The association of CYP11A1 gene polymorphisms with the polycystic ovary syndrome patients.

OBJECTIVE: The objective of this study was to investigate the allele frequencies of polymorphisms in genes CYP11A1 rs4886595 and CYP11A1 rs4887139 that are responsible for the steroidogenesis mechanism in polycystic ovary syndrome patients and control females. METHODS: Samples were obtained from the Department of Obstetrics and Gynecology in the Near East University Hospital from September 2019 to December 2019. Only the nonobese patients between the ages of 18-40 years were included in this study following informed consent. Obese patients and patients more than 40 years of age were excluded from the study. Nonobese women and normal ovulation were included in the control group. DNA was isolated from blood samples. Real-time polymerase chain reaction (PCR) was used to analyze single nucleotide polymorphisms (SNPs) in various genes linked to polycystic ovary syndrome. The studies were carried out using the samples obtained from 120 women, of whom 55 were nonobese and had normal ovulation, and 65 were polycystic ovary syndrome patients. The allelic frequencies of SNPs in genes linked to polycystic ovary syndrome were calculated using real-time PCR outcomes. RESULTS: The variation of the CYP11A1 rs4887139 G>A did not show any significance, while the variation of CYP11A1 rs4886595 C>A showed significant differences between the patient and the control groups (p=0.01), respectively. CONCLUSION: Future research ought to focus on elucidating the susceptible causes of polycystic ovary syndrome with a wide range of SNPs and more sample size. The genome-wide association studies in polycystic ovary syndrome patients of different origin will be important to identify candidate genes as well as proteins that are implied in polycystic ovary syndrome risk.

Exploring gellan gum-based hydrogels for regenerating human embryonic stem cells in age-related macular degeneration therapy: A literature review.

Age-related macular degeneration (AMD) is a progressive ocular disease marked by the deterioration of retinal photoreceptor cells, leading to central vision decline, predominantly affecting the elderly population worldwide. Current treatment modalities, such as anti-VEGF agents, laser therapy, and photodynamic therapy, aim to manage the condition, with emerging strategies like stem cell replacement therapy showing promise. However, challenges like immune rejection and cell survival hinder the efficacy of stem cell interventions. Regenerative medicine faces obstacles in maximizing stem cell potential due to limitations in mimicking the dynamic cues of the extracellular matrix (ECM) crucial for guiding stem cell behaviour. Innovative biomaterials like gellan gum hydrogels offer tailored microenvironments conducive to enhancing stem cell culture efficacy and tissue regeneration. Gellan gum-based hydrogels, renowned for biocompatibility and customizable mechanical properties, provide crucial support for cell viability, differentiation, and controlled release of therapeutic factors, making them an ideal platform for culturing human embryonic stem cells (hESCs). These hydrogels mimic native tissue mechanics, promoting optimal hESC differentiation while minimizing immune responses and facilitating localized delivery. This review explores the potential of Gellan Gum-Based Hydrogels in regenerative AMD therapy, emphasizing their role in enhancing hESC regeneration and addressing current status, treatment limitations, and future directions.

The association of CYP11A1 gene polymorphisms with the polycystic ovary syndrome patients

SUMMARY OBJECTIVE: The objective of this study was to investigate the allele frequencies of polymorphisms in genes CYP11A1 rs4886595 and CYP11A1 rs4887139 that are responsible for the steroidogenesis mechanism in polycystic ovary syndrome patients and control females. METHODS: Samples were obtained from the Department of Obstetrics and Gynecology in the Near East University Hospital from September 2019 to December 2019. Only the nonobese patients between the ages of 18-40 years were included in this study following informed consent. Obese patients and patients more than 40 years of age were excluded from the study. Nonobese women and normal ovulation were included in the control group. DNA was isolated from blood samples. Real-time polymerase chain reaction (PCR) was used to analyze single nucleotide polymorphisms (SNPs) in various genes linked to polycystic ovary syndrome. The studies were carried out using the samples obtained from 120 women, of whom 55 were nonobese and had normal ovulation, and 65 were polycystic ovary syndrome patients. The allelic frequencies of SNPs in genes linked to polycystic ovary syndrome were calculated using real-time PCR outcomes. RESULTS: The variation of the CYP11A1 rs4887139 G>A did not show any significance, while the variation of CYP11A1 rs4886595 C>A showed significant differences between the patient and the control groups (p=0.01), respectively. CONCLUSION: Future research ought to focus on elucidating the susceptible causes of polycystic ovary syndrome with a wide range of SNPs and more sample size. The genome-wide association studies in polycystic ovary syndrome patients of different origin will be important to identify candidate genes as well as proteins that are implied in polycystic ovary syndrome risk.

Mesenchymal Stem Cells Applications in Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder that advances gradually and primarily impacts the hippocampus region of the brain. It is defined by a deterioration in cognitive function as well as an observable loss of memory retention. One of the major characteristics of AD is the impairment of neural generation, resulting in the depletion of neurons and synaptic connections within the nervous system. It is unfortunate to say that, at present, no definitive cure is available for AD, and no medication is effective in halting the progression of neurodegeneration associated with it. Nevertheless, it is crucial to highlight that progress has been achieved in addressing the troubling symptoms of AD. The Food and Drug Administration has granted approval for two categories of medications designed to alleviate these symptoms. The scientific community has been inspired by these advancements to investigate alternative therapeutic options, with an emphasis on stem cell therapy in particular. The main focus of this review will be on the potential for the use of a variety of mesenchymal stem cells as a treatment for AD.

Multi-region machine learning-based novel ensemble approaches for predicting COVID-19 pandemic in Africa.

Coronavirus disease 2019 (COVID-19) has produced a global pandemic, which has devastating effects on health, economy and social interactions. Despite the less contraction and spread of COVID-19 in Africa compared to some other continents in the world, Africa remains amongst the most vulnerable regions due to less technology and unequipped or poor health system. Recent happenings showed that COVID-19 may stay for years owing to the discoveries of new variants (such as Omicron) and new wave of infections in several countries. Therefore, accurate prediction of new cases is vital to make informed decisions and in evaluating the measures that should be implemented. Studies on COVID-19 prediction are limited in Africa despite the risks and dangers that the virus possessed. Hence, this study was performed to predict daily COVID-19 cases in 10 African countries spread across the north, south, east, west and central Africa considering countries with few and large number of daily COVID-19 cases. Machine learning (ML) models due to their nonlinearity and accurate prediction capabilities were employed for this purpose, including artificial neural network (ANN), adaptive neuro-fuzzy inference system (ANFIS), support vector machine (SVM) and conventional multiple linear regression (MLR) models. As any other natural process, the COVID-19 pandemic may contain both linear and nonlinear aspects. In such circumstances, neither nonlinear (ML) nor linear (MLR) models could be sufficient; hence, combining both ML and MLR models may produce better accuracy. Consequently, to improve the prediction efficiency of the ML models, novel ensemble approaches including ANN-E and SVM-E were employed. The advantage of using ensemble approaches is that they provide collective benefits of all the standalone models, thereby reducing their weaknesses and enhancing their prediction capabilities. The obtained results showed that ANFIS led to better prediction performance with MAD = 0.0106, MSE = 0.0003, RMSE = 0.0185 and R2 = 0.9059 in the validation step. The results of the proposed ensemble approaches demonstrated very high improvements in predicting the COVID-19 pandemic in Africa with MAD = 0.0073, MSE = 0.0002, RMSE = 0.0155 and R2 = 0.9616. The ANN-E improved the standalone models performance in the validation step up to 10%, 14%, 42%, 6%, 83%, 11%, 7%, 5%, 7% and 31% for Morocco, Sudan, Namibia, South Africa, Uganda, Rwanda, Nigeria, Senegal, Gabon and Cameroon, respectively. This study results offer a solid foundation in the application of ensemble approaches for predicting COVID-19 pandemic across all regions and countries in the world.

Periconceptional Mediterranean diet during pregnancy on children's health.

During pregnancy, rapid and subtle physiological changes are observed from conception to birth. Nutrition and other lifestyle factors before and during pregnancy have been shown in the literature to influence the health of both mother and child. A healthy and varied diet during pregnancy can provide adequate energy and nutrients for both the mother and the growing fetus. Current research focuses on the periconceptional phase, which includes the early processes of gametogenesis, embryogenesis and placentation. A variety of abnormalities and pregnancy-related problems occur during this period, including congenital defects, fetal loss, miscarriage and preterm birth. A varied and balanced diet during periconception is important to maintain fetal development and growth. To date, numerous studies have been conducted to investigate the effects of consuming different nutrients, foods or food groups during pregnancy on the health of mother and child. For example, the Mediterranean diet is considered as a balanced, nutrient-rich diet due to the low consumption of meat products and fatty foods and the high consumption of vegetables, cheese, olive oil, fish, shellfish and little meat. While many studies have been conducted in the literature to investigate the effects of a Mediterranean diet during pregnancy on fetal health, the results have been inconclusive. The aim of this article is to review the current literature on the Mediterranean diet during pregnancy.

Investigation of allele frequencies of polymorphic variants in genes that are related to polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome is a hormonal disorder that normally affects women of reproductive age in the range of 18-44 years. This study aimed to investigate the allelic frequencies of two polymorphisms, IRS rs18012781 and INSR rs1799817, which are suspected to be involved in polycystic ovary syndrome. METHODS: The samples were obtained from the patients admitted to the Near East University Hospital, Department of Gynecology and Obstetrics. The samples were divided into two groups: control and polycystic ovary syndrome groups. Blood samples were collected from 55 women in the control group and 65 samples from the patient group. DNA from whole blood was obtained. The allelic frequencies of single-nucleotide polymorphisms were determined using real-time PCR. Results were presented as the heterozygous and homozygous state of the single-nucleotide polymorphisms. RESULTS: There were no significant differences in the allelic frequencies of the single-nucleotide polymorphisms between the patient and control groups. Further statistical analysis investigating the INSR Tm using the Mann-Whitney U test value revealed that there was no difference in the homozygous and heterozygous state of INSR rs1799817. The result of this study showed that there was no statistically significant difference between the allelic frequencies of IRS1 rs1801278 and INSR rs1799817 between the patient and control groups. CONCLUSION: These single-nucleotide polymorphisms do not seem to modify the risk of polycystic ovary syndrome, and they cannot be used as a marker in clinical circumstances to evaluate the possible occurrence of polycystic ovary syndrome.

Investigation of allele frequencies of polymorphic variants in genes that are related to polycystic ovary syndrome

SUMMARY OBJECTIVE: Polycystic ovary syndrome is a hormonal disorder that normally affects women of reproductive age in the range of 18-44 years. This study aimed to investigate the allelic frequencies of two polymorphisms, IRS rs18012781 and INSR rs1799817, which are suspected to be involved in polycystic ovary syndrome. METHODS: The samples were obtained from the patients admitted to the Near East University Hospital, Department of Gynecology and Obstetrics. The samples were divided into two groups: control and polycystic ovary syndrome groups. Blood samples were collected from 55 women in the control group and 65 samples from the patient group. DNA from whole blood was obtained. The allelic frequencies of single-nucleotide polymorphisms were determined using real-time PCR. Results were presented as the heterozygous and homozygous state of the single-nucleotide polymorphisms. RESULTS: There were no significant differences in the allelic frequencies of the single-nucleotide polymorphisms between the patient and control groups. Further statistical analysis investigating the INSR Tm using the Mann-Whitney U test value revealed that there was no difference in the homozygous and heterozygous state of INSR rs1799817. The result of this study showed that there was no statistically significant difference between the allelic frequencies of IRS1 rs1801278 and INSR rs1799817 between the patient and control groups. CONCLUSION: These single-nucleotide polymorphisms do not seem to modify the risk of polycystic ovary syndrome, and they cannot be used as a marker in clinical circumstances to evaluate the possible occurrence of polycystic ovary syndrome.

Detection of SARS-CoV-2 N501Y mutation among SARS-CoV-2 variants of concern circulating in Northern Cyprus.

Aim: SARS-CoV-2 variants of concern (VOCs) carry signature mutations particularly in the spike protein. Most VOCs lineages that carry N501Y substitution have been reported to evade viral diagnostic tests and have impact on vaccine effectiveness. Therefore, monitoring the circulating variants represents a major requirement for a public health response worldwide. We aimed to investigate the prevalence of N501Y bearing SARS-CoV-2 samples in Northern Cyprus. Materials & methods: Reverse transcription quantitative PCR technique was used to identify N501Y mutation from 658 samples. Results: Our results indicate that the proportion of N501Y-bearing lineages increased significantly from January through May 2021 (45.2-75.5%) in the region. Conclusion: These results indicate that VOCs are dominant lineages in the country and highlight an alarming situation which require strict governmental measures to minimize COVID-19 morbidity and mortality.

The expression profile of WNT/ß-catanin signalling genes in human oocytes obtained from polycystic ovarian syndrome (PCOS) patients.

Polycystic ovarian syndrome (PCOS) is a chronic hormonal turmoil that is demonstrated in 2.2-27% of women of pre-menopausal age. This disease is a complex multigenic disorder that results from the interaction between excess androgen expression, genetic susceptibility and environmental influences. PCOS is associated with 40% of female infertility and endometrial cancer. The WNT/ß-catenin signalling transduction pathway regulates aspects of cell proliferation, migration and cell fate determination in the tissue along with early embryonic development and controls the proper activation of the female reproductive system, along with regulating hormonal activity in ovarian granulosa cells. In the current study, we investigated the expression profiles of WNT/ß-catenin signalling pathway genes (AXIN2, FZD4, TCF4, WNT3, WNT4, WNT5A, WNT7A, WNT1, APC, GSK3B and ß-catenin) in a total of 13 oocyte samples. Seven of these samples were from polycystic women and six were from healthy women. The results of this study displayed the absence of expression of AXIN2, FZD4, TCF4, WNT5A, WNT3, WNT4 and WNT7A genes in ovaries from women with PCOS and from healthy women. While APC and ß-catenin expression levels were similar in the oocytes of both patients and controls, conversely, WNT1 and GSK3ß genes both showed elevated expression in the oocytes of patients with PCOS, therefore suggesting an association between aberrant expression of WNT1 and GSK3ß and the pathogenesis of PCOS. The observations of the current study could be helpful to provide evidence regarding the pathogenesis of PCOS and its treatment.

How does sperm apoptosis affect the outcome of intrauterine insemination and intracytoplasmic sperm injection?

Up to 20% of male infertility is caused by abnormal DNA organization of the sperm and anomalies of the sperm apoptosis. The aim of this study was to investigate the sperm DNA apoptosis and viability in patients undergoing intrauterine insemination (IUI) and intracytoplasmic sperm injection (ICSI). In the second part of the analysis, sperm DNA apoptosis and viability were investigated in patients with oligozoospermia and normospermia respectively. A total of 45 IUI and 38 ICSI patients were included in this study. Annexin V analysis was performed to investigate the sperm viability, and TUNEL assay was used to evaluate the sperm DNA apoptosis. Further investigations using 12 oligozoospermia and 11 control samples for sperm viability and sperm DNA apoptosis at different incubation periods and temperatures were performed. The results of this study showed a negative correlation between the sperm DNA apoptosis in IUI patients, but no relationship was observed for the ICSI patients. The second part of this study showed that incubation of semen samples at 37°C for 3 h has detrimental effects on the sperm DNA integrity. In conclusion, the incubation of semen at high temperatures affects the sperm quality. The results of this study showed that these tests can be beneficial for the infertile couples to achieve pregnancy.

Cytotoxic Effects of Verbascoside on MCF-7 and MDA-MB-231

Objectives: Verbascoside, also known as acteoside/kusaginin, has attracted a great attention due to its pharmacological features. In this study, we aimed to determine the cytotoxic effects of pure verbascoside isolated from Phlomis nissolii L. plant in both MCF-7 and MDA-MB-231 cell lines in vitro. Materials and Methods: MCF-7 and MDA-MB 231 cells were treated with verbascoside (100, 48, 25, 10, 1, 0.5, and 0.1 µM) for 24, 48, and 72 hours. Cytotoxic effect of verbascoside in MCF-7 and MDA-MB-231 cells was assessed using TEBU-BIO cell counting kit 8. Results and Conclusion: IC50 values for 24, 48, and 72 h verbascoside exposure of MCF-7 cells were determined as 0.127, 0.2174, and 0.2828 µM, respectively. R2 values were calculated as 0.9630, 0.8789 and 0.8752, respectively. Two-Way ANOVA multiple comparison test results showed that 100 µM verbascoside has the highest cytotoxic effect on MCF-7 breast cancer (BC) cells after 72 h of exposure. IC50 values for 24, 48 and 72 h verbascoside exposure of MDA-MB 231 cells were determined as 0.1597, 0.2584 and 0.2563 µM, respectively and R2 values were calculated as 0.8438, 0.5107 and 0.9203, respectively. Two-Way ANOVA multiple comparisons test results showed that 100 µM verbascoside has the highest cytotoxic effect on MDA-MB 231 BC cells after 24, 48 and 72 h of exposure.

Psychomotor Delay in a Child with FGFR3 G380R Pathogenic Mutation Causing Achondroplasia.

Achondroplasia (ACH) is a hereditary disorder of dwarfism that is caused by the aberrant proliferation and differentiation of chondrocyte growth plates. The common findings of macrocephaly and facial anomalies accompany dwarfism in these patients. Fibroblast growth factor receptor 3 ( FGFR3 ) gene mutations are common causes of achondroplasia. The current study presents a case of 2-year-old male child patient presenting with phenotypic characteristics of ACH. The interesting finding of the case is the presence of psychomotor delay that is not very common in these patients. Clinical exome sequencing analyzing 4.813 disease causing genes revealed a de novo c.1138G > A mutation within the FGFR3 gene. In conclusion, the mutation confirms the clinical diagnosis of ACH, and it seems to be causing the psychomotor delay in this patient.

Association of Assisted Reproductive Technology Treatments with Imprinting Disorders.

Assisted reproductive technology (ART) is a broad field in infertility that encompasses different types of treatments. These revolutionary treatment methods aimed to aid infertile or subfertile couples. Treatment was expanded exponentially, as 1 to 3% of the births worldwide takes place with ART procedures. However, treatment is not flawless. Gametes and embryos are exposed to different chemicals and stress through treatment, which leads to disturbance in proper embryo development and results in prenatal and congenital anomalies. When compared with in-vivo development of gametes and preimplantation embryos in mice, in-vitro conditions during ART treatments have been suggested to disturb the gene expression levels, especially imprinted genes. Therefore, ART has been suggested to be associated with increased incidences of different imprinting disorders such as Beckwith-Wiedemann syndrome, Angelman syndrome, and Silver-Russell syndrome, as proved by different case reports and studies. This literature review aims to explain the association of imprinting disorders with this revolutionary treatment procedure.

Should fertile women quit drinking alcohol to produce better quality oocytes?

Alcohol consumption has long been shown to affect both fetal health and pregnancy. In this study, antral follicle count, maturation level of oocytes including morphological assessment and number of metaphase I (MI), metaphase II (MII) and germinal vesicle (GV) stage oocytes obtained from young women (age < 30 years old) with or without alcohol consumption were investigated. In total, 20 healthy women who were social drinkers and 36 healthy women who do not consume alcohol were involved in this study. Women in both study and control groups were undergoing controlled ovarian stimulation. The antral follicle count and the number and quality of the oocytes retrieved were evaluated and recorded. In total, 635 antral follicles, 1098 follicles and 1014 oocytes with 820 MII, 72 MI and 78 GV stage oocytes were collected from the social drinkers. In the control group, 628 antral follicles, 1136 follicles and 1085 oocytes with 838 MII, 93 MI and 102 GV stage oocytes were evaluated. The results of this study showed that the antral follicle count was very similar in both groups. The number of oocytes and MII stage oocytes was slightly higher in the control group, although it was not a significant difference. This study showed that although the consumption of alcohol may have adverse effects post-implantation, it may not have a solid effect during oogenesis in young women. The results of this study are especially important in clinical settings as some women who are social drinkers undergo in vitro fertilization treatments.

Does cigarette smoking really have a clinical effect on folliculogenesis and oocyte maturation?

Infertility is the most common issue in the field of reproductive medicine. Many factors affect fertility status, including life-style choices such as cigarette smoking or alcohol use. The aim of this study was to investigate the effects of cigarette smoking on oocyte quality as well the quantity in young fertile women. In total, 56 young fertile women who were undergoing oocyte donation programmes were included in this study. The effects of cigarette smoking on antral follicle count, number of follicles and oocytes retrieved and morphology were assessed by an expert embryologist. The results of this study showed that cigarette smoking did not have a significant effect on the follicle count or the number of oocytes retrieved from young and fertile women. However, a significant difference was observed in the morphological assessment. In conclusion, although cigarette smoking does not seem to affect oocyte development, it had an effect on cytoplasmic anomalies and therefore may lower pregnancy chance. Therefore, it is crucial to give proper counselling to patients who are trying to become pregnant both naturally and by in vitro fertilization.

In Vitro MCF-7 Cells Apoptosis Analysis of Carboplatin Loaded Silk Fibroin Particles.

Breast cancer ranks as the fifth leading cause of death worldwide. Chemotherapy is commonly used directly or as neo-adjuvant therapy for the management of breast cancer with its attendant adverse effects, underscoring the need to develop biocompatible bioactive compounds for pharmacological applications. The aim of this study is to encapsulate carboplatin (CP) with silk fibroin protein (SF) by using an ionic gelation method as a drug carrier system and assess the apoptotic effect on MCF-7 breast cancer cells during in vitro studies. The characterization of silk fibroin encapsulated carboplatin (SFCP) microparticles was analyzed by FTIR spectrophotometer, SEM, Mastersizer, and biodegradation methods. The encapsulation efficiency and release profile of SFCP microparticles were analyzed by an indirect UV-Vis spectrophotometric method. An apoptotic screening of MCF-7 cells was carried out with 10-200 µg/mL CP loaded SFCP, which were cultured for 24, 48, and 72 h. Data were analyzed using the Student's t test and analysis of variance. FTIR and drug release studies confirmed an interaction of silk fibroin with the carboplatin moiety. SFCP showed successful encapsulation of the carboplatin moiety. Apoptotic screening showed a dose dependent increase in absorbance, indicating significant cell death (p < 0.05). Thus, the direct apoptotic effect of SFCP microparticles on MCF-7 was confirmed.

Inconsistency of Karyotyping and Array Comparative Genomic Hybridization (aCGH) in a Mosaic Turner Syndrome Case.

Purpose Turner syndrome is a sex chromosomal aberration where majority of the patients have 45,X karyotype, while several patients are mosaic involving 45,X/46,XX; 46,X,i(Xq); and other variants. Cytogenetic analysis, karyotyping, is considered to be the "gold standard" to detect numerical and structural chromosomal abnormalities. In the recent years, alternative approaches, such as array comparative genomic hybridization (aCGH), have been widely used in genetic analysis to detect numerical abnormalities as well as unbalanced structural rearrangements. In this study, we report the use of karyotyping as well as aCGH in detecting a possible Turner syndrome variant. Methods An apparent 16-year-old female was clinically diagnosed as Turner syndrome with premature ovarian failure and short stature. The genetic diagnosis was performed for the patient and the parents by karyotyping analysis. aCGH was also performed for the patient. Main Findings Cytogenetic analysis of the patient was performed showing variant Turner syndrome (46,X,i(X)(q10)[26]/46,X,del(X)(q11.2)[11]/45,X[8]/46,XX[5]). The patient's aCGH result revealed that she has a deletion of 57,252kb of Xp22.33-p11.21 region; arr[GRCh37] Xp22.33-p11.21 (310,932-57,563-078)X1. Both aCGH and fluorescence in situ hybridization (FISH) results suggested that short stature Homeobox-containing ( SHOX ) gene, which is located on Xp22.33, was deleted, though FISH result indicated that this was in a mosaic pattern. Conclusion In the recent years, aCGH has become the preferred method in detecting numerical abnormalities and unbalanced chromosomal rearrangements. However, its use is hindered by its failure of detecting mosaicism, especially low-level partial mosaicism. Therefore, although the resolution of the aCGH is higher, the cytogenetic investigation is still the first in line to detect mosaicism.