Environment Impacts the Metabolic Dependencies of Ras-Driven Non-Small Cell Lung Cancer

Cultured cells convert glucose to lactate, and glutamine is the major source of tricarboxylic acid (TCA)-cycle carbon, but whether the same metabolic phenotype is found in tumors is less studied. We infused mice with lung cancers with isotope-labeled glucose or glutamine and compared the fate of these nutrients in tumor and normal tissue. As expected, lung tumors exhibit increased lactate production from glucose. However, glutamine utilization by both lung tumors and normal lung was minimal, with lung tumors showing increased glucose contribution to the TCA cycle relative to normal lung tissue. Deletion of enzymes involved in glucose oxidation demonstrates that glucose carbon contribution to the TCA cycle is required for tumor formation. These data suggest that understanding nutrient utilization by tumors can predict metabolic dependencies of cancers in vivo. Furthermore, these data argue that the in vivo environment is an important determinant of the metabolic phenotype of cancer cells.National Science Foundation (U.S.) (Grant T32GM007287

Numerical Simulation of Asymmetrically Altered Growth as Initiation Mechanism of Scoliosis

The causes of idiopathic scoliosis are still uncertain; buckling is mentioned often, but never proven. The authors hypothesize another option: unilateral postponement of growth of MM Rotatores or of ligamentum flavum and intertransverse ligament. In this paper, both buckling and the two new theories of scoliotic initiation are studied using a new finite element model that simulates the mechanical behavior of the human spine. This model was validated by the stiffness data of Panjabi et al. (J. Biomech. 9:185–192, 1976). After a small correction of the prestrain of some ligaments and the MM Rotatores the model appeared to be valid. The postponement in growth was translated in the numerical model in an asymmetrical stiffness. The spine was loaded axially and the resulting deformation was analyzed for the presence of the coupling of lateral deviation and axial rotation that is characteristic for scoliosis. Only unilateral postponement of growth of ligamentum flavum and intertransverse ligament appeared to initiate scoliosis. Buckling did not initiate scoliosis

Clinical and biological heterogeneity of multisystem inflammatory syndrome in adults following SARS-CoV-2 infection: a case series

ImportanceMultisystem inflammatory syndrome in adults (MIS-A) is a poorly understood complication of SARS-CoV-2 infection with significant morbidity and mortality.ObjectiveIdentify clinical, immunological, and histopathologic features of MIS-A to improve understanding of the pathophysiology and approach to treatment.DesignThree cases of MIS-A following SARS-CoV-2 infection were clinically identified between October 2021 – March 2022 using the U.S. Centers for Disease Control and Prevention diagnostic criteria. Clinical, laboratory, imaging, and tissue data were assessed.FindingsAll three patients developed acute onset cardiogenic shock and demonstrated elevated inflammatory biomarkers at the time of hospital admission that resolved over time. One case co-occurred with new onset Type 1 diabetes and sepsis. Retrospective analysis of myocardial tissue from one case identified SARS-CoV-2 RNA. All three patients fully recovered with standard of care interventions plus immunomodulatory therapy that included intravenous immunoglobulin, corticosteroids, and in two cases, anakinra.ConclusionMIS-A is a severe post-acute sequela of COVID-19 characterized by systemic elevation of inflammatory biomarkers. In this series of three cases, we find that although clinical courses and co-existent diseases vary, even severe presentations have potential for full recovery with prompt recognition and treatment. In addition to cardiogenic shock, glucose intolerance, unmasking of autoimmune disease, and sepsis can be features of MIS-A, and SARS-CoV-2 myocarditis can lead to a similar clinical syndrome

Synthesis, characterization, DNA interaction and pharmacological studies of substituted benzophenone derived Schiff base metal(II) complexes

A new bidentate NO type Schiff base ligand (HL), derived from 2-hydroxy-4-methoxyphenyl)phenylmethanone with aniline and its metal(II) [M = Mn, Co, Ni, Cu and Zn] complexes has been synthesized. The synthesized ligand and the metal(II) complexes were structurally characterized by analytical, spectral (FT-IR, UV–vis., 1H NMR, FAB-Mass, TGA/DTA and EPR) as well as molar conductance and magnetic studies. All the complexes are non-electrolytes having 1:2 stoichiometry. They adopt tetrahedral and octahedral geometry. Thermal behavior of metal(II) complexes (1a–1c) shows loss of coordinated water molecules in the first step followed by the decomposition of ligand moieties in a respective manner and leads to form an air stable metal oxide as the final residue. Micro crystalline nature and the presence of coordinated water molecules have been confirmed by powder XRD, SEM and thermal analyses. The ligand and its complexes have efficient bio-efficacy, DNA binding and cleavage ability

Epigenetic modifications impact metabolite production and lifespan in yeast

Epigenetics have been shown to play a crucial role in regulating gene expression during the aging and immune response processes, with changes in epigenetic marks being linked to age-related diseases and inflammatory responses. Recently it has been revealed that S-adenosyl-l-homocysteine can extend the lifespan of the budding yeast Saccharomyces cerevisiae by mimicking caloric restriction. In this present study, we aimed to activate the production of S-adenosyl-l-homocysteine by S. cerevisiae through introducing epigenetic changes as a result of exposure to benzoic acid, a known epigenetic modifier. The impact of this on metabolite production was evaluated using LC-MS/MS. The study successfully activated and measured an overproduction of S-adenosyl-l-homocysteine (SAH) in yeast previously exposed to benzoic acid and led to lifespan extension. The link between the aging process and immune responses in yeast was further explored in the study. The production of SAH was downregulated while several inflammatory response metabolites were upregulated in aging cells. The upregulation of inflammatory response metabolites with their inherent anti-viral and antimicrobial activities could potentially be valuable for use in human health applications. By contrast, in cells with higher lifespans these inflammatory metabolites were downregulated. This finding supports the concept that aging leads to higher levels of histone methylation and acetylation, which in turn cause the production of immune response metabolites and inflammation. By contrast, it appears that lower levels of histone methylation and acetylation as seen in healthy cells, can increase production of metabolites responsible for lifespan extension, such as SAH. In summary, this study provides insights into the molecular mechanisms involved in lifespan extension and the role of metabolites in regulating aging in yeast. The research sheds light on the interplay between metabolism, epigenetics, immunity and aging and contributes to the growing field of metabolomics

Tracheostomal Myiasis: A Case Report and Review of the Literature

“Myiasis” is considered in Hindu mythology as “God's punishment for sinners.” It is known to infest live human or animal tissue. Literature abounds with reports of myiasis affecting the nasal cavity, ear, nonhealing ulcers, exophytic malignant growth, and cutaneous tissue. But report of myiasis of the tracheal stoma is rare. Only a few cases of tracheal myiasis have been reported in literature. We report a case of tracheostomal myiasis in an elderly male. The species which had infested the stoma was identified as Chrysomya bezziana, an obligate parasite. This is to our knowledge the first case report of an obligate parasite (Chrysomya bezziana) infestation of the tracheostoma from India