Given the prevalence of metabolic perturbations in a variety of neurological and neurodegenerative diseases, understanding and monitoring brain metabolism is a key step in our advancement of therapies. The details of the citric acid cycle were established at the beginning of the last century but only recently have its metabolic intermediates been observed in vivo in the brain. In this study, we employed orthogonal analyses to investigate metabolic alterations in response to acute neuroinflammation in vivo, demonstrating a multi-technique approach that could be used for future studies.Hyperpolarized [1-¹³C] pyruvate spectroscopy revealed an early decline in pyruvate metabolism via pyruvate dehydrogenase (PDH), leading to reduced ¹³C-bicarbonate formation. This metabolic disruption occurred despite the absence of structural or perfusion changes on conventional MRI. Further analysis of polar metabolites in the ipsilateral hemisphere confirmed ongoing inflammatory processes. These findings highlight the potential of this dual technique approach to inform upon metabolic changes due to neuroinflammation.Combining methods to probe metabolism in invasive (metabolomics) and non-invasive (hyperpolarized MRI) manners, this represents a promising translational approach for real-time metabolic assessments in an area of the body, the brain, where studying processes such as metabolism has traditionally been challenging. This study has demonstrated the approach to monitor changes in metabolism in response to inflammation in the brain.

Ligusticum chuanxiong Hort. is an important medicinal plant whose dried rhizomes are used in traditional Chinese medicine for preventing and treating cardiovascular and cerebrovascular diseases. However, this plant tends to accumulate cadmium (Cd), and the Cd content in its rhizomes often exceeds the limit of 1 mg/kg stipulated by the Chinese Pharmacopoeia (2025 edition). This not only adversely affects the synthesis and accumulation of active compounds, but also leads to rejection of exported products, causing significant economic losses. Given three Cd-tolerant strains (Trichoderma afroharzianum F38, Mucor ctenidius F24, and Bacillus proteolyticus B90) isolated from L. chuanxiong roots with a maximum Cd tolerance of 3 mmol/L, this study performed a co-cultivation experiment under 20 mg/L Cd stress in hydroponics. The results demonstrated that Cd stress significantly inhibited plant growth and induced oxidative damage, manifested as increased malondialdehyde content and activation of the antioxidant enzyme system. Inoculation with any of the three Cd-tolerant strains alleviated growth inhibition and oxidative stress. All three strains significantly reduced Cd content in both aerial parts and underground parts, but with distinct characteristics: F38 reduced underground parts Cd content by 54.72% and promoted Cd translocation to aerial parts; F24 decreased aerial parts Cd content by 40.27%; while B90 exhibited a more prominent effect in enhancing overall plant Cd tolerance. Overall, the efficacy of the strains in mitigating Cd toxicity and promoting growth followed the order: F38 > F24 > B90. In conclusion, the Cd-tolerant strains isolated from the roots system of L. chuanxiong effectively reduced Cd accumulation and alleviated Cd stress, providing feasible microbial resources and micro-ecological regulation strategies to address Cd contamination in medicinal plants and ensure the safety of herbal materials.

Sustained exposures to high atmospheric levels of PM2.5 at population scale are associated with increased risks for pulmonary inflammatory diseases. These are marked by activation of the TRPC6 (Transient Receptor Potential Canonical type 6) calcium channel, increased reactive oxygen species (ROS) and oxidative stress. Long term exposures are associated with reduced life span, and increased incidences of cardiovascular diseases, dementia, Parkinson's and Alzheimer disease, and increased risk of autism and autism spectrum disorders. It has been proposed that the PM2.5 toxin is benzo[a]pyrene (B[a]P) that is adsorbed to the surface of the PM2.5 particle.. But the mechanism by which B[a]P might drive pulmonary inflammatory diseases, or any other of the indications above, are not known.

B[a]P was recently reported to bind irreversibly and destructively to the β2 Adrenergic Receptor (β2AR) in the lung. We have therefore hypothesized that B[a]P is the adsorbed PM2.5 toxin, and that β2AR is the B[a]P receptor responsible for TRPC6 activation in lung epithelial cells.

To test this hypothesis, we exposed a polarized organoid model of normal human lung epithelia, polarized lung epithelial 16HBE14o-cells, and tracheobronchial slice cultures from ferret lung to either PM2.5 or B[a]P. We found that both PM2.5 and B[a]P: (i) irreversibly activated of β2AR signaling via G _i to PI3K/AKT; (ii) increased NFκB-activated release of proinflammatory cytokines through IKKαβ activation by PI3K/AKT, which was suppressed by the PI3K inhibitor LY 294002 (iii) desensitized and destroyed the activated β2AR receptor by endocytic recycling; (iv) also destroyed β2AR's signalplex partner CFTR by the same process; (v) activated the CFTR-bound calcium channel protein TRPC6 due to loss of inhibitory CFTR; leading to (vi) increased cytosolic [Ca ²⁺ ] concentration; (vii) increased ROS due to mitochondrial uncoupling; and (viii) increased expression of oxidative stress. Treatment with the TRPC6 inhibitor BI 749327 blocked steps (vi-viii), and preserved CFTR from endocytic loss. Treatment of tracheobronchial slice cultures of ferret lung with either PM2.5 or B[a]P resulted in increased secretion of IL-6, increased expression of TRPC6, and reduced expression of β2AR and CFTR. Finally, we found that exposure of lung organoids to B[a]P significantly reduced expression of the same five microRNAs (miR-126a-3p, miR-30b-5p, miR-103a-3p, miR-26a-5p, and miR-766-3p) previously identified in sera from service members exposed to PM2.5 from burn pit emissions during deployment to Iraq and Afghanistan.

PM2.5 and the PM2.5 toxin benzo[a]pyrene (B[a]P) induce inflammation and oxidative stress in the airway by increased expression of TRPC6 and inactivation of β2AR/CFTR signaling. These discoveries mark the first identification of a mechanism by which exposure to PM2.5 or the PM2.5 toxin B[a]P itself can induce inflammation and TRPC6-dependent oxidative stress in lung epithelia.

Ischemic stroke (IS) accounts for ~85% of all stroke cases and stands as one of the leading global causes of disability and mortality. Its pathological progression is closely intertwined with intricate inflammatory responses, among which post-stroke activated macrophages are widely recognized as the core drivers and regulators of IS pathogenesis. This review systematically elucidates the dual role of macrophages in stroke: they act as the primary drivers of the acute neuroinflammatory storm, while also serving as key regulators of neurorepair during the subacute and chronic phases. By focusing on the spatiotemporal dynamic changes, polarization regulatory mechanisms, and phenotypic/functional transition patterns of macrophages. This review provides a theoretical foundation for the development of precise therapeutic strategies that target the spatiotemporal dynamics and functional transitions of macrophages.

Endothelial dysfunction, chronic inflammation, immune dysregulation, oxidative stress, mitochondrial dysfunction, and metabolic disturbances collectively contribute to cardiovascular diseases (CVDs) associated with blood stasis patterns. Xuefu Zhuyu Decoction (XFZYD) is widely used clinically for the management of CVDs. Based on serum-exposed prototype profiling in rats, two pharmacology-driven core component sets of XFZYD were defined as the core set for the promotion of blood circulation and the elimination of blood stasis (CPBEB; HSYA, GRo, FA, β-ECD, AMY, ALB, PF) and the core set for the regulation of qi and the relief of pain (CRQRP; LIQ, NR, NAR, ROF, HSD, NHP, LTG, NRG, ISL, FNT, NOB, PD, SSa). CPBEB primarily targets vascular pathology by regulating endothelial dysfunction with dyslipidemia-driven arterial lipid deposition. Mechanistically, CPBEB is associated with improved endothelial function, reduced plaque instability, attenuated chronic inflammation and oxidative stress, normalized lipid and bile acid metabolism, and decreased thrombosis. CRQRP primarily modulates vascular tone and systemic energy metabolism. These effects are linked to enhanced AMPK/SIRT1-driven antioxidant defenses and mitochondrial homeostasis, increased NO/cGMP signaling, coordinated crosstalk among the TLR4/NF-κB, JAK/STAT, NLRP3, and PPAR pathways, and remodeling of the gut microbiota-immune network. In summary, this review integrates modern analytical approaches with network pharmacology and the literature evidence to clarify the material basis underlying XFZYD's therapeutic effects in CVDs, thereby supporting the modernization and internationalization of traditional Chinese medicine.

Background/Objectives: Variants of MYPN, encoding a sarcomeric protein myopalladin, are associated with different types of cardiomyopathies and myopathies. However, the molecular mechanisms of MYPN-associated pathologies are still poorly understood. Methods: In this study, we generated induced pluripotent stem cells (iPSCs) from a hypertrophic cardiomyopathy patient carrying a novel p.N989I (c.2966A>T) variant of MYPN and used iPSC-derived cardiomyocytes to examine the impact of the variant on biophysical characteristics and transcriptomic profile. Results: No significant changes in parameters of calcium transients, sodium current and action potential were found in iPSC-derived cardiomyocytes with the p.N989I (c.2966A>T) variant of MYPN compared to non-isogenic cells from an unrelated healthy donor. At the transcriptomic level, MYPN-N989I cardiomyocytes demonstrated an upregulation of genes linked to cell cycle, mitotic spindle, microtubule cytoskeleton organization, and myogenic program genes. Downregulation of sarcomeric, Z-disc- and cell junction-associated genes, as well as genes involved in ATP synthesis, oxidative phosphorylation, and the SRF-signaling pathway, was also revealed. Conclusions: Our data suggest that the p.N989I (c.2966A>T) variant of MYPN plays a dual role in hypertrophic cardiomyopathy pathogenesis, disrupting not only sarcomeric and cytoskeletal organization but also the regulation of the muscle gene program.

Plasma circular RNAs (circRNAs) are stable RNA molecules found in blood, which makes them potential noninvasive biomarkers for acute myocardial infarction (MI). The aim of this study was to describe the plasma circRNA profile in patients with acute MI and to identify circRNA markers that may help detect heart injury and reflect the biological processes involved. We compared plasma samples from patients with acute MI and healthy controls using total RNA sequencing with unique molecular identifiers (UMIs). After sequencing, reads were processed through quality control, alignment, duplicate removal, and circRNA detection. Differential expression was analyzed after adjusting for age, sex, smoking, and technical factors. Several circRNAs were significantly different between MI cases and controls and were able to separate the two groups in principal component and receiver operating characteristic analyses. Among the most increased circRNAs were hsa-PASK_0004, hsa-STXBP3_0002, hsa-RCAN3_0002, and hsa-RANBP9_0044, while hsa-HIF1A_0002, hsa-SUZ12_0049, hsa-PNRC1_0001, and hsa-RAB2A_0002 were decreased. Several candidates showed AUC values above 0.7. Pathway analysis linked the host genes of these circRNAs to inflammation, platelet activation, coagulation, and cardiomyocyte stress responses. Overall, these findings suggest that circulating circRNAs may serve as useful blood-based markers of MI and provide insight into the molecular changes that accompany acute MI.

Oxidative stress disrupts protein function through direct oxidation and triggers adaptive post-translational modifications. Among these, small ubiquitin-like modifier (SUMO)-ylation mediates fast and reversible remodeling of nuclear and cytoplasmic proteins. Redox regulation of the SUMO E1-E2 conjugation complex and specific SUMO proteases, such as SENP1 and SENP3, allows ROS to influence SUMO turnover and substrate selectivity. This defines SUMOylation as a versatile stress-response module under oxidative stress. In this review, we describe oxidative stress-induced remodeling of SUMO conjugation and deconjugation, with a focus on SUMO2/3 responses that transiently adjust transcription, DNA damage repair, and nuclear body dynamics. We discuss disease-relevant SUMO targets and pathological alterations in SUMO regulation across four major disease categories: neurodegenerative diseases, cardiovascular disease, cancer, and diabetes/metabolic diseases. In addition, we summarize emerging evidence connecting redox-sensitive SUMO remodeling to germ-cell function and reproductive health. Together, these perspectives highlight the dual role of SUMOylation as both a driver of stress adaptation and a tractable target for informing therapeutic strategies targeting the SUMO pathway.

Ginsenoside Rg1 (G-Rg1) can effectively ameliorate lipopolysaccharide-induced renal injury. The impact and mechanism of G-Rg1 in renal ischemia-reperfusion (I/R) injury are not yet understood. This study aimed to examine the role and mechanism of G-Rg1 in kidney I/R injury. The renal I/R injury mice and mouse kidney cells were applied as renal I/R injury models. Researchers analyzed the functions and mechanisms of G-Rg1 using techniques like cell proliferation, apoptosis, clone formation assay, ELISA, HE staining, immunohistochemical staining, Immunofluorescence staining, qRT-PCR, and Western blot analysis. Our findings indicate that G-Rg1 pretreatment protects against renal I/R injury by lowering serum creatinine and urea nitrogen levels, mitigating histological damage and apoptosis, and reducing inflammation and oxidative stress. These beneficial effects were accompanied by the suppression of fatty acid binding protein 1 (FABP1) and heme oxygenase-1 (HO-1) expression and the promotion of nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation. However, the therapeutic effect of G-Rg1 was inhibited by FABP1 overexpression. The mechanism by which G-Rg1 ameliorates renal I/R injury may be related to the inhibition of FABP1 expression and thus regulation of the Nrf2/HO-1 pathway.

Background and Objectives: The interaction between the brain and heart has become more interesting in the last 20 years. The most common cardiac complications after stroke are myocardial infarction, heart failure, arrhythmias, electrocardiographic disturbances, repolarization disorders, and sudden cardiac death. The prolonged Tpeak-Tend interval is an indicator of the electrical heterogeneity of the myocardium (abnormal repolarization) that causes malignant arrhythmias. We aimed to investigate whether the Tpeak-Tend interval, which reflects the heterogeneity of repolarization, is prolonged in stroke and its relationship with short-term mortality. Materials and Methods: Individuals over the age of 18 who presented with hemorrhagic or ischemic stroke were included in the study. Demographic characteristics, laboratory and imaging findings of the patients were recorded. ECGs were obtained at the time of admission to the hospital and 24 h later. Patients were followed for in-hospital mortality. Results: 89 (82.4%) of the patients had ischemic stroke, 19 (17.6%) had hemorrhagic stroke. It was determined that Tp-eV2 and Tp-eV5 at hospital admission were significantly longer than the 24th hour values. A total of 92.01 (16.3) ms at Tp-eV2 admission, 84.1 (16.3) ms after 24 h (p = 0.003), 91.9 (7.3) msTp-eV5 at admission, and 81.6 (17.8) ms (p = 0.000) after 24 h. In multivariate logistic regression analysis of in-hospital mortality, Tp-eV2 (HR: 0.96 (95% CI 0.93-0.99) p = 0.008) was determined as an independent predictor among cardiovascular parameters. Conclusions: Tp-e intervals were prolonged in both leads V2 and V5 in patients with stroke. Prolongation of lead V2 in the Tp-e interval is an independent indicator of short-term mortality among cardiovascular parameters.