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Context. Anti-Mullerian hormone (AMH) assay is becoming the best indicator of successful IVF treatment response to fertility drugs and could be a useful marker of embryo implantation potential. Various protocols are being used for controlled ovarian stimulation (COS), but there is an uncertainty regarding the implementation of the best protocol for endometriosis patients and also little evidence is available concerning the clinical value of AMH levels in endometriosis. Objective. This study aimed to evaluate the prognostic value of serum AMH levels for pregnancy in COS using GnRH-agonist(GnRH-a) and GnRHantagonist(GnRH-ant) protocols in endometriosis patients. Design. This is a cross-sectional study between March 2012 and November 2015. Subjects and Methods. Data were collected from 249 COS cycles of endometriosis patients, including 129 cycles with GnRH-a and 120 cycles with GnRH-ant. Patients in each group were classified into three subgroups based on their serum AMH levels. The outcomes of ICSI program were evaluated. Results. The ROC curve analysis showed that embryo and oocyte counts and AMH were equally predictive for pregnancy, as demonstrated by a similar area under the curve (AUC) of 0.69, 0.66 and 0.64, respectively. The sensitivity and specificity for prediction of positive pregnancy were 70.91% and 67.01% for embryo counts, 70.91% and 67.53% for oocyte counts at the cutoff values of 5 and 7, respectively, and 83.64% and 52.58% for AMH levels at the cutoff values of 1.3ng/mL. Conclusions. This study demonstrates that AMH as a single test has substantial accuracy in the prediction of pregnancy using the GnRH antagonist protocol for patients with endometriosis. In other words, AMH assay prior to ovarian stimulation initiation guides the clinicians to choose the antagonist stimulation protocol for the patients with two extreme AMH levels. AMH levels can be used to individualize control ovarian stimulation in endometriosis patients. [ABSTRACT FROM AUTHOR]

Introduction: AMH is not only associated with the oocyte yield after IVF but also is associated with oocyte quality and embryo number, making it a prognostic factor for the chance of a pregnancy and live birth. Several investigators demonstrated lower basal AMH levels among women with endometriosis. However, there are few studies for correlation between serum AMH and ovarian response to COH in women with endometriosis. Materials and Methods: Retrospective data were collected from 126 infertile women undergoing ICSI treatment with the long stimulation protocol. Patients divided into two groups: 66 women with endometriosis diagnosed by laparoscopy and 60 women with tubal factor (study and control groups). AMH level, oocyte and early cleavage embryo number and pregnancy rate were measured. Results: Serum AMH levels were significantly lower in endometriosis compared to the control group (1.99±0.16 vs. 2.65±0.23 ng/mL). In endometriosis patients the mean of retrieved oocytes (7.47±0.61) and embryo number (4.58±0.45) were significantly lower compared with control group (10.12±0.85, 6.78±0.62). The chemical pregnancy rate in women with and without endometriosis was 15 and 37%, respectively. Conclusion: Although ART procedures have been successful in infertile women with endometriosis, poorer results are still expected for these patients. Our data shows that endometriosis patients have a reduced reproductive potential because of decreased AMH levels and consequently, lower retrieved oocytes, embryo number and pregnancy rate. This finding suggests that endometriosis is associated with the reduction of ovarian reserve and poorer results in terms of Control Ovarian Hyperstimulation. [ABSTRACT FROM AUTHOR]

Introduction: Controlled ovarian hyperstimulation (COH) plays important role in reproductive medicine because selection of appropriate ovarian stimulation strategy can improve assisted reproductive technology outcomes. Antimullerian hormone (AMH) is a predictor of ovarian response, which can help to select the best treatment strategies in women undergoing agonist and antagonist protocols to optimize safety and clinical pregnancy rates. Materials and Methods: This study is a retrospective study conducted in a private assisted reproductive unite and a total of 243 patients with tubal factor infertility are selected. Results: In both of GnRH agonist and antagonist protocol, with increasing of AMH level, oocyte and good embryo number is increased. On the other hand in AMH<1.1, > 2.8 ng/ml levels, GnRH agonist leads to higher oocyte and embryo number that is significant. On the contrary, pregnancy rate with increasing of AMH level is not increased and the highest rate of pregnancy is observed in AMH 1.1-2.8 ng/ml levels that it observed with antagonist protocol. Conclusion: Based on AMH levels we can predict assisted reproductive outcomes. In three range of AMH levels, GnRH agonist protocol can lead to better results. In the women with poor prognosis and low and high levels of AMH, it should focus on improving results with increasing of endometrial receptivity or embryo quality. [ABSTRACT FROM AUTHOR]

Introduction: AMH levels correlated significantly with the number of antral follicles, so in high, normal and poor responders is decreased, respectively. AMH-tailored stimulation improved positive clinical outcomes, reduced the incidence of complications and financial burden in ART. Agonist and antagonist protocols administration in women with various range of AMH showed different outcomes therefore we intend to study of antagonist protocols' results. In This retrospective study we assessed 94 women with tubal factor infertility undergoing antagonist protocol. Materials and Methods: In our study, patients divided into group 1 (AMH<1.1 ng/ml), group 2 (1.1⩽AMH <2.8 ng/ml) and group 3 (AMH ⩾2.8 ng/ml). Results: The oocyte number in group 3 (15.6±0.68), group 2 (9.17±0.46) and group 1 (3±0.13) is significantly decreased. Embryos number in group 1 (2±0.19) is significantly lower than group 2 and 3(7±0.47 and 7.4±0.55, respectively). Pregnancy rate in group 2 is significantly higher than group 3 and 1(72%, 20% and 0%, respectively). Good quality oocytes average in group 3 is significantly higher than other groups (5.8±0.62) and in group 1 is lower than group 2 (2±0.13 and 3.53±0.29, respectively). Good quality embryos average in group2 and 3 (2.35±0.13 and 2.5±0.23, respectively) is significantly higher than group 1 (1±0). Conclusion: Results determined increasing AMH levels associated with good quality oocytes and embryos. We observed the highest pregnancy rate in normal range of AMH, thus perhaps antagonist protocol in certain range of AMH levels can lead to optimal results. In AMH <1.1 ng/ml, antagonist protocol lead to suboptimal results, it can be concluded that it isn't proper for them. Therefore, AMH levels may be used for selection of optimal protocol. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is the most common heterogeneous reproductive disorder and can affect approximately 10% of women of reproductive age. Abnormal vasculogenesis is a common event in polycystic ovary syndrome. This study planned to evaluate the antiangiogenic role of apigenin in ovarian histology, gene expression, and vascular density and stability in an experimental model of PCOS. Twenty-eight rats weighing 180-250 g were divided into 4 groups. Seven rats in the control group remain intact and without treatment. In 21 rats, an ovary polycystic model with a single injection of estradiol valerate was established. The PCOS rats were treated with vehicle, apigenin 10, or apigenin 20 mg/kg in three different PCOS groups for 14 days. At the end, a histological assessment of the ovaries was performed to determine collagen density and follicle counting. The endothelial or periendothelial cells were determined by immunohistochemical assay, and angiogenesis gene expression was determined using molecular assessments. Apigenin treatment partially restored follicular development, decreased the number of cysts, and increased corpora lutea in PCOS rats. Also, apigenin decreased the collagen density in the polycystic ovaries. However, apigenin administration mitigated ovarian angiogenesis by a reduction in endothelial and periendothelial cell numbers. A decrease in VEGF and VEGF R2 (kinase insert domain receptor, KDR) expressions was found after the treatment of rats with apigenin. Conclusively, our data revealed that apigenin improves ovarian histological alterations and follicular dynamics in polycystic ovary rats. The effect is partially mediated by suppression of the VEGF signaling system and reduction in endothelial and periendothelial cell proliferation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women, often leading to infertility due to anovulation. Recent advances suggest that endometrial stem cells (EnSCs) hold considerable promise for tissue regeneration, which could be pivotal in treating PCOS. To enhance the survival and stabilization of EnSCs within the ovary, the EnSCs were encapsulated in an injectable alginate/gelatin hydrogel (SC-H), which has excellent biocompatibility to support the survival of EnSCs. Polycystic ovary syndrome was induced in female Wistar rats using intraperitoneal injection of letrozole over 21 days. Then the rats were treated with SC, SC-H and clomiphene citrate for one-month post-PCOS induction. The effects of these treatments were evaluated based on changes in body and ovarian weights, inflammatory markers, endocrine profiles, and ovarian histology. The Induction of PCOS led to a significant increase in body and ovarian cyst weight, elevated serum levels of testosterone, luteinizing hormone (LH), and anti-Müllerian hormone (AMH), alongside reduced follicle-stimulating hormone (FSH) and progesterone levels. Histologically, there was a decrease in granulosa cells, immature follicles, and corpus luteum numbers. Treatment with SC and SC-H significantly mitigated these alterations, indicating improved PCOS conditions. Our findings demonstrate that SC and SC-H treatments can effectively ameliorate the symptoms of letrozole-induced PCOS in rats, primarily through their anti-inflammatory effects. This study lays the groundwork for potential clinical applications of EnSCs encapsulated in alginate/gelatin hydrogel as a novel therapeutic strategy for PCOS, highlighting the importance of biomaterials in stem cell-based therapies., Competing Interests: The authors declare that they have no competing interests., (© 2024 The Author(s).)

Objective: There are ethical and technical challenges in studying human germ cell development. Therefore, the aim of the study is in vitro differentiation of human embryonic stem cells (hESCs), as pluripotent cells, to the germ cells which is a valuable tool for studying molecular and cellular aspects of gametogenesis and understanding causes of infertility., Materials and Methods: In this experimental study, two different complete media [Dulbecco's Modified Eagle Medium (DMEM)+20% fetal bovine serum (FBS) and embryoid bodies (EBs) medium; KOSR/HES without basic fibroblast growth factor (bFGF)] were used in the both of test groups using testicular cells derived conditioned medium (TCCM) and control groups spontaneously differentiated (SD). Thereby, EBs from hESCs (Yazd2; 46XY) were cultured in different conditions EB medium; EB medium and conditioned EB medium; EB medium, DMEM, and FBS without conditioning; EB medium, conditioned DMEM, and FBS medium. EBs were collected after 4, 7, and 14 days and their gene expression profiles were assessed and compared to hESCs, as day 0, using IF and relative reverse transcription quantitative polymerase chain reaction (RT-qPCR)., Results: An increase in the gametogenesis gene expression level in TCCM groups was showed in comparison with SD groups. Additionally, immunostaining of differentiated cells in all groups showed in vitro gametogenesis (IVG)., Conclusion: Our findings showed that human TCCM could be used as a natural niche for in vitro male and female germ cell development. However, further studies are needed to define the factors and metabolites within the human TCCM.

Background: In this phase I clinical trial, our primary objective was to develop an innovative therapeutic approach utilizing autologous bone marrow-derived mesenchymal stromal/stem cells (BM-MSCs) for the treatment of nonobstructive azoospermia (NOA). Additionally, we aimed to assess the feasibility and safety of this approach., Materials and Methods: We recruited 80 participants in this non-randomized, open-label clinical trial, including patients undergoing NOA treatment using autologous BM-MSCs (n=40) and those receiving hormone therapy as a control group (n=40). Detailed participant characteristics, such as age, baseline hormonal profiles, etiology of NOA, and medical history, were thoroughly documented. Autotransplantation of BM-MSCs into the testicular network was achieved using microsurgical testicular sperm extraction (microTESE). Semen analysis and hormonal assessments were performed both before and six months after treatment. Additionally, we conducted an in-silico analysis to explore potential protein-protein interactions between exosomes secreted from BM-MSCs and receptors present in human seminiferous tubule cells., Results: Our results revealed significant improvements following treatment, including increased testosterone and inhibin B levels, elevated sperm concentration, and reduced levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin. Notably, in nine patients (22.5%) previously diagnosed with secondary infertility and exhibiting azoospermia before treatment, the proposed approach yielded successful outcomes, as indicated by hormonal profile changes over six months. Importantly, these improvements were achieved without complications. Additionally, our in-silico analysis identified potential binding interactions between the protein content of BM-MSC-derived exosomes and receptors integral to spermatogenesis., Conclusion: Autotransplantation of BM-MSCs into the testicular network using microTESE in NOA patients led to the regeneration of seminiferous tubules and the regulation of hormonal profiles governing spermatogenesis. Our findings support the safety and effectiveness of autologous BM-MSCs as a promising treatment modality for NOA, with a particular focus on the achieved outcomes in patients with secondary infertility (registration number: IRCT20190519043634N1).

Leishmaniasis is a disease of poverty that imposes a devastating medical, social, and economic burden on over 1 billion people nationwide. To date, no in-depth study to analyze the major global challenges and needs assessment has been carried out. This investigation aimed to explore a comprehensive narrative review of leishmaniasis's main challenges and initially highlight obstacles that might impede the implementation of control measures. Also, we propose a specific list of priorities for needs assessment. The presence of socioeconomic factors, multiple clinical and epidemiological forms, various Leishmania species, the complexity of the life cycle, the absence of effective drugs and vaccines, and the lack of efficient vector and reservoir control make this organism unique and sophisticated in playing a tangled role to react tricky with its surrounding environments, despite extensive efforts and implementation of all-inclusive former control measures. These facts indicate that the previous strategic plans, financial support, and basic infrastructures connected to leishmaniasis surveillance are still insufficient. Strengthening the leishmaniasis framework in a context of accelerated programmatic action and intensification of cross-cutting activities along with other neglected tropical diseases (NTDs) is confidently expected to result in greater effectiveness, cost-benefit, and fruitful management. Sensitive diagnostics, effective therapeutics, and efficacious vaccines are vital to accelerating advancement toward elimination, and reducing morbidity/mortality and program costs. Collective actions devoted by all sectors and policy-makers can hopefully overcome technical and operational barriers to guarantee that effective and coordinated implementation plans are sustained to meet the road map for NTDs 2021- 2030 goals., (© 2024. The Author(s).)

Leishmaniasis is a complex disease. Any change in weather conditions affects the humans' social and agricultural expansion and, consequently, the parasite's life cycle in terms of ecology, biodiversity, social stigma, and exclusion. This population-based prospective longitudinal investigation was conducted between 1991 and 2021 in a well-defined CL (cutaneous leishmaniasis) focus in Bam County, southeastern Iran. A robust health clinic and health surveillance system were responsible for the ongoing systematic documentation, detection, identification, and management of CL cases. The exponential smoothing method via the state space model was used in the univariate time series. The TTR, smooth, and forecast packages were used in R software. Landsat satellite images from 1991, 2001, 2011, and 2021 were employed in the physical development. During this period, the temperature increased while the rainfall and humidity decreased. The findings showed a downward trend in the standardized drought index. Also, the results showed that climate warming and ecological changes profoundly affected the area's agricultural patterns and topographical features. Furthermore, the last three decades witnessed an elimination trend for zoonotic CL (ZCL) and the predominance of anthroponotic CL (ACL). The present findings showed that the critical factors in the predominance of ACL and elimination of ZCL were rising temperature, drought, migration, unplanned urbanization, earthquake, and agrarian reform. The wall-enclosed palm tree gardens excluded the primary ZCL reservoir host. They controlled the disease while providing suitable conditions for the emergence/re-emergence of ACL in the newly established settlements and the unplanned ecozone. Therefore, robust health infrastructures, sustained financial support, and evidence-based research studies are crucial to facilitating the necessary surveillance, monitoring, and evaluation to control and eliminate the disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The objective was to investigate the embryo morphokinitics using a time-lapse monitoring (TLM) system and assessment of clinical outcomes following intracytoplasmic sperm injection (ICSI) with zona pellucida (ZP)-bound sperm selection and conventional methods. A total of 371 metaphase II (MII) oocytes from 50 ICSI cycles were studied. Sibling oocytes were randomly divided into control ( n = 199) and ZP-bound group ( n = 172). All resulting zygotes were cultured and monitored in the TLM system up to Day 3 after ICSI. Fertilization rate, early embryo development, and clinical outcomes were evaluated. No significant differences were found in fertilization rate, time-lapse qualitative and quantitative measures, pronuclear fading time (PNF) t2, t3, t4, t5, t6, and t7 (times of cleavage to 2, 3, 4, 5, 6, and 7 cells), respectively. However, the t8 (time of cleavage to eight cells) and cc3 (duration of third cell cycle) revealed a significant difference between control and ZP-bound groups ( p < .05). A significant difference between the two groups ( p < .05) in the rates of Grade A embryos (according to Basile algorithm), chemical pregnancy, clinical pregnancy, and implantation was observed. Sperm selection using biological materials, such as ZP, improved both embryo quality and pregnancy outcomes, despite not affecting the early embryo development and morphokinetic parameters up to t8. This prospective randomized sibling oocyte trial was registered in October 2020 to January 2022 (IRCT20200705048021N1)., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Xeno-free generation of human embryonic stem cells (hESCs) is important to prevent potential animal contaminations in culture for advanced cell-based therapeutic applications. Xeno-free production of hESCs is the first step for manufacturing clinical-grade hESC lines., Objective: To produce new hESC lines in xeno-free condition., Materials and Methods: This lab resources report was conducted at Stem Cell Biology Research Center, Yazd, Iran from 2019-2022. 4 new hESC lines from 11 (10 fresh and 1 frozen) donated surplus discarded human embryos were established. In this study, we report the xeno-free derivation of new Yazd hESC lines (Yazd4-7), without using immunosurgery, by culturing intact zona-free blastocysts obtained from discarded embryos onto the YhFF#8 cells as a feeder layer in a microdrop culture system. The pluripotency gene expression profile of the cell lines was assessed by reverse transcription polymerase chain reaction and the expression of specific surface markers was detected using immunofluorescent staining. In vitro differentiation was induced using embryoid body formation and gene expression profile of 3 germ layers and germ cells. Reverse transcriptase polymerase chain reaction was investigated to prove their pluripotent capacity., Results: In sum, we have been able to generate 4 new hESC lines (Yazd4-7) from 11 discarded embryos in xeno-free culture conditions using a micro drop culture system and YhFF#8 as a human source feeder layer., Conclusion: The outcome of this work can be the foundation for the future allogeneic cell-based therapeutic application using clinical grade good manufacturing practice-derived hESC derivatives., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2023 Hajizadeh-Tafti et al.)

Based on the modification of carbon paste electrode with NiCo 2 O 4 nanoplates and 1-hexyl-3-methylimidazolium tetrafluoroborate, a new electrochemical sensing platform for the sensing of favipiravir (a drug with potential therapeutic efficacy in treating COVID-19 patients) in the presence of acetaminophen was prepared. For determining the electrochemical behavior of favipiravir, cyclic voltammetry, differential pulse voltammetry, and chronoamperometry have been utilized. When compared to the unmodified carbon paste electrode, the results of the cyclic voltammetry showed that the proposed NiCo 2 O 4 nanoplates/1-hexyl-3-methylimidazolium tetrafluoroborate/carbon paste electrode had excellent catalytic activity for the oxidation of the favipiravir in phosphate buffer solution (pH = 7.0). This was due to the synergistic influence of 1-hexyl-3-methylimidazolium tetrafluoroborate (ionic liquid) and NiCo 2 O 4 nanoplates. In the optimized conditions of favipiravir measurement, NiCo 2 O 4 nanoplates/1-hexyl-3-methylimidazolium tetrafluoroborate/carbon paste electrode had several benefits, such as a wide dynamic linear between 0.004 and 115.0 µM, a high sensitivity of 0.1672 µA/µM, and a small limit of detection of 1.0 nM. Furthermore, the NiCo 2 O 4 nanoplates/1-hexyl-3-methylimidazolium tetrafluoroborate/carbon paste electrode sensor presented a good capability to investigate the favipiravir and acetaminophen levels in real samples with satisfactory recoveries.

Objective: Some reports have indicated that conditioned medium from growing mouse embryonic stem cells (ESCs) provides a supportive condition for small follicles growing, oocyte maturation, and following embryo growth. The aim of this study is assessing in vitro maturation (IVM) and consequent in vitro fertilization (IVF) outcome of immature mouse oocytes using human embryonic stem cells conditioned medium (HESCM)., Materials and Methods: In this experimental study, 240 germinal vesicle (GV) oocytes were took from NMRI female mice, aged 4-6 weeks, 48 hours before injection of 5 IU pregnant mare serum gonadotropin (PMSG). 120 GV oocytes without cumulus cells were cultured in each of the groups. 120 GV were cultured in HESCM as test groups and also 120 GV cultured in human embryonic stem cells medium (HESM) as control groups. After evaluating the metaphase II (MII) oocyte maturation rate at 8, 16 and 24 hours, the MII oocytes subsequently were fertilized in vitro and the two-cell embryo development rate was recorded at days 1, 2, and 3. Statistical analysis was performed by using the generalized estimating equations (GEE) method that calculated their rate ratio., Results: Our data indicated there are significant differences between the maturation rates in HESCM and HESM (P=0.004), also the two-cell embryo development was significant between two culture media (P=0.00)., Conclusion: Similar to some other studies, the secretome of the HESCM showed a significant impact on the IVM outcomes in mice.

An ultrasensitive and selective voltammetric sensor with an ultratrace-level detection limit is introduced for ketoconazole (KTC) determination in real samples using a modified carbon paste electrode with a sheaf-like Ce-BTC MOF nanostructure and ionic liquid. The as-synthesized nanostructure was characterized by several techniques, including energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and field emission scanning electron microscopy (FE-SEM). The electrocatalytic performance of the developed electrode was observed by cyclic voltammetry (CV), differential pulse voltammetry (DPV), linear sweep voltammetry (LSV), and chronoamperometry. The limit of detection (LOD) of the developed sensor for KTC is 0.04 μM, and the response was found to be in the dynamic concentration range of 0.1-110.0 μM in a phosphate buffer solution. The proposed electrode exhibits acceptable electrocatalytic activity for KTC oxidation with a high sensitivity of 0.1342 μA·μM -1 . The ability of the fabricated sensor to monitor KTC in real aqueous samples is demonstrated using standard addition data.

Direct neuronal reprogramming of somatic cells into induced neurons (iNs) has been recently established as a promising approach to generating neuron cells. Previous studies have reported that the biophysical cues of the in vitro microenvironment are potent modulators in the cell fate decision; thus, the present study explores the effects of a customized pattern (named colloidal self-assembled patterns, cSAPs) on iN generation from human fibroblasts using small molecules. The result revealed that the cSAP, composed of binary particles in a hexagonal-close-packed (hcp) geometry, is capable of improving neuronal reprogramming efficiency and steering the ratio of the iN subtypes. Cells exhibited distinct cell morphology, upregulated cell adhesion markers (i.e., SDC1 and ITGAV), enriched signaling pathways (i.e., Hippo and Wnt), and chromatin remodeling on the cSAP compared to those on the control substrates. The result also showed that the iN subtype specification on cSAP was surface-dependent; therefore, the defined physicochemical cue from each cSAP is exclusive. Our findings show that direct cell reprogramming can be manipulated through specific biophysical cues on the artificial matrix, which is significant in cell transdifferentiation and lineage conversion.

Polycystic ovary syndrome (PCOS) is a multifactorial metabolic and most common endocrine disorder that its prevalence, depending on different methods of evaluating PCOS traits, varies from 4% to 21%. Chronic low-grade inflammation and irregular apoptosis of granulosa cells play a crucial role in the pathogenesis of PCOS infertility. Mesenchymal stem cells (MSCs)-derived exosomes and extracellular vesicles (EVs) are lipid bilayer complexes that act as a means of intercellular transferring of proteins, lipids, DNA and different types of RNAs. It seems that this nanoparticles have therapeutic effects on the PCOS ovary such as regulating immunity response, anti-inflammatory (local and systemic) and suppress of granulosa cells (GCs) apoptosis. Although there are few studies demonstrating the effects of exosomes on PCOS and their exact mechanisms is still unknown, in the present study we reviewed the available studies of the functions of MSC-derived exosome, EVs and secretome on apoptosis of granulosa cells and inflammation in the ovary. Therefore, the novel cell-free therapeutic approaches for PCOS were suggested in this study., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Izadi, Rezvani, Aliabadi, Karimi and Aflatoonian.)

Background: Fibroblasts from different parts of the human body have been used in cell biology, drug discovery and cell therapy studies. One of the most available sources of human fibroblasts is neonatal foreskin. Not only do these cells have wound-healing applications, but they are also the most popular source for pluripotent stem cell biotechnology. Moreover, several studies have indicated that different sources of fibroblasts display similar features to mesenchymal stem cells., Objective: Generation and establishment of new human foreskin fibroblast cell lines called Yazd human foreskin fibroblasts (YhFFs)., Materials and Methods: In this lab resources study, the production of 3 YhFF cell lines (YhFF#8, YhFF#17, and YhFF#18) is reported. Their biological features were characterized using immunofluorescence, polymerase chain reaction, and flow-cytometry for mesenchymal markers such as fibronectin, vimentin, CD44, CD73, CD90, CD105, and hematopoietic markers CD34 and CD45., Results: The YhFF cell lines were passaged more than 40 times and their normal karyotype was checked using G-binding. Similarly to previous reports, the flow cytometry analysis revealed that the YhFF cell lines displayed mesenchymal stromal cell characteristics., Conclusion: This study will contribute to the development of clinical-grade cell-based products such as micro-vesicles and exosomes for future therapeutic applications in regenerative medicine., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2022 Hajizadeh-Tafti et al.)

Negligible data are available following major social activities and environmental changes on leishmaniasis. Therefore, how interactions between these events influence cutaneous leishmaniasis (CL) risk is not well-known. This longitudinal study was undertaken to explore the impact of interventions conducted between 1971 and 2020 in Bam county, which has had the highest disease burden in Iran. Only confirmed CL cases during this period were taken into account. Data were analyzed by SPSS 22 using the X2 test to assess the significance of the difference between proportions. Moreover, we used interrupted time series (ITS) to assess the impact of three environmental events during this period. Overall, 40,164 cases of CL occurred in the past five decades. Multiple complex factors were among the leading causes that synergistically induced the emergence/re-emergence of CL outbreaks in Bam. The main factors attributed negatively to CL control were cessation of malaria spraying activity, expansion of the city spaces, and a massive earthquake creating new breeding potentials for the vectors. The highest impact on CL incidence during these years was related to the earthquake [coefficient = 17.8 (95% CI: 11.3, 22.7); p-value < 0.001]. Many factors can contribute to CL outbreaks in endemic foci. They also can cause new foci in new areas. Since humans are the single reservoir for CL in this area, early detection and effective management significantly contribute to controlling CL to reduce the disease burden. However, essential evidence gaps remain, and new tools are crucial before the disease can ultimately be controlled. Nevertheless, sustained funding and more trained task forces are essential to strengthen surveillance and case management and monitor the interventions' impact., Competing Interests: The authors have declared that no competing interests exist.

Neisseria gonorrhoeae and Chlamydia trachomatis are the most common causes of bacterial sexually transmitted diseases (STDs) with complications in women, including pelvic inflammatory disease (PID), ectopic pregnancy, and infertility. The main concern with these infections is that 70% of infected women are asymptomatic and these infections ascend to the upper female reproductive tract (FRT). Primary infection in epithelial cells creates a cascade of events that leads to secretion of pro-inflammatory cytokines that stimulate innate immunity. Production of various cytokines is damaging to mucosal barriers, and tissue destruction leads to ciliated epithelial destruction that is associated with tubal scarring and ultimately provides the conditions for infertility. Mesenchymal stem cells (MSCs) are known as tissue specific stem cells with limited self-renewal capacity and the ability to repair damaged tissues in a variety of pathological conditions due to their multipotential differentiation capacity. Moreover, MSCs secrete exosomes that contain bioactive factors such as proteins, lipids, chemokines, enzymes, cytokines, and immunomodulatory factors which have therapeutic properties to enhance recovery activity and modulate immune responses. Experimental studies have shown that local and systemic treatment of MSC-derived exosomes (MSC-Exos) suppresses the destructive immune response due to the delivery of immunomodulatory proteins. Interestingly, some recent data have indicated that MSC-Exos display strong antimicrobial effects, by the secretion of antimicrobial peptides and proteins (AMPs), and increase bacterial clearance by enhancing the phagocytic activity of host immune cells. Considering MSC-Exos can secrete different bioactive factors that can modulate the immune system and prevent infection, exosome therapy is considered as a new therapeutic method in the treatment of inflammatory and microbial diseases. Here we intend to review the possible application of MSC-Exos in female reproductive system bacterial diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zohrabi, Dehghan Marvast, Izadi, Mousavi and Aflatoonian.)

Some microbial sexually transmitted infections (STIs) have adverse effects on the reproductive tract, sperm function, and male fertility. Given that STIs are often asymptomatic and cause major complications such as urogenital inflammation, fibrosis, and scarring, optimal treatments should be performed to prevent the noxious effect of STIs on male fertility. Among STIs, Chlamydia trachomatis is the most common asymptomatic preventable bacterial STI. C. trachomatis can affect both sperm and the male reproductive tract. Recently, mesenchymal stem cells (MSCs) derived exosomes have been considered as a new therapeutic medicine due to their immunomodulatory, anti-inflammatory, anti-oxidant, and regenerative effects without consequences through the stem cell transplantation based therapies. Inflammation of the genital tract and sperm dysfunction are the consequences of the microbial infections, especially Chlamydia trachomatis . Exosome therapy as a noninvasive approach has shown promising results on the ability to regenerate the damaged sperm and treating asthenozoospermia. Recent experimental methods may be helpful in the novel treatments of male infertility. Thus, it is demonstrated that exosomes play an important role in preventing the consequences of infection, and thereby preventing inflammation, reducing cell damage, inhibiting fibrogenesis, and reducing scar formation. This review aimed to overview the studies about the potential therapeutic roles of MSCs-derived exosomes on sperm abnormalities and male infertility caused by STIs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Izadi, Dehghan Marvast, Rezvani, Zohrabi, Aliabadi, Mousavi and Aflatoonian.)

Zona pellucida (ZP)-bound spermatozoa have normal morphology and motility and can enhance the ICSI outcomes. Selection of zona pellucida-bound spermatozoa is recently considered to find functional spermatozoa for ICSI. This study reviewed the efficacy of ZP-bound sperm selection on the ICSI outcomes includes fertilisation rate, embryo quality, embryo transfer rate and clinical pregnancy rate. The databases searched include PubMed, Scopus and Cochrane databases up to January 2019. All research reports with full text and in English language that addressing the relation between ZP-sperm selection and ICSI outcomes were included. Fifty studies were suitable after screening of the 845 identified articles. After exclusions, five of these studies were included. Meta-analytic pooling of data indicated no association between the ICSI outcomes and ZP-bound sperm selection except a marginal effect on implantation rate. Eliminating one study indicated that ZP-bound sperm selection technique improves embryo quality, implantation rate and clinical pregnancy rate. This study revealed that ZP-bound sperm selection produces only a slight improvement in implantation rate. However, further studies with a large number of couples must be done to clarify the potential beneficial effect of ZP-bound spermatozoa on ICSI outcomes., (© 2021 Wiley-VCH GmbH.)

Background: Human embryonic stem cell-mesenchymal stem/stromal cell (hESCs-MSCs) open a new insight into future cell therapy applications, due to their unique characteristics, including immunomodulatory features, proliferation, and differentiation., Methods: Herein, hESCs-MSCs were characterized by immunofluorescence technique with CD105 and FIBRONECTIN as markers and FIBRONECTIN, VIMENTIN, CD10, CD105, and CD14 genes using reverse transcription-polymerase chain reaction technique. Fluorescence-activated cell sorting was performed for CD44, CD73, CD90, and CD105 markers. Moreover, these fibroblast-like cells, due to multipotent characteristics, differentiated to the osteoblast., Results: MSCs were derived from diploid and triploid hESC lines using sequential three dimensional and two dimensional cultures and characterized with the specific markers. Immunofluorescence showed the expression of FIBRONECTIN and CD105 in hESCs-MSCs. Flow cytometry data indicated no significant difference in the expression of MSC markers after 6 and 13 passages. Interestingly, gene expression profiles revealed slight differences between MSCs from diploid and triploid hESCs. hESCs-MSCs displayed osteogenic differentiation capacity, which was confirmed by Alizarin red staining., Cobnclusion: Our findings reveal that both diploid and triploid hESC lines are capable of forming MSCs; however, there are some differences in their gene expression profiles. Generation of MSCs from hESCs, as a non-invasive procedure in large scale, will lend itself for the future cell-based therapeutic applications.

Background: Epidemics of cutaneous leishmaniasis (CL) are occurring more frequently and spreading faster and farther than before in many areas of the world. The present study aimed to assess a long-lasting emerging epidemic (2005-2019) of 5532 cases with anthroponotic CL (ACL) in peri-urban areas of Kerman city in southeastern Iran., Methods: This descriptive-analytical study was carried out for 15 years in Kerman province, southeastern Iran. The data were passively obtained through the health surveillance system and the Kerman Leishmaniasis Research Center. Every subject was diagnosed using direct smear microscopy. The representative causative agent was further examined by ITS1-PCR, PCR-RFLP, 7SL RNA gene sequencing and phylogenetic analyses. For each subject, a case report form designating demographic and clinical data was recorded., Results: A different pattern of ACL incidence was found in peri-urban areas compared to that in the city of Kerman. The incidence rate of ACL cases has significantly increased (P < 0.001) from 2005 to 2016 in new settlements with a gradual decline after that. The overall average risk of contracting the disease was 7.6 times higher in peri-urban areas compared to Kerman city, an old endemic focus. All isolates consisting of six variants were confirmed to be Leishmania tropica. The overall pattern of the ACL infection indicates that the etiological agent of ACL is propagated and transmitted by the bite of female Phlebotomus sergenti sandflies from person to person from dissimilar clones as reflected by the complexity of the migrants' backgrounds in the province., Conclusions: The movement of populations and establishment of new settlements in peri-urban areas close to endemic areas are major risk factors for and are directly linked to CL. The underlying factors of this emerging ACL epidemic caused by L. tropica were disasters and droughts, among others. A robust commitment to a multilateral approach is crucial to make improvements in this area. This will require decisive coordinated actions through all governmental factions and non-governmental organizations. Furthermore, active and passive case detection strategies, early diagnosis, and effective treatment could help control the disease.

Background: To increase the results of infertility treatment, many efforts have been made to improve the treatment methods. As assisted reproductive technology is mainly using cell culture methods, one of the approaches to improve this technology is conditioned medium from different sources. It is desirable to apply in vitro maturation (IVM) and use oocytes from normal cycles instead of stimulating ovulation., Objective: To investigate the effect of human cumulus cell condition medium (hCCCM) on the IVM of immature mouse oocytes and morphology., Materials and Methods: In this experimental study, 240 germinal vesile oocytes were collected from four-six wk-old mice after 48 hr of 5IU pregnant mare serum gonadotropin (PMSG) injection and cultured in hCCCM (test group, n = 120) and DMEM + 20% FBS (control group, n = 120). The IVM rates and changes in perivitelline space (PVS) and shape were investigated at 8, 16, and 24 hr following the culture. The mature (MII) oocytes were subjected to in vitro fertilization (IVF) and the fertilization rate was assessed in three days., Results: A significant difference was observed between the maturation rates in the hCCCM and control groups (24.16% vs 0%; p = 0.001), as well as morphologic changes between the two groups (p = 0.04, p = 0.05). The development rate for MII oocytes attained from IVM in the hCCCM group was 27.58% (2-cell) and 6.89% (4-cell). Data displayed that hCCCM is an effective medium for oocytes maturation compared to the control medium., Conclusion: hCCCM supports oocyte in vitro growth and maturation. Moreover, hCCCM changes the oocyte shape and size of perivitelline space., Competing Interests: The authors declare no conflicts of interests in with regard to the present study., (Copyright © 2020 Adib et al.)

In this paper, graphene (Gr)/Co 3 O 4 nanocomposite was synthesized and utilized for the development of a novel electrochemical sensor to detect tramadol. Tramadol determination was examined by linear sweep voltammetry, differential pulse voltammetry, cyclic voltammetry, and chronoamperometry on Gr/Co 3 O 4 nanocomposite-modified screen-printed electrode (Gr/Co 3 O 4 /SPE) in phosphate-buffered saline (PBS). Under the optimized condition, the detection limit of tramadol is 0.03 μM (S/N = 3) in the linear ranges of 0.1-500.0 μM. Furthermore, Gr/Co 3 O 4 /SPE was satisfactorily utilized to detect tramadol in tramadol tablet and urine specimens., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Aflatoonian, Tajik, Aflatoonian, Beitollahi, Zhang, Le, Cha, Jang, Shokouhimehr and Peng.)

Background: Human endometrium with consecutive regeneration capability undergoes monthly hormonal changes for probable implantation, which confirms the presence of the cells in the basalis layer known as stem cell., Objective: Previously, we reported the isolation and culture of the mesenchymal-like cells from human endometrium. In this study, we evaluated the biological and stemness characteristics of these cells., Materials and Methods: The characterization of Yazd human endometrial-derived mesenchymal stem/stromal cells (YhEnMSCs) was assessed using immunofluorescence (IF) staining for CD105, VIMENTIN, and FIBRONECTIN as markers and RT-PCR for CD166, CD10, CD105, VIMENTIN, FIBRONECTIN, MHCI , CD14 , and MHCII genes. Flow cytometry (FACS) was performed for CD44, CD73, CD90, and CD105 markers. Moreover, the differentiation capacity of the YhEnMSCs to the osteoblast and adipocytes was confirmed by Alizarin Red and Oil Red staining., Results: YhEnMSCs expressed CD105, VIMENTIN, FIBRONECTIN, CD44, CD73, and CD90 markers and CD166, CD10, CD105, VIMENTIN, FIBRONECTIN, and MHCI, but, did not express CD14 , MHCII ., Conclusion: Our data confirm previous reports by other groups indicating the application of endometrial cells as an available source of MSCs with self-renewal and differentiation capacity. Accordingly, YhEnMSCs can be used as a suitable source for cell-based therapies., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Akyash et al.)

Object: Immunosuppressive and immunomodulatory activity of mesenchymal stem cells derived from different sources, such as placental membranes, umbilical cord, and amniotic fluid has been proved. The heterogeneous nature of human amniocytes have been confirmed due to different clonal subpopulations found in amniotic fluid. The aim of this study was to investigate a 17-gene panel of immunomodulatory markers in two clonal subpopulations of CD90 + amniocytes, divided based on morphology into epithelioid and fibroblastoid cells., Method: Semi-quantitative RT-PCR was used to study the expression of the chosen genes. Flow cytometry analysis confirmed the non-hematopoietic mesenchymal origin of isolated cells, based on lacking the hematopoietic marker of CD31, and the presence of mesenchymal marker of CD90 (both on more than 90% of cells)., Results: Our results showed that besides growth characteristics, the two cell groups were different in expressional profile, so that, fibroblastoid clones displayed higher level of immunosuppression genes as well as mesenchymal surface marker of CD90 compared to epithelioid ones. Our previous investigation on these clones showed that epithelioid cells have a more potential to express the pluripotency genes. It seems there is an inverse relationship between genes associated with immunosuppression and pluripotency., Conclusion: Although many reports have been published regarding the immunosuppressive properties of fetal stem cells, but few studies to date have explained whether the stemness state of human amniocytes may affect their immunosuppressive potential. Further study on amniocytes, which often has self-renewal ability and high immunomodulatory potential, can help to understand the details of this relationship., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Testicular cell conditioned medium (TCCM) has been shown to induce female germ cell development In Vitro from embryonic stem cells (ESCs). Testicular cells (TCs) secrete a variety of growth factors such as growth differentiation factor-9 (GDF-9), bone morphogenetic protein 4 (BMP-4), stem cell factor (SCF), leukemia inhibitory factor (LIF), and other, that could improve oocyte maturation. Here we have investigated the effect of human TCCM (hTCCM) on in vitro maturation (IVM) and morphology of mouse oocytes., Materials and Methods: In this experimental study, 360 germinal vesicle (GV) oocytes were obtained from NMRI mice, aged 4-6 weeks that had received 5 IU pregnant mare's serum gonadotropin (PMSG) 48 hours before. GV oocytes were subjected to IVM. 120 GV oocytes were cultured in each medium; hTCCM as the test group, DMEM + 20%FBS as the control group and Ham's F10 + HFF medium as the sham group. The rates of the IVM and perivitelline space (PVS) changes were recorded at 8, 16 and 24 hours after culture. The metaphase II (MII) oocytes were subjected for in vitro fertilization (IVF) and the fertilization rate was evaluated after 1, 2, and 3 days., Results: There was a significant difference between the maturation rates in hTCCM (31.67% MII) and the control [0% MII, P<0.05, (7.5% MI, 52.5% deg. and 40%GV)] groups but there was not a significant difference between the maturation rates in hTCCM and the sham group (53.33% MII, P>0.05). IVF success rate for MII oocytes obtained from IVM in the hTCCM group was 28.94% (n=11). Our data showed that hTCCM is an effective medium for GV oocyte growth and maturation compared to the control medium., Conclusion: Our findings show that TCCM supports oocyte IVM in mice and affect oocyte morphology., Competing Interests: The authors declare no conflicts of interest., (Copyright© by Royan Institute. All rights reserved.)

Azoospermia is one of the challenging disorders affecting couples who are afflicted with infertility. Human testisderived cells (hTCs) are suitable candidates for the initiation of in-vitro spermatogenesis for these types of patients. The current study aimed to assess the proliferation of hTCs through the cell culture on the three-dimensional (3D) porous scaffolds. Cells harvested from the testicular sperm extraction (TESE) samples of the azoospermic patients were cultured on the 3D porous scaffolds containing human serum albumin (HSA)/tri calcium phosphate nanoparticles (TCP NPs) for two weeks. The proliferation/viability of the cells was assessed using the MTT assay, along with H and E histological staining method. The MTT assay showed that hTCs could stay alive on this scaffold with 50 and 66.66% viability after 7 and 14 days, respectively. Such viability was not significantly different when compared with cells grown on monolayer flask culture (P>0.05). Therefore, 3D HSA/TCP NPs scaffolds could be used for the reconstitution of the artificial human somatic testicular niche for future applications in regenerative medicine for male infertility., Competing Interests: The authors declare no conflicts of interest., (Copyright© by Royan Institute. All rights reserved.)

Background and Objectives: The new beta-coronavirus, which caused Severe Acute Respiratory Coronavirus-2 Syndrome (SARS-CoV-2), a major respiratory outbreak in Wuhan, China in December 2019, is now prevalent in many countries around the world. Identifying PCR-based viruses is a well-known and relatively stable protocol. Unfortunately, the high mutation rates may lead to widespread changes in viral nucleic acid sequences, and so using specific primers for PCR can be recommended. In this study, we evaluated the power of a conventional RT-PCR to detect SARS-CoV-2 RNA among the five set primer sets., Materials and Methods: The five genomic regions of the Coronavirus SARS-2 virus including Nucleocapsids (N), Envelope (E), RNA depended RNA Polymerase (RdRp), ORF1ab and Spike (S) were selected for primer designing. A conventional RT-PCR was performed to compare sensitivity, specificity and other analytical characteristics of primers designed against two Real Time PCR commercial kits., Results: The result of the comparative analysis showed that the ORF1ab, N and RdRp primers had a sensitivity, specificity and positive predictive value higher than other primers. A significant difference in the analytical sensitivity between the studied primer sets in RT-PCR kits was observed., Conclusion: In this study, the ORF1ab, Nucleocapsid and RdRp regions have the best primers for identifying the SARS-CoV-2 RNA between different genes that have been suggested., (Copyright© 2020 Iranian Neuroscience Society.)

The present investigation examines a sensitive electrochemical technique to detect desipramine through Fe 3 O 4 /CuO nanoparticles (NPs). Fe 3 O 4 /CuO NPs were synthesized via a coprecipitation procedure, and the products were characterized via energy disperse spectroscopy, X-ray diffraction, transmission electron microscopy, scanning electron microscopy, and vibrating sample magnetometer. The voltage-current curve and differential pulse voltammetry examinations of Fe 3 O 4 /CuO-modified screen-printed electrode (Fe 3 O 4 /CuO/SPE) were followed by the determination of electro-catalytic activities toward desipramine oxidation in a phosphate buffer solution (pH = 7.0). In addition, the value of diffusion coefficient ( D = 3.0 × 10 -6 cm 2 s -1 ) for desipramine was calculated. Then, based on the optimum conditions, it was observed that the currents of the oxidation peak were linearly proportionate to the concentration of desipramine in the broad range between 0.08 and 400.0 μM and LOD of 0.03 μM (S/N = 3). Finally, our new sensor was successfully utilized to detect desipramine in the real samples, with reasonable recovery in the range of 97.2% to 102.7%., Competing Interests: All the authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)