Urine Metabolomics Reveals Overlapping Metabolic Associations Between Preeclampsia and Gestational Diabetes.

Pregnancy is associated with numerous metabolic adaptations to meet the demands of the growing foetus. These adaptations could be perturbed during pregnancy due to preeclampsia (PE) and gestational diabetes (GDM). As these two obstetric aliments show some overlapping pathophysiology and similar biochemical dysregulation, the present study was undertaken to compare urine metabolome of PE and GDM with normal pregnancy (NT) in all trimesters of gestation using nuclear magnetic resonance spectroscopy-based metabolomics analysis to ascertain and compare metabolome in the study groups. We observed overlapping metabolic perturbations in PE and GDM. Though a study with a small sample size, this is the first report which confirms significantly differential metabolites in urine of both PE and GDM. Dimethylglycine and oxoglutaric acid were decreased while benzoic acid was increased in both the cases in all trimesters. Alanine, aspartate and glutamate metabolism, aminoacyl-tRNA biosynthesis, citrate and butanoate metabolism were the most perturbed pathways in both PE and GDM across pregnancy. These pathways have an association with energy metabolism, glucose homeostasis, insulin sensitivity and oxidative stress which play an important role in the development and progression of PE and GDM. In conclusion, our study showed that urine metabolome could reflect metabolic associations between PE and GDM and also in the identification of biomolecules that could be used as potential biomarker(s) for early detection of the metabolic diseases in pregnancy. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01103-2.

Plant metabolite diosmin as the therapeutic agent in human diseases.

Plant-derived flavonoids have been the focus of research for many years mainly in the last decade owing to their therapeutic properties. So far, about 4000 flavonoids have been identified from plants and diosmin (a flavone glycoside) is one of them. Online databases, previous studies, and reviews have been used to gather information on anti-oxidant, immunomodulatory, anti-cancer, anti-parasitic, and anti-microbialproperties of diosmin. Effects of diosmin in combination with other flavonoids have been reviewed thoroughly and its administrative routes are also summarized. Additionally, we studied the effect of diosmin on critical protein networks. It exhibits therapeutic effects in diabetes and its associated complications such as neuropathy and dyslipidemia. Combination of diosmin with hesperidin is found to be very effective in the treatment of chronic venous insufficiency and haemorrhoids. Diosmin is an exquisite therapeutic agent alone as well as in combination with other flavonoids.

A combined approach against tumorigenesis using glucose deprivation and mitochondrial complex 1 inhibition by rotenone.

Cancer cells exhibit various degrees of mitochondrial metabolic alterations. Owing to their multiple roles, mitochondria are attractive target for cancer therapy. Cancerous cells have high glucose (HG) requirements for their growth. Depriving them of glucose has been an approach used in many studies to restrict their perpetuation. However, such deprivation can negatively affect the surrounding normal cells in vivo. Keeping this in view, we treated HeLa cells with only physiological glucose (PG, 5.5 mM) and a combination of physiological glucose with a very low dose (1 nM) of rotenone (PGT), taking high glucose (HG, 25 mM)-treated HeLa cells as normal. We demonstrated that HeLa cells under PG condition mainly exhibited growth arrest. The PGT combination induced apoptosis in HeLa cells by generation of ROS, decrease in ATP production even with around 1.89-fold increase in glucose consumption, cell cycle arrest at S-phase and substantial increase in sub-diploid (Sub-D) population. The oxidative stress generated in both PG and PGT conditions stabilised p53 by localising it in the nuclei of HeLa cells, which would have otherwise undergone HPV-mediated inactivation. Pre-mature senescence induced due to limited glucose availability was found to be regulated by nuclear translocated p53 which, in turn, induced p21, pAkt and pERK. The cyto-toxic effect of rotenone on glucose deprived HeLa cells, synergistically activated NFκB, caspase-3 and Bax along with reduced expression of hyaluronan, a ROS scavenging molecule on their cell surface. Thus, our finding might be a valuable approach to specifically target cancerous cells in a more physiologically feasible condition and can serve as a relevant biochemical basis to gain new insights into cancer therapy.

Low-dose rotenone exposure induces early senescence leading to late apoptotic signaling cascade in human trabecular meshwork (HTM) cell line: An in vitro glaucoma model.

This study aimed to determine whether the prolonged exposure of the human trabecular meshwork (HTM) cell line to a low dose (1 nM) of rotenone could simulate a glaucomatous-like condition and serve as a cellular model for its etiological analysis. Under 1-nM rotenone exposure for 24-72 h, HTM cells showed a decrease in cell viability as assessed by an MTT assay and showed mitochondrial dysfunction as assessed by measuring H2 DCFDA fluorescence; a decrease in ATP level was also observed. Flow cytometric analysis showed an increase in cellular size and granularity. Elevated AF showed initial senescence. LF staining with SBB and its spectrofluorometric quantification confirmed growth arrest. An accumulation of cytoplasmic myocilin, IL-6, and MMP-9 at 72 h of exposure supported glaucomatous induction. TEM revealed morphological changes in mitochondria and nuclei of treated cells. Signaling cascades were assessed by immunoblotting and immunocytochemical analysis. This study showed a shift in status of the cells from initial senescence to induction of apoptosis in the HTM cell line due to continuous low-dose exposure to rotenone; however, at 72 h, both senescence and apoptotic features are apparent in these cells. This is the first report that reveals the potential of a prolonged low-dose exposure of rotenone to simulate senescence in the HTM cell line to cause a glaucomatous condition.