Induction and characterization of a rat model of endometriosis.

Endometriosis is a common condition that affects 5% to 10% of women during their reproductive years, although the aetiology and pathophysiology are still unknown. This study aimed to create an endometriosis model in rats to investigate the efficacy of natural and synthetic medications in treating endometriosis. An in vivo endometriotic model was established using a surgical induction method and the endocrine-disrupting drug diethylstilbestrol (DES). In brief, the experiment is categorised into three different groups. Each group contains five rats. The first group had no surgery, while in the in the second group of rats (n = 5), two small tissue grafts were fixed at the right and left walls of the abdomen. But in the in the third group of rats (n = 5), two small pieces of tissue have been grafted on the right and left abdomen walls by surgically along with DES treatments. Noninvasive photoacoustic imaging (PAI) was employed in the study to measure factors such as haemoglobin levels, oxygen saturation, and the size of endometriotic lesions. Histopathological analysis was carried out utilising staining techniques such as Hematoxylin and Eosin, Masson's Trichrome, and Periodic Acid Schiff, as well as immunohistochemistry with marker antibodies. Molecular markers in uterine tissue were examined using Western blots and real-time PCR. The developed endometriosis rat model showed a significant increase in the expression of anti-apoptotic Bcl-2, angiogenic marker VEGF and pro-inflammatory (COX-2 and IL-6) protein markers. In contrast to the control group, the treatment group had considerably lower Caspase-3 expression levels. Photoacoustic imaging (PAI) data demonstrated a constant increase in lesion size, as well as a decrease in oxygen saturation levels. The findings suggest that the in vivo endometriosis rat model may accurately assess the efficacy of natural or synthetic endometriosis treatments. This model may help in the improvement of disease understanding and the development of targeted therapeutic drugs.

Association between the MTHFR (rs1801133) gene variation and serum trace elements levels (Copper and Zinc) in individuals diagnosed with neural tube defects.

BACKGROUND AND AIMS: Neural tube defects (NTDs) occur when the neural tube fails to close within 28 days of human embryonic development. This results in central nervous system disorders like anencephaly, spina bifida, and encephalocele. Early diagnosis and treatment are crucial to minimize their impact on an individual's health and well-being. The present study aims to define the association between prenatal exposure to trace elements (Cu and Zn) and the single nucleotide polymorphism (SNP) of the MTHFR gene involved in folate metabolism pathways in neural tube defects in children and their mothers. MATERIAL AND METHODS: A cross-sectional study involving 331 participants (90 NTD cases, 88 healthy mothers, 85 NTD children, and 68 healthy children) from antenatal check-ups in Obstetrics and Gynaecology and Pediatric Surgery for Neural Tube Defects in the Outpatient Department (OPD) and Inpatient Department (IPD). Assessed Cu and Zn concentrations and their associations. Genomic DNA was extracted, and real-time PCR was used to determine genotypes. Atomic absorption spectrophotometry measured trace elements. Statistical analyses included Chi-Square tests, odds ratios, and Mann-Whitney U tests. RESULTS: Significant associations were found between MTHFR C677T genotypes and NTD risk in mothers (p = 0.0491) and children (p = 0.0297). Allelic frequency analysis indicated a T allele association with NTD risk in children (p = 0.0107). Recessive models showed significant associations in mothers (p = 0.0169) and children (p = 0.1678). Cu levels differed significantly between NTD cases and controls (p < 0.0001), with MTHFR genotypes influencing Cu levels. Zinc levels also varied significantly (p < 0.0001). CONCLUSION: This study reveals complex associations between MTHFR C677T genotypes, trace element concentrations, and NTD risk in mothers and children. This targeted approach allows healthcare providers to identify at-risk pregnancies early, enabling personalised interventions like folic acid supplementation and counselling to moderate neural tube defect (NTD) risk in a future pregnancy.

Elevated Circulatory Proline to Glutamine Ratio (PQR) in Endometriosis and Its Potential as a Diagnostic Biomarker.

Endometriosis (EM) is a hormone-dependent gynecological disease associated with chronic pelvic pain and altered immuno-inflammatory processes. It shares some cancer-like characteristics such as increased proline biosynthesis and activated glutaminolysis. Both proline and glutamine are interconvertible metabolically, and studies have shown their roles in cancer cell metabolic reprogramming, redox homeostasis, occurrence/development of endometrial carcinoma, and its further progression toward the malignant state. So based on this, we hypothesized that the circulatory proline to glutamine ratio (PQR) would be altered in EM and may serve as an indicative biomarker to improve the clinical diagnosis of EM. In present study, the circulatory-PQR levels were estimated for 39 EM patients and 48 age matched healthy female subjects using 800 MHz NMR spectroscopy. Among 39 EM patients, 15 were in the clinical stages I to II and referred to here as moderate EM (MEM) patients and 24 were in the clinical stages III to IV and referred here as severe EM (SEM) patients. The circulatory-PQR levels were significantly increased in EM patients (0.99 ± 0.13 µM in MEM; 1.39 ± 0.22 µM in SEM) compared to normal control (NC) subjects (0.52 ± 0.05 µM in NC). Further, the circulatory PQR levels exhibit the highest diagnostic potential with area under receiver operating characteristic (AUROC) curve values equal to 0.87 ± 0.04 [95%CI = 0.79-0.96] for MEM and 0.89 ± 0.04 [95% CI = 0.82-0.96] for SEM. These results suggested that circulatory-PQR has significant potential to serve as a noninvasive biomarker for diagnostic/prognostic screening of EM and further underscored the importance of these two nonessential amino acids (proline and glutamine) in cancer metabolism.

Estradiol correlates with the accumulation of Monocytic Myeloid-Derived Suppressor Cells in Pre-term birth: A possible explanation of immune suppression in pre-term babies.

Synergistic interplay of immune endocrine interaction is prerequisite for an effective maternal fetal tolerance. Pre-term birth (PTB) may be a consequence of altered immune-endocrine crosstalk during third trimester resulting in early breakdown of this tolerance. Myeloid derived suppressor cells (MDSCs), a heterogenous population of immature immune cells are increased in pregnant women and healthy newborns, but their role in PTB still remains obscure. We now report that granulocytic MDSCs (G-MDSCs) is decreased in women delivering prematurely, suggesting their potential role in maintaining maternal fetal tolerance. Interestingly, in contrast statistically significant increase in MDSCs and monocytic MDSCs (M-MDSCs) along with positive correlation with cord serum estradiol (E2), and overexpressed ER-α in placental tissue suggested E2 mediated accumulation of M-MDSCs in PTB babies. MDSCs mediated immune suppression is accompanied with subsequent decline in total T cells and its subtypes: Th and Tc in PTB babies, which signifies their potential contribution towards the impaired immune system of PTB babies.

Altered cord serum 25-hydroxyvitamin D signaling and placental inflammation is associated with pre-term birth.

PROBLEM: Vitamin D is well-known for having anti-inflammatory and immunomodulatory properties. Impaired maternal vitamin D status has been known to increase the risk of adverse pregnancy outcomes like pre-term birth. The present study aims to evaluate the impact of fetal cord serum 25-hydroxyvitamin D-mediated signaling in mediating inflammatory responses in placenta during pre-term birth. METHOD OF STUDY: For the above purpose, cord serum 25 hydroxyvitamin D 25(OH)D were measured in term (n = 20) and pre-term (n = 20) born babies using ELISA. Vitamin D downstream signaling has also been checked in placenta (VDR, CYP27B1, cathelicidin LL37) along with expression of inflammatory markers (S100A8, HMGB1, TLR2, p-NF-kappaB) using Western blotting and immunohistochemistry. Pearson correlation model was used to do correlation study. RESULTS: Compared with term born babies (59.31 ± 3.476), decline in cord serum 25(OH)D levels is observed in pre-term born babies (22.26 ± 1.083, P = <0.0001) that showed strong positive correlation with gestational age (r = .9368***) and birthweight (r = .9559***). On the other hand, vitamin D signaling markers were found to be downregulated and inflammatory markers were upregulated in placental tissue of pre-term born babies. CONCLUSION: Thus, our study demonstrated that insufficient cord 25(OH)D levels may disturb the homeostasis of inflammation in placenta. Altered cord serum 25(OH)D mediated anti-inflammatory signaling may be acting as trigger signals in modulating inflammatory responses in placenta and eliciting premature activation of spontaneous labor in pre-term birth.

The Yin and Yang of Myeloid Derived Suppressor Cells.

In recent years, most of our knowledge about myeloid derived suppressor cells (MDSCs) has come from cancer studies, which depicts Yin side of MDSCs. In cancer, inherent immunosuppressive action of MDSCs favors tumor progression by inhibiting antitumor immune response. However, recently Yang side of MDSCs has also been worked out and suggests the role in maintenance of homeostasis during non-cancer situations like pregnancy, obesity, diabetes, and autoimmune disorders. Continued work in this area has armored the biological importance of these cells as master regulators of immune system and prompted scientists all over the world to look from a different perspective. Therefore, explicating Yin and Yang arms of MDSCs is obligatory to use it as a double edged sword in a much smarter way. This review is an attempt toward presenting a synergistic coalition of all the facts and controversies that exist in understanding MDSCs, bring them on the same platform and approach their "Yin and Yang" nature in a more comprehensive and coherent manner.