of plasmid-mediated quinolone resistance (PMQR) genes among Escherichia coli isolates. METHODS: This study was performed on a collection of 121 E. coli isolates derived from patients with UTI. Antimicrobial susceptibility to nalidixic acid, ciprofloxacin, levofloxacin, norfloxacin, and ofloxacin was specified by the disk diffusion method. The presence of PMQR genes was determined by PCR method. RESULTS: Antibiotic susceptibility results showed that the highest and lowest resistance rates were against nalidixic acid (71.9%) and norfloxacin (44.6%), respectively. The molecular results showed that 40 (33.1%) and 15 (12.4%) of the isolates were positive for qnrS and qnrB genes, respectively. Meanwhile, 5 (4.1%) of the isolates were found positive for both genes, while none were found to be positive for qnrA gene. There was no significant association between the presence of qnr genes and higher antibiotic resistance. CONCLUSION: We found high levels of quinolones resistance (more than 40%) among E. coli strains isolated from patients with UTIs in the south of Iran. We further report the prevalence of PMQR genes among uropathogenic E. coli; however, it seems that these genes are not the main components of quinolone resistance in our region.

In vitro activities of colistin, imipenem and ceftazidime against drug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii isolates in the south of Iran.

OBJECTIVE: The present study aimed to determine in vitro activity of colistin and other agents against drug-resistant isolates of Pseudomonas aeruginosa and Acinetobacter baumannii. RESULTS: This in vitro study performed on a collection of non-fermenting Gram-negative bacilli (NFB) consist of 18 A. baumannii and 21 P. aeruginosa isolates. Non-duplicated isolates (one per patient) were isolated from blood, endotracheal tube and sputum samples of hospitalized patients in the south of Iran. The minimum inhibitory concentrations (MICs) of each isolate was determined using Epsilometer (E)-test strips containing colistin, imipenem, and ceftazidime. In overall, all A. baumannii isolates were non-susceptible to imipenem and ceftazidime. In contrast, all isolates were susceptible to colistin with MIC50 and MIC90 of 0.75/1.5 µg/mL, respectively. Antibiotic susceptibility results showed that 81% and 23.8% of P. aeruginosa isolates were susceptible to ceftazidime and imipenem, respectively. While, all of the P. aeruginosa isolates were susceptible to colistin with MIC50 and MIC90 of 0.5/1 µg/mL, respectively. In summary, colistin showed the promising in vitro activity against drug-resistant strains of two clinically important NFB in our region. However, investigation on a larger collection of drug-resistant strains demands to support these observations in the near future.

Isolation and Molecular Identification of Aeromonas Wound Infection in Iranian Burn Patients.

INTRODUCTION: Aeromonas have recently emerged as opportunistic pathogens and only a few studies are available regarding the isolation of these bacteria from burn wound infections. This study aimed at isolating Aeromonas as an infrequent cause of infection in this group of immunocompromised patients. METHODS: A total of 300 samples were collected from the wounds of burn patients hospitalized in Gotbodin Shirazi Burn Center in 2013. The samples were cultured on Aeromonas specific media and then confirmed using standard biochemical tests and 16S rRNA gene amplification and sequencing. The antibiotic susceptibility of the isolates was determined using the disk diffusion and broth microdilution methods. RESULTS: Biochemical tests demonstrated five presumptive samples of Aeromonas, while, molecular testing confirmed only three. All isolates were resistant to ampicillin-sulbactam, erythromycin, oxacillin, and vancomycin. However, they were susceptible to gentamicin, meropenem, nitrofurantoin, chloramphenicol, cephalexin, and cefotaxime. Two Aeromonas veronii isolates were resistant to sulfamethoxazole-trimethoprim and sensitive to nalidixic acid, while Aeromonas bestiarum was sensitive to the former and resistant to the latter antibiotics. Lastly, only one of the A. veronii isolates was found to be resistant to tetracycline. CONCLUSION: This study is the first to report on the isolation of Aeromonas spp. from burn patients in Iran. Moreover, this is the first report of isolating A. bestiarum from burn wounds. The results of this study confirm earlier findings that the use of molecular methods is essential to accurately identify these bacteria.

Gonorrhea and syphilis co-infection and related risk factors in HIV patients from Shiraz, South of Iran.

BACKGROUND: Neisseria gonorrhea and Treponema pallidum as an obligate human pathogen are two common causes of sexually transmitted diseases (STDs). The present study aimed to determine the prevalence of N. gonorrhoeae and T. pallidum among human immunodeficiency virus (HIV) patients in the southwest Iran. METHODS: This retrospective study was performed from 2004 to 2013, on HIV patients who were tested for detection of gonorrhea and syphilis infection at Shiraz HIV/AIDS Research Center. ELISA technique was used for preliminary detection of HIV and confirmed by a Western Blotting test. Gonorrhea was routinely diagnosed using direct Gram-staining and culturing on selective agar. Syphilis was routinely diagnosed by RPR test. RESULTS: Of the 806 HIV patients, 39 (2.6%) cases had co-infection with gonorrhea. Compared with mono-HIV infected patients, gonorrhea was significantly more likely among the males (69.4% vs. 92.3%, P=0.002). History of addiction and prison seems to be a significant risk factor for gonorrhea infection (P<0.05). Also, the mean of CD4+lymphocyte was higher among gonorrhea infected patients (368±238 vs. 415±328). Logistic regression analysis showed that sexual contact increased risk of gonococcal infection about 4 fold (OR: 4, CI: 1.7-9.39, P=0.001). None of the HIV patients had syphilis co-infection. CONCLUSIONS: As a preliminary survey, our findings provided unique information on the prevalence of gonorrhea and syphilis co-infections among HIV patients. Moreover, we introduced the main risk factors associated with gonorrhea co-infection in HIV patients in our region including gender, history of addiction and prison, CD4+lymphocyte count, and transmission routes for effective management of STDs.

Distribution of virulence genes and their association with antimicrobial resistance among uropathogenic Escherichia coli isolates from Iranian patients.

BACKGROUND: Urinary tract infections (UTIs) are one of the most frequent diseases encountered by humans worldwide. The presence of multidrug-resistant (MDR) uropathogenic Escherichia coli (UPEC) harboring several virulence factors, is a major risk factor for inpatients. We sought to investigate the rate of antibiotic resistance and virulence-associated genes among the UPECs isolated from an Iranian symptomatic population. METHODS: A total of 126 isolates from inpatients with UTI from different wards were identified as UPEC using the conventional microbiological tests. After identification of UPECs, all the isolates were subjected to antimicrobial susceptibility test and polymerase chain reaction (PCR) to identify the presence of 9 putative virulence genes and their association with the clinical outcomes or antimicrobial resistance. RESULTS: The data showed that the highest and the lowest resistance rates were observed against ampicillin (88.9%), and imipenem (0.8%), respectively. However, the frequency of resistance to ciprofloxacin was found to be 55.6%. High prevalence of MDR (77.8%) and extended-spectrum ß-lactamase (ESBL) (54.8%) were substantial. PCR results revealed the frequency of virulence genes ranged from 0 to 99.2%. Among 9 evaluated genes, the frequency of 4 genes (fimH, sfa, iutA, and PAI marker) was > 50% among all the screened isolates. The iutA, pap GII, and hlyA genes were more detected in the urosepsis isolates with significantly different frequencies. The different combinations of virulence genes were characterized as urovirulence patterns. The isolates recovered from pyelonephritis, cystitis, and urosepsis cases revealed 27, 22, and 6 virulence patterns, respectively. A significant difference was determined between ESBL production with pap GII, iutA, and PAI marker genes. CONCLUSIONS: Our study highlighted the MDR UPEC with high heterogeneity of urovirulence genes. Considering the high rate of ciprofloxacin resistance, alternative drugs and monitoring of the susceptibility profile for UPECs are recommended.

Phenotypic and genotypic characterization of macrolide, lincosamide and streptogramin B resistance among clinical isolates of staphylococci in southwest of Iran.

OBJECTIVE: The present study aimed to determine the phenotypic and genotypic profile of macrolide, lincosamide and streptogramin B (MLSB) resistance in clinical isolates of staphylococci. RESULTS: This cross-sectional study was conducted on 164 non-duplicated staphylococci isolates collected during August 2015 to February 2016 from two tertiary care hospitals in Shiraz, southwest of Iran. Of the 164 isolates, 86 erythromycin-resistant isolates consist of 35 Staphylococcus aureus and 51 coagulase negative staphylococci (CoNS) were included in the study. Of the 35 S. aureus, the prevalence of cMLS (constitutive), iMLS (inducible), and MS phenotypes were found 82.9%, 8.6% and 8.6%, respectively. Among 51 CoNS, the frequencies of cMLS, iMLS, and MS phenotypes were detected 66.7%, 11.8% and 21.6%, respectively. Among S. aureus isolates, the predominant genes were ermC in 82.9% isolates, followed by ermA in 57.1% and msrA in 28.6% of isolates. Among CoNS isolates, the most frequent genes were diagnosed ermC in 70.6% isolates followed by msrA in 68.6% and ermA in 11.8% of isolates. In conclusion, regarding the presence of MLSB resistance in our region, diagnosis of this resistance type on a routine basis in staphylococcal clinical isolates is of particular importance.

Epidemiology of Panton-Valentine Leukocidin harbouring Staphylococcus aureus in cutaneous infections from Iran: a systematic review and meta-analysis.

Panton-Valentine Leukocidin (PVL) producing Staphylococcus aureus has been associated with severity of skin infections and pathology that suggest a major role in pathogenicity. The present study aimed to determine the overall prevalence of PVL harbouring S. aureus isolates from cutaneous infections in Iran. A systematic search was performed by using Medline electronic databases (PubMed) from the papers published by Iranian authors to the end of March 2017. Ten publications which met our inclusion criteria were then selected for data extraction and analysis by Comprehensive Meta-Analysis Software. The pooled prevalence of PVL in cutaneous infections was estimated at 27.9% (95% CI: 17.9-40.6). The range of PVL positivity among S. aureus isolates obtained from cutaneous infections was from 7.4% to 55.6%. In summary, despite the emergence of multiple-drug resistant strains, it seems that the overall prevalence of PVL carrying S. aureus in Iran remains steady regardless of methicillin resistance. However, further research is required to elucidate the interplay between the risk of invasive disease and PVL, especially in Iran.