The sequestosome 1 protein: therapeutic vulnerabilities in ovarian cancer

Ovarian cancer (OC) is the most deadly tumor that may develop in a woman's reproductive system. It is also one of the most common causes of death among those who have been diagnosed with cancer in women. An adapter protein known as sequestosome 1(SQSTM1) or p62 is primarily responsible for the transportation, degradation, and destruction of a wide variety of proteins. This adapter protein works in conjunction with the autophagy process as well as the ubiquitin proteasome degradation pathway. In addition, the ability of SQSTM1 to interact with multiple binding partners link SQSTM1 to various pathways in the context of antioxidant defense system and inflammation. In this review, we outline the processes underlying the control that SQSTM1 has on these pathways and how their dysregulation contributes to the development of OC. At the final, the therapeutic approaches based on SQSTM1 targeting have been discussed (AU)

HELLP syndrome complicated by ischemic colitis: A case report.

Key Clinical Message: HELLP syndrome is a complicated disorder associated with many unknown complications, which ischemic colitis might be one of. Timely diagnosis and prompt management with multidisciplinary approach is the key for a favorable outcome. Abstract: HELLP syndrome is a triad of hemolysis (H), elevated liver enzymes (EL), and low platelet count (LP) which is considered a rare but serious pregnancy complication. HELLP syndrome is mainly associated with pre-eclampsia, but can also occur individually. It may cause maternal and fetal mortality and some life-threatening morbidity. The best management considered for HELLP syndrome is immediate delivery in most cases. We report a 32-week pregnant woman with pre-eclampsia who developed HELLP syndrome shortly after admission which led to a preterm cesarean section. Rectal bleeding and diarrhea started the day after delivery, and all the workups and imaging suggested ischemic colitis. She received intensive care and supportive management. The patient recovered and was discharged uneventfully. HELLP syndrome may be associated with many unknown complications, and ischemic colitis might be one of them. Timely diagnosis and prompt management with a multidisciplinary approach is the key to a favorable outcome.

The sequestosome 1 protein: therapeutic vulnerabilities in ovarian cancer.

Ovarian cancer (OC) is the most deadly tumor that may develop in a woman's reproductive system. It is also one of the most common causes of death among those who have been diagnosed with cancer in women. An adapter protein known as sequestosome 1(SQSTM1) or p62 is primarily responsible for the transportation, degradation, and destruction of a wide variety of proteins. This adapter protein works in conjunction with the autophagy process as well as the ubiquitin proteasome degradation pathway. In addition, the ability of SQSTM1 to interact with multiple binding partners link SQSTM1 to various pathways in the context of antioxidant defense system and inflammation. In this review, we outline the processes underlying the control that SQSTM1 has on these pathways and how their dysregulation contributes to the development of OC. At the final, the therapeutic approaches based on SQSTM1 targeting have been discussed.

The Role of Interferon (IFN)-γ in Extravillous Trophoblast Cell (EVT) Invasion and Preeclampsia Progression.

The involvement of the immune system in pregnancy is a controversial subject. The functions of T helper (Th) 1 and Th2 cells have been proposed, that Th1 cytokines promoting allograft rejection may impair pregnancy, whereas Th2-type cytokines suppressing Th1 responses improve allograft tolerance and hence embryonic survival. Maternal-fetal tolerance begins in the uterus; therefore, optimal adaptation to the fetus is the result of a complex interference. The invasion of extravillous trophoblast cells (EVTs) into the decidua and the inner third of the myometrium is essential for a healthy pregnancy. The mechanisms that influence trophoblast invasion are unknown; however, cytokines from uterine natural killer (uNK) cells, NKT cells, macrophages, and T cells appear to be involved. All these cells are major sources of interferon gamma (IFN-γ). Recent studies have shown that IFN-γ can inhibit EVT invasion via a mechanism dependent on an increase in EVT apoptosis and a decrease in matrix metalloproteinases (MMPs). Regarding controversies in this context, this study aimed to comprehensively review the role of IFN-γ and IFN-γ-producing cells in EVT invasion, successful pregnancy, and preeclampsia.

Comparison of diagnostic value of two-dimensional ultrasound and clinical examination in fetal weight estimation.

Background: Estimation of fetal weight during pregnancy plays an important role in prenatal and intrapartum care and is more important in pregnancies after 37 weeks to determine the type of delivery. The aim of this study was to compare and evaluate the accuracy and diagnostic value of two-dimensional ultrasound and clinical examination in estimating fetal weight and pregnancy outcomes. Materials and Methods: This cross-sectional study was conducted on 300 pregnant women without abnormal fetuses and pregnancies after 37 weeks; mothers who had a normal delivery or cesarean section were evaluated by the available method. The weight of the fetus was estimated before and after delivery, using ultrasound and clinical examination. Newborns were classified into five groups based on their fetal weight. Analysis of collected data was performed with SPSS software. Results: The mean age of the patients was 31 years and the mean weight of the neonates was 3450 g. At a weight of less than 3000 g, ultrasound and clinical evaluation were strongly correlated with the actual weight of the infant, but at weights of more than 3500 and 4000 g, weight estimation with ultrasound was highly accurate, and clinical examination had poor accuracy. In lower weights, square errors were fewer in both ultrasound and clinical examination, in comparison with higher weights. In higher weights, ultrasound is more reliable, and the diagnostic accuracy of clinical examination is reduced. Conclusion: Estimation of fetal weight with prenatal ultrasound is highly accurate. Clinical examination is more accurate in determining the weight of small fetuses and does not pay much attention to the diagnosis of macrosomic fetuses and even leads to overestimation, while ultrasound is much more accurate in diagnosing fetal macrosomia.

The association between fetal renal artery indices in late pregnancy and birth weight in gestational diabetes mellitus: A cohort study.

Background: Estimation of the fetal birth weight and diagnosis of small for gestational age in the fetuses of women with gestational diabetes mellitus (GDM) are currently imprecise. Objective: We aimed to evaluate the association between fetal renal artery Doppler indices and neonatal birth weight in women with GDM in late pregnancy. Materials and Methods: This cohort study recruited 246 pregnant women from Shariati Hospital in Tehran, Iran, in two GDM and healthy control groups. Participants underwent weekly Doppler ultrasounds in the late pregnancy period (37-40 wk) to determine the Doppler indices of the umbilical artery, middle cerebral, and renal arteries. Fetal growth indices including biparietal diameter, abdominal circumference, head circumference, and femur length were also recorded and compared between the two groups. Results: Fetal growth indices and estimated fetal weight were not significantly different between the two groups. Neonatal birth weight was significantly higher in the GDM group (p < 0.01). The GDM group had significantly higher renal artery indices (resistance index: p = 0.01, pulsatility index [PI]: p = 0.03, and systolic/diastolic ratio [S/D]: p = 0.01) compared to the control group. Also, there was an inverse linear correlation between umbilical indices and birth weight (PI: p = 0.01, S/D: p < 0.01), and between renal artery indices and birth weight (resistance index: p = 0.02, PI: p = 0.01, and S/D: p = 0.03). In the control group, only umbilical artery PI had an inverse linear correlation with birth weight (p = 0.03) and there was no correlation between renal artery indices and birth weight. Conclusion: Using Doppler hemodynamic indices of the renal artery in late pregnancy in women with GDM can be helpful for early detection of hypoxic fetuses, who are at risk of being small for gestational age or having intrauterine growth restriction, even when of normal weight.

Coronavirus disease 2019 (COVID-19) in a pregnant women with treatment resistance thrombocytopenic purpura with and suspicion to HELLP syndrome: a case report.

BACKGROUND: Coronavirus disease 2019 (COVID-19) still is a global emergency. According to the studies, pregnant women are of the at risk populations and any underlying disease(s) might even worsen their condition. The aim of this study is reporting a complex case of immune thrombocytopenic purpura (ITP) during pregnancy who has been diagnosed with COVID-19 as well as suspicion of HELLP syndrome. CASE PRESENTATION: A 24-year-old woman with a platelet count of 6000/mL and resistance to conventional therapies was referred. A day after starting 0.5 g/day of methylprednisolone for her, fever and a decrease in SpO2 presented. According to the paraclinical investigations, COVID-19 was diagnosed and the conventional COVID-19 treatments started for her (the methylprednisolone pulse stopped). Due to the increased liver enzymes and low platelet count, with suspicion of HELLP syndrome, cesarean section surgery was performed which resulted in a healthy neonate. Then, the methylprednisolone pulse was restarted for and she developed an increase in the platelet count. CONCLUSION: It is not clear how COVID-19 and pregnancy affected the patient's condition and the underlying disease; however, it seems the delivery and/or restarting the methylprednisolone pulses caused improvement in her condition.

Association of coronavirus pathogencity with the level of antioxidants and immune system.

Viruses are non-living organisms that annually cause many problems for human societies. The spread of some of the most dangerous viruses causing acute pneumonia, including novel Corona virus has led to the largest death toll in the world. With a long incubation period, Corona virus causes many problems for the immune system. Studies have shown that antioxidant enzymes play an important role in reducing infection and boosting the immune system. The immune system of people with chronic infections is often weak. Specific immunity is one of the most important responses to the virus. The present study therefore investigates association of Coronavirus pathogenicity with the level of antioxidants and immune system.

Can delivery mode influence future ovarian reserve? Anti-Mullerian hormone levels and antral follicle count following cesarean section: a prospective cohort study.

BACKGROUND: The incidence of Cesarean has increased in recent years. The purpose of this study is to evaluate the effect of cesarean section on ovarian reserve. This is a prospective cohort study from January 2016 to November 2017. Inclusion criteria included singleton primigravid pregnant women whose gestational age was above 37 weeks. Exclusion criteria included history of infertility, pelvic surgery, underlying chronic diseases, any adverse pregnancy outcome and postpartum complication in current pregnancy and hormonal medication within six months of delivery. Anti-Mullerian hormone was measured at the admission time for delivery. The type of delivery was determined based on obstetrics indications. Six months after delivery, antral follicle count was performed and anti-Mullerian hormone was measured again. RESULT(S): First blood sample was taken from 730 women. After excluding 550 women, the second blood sample was taken from 180 participants. The mean of first anti-Mullerian hormone in women with cesarean and vaginal delivery were 1.01 ng/mL (95% CI 0.82 to 1.18) and 1.18 ng/mL (95% CI 0.96 to 1.40) respectively (P = 0.211). The mean of second anti-Mullerian hormone in women with cesarean and vaginal delivery were 4.77 ng/mL (95% CI:3.91 to 5.63) and 4.92 ng/mL (95% CI: 4.01 to 5.82) respectively (P = 0.818). No statistically significant difference existed in total AFC between cesarean and vaginal delivery groups (MD: 0.41, 95% CI: - 1.05 to 1.89, P = 0.576). CONCLUSION: Antral follicle count and anti-Mullerian hormone, six month after delivery, are not affected by delivery mode even after adjusting for women's age, baseline Anti-Mullerian hormone, body mass index, gestational age at delivery, breastfeeding, postpartum menstruation, neonatal sex and weight. Based on our best knowledge, this is the first report that investigates the effects of delivery mode on ovarian reserve. Decreased fertility following cesarean has been shown in some previous studies but most of them had assessed this association based on the incidence of subsequent pregnancy. Since subsequent pregnancy can be influenced by several confounding factors, we investigated the effect of cesarean on fertility using its impact on anti-Mullerian hormone levels and antral follicle count. We hope that this study will be a beginning of more detailed studies in this field. We believe that this link is yet to be studied.