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Sarvenaz Esfahani, Roya Ahmadrajabi, Hamidreza Mollaei, Fereshteh Saffari Department of Microbiology and Virology, School of Medicine, Kerman University of Medical Sciences, Kerman, IranCorrespondence: Fereshteh Saffari Email fsafari@kmu.ac.irIntroduction: Enterococcus faecalis is one of the most common pathogens in urinary tract infections (UTIs). Fluoroquinolones have been frequently used to treat E. faecalis UTIs, and the emergence of fluoroquinolone-resistant E. faecalis strains has recently been reported in several countries. This study aimed to elucidate the mechanisms involved in fluoroquinolone resistance in clinical E. faecalis isolates by analyzing mutations in quinolone- resistance-determining regions (QRDRs) of gyrA and parC and investigating the role of some efflux pumps.Methods: In total, 70 clinical E. faecalis isolates collected from UTIs were identified by phenotypic and genotypic methods. Antimicrobial susceptibility testing was performed and multidrug-resistant (including ciprofloxacin resistant) isolates were studied for minimum inhibitory concentrations to ciprofloxacin, levofloxacin, and ofloxacin. In the following, mutations in QRDRs of gyrA and parC and expression of EfrA, EfrB, and EmeA efflux pumps were investigated in 20 high-level ciprofloxacin resistant and two ciprofloxacin susceptible isolates.Results: High-level resistance to ciprofloxacin was detected in 97.5% of isolates. Sequencing of QRDRs revealed that 65% and 75% of isolates carried mutations in gyrA and parC, respectively. The presence of efflux genes was detected in all studied isolates, but expression of efrA, emeA, and efrB was demonstrated in 50%, 40%, and 30% of resistant isolates, respectively. Neither QRDR mutation nor the expression of efflux genes showed any significant association with MIC.Conclusion: Co-incidence of mutation and efflux gene expression in more than half of isolates (13/20) suggests that both mechanisms may play a role in fluoroquinolone resistance. The other unknown mechanisms including different efflux pumps and probably other QRDRs mutations may contribute to fluoroquinolone resistance in E. faecalis.Keywords: E. faecalis, UTI, gyrA, parC, efflux pump

MicroRNA-98 (miR-98) stands as an important molecule in the intricate landscape of oncology. As a subset of microRNAs, these small non-coding RNAs have accompanied a new era in cancer research, underpinning their significant roles in tumorigenesis, metastasis, and therapeutic interventions. This review provides a comprehensive insight into the biogenesis, molecular properties, and physiological undertakings of miR-98, highlighting its double-edged role in cancer progression-acting both as a tumor promoter and suppressor. Intriguingly, miR-98 has profound implications for various aspects of cancer progression, modulating key cellular functions, including proliferation, apoptosis, and the cell cycle. Given its expression patterns, the potential of miR-98 as a diagnostic and prognostic biomarker, especially in liquid biopsies and tumor tissues, is explored, emphasizing the hurdles in translating these findings clinically. The review concludes by evaluating therapeutic avenues to modulate miR-98 expression, addressing the challenges in therapy resistance, and assessing the efficacy of miR-98 interventions. In conclusion, while miR-98's involvement in cancer showcases promising diagnostic and therapeutic avenues, future research should pivot towards understanding its role in tumor-stroma interactions, immune modulation, and metabolic regulation, thereby unlocking novel strategies for cancer management., (© 2024. The Author(s).)

MicroRNA production in tumorigenesis is dysregulated by a variety of processes, such as proliferation and removal of microRNA genes, aberrant transcriptional regulation of microRNAs, disrupted epigenetic alterations, and failures in the miRNA biogenesis machinery. Under some circumstances, miRNAs may act as tumorigenic and maybe anti-oncogenes. Tumor aspects such as maintaining proliferating signals, bypassing development suppressors, delaying apoptosis, stimulating metastasis and invasion, and promoting angiogenesis have been linked to dysfunctional and dysregulated miRNAs. MiRNAs have been found as possible biomarkers for human cancer in a great deal of research, which requires additional evaluation and confirmation. It is known that hsa-miR-28 can function as an oncogene or tumor suppressor in many malignancies, and it does this by modulating the expression of several genes and the downstream signaling network. MiR-28-5p and miR-28-3p, which originate from the same RNA hairpin precursor miR-28, have essential roles in a variety of cancers. This review outlines the function and mechanisms of miR-28-3p and miR-28-5p in human cancers and illustrates the miR-28 family's potential utility as a diagnostic biomarker for prognosis and early detection of cancers., Competing Interests: Conflict of interest statement The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Triple negative breast cancer (TNBC) is characterized as a heterogeneous disease with severe malignancy and high mortality. Aberrant Wnt/β-catenin signaling is responsible for self-renewal and mammosphere generation, metastasis and resistance to apoptosis and chemotherapy in TNBC. Nonetheless, in the absence of a targeted therapy, chemotherapy is regarded as the exclusive treatment strategy for the treatment of TNBC. This review aims to provide an unprecedented overview of the plants and herbal derivatives which repress the progression of TNBC through prohibiting the Wnt/β-catenin pathway. Herbal medicine extracts and bioactive compounds (alkaloids, retinoids. flavonoids, terpenes, carotenoids and lignans) alone, in combination with each other and/or with chemotherapy agents could interrupt the various steps of Wnt/β-catenin signaling, i.e., WNT, FZD, LRP, GSK3β, Dsh, APC, β-catenin and TCF/LEF. These phytotherapy agents diminish proliferation, metastasis, breast cancer stem cell self-renewal and induce apoptosis in cell and animal models of TNBC through the down-expression of the downstream target genes of Wnt signaling. Some of the herbal derivatives simultaneously impede Wnt/β-catenin signaling and other overactive pathways in triple negative breast cancer, including: mTORC1; ER stress and SATB1 signaling. The herbal remedies and their bioactive ingredients perform essential roles in the treatment of the very fatal TNBC via repression of Wnt/β-catenin signaling.

Background and Objectives: The viral transactivator HBx protein affect cellular, viral and pregenomic factors pathway. Mutations in this protein can produce new viruses with new antigenic determinants that are generally related to developing cancerous., Materials and Methods: In this cross-sectional study, 33 serum samples of patients diagnosed with acute HBV infection were investigated for HBeAg and HBV DNA viral load and HBx gene mutations. mutation in the HBx protein detected by sequencing analysis., Results: Out of the 33 samples, 19 samples were males (57.6%), and 14 samples were females. 15 (45.5%) were positive for HBx DNA and 18 patients were negative for HBx DNA (54.5%). After sequencing, three mutations were recognized in HBx at nucleotide positions 147, 148, and 391 that were stationed to G1524A, G1525A, and G1767C mutations., Conclusion: The analysis result of this study shows G1524A and G1525A mutations that an important role in altering the inhibition function of the HBx activity domain. The G1767C mutation inactivates HBx transactivation activity. These mutations have a critical role in the pathogenicity of the virus, and the intensity of hepatic tissue demolition and the development of cirrhosis or carcinoma in patients can be understood., (Copyright © 2022 The Authors. Published by Tehran University of Medical Sciences.)

Vitiligo is the most common cause of skin, hair, and oral depigmentation which is known as an autoimmune disorder. Genetic and environmental factors have important roles in the progression of the disease. Dysregulation of gene expression, like microRNAs (miRNA), may serve as major relevant factors. Several biological processes are involved in vitiligo disease and developing a comprehensive approach helps us to better understand the molecular mechanisms of disease. In this research, we describe how a weighted gene co-expression network analysis as a systems biology approach assists to define the primary gene modules, hub genes, and messenger RNA (mRNA)-miRNA regulatory network in vitiligo disease as the novel biomarkers. The results demonstrated a module with a high correlation with vitiligo state. Moreover, gene enrichment analysis showed that this module's genes were mostly involved in some biological activities including G protein-coupled receptors signaling pathway, lymphocyte chemotaxis, chemokine activity, neutrophil migration, granulocyte chemotaxis, etc. The co-expression network was constructed using top hub genes of the correlated module which are named as CXCL10, ARL9, AKR1B10, COX7B, RPL26, SPA17, NDUFAF2, RPF2, DAPL1, RPL34, CWC15, NDUFB3, RPL26L1, ACOT13, HSPB11, and NSA2. MicroRNAs prediction tool (miRWalk) revealed top miRNAs correlated with the interested module. Finally, a drug-target network was constructed which indicated interactions of some food and drug administration (FDA) approved drugs with hub genes. Our findings specified one important module and main hub genes which can be considered as novel biomarkers for vitiligo therapeutic purposes.

(1) Background: Psoriasis is a multifactorial chronic inflammatory disorder of the skin, with significant morbidity, characterized by hyperproliferation of the epidermis. Even though psoriasis' etiology is not fully understood, it is believed to be multifactorial, with numerous key components. (2) Methods: In order to cast light on the complex molecular interactions in psoriasis vulgaris at both protein-protein interactions and transcriptomics levels, we studied a set of microarray gene expression analyses consisting of 170 paired lesional and non-lesional samples. Afterwards, a network analysis was conducted on the protein-protein interaction network of differentially expressed genes based on micro- and macro-level network metrics at a systemic level standpoint. (3) Results: We found 17 top communicative genes, all of which were experimentally proven to be pivotal in psoriasis, which were identified in two modules, namely the cell cycle and immune system. Intra- and inter-gene interaction subnetworks from the top communicative genes might provide further insight into the corresponding characteristic interactions. (4) Conclusions: Potential gene combinations for therapeutic/diagnostics purposes were identified. Moreover, our proposed workflow could be of interest to a broader range of future biological network analysis studies.

Background: Functional dyspepsia is a common chronic digestive disorder. The purpose of this study was to compare the effectiveness of dialectical behavior therapy and anti-anxiety medication in patients with functional dyspepsia., Materials and Methods: The present study was a randomized, controlled clinical trial with sixty patients who were suffering from functional dyspepsia that identified by the ROME III criteria. Patients were divided into three groups by using pre- and posttest design, including Group A (dialectal treatment and pantoprazole), Group B (anxiolytic drug treatment and pantoprazole), and Group C (no intervention, only pantoprazole were used). The Beck Anxiety Inventory and the patient assessment of Gastrointestinal Symptom Severity Index Questionnaire were completed by the patients after receiving the written consent. Finally, the data were analyzed using the Statistical Package for the Social Sciences software version 20., Results: There was a significant improvement in the severity of dyspepsia after intervention in all three groups. The greatest decrease in the severity of functional dyspepsia was observed in the dialectical behavioral therapy group as compared to the other groups (Group A: -15.4 ± 6.61, Group B: -3.85 ± 2.77, and Group C: -7.8 ± 4.02; P = 0.001). Furthermore, the Beck Anxiety Inventory scores were statistically significantly improved in all three groups (Group A: -5.75 ± 2.53, Group B: -7.3 ± 3.19, and Group C: -2.60 ± 1.5; P = 0.001). There was a positive correlation between the change in dyspepsia score and change in anxiety score across different intervention groups ( r = 0.55; P < 0.001)., Conclusion: Dialectical behavioral therapy can be effective in reducing anxiety and improving the dyspepsia symptoms in patients with functional dyspepsia compared to anti-anxiety medication or conventional therapy. Therefore, communication between the physicians and psychologists and psychiatrists can have positive effects on the treatment of these patients., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Research in Medical Sciences.)

BACKGROUND Irritable bowel syndrome (IBS) is the most common chronic gastrointestinal (GI) disorder. Patients with IBS usually suffer from anxiety and depression. A combination of psychological approaches and pharmacological treatments can be a significantly effective treatment for IBS. The main objective of the present study was to provide a therapeutic plan based on laughter yoga and anti-anxiety medication, employed for the very first time, and to determine the effectiveness of these treatments on the anxiety and GI symptoms of patients with IBS. METHODS In this randomized, controlled, clinical trial, the participants were 60 patients selected from those who referred to the GI clinic of Vali-asr Hospital (Birjand, Iran) during the study period (April 2017 to March 2017) and were diagnosed as having IBS based on ROME III criteria. The participants were randomly assigned to either the laughter yoga group, the anti-anxiety medication group, or the symptomatic treatment (control) group. Severity levels of anxiety and GI symptoms before and after intervention were determined and compared among these three groups according to approved protocols. RESULTS The severity of IBS symptoms after the interventions was more greatly reduced in the laughter yoga group than in the anti-anxiety medication and control groups ( p = 0.006). The severity of anxiety after interventions decreased in all three groups, especially in the yoga treatment group, but the difference was not statistically significant ( p = 0.1). CONCLUSION Laughter yoga is more effective than anti-anxiety medication in reducing the GI symptoms of patients with IBS. Therefore, applying laughter yoga along with common pharmacological therapies for patients with IBS might be strongly advised., Competing Interests: CONFLICT OF INTEREST The authors declare no conflict of interest related to this work., (© 2019 The Author(s).)

Background: Human parvovirus B19 was known as one of the possible cause of mild respiratory tract diseases in previous studies. However, there are some reports of acute obstructive respiratory disease and severe pneumonia. The purpose of current study was to assess the prevalence and clinical features of parvovirus B19 in respiratory infection. Methods: This study was conducted on 156 patients diagnosed with respiratory infection at the Iran University of Medical Sciencesaffiliated hospitals. After extraction of viral DNA from swab samples, detection of parvovirus B19 was performed by real-time PCR assay. Results: In 156 patient's samples, parvovirus B19 was found in 8 (5.1 %) cases including 5 males (5.9%) and 3 females (4.1%). The most common clinical symptoms were wheezing (100%), tachypnea (100%), fever (75%) and rhinorrhea/pharyngitis (75%). Conclusion: This is the first attempt to assess the prevalence of parvovirus B19 infection in Iranian patients with respiratory infection. The low frequency of parvovirus B19 detected in our study does not support the role of this virus in the development of respiratory infection. However, further studies are needed to better evaluate the etiological role of parvovirus B19 in respiratory infection.

The aim of the present study was to determine whether mesenchymal stem cell-conditioned medium (MSC-CM) modulates apoptotic and stress-related gene expression, and ameliorates maturation and developmental potential of immature human oocytes after artificial activation. A total of 247 surplus immature germinal vesicle (GV) oocytes obtained from infertile women were allocated into two in vitro maturation (IVM) groups: 1: GV oocytes ( n = 116) matured in vitro (fIVM), and 2: GV oocytes ( n = 131) that were vitrified, then in vitro matured (vIVM). Also, two maturation media were used: Alpha-minimum essential medium (α-MEM) and human umbilical cord-derived MSCs (hUCM). After 36 h of incubation, the IVM oocytes were examined for nuclear maturation. In IVM-matured oocytes, cytoplasmic maturation was evaluated after artificial activation through Ionomycin. Moreover, the quantitative expressions of B-cell CLL/lymphoma 2 ( BCL2 ), BCL2-associated X protein ( BAX ), superoxide dismutase ( SOD ), and Heat shock proteins ( HSP70 ) in matured oocytes were assessed by quantitative Real-time polymerase chain reaction (qRT-PCR) and compared with fresh and vitrified in vivo matured oocytes, which were used as fIVM and vIVM controls, respectively. The highest maturation rate was found in hUCM in fIVM, and the lowest maturation rate was found using α-MEM in vIVM (85.18% and 71.42%, respectively). The cleavage rate in fIVM was higher than that in vIVM (83.4% vs. 72.0%). In addition, the cleavage rate in α-MEM was lower than that in the hUCM (66.0% vs. 89.4%). Furthermore, the difference between parthenote embryo arrested in 4-8 cells ( p < 0.04) and the quality of embryo arrested in 8-cell ( p < 0.007) were significant. The developmental stages of parthenote embryos in hUCM versus α-MEM were as follows: 2-4 cell (89.45% vs. 66.00%, respectively), 4-8 cell (44.31% vs. 29.11%, respectively), morula (12.27% vs. 2.63%, respectively), and blastocysts (2.5% vs. 0%, respectively). The messenger RNA (mRNA) expression levels of BCL2, BAX and SOD were significantly different ( p < 0.05) between the matured IVM oocytes. Overall, hUCM showed potential efficacy in terms of ameliorating oocyte maturation and in promoting the development and mRNA expression of BAX, BCL2, and SOD., Competing Interests: The authors declare no conflict of interest.

Background: Human parvovirus B19 (B19V) is one of the smallest DNA viruses and shows great resistance to most disinfectants. Therefore, it is one of the common contaminant pathogens present in blood and plasma products. Parvovirus 4 (PARV4) is a newly identified parvovirus, which is also prevalent in parenteral transmission. In this study, we aimed to evaluate the prevalence of B19V and PARV4 DNA among patients with hemophilia in Birjand County in eastern Iran., Methods: This was a cross-sectional epidemiological study comprising nearly all people with hemophilia in this region. Whole blood samples were taken after patient registration and sent for plasma isolation. After nucleic acid extraction, B19V was detected with real-time polymerase chain reaction, PARV4 DNA was then detected using sensitive semi-nested PCR., Results: In total, there were 86 patients with hemophilia, with mean age 28.5±1.5 years. Of these, 90.7% were men and 9.3% women; 84.9% had hemophilia A and 7.0% had hemophilia B. We found 11 patients (12.8%) were positive for B19V DNA and 8 were positive (9.3%) for PARV4 DNA. The prevalence of B19V was higher in middle-aged groups rather than younger people, whereas PARV4 infection was more common in younger patients ( P <0.05)., Conclusion: There was a high prevalence of B19V and PARV4 infection in this high-risk group of patients with hemophilia. Due to the clinical significance of the B19 virus, imposing more precautionary measures for serum and blood products is recommended., Competing Interests: Authors' Disclosures of Potential Conflicts of Interest: No potential conflicts of interest relevant to this article were reported.

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder associated with reproductive disorders and metabolic dysfunctions including insulin resistance. The roles of vitamin D in the regulation of metabolic modulations specifically involving insulin and reproduction processing are introduced. In addition, obesity appears to be closely associated with severity of PCOS. The present study is to evaluate the effect of body mass index (BMI) on vitamin D levels in follicular fluid and vitamin D receptor (VDR) expression levels in granulos cells., Materials and Methods: A comparative study was conducted on 80 women with average age of 20-35 years referred for in vitro fertilization (IVF). Patients were divided into four groups, and serum levels of testosterone and insulin resistance (IR) were evaluated at the puncture time. Also, vitamin D levels of follicular fluid were evaluated. VDR gene expression was assayed by quantified-polymerase chain reaction (PCR) technique. Correlations were evaluated with calculation of the Spearman coefficient, and also independent relationships were assessed by means of multiple regression analysis., Results: Vitamin D levels of follicular fluid decreased in PCOS patients compared with non-PCOS. Also, over-weight individuals had lower vitamin D levels compared with normal-weight patients. Vitamin D levels of follicular fluid were highly correlated with BMI (r=-0.51, P<0.01). Homeostatic model assessment-IR (HOMA-IR) values were significantly higher in women of PCOS/overweight and PCOS/normal weight in comparison with women of non-PCOS/normal weight (P<0.01). The gene expression data of VDR in granulosa cells were significantly lower in the PCOS/overweight group compared with the non-PCOS/normal weight (P<0.01)., Conclusion: The findings indicated significant differences in VDR gene expression in granulosa cells and vitamin D of follicular fluid in PCOS/overweight patients.

Despite recent advances in cancer medication, malignant tumors continue to be the second leading cause of death worldwide. Furthermore, introducing a therapeutic compound with low-side effects as well as low-price for consumers is controversial. Recent efforts have been focusing on traditional medicines as a rich source of herbal agents. Curcumin, the major turmeric phytochemical, has been widely assessed as an anti-cancer compound in vitro and in vivo. However, the use of curcumin in cancer treatment has limitations because of its low solubility, poor tissue absorption, rapid metabolism and rapid systemic elimination. Recent work has focused on improving the stability of curcumin to facilitate clinical application. Dendrosomal nano-corcumin (DNC) is one of the most successful compounds showing significant cellular absorption and also anti-tumor effects. The present overview of newest applicable strategies for curcumin-based therapy and their clinical potential usefulness has the emphasis on DNC., (Creative Commons Attribution License)

Background: Due to the tropism of human parvovirus B19 to erythroid progenitor cells, infection in patients with an underlying hemolytic disorder such as beta-thalassemia major leads to suppression of erythrocyte formation, referred to as transient aplasia crisis (TAC), which may be life-threatening. We investigated the prevalence of parvovirus B19 among patients with beta thalassemia major attending the Zafar Adult Thalassemia Clinic in Tehran, Iran., Methods: This cross-sectional study was performed to determine the presence of parvovirus B19 DNA in blood samples and parvovirus B19 genotypes in plasma samples of patients with thalassemia major. The population consisted of 150 patients with beta-thalassemia major who attended the Zafar clinic in Tehran. Specimens were studied using a real-time polymerase chain reaction assay., Results: The prevalence of parvovirus B19 in our study population was 4%. Of 150 patients with thalassemia, six (4%) were positive for B19 DNA. There was no significant correlation between blood transfusion frequency and B19 DNA positivity. Finally, phylogenetic analysis of human parvovirus B19 revealed genotype I in these six patients., Conclusion: In this study, acute B19 infections were detected in patients with beta thalassemia major. Screening of such high-risk groups can considerably reduce the incidence and prevalence of B19 infection; thus, screening is required for epidemiologic surveillance and disease-prevention measures., Competing Interests: Authors' Disclosures of Potential Conflicts of Interest: No potential conflicts of interest relevant to this article were reported.

In more than half of infertile men, the cause of their infertility is unknown. Several studies revealed the role of viral infections in male infertility. The aim of the present study was to determine the prevalence of herpes simplex virus-1 (HSV-1) and HSV-2 in semen from asymptomatic infertile male patients, and its association with altered semen parameters. A total of 70 semen samples were collected from infertile men who attended the Research and Clinical Center for Infertility in Yazd, Iran. Semen analysis and diagnostic real-time PCR using specific primers and probes for HSV-1 and HSV-2 DNA were performed. Comparison of semen parameters between virally infected and non-infected samples were performed with independent t-test and Mann-Whitney test. Semen analysis showed that infertile men fell into two groups, the male factor group and the unexplained group. HSV-1 and HSV-2 DNA was detected in 16 (22.9%) and 10 (14.3%) of 70 semen samples, respectively. All HSV-positive samples had abnormal semen parameters (the male factor group). Although HSV infection was not associated with sperm motility and morphological defects, it was correlated with lower sperm count in the seminal fluid. The findings suggest that asymptomatic seminal infection of HSV plays an important role in male infertility by adversely affecting sperm count.

Introduction: HPV has been found repeatedly in esophageal squamous cell carcinoma (ESCC) tissues. However, reported detection rates of HPV DNA in these tumors have varied markedly. Differences in detection methods, sample types, and geographic regions of sample origin have been suggested as potential causes of variation. We have reported that infection of HPV DNA in ESCC tumors depends on anatomical sites of esophagus of the patients from Mazandaran, north of Iran., Materials and Methods: HPV DNA was examined in 46 upper, 69 middle and 62 lower third anatomical sites of esophageal squamous cell carcinoma specimens collected from Mazandaran province in north Iran, near the Caspian Littoral as a region with high incidence of ESCC. HPV L1 DNA was detected using Qualitative Real time PCR and MY09/MY11 primers., Results: 28.3% of upper, 29% of middle and 25.8% of lower third of ESCC samples were positive for HPV DNA. 13.6% for males and 14.1% for females were HPV positive in all samples., Conclusions: HPV infection is about one third of ESCC in this area. Findings in this study increase the possibility that HPV is involved in esophageal carcinogenesis. Further investigation with a larger sample size is necessary.