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The Journal of Toxicological Sciences 2024To examine the effects of decreased food consumption on toxicological parameters in juvenile rats, rats on postnatal day 21 were fed 40%, 50% (only four weeks), and 60%...
To examine the effects of decreased food consumption on toxicological parameters in juvenile rats, rats on postnatal day 21 were fed 40%, 50% (only four weeks), and 60% less food, compared to that of controls for four or eight weeks, and clinical observations, measurement of body and organ weights, morphological differentiation analysis, clinical pathology, and macroscopic and microscopic examinations were conducted. The body weight decreased depending on the degree of food restriction (FR). Cleavage of the balano-preputial skinfold was delayed, and cell debris in the epididymal lumen was noted as a related finding after four-week FR. Vaginal opening was also delayed, and some histopathological findings, such as absence of corpus luteum in the ovary, mucinous degeneration in the vagina, and immature uterus, were noted after eight-week FR. Erythrocyte count increased after four-week FR, but slightly decreased in males only after eight-week FR, and decreased leukocyte and/or reticulocyte counts, accompanied by related histopathological findings were noted after four- and eight-week FR. In blood chemistry, the levels of total protein including globulin, glucose, triglyceride, and calcium decreased, and sodium and chloride increased after four- and eight-week FR. Increases in activities of aspartate transaminase and lactate dehydrogenase and total bilirubin levels were noted after four-week FR, which were attenuated after eight-week FR. The effects of FR seemed to be more remarkable after four weeks. In drug safety evaluation, findings caused by malnutrition should be considered in juvenile toxicity studies when decreased food consumption is observed.
Topics: Animals; Male; Female; Body Weight; Organ Size; Rats; Caloric Restriction; Time Factors; Food Deprivation; Rats, Sprague-Dawley; Rats, Wistar
PubMed: 38945843
DOI: 10.2131/jts.49.321 -
New Biotechnology Jun 2024Chinese hamster ovary (CHO) cells represent the most preferential host cell system for therapeutic monoclonal antibody (mAb) production. Enhancing mAb production in CHO...
Chinese hamster ovary (CHO) cells represent the most preferential host cell system for therapeutic monoclonal antibody (mAb) production. Enhancing mAb production in CHO cells can be achieved by adding chemical compounds that regulate the cell cycle and cell survival pathways. This study investigated the impact of ectoine supplementation on mAb production in CHO cells. The results showed that adding ectoine at a concentration of 100mM on the 3 day of cultivation improved mAb production by improving cell viability and extending the culture duration. RNA sequencing analysis revealed differentially expressed genes associated with cell cycle regulation, cell proliferation, and cellular homeostasis, in particular promotion of cell cycle arrest, which was then confirmed by flow cytometry analysis. Ectoine-treated CHO cells exhibited an increase in the number of cells in the G0/G1 phase. In addition, the cell diameter was also increased. These findings support the hypothesis that ectoine enhances mAb production in CHO cells through mechanisms involving cell cycle arrest and cellular homeostasis. Overall, this study highlights the potential of ectoine as a promising supplementation strategy to enhance mAb production not only in CHO cells but also in other cell lines.
PubMed: 38945523
DOI: 10.1016/j.nbt.2024.06.006 -
Journal of Ethnopharmacology Jun 2024Zuogui Pill (ZGP) is a traditional herbal formula of Chinese Medicine with a long history of use in alleviating ovarian aging.
Zuogui Pills Alleviate Cyclophosphamide-induced Ovarian Aging by Reducing Oxidative Stress and Restoring the Stemness of Oogonial Stem Cells through the Nrf2/HO-1 Signaling Pathway.
ETHNOPHARMACOLOGICAL RELEVANCE
Zuogui Pill (ZGP) is a traditional herbal formula of Chinese Medicine with a long history of use in alleviating ovarian aging.
AIM OF THE STUDY
To examine the impact of ZGP on oxidative stress and the stemness of oogonial stem cells (OSCs) in cyclophosphamide (CTX)-induced ovarian aging, as well as its molecular mechanisms involving the nuclear factor erythroid 2-related factor 2 (Nrf2, NFE2L2)/heme oxygenase-1 (HO-1, Hmox1) pathway.
MATERIALS AND METHODS
Female Sprague-Dawley (SD) rats were randomly divided into seven groups: control, model (CTX), estradiol valerate (EV, 0.103 mg/kg), ZGP-L (low dose Zuogui Pill, 1.851 g/kg), ZGP-H (high dose Zuogui Pill, 3.702 g/kg), ML385 (30 mg/kg), and ML385+ZGP-L. After CTX modeling, the EV, ZGP-L, ZGP-H, and ML385+ZGP-L groups were treated by gavage for 8 weeks, while the ML385 and ML385+ZGP-L groups were administered the Nrf2 antagonist ML385 twice a week. OSCs were isolated after modeling and then treated with drug serum containing 10% ZGP or 10 μM ML385. The general conditions of the rats, including body weight, ovarian weight/body weight ratio, and estrous cycle, were observed. Ovarian ultrastructure, follicle and corpus luteum counts were assessed via hematoxylin and eosin (H&E) staining. Serum hormone levels were measured using enzyme-linked immunosorbent assay (ELISA). Nrf2/HO-1 pathway, stem cell, germ cell, and cell cycle biomarkers were analyzed by qPCR and Western blot. Cell viability was assessed by cell counting kit-8 (CCK-8) assay. Oxidative stress biomarkers were evaluated using flow cytometry and assay kits. Immunofluorescence was employed to detect and locate OSCs in the ovary, quantify the average fluorescence intensity, and identify OSCs.
RESULTS
After ZGP treatment, rats with CTX-induced ovarian aging exhibited improved general condition, increased body weight, higher total ovarian weight to body weight ratio, and a restoration of the estrous cycle similar to the control group. Serum levels of estradiol (E) and follicle stimulating hormone (FSH), two sex hormones, were also improved. Ovarian ultrastructure and follicle count at all stages showed improvement. Moreover, the viability and proliferation capacity of OSCs were enhanced following ZGP intervention. The Nrf2/HO-1 pathway was found to be down-regulated in CTX-induced aging ovarian OSCs. However, ZGP reversed this effect by activating the expression of Nrf2, HO-1, and NAD(P)H oxidoreductase 1 (NQO1), increasing the activity of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), and reducing the accumulation of malonaldehyde (MDA) and reactive oxygen species (ROS), thus restoring resistance to oxidative stress. Additionally, ZGP improved the cell cycle of OSCs, up-regulated the expression of Cyclin D1 and Cyclin E1, restored cell stemness, promoted proliferation, enhanced the expression of cell stemness markers octamer-binding transcription factor 4 (Oct4) and mouse VASA homolog (MVH), and down-regulated the expression of P21, thereby inhibiting apoptosis. The therapeutic effects of ZGP against oxidative stress and restoration of cell stemness were attenuated following inhibition of the Nrf2 signaling pathway using ML385.
CONCLUSIONS
ZGP protected against CTX-induced ovarian aging by restoring normal ovarian function, alleviating oxidative stress in aging OSCs, promoting OSCs proliferation, and restoring their stemness in rats, possibly through regulating the Nrf2/HO-1 pathway.
PubMed: 38945466
DOI: 10.1016/j.jep.2024.118505 -
American Journal of Preventive Medicine Jun 2024Gynecological diseases ranked second among new cases of noncommunicable diseases in women of reproductive age in 1990 and 2019 globally. The aim of this study was to...
INTRODUCTION
Gynecological diseases ranked second among new cases of noncommunicable diseases in women of reproductive age in 1990 and 2019 globally. The aim of this study was to estimate the disease burden of gynecological diseases and describe their trends in women of all ages from 1990 to 2019.
METHODS
Using data from the Global Burden of Diseases, Injuries and Risk Factors Study (GBD 2019), we examined the incidence, disability-adjusted life years (DALYs) and deaths from gynecological diseases by age in 204 countries and territories worldwide from 1990 to 2019. Analyses were conducted in 2022.
RESULTS
Globally, the age-standardized incidence rate (ASIR) and age-standardized DALY rate (ASDR) of gynecological diseases decreased by -0.176 % and -0.245 %, respectively from 1990 to 2019. Low socioeconomic development index (SDI) countries had the highest ASIR and ASDR in 2019. The age-specific incidence rate of gynecological diseases in women aged 15-29 years increased from 1990 to 2019, and the 20-24-year age group increased the greatest by 0.21%. Polycystic ovary syndrome and other types of benign disorders contributed to the major increase.
CONCLUSIONS
Although the disease burden of gynecological diseases decreased slightly between 1990 and 2019 globally, it remained highest in low SDI countries. The disease burden in 20-24-year age group exhibited the fastest growth, with polycystic ovary syndrome and other types of benign disorders playing a significant role. Urgent and effective measures should be taken to target different age groups, types of gynecological disease and regions with high disease burdens.
PubMed: 38945179
DOI: 10.1016/j.amepre.2024.06.022 -
European Journal of Obstetrics,... Jun 2024Isntroduction. Polycystic ovary syndrome (PCOS) is a multifaceted endocrine-gynecological condition affecting a substantial number of women during their reproductive... (Review)
Review
Comparative efficacy of metformin combined with cabergoline versus metformin alone in patients with PCOS and hyperprolactinemia: A systematic review and meta-analysis of randomized controlled trials.
UNLABELLED
Isntroduction. Polycystic ovary syndrome (PCOS) is a multifaceted endocrine-gynecological condition affecting a substantial number of women during their reproductive years. Metformin (MET) has been shown to improve ovarian function in PCOS-related conditions, while cabergoline is recognized for its powerful and sustained ability to reduce prolactin levels. This study investigates the potential impact of combining cabergoline with metformin while comparing it with metformin alone in the treatment of PCOS alongside hyperprolactinemia.
METHOD
To gather data, we searched PubMed, Google Scholar, ScienceDirect, and Cochrane Central. Eligible studies were randomized controlled trials involving patients with PCOS and hyperprolactinemia. Outcome measures included changes in the levels of prolactin, testosterone, DHEAS, BMI and menstrual irregularities. RevMan version 5.4 was used to analyze outcomes.
RESULT
This study incorporated three Randomized Controlled Trials (RCTs) involving 405 participants in total. Patients receiving a combination of metformin and cabergoline experienced significant reductions in prolactin and testosterone levels (p= <0.0001 and p=<0.0001, respectively). Conversely, alterations in DHEAS levels and BMI did not reach statistical significance (p = 0.19 and p = 0.71, respectively). Notably, women solely prescribed metformin exhibited significantly higher rates of menstrual irregularities compared to those receiving both metformin and cabergoline (p=<0.0001).
CONCLUSION
Our analysis underscores the synergistic effect achieved by pairing metformin and cabergoline in patients with PCOS and hyperprolactinemia. However, we encountered only a restricted number of studies meeting our criteria. It is imperative to consistently assess the combined effects of metformin and cabergoline to gain deeper insights into their effectiveness in addressing PCOS and hyperprolactinemia.
PubMed: 38945085
DOI: 10.1016/j.ejogrb.2024.06.037 -
Cancer Genomics & Proteomics 2024Clear cell carcinoma is a prevalent histological type of ovarian cancer in East Asia, particularly in Japan, known for its resistance to chemotherapeutic agents and poor...
BACKGROUND/AIM
Clear cell carcinoma is a prevalent histological type of ovarian cancer in East Asia, particularly in Japan, known for its resistance to chemotherapeutic agents and poor prognosis. ARID1A gene mutations, commonly found in ovarian clear cell carcinoma (OCCC), contribute to its pathogenesis. Recent data revealed that the ARID1A mutation is related to better outcomes of cancer immunotherapy. Thus, this study aimed to investigate the immunotherapy treatment susceptibility of OCCC bearing ARID1A mutations.
MATERIALS AND METHODS
Expression of ARID1A was analyzed using western blotting in ovarian cancer cell lines. OCCC cell lines JHOC-9 and RMG-V were engineered to overexpress NY-ESO-1, HLA-A*02:01, and ARID1A. Sensitivity to chemotherapy and T cell receptor-transduced T (TCR-T) cells specific for NY-ESO-1 was assessed in ARID1A-restored cells compared to ARID1A-deficient wild-type cells.
RESULTS
JHOC-9 cells and RMG-V cells showed no expression of ARID1A protein. Overexpression of ARID1A in JHOC-9 and RMG-V cells did not impact sensitivity to gemcitabine. While ARID1A overexpression decreased sensitivity to cisplatin in RMG-V cells, it had no such effect in JHOC-9 cells. ARID1A overexpression reduced the reactivity of NY-ESO-1-specific TCR-T cells, as observed by the IFNγ ESLIPOT assay.
CONCLUSION
Cancer immunotherapy is an effective approach to target ARID1A-deficient clear cell carcinoma of the ovary.
Topics: Humans; Female; Ovarian Neoplasms; Transcription Factors; DNA-Binding Proteins; Adenocarcinoma, Clear Cell; T-Lymphocytes, Cytotoxic; Cell Line, Tumor; Antigens, Neoplasm; HLA-A2 Antigen; Membrane Proteins
PubMed: 38944423
DOI: 10.21873/cgp.20460 -
Fertility and Sterility Jun 2024As part of the 2023 International Evidence-based PCOS Guideline, this meta-analysis investigated the inclusion of Anti-Müllerian Hormone (AMH) in the diagnostic... (Review)
Review
IMPORTANCE
As part of the 2023 International Evidence-based PCOS Guideline, this meta-analysis investigated the inclusion of Anti-Müllerian Hormone (AMH) in the diagnostic criteria for Polycystic Ovary Syndrome (PCOS).
OBJECTIVE
A systematic review and three meta-analyses were performed to answer the following three questions: 1) Is AMH effective to diagnose PCOS in adult women? 2) Is AMH effective to diagnose PCOS in adolescents? 3) Is AMH effective to diagnose PCOM?
DATA SOURCES
Searches were conducted in six databases until July 31st 2023.
STUDY SELECTION AND SYNTHESIS
Eligible studies were those conducted in humans, published in English and reported sensitivity, specificity, and/or area under the curve. Extracted data included study population, age, body mass index (BMI), AMH assay, cut off value of AMH, sensitivity, specificity, and area under the curve (AUC). Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. Random effects model were used to test diagnostic accuracy.
MAIN OUTCOMES
Pooled sensitivity and specificity to use AMH for PCOS diagnosis in adults and adolescents, and for detecting PCOM in adults.
RESULTS
Eighty-two studies were included. The adult AMH-PCOS meta-analyses (n = 68) showed a pooled sensitivity and specificity of 0.79 [95% CI 0.76; 0.82; I = 86%] and 0.87 [95% CI 0.84; 0.89; I = 91%]. The adolescent AMH-PCOS meta-analysis (n = 11) showed a pooled sensitivity and specificity of 0.66 [95% CI 0.58; 0.73; I = 74%] and 0.78 [95% CI 0.71; 0.83; I = 45%]. The adult AMH-PCOM meta-analysis (n = 7) showed a pooled sensitivity and specificity of 0.79 [95% CI 0.72; 0.85; I = 94%] and 0.87 [95% CI 0.78; 0.93; I = 94%].
CONCLUSION AND RELEVANCE
This study investigated the most profound change in the 2023 International Evidence-based PCOS Guideline, which now recommends AMH for defining PCOM in adults, in accordance with the diagnostic algorithm. AMH alone is insufficient for PCOS diagnosis and is nonspecific for PCOM in adolescents. Multiple factors influence AMH levels and caused heterogeneity and limitations in this study. Consequently, no international cut off value could be recommended, emphasizing the need for research on more individualized cut offs.
PubMed: 38944177
DOI: 10.1016/j.fertnstert.2024.05.163 -
Journal of Diabetes Investigation Jun 2024The recent adverse reactions associated with semaglutide have led the Food and Drug Administration (FDA) to issue a "black box warning", and it is necessary to analyze...
AIM/INTRODUCTION
The recent adverse reactions associated with semaglutide have led the Food and Drug Administration (FDA) to issue a "black box warning", and it is necessary to analyze all reports of adverse reactions to improve the safety of its clinical use.
MATERIALS AND METHODS
Statistical analyses and signal mining were performed by obtaining the adverse event reports related to semaglutide in the FAERS database from the first quarter of 2018 to the fourth quarter of 2023. We used disproportionality and Bayesian analysis to examine clinical and demographic attributes, trends reported quarterly, and contrasts between two distinct indications (obesity and type 2 diabetes).
RESULTS
We found 10 unexpected adverse signals related to "pancreatic cancer", "intestinal obstruction", "cholecystitis", and "polycystic ovary" and both the two different indications had the same serious adverse reaction events occurring.
CONCLUSIONS
This study identified many unexpected signals of serious adverse reactions, suggesting the importance of continuous post-marketing surveillance of semaglutide to understand its potential risks.
PubMed: 38943656
DOI: 10.1111/jdi.14229 -
Biology of Reproduction Jun 2024Previous in vitro studies have suggested that SLIT ligands could play roles in regulating ovarian granulosa cell proliferation and gene expression, as well as...
Previous in vitro studies have suggested that SLIT ligands could play roles in regulating ovarian granulosa cell proliferation and gene expression, as well as luteolysis. However, no in vivo study of Slit gene function has been conducted to date. Here we investigated the potential role of Slit1 in ovarian biology using a Slit1-null mouse model. Female Slit1-null mice were found to produce larger litters than their wild-type counterparts due to increased ovulation rates. Increased ovarian weights in Slit1-null animals were found to be due to the presence of greater numbers of healthy antral follicles with similar numbers of atretic ones, suggesting both an increased rate of follicle recruitment and a decreased rate of atresia. Consistent with this, treatment of cultured granulosa cells with exogenous SLIT1 induced apoptosis in presence or absence of FSH, but had no effect on cell proliferation. Although few alterations in the mRNA levels of FSH-responsive genes were noted in granulosa cells of Slit1-null mice, LH target gene mRNA levels were greatly increased. Finally, increased phospho-AKT levels were found in granulosa cells isolated from Slit1-null mice, and SLIT1 pretreatment of cultured granulosa cells inhibited the ability of both FSH and LH to increase AKT phosphorylation, suggesting a mechanism whereby SLIT1 could antagonize gonadotropin signaling. These findings therefore represent the first evidence for a physiological role of a SLIT ligand in the ovary, and define Slit1 as a novel autocrine/paracrine regulator of follicle development.
PubMed: 38943353
DOI: 10.1093/biolre/ioae106 -
Nigerian Journal of Clinical Practice Jun 2024Unexplained infertility is defined as the absence of any pathology in the basic evaluation performed in couples who cannot achieve pregnancy after 1 year of unprotected...
BACKGROUND
Unexplained infertility is defined as the absence of any pathology in the basic evaluation performed in couples who cannot achieve pregnancy after 1 year of unprotected sexual intercourse. The results of tests examining the causes of infertility show no identifiable cause in almost 15% of couples.
AIM
The aim of this study was to investigate the effects of reactive oxygen species (ROS) on pregnancy and embryos.
METHODS
This study included 200 patients, aged between 20-44 years, with unexplained infertility, who had recurrent intrauterine inseminations failures and hence started in vitro fertilization (IVF)/intracytoplasmic sperm injection treatment. Some amounts of waste follicular fluid samples were collected by embryologists from the oocytes of these patients during the ovum pick-up procedure. Next, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) values were calculated in the biochemistry laboratory.
RESULTS
In terms of pregnancy status, both follicular TOS and OSI values were not significantly different in patients with biochemical and clinical pregnancy, whereas TAS values were significantly higher in patients with pregnancy (P < 0.05). In terms of embryo quality, no significant difference was observed in TAS, TOS, and OSI values between grade 1 and 2 embryos, whereas pregnancy rates were significantly higher in patients who received grade 1 embryo transfer (P < 0.05). However, the follicular fluid TAS levels were significantly lower in smoking patients than in those who did not smoke; TOS and OSI levels were significantly higher.
CONCLUSION
This study showed that exposure to oxidative stress might be a causative factor for infertility. In addition, ROS decreased the level of TAS by increasing OSI in the follicular fluid; thus, antioxidant supplementation might be a necessity.
Topics: Humans; Follicular Fluid; Female; Adult; Antioxidants; Pregnancy; Oxidants; Oxidative Stress; Fertilization in Vitro; Reactive Oxygen Species; Young Adult; Pregnancy Rate; Infertility, Female; Sperm Injections, Intracytoplasmic; Infertility
PubMed: 38943298
DOI: 10.4103/njcp.njcp_836_23