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Theriogenology Jun 2024Tumour necrosis factor (TNF) superfamily member 11 (TNFSF11), also known as RANKL, plays a crucial role in regulating several physiological and pathological activities....
Tumour necrosis factor (TNF) superfamily member 11 (TNFSF11), also known as RANKL, plays a crucial role in regulating several physiological and pathological activities. Additionally, it is a vital factor in bone physiology, and the sex hormone progesterone regulates the expansion of stem cells and the proliferation of mammary epithelial cells. It is essential for animal growth and reproductive physiological processes. This study aimed to evaluate the tissue-specific expression characteristics and promoter activity of the TNFSF11 gene in pigs. As a result, the study examined the presence of TNFSF11 expression in the tissues of Xiangsu pigs at 0.6 and 12 months of age. Moreover, the core promoter region of TNFSF11 was also identified by utilizing a combination of bioinformatic prediction and dual-luciferase activity tests. Finally, the effect of transcription factors on the transcriptional activity of the core promoter region was determined using site-directed mutagenesis. TNFSF11 was uniformly expressed in all tissues; however, its expression in muscles was comparatively low. The core promoter region of TNFSF11 was located in the -555 to -1 region. The prediction of the transcription start site of TNFSF11 gene-2000 ∼ + 500bp showed that there was a CpG site in 17 ∼ + 487bp. Analysis of mutations in the transcription factor binding sites revealed that mutations in the Stat5b, Myog, Trl, and EN1 binding sites had significant effects on the transcriptional activity of the TNFSF11 gene, particularly following the EN1 binding site mutation (P < 0.001). This study provides insights into both the tissue-specific expression patterns of TNFSF11 in the tissues of Xiangsu pigs and the potential regulatory effects of transcription factors on its promoter activity. These results may be helpful for future research aimed at clarifying the expression and role of the porcine TNFSF11 gene.
PubMed: 38954996
DOI: 10.1016/j.theriogenology.2024.06.018 -
Tropical Animal Health and Production Jun 2024To predict the sex of the foetus, healthy pregnant dromedary camels (n = 24) were included. Blood samples were collected for measurements of progesterone, estradiol,...
To predict the sex of the foetus, healthy pregnant dromedary camels (n = 24) were included. Blood samples were collected for measurements of progesterone, estradiol, testosterone, and cortisol as well as total proteins, albumin, glucose, creatinine, blood urea nitrogen, phosphorus, calcium, creatine kinase, alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), calcium, phosphorus, and magnesium. Statistical analysis revealed differences between pregnant camels and pregnant camels in terms of female or male foetuses depending on the actual sex of the born calf. The results revealed that testosterone and ALP concentrations were significantly (P < 0.001) greater in camels given to males than in those given to calves. There were strong positive correlations between male calf birth and testosterone and ALP concentrations (r = 0.864; P < 0.0001 and r = 0.637; P < 0.001, respectively). On the other hand, the cortisol, glucose and creatinine concentrations were significantly lower (P lower in camel calved males than in females). There were significant negative correlations between male calf birth and the cortisol, glucose and creatinine concentrations (r =-0.401; P = 0.052; r =-0.445; P = 0.029 and r =-0.400; P = 0.053, respectively). The concentrations of calcium, phosphorus, calcium/phosphorus ratio, magnesium, and albumin and the albumin/globulin ratio were not significantly different (P > 0.05) between the two groups. In conclusion, testosterone could be used as a biomarker to determine the sex of foetuses in dromedary camels.
Topics: Animals; Camelus; Female; Male; Pregnancy; Sex Determination Analysis; Hydrocortisone; Testosterone; Creatinine; Fetus; Estradiol; Gonadal Steroid Hormones
PubMed: 38951353
DOI: 10.1007/s11250-024-04053-4 -
Journal of Breast Cancer Jun 2024Oncotype DX (ODX) predicts the risk of recurrence and benefits of adding chemotherapy for patients with estrogen receptor positive (ER+)/human epidermal growth factor...
PURPOSE
Oncotype DX (ODX) predicts the risk of recurrence and benefits of adding chemotherapy for patients with estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) early-stage breast cancer. We aimed to develop a simplified scoring system using readily available clinicopathological parameters to predict a high-risk ODX recurrence score (RS) while minimizing reproducibility issues regarding Ki-67 index evaluation methods.
METHODS
We enrolled 300 patients with ER+/HER2- early breast cancer, for whom ODX RS data were available in the test set. Using the QuPath image analysis platform, we systematically evaluated the average, hotspot, and hottest spot Ki-67 scores in the test set. Logistic regression analyses were conducted to establish a predictive scoring system for high-risk ODX RS. An independent validation set comprising 117 patients over different periods was established.
RESULTS
Factors such as age ≤ 50 years, invasive ductal carcinoma tumor type, histologic grade 2 or 3, tumor necrosis, progesterone receptor negativity, and a high Roche-analyzed Ki-67 score (> 20) were associated with high-risk ODX RS. These variables were incorporated into our scoring system. The area under the curve of the scoring system was 0.8057. When applied to both the test and validation sets with a cutoff value of 3, the sensitivity of our scoring system was 92%.
CONCLUSION
We successfully developed a scoring system based on the systematic evaluation of Ki-67 scoring methods. We believe that our user-friendly predictive scoring system for high risk ODX RS could help clinicians in identifying patients who may or may require additional ODX testing.
PubMed: 38951111
DOI: 10.4048/jbc.2024.0065 -
Theriogenology Jun 2024The potential of using long in vitro culture (LIVC) of cumulus-oocyte complexes (COCs) from early antral follicles (EAFs) as an assisted reproductive technology in...
The potential of using long in vitro culture (LIVC) of cumulus-oocyte complexes (COCs) from early antral follicles (EAFs) as an assisted reproductive technology in cattle has shown promising results. This study explored the feasibility of applying this technology to sheep as seasonal breeding animals. Ovaries from sheep were collected during both the breeding and non-breeding seasons. COCs were isolated from EAFs (350-450 μm) and cultured in TCM199 medium supplemented with 0.15 μg/mL Zn sulfate, 10IU/mL FSH, 10 ng/mL estradiol, 50 ng/mL testosterone, 50 ng/mL progesterone, and 5 μM Cilostamide. After five days of LIVC, the COCs were submitted to an in vitro maturation procedure. The results indicate successful in vitro development of COCs, evidenced by a significant increase in oocyte diameter (p < 0.000) and the preservation of gap junction communication between oocyte and cumulus cells. The gradual uncoupling was accompanied by a progressive chromatin transition from the non-surrounded nucleolus (NSN) to the surrounded nucleolus (SN) (p < 0.000), coupled with a gradual decrease in global transcriptional activity and an increase in oocyte meiotic competence (p < 0.000). Maintenance of oocyte-cumulus investment architecture, viability, and metaphase II capability was significantly higher in COCs collected during the breeding season (p < 0.000), suggesting higher quality than those obtained during the non-breeding season. In conclusion, our study confirms LIVC feasibility in sheep, emphasizing increased effectiveness during the breeding season in isolating higher-quality COCs from EAFs. These findings can influence improving the LIVC system in mammals with seasonal reproduction.
PubMed: 38950486
DOI: 10.1016/j.theriogenology.2024.06.030 -
F1000Research 2023To report the ocular surface and meibomian gland changes in polycystic ovarian syndrome (PCOS) women taking hormone supplementation. Case series. Three women (27 ±...
To report the ocular surface and meibomian gland changes in polycystic ovarian syndrome (PCOS) women taking hormone supplementation. Case series. Three women (27 ± 11 years) already diagnosed with PCOS presented with dry eye symptoms (mean OSDI, 37.5) for a mean duration of 13 months and were taking hormonal supplements for a mean duration of 60 ± 11 months. The hormonal supplements included oral estrogen (n=3), oral progesterone (n=3), antiandrogen cyproterone (n=1) and isotretinoin (n=1). Ocular surface evaluation revealed mean NIBUT of 9.9 ± 1.6 seconds and mean TMH of 0.27 ± 0.05 mm, assessed non-invasively using Oculus keratograph 5M (K5M). Meibography (K5M) showed near total loss of all meibomian glands (n=8/12 eyelids) with residual ghost glands in all four eyelids of two patients, and gland shortening alone in one patient. The gland morphology did not change following intense thermal pulsation treatment or cessation of hormonal therapy. Near-total irreversible meibomian gland loss was seen in two young PCOS women taking hormonal supplements. Collaboration between ophthalmologists and gynecologists is advisable for early detection and better understanding of dry eye disease (DED) progression in these patients.
Topics: Humans; Female; Polycystic Ovary Syndrome; Adult; Meibomian Glands; Estrogens; Progesterone; Young Adult; Dry Eye Syndromes
PubMed: 38948507
DOI: 10.12688/f1000research.139229.1 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... May 2024This study aims to analyze the relationship between reproductive tract microecological changes, metabolic differences, and pregnancy outcomes at different time points in...
OBJECTIVE
This study aims to analyze the relationship between reproductive tract microecological changes, metabolic differences, and pregnancy outcomes at different time points in the frozen-thawed embryo transfer cycle while patients are undergoing hormone replacement therapy, which will be a breakthrough point for improving outcomes.
METHODS
A total of 20 women undergoing frozen-thawed single blastocyst transfer for the first time at the Reproductive Medicine Center of Fujian Maternal and Child Health Hospital between July 2022 and January 2023 were recruited for this study. Their vaginal and cervical secretions were collected for 16S rRNA sequencing and non-targeted metabolomics analysis on days 2-5 of menstruation, day 7 after estrogen replacement therapy started, the day when progesterone was added, and the day of transplantation. The subjects were divided into different groups according to their clinical pregnancy status and the sequencing results were analyzed using bioinformatics methods.
RESULTS
1) The alpha-diversity index of the vaginal and cervical microbiota was higher on days 2-5 of menstruation (<0.01), but did not differ significantly on day 7 after oral estrogen replacement therapy started, the day of progesterone administration, and the day of transplantation (≥0.1). 2) Both the pregnant group and the non-pregnant group showed a variety of microorganisms and metabolites with significant differences in the lower reproductive tract at different time points. 3) Microbial analysis at different time points showed that there were significant differences in vaginal flora, including , , , , , , , , , and in the pregnant group (<0.05). 4) Metabolite analysis at different time points showed that there were significant differences in 3-hydroxybenzoic acid, linatine, (R)-amphetamine, hydroxychloroquine, and L-altarate in the vaginal secretions of the pregnant group (<0.05), and that there were significant differences in isocitric acid, quassin, citrinin, and 12(R)-HETE in the cervical secretions (<0.05). 5) Metabolite analysis at different time points showed that, in the non-pregnant group, there were significant differences in linatine, decanoyl-L-carnitine, aspartame, sphingosine, and hydroxychloroquine in the vaginal secretions (<0.05), and the isocitric acid, quassin, ctrinin, and 12(R)-HETE in the cervical secretions (<0.05). 6) Combined microbiome and metabolomics analysis showed that certain metabolites were significantly associated with microbial communities, especially .
CONCLUSIONS
Significant differences in the microbiota genera and metabolites at different time points were found during the frozen-embryo transfer cycle of hormone replacement therapy, which may be used as potential biomarkers to predict pregnancy outcomes of embryo transfer.
Topics: Humans; Female; Pregnancy; Embryo Transfer; Pregnancy Outcome; Microbiota; Vagina; Progesterone; Adult; Cryopreservation; RNA, Ribosomal, 16S; Cervix Uteri
PubMed: 38948288
DOI: 10.12182/20240560509 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... May 2024Recurrent pregnancy loss (RPL) presents a formidable challenge for individuals undergoing fertilization-embryo transfer (IVF-ET), forming both a clinical dilemma and a...
OBJECTIVE
Recurrent pregnancy loss (RPL) presents a formidable challenge for individuals undergoing fertilization-embryo transfer (IVF-ET), forming both a clinical dilemma and a focal point for scientific inquiry. This study endeavors to investigate the intricate interplay between clinical features, such as age, body mass index (BMI), and waist-to-hip ratio (WHR), and routine laboratory parameters, including sex hormones, blood composition, liver and thyroid functions, thyroid antibodies, and coagulation indicators, in RPL patients undergoing IVF-ET. By meticulously analyzing these variables, we aim to uncover the latent risk factors predisposing individuals to RPL. Identifying potential factors such as advanced maternal age, obesity, and insulin resistance will provide clinicians with vital insights and empirical evidence to strengthen preventive strategies aimed at reducing miscarriage recurrence.
METHODS
This retrospective case-controlled study included RPL patients who underwent IVF-ET treatment at Sun Yat-sen Memorial Hospital, Sun Yat-sen University, between January 2012 and March 2021 as the case cohort, compared with women receiving assisted reproductive treatment due to male infertility as the control cohort. The fasting peripheral blood was collected 5 days before the first menstrual cycle at least 12 weeks after the last abortion. The clinical characteristics and relevant laboratory indexes of the two groups were compared. Employing both univariate and multivariate logistic regression analyses, we sought to unearth potential high-risk factors underlying RPL. Additionally, a linear trend analysis was conducted to assess the linear relationship between total testosterone (TT) levels and the number of miscarriages.
RESULTS
In contrast to the control cohort, the RPL cohort exhibited significant increases in age, BMI, and WHR (<0.05). Notably, TT levels were markedly lower in the RPL cohort (=0.022), while no significant differences were observed between the two groups concerning basal follicle-stimulating hormone, luteinizing hormone, estradiol, progesterone, prolactin levels, and anti-Müllerian hormone levels (>0.05). Moreover, fasting insulin (FINS) levels and HOMA-IR index were notably elevated in the RPL cohort relative to the control cohort (<0.001), although no significant differences were observed in fasting blood glucose levels (>0.05). Furthermore, the neutrophil (NEU) count and NEU-to-lymphocyte ratio were notably higher in the RPL cohort (<0.01). Univariate logistic regression analysis identified several factors, including age≥35 years old, BMI≥25 kg/m, WHR>0.8, FINS>10 mU/L, HOMA-IR>2.14, NEU count>6.3×10 L, and an elevated NEU/lymphocyte ratio (NLR), as significantly increasing the risk of RPL (<0.05). Although TT levels were within the normal range for both cohorts, higher TT levels were associated with a diminished RPL risk (odds ratio [OR]=0.67, 95% confidence interval [CI]: 0.510-0.890, =0.005). After adjustments for confounding factors, age≥35 years old (OR=1.91, 95% CI: 1.06-3.43), WHR>0.8 (OR=2.30, 95% CI: 1.26-4.19), and FINS>10 mU/L (OR=4.50, 95% CI: 1.30-15.56) emerged as potent risk factors for RPL (<0.05). Conversely, higher TT levels were associated with a reduced RPL risk (OR=0.59, 95% CI: 0.38-0.93, =0.023). Furthermore, the linear trend analysis unveiled a discernible linear association between TT levels and the number of miscarriages ( =0.003), indicating a declining trend in TT levels with escalating miscarriage occurrences.
CONCLUSION
In patients undergoing IVF-ET, advanced maternal age, lower TT levels, increased WHR, and elevated FINS levels emerged as potent risk factors for RPL. These findings provide clinicians with valuable insights and facilitate the identification of patients who are at high risks and the formulation of preventive strategies to reduce the recurrence of miscarriages.
Topics: Humans; Female; Fertilization in Vitro; Abortion, Habitual; Embryo Transfer; Risk Factors; Retrospective Studies; Pregnancy; Case-Control Studies; Adult; Body Mass Index; Insulin Resistance; Obesity; Maternal Age; Male
PubMed: 38948280
DOI: 10.12182/20240560102 -
MethodsX Jun 2024Chromatography combined with mass spectrometry is a gold standard technique for steroid measurement, however the type of sample preparation, the dynamic range and...
Chromatography combined with mass spectrometry is a gold standard technique for steroid measurement, however the type of sample preparation, the dynamic range and reliability of the calibration curve, the chromatographic separation and mass spectrometry settings ultimately determine the success of the method. The steroid biosynthetic pathway is conserved in higher mammals and literature demonstrates that the concentration ranges of different steroid groups are relatively comparable across species. We sought to develop a robust and reliable multi steroid targeted analysis method for blood that would have wide application across higher mammals. The method was developed following bioanalytical method validation guidelines to standards typically applied to human clinical studies, including isotopically labelled internal standards where at all possible. Here we describe the practical approach to a 96-well supported liquid extraction (SLE) method of extraction from plasma (200 µL) using an Extrahera liquid handling robot (Biotage, Sweden), including quality control samples, followed by a comprehensive separation and targeted LC-MS/MS analysis of 18 steroids in plasma (pregnenolone, progesterone, 17α-hydroxyprogesterone, 11-deoxycorticosterone, corticosterone, 11-dehydrocorticosterone, aldosterone, 11-deoxycortisol, 21-deoxycortisol, cortisol, cortisone, androstenedione, testosterone, 5α-dihydrotestosterone, dehydroepiandrosterone, estrone, 17β-estradiol and estriol). •SLE in a 96-well format of up to 74 biological plasma samples, enriched with multiple isotopically labelled internal standards, a 12-point aqueous calibration curve, and 6 serum quality controls, designed to monitor long-term performance of the method•Chromatographic separation of multiple steroids along the gradient, with ammonium fluoride mobile phase additive to improve sensitivity, followed by electrospray ionisation and constant polarity switching•Aqueous calibration standards that cover physiologically relevant ranges - high nanomolar glucocorticoids, low nanomolar androgens and picomolar ranges for estrogens and steroid intermediates.
PubMed: 38948242
DOI: 10.1016/j.mex.2024.102728 -
World Journal of Transplantation Jun 2024In this editorial, we talk about a compelling case focusing on posterior reversible encephalopathy syndrome (PRES) as a complication in patients undergoing liver...
In this editorial, we talk about a compelling case focusing on posterior reversible encephalopathy syndrome (PRES) as a complication in patients undergoing liver transplantation and treated with Tacrolimus. Tacrolimus (FK 506), derived from , is a potent immunosuppressive macrolide. It inhibits T-cell transcription by binding to FK-binding protein, and is able to amplify glucocorticoid and progesterone effects. Tacrolimus effectively prevents allograft rejection in transplant patients but has adverse effects such as Tacrolimus-related PRES. PRES presents with various neurological symptoms alongside elevated blood pressure, and is primarily characterized by vasogenic edema on neuroimaging. While computed tomography detects initial lesions, magnetic resonance imaging, especially the Fluid-Attenuated Inversion Recovery sequence, is superior for diagnosing cortical and subcortical edema. Our discussion centers on the incidence of PRES in solid organ transplant recipients, which ranges between 0.5 to 5 +ACU-, with varying presentations, from seizures to visual disturbances. The case of a 66-year-old male status post liver transplantation highlights the diagnostic and management challenges associated with Tacrolimus-related PRES. Radiographically evident in the parietal and occipital lobes, PRES underlines the need for heightened vigilance among healthcare providers. This editorial emphasizes the importance of early recognition, accurate diagnosis, and effective management of PRES to optimize outcomes in liver transplant patients. The case further explores the balance between the efficacy of immunosuppression with Tacrolimus and its potential neurological risks, underlining the necessity for careful monitoring and intervention strategies in this patient population.
PubMed: 38947962
DOI: 10.5500/wjt.v14.i2.91146 -
Journal of Veterinary Research Jun 2024is a well-known medicinal plant with various health benefits. This study was designed to evaluate the administration of Indonesian maceration for its effect on...
INTRODUCTION
is a well-known medicinal plant with various health benefits. This study was designed to evaluate the administration of Indonesian maceration for its effect on promoting growth and development of the ovary and uterus before mating in female albino rats.
MATERIAL AND METHODS
A total of 15 female Sprague Dawley rats in their dioestrous phase were assigned into three different groups: the Control group (mineral water); the Cur-Low group (mineral water with 1% maceration) and the Cur-High group (mineral water with 5% maceration). The treatments were given for 20 days. Serum concentrations of follicle-stimulating hormone, oestradiol and progesterone were determined. After the sacrifice of the rats, ovary and uterine relative weight, uterine cornua diameter and length, uterine gland diameter (by histology), the number of primary, secondary, tertiary, and Graafian follicles, the number of corpora lutea and vascular endothelial growth factor (VEGF) expression in the ovary were measured. Uterine vascularisation was also evaluated.
RESULTS
Administration of maceration significantly improved the relative weights of the uterus and ovary; uterine cornua diameter, length and vascularisation; uterine gland diameter; and expression of VEGF in the ovary. It also increased the number of tertiary follicles and corpora lutea, albeit not significantly. Follicle-stimulating hormone serum concentrations were lower in the administered rats.
CONCLUSION
Oestradiol and progesterone levels rose with maceration treatment. The maceration improved the reproductive organs of unmated rats and had potential to optimise the uterine environment for supporting pregnancy in order to produce high-quality offspring.
PubMed: 38947163
DOI: 10.2478/jvetres-2024-0020