During pregnancy, regulated generation of reactive oxygen species (ROS) is important for activation of signaling pathways and placentation. In the current study, the effect of H2O2 on invasion of ...HTR‐8/SVneo cells, a human extravillous trophoblast cell line, is investigated. Treatment of HTR‐8/SVneo cells for 24 hr with H2O2 (25 µM) leads to a significant increase in invasion without affecting cell proliferation, viability, and apoptosis. Concomitantly, a significant increase in the matrix metalloproteinase‐9 (MMP‐9)/tissue inhibitor of metalloproteinases‐1 (TIMP‐1) ratio is observed. Further, significant increase in phosphorylation of signal transducer and activator of transcription 1 (STAT‐1) and STAT‐3 (both at ser727 residue) is observed on treating HTR‐8/SVneo cells with 25 µM of H2O2 accompanied by an increase in the secretion of interleukin‐8 (IL‐8) and macrophage inflammatory protein‐1β (MIP‐1β). A significant decrease in H2O2‐mediated invasion of HTR‐8/SVneo cells and reduced expression of IL‐8 and MIP‐1β accompanied by decrease in MMP‐9/TIMP‐1 ratio are observed on inhibiting STAT‐1 and STAT‐3 by small interfering RNA (siRNA). Inhibition of STAT‐1 activity by fludarabine and STAT‐3 activity by Stattic also leads to a decrease in H2O2‐mediated increase in HTR‐8/SVneo cell invasion. Inhibition of IL‐8 and MIP‐1β by siRNA also leads to a significant decrease in both basal and H2O2‐mediated invasion. Interestingly, inhibition of MIP‐1β by siRNA leads to a significant reduction in H2O2‐mediated increase in IL‐8. However, no significant effect of IL‐8 silencing on H2O2‐mediated MIP‐1β expression was observed. From the above results, it can be concluded that H2O2 activates STAT signaling, MIP‐1β & IL‐8 secretion and increases MMP‐9/TIMP‐1 ratio leading to an increased invasion of HTR‐8/SVneo cells without affecting their viability.
Synergizing satellite remote sensing data with vertical profiles of atmospheric thermodynamics and regional climate model simulations, we investigate the relative importance, transport pathways, and ...seasonality of contribution of dust from regional (Thar Desert and adjoining arid regions) and remote (southwest Asia and northeast Africa) sources over the northeast Indian Ocean i.e., the Bay of Bengal (BOB). We show that while over the northern BOB dust from the regional sources contribute more than 50% to the total dust load during the southwest monsoon period (June–September), interestingly; the remote dust sources dominate rest of the year. On the other hand, over the southern BOB, dust transported from the remote-source regions dominate throughout the year. During June, the dry elevated layer (at altitudes between 850 and 700 hPa) of dust, transported across the Indo-Gangetic Plain to the northern BOB, arises primarily from the Thar Desert. Dust from remote sources in the far west reaches the southern BOB after traversing over and around the southern Indian Peninsula. Since dust from these distinct source regions have different mineral composition (hence optical properties) and undergo distinct changes during atmospheric transport, it is important to understand source-specific dust contribution and transport pathways to address dust–climate feedback.
Accumulation of senescent cells has a causative role in the pathology of age-related disorders including atherosclerosis (AS) and cardiovascular diseases (CVDs). However, the concept of senescence is ...now drastically changing, and the new concept of senescence-associated reprogramming/stemness has emerged, suggesting that senescence is not merely related to “cell cycle arrest” or halting various cellular functions. It is well known that disturbed flow (D-flow) accelerates pre-mature aging and plays a significant role in the development of AS. We will discuss in this review that pre-mature aging induced by D-flow is not comparable to time-dependent aging, particularly with a focus on the possible involvement of senescence-associated secretory phenotype (SASP) in senescence-associated reprogramming/stemness, or increasing cell numbers. We will also present our outlook of nicotinamide adenine dinucleotides (NAD)+ deficiency-induced mitochondrial reactive oxygen species (mtROS) in evoking SASP by activating DNA damage response (DDR). MtROS plays a key role in developing cross-talk between nuclear-mitochondria, SASP, and ultimately atherosclerosis formation. Although senescence induced by time and various stress factors is a classical concept, we wish that the readers will see the undergoing Copernican-like change in this concept, as well as to recognize the significant contrast between pre-mature aging induced by D-flow and time-dependent aging.
Improving feed efficiency (FE) is a major goal of pig breeding, reducing production costs and providing sustainability to the pig industry. Reliable predictors for FE could assist pig producers. We ...carried out untargeted blood metabolite profiling in uncastrated males from Danbred Duroc (n = 59) and Danbred Landrace (n = 50) pigs at the beginning and end of a FE testing phase to identify biomarkers and biological processes underlying FE and related traits. By applying linear modeling and clustering analyses coupled with WGCNA framework, we identified 102 and 73 relevant metabolites in Duroc and Landrace based on two sampling time points. Among them, choline and pyridoxamine were hub metabolites in Duroc in early testing phase, while, acetoacetate, cholesterol sulfate, xanthine, and deoxyuridine were identified in the end of testing. In Landrace, cholesterol sulfate, thiamine, L-methionine, chenodeoxycholate were identified at early testing phase, while, D-glutamate, pyridoxamine, deoxycytidine, and L-2-aminoadipate were found at the end of testing. Validation of these results in larger populations could establish FE prediction using metabolomics biomarkers. We conclude that it is possible to identify a link between blood metabolite profiles and FE. These results could lead to improved nutrient utilization, reduced production costs, and increased FE.
Introduction: Cardiovascular Autonomic Neuropathy (CAN) may be seen in patients of Type 2 Diabetes Mellitus (T2DM). In many previous studies it was seen that there is reduced heart rate variability ...in DM patients. Reduced heart rate variability is earliest indicator for the CAN. In different earlier studies, it was found that results of Short-term Heart Rate Variability (HRV) analysis of five minutes is comparable to standard 24 hours HRV analysis. In DM patients CAN is mostly found to be associated with a longer duration of disease, but according to some studies CAN may be present in newly diagnosed diabetes patients also, but the percentage is lower. Aim: To assess the short-term HRV profile as cardiovascular risks among newly diagnosed T2DM patients and to find the correlation of HRV parameters with duration of disease and biochemical parameters; Fasting Plasma Glucose (FPG) and Postprandial Plasma Glucose (PPPG) for early detection and management of CAN. Materials and Methods: The present study was a cross-sectional study conducted in the Department of Physiology in collaboration with the Department of Endocrinology at R.G. Kar Medical College and Hospital, Kolkata, West Bengal, India, from September 2020 to August 2021 on 56 newly diagnosed T2DM (age group 30 to 64 years). Study subjects were grouped according to the Standard deviation of NN intervals (SDNN) (millisecond) value as cardiovascular risk factor. Group 1 was the low risk group, group 2 was the moderate risk group, group 3 was the high-risk group. HRV testing was done with Physiograph Polyrite-D instrument with bio-amplifiers, 4 channels and accessories (RMS latest software-Version 3.0.16) in Autonomic Function Research Laboratory to measure HRV parameters. After collecting data, analysis was done using Statistical Package for Social Sciences (IBM, SPSS) version 23.0 Unpaired student’s t-test, Chi-square test, Analysis of Variance (ANOVA) test, Pearson correlation test were performed and statistical significance of different parameters were evaluated. It was considered statistically significant when p-value <0.05. Results: By assessing HRV parameters as cardiovascular risk factors among newly diagnosed T2DM patients the present study showed there was significantly (p-value=0.0065) high LF/HF ratio in males (1.70±1.19) than in females (0.99±0.69). The SDNN value was significantly highest in low cardiovascular risk group (137.29±25.49 ms) and lowest in high cardiovascular risk group (26.07±12.03 ms) (p-value=0.00001). Low Frequency and High Frequency Ratio (LF:HF ratio) was significantly more in age group of 51-60 years. Among all the patients, 34 (61%) patients had increased parasympathetic activity and 22 (39%) subjects had increased sympathetic activity. Female patients showed significantly more increased parasympathetic 24 (75%) activity than males 10 (41.7%). There was a significant association between SDNN values with the duration of disease (p-value=0.004). Conclusion: The present study showed that cardiac autonomic neuropathy is present even at the time of diagnosis of newly diagnosed T2DM as there was sympathovagal imbalance. Female patients have more parasympathetic drive than males which indicates that females are more cardioprotective.
Poor endometrial perfusion during implantation window is reported to be one of the possible causes of idiopathic recurrent spontaneous miscarriage (IRSM). We have tested the hypothesis that certain ...angiogenic and vasoactive factors are associated with vascular dysfunction during implantation window in IRSM and, therefore, could play a contributory role in making the endometrium unreceptive in these women. This is a prospective case-controlled study carried out on 66 women with IRSM and age and BMI matched 50 fertile women serving as controls. Endometrial expression of pro-inflammatory (IL-1β, TNF-α, IFN-γ, TGF-β1), anti-inflammatory (IL-4, -10), angiogenesis-associated cytokines (IL-2, -6, -8), angiogenic and vasoactive factors including prostaglandin E2 (PGE2), vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), nitric oxide (NO) and adrenomedullin (ADM) were measured during implantation window by ELISA. Subendometrial blood flow (SEBF) was assessed by color Doppler ultrasonography. Multivariate analysis was used to identify the significant factor(s) responsible for vascular dysfunction in IRSM women during window of implantation and further correlated with vascular dysfunction. Endometrial expression of pro-inflammatory cytokines and PGE2 were up-regulated and anti-inflammatory and angiogenesis-associated cytokines down-regulated in IRSM women as compared with controls. Further, the angiogenic and vasoactive factors including VEGF, eNOS, NO and ADM were found to be down-regulated and SEBF grossly affected in these women. Multivariate analysis identified IL-10, followed by VEGF and eNOS as the major factors contributing towards vascular dysfunction in IRSM women. Moreover, these factors strongly correlated with blood flow impairment. This study provides an understanding that IL-10, VEGF and eNOS are the principal key components having a contributory role in endometrial vascular dysfunction in women with IRSM. Down-regulation of these factors is also associated with impaired endometrial perfusion which possibly makes the endometrium unreceptive that may eventually cause early pregnancy loss.
The effect of the interplay among inflammation, angiogenesis, extracellular matrix (ECM) degradation, and oxidative stress (OS) on the pathogenesis of endometriosis remains unclear. Previously, we ...demonstrated the role of OS in endometriosis. Here, we performed a comprehensive investigation of several molecules involved in inflammation, angiogenesis, and ECM degradation in women with endometriosis to study their interplay with OS.
Blood samples were collected from women with endometriosis (N=80), as well as from women with tubal factor infertility as controls (N=80). Interleukin (IL)-1β, tumor necrosis factor-alpha, interferon-gamma, transforming growth factor-beta, IL-4, -10, -2, -6, -8, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, -9, tissue inhibitor of metalloproteinases (TIMP)-1, -2, and cyclooxygenase (COX)-2 levels in serum samples were measured using an ELISA. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in peripheral blood mononuclear cells was measured using flow cytometry.
Cytokines, VEGF, MMPs, and COX-2 were significantly higher and TIMPs were significantly lower in patients with endometriosis. Multivariate statistical analysis indicated that IL-10 was the most significant variable capable of discriminating endometriosis samples from controls.
Deregulation of NF-κB activation by OS affects the expression of various cytokines in endometriosis. Elevated cytokine levels further up-regulate IL-10, which subsequently activates the MMPs, leading to excessive ECM degradation and angiogenesis. Moreover, IL-10 emerged as the most important molecule involved in the pathogenesis of endometriosis. Measurement of these molecules may help in better management of the patients with endometriosis.
Interactions among genomic loci have often been overlooked in genome-wide association studies, revealing the combinatorial effects of variants on phenotype or disease manifestation. Unexplained ...genetic variance, interactions among causal genes of small effects, and biological pathways could be identified using a network biology approach. The main objective of this study was to determine the genome-wide epistatic variants affecting feed efficiency traits feed conversion ratio (FCR) and residual feed intake (RFI) based on weighted interaction SNP hub (WISH-R) method. Herein, we detected highly interconnected epistatic SNP modules, pathways, and potential biomarkers for the FCR and RFI in Duroc and Landrace purebreds considering the whole population, and separately for low and high feed efficient groups. Highly interacting SNP modules in Duroc (1,247 SNPs) and Landrace (1,215 SNPs) across the population and for low feed efficient (Duroc-80 SNPs, Landrace-146 SNPs) and high feed efficient group (Duroc-198 SNPs, Landrace-232 SNPs) for FCR and RFI were identified. Gene and pathway analyses identified
,
,
,
,
, and
from chromosomes 1, 2, 5, and 13 underlying ErbB, Ras, Rap1, thyroid hormone, axon guidance pathways in Duroc.
,
and
genes from chromosomes 1, 3, and 6 pointed towards thyroid hormone, cGMP-PKG and cAMP pathways in Landrace. From Duroc low feed efficient group, the
gene was found involved with thiamine metabolism, whereas
,
were involved with the hippo signaling pathway in high feed efficient group.
and
genes were involved with lysine degradation in low feed efficient group in Landrace, while high feed efficient group pointed to genes underpinning valine, leucine, isoleucine degradation, and fatty acid elongation. Some SNPs and genes identified are known for their association with feed efficiency, others are novel and potentially provide new avenues for further research. Further validation of epistatic SNPs and genes identified here in a larger cohort would help to establish a framework for modelling epistatic variance in future methods of genomic prediction, increasing the accuracy of estimated genetic merit for FE and helping the pig breeding industry.
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