Copper is essential for mitochondrial respiration, antioxidant defense, extracellular matrix maturation, and cellular signaling, yet disturbances in its abundance or intracellular distribution can damage the kidney through mechanistically distinct pathways. Cuproptosis is a specific copper-dependent form of regulated cell death in which copper binds lipoylated mitochondrial proteins, promotes aggregation of tricarboxylic acid cycle components, destabilizes iron-sulfur cluster proteins, and elicits FDX1- and protein lipoylation-dependent proteotoxic stress. This mechanism should be distinguished from broader copper-associated injury, including redox imbalance, glutathione depletion, respiratory-chain inhibition, senescence, apoptosis, and lysyl oxidase-mediated matrix remodeling. This narrative review examines how renal copper uptake, trafficking, and compartmentalization interact with cell-specific metabolism to shape copper-related cell fates across acute kidney injury, nephrotoxicity, renal ischemia-reperfusion injury, crystal- and lipid-related tubular injury, diabetic kidney disease, podocyte injury, chronic kidney disease and renal fibrosis, end-stage renal disease, renal cell carcinoma, and hereditary copper disorders. Mechanistic evidence is strongest in selected acute tubular, crystal-injury, and renal cancer models, in which transporter manipulation, DLAT oligomerization, iron-sulfur perturbation, or functional rescue has been demonstrated. In chronic kidney disease and fibrosis, copper-DLAT interactions, complex IV inhibition, COMMD1-SOD1 dysfunction, and ATP7A-FBLN4-LOX signaling establish pathogenic copper dependence but do not yet demonstrate a complete canonical cuproptosis pathway. By integrating disease-specific evidence with the molecular determinants of copper handling and protein lipoylation, this review identifies current therapeutic opportunities, candidate biomarkers, and key research priorities while preserving the distinction between cuproptosis and other forms of copper-associated kidney injury.

Gastric cancer is one of the malignancies with the highest incidence and mortality worldwide. Helicobacter pylori (H. pylori) infection is the primary driving factor in its development. The progression of gastric mucosal malignancy follows the Correa cascade model: “chronic non-atrophic gastritis → chronic atrophic gastritis (CAG) → intestinal metaplasia (IM) → dysplasia (Dys) → gastric cancer.” Currently, clinical management faces major challenges, including increasing antibiotic resistance in H. pylori, limited pharmacological options for gastric precancerous lesions, and treatment resistance and toxicity in established gastric cancer. This review synthesizes current evidence on BBR, COP, EPI, PAL, and JAT and organizes their reported actions into a three-tier intervention framework. At the first tier, etiologic and inflammatory interception, individual alkaloids suppress H. pylori persistence through direct antibacterial injury, urease inhibition, and modulation of bacterial virulence and antibiotic susceptibility, while attenuating infection-driven inflammatory and immune responses. At the second tier, modulation of precancerous mucosal progression, preclinical studies indicate that these compounds can ameliorate gastric glandular injury and may attenuate biological processes associated with progression toward intestinal metaplasia and dysplasia. At the third tier, antitumor and adjunctive intervention in established gastric cancer, alkaloids inhibit proliferation, induce cell-cycle arrest and apoptosis, suppress invasion and metastasis, and regulate non-coding RNA and epigenetic networks; BBR-centered preclinical studies further suggest potential chemosensitizing and supportive effects. This review integrates the five alkaloids BBR, COP, EPI, PAL, and JAT and systematically elucidates their mechanisms of action across the pathological continuum from H. pylori infection and chronic inflammation to precancerous lesions and ultimately gastric cancer. It establishes a stage-oriented, compound-specific analytical framework to clarify the pharmacological positioning of these compounds, identify priorities requiring further validation, and guide future mechanistic and translational research.

Vascular dementia (VaD), the second most common form of dementia, lacks approved disease-modifying therapies. White matter injury and demyelination are major pathological features, and oligodendrocyte-lineage damage directly limits myelin repair. M2-associated microglial responses regulate inflammation, clear cellular and myelin debris, and support oligodendrocyte differentiation and maturation. Single-cell studies, however, have exposed the limitations of the classical M1/M2 dichotomy in brain disease. In this review, M2a-, M2b-, and M2c-like states are interpreted based on experimentally specified inducing conditions and concordant molecular or functional evidence. We examine how these programs relate to oligodendrocyte injury, myelin loss, and white matter repair in VaD. with particular attention to their potentially stage-dependent contributions. Integrating these findings may inform the timing and functional focus of future interventions aimed at preserving oligodendrocyte function and promoting white matter repair in VaD.

Ischemic stroke (IS), characterised by vascular occlusion, is the most common type of stroke. Focal cerebral ischemia triggers a robust immune response, with immune cells and the associated inflammatory reactions emerging shortly after the ischemic event and persisting over time. The inflammatory mediators released during this process not only induce immune dysregulation but also exacerbate brain injury, adversely affecting post-stroke prognosis. Although increasing attention has been directed toward the interactions between the central nervous system and peripheral immunity following stroke, the progression of inflammation and the intercellular interactions among immune cells during the acute and chronic phases of ischemia remain insufficiently understood. Therefore, this review takes peripheral immune cells (T lymphocytes, neutrophils, B cells, and natural killer cells) as examples to summarise the dynamic interrelationships and influences between peripheral immune cells and central immune cells (microglia and astrocytes) at different stages following IS. The mechanisms underlying these immune cell interactions and the cytokines involved are discussed, with illustrative examples. Additionally, the impact of comorbidities on the progression of IS is explored, providing insights for further research on the interplay between the central nervous system and peripheral immunity.

Ischemic stroke evolves beyond arterial occlusion through an inflammation-centered network linking neurovascular dysfunction, immune remodeling, metabolic reprogramming, and regulated cell death. These interactions are organized across the hyperacute, acute, subacute, and chronic phases. Hyperacute energy failure, excitotoxicity, thromboinflammation, pericyte contraction, and capillary stalling can sustain microcirculatory no-reflow despite recanalization. Acute injury is characterized by blood–brain barrier disruption, innate immune amplification, mitochondrial stress, as well as ferroptotic, necroptotic, pyroptotic, and proposed cuproptotic pathways. Subacute recovery involves debris clearance, immune resolution, angiogenesis, metabolic adaptation, and oligodendrocyte-lineage repair, whereas chronic outcomes reflect persistent inflammation, white-matter remodeling, and neural plasticity. Cell-specific metabolism and brain-border and systemic immune–metabolic communication further shape injury and recovery. Experimental evidence is distinguished from findings in human blood, thrombectomy-derived samples, imaging, and brain tissue. Therapeutic translation requires stage-matched interventions compatible with reperfusion and rehabilitation, clinically realistic post-onset dosing, mechanistic biomarkers, and appropriate safety evaluation. This framework links early microvascular rescue with immune resolution, metabolic recovery, and network repair.

BACKGROUND Ulcerative colitis (UC) is a chronic inflammatory bowel disease for which effective therapies are lacking. Niu Huang (NH) is a traditional Chinese medicine used for inflammatory disorders. However, its protective effect on UC and its underlying mechanisms are unknown. AIM To uncover the mechanisms underlying the anti-colitis effects of the NH. METHODS Network pharmacology was applied to predict the active ingredients and targets of NH. Experimental validation was conducted in a dextran sulfate sodium-induced murine colitis model. The therapeutic efficacy was assessed using symptoms, histopathology, quantitative polymerase chain reaction, western blotting, immunohistochemistry and enzyme linked immunosorbent assay, while the underlying mechanism was investigated through integrated transcriptomic and proteomic analyses. In addition, the critical role of farnesoid X receptor (FXR) in mediating the effects of NH was validated using the FXR inhibitor guggulsterone and Fxr-/- mouse models. RESULTS Network pharmacology revealed that the bioactive component of NH is bile acid. Our animal experiments demonstrated that NH treatment significantly alleviated colitis symptoms and pathological damage. NH preserved intestinal mucosal integrity by upregulating occludin, claudin3, E-cadherin and leucine rich repeat containing G protein-coupled receptor 5 expression. Transcriptomic and proteomic analyses revealed that bile secretion, the nuclear factor kappa B signaling pathway and the complement and coagulation cascade pathway are key targets of NH. Western blotting confirmed that NH increased FXR levels and reduced P65, complement component 3 (C3) and NOD-like receptor family pyrin domain containing 3 (NLRP3) expression. Furthermore, experiments using Fxr-/- mice and the FXR antagonist revealed that FXR is a pivotal target through which NH attenuates UC. Mechanistic analysis revealed that the effects of NH on UC are mediated by the modulation of targets involved in the activation of FXR and the subsequent inhibition of C3/NLRP3 activation. CONCLUSION This study demonstrates the therapeutic effects of NH on UC. Mechanistically, NH acts by activating FXR, which subsequently inhibits the nuclear factor kappa B pathway to reduce C3 accumulation and suppress excessive NLRP3 inflammasome activation in colon tissue.

Cognitive impairment encompasses a range of clinical syndromes resulting from various brain disorders. Among these, Alzheimer’s disease and related dementias, Parkinson’s disease, and stroke represent the most prevalent and significant cerebrovascular conditions that impact cognitive function and lead to neurodegenerative damage. Microglia, serving as the principal immune regulators within brain tissue, exhibit diverse phenotypes, including M1 and M2, in response to inflammatory environments, thereby collectively contributing to the restoration of homeostasis. However, under sustained stimulation, microglia undergo cell death and release inflammatory factors through different mechanisms of cell death, thereby influencing the prognosis of cerebrovascular diseases. Although there is a growing recognition of the regulatory role of microglial phenotypic transformation in the progression of cerebrovascular diseases, research remains insufficient regarding the developmental processes of these diseases following the death of microglial cells with varying phenotypes. This article centres on cerebrovascular disease-induced cognitive impairment as its primary focus. It provides a comprehensive review of common acute cerebrovascular diseases, such as ischemic stroke, alongside neurodegenerative conditions including Alzheimer’s disease, Parkinson’s disease, and vascular dementia. The discussion extends to the common phenotypes of microglia and their impact on cerebrovascular diseases. Additionally, the article explores how inflammatory cell death mechanisms of microglia, namely necroptosis, pyroptosis, ferroptosis, and autophagy, regulate disease progression, thereby providing insights for future research on the role of microglia in cerebrovascular pathology. This literature search selected two major international mainstream academic databases, PubMed and Web of Science, to include high-quality original research and review papers in the field. Based on the research topic of this study, a combination of subject terms and free words was used to conduct a search of articles from January 2000 to June 2026. The English search keywords were: microglia, phenotype, necroptosis, pyroptosis, ferroptosis, autophagy, PANoptosis, Alzheimer's disease, Parkinson's disease, vascular dementia, ischemic stroke, cytokines, signaling pathway. Academic literature that was officially published and had the complete full text available was selected. Subsequently, a preliminary screening was conducted by reading the titles and abstracts, and those obviously not related to the topic were eliminated. Finally, a re-screening was carried out by reading the full texts, and the final list of included literature was determined strictly according to the inclusion and exclusion criteria, ensuring the scientificity, representativeness and rigor of the literature materials of this review.

Ischemic stroke (IS) remains a leading cause of global mortality and neurological disability, with neuronal mitochondrial dysfunction as a central pathological mechanism. Astrocytes, the metabolic custodians of the central nervous system, exert neuroprotection by transferring functional mitochondria to compromised neurons via tunneling nanotubes (TNTs), extracellular vesicles (EVs), connexin 43 (Cx43) mediated gap junctions, and membrane fusion. These transfers replenish neuronal energy reserves, mitigate oxidative stress, and enhance synaptic plasticity. This review systematically delineates the molecular mechanisms of astrocyte-mediated mitochondrial transfer, its regulatory roles in oxidative stress, calcium dyshomeostasis, and ferroptosis, and its therapeutic potential in IS. Experimental models demonstrate that pharmacological enhancement of mitochondrial transfer or exogenous transplantation significantly reduces infarct volume and improves neuronal survival. However, clinical translation faces challenges including low mitochondrial viability, immune rejection, and inefficient delivery. Future research should integrate gene-editing tools, nanocarrier systems, and organoid models to optimize mitochondrial dynamics and develop precision therapies. By bridging mechanistic insights with translational innovations, astrocytic mitochondrial transfer emerges as a groundbreaking strategy for ischemic stroke treatment.

Ischemic stroke (IS) is a major neurological disease that causes death and long-term disability worldwide. After ischemic injury, the brain undergoes complex pathological changes. As core components of the blood-brain barrier (BBB), endothelial cells and pericytes are crucial for maintaining barrier integrity, regulating cerebral blood flow, and mediating angiogenesis. Recent studies have demonstrated that, following IS, endothelial cells and pericytes can engage in mitochondrial transfer and exosome release through multiple pathways. This review constructs a signaling interaction network between endothelial cells and pericytes during IS, summarizing the cellular and molecular mechanisms underlying mitochondrial transfer networks and exosome-mediated communication. Furthermore, the physiological relevance of endothelial cell–pericyte interactions is discussed from the perspectives of vascular risk factors, non-coding RNAs, and cellular heterogeneity, as well as their potential therapeutic applications in the treatment of IS.

Decidual protein induced by progesterone 1 (DEPP1), also known as DEPP or C10ORF10, was originally identified as a progesterone-induced protein in endometrial stromal cells. Over the past two decades, research has progressively elucidated its involvement in various biological processes such as energy metabolism, redox regulation, and cellular autophagy. Additionally, DEPP1 has been implicated in the pathogenesis of several diseases, including diabetes, atherosclerosis, ischemic cardiomyopathy, breast cancer, and colon cancer. In this review, we systematically summarise the research progress on DEPP1, with particular emphasis on its molecular mechanisms in the crosstalk between oxidative stress and autophagy. Its cellular localization and functional uniqueness are discussed within the context of the classical redox-autophagy regulatory network. Furthermore, key issues in DEPP1 research and its potential translational applications are discussed to provide insights and perspectives for future studies centred on DEPP1.

Vascular dementia (VaD), a primary cognitive disorder caused by cerebrovascular pathology, features significant white matter damage from chronic cerebral hypoperfusion strongly correlated with cognitive decline. Myelin integrity disruption represents a core pathological foundation in VaD, with dysfunctional oligodendrocytes (OLs) and microglia (MG) forming a critical pathogenic nexus. OLs govern myelin formation and maintenance while MGs modulate myelination through cerebral microenvironment regulation. In the central nervous system, precise communication and synergistic interaction between cells are the basis for maintaining homeostasis and cognitive function. The complement system, cytokine network, and extracellular vesicles together form its core communication axis. The complement system is at the forefront of the rapid innate immune response, cytokines dynamically regulate the initiation and resolution of inflammation, as carriers of functional molecules between cells, extracellular vesicles target and deliver information of bioactive molecules, upgrading intercellular communication to an active and programmed network regulation system. The three work together to maintain the homeostasis of the neural microenvironment. Their dysregulation can lead to uncontrolled neuroinflammation and tissue damage, which is the core pathological link in diseases such as VaD. This review examines the interplay between OLs and MG in VaD demyelination, detailing their complex communication networks via the complement system (including C1q, C3, C5 fragments), key cytokines (TNF-α, IL-1β, IL-4, IL-10), and extracellular vesicle signaling. Notably, these pathways exhibit bidirectionality: moderate activation promotes repair mechanisms, whereas excessive responses exacerbate injury. Future research should elucidate the spatiotemporal dynamics of OLs-MG interactions and identify precise therapeutic targets to restore cellular equilibrium, thereby informing novel VaD intervention strategies.

Insomnia is associated with disrupted sleep architecture, hippocampal pathological alterations, neurotransmitter imbalance, and neuroinflammatory responses. This study evaluated the effects of the Prunella vulgaris compound (PVC) on sleep architecture and hippocampal alterations in p-chlorophenylalanine (PCPA)-induced insomnia model mice and examined their association with NLRP3-related pyroptotic signaling. PVC was characterized using UPLC-Q-Exactive Orbitrap MS and targeted HPLC quantification. PCPA-induced insomnia models were established in ICR and C57BL/6N mice for pharmacodynamic and molecular assessments and EEG/EMG recording, respectively. Sleep outcomes were assessed using the pentobarbital-induced sleep test and EEG/EMG; hippocampal histomorphology, neurotransmitters, and inflammasome- and pyroptosis-related markers were evaluated using histological, biochemical, RT-qPCR, and Western blot analyses. UPLC-MS tentatively characterized 198 constituents, and salviaflaside, rosmarinic acid, and linarin were quantified by HPLC. PVC shortened sleep latency, prolonged sleep duration, reduced wakefulness, increased NREM and REM sleep, and improved sleep continuity. It also attenuated hippocampal histomorphological alterations; modulated 5-HT, GABA, glutamate, and dopamine levels; and reduced NLRP3 inflammasome- and pyroptosis-related markers together with IL-1β and IL-18. PVC improved insomnia-like phenotypes and attenuated hippocampal pathological alterations in PCPA-induced insomnia model mice. These effects were associated with improved sleep architecture and neurotransmitter homeostasis and with reduced NLRP3/caspase-1/GSDMD-related signaling.

Objective To investigate the pharmacodynamic effects of Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou (Z. jujuba, Suan Zao Ren) fermented with the fungus of Poria cocos (Schw.) Wolf (P. cocos strain) and Massa Medicata Fermentata (MMF) on hippocampal monoamine neurotransmitters in mice with blood-deficiency insomnia. Methods Fermented Z. jujuba products were prepared from P. cocos strain (PCS) and MMF. A mouse model of blood-deficiency insomnia was established via intraperitoneal injection of cyclophosphamide and p-chlorophenylalanine. Model evaluation included general physical status, a pentobarbital sodium-induced sleep test, and peripheral blood analysis, including white blood cells, red blood cells (RBC), and hemoglobin (Hb). Hippocampal levels of norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were measured using high-performance liquid chromatography with electrochemical detection. Results Compared to the control group, mice in the model group exhibited shortened sleep duration (P = .003), decreased RBC and Hb levels (P = .005 and P = .008, respectively), confirming successful modeling. In the hippocampal tissue of model mice, the levels of NE, 5-HT, and 5-HIAA were significantly decreased (all P < .05), whereas DA levels were significantly increased (P = .024). Treatment with fermented Z. jujuba significantly prolonged sleep duration (both P < .01). Moreover, The PCS group had significantly higher hippocampal NE, 5-HT, and 5-HIAA levels (all P < .01). The MMF group showed increased 5-HT and 5-HIAA (P = .040 and P = .0085) but decreased DA (P = .033). Additionally, NE was significantly lower in the MMF group than in the PCS group (P = .008). Conclusion Fermented Z. jujuba products effectively ameliorated sleep disorders in mice with blood-deficiency insomnia. These pharmacological effects may relate to the targeted remodeling of monoamine neurotransmitter homeostasis in the hippocampus, specifically by upregulating NE, 5-HT, and 5-HIAA levels and downregulating DA levels.

Background: Ischemic stroke (IS) is probably the most important acute serious illness, where interdisciplinary approach is essential to offer the best chance for survival and functional recovery of patients. Carbon dots (CDs) with multifaceted advantages have provided hope for development brand-new nanodrug for treating thorny diseases. Methods: This study developed a green and environmentally responsible calcination method to prepare novel Gardenia jasminoides Carbonisata (GJC-CDs) as promising drug for ischemic stroke treatment. Results: In this work, we isolated and characterized for the first time a novel carbon dots (GJC-CDs) from the natural plant G. jasminoides. Results displayed that green GJC-based CDs with tiny sizes and abundant functional groups exhibited solubility, which may be beneficial for its settled biological activity. The neuroprotective effect of carbon dots from G. jasminoides were evaluated using the classical middle cerebral artery occlusion (MCAO) model. Assessing the infarct volume content of the ischemic cerebral hemisphere and determining the serum tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), reduced glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) levels of the mice in each group, it was evident that pre-administration of the drug by GJC-CDs significantly reduced the infarct volume as well as attenuated inflammatory responses and excessive oxidative stress in MCAO mice. Furthermore, in vitro cellular experiments demonstrated that GJC-CDs have good biosafety and anti-inflammatory and antioxidant capacity. Conclusions: Overall, GJC-CDs performs neuroprotective effect on cerebral ischemia and reperfusion injury, which not only provides evidence for further broadening the biological application of acute ischemic stroke but also offers novel strategy for the application of nanomedicine to treat acute diseases.

IntroductionIschemic stroke (IS) represents a significant global health challenge, characterized by elevated morbidity and mortality rates, largely driven by inflammatory responses. Double-negative T cells (DNTs), a distinct subset of T cells lacking both CD4 and CD8 markers, have been implicated in the pathogenesis of IS, exhibiting potentially dual roles. However, the precise functional contributions of DNTs in this context remain poorly understood.MethodsIn this study, we investigated the role of DNTs during the acute phase of IS and assessed the influence of Huang-Lian-Jie-Du Decoction (HLJD), a traditional Chinese medicinal formula, on these cells. Using single-cell transcriptomics, we identified two distinct subtypes of DNTs: an activated, cytotoxic phenotype (Kill+) and a resting, immunosuppressive phenotype (Kill-).ResultsOur findings indicate that HLJD treatment modulates the balance between these DNT subtypes, specifically reducing the proportion of cytotoxic DNTs while promoting an increase in immunosuppressive DNTs. This shift was associated with a reduction in immune cell infiltration and inflammation within the brain tissue, potentially mitigating neuronal damage.DiscussionThese results suggest that HLJD exerts neuroprotective effects in IS by modulating the activity and distribution of DNT cells, offering valuable insights into the therapeutic potential of traditional Chinese medicine for the treatment of IS. Further studies are required to elucidate the mechanisms underlying DNT-mediated immune responses in IS and to explore the broader applications of HLJD in other neuroinflammatory conditions.

Ischemic stroke (IS) is caused by temporary or permanent obstruction of the brain's blood supply. The disruption in glucose and oxygen delivery that results from the drop in blood flow impairs energy metabolism. A significant pathological feature of IS impaired energy metabolism. Astrocytes, as the most prevalent glial cells in the brain, sit in between neurons and the microvasculature. By taking advantage of their special anatomical location, they play a crucial part in regulating cerebral blood flow (CBF) and metabolism. Astrocytes can withstand hypoxic and ischemic conditions better than neurons do. Additionally, astrocytes are essential for maintaining the metabolism and function of neurons. Therefore, the "neurocentric" perspective on neuroenergetics is gradually giving way to a more comprehensive perspective that takes into account metabolic interaction between astrocytes and neurons. Since neurons in the core region of the infarct are unable to undergo oxidative metabolism, the focus of attention in this review is on neurons in the peri-infarct region. We'll go over the metabolic crosstalk of astrocytes and neurons during the acute phase of IS using three different types of metabolites: lactate, fatty acids (FAs), and amino acids, as well as the mitochondria. After IS, astrocytes in the peri-infarct zone can produce lactate, ketone bodies (KBs), glutamine (Gln), and l-serine, shuttling these metabolites, along with mitochondria, to neurons. This process helps maintain the energy requirements of neurons, preserves their redox state, and regulates neurotransmitter receptor activity.

The primary mechanism of secondary injury after cerebral ischemia may be the brain inflammation that emerges after an ischemic stroke, which promotes neuronal death and inhibits nerve tissue regeneration. As the first immune cells to be activated after an ischemic stroke, microglia play an important immunomodulatory role in the progression of the condition. After an ischemic stroke, peripheral blood immune cells (mainly T cells) are recruited to the central nervous system by chemokines secreted by immune cells in the brain, where they interact with central nervous system cells (mainly microglia) to trigger a secondary neuroimmune response. This review summarizes the interactions between T cells and microglia in the immune-inflammatory processes of ischemic stroke. We found that, during ischemic stroke, T cells and microglia demonstrate a more pronounced synergistic effect. Th1, Th17, and M1 microglia can co-secrete pro-inflammatory factors, such as interferon-γ, tumor necrosis factor-α, and interleukin-1β, to promote neuroinflammation and exacerbate brain injury. Th2, Treg, and M2 microglia jointly secrete anti-inflammatory factors, such as interleukin-4, interleukin-10, and transforming growth factor-β, to inhibit the progression of neuroinflammation, as well as growth factors such as brain-derived neurotrophic factor to promote nerve regeneration and repair brain injury. Immune interactions between microglia and T cells influence the direction of the subsequent neuroinflammation, which in turn determines the prognosis of ischemic stroke patients. Clinical trials have been conducted on the ways to modulate the interactions between T cells and microglia toward anti-inflammatory communication using the immunosuppressant fingolimod or overdosing with Treg cells to promote neural tissue repair and reduce the damage caused by ischemic stroke. However, such studies have been relatively infrequent, and clinical experience is still insufficient. In summary, in ischemic stroke, T cell subsets and activated microglia act synergistically to regulate inflammatory progression, mainly by secreting inflammatory factors. In the future, a key research direction for ischemic stroke treatment could be rooted in the enhancement of anti-inflammatory factor secretion by promoting the generation of Th2 and Treg cells, along with the activation of M2-type microglia. These approaches may alleviate neuroinflammation and facilitate the repair of neural tissues.

This study aims to provide new insights into PM2.5-induced lung diseases through a focus on the pulmonary epithelial barrier and epithelial-mesenchymal transition (EMT). Firstly, we analyzed the mechanisms by which PM2.5 damages the airway epithelial barrier, including inflammatory responses, immune imbalance, oxidative stress, apoptosis, and autophagy. Subsequently, we investigated the mechanisms by which PM2.5 induces EMT, which involve the synergistic effect of oxidative stress and inflammation, the activation of key signaling pathways, and the regulatory role of non-coding RNAs. Furthermore, we explored the interaction between the airway epithelial barrier and EMT, especially the induction of EMT by epithelial barrier damage and the impact of EMT on epithelial barrier repair. Regarding lung injury diseases, we focused on the roles of the epithelial barrier and EMT in the development of pulmonary fibrosis and lung cancer, providing evidence from in vitro and in vivo studies. Emphasizing the translational prospects from basic research to clinical applications, and we proposed new ideas for treating PM2.5-related lung diseases from four aspects-anti-inflammatory and antioxidant drugs, signaling pathway inhibitors, non-coding RNA-targeted therapies, and gene editing and cell therapies-by focusing on the two key links of the airway epithelial barrier and EMT.

This study is aimed at exploring the therapeutic potential of berberine (BBR) in mitigating metabolic dysfunction-associated steatotic liver disease (MASLD) and at elucidating its mechanisms of action, with a focus on the modulation of glucose and lipid metabolism via the PI3K/Akt and STING signaling pathways. Male C57BL/6 J mice were fed a high-fat diet (HFD) to induce MASLD and subsequently treated with BBR or metformin. HepG2 cells were cultured in vitro, and palmitic acid (PA) was used to construct the cell model. Comprehensive analyses, including network pharmacology, transcriptome sequencing, and Western blotting, were conducted to identify critical pathways and molecular targets. Biochemical, histological, and molecular assays were performed to evaluate metabolic and inflammatory responses. BBR significantly attenuated HFD-induced hepatic steatosis, inflammation, and glucose intolerance. It effectively reduced lipid accumulation, enhanced insulin sensitivity, and modulated the expression of genes involved in lipid metabolism. Network pharmacology and transcriptome analysis highlighted the involvement of the PI3K/Akt and STING pathways. BBR activated PI3K/Akt signaling while suppressing the STING pathway, thereby reducing lipid accumulation in both in vivo and in vitro models. The inhibition of AKT negated the beneficial effects of BBR, underscoring the pivotal role of PI3K/Akt in regulating STING signaling. BBR ameliorates MASLD by activating the PI3K/Akt pathway and inhibiting the STING pathway, leading to improved glucose and lipid metabolism. These findings position BBR as a promising therapeutic candidate for the treatment of MASLD.

[This corrects the article DOI: 10.3389/fnins.2022.943400.].