Longitudinal Metabolomics Reveals Metabolic Dysregulation Dynamics in Patients with Severe COVID-19.

A dysregulated metabolism has been studied as a key aspect of the COVID-19 pathophysiology, but its longitudinal progression in severe cases remains unclear. In this study, we aimed to investigate metabolic dysregulation over time in patients with severe COVID-19 requiring mechanical ventilation (MV). In this single-center, prospective, observational study, we obtained 236 serum samples from 118 adult patients on MV in an ICU.

Exercise therapy for chronic pain: How does exercise change the limbic brain function?

We are exposed to various external and internal threats which might hurt us. The role of taking flexible and appropriate actions against threats is played by "the limbic system" and at the heart of it there is the ventral tegmental area and nucleus accumbens (brain reward system). Pain-related fear causes excessive excitation of amygdala, which in turn causes the suppression of medial prefrontal cortex, leading to chronification of pain.

Determination of the Minimum Sample Amount for Capillary Electrophoresis-Fourier Transform Mass Spectrometry (CE-FTMS)-Based Metabolomics of Colorectal Cancer Biopsies.

The minimum sample volume for capillary electrophoresis-Fourier transform mass spectrometry (CE-FTMS) useful for analyzing hydrophilic metabolites was investigated using samples obtained from colorectal cancer patients. One, two, five, and ten biopsies were collected from tumor and nontumor parts of the surgically removed specimens from each of the five patients who had undergone colorectal cancer surgery. Metabolomics was performed on the collected samples using CE-FTMS.

Voluntary running-induced activation of ventral hippocampal GABAergic interneurons contributes to exercise-induced hypoalgesia in neuropathic pain model mice.

The exact mechanism of exercise-induced hypoalgesia (EIH) in exercise therapy to improve chronic pain has not been fully clarified. Recent studies have suggested the importance of the ventral hippocampus (vHPC) in inducing chronic pain. We investigated the effects of voluntary running (VR) on FosB cells and GABAergic interneurons (parvalbumin-positive [PV] and somatostatin-positive [SOM]) in the vHPC-CA1 in neuropathic pain (NPP) model mice.

Exercise-induced increase in M2 macrophages accelerates wound healing in young mice.

Moderate-intensity exercise performed during wound healing has been reported to decrease inflammatory cytokines and chemokines and accelerate wound healing. However, its effect on macrophage phenotype and the mechanism by which exercise accelerates wound healing remain unclear. The purpose of this study was to investigate the effect of exercise on macrophage phenotype during wound healing and to clarify the relationship between angiogenesis and wound healing.

Metabolomics with severity of radiographic knee osteoarthritis and early phase synovitis in middle-aged women from the Iwaki Health Promotion Project: a cross-sectional study.

Background: Osteoarthritis (OA) is one of the costliest and most disabling forms of arthritis, and it poses a major public health burden; however, its detailed etiology, pathophysiology, and metabolism remain unclear. Therefore, the purpose of this study was to investigate the key plasma metabolites and metabolic pathways, especially focusing on radiographic OA severity and synovitis, from a large sample cohort study.

Methods: We recruited 596 female volunteers who participated in the Iwaki Health Promotion Project in 2017.

Brain Mechanisms of Exercise-Induced Hypoalgesia: To Find a Way Out from "Fear-Avoidance Belief".

It is well known that exercise produces analgesic effects (exercise-induced hypoalgesia (EIH)) in animal models and chronic pain patients, but the brain mechanisms underlying these EIH effects, especially concerning the emotional aspects of pain, are not yet fully understood. In this review, we describe drastic changes in the mesocorticolimbic system of the brain which permit the induction of EIH effects. The amygdala (Amyg) is a critical node for the regulation of emotions, such as fear and anxiety, which are closely associated with chronic pain.

Uncovering the Role of Gut Microbiota in Amino Acid Metabolic Disturbances in Heart Failure Through Metagenomic Analysis.

Circulating amino acid (AA) abnormalities serve as predictors of adverse outcomes in patients with heart failure (HF). However, the role of the gut microbiota in AA disturbances remains unknown. Thus, we investigated gut microbial functions and their associations with AA metabolic alterations in patients with HF.

Nontargeted Serum Lipid Profiling of Nonalcoholic Steatohepatitis by Multisegment Injection-Nonaqueous Capillary Electrophoresis-Mass Spectrometry: A Multiplexed Separation Platform for Resolving Ionic Lipids.

New methods are needed for global lipid profiling due to the complex chemical structures and diverse physicochemical properties of lipids. Herein we introduce a robust data workflow to unambiguously select lipid features from serum ether extracts by multisegment injection-nonaqueous capillary electrophoresis-mass spectrometry (MSI-NACE-MS). An iterative three-stage screening strategy is developed for nontargeted lipid analyses when using multiplexed electrophoretic separations coupled to an Orbitrap mass analyzer under negative ion mode.

Metagenomic analysis of gut microbiota reveals its role in trimethylamine metabolism in heart failure.

Background: We had previously reported an increase in trimethylamine N-oxide (TMAO) levels in patients with both compensated and decompensated heart failure (HF) and alteration in gut microbiota composition using 16S rRNA gene amplicon analysis. Although a metagenome-wide analysis showed that choline-TMA lyase levels increased in HF patients, which TMA generation pathway from choline, carnitine, or betaine contributes to the increase in TMAO levels in HF needs to be elucidated.

Methods: We conducted a metagenome-wide shotgun sequencing analysis of gut microbiota and measured the TMAO levels in plasma of 22 HF patients during the compensated phase and 11 age-, sex-, and comorbidity-matched control subjects, whose gut microbiota compositions were reported in a previous 16S rRNA-based analysis.

Capillary Electrophoresis Mass Spectrometry-Based Metabolomics of Plasma Samples from Healthy Subjects in a Cross-Sectional Japanese Population Study.

For large-scale metabolomics, such as in cohort studies, normalization protocols using quality control (QC) samples have been established when using data from gas chromatography and liquid chromatography coupled to mass spectrometry. However, normalization protocols have not been established for capillary electrophoresis-mass spectrometry metabolomics. In this study, we performed metabolome analysis of 314 human plasma samples using capillary electrophoresis-mass spectrometry.

Plastic changes in amygdala subregions by voluntary running contribute to exercise-induced hypoalgesia in neuropathic pain model mice.

Physical exercise has been established as a low-cost, safe, and effective way to manage chronic pain, but exact mechanisms underlying such exercise-induced hypoalgesia (EIH) are not fully understood. Since a growing body of evidence implicated the amygdala (Amyg) as a critical node in emotional affective aspects of chronic pain, we hypothesized that the Amyg may play important roles to produce EIH effects. Here, using partial sciatic nerve ligation (PSL) model mice, we investigated the effects of voluntary running (VR) on the basal amygdala (BA) and the central nuclei of amygdala (CeA).

Metabolomic profiling of gastric cancer tissues identified potential biomarkers for predicting peritoneal recurrence.

Background: Metabolomics is useful for analyzing the nutrients necessary for cancer progression, as the proliferation is regulated by available nutrients. We studied the metabolomic profile of gastric cancer (GC) tissue to elucidate the associations between metabolism and recurrence.

Methods: Cancer and adjacent non-cancerous tissues were obtained in a pair-wise manner from 140 patients with GC who underwent gastrectomy.

Role of 72-kDa Heat Shock Protein in Heat-stimulated Regeneration of Injured Muscle in Rat.

The regeneration of injured muscles is facilitated by intermittent heat stress. The 72-kDa heat shock protein (HSP72), the level of which is increased by heat stress, is likely involved in this effect, but the precise mechanism remains unclear. This study was conducted to investigate the localization and role(s) of HSP72 in the regenerating muscles in heat-stressed rats using immunohistochemistry.

Extraction of Aqueous Metabolites from Cultured Adherent Cells for Metabolomic Analysis by Capillary Electrophoresis-Mass Spectrometry.

Metabolomic analysis is a promising omics approach to not only understand the specific metabolic regulation in cancer cells compared to normal cells but also to identify biomarkers for early-stage cancer detection and prediction of chemotherapy response in cancer patients. Preparation of uniform samples for metabolomic analysis is a critical issue that remains to be addressed. Here, we present an easy and reliable protocol for extracting aqueous metabolites from cultured adherent cells for metabolomic analysis using capillary electrophoresis-mass spectrometry (CE-MS).

Gut Microbiome and Plasma Microbiome-Related Metabolites in Patients With Decompensated and Compensated Heart Failure.

Background: Gut microbiome composition or circulating microbiome-related metabolites in patients with heart failure (HF) have not been investigated at different time points (i.e., in the decompensated (Decomp) and compensated (Comp) phases).

Activation of mesolimbic reward system via laterodorsal tegmental nucleus and hypothalamus in exercise-induced hypoalgesia.

Ventral tegmental area (VTA) dopamine (DA) neurons are the primary source of dopamine in target structures that constitute the mesolimbic reward system. Previous studies demonstrated that voluntary wheel running (VWR) by neuropathic pain (NPP) model mice produces exercise-induced hypoalgesia (EIH), and that activation of mesolimbic reward system may lead to EIH. However, the neuronal mechanism by which the mesolimbic reward system is activated by VWR is unknown.

Metabolome analysis of esophageal cancer tissues using capillary electrophoresis-time-of-flight mass spectrometry.

Reports of the metabolomic characteristics of esophageal cancer are limited. In the present study, we thus conducted metabolome analysis of paired tumor tissues (Ts) and non-tumor esophageal tissues (NTs) using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). The Ts and surrounding NTs were surgically excised pair-wise from 35 patients with esophageal cancer.

Mycoplasma infection and hypoxia initiate succinate accumulation and release in the VM-M3 cancer cells.

Succinate is known to act as an inflammatory signal in classically activated macrophages through stabilization of HIF-1α leading to IL-1β production. Relevant to this, hypoxia is known to drive succinate accumulation and release into the extracellular milieu. The metabolic alterations associated with succinate release during inflammation and under hypoxia are poorly understood.

Language continuity despite population replacement in Remote Oceania.

Recent genomic analyses show that the earliest peoples reaching Remote Oceania-associated with Austronesian-speaking Lapita culture-were almost completely East Asian, without detectable Papuan ancestry. However, Papuan-related genetic ancestry is found across present-day Pacific populations, indicating that peoples from Near Oceania have played a significant, but largely unknown, ancestral role. Here, new genome-wide data from 19 ancient South Pacific individuals provide direct evidence of a so-far undescribed Papuan expansion into Remote Oceania starting ~2,500 yr BP, far earlier than previously estimated and supporting a model from historical linguistics.

A new aspect of chronic pain as a lifestyle-related disease.

Physical exercise has been established as a low-cost, safe, and effective way to manage chronic intractable pain. We investigated the underlying mechanisms of exercise-induced hypoalgesia (EIH) using a mouse model of neuropathic pain (NPP). Epigenetic changes in activated microglia and maintained GABA synthesis in the spinal dorsal horn may contribute to EIH.

CD44 variant 9 expression as a predictor for gastric cancer recurrence: immunohistochemical and metabolomic analysis of surgically resected tissues.

CD44 variant 9 (CD44v9) and the heavy chain of 4F2 cell-surface antigen (CD98hc) appear important for regulation of reactive oxygen species defence and tumor growth in gastric cancer. This study examined the roles of CD44v9 and CD98hc as markers of gastric cancer recurrence, and investigated associations with energy metabolism. We applied capillary electrophoresis time-of-flight mass spectrometry to metabolome profiling of gastric cancer specimens from 103 patients who underwent resection with no residual tumor or microscopic residual tumor, and compared metabolite levels to immunohistochemical staining for CD44v9 and CD98hc.