Nitric oxide synthase dysfunctionality in the umbilical cord vascular system during twin birth correlated with maturity and birthweight of the neonates

The maternal physiological state during pregnancy have an excess demand for oxygen supply which can easily disrupt the redox homeostasis balance. There is a change in the maternal haemodynamic profile with an increased cardiac output, reduced systemic vascular resistance and blood pressure (de Haas et al., 2017). In response to this high oxygen demand red blood cell (RBC) mass level steadily increases by 20-30% from 8 to 10 weeks of the gestational period till the end of pregnancy (Foley, 2018). In connection to that, there are increasing evidences of enhanced oxidative insults during intrauterine development leading to severe abnormalities or pathological states like spontaneous miscarriage, preterm delivery, preeclampsia, ectopic pregnancy, intrauterine growth restriction (IUGR), placental abruption, perinatal death etc. Moreover, in cases of multiple/twin pregnancy there is an additional stress with the greater risks of miscarriage, anaemia, preterm delivery, gestational hypertensive disorders, IUGR, diabetes operative delivery and related postnatal and neonatal illnesses. Modern usage of in-vitro fertilization (IVF) therapies led to higher incidence of multiple pregnancies. There have been relevant data on the increasing foetal, neonatal and perinatal mortality rate of 3-6 times in twin and 5-15 times in other multiple pregnancies with comparison to the singleton pregnancies. During pregnancy, the connection between the mother and the foetus is provided by the placenta and the umbilical cord. The umbilical cord vascular system is the sole pathway of oxygen and nutrient transport to the foetus from the placenta. Therefore, the major obstetric complications are directly or indirectly connected to the placental or umbilical cord disorders causing intrauterine hypoxia and/or impaired blood flow to the developing foetus. The major part of umbilical cord lacks innervations and hence the vascular tone is mainly regulated by nitric oxide (NO), i.e. derived from the endothelial nitric oxide synthase (NOS3). The NO being a potent vasoactive agent causes vasodilation and increases the rate of perfusion, nutrient and oxygen supply. Usually intensive prenatal care and surveillances are done in high risk cases like multiple/twin pregnancy by the advanced non-invasive biomedical devices. The usage of high performance equipment like Blood oxygen level-dependent–magnetic resonance imaging was utilized to study changes in the placental oxygenation status in human pregnancies. It can also assess the placental perfusion and oxygen transport. Similarly, ultrasound and Doppler flow measuring techniques not only can visualize the umbilical cord but simultaneously can assess the foetal blood flow parameters through the umbilical cord vessels. These approaches can easily detect any abnormalities in the umbilical cord circulation, but lacks to highlight the underlying molecular mechanisms behind any kind of impaired functionality in the foetal vascular system that can highly influence the in-utero development. Further on this topic we elaborated in details

Molecular Study on Twin Cohort with Discordant Birth Weight

The increased rate of twinning has pointed out newer challenges in clinical practices related to gestational complications, intrauterine growth restriction, perinatal mortality, and comorbidities. As a twin pregnancy progresses, the increased demand for oxygen supply can easily disrupt the redox homeostasis balance and further impose a greater challenge for the developing fetuses. A substantial birth-weight difference acts as an indicator of a deficit in oxygenation or blood flow to one of the fetuses, which might be related to a low bioavailable nitric oxide level. Therefore, in this study, we focused on networks involved in the adjustment of oxygen supply, like the activation of inducible and endothelial nitric oxide synthase (NOS3) along with free radical and lipid peroxide formation in mature twin pairs with high birth-weight differences. The selected parameters were followed by immunofluorescence staining, fluorescence-activated cell sorting analysis, and biochemical measurements in the umbilical cord vessels and fetal red blood cells. Based on our data set, it is clear that the lower-weight siblings are markedly exposed to persistent intrauterine hypoxic conditions, which are connected to a decreased level in NOS3 activation. Furthermore, the increased level of peroxynitrite aggravates lipid peroxidation and induces morphological and functional damage and loss in redox homeostasis

Depressive Symptoms and Perception of COVID-19 Risk in Ohio Adults

Background: We assessed the relationship between depressive symptoms and perceived COVID-19 risk in the next month. Methods: This analysis used survey data collected during a July 2020 cross-sectional study using a household-based probability sampling design. A total of 615 noninstitutionalized, English- and/or Spanish-speaking adults in Ohio were included. Depressive symptoms screening occurred using the Patient Health Questionnaire-2 (PHQ-2). We applied survey weights so that presented analyses represent the adult population in Ohio. We performed log-risk regression modeling (generalized linear model with binomial distribution and log link) to estimate unadjusted and covariate-adjusted prevalence ratios examining the association between screening positive for depressive symptoms and perceived risk of COVID-19 in the next month. Results: The study population was majority female (59.1%) and White (90.3%). The mean age was 55.9 years (standard deviation (SD)=17.3). About 1 in 20 (4.6%) screened positive for depressive symptoms. A positive depressive symptoms screen was not significantly associated with perceived risk of COVID-19 in the next month (prevalence ratio [PR]=0.75; 95% confidence interval [CI]=0.25–2.24). After confounder adjustment, the adjusted prevalence ratio (aPR) was nearly unchanged (aPR=0.78; 95% CI=0.24–2.55). Conclusion: As depression is often associated with anxiety and pessimism toward the future, the lack of association between depressive symptoms screening and perception of COVID-19 risk in the next month is surprising. Social withdrawal, which is also associated with depression, may have concealed any increased perceived COVID-19 risk, as depressed individuals who remained socially isolated may have had lower perceived COVID-19 risk

Molecular Background of Toxic-Substances-Induced Morphological Alterations in the Umbilical Cord Vessels and Fetal Red Blood Cells

The relationship between smoking and human health has been investigated mostly in adults, despite the fact that the chemicals originating from sustained maternal smoking disrupt the carefully orchestrated regulatory cascades in the developing fetus. In this study, we followed molecular alterations in the umbilical cord (UC) vessels and fetal red blood cells (RBCs), which faithfully reflect the in vivo status of the fetus. We showed evidence for the decreased level of DNA-PKcs-positive nuclei in samples with smoking origin, which is associated with the impaired DNA repair system. Furthermore, we pointed out the altered ratio of MMP-9 metalloproteinase and its endogenous inhibitor TIMP-1, which might be a possible explanation for the morphological abnormalities in the UC vessels. The presented in vivo dataset emphasizes the higher vulnerability of the veins, as the primary target for the toxic materials unfiltered by the placenta. All these events become amplified by the functionally impaired fetal RBC population via a crosstalk mechanism between the vessel endothelium and the circulating RBCs. In our ex vivo approach, we looked for the molecular explanation of metal-exposure-induced alterations, where expressions of the selected genes were upregulated in the control group, while samples with smoking origin showed a lack of response, indicative of prior long-term in utero exposure

Looking into the possibilities of cure of the type 2 diabetes mellitus by nanoparticle-based RNAi and CRISPR-Cas9 system: A review

Hyperglycemia is the hallmark of T2DM, related to many candidate genes, e.g., MAPK4, GCKR, STAT3, SOCS3, PTPN1 and PEPCK. To detect new variants of the susceptible genes related to T2DM, a genome-wide association study (GWAS) is being undertaken as well. The existing treatments are unable to address the root cause of the disease at the genetic level and in this regard, the concept of RNAi and most recently, the invention of CRISPR-Cas9 system holds a huge promise and paves a new direction in the treatment strategy of the disease at the genetic level, with a possibility for complete cure, although, issues like low efficiency and off-target problems have impeded their applicability. Additionally, the target-specific delivery using viral carriers also poses serious safety issues. Hence, the current scenario underscores the need for suitable nanocarriers for delivery of the above payloads to the target site and in the present narrative review, we attempt to draw the current understanding of RNAi on the T2DM treatment with the help of nanoparticle encapsulated anti-miR, siRNA, shRNA delivery, also nanoparticle-based CRISPR-Cas9 delivery, to explore the prospect of the complete cure of the disease

A novel composition of bioactive glass with potent haemostatic action and antibacterial competence

Haemorrhagic bleeding is a crucial area of concern related to military as well as civilian trauma. In recent years, bioactive glass is gaining attention in a number of healthcare applications, including haemostasis. Herewith, we report a unique composition of bioactive glass, 70 SiO2: (30-x-y) CaO: x.Al2O3: y.ZnO, where x = 10–18 mole% and y = 0–8 mole%, (Al-BAG) exhibiting haemostatic property as well as antibacterial activity. The as-prepared glass was characterized using XRD, SEM-EDX, FTIR and TG-DSC along with in-vitro degradation study and biological studies e.g., cytocompatibility, haemocompatibility, in-vitro thrombus formation, in-vitro blood absorption capacity, blood coagulation assays (PT, aPTT), in-vitro antibacterial assay against Staph. aureus as well as in-vivo acute dermal toxicity followed by histopathological analysis) and in-vivo haemostasis efficacy were undertaken. The novel bioactive glass composition exhibits promises to be an efficient haemostatic agent with antibacterial activity