Energy Metabolism Mechanisms Research Articles

The Role of Heat Shock Factor 1 in Preserving Proteomic Integrity During Copper-Induced Cellular Toxicity

Copper is crucial for many physiological processes across mammalian cells, including energy metabolism, neurotransmitter synthesis, and antioxidant defense mechanisms. However, excessive copper levels can lead to cellular toxicity and “cuproptosis”, a form of programmed cell death characterized by the accumulation of copper within mitochondria. Tumor cells are less sensitive to this toxicity than normal cells, the mechanism for which remains unclear. We address this important issue by exploring the role of heat shock factor 1 (HSF1), a transcription factor that is highly expressed across several types of cancer and has a crucial role in tumor survival, in protecting against copper-mediated cytotoxicity. Using pancreatic ductal adenocarcinoma cells, we show that excessive copper triggers a proteotoxic stress response (PSR), activating HSF1 and that overexpressing HSF1 diminishes intracellular copper accumulation and prevents excessive copper-induced cell death and amyloid fibrils formation, highlighting HSF1′s role in preserving proteasomal integrity. Copper treatment decreases the lipoylation of dihydrolipoamide S-acetyltransferase (DLAT), an enzyme necessary for cuproptosis, induces DLAT oligomerization, and induces insoluble DLAT formation, which is suppressed by overexpressing HSF1, in addition to enhancing the interaction between HSF1 and DLAT. Our findings uncover how HSF1 protects against copper-induced damage in cancer cells and thus represents a novel therapeutic target for enhancing copper-mediated cancer cell death.

Phospholipid biosynthesis regulation for improving pigment production by Monascus in response to ammonium chloride stress.

In the actual industrial production process, the efficient biosynthesis and secretion of Monascus pigments (MPs) tend to take place under abiotic stresses, which often result in an imbalance of cell homeostasis. The present study aimed to thoroughly describe the changes in lipid profiles in Monascus purpureus by absolute quantitative lipidomics and tandem mass tag-based quantitative proteomics. The results showed that ammonium chloride stress (15 g/L) increased MP production while inhibiting ergosterol biosynthesis, leading to an imbalance in membrane lipid homeostasis in Monascus. In response to the imbalance of lipid homeostasis, the regulation mechanism of phospholipids in Monascus was implemented, including the inhibition of lysophospholipids production, maintenance of the ratio of PC/PE, and improvement of the biosynthesis of phosphatidylglycerol, phosphatidylserine, and cardiolipin with high saturated and long carbon chain fatty acids through the CDP-DG pathway rather than the Kennedy pathway. The inhibition of lysophospholipid biosynthesis was attributed to the upregulated expression of protein and its gene related to lysophospholipase NTE1, while maintenance of the PC/PE ratio was achieved by the upregulated expression of protein and its gene related to CTP: phosphoethanolamine cytidylyltransferase and phosphatidylethanolamine N-methyltransferase in the Kennedy pathway. These findings provide insights into the regulation mechanism of MP biosynthesis from new perspectives.IMPORTANCEMonascus is important in food microbiology as it produces natural colorants known as Monascus pigments (MPs). The industrial production of MPs has been achieved by liquid fermentation, in which the nitrogen source (especially ammonium chloride) is a key nutritional parameter. Previous studies have investigated the regulatory mechanisms of substance and energy metabolism, as well as the cross-protective mechanisms in Monascus in response to ammonium chloride stress. Our research in this work demonstrated that ammonium chloride stress also caused an imbalance of membrane lipid homeostasis in Monascus due to the inhibition of ergosterol biosynthesis. We found that the regulation mechanism of phospholipids in Monascus was implemented, including inhibition of lysophospholipids production, maintenance of the ratio of PC/PE, and improvement of biosynthesis of phosphatidylglycerol, phosphatidylserine, and cardiolipin with high saturated and long carbon chain fatty acids through the CDP-DG pathway. These findings further refine the regulatory mechanisms of MP production and secretion.

Integrated transcriptomic and epigenomic analyses to disclose the transcriptional regulatory mechanisms of lipid and energy metabolism under cold stress in grass carp

Cold-induced injuries significantly restrict the potential and efficacy of suivival and growth, necessitating a deeper understanding of cold response in ectothermic fish. Understanding the mechanisms by which fish respond to low-temperature stress has thus become a critical research focus in aquaculture. This study aims to investigate the effects of different temperature gradients (28 °C, 10 °C, and 2 °C) on global gene transcription in grass carp Ctenopharyngodon idellus. Additionally, the study examines cold-induced chromatin accessibility and transcriptional regulation through an integration of RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin using sequencing (ATAC-seq) analyses. Transcriptome analysis revealed that mitochondrial damage and endoplasmic reticulum stress are major factors contributing to grass carp mortality under cold stress. The dataset also disclosed hepatocyte nuclear factor 1 beta (Hnf1b) and peroxisome proliferator-activated receptor alpha (PPARa) as key transcription factors for lipid and energy metabolism in grass carp under cold stress. Notably, Hnf1b and PPARa form a complex transcriptional regulatory network with other transcription factors, decreasd binding activity inactivates the expression of genes related to lipid and energy metabolism under cold stress. These results highlight the transcriptional regulation of lipid and energy metabolism in response to cold stress in grass carp. Overall, this study enhances our understanding of low-temperature response mechanisms in grass carp, providing valuable insights for further investigations.

DAZAP1 Phase Separation Regulates Mitochondrial Metabolism to Facilitate Invasion and Metastasis of Oral Squamous Cell Carcinoma.

Tumor invasion and metastasis are the underlying causes of the high mortality rate of oral squamous cell carcinoma (OSCC). Energy metabolism reprogramming has been identified as a crucial process mediating tumor metastasis, thus indicating an urgent need for in-depth investigation of the specific mechanisms of tumor energy metabolism. Here, we identified an RNA-binding protein, DAZ associated protein 1 (DAZAP1), as a tumor-promoting factor with an important role in OSCC progression. DAZAP1 was significantly upregulated in OSCC, which enhanced the migration and invasion of OSCC cells and induced the epithelial-mesenchymal transition (EMT). RNA-seq analysis and experimental validation demonstrated that DAZAP1 regulates mitochondrial energy metabolism in OSCC. Mechanistically, DAZAP1 underwent liquid-liquid phase separation (LLPS) to accumulate in the nucleus where it enhanced cytochrome-c oxidase 16 (COX16) expression by regulating pre-mRNA alternative splicing, thereby promoting OSCC invasion and mitochondrial respiration. In mouse OSCC models, loss of DAZAP1 suppressed EMT, downregulated COX16, and reduced tumor growth and metastasis. In OSCC patient samples, expression of DAZAP1 positively correlated with COX16, and high expression of both proteins was associated with poor patient prognosis. Together, these findings revealed a mechanism by which DAZAP1 supports mitochondrial metabolism and tumor development of OSCC, suggesting the potential of therapeutic strategies targeting DAZAP1 to block OSCC invasion and metastasis.

Analysis of the Molecular Mechanism of Energy Metabolism in the Sex Differentiation of Chickens Based on Transcriptome Sequencing.

The determination of sex in mammals is established and controlled by various complex mechanisms. In contrast, sex control in poultry remains an unresolved issue. In this study, RNA-sequencing was conducted for male gonads and ovarian tissues in chicken embryos of up to 18.5 days to identify metabolic factors influencing male and female sex differentiation, as well as gonadal development. Our results reveal that PKM2, a critical glycolysis-related protein, plays a significant role in chicken sex differentiation via PPARG, a crucial hormone gene. We propose that our discoveries bolster the notion that glycolysis and oxidative phosphorylation function as antecedent contributors to sexual phenotypic development and preservation.

Cellular Mechanisms for pH Regulation and Energy Metabolism in Sharks and Rays

Similar to mammalian kidney distal tubule cells, specialized shark and ray gill epithelial cells maintain blood pH homeostasis. These shark and ray gill cells are either enriched with the Na+/K+-ATPase (NKA) and responsible for acid secretion or enriched for the vacuolar H+-ATPase (VHA) and responsible for base secretion. Moreover, both cell types contain abundant mitochondria and glycogen, and glycogen content decreases in active acid-base regulatory cells in vivo. Additional experiments with isolated gill cells in vitro show that glycogen coincides with the subcellular localization of NKA and VHA. Under control conditions, glycogen and NKA are at the cell membrane of acid-secreting cells while glycogen and VHA are in the cytoplasm of base-secreting cells. During exposure to alkalosis, NKA and glycogen localization remains unchanged in acid-secreting cells; however, both VHA and glycogen translocate to the cell membrane of base-secreting cells. Interestingly, this process is prevented by pharmacological inhibition of the acid-base sensing enzyme, soluble adenylyl cyclase (sAC). This suggests a novel mechanism, a coupling of glycogen metabolism with acid-base regulation that sustains ATPase function during sudden periods of increased energy demand. Since VHA, sAC, and glycogen are evolutionarily widespread, this mechanism is likely to apply broadly to other organisms and systems, perhaps including chronic kidney disease. APS Porter Predoctoral Fellowship and National Science Foundation Postdoctoral Research Fellowship in Biology #1709911 to JR, National Science Foundation Grant IOS 1354181 to MT. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

SGLT2 inhibitors: from glucose-lowering to cardiovascular benefits.

An increasing number of individuals are at high risk of type 2 diabetes (T2D) and its cardiovascular complications, including heart failure (HF), chronic kidney disease (CKD), and eventually premature death. The sodium-glucose co-transporter-2 (SGLT2) protein sits in the proximal tubule of human nephrons to regulate glucose reabsorption and its inhibition by gliflozins represents the cornerstone of contemporary T2D and HF management. Herein, we aim to provide an updated overview of the pleiotropy of gliflozins, provide mechanistic insights and delineate related cardiovascular (CV) benefits. By discussing contemporary evidence obtained in preclinical models and landmark randomized controlled trials, we move from bench to bedside across the broad spectrum of cardio- and cerebrovascular diseases. With landmark randomized controlled trials confirming a reduction in major adverse CV events (MACE; composite endpoint of CV death, non-fatal myocardial infarction, and non-fatal stroke), SGLT2 inhibitors strongly mitigate the risk for heart failure hospitalization in diabetics and non-diabetics alike while conferring renoprotection in specific patient populations. Along four major pathophysiological axes (i.e. at systemic, vascular, cardiac, and renal levels), we provide insights into the key mechanisms that may underlie their beneficial effects, including gliflozins' role in the modulation of inflammation, oxidative stress, cellular energy metabolism, and housekeeping mechanisms. We also discuss how this drug class controls hyperglycaemia, ketogenesis, natriuresis, and hyperuricaemia, collectively contributing to their pleiotropic effects. Finally, evolving data in the setting of cerebrovascular diseases and arrhythmias are presented and potential implications for future research and clinical practice are comprehensively reviewed.

Bioinformatics identifies key genes and potential drugs for energy metabolism disorders in heart failure with dilated cardiomyopathy.

Background: Dysfunction in myocardial energy metabolism plays a vital role in the pathological process of Dilated Cardiomyopathy (DCM). However, the precise mechanisms remain unclear. This study aims to investigate the key molecular mechanisms of energy metabolism and potential therapeutic agents in the progression of dilated cardiomyopathy with heart failure. Methods: Gene expression profiles and clinical data for patients with dilated cardiomyopathy complicated by heart failure, as well as healthy controls, were sourced from the Gene Expression Omnibus (GEO) database. Gene sets associated with energy metabolism were downloaded from the Molecular Signatures Database (MSigDB) for subsequent analysis. Weighted Gene Co-expression Network Analysis (WGCNA) and differential expression analysis were employed to identify key modules and genes related to heart failure. Potential biological mechanisms were investigated through Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and the construction of a competing endogenous RNA (ceRNA) network. Molecular docking simulations were then conducted to explore the binding affinity and conformation of potential therapeutic drugs with hub genes. Results: Analysis of the left ventricular tissue expression profiles revealed that, compared to healthy controls, patients with dilated cardiomyopathy exhibited 234 differentially expressed genes and 2 genes related to myocardial energy metabolism. Additionally, Benzoylaconine may serve as a potential therapeutic agent for the treatment of dilated cardiomyopathy. Conclusion: The study findings highlight the crucial role of myocardial energy metabolism in the progression of Dilated Cardiomyopathy. Notably, Benzoylaconine emerges as a potential candidate for treating Dilated Cardiomyopathy, potentially exerting its therapeutic effects by targeted modulation of myocardial energy metabolism through NRK and NT5.

Investigating the Respiratory and Energy Metabolism Mechanisms behind ε-Poly-L-lysine Chitosan Coating's Improved Preservation Effectiveness on Tremella fuciformis.

Freshly harvested Tremella fuciformis contains high water content with an unprotected outer surface and exhibits high respiration rates, which renders it prone to moisture and nutrient loss, leading to decay during storage. Our research utilized ε-poly-L-lysine (ε-PL) and chitosan as a composite coating preservative on fresh T. fuciformis. The findings revealed that the ε-PL + chitosan composite coating preservative effectively delayed the development of diseases and reduced weight loss during storage compared to the control group. Furthermore, this treatment significantly decreased the respiration rate of T. fuciformis and the activity of respiratory metabolism-related enzymes, such as alternative oxidase (AOX), cytochrome c oxidase (CCO), succinic dehydrogenase (SDH), 6-phosphogluconate dehydrogenase, and glucose-6-phosphate dehydrogenase (6-PGDH and G-6-PDH). Additionally, the composite coating preservative also delayed the depletion of ATP and ADP and maintained higher levels of the energy charge while preserving low levels of AMP. It also sustained heightened activities of Mg2+-ATPase, Ca2+-ATPase, and H+-ATPase enzymes. These results demonstrate that utilizing the ε-PL + chitosan composite coating preservative can serve as a sufficiently safe and efficient method for prolonging the shelf life of post-harvest fresh T. fuciformis.

Energy Metabolism in Residents in the Low- and Moderate Altitude Regions of Central Asia with MAFLD and Type 2 Diabetes Mellitus.

The knowledge about the features of energy metabolism in MAFLD in the population living at different climatic and geographic heights is lacking. The goal of this study is to explore the biochemical parameters of blood and erythrocyte energy consumption in patients with MAFLD with and without DM2 living in the low- and moderate-altitude regions of Central Asia. Our study was carried out on patients living in low-altitude mountains: Bishkek, altitude=750-800 m; n=67 (MAFLD with DM 2: n=24; MAFLD without DM2: n=25; control: n=18), and At-Bashy District, Naryn Region, altitude=2046-2300 m; n=58 (MAFLD with DM2: n=28; MAFLD without DM2: n=18; control: n=12). Non-alcoholic fatty liver disease was diagnosed according to history, laboratory tests, liver ultrasound, and exclusion of other liver diseases. The level of liver fibrosis was determined using the FIB-4 score. Blood adenosine 5'-triphosphate (ATP) was determined using the CellTiter-Glo method. Healthy residents living in moderate altitudes have significantly higher levels of cytosolic ATP in their blood (p+≤+0.05) than residents living in low mountains. MAFLD is characterized by an increase in the level of ATP concentration in their blood. ATP concentration decreased significantly in patients with MAFLD with DM2 living in moderate-altitude in comparison to those living in low-altitude mountains. The results suggest that chronic altitude hypoxia leads to a breakdown in adaptive mechanisms of energy metabolism of ATP in patients with MAFLD with type 2 DM.

Itraconazole inhibits tumor growth via CEBPB-mediated glycolysis in colorectal cancer.

Advanced colorectal cancer (CRC) is characterized by a high recurrence and metastasis rate, which is the primary cause of patient mortality. Unfortunately, effective anti-cancer drugs for CRC are still lacking in clinical practice. We screened FDA-approved drugs by utilizing targeted organoid sequencing data and found that the antifungal drug itraconazole had a potential therapeutic effect on CRC tumors. However, the effect and mechanism of itraconazole on CRC tumors have not been investigated. A cell line-derived xenograft model in tumor-bearing mice was established and single-cell RNA sequencing was performed on tumor samples from four mice with or without itraconazole treatment. The proportion of cell populations and gene expression profiles was significantly different between the two groups. We found that itraconazole could inhibit tumor growth and glycolysis. We revealed that CEBPB was a new target for itraconazole, and that silencing CEBPB could repress CRC glycolysis and tumor growth by inhibiting ENO1 expression. Clinical analysis showed that CEBPB expression was obviously elevated in CRC patients, and was associated with poor survival. In summary, itraconazole treatment remodeled cell composition and gene expression profiles. Itraconazole inhibited cell glycolysis and tumor growth via the CEBPB-ENO1 axis. In this study, we illustrate a new energy metabolism mechanism for itraconazole on tumor growth in CRC that will provide a theoretical basis for CRC targeting/combination therapy.

The Regulatory Role and Mechanism of Energy Metabolism in Vascular Diseases.

Vascular diseases are amongst the most serious diseases affecting human life and health globally. Energy metabolism plays a crucial role in multiple vascular diseases, and the imbalance of energy metabolism in cells from the blood vessel wall can cause various vascular diseases. Energy metabolism studies have often focused on atherosclerosis (AS) and pulmonary hypertension (PH). However, the roles of energy metabolism in the development of other vascular diseases is becoming increasingly appreciated as both dynamic and essential. This review summarizes the role of energy metabolism in various vascular diseases, including AS, hemangioma, aortic dissection, PH, vascular aging, and arterial embolism. It also discusses how energy metabolism participates in the pathophysiological processes of vascular diseases and potential drugs that may interfere with energy metabolism. This review presents suggestions for the clinical prevention and treatment of vascular diseases from the perspective of energy metabolism.

Regulation of PGC-1α of the Mitochondrial Energy Metabolism Pathway in the Gills of Indian Medaka (Oryzias dancena) under Hypothermal Stress.

Ectothermic fish exposure to hypothermal stress requires adjusting their metabolic molecular machinery, which was investigated using Indian medaka (Oryzias dancena; 10 weeks old, 2.5 ± 0.5 cm) cultured in fresh water (FW) and seawater (SW; 35‱) at room temperature (28 ± 1 °C). The fish were fed twice a day, once in the morning and once in the evening, and the photoperiod was 12 h:12 h light: dark. In this study, we applied two hypothermal treatments to reveal the mechanisms of energy metabolism via pgc-1α regulation in the gills of Indian medaka; cold-stress (18 °C) and cold-tolerance (extreme cold; 15 °C). The branchial ATP content was significantly higher in the cold-stress group, but not in the cold-tolerance group. In FW- and SW-acclimated medaka, the expression of genes related to mitochondrial energy metabolism, including pgc-1α, prc, Nrf2, tfam, and nd5, was analyzed to illustrate differential responses of mitochondrial energy metabolism to cold-stress and cold-tolerance environments. When exposed to cold-stress, the relative mRNA expression of pgc-1α, prc, and Nrf2 increased from 2 h, whereas that of tfam and nd5 increased significantly from 168 h. When exposed to a cold-tolerant environment, prc was significantly upregulated at 2 h post-cooling in the FW and SW groups, and pgc-1α was significantly upregulated at 2 and 12 h post-cooling in the FW group, while tfam and nd5 were downregulated in both FW and SW fish. Hierarchical clustering revealed gene interactions in the cold-stress group, which promoted diverse mitochondrial energy adaptations, causing an increase in ATP production. However, the cold-tolerant group demonstrated limitations in enhancing ATP levels through mitochondrial regulation via the PGC-1α energy metabolism pathway. These findings suggest that ectothermic fish may develop varying degrees of thermal tolerance over time in response to climate change. This study provides insights into the complex ways in which fish adjust their metabolism when exposed to cold stress, contributing to our knowledge of how they adapt.

The energy metabolism of Balantidium polyvacuolum inhabiting the hindgut of Xenocypris davidi

Anaerobic parasitic ciliates are a specialized group of ciliates that are adapted to anoxic and oxygen-depleted habitats. Among them, Balantidium polyvacuolum, which inhabits the hindgut of Xenocyprinae fishes, has received very limited scientific attention, so the molecular mechanism of its adaptation to the digestive tract microenvironment is still unclear. In this study, transmission electron microscopy (TEM) and single-cell transcriptome analysis were used to uncover the metabolism of B. polyvacuolum. Starch granules, endosymbiotic bacteria, and multiple specialized mitochondrion-related organelles (MROs) of various shapes were observed. The MROs may have completely lost the electron transport chain (ETC) complexes I, III, IV, and V and only retained succinate dehydrogenase subunit A (SDHA) of complex II. The tricarboxylic acid (TCA) cycle was also incomplete. It can be inferred that the hypoxic intestinal environment has led to the specialization of the mitochondria in B. polyvacuolum. Moreover, carbohydrate-active enzymes (CAZymes), including carbohydrate esterases, enzymes with a carbohydrate-binding module, glycoside hydrolases, and glycosyltransferases, were identified, which may constitute evidence that B. polyvacuolum is able to digest carbohydrates and starch. These findings can improve our knowledge of the energy metabolism and adaptive mechanisms of B. polyvacuolum.

Effects of Chaihu Shugan San on Brain Functional Network Connectivity in the Hippocampus of a Perimenopausal Depression Rat Model.

In this study, we used Chaihu Shugan San (CSS), a traditional Chinese herbal formula, as a probe to investigate the involvement of brain functional network connectivity and hippocampus energy metabolism in perimenopausal depression. A network pharmacology approach was performed to discover the underlying mechanisms of CSS in improving perimenopausal depression, which were verified in perimenopausal depression rat models. Network pharmacology analysis indicated that complex mechanisms of energy metabolism, neurotransmitter metabolism, inflammation, and hormone metabolic processes were closely associated with the anti-depressive effects of CSS. Thus, the serum concentrations of estradiol (E2), glutamate (Glu), and 5-hydroxytryptamine (5-HT) were detected by ELISA. The brain functional network connectivity between the hippocampus and adjacent brain regions was evaluated using resting-state functional magnetic resonance imaging (fMRI). A targeted metabolomic analysis of the hippocampal tricarboxylic acid cycle was also performed to measure the changes in hippocampal energy metabolism using liquid chromatography-tandem mass spectrometry (LC-MS/MS). CSS treatment significantly improved the behavioral performance, decreased the serum Glu levels, and increased the serum 5-HT levels of PMS + CUMS rats. The brain functional connectivity between the hippocampus and other brain regions was significantly changed by PMS + CUMS processes but improved by CSS treatment. Moreover, among the metabolites in the hippocampal tricarboxylic acid cycle, the concentrations of citrate and the upregulation of isocitrate and downregulation of guanosine triphosphate(GTP) in PMS + CUMS rats could be significantly improved by CSS treatment. A brain functional network connectivity mechanism may be involved in perimenopausal depression, wherein the hippocampal tricarboxylic acid cycle plays a vital role.

Upregulated miR‑378a‑3p expression suppresses energy metabolism and promotes apoptosis by targeting a GLUT‑1/ALDOA/PKM2 axis in esophageal carcinoma.

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy of the digestive system with increasing incidence and mortality rates. The biological roles of microRNA (miR)-378a-3p in tumor cells remain contested, and the mechanisms underlying the functions, energy metabolism, and cell survival mechanisms in ESCC cells are yet to be fully elucidated. In the present study, miR-378a-3p overexpression and negative control plasmids were transfected into ECA-109 cells using electroporation. Western blotting was used to detect the relative expression of proteins, and flow cytometry was used to detect cell apoptosis. Subsequently, ELISA assays were performed to determine enzyme activity, and an ATP detection kit was used to measure ATP content. Dual-luciferase reporter assays were performed to identify the target genes of miR-378a-3p. The results of the present study demonstrated that miR-378a-3p inhibited the gene expression and enzyme activities of glucose transporter protein 1 (GLUT-1), Aldolase A (ALDOA), and pyruvate kinase M2 (PKM2), all of which are involved in the glycolytic pathway of cells. Energy metabolism was suppressed by miR-378a-3p by reducing ATP content, and this downregulated the expression of Bcl-2 and Survivin. Moreover, increased miR-378a-3p expression promoted cell apoptosis in the early stages by increasing the expression levels and the activity of Bad and Caspase-3, while inhibiting the expression levels of Bcl-2 and Survivin. The results of the present study also demonstrated that GLUT-1/ALDOA/PKM2 were target genes of miR-378a-3p. Notably, miR-378a-3p blocked energy production and promoted the apoptosis of tumor cells via the downregulation of glycolytic enzyme expression and by reducing the mitochondrial membrane potential in ESCC. Bad, Caspase-3, Survivin, and Bcl-2 may be associated with blocking energy production and promoting apoptosis via miR-378a-3p in ESCC cells.

Molecular phylogeny and taxonomy of three anaerobic plagiopyleans (Alveolata: Ciliophora), retrieved from two geographically distant localities in Asia and North America

Abstract Anaerobic ciliates are key organisms for studying adaptations to an anaerobic lifestyle, the evolution of eukaryotic cell organelles, mechanisms of energy metabolism, and symbiosis with prokaryotes; however, the biodiversity of their marine representatives remains poorly known. In this study, three species of ciliates belonging to the class Plagiopylea, i.e. Trimyema foissnerisp. nov.,Plagiopyla rarisetasp. nov., and Plagiopyla frontata, collected from various marine anoxic habitats from two geographically distant continents, Asia and North America, were investigated using morphological and molecular methods. Trimyema foissneri can be recognized by three complete somatic ciliary girdles, special arrangement of kinetosomes near the anterior end of the oral kineties, and the presence of a ventrolateral fragment. Plagiopyla rariseta is distinguished by sparse cilia on the frontal region and particular orientation of the buccal cavity. Plagiopyla frontata is newly recorded and is redescribed in detail and redefined based on new populations. Phylogenetic analyses based on the small subunit ribosomal ribonucleic acid (SSU rRNA) gene supported the generic assignment of the three species and corroborated the monophyly of the families Trimyemidae and Plagiopylidae. An improved key to the identification of the valid species of genus Trimyema is also supplied.

Role of long pentraxin PTX3 in cancer.

Cancer has become a leading cause of death and disease burden worldwide, closely related to rapid socioeconomic development. However, the fundamental reason is the lack of comprehensive understanding of the mechanism of cancer, accurate identification of preclinical cancer, and effective treatment of the disease. Therefore, it is particularly urgent to study specific mechanisms of cancer and develop effective prediction and treatment methods. Long Pentraxin PTX3 is a soluble pattern recognition molecule produced by various cells in inflammatory sites, which plays a role as a promoter or suppressor of cancer in multiple tumors through participating in innate immune response, neovascularization, energy metabolism, invasion, and metastasis mechanisms. Based on this, this article mainly reviews the role of PTX3 in various cancers.

Energy metabolism disturbance in migraine: From a mitochondrial point of view.

Migraine is a serious central nervous system disease with a high incidence rate. Its pathogenesis is very complex, which brings great difficulties for clinical treatment. Recently, many studies have revealed that mitochondrial dysfunction may play a key role in migraine, which affects the hyperosmotic of Ca2+, the excessive production of free radicals, the decrease of mitochondrial membrane potential, the imbalance of mPTP opening and closing, and the decrease of oxidative phosphorylation level, which leads to neuronal energy exhaustion and apoptosis, and finally lessens the pain threshold and migraine attack. This article mainly introduces cortical spreading depression, a pathogenesis of migraine, and then damages the related function of mitochondria, which leads to migraine. Oxidative phosphorylation and the tricarboxylic acid cycle are the main ways to provide energy for the body. 95 percent of the energy needed for cell survival is provided by the mitochondrial respiratory chain. At the same time, hypoxia can lead to cell death and migraine. The pathological opening of the mitochondrial permeability transition pore can promote the interaction between pro-apoptotic protein and mitochondrial, destroy the structure of mPTP, and further lead to cell death. The increase of mPTP permeability can promote the accumulation of reactive oxygen species, which leads to a series of changes in the expression of proteins related to energy metabolism. Both Nitric oxide and Calcitonin gene-related peptide are closely related to the attack of migraine. Recent studies have shown that changes in their contents can also affect the energy metabolism of the body, so this paper reviews the above mechanisms and discusses the mechanism of brain energy metabolism of migraine, to provide new strategies for the prevention and treatment of migraine and promote the development of individualized and accurate treatment of migraine.

Molecular/Nanomechanical Insights into Electrostimulation-Inhibited Energy Metabolism Mechanisms and Cytoskeleton Damage of Cancer Cells.

Inhibiting energy metabolism of cancer cells is an effective way to treat cancer but remains a great challenge. Herein, electrostimulation (ES) is applied to effectively suppress energy metabolism of cancer cells to induce rapid cell death, and deeply reveal the underlying mechanisms at the molecular and nanomechanical levels by combined use of fluorescence imaging and atomic force microscopy. Cancer cells are found significantly less tolerant to ES than normal cells; and ES causes "domino effect" to induce mitochondrial dysfunction to impede electron transport chain (ETC) and tricarboxylic acid (TCA) cycle pathways, leading to fatal energy-supply crisis and death of cancer cells. From the perspective of cell mechanics, the Young's modulus decreases and cytoskeleton destruction of MCF-7 cell membranes caused by F-actin depolymerization occurs, along with down-regulation and sporadic distribution of glucose transporter 1 (GLUT1) after ES. Such a double whammy renders ES highly effective and promising for potential clinical cancer treatments.