Objective: To investigate the effects of Zuogui Jiangtang Jieyu Formula (ZGJTJYF) on histone H3 lysine 18 lactylation (H3K18la) in the hippocampus of rats with diabetes mellitus complicated with depression (DD) and predict the regulatory genes of H3K18la. Methods: Male Sprague-Dawley rats were divided into control, model, and positive drug (metformin [0.18 g/kg] and fluoxetine [1.8 mg/kg]) groups, and the three groups were treated with high, medium, and low ZGJTJYF doses (20.52, 10.26, and 5.13 g/kg, respectively), with 10 rats per group. After treatment, the forced swimming and water maze tests were performed to assess depressive-like behaviors and cognitive function. An enzyme-linked immunosorbent assay was used to measure blood insulin, glycosylated hemoglobin, lactate levels, and lactate content in the hippocampus. Western blotting was used to detect H3K18la expression in the hippocampus. Cleavage Under Targets and lagmentation(CUT&Tag) experiments targeted hippocampal H3K18la epigenetic modification regions to analyze the transcription factors bound by H3K18la. Kyoto Encyclopedia of Genes and Genomes and Protein-Protein Interaction networks were constructed to identify key pathways and target genes regulated by H3K18la. Results: Compared with the normal group, the model group rats showed prolonged immobility time in the forced swim test, increased escape latency in the water maze experiment, decreased target quadrant distance ratio (P<0.01), increased serum lactate content, and decreased lactate content in hippocampal homogenate (P<0.01), as well as decreased H3K18la protein expression in the hippocampus (P<0.01). Compared with the model group, ZGJTJYF reduced the immobility time in the forced swim test and the escape latency in the water maze test (P<0.01), while the distance ratio in the target quadrant increased (P<0.01) in model rats. Lowered fasting blood glucose, insulin, and glycosylated hemoglobin levels (P<0.05, P<0.01) were also observed. ZGJTJYF also increased the lactate content and H3K18la protein expression in hippocampal homogenate (P<0.05, P<0.01). The DNA sequences bound by H3K18la were predominantly enriched at the transcription start sites. ZGJTJYF modulated H3K18la-associated pathways, including cell adhesion junctions, tumor growth factor-beta (TGF-β) signaling, stem cell pluripotency regulation, mitogen-activated protein kinase(MAPK) signaling pathway, and insulin resistance, leading to the identification of 12 target genes. Conclusion ZGJTJYF enhances hippocampal lactate levels and H3K18la modification in DD rats, which may regulate neural cell interactions, neurogenic stem cell function, TGF-β signaling, MAPK signaling, and insulin resistance pathways.

Rubi Fructus has a long history of medicinal and edible use in China. It contains chemical components such as terpenes, flavonoids, phenolic acids, fatty acids, and alkaloids, and possesses various pharmacological activities, including antioxidant, anti-inflammatory, hypoglycemic, anti-tumor, anti-osteoporosis, and liver-protective effects. Rubi Fructus is widely applied in medical, health, and food fields. The quality of Rubi Fructus can directly affect the safety and effectiveness of clinical medication. Therefore, this article reviews the research progress on the chemical constituents and pharmacological effects of Rubi Fructus. Based on the concept of traditional Chinese medicine(TCM) quality markers(Q-markers), the article explores the screening and determination of Q-markers for Rubi Fructus from various aspects, including plant kinship, traditional efficacy, medicinal properties, measurability of chemical composition, different processing methods, producing areas, harvesting periods, and planting conditions. The components ellagic acid, kaempferol, quercetin, kaempferol-3-O-rutinoside, rutin, astragalin, tiliroside, and hyperoside are preliminarily proposed as Q-markers for Rubi Fructus, providing a reference for the quality control of Rubi Fructus.
Drugs, Chinese Herbal/pharmacology* ; Humans ; Rubus/chemistry* ; Fruit/chemistry* ; Quality Control ; Animals

Eucommiae Cortex, the dried bark of Eucommia ulmoides( Eucommiaceae), has both medicinal and edible values.Modern research has shown that Eucommiae Cortex contains various components such as flavonoids, lignans, iridoids, phenolic acids,terpenoids, and steroids, which have anti-osteoporosis, antioxidant, anti-inflammatory, blood glucose-lowering, and gastrointestinal tract-protecting effects. Eucommiae Cortex has applications in multiple fields such as healthcare, industry, and animal husbandry,demonstrating broad development prospects. This article reviews the chemical constituents, pharmacological effects, and quality control status of Eucommiae Cortex. Furthermore, according to the concept of quality marker(Q-marker), this article predicts the Q-markers of Eucommiae Cortex from traditional medicinal properties, traditional medicinal effects, new medicinal effects, measurability of chemical components, compatibility, harvesting periods, and geographical origins. The components such as pinoresinol diglucoside,chlorogenic acid, caffeic acid, quercetin, baicalein, baicalin, olivil, coniferyl ferulate, and kaempferol can be used as Q-markers for Eucommiae Cortex, which provide reference for establishing a systematic quality control system for Eucommiae Cortex.
Eucommiaceae/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Quality Control ; Humans ; Animals

OBJECTIVE: To investigate possible associations between physical function assessment scales, such as Short Physical Performance Battery (SPPB) and Berg Balance Scale (BBS), with all-cause mortality in acute decompensated heart failure (ADHF) patients. METHODS: A total of 108 ADHF patients were analyzed from October 2020 to October 2022, and followed up to May 2023. The association between baseline clinical characteristics and all-cause mortality was analyzed by univariate Cox regression analysis, while for SPPB and BBS, univariate Cox regression analysis was followed by receiver operating characteristic curves, in which the area under the curve represented their predictive accuracy for all-cause mortality. Incremental predictive values for both physical function assessments were measured by calculating net reclassification index and integrated discrimination improvement scores. Optimal cut-off value for BBS was then identified using restricted cubic spline plots, and survival differences below and above that cut-off were compared using Kaplan-Meier survival curves and the log-rank test. The clinical utility of BBS was measured using decision curve analysis. RESULTS: For baseline characteristics, age, female, blood urea nitrogen, as well as statins, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or angiotensin receptor-neprilysin inhibitors, were predictive for all-cause mortality for ADHF patients. With respect to SPPB and BBS, higher scores were associated with lower all-cause mortality rates for both assessments; similar area under the curves were measured for both (0.774 for SPPB and 0.776 for BBS). Furthermore, BBS ≤ 36.5 was associated with significantly higher mortality, which was still applicable even adjusting for confounding factors; BBS was also found to have great clinical utility under decision curve analysis. CONCLUSIONS BBS or SPPB could be used as tools to assess physical function in ageing ADHF patients, as well as prognosticate on all-cause mortality. Moreover, prioritizing the improvement of balance capabilities of ADHF patients in cardiac rehabilitation regimens could aid in lowering mortality risk.

Cardiac arrest (CA) is a critical condition in the field of cardiovascular medicine. Despite successful resuscitation, patients continue to have a high mortality rate, largely due to post CA syndrome (PCAS). However, the injury and pathophysiological mechanisms underlying PCAS remain unclear. Experimental animal models are valuable tools for exploring the etiology, pathogenesis, and potential interventions for CA and PCAS. Current CA animal models include electrical induction of ventricular fibrillation (VF), myocardial infarction, high potassium, asphyxia, and hemorrhagic shock. Although these models do not fully replicate the complexity of clinical CA, the mechanistic insights they provide remain highly relevant, including post-CA brain injury (PCABI), post-CA myocardial dysfunction (PAMD), systemic ischaemia/reperfusion injury (IRI), and the persistent precipitating pathology. Summarizing the methods of establishing CA models, the challenges encountered in the modeling process, and the mechanisms of PCAS can provide a foundation for developing standardized CA modeling protocols.
Animals ; Disease Models, Animal ; Post-Cardiac Arrest Syndrome/physiopathology* ; Heart Arrest/physiopathology* ; Humans ; Ventricular Fibrillation/complications*

Patients with depression are more likely to have chronic gastrointestinal (GI) symptoms than the general population, but such symptoms are considered only somatic symptoms of depression and lack special attention. There is a chronic lack of appropriate diagnosis and effective treatment for patients with depression accompanied by GI symptoms, and studying the association between depression and GI disorders (GIDs) is extremely important for clinical management. There is growing evidence that depression is closely related to the microbiota present in the GI tract, and the microbiota-gut-brain axis (MGBA) is creating a new perspective on the association between depression and GIDs. Identifying and treating GIDs would provide a key opportunity to prevent episodes of depression and may also improve the outcome of refractory depression. Current studies on depression and the microbially related gut-brain axis (GBA) lack a focus on GI function. In this review, we combine preclinical and clinical evidence to summarize the roles of the microbially regulated GBA in emotions and GI function, and summarize potential therapeutic strategies to provide a reference for the study of the pathomechanism and treatment of depression in combination with GI symptoms.
Humans ; Gastrointestinal Microbiome/physiology* ; Depression/microbiology* ; Gastrointestinal Diseases/physiopathology* ; Brain ; Animals ; Brain-Gut Axis ; Gastrointestinal Tract/microbiology*

The development of anticancer drugs to treat triple-negative breast cancer (TNBC) is an ongoing challenge. Immunogenic cell death (ICD) has garnered considerable interest worldwide as a promising synergistic modality for cancer chemoimmunotherapy. However, only few drugs or treatment modalities can trigger an ICD response and none of them exert a considerable clinical effect against TNBC. Therefore, new agents with potentially effective chemoimmunotherapeutic response are required. In this study, five new cyclometalated Ir(III) complexes containing isoquinoline alkaloid CˆN ligands were designed and synthesized. Among them, Ir-1 exhibited the highest in vitro cytotoxicity. Mechanistically, Ir-1 could trigger autophagy-dependent ferroptosis and a subsequent ferroptosis-dependent ICD response as well as indoleamine 2,3-dioxygenase (IDO) inhibition via reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress in MDA-MB-231 cells. When immunocompetent BALB/c mice were vaccinated with Ir-1-treated dying TNBC cells, antitumor CD8⁺ T-cell response and Foxp3⁺ T-cell depletion were induced, resulting in long-lasting antitumor immunity in TNBC cells. Moreover, combination therapy with Ir-1 and anti-PD1 could substantially augment in vivo therapeutic effects. Based on these results, Ir-1 is a promising candidate for chemoimmunotherapy against TNBC and its effects are mediated synergistically via ICD induction and IDO blockage.

Liver transplantation (LT) has become a standard treatment for end-stage liver diseases, and graft injury is intricately associated with poor prognosis. Granzyme B (GZMB) plays a vital role in natural killer (NK) cell biology, but whether NK-derived GZMB affects graft injury remains elusive. Through the analysis of single-cell RNA-sequencing data obtained from human LT grafts and the isolation of lymphocytes from mouse livers following ischemia-reperfusion injury (IRI), we demonstrated that 2NK cells with high expression of GZMB are enriched in patients and mice. Both systemically and liver-targeted depletion of NK cells led to a notable reduction in GZMB⁺ cell infiltration, subsequently resulting in diminished graft injury. Notably, the reconstitution of Il2rg ^-/- Rag2 ^-/- mice with purified Gzmb-KO NK cells demonstrated superior outcomes compared to those with wild-type NK cells. Crucially, global knockout of GZMB and pharmacological inhibition exhibited remarkable improvements in liver function in both mouse IRI and rat LT models. Moreover, a phosphorylated derivative of FDA-approved vidarabine was identified as an effective inhibitor of mouse GZMB activity by molecular dynamics, which could provide a potential avenue for therapeutic intervention. Therefore, targeting NK cell-derived GZMB during the LT process suggests potential therapeutic strategies to improve post-transplant outcomes.