Metabolic alterations unravel the maternofetal immune responses with disease severity in pregnant women infected with SARS-CoV-2.

Pregnancy being an immune compromised state, coronavirus disease of 2019 (COVID-19) disease poses high risk of premature delivery and threat to fetus. Plasma metabolome regulates immune cellular responses, therefore we aimed to analyze the change in plasma secretome, metabolome, and immune cells with disease severity in COVID-19 positive pregnant females and their cord blood. COVID-19 reverse transcriptase-polymerase chain reaction positive pregnant females (n = 112) with asymptomatic (Asy) (n = 82), mild (n = 21), or moderate (n = 9) disease, healthy pregnant (n = 18), COVID-19 positive nonpregnant females (n = 7) were included. Eighty-two cord blood from COVID-19 positive and seven healthy cord blood were also analyzed. Mother's peripheral blood and cord blood were analyzed for untargeted metabolome profiling and cytokines by using high-resolution mass spectrometry and cytokine bead array. Immune scan was performed only in mothers' blood by flow cytometry. In Asy severe acute respiratory syndrome coronavirus 2 infection, the amino acid metabolic pathways such as glycine, serine, l-lactate, and threonine metabolism were upregulated with downregulation of riboflavin and tyrosine metabolism. However, with mild-to-moderate disease, the pyruvate and nicotinamide adenine dinucleotide (NAD+ ) metabolism were mostly altered. Cord blood mimicked the mother's metabolomic profiles by showing altered valine, leucine, isoleucine, glycine, serine, threonine in Asy and NAD+ , riboflavin metabolism in mild and moderate. Additionally, with disease severity tumor necrosis factor-α, interferon (IFN)-α, IFN-γ, interleukin (IL)-6 cytokine storm, IL-9 was raised in both mothers and neonates. Pyruvate, NAD metabolism and increase in IL-9 and IFN-γ had an impact on nonclassical monocytes, exhausted T and B cells. Our results demonstrated that immune-metabolic interplay in mother and fetus is influenced with increase in IL-9 and IFN-γ regulated pyruvate, lactate tricarboxylic acid, and riboflavin metabolism with context to disease severity.

Identification of potential targets with high centrality indicated by diethylnitrosamine + thioacetamide-induced hepatocellular carcinoma model.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC), a primary liver malignancy, represents a continuous challenge to clinicians as it is a leading cause of death due to cancer widely. Early detection is the only hope to cure patients from this deadly disease or possibly increase life expectancy. Mouse models are most acceptable studies as they have ability to manipulate their genome and transcriptome to evaluate mechanistic changes. In addition, system biology can improvise the understanding of molecular mechanism of HCC and also can reveal the protein hub involved in every stage of HCC. MATERIALS AND METHODS: Herein, diethylnitrosamine and thioacetamide (TAA) were used to develop stage-specific HCC in Wistar rats. Histopathological changes, biochemical parameters, and the oxidative stress were measured in hepatocytes. We have reanalyzed the microarray dataset to identify the complex signaling pathways involved in hepatocarcinogenesis induced by TAA. GSE45050 dataset was downloaded from Gene Expression Omnibus database, and the gene expression profile of nontumor, cirrhosis, and HCC was compared. RESULTS: The study reveals stage-specific development of chronic HCC rat model and promising stage-specific targets (EHMT2, GMPS, and SPRY2) of HCC. CONCLUSIONS: EHMT2, GMPS, and SPRY found as high centrality nodes in protein-protein interaction studies using high-throughput microarray data which tend to be present in signaling pathways and co-occur in a biological state of HCC. These genes can be targeted to understand the possible pathology, molecular changes, and target strategy under cirrhosis and HCC condition.

Unique pattern of mutations in ß-thalassemia patients in Western Uttar Pradesh.

CONTEXT: ß-thalassemia is one of the most common heterogeneous inherited single gene disorders. The disease results from one or more of 380 different mutations in the ß-globin gene. Uttar Pradesh (U.P.) is the most populous state of India, comprising various ethnic groups and Bareilly is one of the largest cities situated in Western U.P. AIMS: To examine the prevalence of five common ß-thalassemian mutations: Intervening Sequence IVS 1-5 (c. 92 + 5 G > C), codon 8/9 (c. 27_28insG), codon 41/42 (c. 124_127delTTCT), IVS 1-1 (c. 92 + 1 G > T) and codon 26 G-A (c. 79G > A) in Western U.P. SETTINGS AND DESIGN: Patients attending camps organized by the Thalassemia Society, Bareilly were selected for the study. MATERIALS AND METHODS: A total of 48 blood samples were collected from the patients of transfusion dependent ß-thalassemia from July 2011 to May 2012. All the samples were analyzed for five common mutations by using the Amplification Refractory Mutation System (ARMS)-hot start-polymerase chain reaction (PCR) technique. RESULTS: Among the five common mutations prevalent in India, we were able to detect all except codon 26 G-A (c. 79G > A), which is prevalent in northeast India. These four mutations accounted for 58% of the total number of our patients. The IVS 1-5 (G-C) was found to be the most common mutation with a frequency of 46% and the 2 (nd)most common mutation was Fr8/9 (+G) with a frequency of 21%. The frequency of other mutations was IVS1-1 (12%) and Cd 41/42 (4%). CONCLUSION: This study provides evidence that the pattern of mutations in Western U.P. is different from the rest of India and even from the neighboring states (Delhi and Punjab). To the best of our knowledge, mutation Fr8/9, the 2(nd)most common mutation in our study has never been reported to be so common from anywhere in India. Some mutations, which are prevalent in other regions are absent in our region (mutation for ε-globin). Hence, these findings can be called unique to Western U.P.