We aimed to analyze the association between CYP7B1 and prostate cancer, along with its association with proteins involved in cancer and metabolic processes. A retrospective analysis was performed on 390 patients with prostate cancer (PC) or benign prostatic hyperplasia (BPH). We investigated the interactions between CYP7B1 expression and proteins associated with PC and metabolic processes, followed by an analysis of the risk of biochemical recurrence based on CYP7B1 expression. Of the 139 patients with elevated CYP7B1 expression, 92.8% had prostate cancer. Overall, no increased risk of biochemical recurrence was associated with CYP7B1 expression. However, in a non-diabetic subgroup analysis, higher CYP7B1 expression indicated a higher risk of biochemical recurrence, with an HR of 1.78 (CI: 1.0-3.2, p = 0.05). PC is associated with elevated CYP7B1 expression. In a subgroup analysis of non-diabetic patients, elevated CYP7B1 expression was associated with an increased risk of biochemical recurrence, suggesting increased cancer aggressiveness.

BACKGROUND: There are a lot of studies on the treatment of tumors with hyperbaric oxygen, while most of them are in breast cancer, prostate cancer and so on. However, there are still few studies on hyperbaric oxygen in treating hepatocellular carcinoma (HCC). According to the current data, hyperbaric oxygen is an effective means to intervene in tumors. The Warburg effect is a unique marker of glucose metabolism in tumors related to hypoxia, making it possible for hyperbaric oxygen to interfere with the tumor through the Warburg effect.
METHODS: We used the hypoxia/hyperbaric oxygen(HBO)-exposed HCC cells for in vitro studies. Glucose uptake, lactic acid, and adenosine triphosphate (ATP) assessed the Warburg effect. The expression of miR-103a-3p in HCC was detected by using qRT-PCR. The effect of miR-103a-3p/TRIM35 expression level on the cells was measured using the CCK8 method and flow cytometry. The molecular biological mechanism of miR-103a-3p in HCC was examined using the luciferase reporter, MS2-RIP assays.
RESULTS: HBO inhibited the Warburg effect in hypoxic HCC cells. HBO suppressed the expression of miR-103a-3p in hypoxic HCC cells, and miR-103a-3p inhibited the expression of TRIM35 in hypoxic HCC cells. With HBO exposure, miR-103a-3p/TRIM35 regulated the Warburg effect of hypoxic HCC cells.
CONCLUSIONS: These findings reveal that HBO regulates the Warburg effect of hypoxic HCC cells through miR-103a-3p/TRIM35 and inhibits tumor growth.

As mass coral bleaching events become more frequent, it is increasingly important to elucidate the factors underlying coral susceptibility and survival. We measured photosynthesis, respiration, and O2 concentration at the coral tissue surface, Symbiodiniaceae genotypes, and energy metabolic enzyme activities in Agaricia agaricites and Orbicella franksi throughout experimentally-induced thermal bleaching (+3 °C). A. agaricites colonies started to bleach two days into the thermal treatment and were fully bleached between Days 19-31. In contrast, O. franksi colonies only started to bleach on Day 12 and five colonies fully bleached between Days 24-38 while the remining three colonies took up 55 days. Both species experienced decreased photosynthesis and respiration rates as bleaching progressed. As a result, daytime O2 concentration at the coral surface shifted from hyperoxia in unbleached corals to normoxia in partially bleached corals, and to near hypoxia in fully bleached corals. Additionally, nighttime tissue surface O2 concentration shifted from hypoxia to normoxia, likely resulting from decreased symbiotic algae density, respiration, and photosynthates that fuel coral aerobic respiration. Genetic profiling of internal transcribed spacer 2 (ITS2) revealed differences in Symbiodiniaceae clade proportions between control and bleached colonies. Activity levels of energy metabolic enzymes did not significantly vary between control and bleached A. agaricites, but malate dehydrogenase and strombine dehydrogenase activities were significantly higher in bleached O. franksi colonies compared to controls. These differences were driven by the three O. franksi colonies that took the longest to bleach and contained >98 % Durusdinium sp. D1. The shifts in O2 dynamics within the microhabitat of bleached corals may have important implications for the metabolism of the coral holobiont while the changes in Symbiodiniaceae ITS2 profile and the upregulation of energy metabolic enzymes identify a potential factor contributing to bleaching dynamics.

This study aimed to implement a multimodal 1H/HP-13C imaging protocol to augment the serial monitoring of patients with glioma, while simultaneously pursuing methods for improving the robustness of HP-13C metabolic data. A total of 100 1H/HP [1-13C]-pyruvate MR examinations (104 HP-13C datasets) were acquired from 42 patients according to the comprehensive multimodal glioma imaging protocol. Serial data coverage, accuracy of frequency reference, and acquisition delay were evaluated using a mixed-effects model to account for multiple exams per patient. Serial atlas-based HP-13C MRI demonstrated consistency in volumetric coverage measured by inter-exam dice coefficients (0.977 ± 0.008, mean ± SD; four patients/11 exams). The atlas-derived prescription provided significantly improved data quality compared to manually prescribed acquisitions (n = 26/78; p = 0.04). The water-based method for referencing [1-13C]-pyruvate center frequency significantly reduced off-resonance excitation relative to the coil-embedded [13C]-urea phantom (4.1 ± 3.7 Hz vs. 9.9 ± 10.7 Hz; p = 0.0007). Significantly improved capture of tracer inflow was achieved with the 2-s versus 5-s HP-13C MRI acquisition delay (p = 0.007). This study demonstrated the implementation of a comprehensive multimodal 1H/HP-13C MR protocol emphasizing the monitoring of steady-state/dynamic metabolism in patients with glioma.

The uncoupling protein UCP2 is a mitochondrial carrier for which transport activity remains controversial. The physiological contexts in which UCP2 is expressed have led to the assumption that, like UCP1, it uncouples oxidative phosphorylation and thereby reduces the generation of reactive oxygen species. Other reports have involved UCP2 in the Warburg effect, and results showing that UCP2 catalyzes the export of matrix C4 metabolites to facilitate glutamine utilization suggest that the carrier could be involved in the metabolic adaptations required for cell proliferation. We have examined the role of UCP2 in the energy metabolism of the lung adenocarcinoma cell line A549 and show that UCP2 silencing decreased the basal rate of respiration, although this inhibition was not compensated by an increase in glycolysis. Silencing did not lead to either changes in proton leakage, as determined by the rate of respiration in the absence of ATP synthesis, or changes in the rate of formation of reactive oxygen species. The decrease in energy metabolism did not alter the cellular energy charge. The decreased cell proliferation observed in UCP2-silenced cells would explain the reduced cellular ATP demand. We conclude that UCP2 does not operate as an uncoupling protein, whereas our results are consistent with its activity as a C4-metabolite carrier involved in the metabolic adaptations of proliferating cells.

This paper, aligned with contemporary thinking in terms of patient-centered care and co-creation of patient care, highlights the limitations of the reductionist approaches to psychiatry, offering an alternative, \"emergent\" perspective and approach. Assuming that psychopathological phenomena are essentially relational, what kind of epistemological framework and \'logic of discovery\' should be adopted? I review two standard methods I call \'ticking boxes\' and \'drafting arrows\'. Within the ticking boxes framework, the clinician\'s main goal is to discover whether a patient showing psychopathological phenomena meets pre-given diagnostic criteria. The process of discovery can be compared to two people assembling a puzzle where the patient has the pieces and the interviewer has the image of the completed design. Drafting arrows consists in constructing pathogenetic diagrams that display linear causative relationships between variables connected by an arrow to other nodes. These explanatory narratives include psychodynamic (motivational) and biological (causal) diagrams. I argue for a third approach called \'linking dots\', a method of discovery based on the emergent properties of psychopathological phenomena. I build on and develop the approach to images and discovery devised by art historian Aby Warburg in his atlas of images Bilderatlas Mnemosyne. The visual constellations created by Warburg in the panels of the Bilderatlas can be understood as a method to reveal the layers of memory and the web of relationships manifested in them, inviting the viewer to participate in the production of meanings, forging ever new connections between the images. It is the viewer\'s acts of perception that draw relationships between singularities. I suggest that this method is of enormous significance in the context of today\'s socio-cultural transformation processes and related forms of psychopathological conditions, which can no longer be comprehended using the categories of existing knowledge systems.

Over the last years, we have learned that the metabolic phenotype of immune cells is closely connected to the cell\'s effector function. Understanding these changes will allow us to better understand allergic disease pathology and improve allergy treatment by modulating immune metabolic pathways. As part two of a two-article series, this review reports on the recent studies investigating the metabolism of the cell types involved in allergies and discusses the initial application of these discoveries in allergy treatment.
The cell types involved in allergic reactions display pronounced and highly specific metabolic changes (here discussed for epithelial cells, APCs, ILC2s, mast cells, eosinophils, and Th2 cells). Currently, the first drugs targeting metabolic pathways are tested for their potential to improve allergy treatment. Immune-metabolic changes observed in allergy so far are complex and depend on the investigated disease and cell type. However, our increased understanding of the underlying principles has pointed to several promising target molecules that are now being investigated to improve allergy treatment.

Trained immune responses, based on metabolic and epigenetic changes in innate immune cells, are de facto innate immune memory and, therefore, are of great interest in vaccine development. In previous studies, the recombinant fusion protein rFlaA:Betv1, combining the adjuvant and toll-like receptor (TLR)5-ligand flagellin (FlaA) and the major birch pollen allergen Bet v 1 into a single molecule, significantly suppressed allergic sensitization in vivo while also changing the metabolism of myeloid dendritic cells (mDCs). Within this study, the immune-metabolic effects of rFlaA:Betv1 during mDC activation were elucidated. In line with results for other well-characterized TLR-ligands, rFlaA:Betv1 increased glycolysis while suppressing oxidative phosphorylation to different extents, making rFlaA:Betv1 a suitable model to study the immune-metabolic effects of TLR-adjuvanted vaccines. In vitro pretreatment of mDCs with cerulenin (inhibitor of fatty acid biosynthesis) led to a decrease in both rFlaA:Betv1-induced anti-inflammatory cytokine Interleukin (IL) 10 and T helper cell type (TH) 1-related cytokine IL-12p70, while the pro-inflammatory cytokine IL 1β was unaffected. Interestingly, pretreatment with the glutaminase inhibitor BPTES resulted in an increase in IL-1β, but decreased IL-12p70 secretion while leaving IL-10 unchanged. Inhibition of the glycolytic enzyme hexokinase-2 by 2-deoxyglucose led to a decrease in all investigated cytokines (IL-10, IL-12p70, and IL-1β). Inhibitors of mitochondrial respiration had no effect on rFlaA:Betv1-induced IL-10 level, but either enhanced the secretion of IL-1β (oligomycin) or decreased IL-12p70 (antimycin A). In extracellular flux measurements, mDCs showed a strongly enhanced glycolysis after rFlaA:Betv1 stimulation, which was slightly increased after respiratory shutdown using antimycin A. rFlaA:Betv1-stimulated mDCs secreted directly antimicrobial substances in a mTOR- and fatty acid metabolism-dependent manner. In co-cultures of rFlaA:Betv1-stimulated mDCs with CD4+ T cells, the suppression of Bet v 1-specific TH2 responses was shown to depend on fatty acid synthesis. The effector function of rFlaA:Betv1-activated mDCs mainly relies on glycolysis, with fatty acid synthesis also significantly contributing to rFlaA:Betv1-mediated cytokine secretion, the production of antimicrobial molecules, and the modulation of T cell responses.

Aggressive cancers commonly ferment glucose to lactic acid at high rates, even in the presence of oxygen. This is known as aerobic glycolysis, or the \"Warburg Effect.\" It is widely assumed that this is a consequence of the upregulation of glycolytic enzymes. Oncogenic drivers can increase the expression of most proteins in the glycolytic pathway, including the terminal step of exporting H+ equivalents from the cytoplasm. Proton exporters maintain an alkaline cytoplasmic pH, which can enhance all glycolytic enzyme activities, even in the absence of oncogene-related expression changes. Based on this observation, we hypothesized that increased uptake and fermentative metabolism of glucose could be driven by the expulsion of H+ equivalents from the cell.
To test this hypothesis, we stably transfected lowly glycolytic MCF-7, U2-OS, and glycolytic HEK293 cells to express proton-exporting systems: either PMA1 (plasma membrane ATPase 1, a yeast H+-ATPase) or CA-IX (carbonic anhydrase 9). The expression of either exporter in vitro enhanced aerobic glycolysis as measured by glucose consumption, lactate production, and extracellular acidification rate. This resulted in an increased intracellular pH, and metabolomic analyses indicated that this was associated with an increased flux of all glycolytic enzymes upstream of pyruvate kinase. These cells also demonstrated increased migratory and invasive phenotypes in vitro, and these were recapitulated in vivo by more aggressive behavior, whereby the acid-producing cells formed higher-grade tumors with higher rates of metastases. Neutralizing tumor acidity with oral buffers reduced the metastatic burden.
Therefore, cancer cells which increase export of H+ equivalents subsequently increase intracellular alkalization, even without oncogenic driver mutations, and this is sufficient to alter cancer metabolism towards an upregulation of aerobic glycolysis, a Warburg phenotype. Overall, we have shown that the traditional understanding of cancer cells favoring glycolysis and the subsequent extracellular acidification is not always linear. Cells which can, independent of metabolism, acidify through proton exporter activity can sufficiently drive their metabolism towards glycolysis providing an important fitness advantage for survival.

Prostate cancer (PCa) is the second leading cause of cancer deaths in men. Unfortunately, a very limited number of drugs are available for the relapsed and advanced stages of PCa, adding only a few months to survival; therefore, it is vital to develop new drugs. 5´ AMP-activated protein kinase (AMPK) is a master regulator of cell metabolism. It plays a significant role in the metabolism of PCa; hence, it can serve well as a treatment option for the advanced stages of PCa. However, whether this pathway contributes to cancer cell survival or death remains unknown. The present study reviews the possible pathways by which AMPK plays role in the advanced stages of PCa, drug resistance, and metastasis: (1) AMPK has a contradictory role in promoting glycolysis and the Warburg effect which are correlated with cancer stem cells (CSCs) survival and advanced PCa. It exerts its effect by interacting with hypoxia-induced factor 1 (HIF1) α, pyruvate kinase 2 (PKM2), glucose transporter (GLUT) 1 and pyruvate dehydrogenase complex (PDHC), which are key regulators of glycolysis; however, whether it promotes or discourage glycolysis is not conclusive. It can also exert an anti-CSC effect by negative regulation of NANOG and epithelial-mesenchymal transition (EMT) transcription factors, which are the major drivers of CSC maintenance; (2) the regulatory effect of AMPK on autophagy is also noticeable. Androgen receptors\' expression increases AMPK activation through Calcium/calmodulin-dependent protein kinase 2 (CaMKK2) and induces autophagy. In addition, AMPK itself increases autophagy by downregulating the mammalian target of rapamycin complex (mTORC). However, whether increased autophagy inhibits or promotes cell death and drug resistance is contradictory. This study reveals that there are numerous pathways other than cell metabolism by which AMPK exerts its effects in the advanced stages of PCa, making it a priceless treatment target. Finally, we mention some drugs developed to treat the advanced stages of PCa by acting on AMPK.