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Background & aimsStunting in children is a comorbid condition in undernutrition that may be ameliorated by the provision of high-quality foods that provide protein and micronutrients. Addressing this problem in lower social economic environments requires, in part, affordable and scalable food-based solutions with efficacious food products. Towards this end, biochemical/metabolic indicators for fast-throughput screening of foods and their components are desired. A highly acceptable and economical micronutrient-fortified food product with different levels of legume protein was provided to stunted Indian children for one month, to determine change in their linear growth and explore associated biochemical, metabolomic and microbiome indicators.MethodsA randomized controlled pilot trial was conducted with 100 stunted children (6-10 years of age) to elucidate metabolic and microbiome-based biomarkers associated with linear growth. They were randomized into 4 groups receiving 6, 8, 10 or 12 g of legume-based protein for one month. Anthropometry, blood biochemistry, aminoacidomics, acylcarnitomics and fecal microbiome were measured before and after feeding.ResultsNo significant differences were observed between groups in height, height-for-age Z-score (HAZ) or BMI-for-age Z-score (BAZ); however, 38 serum metabolites were altered significantly (Bonferroni adjusted P  0.2, P = 0.02), while serine and ornithine (ρ  1.5) were significantly correlated with change in height.ConclusionsIn this pilot trial, a number of fasting serum metabolomic and fecal microbiome signatures were associated with linear growth after a short-term dietary intervention. The alterations of these markers should be validated in long-term dietary intervention trials as potential screening indicators towards the development of food products that favor growth. This trial was registered at www.ctri.nic.in as CTRI/2016/12/007564.

Arterial morphogenesis is an important and poorly understood process. In particular, the signaling events controlling arterial formation have not been established. We evaluated whether alterations in the balance between ERK1/2 and PI3K signaling pathways could stimulate arterial formation in the setting of defective arterial morphogenesis in mice and zebrafish. Increased ERK1/2 activity in mouse ECs with reduced VEGF responsiveness was achieved in vitro and in vivo by downregulating PI3K activity, suppressing Akt1 but not Akt2 expression, or introducing a constitutively active ERK1/2 construct. Such restoration of ERK1/2 activation was sufficient to restore impaired arterial development and branching morphogenesis in synectin-deficient mice and synectin-knockdown zebrafish. The same approach effectively stimulated arterial growth in adult mice, restoring arteriogenesis in mice lacking synectin and in atherosclerotic mice lacking both LDL-R and ApoB48. We therefore conclude that PI3K-ERK1/2 crosstalk plays a key role in the regulation of arterial growth and that the augmentation of ERK signaling via suppression of the PI3K signaling pathway can effectively stimulate arteriogenesis., Introduction Effective stimulation of arteriogenesis has long been an important therapeutic aim in clinical medicine. Attempts at stimulating it using various growth factors have failed largely because of impaired signaling [...]

The belief that the divine is embedded in nature is part of the spiritual discourse of the religions of antiquity. Nature has been worshipped in one form or the other in different cultures of the world. In India, rivers are considered sacred, purifying, life-giving, and redeeming. The corporeality of the rivers is subsumed and often modified by its metaphorical, mystical, and transcendental associations. The Ganga (Ganges), the Yamuna, the Sarasvati, the Narmada, and other major and minor rivers of India are narrativized within a sacred discourse. The myths, rituals, and belief systems surrounding river worship in India are woven into the syncretic and composite cultural mosaic. However, the contemporary realities of globalization and environmental crises raise quite a few questions regarding the paradoxical nature of this sacred discourse. This essay explores the cultures of river worship in India in its scriptural as well as quotidian forms and attempts to understand the tangible and intangible issues contributing to its continuance and to locate the interface between religious discourse and environmental ethics. [ABSTRACT FROM AUTHOR]

Objectives: Aberrations in placental vascular development compromising fetal supply of oxygen and essential nutrients can be a significant contributor to intrauterine growth restriction (IUGR). The development of placental vascular tree is under the influence of two families of growth factors, namely the vascular endothelial growth factor (VEGF) family and angiopoietin/TEK family. In this study, we have examined the expression of angiogenesis-related growth factors, mainly VEGF family and angiopoietin-TEK (endothelial-specific receptor tyrosine kinase) family genes in placentae from IUGR pregnancies uncomplicated by preeclampsia (PE) compared to normal pregnancies. Methods: Placentae from normotensive IUGR (n = 42) and appropriate for gestational age (AGA) pregnancies (n = 47) were collected and examined histologically. Clinical parameters were obtained from the medical records. Real-time quantitative PCR was performed to assess placental transcript abundance of VEGF, PGF, FLT1, ANGPT1, ANGPT2, and TEK normalized to a panel of reference genes. Associations of placental transcript abundance of the genes with maternal, placental, and neonatal parameters were tested. Results: Placental transcript abundance for VEGF (relative expression 10.81 versus 12.98, p <.001), PGF (12.14 versus 13.8, p <.001) and ANGPT2 (3.67 versus 9.55, p =.002) were significantly lower in IUGR placentae compared to AGA. The transcript level of VEGF showed significant negative correlation with birth weight (r = −0.419, p =.006), placental weight (r = −0.318, p =.040), placental length (r = −0.389, p =.011) and breadth (r = −0.308, p =.047) only in the IUGR group. Presence of histopathological features of hypoxia correlated with significantly higher transcript levels of PGF in IUGR placentae (12.6 versus 10.9, p =.046). Conclusion: The low levels of VEGF transcripts may be responsible for the impaired angiogenesis in IUGR placentae. The significance of higher relative expression of PGF in the presence of chronic hypoxia needs to be explored. [ABSTRACT FROM AUTHOR]

The prevalence of the double burden of malnutrition in society is well known with the coexistence of undernutrition with an increase in overweight/obesity; this has been increasing globally with nutritional imbalances and infectious diseases being the major etiological factors. However, there is also the coexistence of inappropriate adiposity or metabolic dysfunction in an individual who appears currently undernourished by anthropometric standards (stunted or underweight); this is the intraindividual double burden of malnutrition. It could also occur in temporal sequence, as anthropometric overweight in an individual who has previously endured childhood under-nutrition. IIDBM has increased the risk for diet-related non-communicable diseases over the past few decades, as it tracks into adulthood, warranting an urgent need for intervention and prevention. While gut dysbiosis has been associated with various forms of malnutrition, the early life gut microbiome composition and its related metabolites and regulatory factors, are possibly linked to the development of inflammatory and metabolic conditions in IIDBM. The possible underlying physiological mechanisms are reviewed here, working through host dietary influences, gut microbial metabolites, host inflammation and metabolic dysregulation. When validated experimentally and tested through appropriately designed randomised, controlled trials, these mechanistic insights will likely lead to development of preventive strategies. [ABSTRACT FROM AUTHOR]

Arterial morphogenesis is an important and poorly understood process. In particular, the signaling events controlling arterial formation have not been established. We evaluated whether alterations in the balance between ERK1/2 and PI3K signaling pathways could stimulate arterial formation in the setting of defective arterial morphogenesis in mice and zebrafish. Increased ERK1/2 activity in mouse ECs with reduced VEGF responsiveness was achieved in vitro and in vivo by downregulating PI3K activity, suppressing Akt1 but not Akt2 expression, or introducing a constitutively active ERK1/2 construct. Such restoration of ERK1/2 activation was sufficient to restore impaired arterial development and branching morphogenesis in synectin-deficient mice and synectin-knockdown zebrafish. The same approach effectively stimulated arterial growth in adult mice, restoring arteriogenesis in mice lacking synectin and in atherosclerotic mice lacking both LDL-R and ApoB48. We therefore conclude that PI3K-ERK1/2 crosstalk plays a key role in the regulation of arterial growth and that the augmentation of ERK signaling via suppression of the PI3K signaling pathway can effectively stimulate arteriogenesis. [ABSTRACT FROM AUTHOR]

Antivascular agents have become a standard of treatment for many malignancies. However, most of them target the VEGF pathway and lead to refractoriness. To improve the diversity of options for antivascular therapy, we applied a high-throughput screen for small molecules targeting cell adhesion. We then assayed the resulting antiadhesion hits in a transgenic zebrafish line with endothelial expression of EGFP (Tg(fli1:EGFP)(y1)) to identify nontoxic molecules with antivascular activity selective to neovasculature. This screen identified dehydro-α-lapachone (DAL), a natural plant product. We found that DAL inhibits vessel regeneration, interferes with vessel anastomosis, and limits plexus formation in zebrafish. Furthermore, DAL induces vascular pruning and growth delay in orthotopic mammary tumors in mice. We show that DAL targets cell adhesion by promoting ubiquitination of the Rho-GTPase Rac1, which is frequently up-regulated in many different cancers.