Integrative multi-omics database (iMOMdb) of Asian pregnant women

Asians are underrepresented across many omics databases, thereby limiting the potential of precision medicine in nearly 60% of the global population. As such, there is a pressing need for multi-omics derived quantitative trait loci (QTLs) to fill the knowledge gap of complex traits in populations of Asian ancestry. Here, we provide the first blood-based multi-omics analysis of Asian pregnant women, constituting high-resolution genotyping (N= 1079), DNA methylation (N=915) and transcriptome profiling (N=238). Integrative omics analysis identified 219 154 CpGs associated with cis-DNA methylation QTLs (meQTLs) and 3703 RNAs associated with cis-RNA expression QTLs (eQTLs). Ethnicity was the largest contributor of inter-individual variation across all omics datasets, with 2561 genes identified as hotspots of this variation; 395 of these hotspot genes also contained both ethnicity-specific eQTLs and meQTLs. Gene set enrichment analysis of these ethnicity QTL hotspots showed pathways involved in lipid metabolism, adaptive immune system and carbohydrate metabolism. Pathway validation by profiling the lipidome (similar to 480 lipids) of antenatal plasma (N = 752) and placenta (N = 1042) in the same cohort showed significant lipid differences among Chinese, Malay and Indian women, validating ethnicity-QTL gene effects across different tissue types. To develop deeper insights into the complex traits and benefit future precision medicine research in Asian pregnant women, we developed iMOMdb, an open-access database.Peer reviewe

Population-based plasma lipidomics reveals developmental changes in metabolism and signatures of obesity risk : a mother-offspring cohort study

Publisher Copyright: © 2022, The Author(s).Background: Lipids play a vital role in health and disease, but changes to their circulating levels and the link with obesity remain poorly characterized in expecting mothers and their offspring in early childhood. Methods: LC-MS/MS-based quantitation of 480 lipid species was performed on 2491 plasma samples collected at 4 time points in the mother-offspring Asian cohort GUSTO (Growing Up in Singapore Towards healthy Outcomes). These 4 time points constituted samples collected from mothers at 26–28 weeks of gestation (n=752) and 4–5 years postpartum (n=650), and their offspring at birth (n=751) and 6 years of age (n=338). Linear regression models were used to identify the pregnancy and developmental age-specific variations in the plasma lipidomic profiles, and their association with obesity risk. An independent birth cohort (n=1935), the Barwon Infant Study (BIS), comprising mother-offspring dyads of Caucasian origin was used for validation. Results: Levels of 36% of the profiled lipids were significantly higher (absolute fold change > 1.5 and Padj < 0.05) in antenatal maternal circulation as compared to the postnatal phase, with phosphatidylethanolamine levels changing the most. Compared to antenatal maternal lipids, cord blood showed lower concentrations of most lipid species (79%) except lysophospholipids and acylcarnitines. Changes in lipid concentrations from birth to 6 years of age were much higher in magnitude (log2FC=−2.10 to 6.25) than the changes observed between a 6-year-old child and an adult (postnatal mother) (log2FC=−0.68 to 1.18). Associations of cord blood lipidomic profiles with birth weight displayed distinct trends compared to the lipidomic profiles associated with child BMI at 6 years. Comparison of the results between the child and adult BMI identified similarities in association with consistent trends (R2=0.75). However, large number of lipids were associated with BMI in adults (67%) compared to the children (29%). Pre-pregnancy BMI was specifically associated with decrease in the levels of phospholipids, sphingomyelin, and several triacylglycerol species in pregnancy. Conclusions: In summary, our study provides a detailed landscape of the in utero lipid environment provided by the gestating mother to the growing fetus, and the magnitude of changes in plasma lipidomic profiles from birth to early childhood. We identified the effects of adiposity on the circulating lipid levels in pregnant and non-pregnant women as well as offspring at birth and at 6 years of age. Additionally, the pediatric vs maternal overlap of the circulating lipid phenotype of obesity risk provides intergenerational insights and early opportunities to track and intervene the onset of metabolic adversities. Clinical trial registration: This birth cohort is a prospective observational study, which was registered on 1 July 2010 under the identifier NCT01174875.Peer reviewe

Evaluation of Normalization Approaches for Quantitative Analysis of Bile Acids in Human Feces

10.3390/metabo12080723METABOLITES12

Molecular Docking of Bacterial Protein Modulators and Pharmacotherapeutics of <i>Carica papaya</i> Leaves as a Promising Therapy for Sepsis: Synchronising In Silico and In Vitro Studies

Sepsis is a serious health concern globally, which necessitates understanding the root cause of infection for the prevention of proliferation inside the host’s body. Phytochemicals present in plants exhibit antibacterial and anti-proliferative properties stipulated for sepsis treatment. The aim of the study was to determine the potential role of Carica papaya leaf extract for sepsis treatment in silico and in vitro. We selected two phytochemical compounds, carpaine and quercetin, and docked them with bacterial proteins, heat shock protein (PDB ID: 4PO2), surfactant protein D (PDB ID: 1PW9), and lactobacillus bacterial protein (PDB ID: 4MKS) against imipenem and cyclophosphamide. Quercetin showed the strongest interaction with 1PW9 and 4MKS proteins. The leaves were extracted using ethanol, methanol, and water through Soxhlet extraction. Total flavonoid content, DPPH assay, HPTLC, and FTIR were performed. In vitro cytotoxicity of ethanol extract was screened via MTT assay on the J774 cell line. Ethanol extract (EE) possessed the maximum number of phytocomponents, the highest amount of flavonoid content, and the maximum antioxidant activity compared to other extracts. FTIR analysis confirmed the presence of N-H, O-H, C-H, C=O, C=C, and C-Cl functional groups in ethanol extract. Cell viability was highest (100%) at 25 µg/mL of EE. The present study demonstrated that the papaya leaves possessed antibacterial and cytotoxic activity against sepsis infection

Deciphering the response of thirteen apple cultivars for growth, fruit morphology and fruit physico-chemical attributes during different years

Apple cultivation is one of the most significant means of subsistence in the Kashmir region of the northwestern Himalayas. It is considered as the backbone of the region's economy. Apple cultivation in the region is dominated by a late maturing cultivar “Red Delicious” which usually on maturity causes glut in the market. In order to bring new cultivars in the cultivation, and to expand the maturity season, it is necessary to evaluate the new cultivars on fruit physico-chemical attributes which ultimately decide the market rates before recommending to farmers for cultivars adoption. Therefore, the current study was carried out to evaluate thirteen apple cultivars on physico-chemical attributes over two years, 2017 and 2018 under agro-climatic conditions of Kashmir region The results revealed that cultivars differed significantly in terms of physico-chemical properties. Cultivars with the highest and lowest values for initial fruit set, fruit drop, final fruit retention, and fruit firmness in 2017 did not follow the same trend in 2018. During 2017 and 2018, cultivar Mollie's Delicious possessed the highest fruit length (72.39 mm and 81.45 mm), fruit diameter (81.18 mm and 84.14 mm), and fruit weight (205.85 g and 247.16 g), whereas cultivar Baleman's Cider had the lowest values (50.76 mm and 52.83 mm, 60.10 mm and 62.08 mm, and 71.46 g and 86.94 g), respectively. The harvesting dates were quite spread out during both years of study. Cultivar Mollie's Delicious was harvested the earliest in both years, on August 5th, 2017 and August 8th, 2018. Cultivar Fuji Zehn Aztec was the last cultivar harvested in 2017 on October 2 and in 2018 on October 5. The maximum number of seeds per fruit was noticed in the cultivar Mollie's Delicious (8.34 and 8.71) during both 2017 and 2018, respectively. Cultivar Starkrimson had the fewest seeds per fruit in 2017 (7.11) and 2018 (7.42). Cultivar Baleman's Cider had the highest acidity in 2017 (0.63%) and 2018 (0.52%). In both 2017 (0.25%) and 2018 (0.23%), the Adam's Pearmain cultivar was the least acidic. Cultivar Allington Pippin (16.13 °Brix) and Red Gold (16.73 °Brix) had the highest TSS in 2017 and 2018, respectively, whereas Vance Delicious (12.30 °Brix) and Top Red (10.78 °Brix) had the lowest TSS in 2017 and 2018, respectively. The cultivars Mollie's Delicious and Red Gold had the highest total sugars (11.33 and 11.40%) in 2017 and 2018, respectively. Cultivar Baleman's Cider had the lowest total sugars (9.82%) in 2017 while Top Red (9.78%) in 2018. The cultivar Vance Delicious had the highest ratio of leaves to fruits in 2017 (55.44) and for Shalimar Apple-2 in 2018 (49.65). In 2017, cultivars Fuji Zehn Aztec (29.26) and Silver Spur (24.51), had the fewest leaves per fruit. The highest leaf chlorophyll content was recorded in cultivar Shireen (3.50 and 3.57 mg g−1 fresh weight) during the years 2017 and 2018, respectively. Cultivar Baleman's Cider had the lowest leaf chlorophyll content (2.15 mg g−1 fresh weight) during 2017, while cultivar Allington Pippin (2.09 mg g−1 fresh weight) had the lowest leaf chlorophyll content in 2018. The cultivars Fuji Zehn Aztec, with a yield efficiency of 0.78 kg/cm2 and Silver Spur with a yield efficiency of 1.14 kg/cm2 were the most yield efficient during the years 2017 and 2018, respectively. Cultivar Shalimar Apple-2 was least performing with yield efficiencies of 0.05 and 0.07 kg/cm2 during 2017 and 2018, respectively.The findings suggest that cultivar Mollie's Delicious commercially matures first and has the highest fruit length, diameter, and weight; hence, it can be a good option for cultivation so as to fetch the maximum price in the market when other cultivars are still maturing. Shalimar Apple-2 is precluded for cultivation due to least yield efficiency, whereas cultivars Fuji Zehn Aztec and Silver Spur are recommended to farmers for their higher yield efficiency

Lipidomic Analysis of Archival Pathology Specimens Identifies Altered Lipid Signatures in Ovarian Clear Cell Carcinoma

Cancer metabolism is associated with the enhanced lipogenesis required for rapid growth and proliferation. However, the magnitude of dysregulation of diverse lipid species still requires significant characterization, particularly in ovarian clear cell carcinoma (OCCC). Here, we have implemented a robust sample preparation workflow together with targeted LC-MS/MS to identify the lipidomic changes in formalin-fixed paraffin-embedded specimens from OCCC compared to tumor-free ovarian tissue. We quantitated 340 lipid species, representing 28 lipid classes. We observed differential regulation of diverse lipid species belonging to several glycerophospholipid classes and trihexosylceramide. A number of unsaturated lipid species were increased in OCCC, whereas saturated lipid species showed a decrease in OCCC compared to the controls. We also carried out total fatty acid analysis and observed an increase in the levels of several unsaturated fatty acids with a concomitant increase in the index of stearoyl-CoA desaturase (SCD) in OCCC. We confirmed the upregulation of SCD (the rate-limiting enzyme for the synthesis of monounsaturated fatty acids) by immunohistochemistry (IHC) assays. Hence, by carrying out a mass spectrometry analysis of archival tissue samples, we were able to provide insights into lipidomic alterations in OCCC

Lipid bilayer composition as a determinant of cancer cell sensitivity to tumoricidal protein-lipid complexes

Complexes formed by the alpha1 N-terminal peptide of alpha-lactalbumin and oleic acid (alpha1-oleate) interact with lipid bilayers. Plasma membrane perturbations trigger tumor cell death but normal differentiated cells are more resistant, and their plasma membranes are less strongly affected. This study examined membrane lipid composition as a determinant of tumor cell reactivity. Bladder cancer tissue showed a higher abundance of unsaturated lipids enriched in phosphatidylcholine, PC (36:4) and PC (38:4), and sphingomyelin, SM (36:1) than healthy bladder tissue, where saturated lipids predominated and the lipid extracts from bladder cancer tissue inhibited the tumoricidal effect of the complex more effectively than healthy tissue extracts. Furthermore, unsaturated PC in solution inhibited tumor cell death, and the complex interacted with giant unilamellar vesicles formed by PC, confirming the affinity of alpha1-oleate for fluid membranes enriched in PC. Quartz Crystal Microbalance with dissipation monitoring (QCM-D) detected a preference of the complex for the liquid-disordered phase, suggesting that the insertion into PC-based membranes and the resulting membrane perturbations are influenced by membrane lipid saturation. The results suggest that the membrane lipid composition is functionally important and that specific unsaturated membrane lipids may serve as “recognition motifs” for broad-spectrum tumoricidal molecules such as alpha1-oleate

Plasma lipidomic profiling reveals metabolic adaptations to pregnancy and signatures of cardiometabolic risk : a preconception and longitudinal cohort study

BackgroundAdaptations in lipid metabolism are essential to meet the physiological demands of pregnancy and any aberration may result in adverse outcomes for both mother and offspring. However, there is a lack of population-level studies to define the longitudinal changes of maternal circulating lipids from preconception to postpartum in relation to cardiometabolic risk factors.MethodsLC-MS/MS-based quantification of 689 lipid species was performed on 1595 plasma samples collected at three time points in a preconception and longitudinal cohort, Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO). We mapped maternal plasma lipidomic profiles at preconception (N = 976), 26-28 weeks' pregnancy (N = 337) and 3 months postpartum (N = 282) to study longitudinal lipid changes and their associations with cardiometabolic risk factors including pre-pregnancy body mass index, body weight changes and glycaemic traits.ResultsAround 56% of the lipids increased and 24% decreased in concentration in pregnancy before returning to the preconception concentration at postpartum, whereas around 11% of the lipids went through significant changes in pregnancy and their concentrations did not revert to the preconception concentrations. We observed a significant association of body weight changes with lipid changes across different physiological states, and lower circulating concentrations of phospholipids and sphingomyelins in pregnant mothers with higher pre-pregnancy BMI. Fasting plasma glucose and glycated haemoglobin (HbA1c) concentrations were lower whereas the homeostatic model assessment of insulin resistance (HOMA-IR), 2-h post-load glucose and fasting insulin concentrations were higher in pregnancy as compared to both preconception and postpartum. Association studies of lipidomic profiles with these glycaemic traits revealed their respective lipid signatures at three physiological states. Assessment of glycaemic traits in relation to the circulating lipids at preconception with a large sample size (n = 936) provided an integrated view of the effects of hyperglycaemia on plasma lipidomic profiles. We observed a distinct relationship of lipidomic profiles with different measures, with the highest percentage of significant lipids associated with HOMA-IR (58.9%), followed by fasting insulin concentration (56.9%), 2-h post-load glucose concentration (41.8%), HbA1c (36.7%), impaired glucose tolerance status (31.6%) and fasting glucose concentration (30.8%).ConclusionsWe describe the longitudinal landscape of maternal circulating lipids from preconception to postpartum, and a comprehensive view of trends and magnitude of pregnancy-induced changes in lipidomic profiles. We identified lipid signatures linked with cardiometabolic risk traits with potential implications both in pregnancy and postpartum life. Our findings provide insights into the metabolic adaptations and potential biomarkers of modifiable risk factors in childbearing women that may help in better assessment of cardiometabolic health, and early intervention at the preconception period.Peer reviewe