Sexually Dimorphic Response to Hepatic Injury in Newborn Suffering from Intrauterine Growth Restriction.

Intrauterine growth restriction (IUGR), when a fetus does not grow as expected, is associated with a reduction in hepatic functionality and a higher risk for chronic liver disease in adulthood. Utilizing early developmental plasticity to reverse the outcome of poor fetal programming remains an unexplored area. Focusing on the biochemical profiles of neonates and previous transcriptome findings, piglets from the same fetus are selected as models for studying IUGR. The cellular landscape of the liver is created by scRNA-seq to reveal sex-dependent patterns in IUGR-induced hepatic injury. One week after birth, IUGR piglets experience hypoxic stress. IUGR females exhibit fibroblast-driven T cell conversion into an immune-adapted phenotype, which effectively alleviates inflammation and fosters hepatic regeneration. In contrast, males experience even more severe hepatic injury. Prolonged inflammation due to disrupted lipid metabolism hinders intercellular communication among non-immune cells, which ultimately impairs liver regeneration even into adulthood. Additionally, Apolipoprotein A4 (APOA4) is explored as a novel biomarker by reducing hepatic triglyceride deposition as a protective response against hypoxia in IUGR males. PPARα activation can mitigate hepatic damage and meanwhile restore over-expressed APOA4 to normal in IUGR males. The pioneering study offers valuable insights into the sexually dimorphic responses to hepatic injury during IUGR.

Laparoscopic treatment of colonic endometriosis causing periodic abdominal pain and hematochezia: A case report.

RATIONALE: Endometriosis, a benign disease, has a malignant biological behavior and is highly prone to recurrence. Although gastrointestinal involvement is the most common site for extra-genital endometriosis, deep infiltrative endometriosis, which affects the mucosal layer, is very rare. PATIENT CONCERNS: A 44-year-old woman with a 6-month history of recurring abdominal pain and Hematochezia. The patient visited several hospitals over the past six months and was suspected to have been diagnosed with a digestive disease, for which medication was ineffective, leading to a great deal of anxiety. DIAGNOSES: Colonic endometriosis. INTERVENTIONS: After a thorough imaging evaluation and preoperative discussion, laparoscopic colonic endometriosis resection under indocyanine green indication was performed by gynecologists and gastroenterologists. OUTCOMES: After laparoscopic treatment, the patient's symptoms improved significantly, with occasional pain felt and no blood in the stool. LESSONS: This case provides a rare example of sigmoid endometriosis causing periodic abdominal pain and Hematochezia. We report a clinical case to investigate the feasibility of an indocyanine green fluorescent contrast technique to guide the scope of surgery in laparoscopic deep infiltrative endometriosis surgery. In intestinal endometriosis surgery, indocyanine green fluoroscopy may indicate the lesion's precise localization.

Knockdown of PROM2 Enhances Paclitaxel Sensitivity in Endometrial Cancer Cells by Regulating the AKT/FOXO1 Pathway.

BACKGROUND: Endometrial cancer is a very common and highly lethal reproductive malignant tumour in women. Paclitaxel (PTX) is a usual drug utilized in chemotherapy for endometrial cancer. It has been uncovered that PROM2 participates in the progression of various cancers through playing a promoter. However, the regulatory function of PROM2 in PTX treatment for endometrial cancer remains unclear. METHODS: The cell viability (IC50) was examined through CCK8 assay. The mRNA and protein expressions of genes were measured through RT-qPCR and western blot. The proliferation was evaluated through colony formation and EdU assays. The cell apoptosis was assessed through flow cytometry. RESULTS: In this work, through bioinformatic analysis on online websites, it is found that the up-regulated expression of PROM2 existed in endometrial cancer. In addition, the survival probability of UCEC patients with high PROM2 expression was worse. This study adopted PTX treatment for obtaining the PTX-resistant cells (HEC-1A/PTX and KLE/PTX). Furthermore, suppression of PROM2 enhanced PTX sensitivity through decreasing IC50 and proliferation in endometrial cancer. Additionally, knockdown of PROM2 facilitated cell apoptosis in HEC-1A/PTX and KLE/PTX cells. Next, we found that silencing of PROM2 retards the AKT/FOXO1 pathway. At last, rescue assays reversed the strengthened PTX sensitivity mediated by PROM2 inhibition after SC79 treatment (AKT activator). CONCLUSION: Knockdown of PROM2 enhanced PTX sensitivity in endometrial cancer through modulating the AKT/FOXO1 pathway. This study hinted that PROM2 may be a useful therapeutic target for PTX treatment in endometrial cancer.

Autophagy-dependent ferroptosis is involved in the development of endometriosis.

OBJECTIVE: Endometriosis (EMS) is an estrogen-dependent condition with unclear pathogenesis. Recent findings suggest implicate autophagy and ferroptosis in EMS development. METHODS: We assessed autophagy and ferroptosis proteins in EMS patients using immunohistochemistry and western blot and established an EMS rat model through allograft endometrial transplantation, confirmed via hematoxylin and eosin staining and epithelial-mesenchymal transition -related proteins. Primary EMS cells were isolated from the model rats and cultured under five conditions: control, EMS, EMS with Rapamycin (autophagy inducer), EMS with si-Atg5 (autophagy inhibitor), and EMS with si-Atg5 plus Erastin (ferroptosis inducer). We evaluated cell viability, iron content, oxidative stress, and mitochondrial morphologyin EMS cells, and detected autophagy and ferroptosis proteins through immunofluorescence, western blot, and monodansylcadaverine staining. RESULTS: Autophagy proteins Beclin1 and LC3 were highly expressed, whereas p62, glutathione peroxidase 4, and p53 were lowly expressed in EMS patients. Rapamycin decreased cell viability but increased iron content, reactive oxygen species, lipid peroxide production, the number of ferroptotic mitochondria, and the expression of autophagy proteins in EMS cells, while si-Atg5 showed opposite effects. Additionally, Erastin reversed the impact of si-Atg5 on EMS cells. CONCLUSION: Our findings suggest that autophagy-dependent ferroptosis plays a role in EMS progression.

Study on the mechanism of estrogen regulating endometrial fibrosis after mechanical injury via miR-21-5p/PPARα/FAO axis.

BACKGROUND: Intrauterine adhesion (IUA) caused by endometrial mechanical injury has been found as a substantial risk factor for female infertility (e.g., induced abortion). Estrogen is a classic drug for the repair of endometrial injury, but its action mechanism in the clinical application of endometrial fibrosis is still unclear. OBJECTIVE: To explore the specific action mechanism of estrogen treatment on IUA. METHODS: The IUA model in vivo and the isolated endometrial stromal cells (ESCs) model in vitro were built. Then CCK8 assay, Real-Time PCR, Western Blot and Dual-Luciferase Reporter Gene assay were applied to determine the targeting action of estrogen on ESCs. RESULTS: It was found that 17ß-estradiol inhibited fibrosis of ESCs by down-regulating miR-21-5p level and activating PPARα signaling. Mechanistically, miR-21-5p significantly reduced the inhibitory effect of 17ß-estradiol on fibrotic ESCs (ESCs-F) and its maker protein (e.g., α-SMA, collagen I, and fibronectin), where targeting to PPARα 3'-UTR and blocked its activation and transcription, thus lowering expressions of fatty acid oxidation (FAO) associated key enzyme, provoking fatty accumulation and reactive oxygen species (ROS) production, resulting in endometrial fibrosis. Nevertheless, the PPARα agonist caffeic acid counteracted the facilitation action of miR-21-5p on ESCs-F, which is consistent with the efficacy of estrogen intervention. CONCLUSION: In brief, the above findings revealed that the miR-21-5p/PPARα signal axis played an important role in the fibrosis of endometrial mechanical injury and suggested that estrogen might be a promising agent for its progression.

Copious vaginal discharge finally diagnosed as cervical adenocarcinoma: A case report.

RATIONALE: Copious vaginal discharge is a frequent manifestation of reproductive tract infections. However, when little effect can obtain treated as vaginitis, cervical disease should be highly suspected. PATIENT CONCERNS: A 41-year-old woman had suffering from abnormally increased vaginal discharge without any other signs of discomfort for the past 4 years. A lot of medical examinations and treatment of vaginosis were administered, resulting in unclear diagnosis and little effect. DIAGNOSES: Cervical adenocarcinoma. INTERVENTIONS: Gynecological examination, vaginal microbiome culture, and primary cervical cancer screening were negative, and a positron emission tomography revealed an increased 18F-fluorodeoxyglucose metabolism in the local cervix. After a thorough description, the patient demanded a hysterectomy and bilateral salpingo-oophorectomy. OUTCOMES: Histopathological evaluation confirmed adenocarcinoma in situ of the uterine cervix. LESSONS: The correct diagnosis of symptomatic patients with increased vaginal discharge is challenging. Human papillomavirus-negative patients presenting profuse watery vaginal discharge with an abnormal signal of cervix lesion on positron emission tomography or magnetic resonance imaging should be alert to cervical adenocarcinoma. Deep-seated cervical biopsy, conization, or even hysterectomy is conducive to early diagnosis, treatment and improvement of prognosis.