PubMed

J Steroid Biochem Mol Biol. 2025 Jan 14:106677. doi: 10.1016/j.jsbmb.2025.106677. Online ahead of print.ABSTRACTVitiligo is a common chronic skin depigmentation disorder that seriously decreases the patients' overall quality of life. Human blood metabolites could contribute to unraveling the underlying biological mechanisms of vitiligo. We used GWAS summary statistics to assess the causal association between genetically predicted 1,400 serum metabolites and vitiligo risk by Mendelian randomization (MR). Then, after constructing the mouse model of vitiligo, we did non-targeted metabolomics analysis on the mouse serum and validated MR's pathway enrichment results ulteriorly. In the initial phase, MR analysis revealed causative associations between 36 metabolites and vitiligo risk, including 8 metabolite ratios and 28 individual metabolites (19 known and 9 unknown metabolites). In the validation stage, 7 metabolites were successfully validated. Of the 28 individual metabolites, most are related to lipid metabolism. Genetically predicted higher 4-oxo-retinoic acid showed the strongest protective effect on vitiligo, while the most potent risk effect was the increase in quinate. The metabolites associated with vitiligo risk are mainly enriched in alpha-linolenic acid metabolism, linoleic acid metabolism, arginine biosynthesis and metabolism pathways, validated through the serum metabolomics of vitiligo mouse. By integrating genomics and metabolomics, this study provides new insights into the association between metabolites and vitiligo, highlighting the potential roles of specific metabolites in the pathogenesis of vitiligo. These metabolites associated with vitiligo could serve as new biomarkers, further research could help to reveal how these metabolites influence specific pathways in the development of vitiligo.PMID:39818343 | DOI:10.1016/j.jsbmb.2025.106677

J Affect Disord. 2025 Jan 14:S0165-0327(25)00081-3. doi: 10.1016/j.jad.2025.01.064. Online ahead of print.ABSTRACTMetabolomics provides powerful tools that can inform about heterogeneity in disease and response to treatments. In this exploratory study, we employed an electrochemistry-based targeted metabolomics platform to assess the metabolic effects of three randomly-assigned treatments: escitalopram, duloxetine, and Cognitive-Behavioral Therapy (CBT) in 163 treatment-naïve outpatients with major depressive disorder. Serum samples from baseline and 12 weeks post-treatment were analyzed using targeted liquid chromatography-electrochemistry for metabolites related to tryptophan, tyrosine metabolism and related pathways. Changes in metabolite concentrations related to each treatment arm were identified and compared to define metabolic signatures of exposure. In addition, association between metabolites and depressive symptom severity (assessed with the 17-item Hamilton Rating Scale for Depression [HRSD17]) and anxiety symptom severity (assessed with the 14-item Hamilton Rating Scale for Anxiety [HRSA14]) were evaluated, both at baseline and after 12 weeks of treatment. Significant reductions in serum serotonin level and increases in tryptophan-derived indoles that are gut bacterially derived were observed with escitalopram and duloxetine arms but not in CBT arm. These include indole-3-propionic acid (I3PA), indole-3-lactic acid (I3LA) and Indoxyl sulfate (IS), a uremic toxin. Purine-related metabolites were decreased across all arms. Different metabolites correlated with improved symptoms in the different treatment arms revealing potentially different mechanisms between response to antidepressant medications and to CBT.PMID:39818336 | DOI:10.1016/j.jad.2025.01.064

Ecotoxicol Environ Saf. 2025 Jan 15;290:117748. doi: 10.1016/j.ecoenv.2025.117748. Online ahead of print.ABSTRACTGiven the extensive use of plastic materials in modern society, there is an escalating concern about the potential risks associated with exposure to plastic products. This study investigated the impact of plastic leachates from boiled-water-treated cups, including polypropylene (PP), high-density polyethylene (HDPE), low-density polyethylene (LDPE), polystyrene (PS), and polyethylene terephthalate (PET), on male reproductive health. Experimental mice were administered daily doses of the plastic leachates for 180 consecutive days. Histological analysis of the testes and epididymis was conducted, revealing vacuolization and absence of sperms in the seminiferous tubules of mice treated with PP, HDPE, LDPE, and PS, while PET exhibited lower reproductive toxicity. Furthermore, transcriptomic and metabolomic profiling were employed to identify key genes and metabolites related to plastic exposure. Transcriptome analysis showed significant changes in genes associated with spermatogenesis following exposure to leachates, while metabolome analysis indicated an impact on the lipid metabolism pathway. Overall, the study provides evidence that oral exposure to leachates from boiled-water-treated plastic cups could negatively affect spermatogenesis and lipid metabolism, thereby posing risks to male reproductive health. These findings offer crucial insights into the potential risks associated with plastic consumption and may advocate for the selection of relatively safe plastic cups for everyday use.PMID:39818138 | DOI:10.1016/j.ecoenv.2025.117748

Food Chem. 2025 Jan 10;471:142863. doi: 10.1016/j.foodchem.2025.142863. Online ahead of print.ABSTRACTIn this study, steam explosion (SE) was applied to produce Xuehua pear soup (XPS) at different steam explosion pressure. The results showed that 0.3-0.6 MPa was the optimal pressure to improve the XPS quality. After SE treatment, the titratable acid of XPS decreased whereas it became darker. 0.6 MPa was the optimal pressure to enhance total flavonoid content and concentrated catechin, protocatechuic and rutin, endowing XPS with good antioxidant activity. 0.3 MPa was conducive to enrich arbutin, caffeic acid and gallic acid, endowing XPS with good immunomodulatory effect in vitro. XPS possessed the cake and caramel flavor due to SE treatment and its green, sweet, caramel and herbal odor increased. Finally, 5 metabolic pathways were screened to clarify the formation mechanism involving 21 metabolites. These results proved steam explosion had the potential to concentrated nutrients and improve flavor during food processing.PMID:39818094 | DOI:10.1016/j.foodchem.2025.142863

Chemosphere. 2025 Jan 15;372:144096. doi: 10.1016/j.chemosphere.2025.144096. Online ahead of print.ABSTRACTAcetaminophen (APAP), one of the most frequently used antipyretic and analgesic medications, has recently grown into a persistent organic contaminant of emerging concern due to its over-the-counter and widespread use. The excessive accumulation of APAP and its derivatives in various environmental matrices is threatening human health and the ecosystem. The complexity of APAP and its intermediates augments the need for adequate innovative and sustainable strategies for the remediation of contaminated environments. Bioremediation serves as an efficient, eco-friendly, cost-effective, and sustainable approach to mitigate the toxic impacts of APAP. The present review provides comprehensive insights into the ecotoxicity of APAP, its complex biodegradation pathways, and the various factors influencing biodegradation. The omics approaches viz., genomics/metagenomics, transcriptomics/metatranscriptomics, proteomics, and metabolomics have emerged as powerful tools for understanding the diverse APAP-degraders, degradation-associated genes, enzymatic pathways, and metabolites. The outcomes revealed amidases, deaminases, oxygenases, and dioxygenases as the lead enzymes mediating degradation via 4-aminophenol, hydroquinone, hydroxyquinol, 3-hydroxy-cis, cis-muconate, etc. as the major intermediates. Overall, a holistic approach with the amalgamation of omics aspects would accelerate the bioaugmentation processes and play a significant role in formulating strategies for remediating and reducing the heavy loads of acetaminophen from the environmental matrices.PMID:39818083 | DOI:10.1016/j.chemosphere.2025.144096

Plant Physiol Biochem. 2025 Jan 11;220:109484. doi: 10.1016/j.plaphy.2025.109484. Online ahead of print.ABSTRACTPlant height is a key trait that significantly influences plant architecture, disease resistance, adaptability to mechanical cultivation, and overall economic yield. Galactinol synthase (GolS) is a crucial enzyme involved in the biosynthesis of raffinose family oligosaccharides (RFOs). It plays a significant role in carbohydrate transport and storage, combating abiotic and biotic stresses, and regulating plant growth and development. The present study employed CRISPR/Cas9 gene-editing technology to create the gols4 mutant in tomato (Solanum lycopersicum), which exhibits a semi-dwarf phenotype. Results showed that glucose, sucrose, myo-inositol, galactinol, and raffinose levels were significantly reduced in the slgols4 mutant, impairing material transport and affecting the balance of soluble carbohydrates. Integration of transcriptomics and metabolomics data indicated not only a decrease in the expression of synthesis genes related to phenylpropanoid biosynthesis but also a significant reduction in the content of lignin and flavonoids, which are byproducts of phenylpropanoid metabolism. This may be a key factor contributing to dwarfism. Overall, these findings provide evidence for the role of SlGolS4 in regulating sugar metabolism and phenylpropanoid metabolism, offering new insights into tomato dwarfing cultivation and germplasm resources.PMID:39818071 | DOI:10.1016/j.plaphy.2025.109484

Plant Physiol Biochem. 2025 Jan 11;220:109482. doi: 10.1016/j.plaphy.2025.109482. Online ahead of print.ABSTRACTLagerstroemia excelsa is a unique plant species from China, holds a significant aesthetic and economic value, and plays a crucial role in landscape architecture and horticulture. Thus far, there is little genetic and genomic information available about this species, which limits its use in development of new cultivars. In this study, a high-quality genome map of L. excelsa was obtained via whole-genome sequencing. Results showed that its genome size is about 330.4 Mb and a scaffold mapping rate is approximately 97.20%, resulting in 24 pseudochromosomes. L. excelsa might have undergone a recent whole-genome triplication event and diverged from the pomegranate about 32.3 million years ago (MYA). Subsequently, the divergence time between L. indica and L. excelsa was around 5.9 MYA. The transcriptomic and metabolomic analyses of L. excelsa and L. indica indicated that the chalcone synthase pathway may play a key role in regulating flower color differentiation between the two species. Additionally, a transcription factor LeMYB103 may be involved in regulating anthocyanin synthesis by interacting with LeMYB66, resulting in the accumulation of anthocyanins in the stem bark. This study is the first step toward genomic analysis of L. excelsa, which may provide a foundation for further molecular investigation of this species and offer valuable insights into the molecular mechanisms underlying the flower and stem bark colors in L. excelsa, two important ornamental traits in Lagerstroemia breeding.PMID:39818068 | DOI:10.1016/j.plaphy.2025.109482

Environ Int. 2025 Jan 9;195:109257. doi: 10.1016/j.envint.2025.109257. Online ahead of print.ABSTRACTMicro-and-nano plastics (MNPs) are pervasive in terrestrial ecosystems and represent an increasing threat to plant health; however, the mechanisms underlying their phytotoxicity remain inadequately understood. MNPs can infiltrate plants through roots or leaves, causing a range of toxic effects, including inhibiting water and nutrient uptake, reducing seed germination rates, and impeding photosynthesis, resulting in oxidative damage within the plant system. The effects of MNPs are complex and influenced by various factors including size, shape, functional groups, and concentration. Recent advancements in omics technologies such as proteomics, metabolomics, transcriptomics, and microbiomics, coupled with emerging technologies like 4D omics, phenomics, spatial transcriptomics, and single-cell omics, offer unprecedented insight into the physiological, molecular, and cellular responses of terrestrial plants to MNPs exposure. This literature review synthesizes current findings regarding MNPs-induced phytotoxicity, emphasizing alterations in gene expression, protein synthesis, metabolic pathways, and physiological disruptions as revealed through omics analyses. We summarize how MNPs interact with plant cellular structures, disrupt metabolic processes, and induce oxidative stress, ultimately affecting plant growth and productivity. Furthermore, we have identified critical knowledge gaps and proposed future research directions, highlighting the necessity for integrative omics studies to elucidate the complex pathways of MNPs toxicity in terrestrial plants. In conclusion, this review underscores the potential of omics approaches to elucidate the mechanisms of MNPs-phytotoxicity and to develop strategies for mitigating the environmental impact of MNPs on plant health.PMID:39818003 | DOI:10.1016/j.envint.2025.109257

Acta Physiol (Oxf). 2025 Feb;241(2):e14273. doi: 10.1111/apha.14273.ABSTRACTPURPOSE: Homoarginine (hArg) is an arginine metabolite that has been known for years, but its physiological role in the body remains poorly understood. For instance, it is well known that high hArg concentrations in the blood are protective against several disease states, yet the mechanisms behind these health benefits are unclear. This review compiles what is known about hArg, namely its synthetic pathways, its role in different diseases and conditions, and its proposed mechanisms of action in humans and experimental animals.FINDINGS: Previous work has identified multiple pathways that control hArg synthesis and degradation in the body. Furthermore, endogenous hArg can modulate the cardiovascular system, with decreased hArg being associated with cardiovascular complications and increased mortality. Studies also suggest that hArg could serve as a diagnostic biomarker for a variety of immune, pancreatic, renal, and hepatic dysfunctions. Finally, in women, hArg concentrations rapidly increase throughout pregnancy and there are suggestions that alterations in hArg could indicate pregnancy complications like pre-eclampsia.SUMMARY: Homoarginine is an under-appreciated amino acid with potential wide-ranging roles in systemic health, pregnancy, and pathophysiology. Although recent research has focused on its health or disease associations, there is a need for more investigations into understanding the mechanistic pathways by which hArg may operate. This could be aided using metabolomics, which provides a comprehensive approach to correlating multiple metabolites and metabolic pathways with physiological effects. Increasing our knowledge of hArg's roles in the body could pave the way for its routine use as both a diagnostic and therapeutic molecule.PMID:39817883 | DOI:10.1111/apha.14273

Elife. 2025 Jan 16;13:RP101701. doi: 10.7554/eLife.101701.ABSTRACTEstrogen significantly impacts women's health, and postmenopausal hypertension is a common issue characterized by blood pressure fluctuations. Current control strategies for this condition are limited in efficacy, necessitating further research into the underlying mechanisms. Although metabolomics has been applied to study various diseases, its use in understanding postmenopausal hypertension is scarce. Therefore, an ovariectomized rat model was used to simulate postmenopausal conditions. Estrogen levels, blood pressure, and aortic tissue metabolomics were analyzed. Animal models were divided into Sham, OVX, and OVX +E groups. Serum estrogen levels, blood pressure measurements, and aortic tissue metabolomics analyses were performed using radioimmunoassay, UHPLC-Q-TOF, and bioinformatics techniques. Based on the above research content, we successfully established a correlation between low estrogen levels and postmenopausal hypertension in rats. Notable differences in blood pressure parameters and aortic tissue metabolites were observed across the experimental groups. Specifically, metabolites that were differentially expressed, particularly L-alpha-aminobutyric acid (L-AABA), showed potential as a biomarker for postmenopausal hypertension, potentially exerting a protective function through macrophage activation and vascular remodeling. Enrichment analysis revealed alterations in sugar metabolism pathways, such as the Warburg effect and glycolysis, indicating their involvement in postmenopausal hypertension. Overall, this current research provides insights into the metabolic changes associated with postmenopausal hypertension, highlighting the role of L-AABA and sugar metabolism reprogramming in aortic tissue. The findings suggest a potential link between low estrogen levels, macrophage function, and vascular remodeling in the pathogenesis of postmenopausal hypertension. Further investigations are needed to validate these findings and explore their clinical implications for postmenopausal women.PMID:39817721 | DOI:10.7554/eLife.101701

FASEB J. 2025 Jan 31;39(2):e70292. doi: 10.1096/fj.202401801RR.ABSTRACTSerum uric acid is an end-product of purine metabolism. Uric acid concentrations in excess of the physiological range may lead to diseases such as gout, cardiovascular disease, and kidney injury. The kidney includes a variety of cell types with specialized functions such as fluid and electrolyte homeostasis, detoxification, and endocrine functions. Two-thirds of uric acid is excreted through kidney, however, the exploration of markers and new therapeutic targets in renal tissue of hyperuricemia is still lacking. Single-cell and spatial omics techniques represent major milestones in life sciences. The combined measurement of the physical structure and molecular characteristics of tissues facilitates the exploration of the pathophysiological processes underlying disease development and the discovery of possible therapeutic targets. Here, the spatiotemporal atlas of hyperuricemic nephropathy was investigated using single-cell RNA sequencing, spatial transcriptomics, spatial proteomics, and spatial metabolomics in a urate oxidase knockout mouse model. Several emerging targets and pathways especially ribosome and metabolism related to uric acid excretion were discovered and will be investigated further in studies on lowering uric acid.PMID:39817712 | DOI:10.1096/fj.202401801RR

Gut Microbes. 2025 Dec;17(1):2452235. doi: 10.1080/19490976.2025.2452235. Epub 2025 Jan 16.ABSTRACTIrritable bowel syndrome (IBS) is a multifactorial condition with heterogeneous pathophysiology, including intestinal permeability alterations. The aim of the present study was to assess the ability of a probiotic blend (PB) consisting of two Lactiplantibacillus plantarum strains (CECT7484 and CECT7485) and one strain of Pediococcus acidilactici (CECT7483) to recover the permeability increase induced by mediators from IBS mucosal biopsies and to highlight the underlying molecular mechanisms. Twenty-one IBS patients diagnosed according to ROME IV criteria (11 IBS-D and 10 IBS-M) and 7 healthy controls were enrolled. Mucosal mediators spontaneously released by IBS and HC biopsies were collected and incubated with/without the PB (104 and 106 CFU/ml). Paracellular permeability was assessed by evaluating the amount of sulfonic-acid-conjugated to fluorescein passing through the Caco-2 monolayer. RNA was extracted from Caco-2 cells and used to perform qPCR analyses, to evaluate the expression of ZO-1 and β-actin, and RNAseq to evaluate the transcriptomic profile. Untargeted metabolomics was used to characterize metabolites produced by the PB. The PB significantly reduced paracellular permeability after 3 h of incubation. Both doses of the PB significantly recovered the increase in paracellular permeability induced by IBS mediators. qPCR analyses showed that both doses of the PB co-incubated with IBS mediators induced a significant increase in beta-actin expression compared to IBS mediators alone. Concerning IBS subtypes, the high dose of the PB recovered the increase of permeability induced by IBS-D mediators. Transcriptomic analyses, confirmed by qPCR, showed that the high dose of the PB significantly increased CYP1A1 compared to IBS mediators alone. The PB produced a high amount of indole-3-lactic acid. The PB recovers the permeability increase induced by IBS mediators inducing the up-regulation of β-actin. In addition, the PB up-regulates the expression of CYP1A1, known to be involved in the metabolism of xenobiotics, possibly through the production of the indole-3-lactic acid.PMID:39817446 | DOI:10.1080/19490976.2025.2452235

ALTEX. 2025;42(1):167-180. doi: 10.14573/altex.2412171.NO ABSTRACTPMID:39817434 | DOI:10.14573/altex.2412171

J Gastroenterol Hepatol. 2025 Jan 16. doi: 10.1111/jgh.16882. Online ahead of print.ABSTRACTBACKGROUND AND AIM: Colorectal cancer (CRC) is a significant global health burden, and screening can greatly reduce CRC incidence and mortality. Previous studies investigated the economic effects of CRC screening. We performed a systematic review to provide the cost-effectiveness of CRC screening strategies across countries with different income levels.METHODS: We searched relevant scientific databases (PubMed, Embase, Ovid, Web of Science, Scopus) from January 1, 2010, to December 31, 2023. We selected English-language studies related to model-based economic evaluations of CRC screening strategies. Information such as the characters of screening tests, model characteristics, and key cost-effectiveness findings were collected. The net monetary benefit approach was used to compare the outcomes of various strategies.RESULTS: A total of 56 studies were identified, including 46 from high-income countries (HICs), 6 from upper-middle-income countries (UMICs), and 4 from lower-middle-income countries (LMICs). Most annual fecal occult blood tests and fecal immunochemical tests were cost-saving, and colonoscopy every 10 years was cost-saving. Other strategies involving multitarget fecal FIT-DNA detection, computed tomography colonography, and flexible sigmoidoscopy were cost-effective compared with no screening. Newer strategies such as magnetic resonance colonography every 5 years, annual urine metabolomic tests, and fecal bacterial biomarkers were cost-effective compared with no screening.CONCLUSION: In our updated review, we found that common CRC screening strategies and magnetic resonance colonography continued to be cost-effective compared with no screening. Areas for further development include accurately modeling the natural history of colorectal cancer and obtaining more evidence from UMICs and LMICs.PMID:39817422 | DOI:10.1111/jgh.16882

Hypertension. 2025 Jan 16. doi: 10.1161/HYPERTENSIONAHA.124.23666. Online ahead of print.ABSTRACTBACKGROUND: Adrenomedullin 2 (AM2) plays critical roles in regulating blood pressure and fluid balance. However, the specific involvement of AM2 in cardiac hypertrophy has not been comprehensively elucidated, warranting further investigation into its molecular mechanisms and therapeutic implications.METHODS: Cardiac hypertrophy was induced in adult mice lacking AM2 (AM2-/-) using transverse aortic constriction surgery. Comprehensive cardiac morphology, function, histology, and transcriptome/metabolome analyses were conducted. Signal transduction underlying AM2 stimulation in the cardiomyocytes was explored.RESULTS: The absence of endogenous AM2 led to the development of severe heart failure after transverse aortic constriction surgery, which was characterized by alterations in the mitochondrial morphology and function associated with glycolysis and the tricarboxylic acid cycle in the heart and cardiomyocytes of transverse aortic constriction-operated AM2-/- mice. AM2 stimulation was associated with the receptor-modifying factor RAMP2 (receptor activity-modifying protein 2), which primarily transduces signals through the MAPK pathway and affects the expression of genes involved in glycolysis, β-oxidation, and oxidative phosphorylation. The administration of exogenous AM2 alleviated heart failure following transverse aortic constriction.CONCLUSIONS: AM2 crucially regulates mitochondrial functions associated with the glycolysis and tricarboxylic acid cycles in the cardiomyocytes, thereby exerting a protective effect on the heart under pressure overload conditions.PMID:39817339 | DOI:10.1161/HYPERTENSIONAHA.124.23666

Front Parasitol. 2024 Sep 4;3:1461641. doi: 10.3389/fpara.2024.1461641. eCollection 2024.ABSTRACTArtemisinin-based treatments (ACTs) are the first therapy currently used to treat malaria produced by Plasmodium falciparum. However, in recent years, increasing evidence shows that some strains of P. falciparum are less susceptible to ACT in the Southeast Asian region. A data reanalysis of several omics approaches currently available about parasites of P. falciparum that have some degree of resistance to ACT was carried out. The data used were from transcriptomics and metabolomics studies. One mitochondrial carrier of the parasite possibly involved in the mechanisms of tolerance to oxidative stress was modeled and subjected to molecular dockings with citrate and oxoglutarate. An increase in glutathione production was detected, changing the direction of the flux of metabolites in the tricarboxylic acid cycle and boosting the glucose consumed. The models of the mitochondrial carrier, called PfCOCP, show that it may be important in transporting citrate and oxoglutarate from the mitochondrial matrix to the cytosol. If so, it may allow the parasite to tolerate the oxidative stress produced by artemisinin. This in-silico analysis shows that P. falciparum may tolerate artemisinin's oxidative stress through metabolic changes not reported before, showing the need for further experimental research on the many metabolic aspects linked to this phenotype.PMID:39817177 | PMC:PMC11731681 | DOI:10.3389/fpara.2024.1461641

J Diabetes Metab Disord. 2025 Jan 13;24(1):47. doi: 10.1007/s40200-024-01545-w. eCollection 2025 Jun.ABSTRACTINTRODUCTION: The effects of Sodium-glucose cotransporter-2 (SGLT-2) inhibitors on cardiac outcomes, cardiovascular mortality (CVM), and all-cause mortality (ACM) in type 2 diabetes mellitus (T2DM) patients have been reported heterogeneously in different studies.METHODS: PubMed, Scopus, Embase, Cochrane Library, and Scholar databases were searched with relevant MeSH terms from January 1, 2010, to November 14, 2023. The study used Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The primary outcomes in all trials included the risk of ACM, CVM, hospitalization for heart failure (HHF), myocardial infarction (MI), and cerebrovascular accidents (CVA) in T2DM patients who were treated with one of the SGLT-2 inhibitors. Heterogeneity between studies was evaluated using Cochran's Q and I2 tests. The Egger's test was used to check for publication bias.RESULTS: Eighteen studies, including 70,830 participants, were included. A pooled estimate showed that SGLT-2 inhibitor treatment was significantly associated with reduced ACM (OR: 0.82, 95% CI: 0.75-0.90, p-value: 0.001, I2: 35.1%), CVM (OR: 0.88, 95% CI: 0.80-0.96, p-value: 0.001, I2: 0%), MI (OR: 0.88, 95% CI: 0.79-0.98, p-value: 0.001, I2: 0%), and HHF (OR: 0.67, 95% CI: 0.58-0.77, p-value: 0.001). SGL-2 inhibitor treatment had no significant relationship with CVA (stroke) (OR: 0.95, 95% CI: 0.8-1.10, p-value: 0.896). Subgroup analysis showed that the effect of SGLT-2 inhibitor treatment on outcomes varied based on the type of SGLT-2 inhibitor.CONCLUSION: SGLT-2 inhibitor treatment significantly reduced CVM, ACM, MI, and HHF. Empagliflozin, Canagliflozin, and Dapagliflozin significantly reduced ACM. Canagliflozin was significantly associated with a reduction in CVM. All SGLT-2 inhibitor treatments were associated with a reduction in HHF.PMID:39816986 | PMC:PMC11730052 | DOI:10.1007/s40200-024-01545-w

Prostate Int. 2024 Sep;12(3):167-177. doi: 10.1016/j.prnil.2024.07.003. Epub 2024 Jul 25.ABSTRACTBACKGROUND: The causal associations and potential mechanisms between prostatic diseases, the predominant male urological disorders, and the course of COVID-19 remain unclear.METHODS: A two-sample Mendelian randomization (MR) analysis was performed to evaluate causal associations between prostate cancer, benign prostatic hyperplasia, and prostatitis and different COVID-19 outcomes (SARS-CoV-2 infection, hospitalized COVID-19, and severe COVID-19). Reverse MR, linkage disequilibrium score regression, and Bayesian colocalization analyses were subsequently performed to strengthen the identified causal relationships. Furthermore, immunome- and metabolome-wide MR analysis was conducted to prioritize COVID-19-associated immune characteristics and metabolites. Two-step MR analysis was performed to evaluate the mediating effects of the immunome and metabolome on the associations between prostatic diseases and COVID-19.RESULTS: Genetically predicted prostatic diseases were not causally associated with severe COVID-19, while prostatitis was suggested to be an independent risk factor for SARS-CoV-2 infection (odds ratio (OR) = 1.11, 95% confidence interval (CI) 1.01 to 1.23; P = 0.03). Multiple sensitivity tests verified the reliability of the established causal relationships. Dozens of blood immune and metabolic features were identified to reveal the immune and metabolic profiles of different COVID-19 courses. Moreover, PDL-1 on monocyte was found to mediate the interaction between prostatitis and SARS-CoV-2 infection, with a mediation proportion of 9.2%.CONCLUSION: Our study identified the causal relationships of prostatic diseases with COVID-19 and suggested pathways explaining these associations through alterations in the blood immunome and metabolome.PMID:39816935 | PMC:PMC11733763 | DOI:10.1016/j.prnil.2024.07.003

Transl Cancer Res. 2024 Dec 31;13(12):6956-6969. doi: 10.21037/tcr-2024-2379. Epub 2024 Dec 27.ABSTRACTBACKGROUND: Many cancer cells exhibit aberrant metabolic reprogramming through abnormal mitochondrial respiration. Protein tyrosine phosphatase mitochondrial 1 (PTPMT1) is a protein tyrosine phosphatase localized to the mitochondria and linked to mitochondrial respiration. However, the expression and role of PTPMT1 in regulating the biological characteristics of small cell lung cancer (SCLC) has not yet been explored. The aim of this study was to evaluate the role of PTPMT1 on SCLC cell survival and mitochondrial function.METHODS: SCLC and adjacent normal tissues were obtained from surgery. The expression level of PTPMT1 in the SCLC tissues and cell lines was determined by immunohistochemical staining, western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). PTPMT1 knockdown was induced by lentivirus-mediated short-hairpin RNA (shRNA) transduction and PTPMT1 inhibition (alexidine dihydrochloride). The biological characteristics of the cells were measured by cell counting kit 8 (CCK-8), colony formation assay, and cell migration assay. The mitochondrial function of the cells was measured by 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining. The H69 cells were treated with alexidine dihydrochloride, after which transcriptome sequencing and an untargeted metabolomic analysis were performed. The transcriptome differentially expressed genes were measured by qRT-PCR.RESULTS: PTPMT1 was upregulated in the SCLC tissues compared to the adjacent normal tissues. PTPMT1 inhibition by lentiviral shRNA transduction or specific inhibition resulted in significant growth arrest and apoptosis. The transcriptome sequencing analysis revealed that pathways related to the respiration chain and mitochondrial member protein were disrupted. Several mitochondrial metabolism-related genes, such as FGF21, GDF-15, APLN, and MT-DN6, were dysregulated. Further, PTPMT1 inhibition was found to downregulate Glut expression and disturb mitochondrial function.CONCLUSIONS: PTPMT1 was shown to play a critical role in the survival and growth of SCLC cells, and may become a potential therapeutic target.PMID:39816544 | PMC:PMC11730198 | DOI:10.21037/tcr-2024-2379

Heliyon. 2024 Dec 21;11(1):e41309. doi: 10.1016/j.heliyon.2024.e41309. eCollection 2025 Jan 15.ABSTRACTIsocitrate dehydrogenase wild-type glioblastoma (GBM) is characterised by a heterogeneous genetic landscape resulting from dynamic competition between tumour subclones to survive selective pressures. Improvements in metabolite identification and metabolome coverage have led to increased interest in clinically relevant applications of metabolomics. Here, we use liquid chromatography-mass spectrometry and gene expression microarray to profile integrated intratumour metabolic heterogeneity, as a direct functional readout of adaptive responses of subclones to the tumour microenvironment. Multi-region surgical sampling was performed on five adult GBM patients based on pre-operative brain imaging and fluorescence-guided surgery. Polar and hydrophobic metabolites extracted from tumour fragments were assessed, followed by putative assignment of metabolite identifications based on retention times and molecular mass. Class discrimination between tumour regions through showed clear separation of tumour regions based on polar metabolite profiles. Metabolic pathway assignments revealed several significantly altered metabolites between the tumour core and invasive region to be associated with purine and pyrimidine metabolism. This proof-of-principle study assesses intratumour heterogeneity through mass spectrometry-based metabolite profiling of multi-region biopsies. Bioinformatic interpretation of the GBM metabolome has highlighted the invasive region to be biologically distinct compared to tumour core and revealed putative drug-targetable metabolic pathways associated with purine and pyrimidine metabolism.PMID:39816516 | PMC:PMC11732679 | DOI:10.1016/j.heliyon.2024.e41309