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Intracerebral hemorrhage (ICH) is a subtype of hemorrhagic stroke with high mortality and morbidity. The resulting hematoma within brain parenchyma induces a series of adverse events causing primary and secondary brain injury. The mechanism of injury after ICH is very complicated and has not yet been illuminated. This review discusses some key pathophysiology mechanisms in ICH such as oxidative stress (OS), inflammation, iron toxicity, and thrombin formation. The corresponding therapeutic targets and therapeutic strategies are also reviewed.

Transcranial direct current stimulation is a noninvasive technique that has been experimentally tested for a number of psychiatric and neurological conditions. Preliminary observations suggest that this approach can indeed influence a number of cellular and molecular pathways that may be disease relevant. However, the mechanisms of action underlying its beneficial effects are largely unknown and need to be better understood to allow this therapy to be used optimally. In this review, we summarize the physiological responses observed in vitro and in vivo, with a particular emphasis on cellular and molecular cascades associated with inflammation, angiogenesis, neurogenesis, and neuroplasticity recruited by direct current stimulation, a topic that has been largely neglected in the literature. A better understanding of the neural responses to transcranial direct current stimulation is critical if this therapy is to be used in large-scale clinical trials with a view of being routinely offered to patients suffering from various conditions affecting the central nervous system.

Background: Visceral white adipose tissue (vWAT) inflammation is a critical pathology of obesity-caused heart damage and is closely associated with adipocyte endoplasmic reticulum (ER) dysfunction. Serine (or cysteine) peptidase inhibitor, clade A, member 3C (Serpina3c) has been identified as an adipokine with anti-vWAT inflammatory effects. However, it remains unclear whether Serpina3c deficiency promotion of vWAT inflammation involves adipocyte ER dysfunction and whether it further contributes to heart damage in obesity. Methods: Wild type and Serpina3c knockout (Serpina3c -/- ) mice were fed a high-fat diet (HFD) for 12 weeks. An adeno-associated virus (AAV) was injected locally into epididymal white adipose tissue (eWAT) of Serpina3c -/- mice to induce eWAT-adipocyte-specific overexpression of Serpina3c (AAV-Serpina3c) or knockdown of hypoxia-inducible factor 1α (AAV-shHIF1α). In vitro experiments were performed in 3T3-L1 adipocytes. Results: Serpina3c -/- mice exhibited more severe eWAT, serum and heart inflammation after HFD feeding. Consistently, these adverse phenotypes were mitigated in AAV-Serpina3c and AAV-shHIF1α mice. Mechanistically, ER oxidoreductase 1α (Ero1α) and protein disulfide isomerase (PDI) family members PDIA3 and PDIA4 were found to be target genes of HIF1α. In the obese mice, Serpina3c deficiency caused adipocyte more hypertrophy, and activated HIF1α-Ero1α/PDI mediated ER overoxidation and ER stress in eWAT. Subsequently, this led to increased adipocyte apoptosis and chemokine production and decreased adiponectin expression, which promoted macrophage infiltration and M1 polarization in eWAT, thus exacerbating eWAT inflammation and ultimately facilitating serum and distal heart inflammation. Conclusion: These findings indicate that Serpina3c is a significant regulator of adipocyte ER redox homeostasis, thus highlighting Serpina3c as a potential therapeutic target for obesity-related eWAT inflammation and heart damage.

There is growing evidence that psychosocial interventions can have psychological benefits for people affected by cancer, including improved symptoms of mental health and wellbeing and optimised immune responses. However, despite growing numbers of music interventions, particularly singing, in cancer care, there is less research into their impact. We carried out a multicentre single-arm preliminary study to assess the impact of singing on mood, stress and immune response in three populations affected by cancer: carers (n = 72), bereaved carers (n = 66) and patients (n = 55). Participants were excluded if pregnant or if they were currently being treated with chemotherapy, radiotherapy or oral immunosuppressive drugs. Participants were regular participants in five choirs across South Wales and took part in one hour of group singing. Before and after singing, visual analogue mood scales, stress scales and saliva samples testing for cortisol, beta-endorphin, oxytocin and ten cytokines were taken. Across all five centres and in all four participant groups, singing was associated with significant reductions in negative affect and increases in positive affect (p < .01) alongside significant increases in cytokines including GM-CSF, IL17, IL2, IL4 and sIL-2rα (all p < .01). In addition, singing was associated with reductions in cortisol, beta-endorphin and oxytocin levels. This study provides preliminary evidence that singing improves mood state and modulates components of the immune system. Further work is needed to ascertain how this differs for more specific patient groups and whether repeat exposure could lead to meaningful, longitudinal effects.

Bupleuri Radix (BR) is a traditional Chinese medicine and widely used for cold and fever, influenza, inflammation, hepatitis and menstrual diseases. Two authentic medicinal plants of Bupleuri chinense DC. (Beichaihu, BCH) and B. scorzonerifolium Willd. (Nanchiahu, NCH) are recommended by the current Chinese Pharmacopoeia for BR. In the present study, the comparative investigations on the anti-inflammatory effects and gas chromatography-mass spectrometry (GC-MS)-based metabolomics for the species discrimination of BCH and NCH were conducted and reported. The in vitro evaluations indicated that the supercritical fluid extracts (SFEs) (IC 50 of 6.39 ± 0.52 and 1.32 ± 0.05 mg (herb)/mL for BCH and NCH) were determined to be more potent than those of the hydro-distillation extracts (HDEs) (IC 50 of 203.90 ± 8.08 and 32.32 ± 2.27 mg (herb)/mL for BCH and NCH) against LPS-induced inflammation in RAW264.7 macrophages. The higher anti-inflammatory effects of NCH were associated to its different chemical compositions to the BCH as characterized by the GC-MS analysis. Furthermore, based on the metabolomics and deep chemometric approaches, a minimum combination containing 15 chemical markers was optimized from the identified components and successfully applied for the species discrimination of BCH and NCH. This study not only helps to comparative understand BCH and NCH both in phytochemistry and pharmacology, but also provides the potential chemical markers for improvement of methods for the quality control of BCH and NCH.

Background: Peroxisome proliferator‐activated receptor‐gamma coactivator‐1α (PGC‐1α), a regulator of mitochondrial function, plays a critical role in inflammation and may be involved in cystitis glandularis (CG) development. Methods: LPS was administered to establish a CG model in female Sprague–Dawley (SD) rats and to induce cellular injury in the human urothelial cell line SV‐HUC‐1. Subsequently, to elucidate the role of PGC‐1α signaling in CG, both the animal and cellular models were treated with ZLN005, a specific activator of PGC‐1α. Cell viability was assessed using the cell‐counting kit‐8 (CCK8) assay. Mitochondrial damage was quantified by measuring reactive oxygen species (ROS), assessing mitochondrial membrane potential, and examining mitochondrial ultrastructure via transmission electron microscopy (TEM). Enzyme‐linked immunosorbent assays (ELISA) were utilized to determine the levels of inflammatory cytokines, namely, IL‐1β, IL‐6, and TNF‐α. Furthermore, the protein expression of silent information regulation 1 (SIRT1), PGC‐1α, mitochondrial transcription factor A (TFAM), nuclear respiratory factor 1 (NRF1), and nuclear respiratory factor 2 (NRF2) was evaluated using immunohistochemistry and/or Western blot analysis. Results: LPS‐treated rat bladder exhibited histological characteristics of CG, including increased urothelial proliferation and inflammation. PGC‐1α protein levels were downregulated in human CG tissues, LPS‐treated rat bladders, and SV‐HUC‐1 cells. Mitochondrial damage was observed in both rat CG and LPS‐irritated cells with elevated ROS and diminished mitochondrial membrane potential. TEM documented mitochondrial morphological injury of the urothelium in rat CG. ZLN005 attenuated LPS‐induced epithelial hyperplasia and inflammatory cytokine secretion in the rat CG model. Furthermore, ZLN005 partially reversed LPS‐induced mitochondrial damage, as indicated by reduced ROS levels, restored mitochondrial membrane potential, and mitigated mitochondrial morphological injury in both rat CG and LPS‐stimulated cells. In addition, ZLN005 restored the expression of PGC‐1α and its associated signaling proteins SIRT1, TFAM, NRF1, and NRF2. Conclusions: The downregulation of PGC‐1α suggests its potential as a molecular marker for the progression of CG. Targeting the PGC‐1α signaling pathway may offer an effective therapeutic intervention for the clinical management of CG.

Background: Visceral white adipose tissue (vWAT) inflammation is a critical pathology of obesity-caused heart damage and is closely associated with adipocyte endoplasmic reticulum (ER) dysfunction. Serine (or cysteine) peptidase inhibitor, clade A, member 3C (Serpina3c) has been identified as an adipokine with anti-vWAT inflammatory effects. However, it remains unclear whether Serpina3c deficiency promotion of vWAT inflammation involves adipocyte ER dysfunction and whether it further contributes to heart damage in obesity.Methods: Wild type and Serpina3c knockout (Serpina3c–/–) mice were fed a high-fat diet (HFD) for 12 weeks. An adeno-associated virus (AAV) was injected locally into epididymal white adipose tissue (eWAT) of Serpina3c–/– mice to induce eWAT-adipocyte- specific overexpression of Serpina3c (AAV-Serpina3c) or knockdown of hypoxia-inducible factor 1α (AAV-shHIF1α). In vitro experiments were performed in 3T3-L1 adipocytes.Results: Serpina3c–/– mice exhibited more severe eWAT, serum and heart inflammation after HFD feeding. Consistently, these adverse phenotypes were mitigated in AAV-Serpina3c and AAV-shHIF1α mice. Mechanistically, ER oxidoreductase 1α (Ero1α) and protein disulfide isomerase (PDI) family members PDIA3 and PDIA4 were found to be target genes of HIF1α. In the obese mice, Serpina3c deficiency caused adipocyte more hypertrophy, and activated HIF1α-Ero1α/PDI mediated ER overoxidation and ER stress in eWAT. Subsequently, this led to increased adipocyte apoptosis and chemokine production and decreased adiponectin expression, which promoted macrophage infiltration and M1 polarization in eWAT, thus exacerbating eWAT inflammation and ultimately facilitating serum and distal heart inflammation.Conclusion: These findings indicate that Serpina3c is a significant regulator of adipocyte ER redox homeostasis, thus highlighting Serpina3c as a potential therapeutic target for obesity-related eWAT inflammation and heart damage.

Recent evidence suggests that Alzheimer’s disease (AD) genetic risk variants (rs1582763 and rs6591561) of the MS4A locus are genome-wide significant regulators of soluble TREM2 levels such that the minor allele of the protective variant (rs1582763) is associated with higher sTREM2 and lower AD risk while the minor allele of (rs6591561) relates to lower sTREM2 and higher AD risk. Our group previously found that higher sTREM2 relates to higher Aβ 40 , worse blood–brain barrier (BBB) integrity (measured with the CSF/plasma albumin ratio), and higher CSF tau, suggesting strong associations with amyloid abundance and both BBB and neurodegeneration complicate interpretation. We expand on this work by leveraging these common variants as genetic tools to tune the interpretation of high CSF sTREM2, and by exploring the potential modifying role of these variants on the well-established associations between CSF sTREM2 as well as TREM2 transcript levels in the brain with AD neuropathology. Biomarker analyses leveraged data from the Vanderbilt Memory & Aging Project ( n  = 127, age = 72 ± 6.43) and were replicated in the Alzheimer’s Disease Neuroimaging Initiative ( n  = 399, age = 73 ± 7.39). Autopsy analyses were performed leveraging data from the Religious Orders Study and Rush Memory and Aging Project ( n  = 577, age = 89 ± 6.46). We found that the protective variant rs1582763 attenuated the association between CSF sTREM2 and Aβ 40 (β = -0.44, p -value = 0.017) and replicated this interaction in ADNI (β = -0.27, p = 0.017). We did not observe this same interaction effect between TREM2 mRNA levels and Aβ peptides in brain (Aβ total β = -0.14, p =  0.629; Aβ 1-38 , β = 0.11, p =  0.200). In contrast to the effects on Aβ, the minor allele of this same variant seemed to enhance the association with blood–brain barrier dysfunction (β = 7.0e-4, p =  0.009), suggesting that elevated sTREM2 may carry a much different interpretation in carriers vs. non-carriers of this allele. When evaluating the risk variant (rs6591561) across datasets, we did not observe a statistically significant interaction against any outcome in VMAP and observed opposing directions of associations in ADNI and ROS/MAP on Aβ levels. Together, our results suggest that the protective effect of rs1582763 may act by decoupling the associations between sTREM2 and amyloid abundance, providing important mechanistic insight into sTREM2 changes and highlighting the need to incorporate genetic context into the analysis of sTREM2 levels, particularly if leveraged as a clinical biomarker of disease in the future.

Background: In southwest China, especially in Nujiang, lacquer oil from the drupes of Toxicodendron vernicifluum (Stokes) F. A. Barkley, including black lacquer oil (BLO) and white lacquer oil (WLO), is one of the most important edible oils for the local people. Through the field investigation, the locals believe that lacquer oil has benefits for parturient women and for the treatment of “Yuezi” disease. However, studies on bioactivities and the chemical compositions of lacquer oil are limited. Purpose: This study was designed to reveal the mystery of lacquer oil for the treatment of “Yuezi” disease by testing its anti-inflammatory and anti-postpartum depressant activities and related bioactive compounds. Methods: The anti-inflammatory effects of lacquer oil were examined by establishing a lipopolysaccharide (LPS)-induced RAW264.7 cell inflammation model and detecting the level of pro-inflammatory factors such as NO, IL-6 and TNF-α. The antidepressant effects of lacquer oil were studied by building a mouse model of postpartum depression (PPD), and the animal behavior changes of PPD model mice were assessed by open field test (OFT), forced swimming test (FST) and tail suspension test (TST). The chemical profiles of BLO and WLO were detected by lipidomic and the untargeted metabolomic research methods based on UPLC-MS/MS. Results: The results showed that BLO and WLO exerted anti-inflammatory effects by reducing the release of pro-inflammatory factors and BLO had better anti-inflammatory effects than WLO. While only BLO had anti-postpartum depressant activities, as evidenced by the significantly reduced the immobility time of the BLO-treated PPD mice in TST and FST compared to the PPD model mice. The comparative lipidomic analysis revealed that BLO contained high levels of Diacylglycerols (DAG) and Diacylglyceryl trimethylhomoserines (DGTS) but low level of ceramides (Cer), sphingomyelines (SM), phosphatidylcholines (PC) and phosphatidylethanolamines (PE) compared with WLO. Metabolomics analysis showed that there were 57 chemical markers between BLO and WLO, of which 17 potential biomarkers have been declared to possess anti-inflammatory and/or antidepressant activities. Conclusion: The findings of this study furnish a scientific support for the traditional uses of lacquer oil for the treatment of “Yuezi” disease from anti-inflammation and anti-postpartum depression perspective.

Background and Aims To investigate the effects of a 6‐month supervised, personalized combined aerobic and resistance training program on oxidative stress, antioxidant capacity, infection‐related biomarkers, and body composition in maintenance hemodialysis (MHD) patients. Methods In this single‐center, randomized controlled trial (nonblinded, parallel design), 61 MHD patients (standard thrice‐weekly 4‐h sessions) were randomly assigned to either an exercise group (n = 36) or a control group (n = 35). The exercise intervention comprised: The exercise group received 6 months of supervised training (three times a week, 2 h before dialysis), including: ①Aerobic exercise: A 20‐min stationary cycling session at RPE 13 (with heart rate maintained at 60%–70% of maximum heart rate). ②Resistance training: Four lower‐body exercises (leg extension, straight leg raise, hip abduction, hip flexion) using ethylene‐vinyl acetate resistance bands (10 reps/set, RPE 13). The control group received standard care. Primary outcomes were oxidative stress markers (MDA, AOPP), antioxidant indicators (CAT, THIOL, TBIL), infection markers (IL‑6, PCT, CRP, Hcy), and body composition measures (muscle mass, BMI). Results After 6 months of intervention, the exercise group exhibited significantly reduced levels of MDA (p < 0.05) and AOPP (p < 0.05). CAT activity (p < 0.05), THIOL levels (p < 0.05), and TBIL levels (p < 0.001) were significantly increased. IL‐6, PCT, CRP, and Hcy were lower than those in the control group (p < 0.05). The exercise group also demonstrated improved Kt/V (p < 0.05) and attenuated declines in muscle mass and BMI compared to controls (p < 0.05). Conclusion This structured exercise program effectively mitigates oxidative damage, boosts antioxidant defenses, reduces infection markers, and enhances dialysis efficiency and body composition in MHD patients. These findings provide evidence for incorporating supervised exercise as a novel therapeutic strategy in nephrology care.