A peripheral system disease-Pulmonary hypertension.

Pulmonary hypertension (PH) is a cardiovascular disorder characterized by substantial morbidity and mortality rates. It is a chronic condition characterized by intricate pathogenesis and uncontrollable factors. We summarized the pathological effects of estrogen, genetics, neuroinflammation, intestinal microbiota, metabolic reorganization, and histone modification on PH. PH is not only a pulmonary vascular disease, but also a systemic disease. The findings emphasize that the onset of PH is not exclusively confined to the pulmonary vasculature, consequently necessitating treatment approaches that extend beyond targeting pulmonary blood vessels. Hence, the research on the pathological mechanism of PH is not limited to target organs such as pulmonary vessels, but also focuses on exploring other fields (such as estrogen, genetics, neuroinflammation, intestinal microbiota, metabolic reorganization, and histone modification).

CCR5 and inflammatory storm.

Chemokines and their corresponding receptors play crucial roles in orchestrating inflammatory and immune responses, particularly in the context of pathological conditions disrupting the internal environment. Among these receptors, CCR5 has garnered considerable attention due to its significant involvement in the inflammatory cascade, serving as a pivotal mediator of neuroinflammation and other inflammatory pathways associated with various diseases. However, a notable gap persists in comprehending the intricate mechanisms governing the interplay between CCR5 and its ligands across diverse and intricate inflammatory pathologies. Further exploration is warranted, especially concerning the inflammatory cascade instigated by immune cell infiltration and the precise binding sites within signaling pathways. This study aims to illuminate the regulatory axes modulating signaling pathways in inflammatory cells by providing a comprehensive overview of the pathogenic processes associated with CCR5 and its ligands across various disorders. The primary focus lies on investigating the pathomechanisms associated with CCR5 in disorders related to neuroinflammation, alongside the potential impact of aging on these processes and therapeutic interventions. The discourse culminates in addressing current challenges and envisaging potential future applications, advocating for innovative research endeavors to advance our comprehension of this realm.

Phosphoproteomic analysis of APP/PS1 mice of Alzheimer's disease by DIA based mass spectrometry analysis with PRM verification.

Traditional Chinese medicine has been utilized in China for approximately thousands of years in clinical settings to prevent Alzheimer's disease (AD) and enhance memory, despite the lack of a systematic exploration of its biological underpinnings. Exciting research has corroborated the beneficial effects of tetrahydroxy stilbene glycoside (TSG), an extract derived from Polygonum multiflorum, in delaying learning and memory impairment in a model that mimics AD. Therefore, the primary objective of this study is to investigate the major function of TSG upon protein regulation in AD. Herein, a novel approach, encompassing data independent acquisition (DIA), DIA phosphorylated proteomics, and parallel reaction monitoring (PRM), was utilized to integrate quantitative proteomic data collected from APP/PS1 mouse model exhibiting toxic intracellular aggregation of Aß. Initially, we deliberated upon both single and multi-dimensional data pertaining to AD model mice. Furthermore, we authenticated disparities in protein phosphorylation quantity and expression, phosphorylation function, and ultimately phosphorylation kinase analysis. In order to validate the results, we utilized PRM ion monitoring technology to identify potential protein or peptide biomarkers. In the mixed samples, targeted detection of 50 target proteins revealed that 26 to 33 target proteins were stably detected by PRM. In summary, our findings provide new candidates for AD biomarker, which have been identified and validated through protein researches conducted on mouse brains. This offers a wealth of potential resources for extensive biomarker validation in neurodegenerative diseases. SIGNIFICANCE: DIA phosphorylated proteomics technique was used to detect and analyze phosphorylated proteins in brain tissues of mice with AD. Data were analyzed by various bioinformatics tools to explore the phosphorylation events and characterize them related to TSG. The results of DIA were further verified by PRM. Besides, we mapped the major metabolite classes emerging from the analyses to key biological pathways implicated in AD to understand the potential roles of the molecules and the interactions in triggering symptom onset and progression of AD. Meanwhile, we clarified that in the context of AD onset and TSG intervention, the changes in proteins, protein phosphorylation, phosphorylation kinases, and the internal connections.

Ferroptosis is Involved in the Pharmacological Effect of Ginsenoside.

Ginsenoside is the principal active ingredient in ginseng. Several investigations have found that ginsenosides have anti-inflammatory, antioxidant, anti-apoptotic, anti-cancer, and antiallergic activities. Ferroptosis is an iron-dependent, non-apoptotic form of cell-regulated death caused by lipid peroxidation. Iron, lipid, and amino acid metabolism orchestrate the complex ferroptosis response through direct or indirect regulation of iron accumulation or lipid peroxidation. More and more research has demonstrated that ginsenoside impacts illnesses via ferroptosis, implying that ferroptosis might be employed as a novel target of ginsenoside for disease therapy. This article examines the molecular mechanism of ferroptosis as well as the current advancement of ginsenoside in influencing disorders via ferroptosis.

Quercetin attenuates cerebral ischemic injury by inhibiting ferroptosis via Nrf2/HO-1 signaling pathway.

AIMS: Ischemic stroke is a severe cerebrovascular disease in which neuronal death continually occurs through multiple forms, including apoptosis, autophagy, pyroptosis and ferroptosis. Quercetin (QRC), as a natural flavonoid compound, has been reported to have pharmacological effects on ischemic injury accompanied by unclear anti-ferroptotic mechanisms. This study is designed to investigate the therapeutic effects of QRC against ferroptosis in ischemic stroke. MATERIALS AND METHODS: In vivo, the model of MCAO rats were used to assess the protective effect of QRC on cerebral ischemic. Additionally, we constructed oxidative stressed and ferroptotic cell models to explore the effects and mechanisms of QRC on ferroptosis. The related proteins were analysed by western blotting, immunohistochemical and immunofluorescence techniques. RESULTS: The experiments demonstrated that QRC improves neurological deficits, infarct volume, and pathological features in MCAO rats, also increased the viability of HT-22 cells exposed to H2O2 and erastin. These results, including MDA, SOD, GSH, ROS levels and iron accumulation, indicated that QRC suppresses the generation of lipid peroxides and may involve in the regulatory of ferroptosis. Both in vitro and in vivo, QRC was found to inhibit ferroptosis by up-regulating GPX4 and FTH1, as well as down-regulating ACSL4. Furthermore, we observed that QRC enhances the nuclear translocation of Nrf2 and activates the downstream antioxidative proteins. Importantly, the effect of QRC on ferroptosis can be reversed by the Nrf2 inhibitor ML385. CONCLUSIONS: This study provides evidence that QRC has a neuroprotective effect by inhibiting ferroptosis, demonstrating the therapeutic potential for cerebral ischemic stroke.

Ginsenoside Rg1 treats ischemic stroke by regulating CKLF1/CCR5 axis-induced neuronal cell pyroptosis.

BACKGROUND: Ischemic stroke, a severe and life-threatening neurodegenerative condition, currently relies on thrombolytic therapy with limited therapeutic window and potential risks of hemorrhagic transformation. Thus, there is a crucial need to explore novel therapeutic agents for ischemic stroke. Ginsenoside Rg1 (Rg1), a potential neuroprotective agent, exhibits anti-ischemic effects attributed to its anti-inflammatory, anti-oxidant, and anti-apoptotic properties. Nevertheless, the precise underlying mechanism of action remains to be fully elucidated. PURPOSE: This study aimed to explore whether Rg1 exerts anti-ischemic stroke effects by inhibiting pyroptotic neuronal cell death through modulation of the chemokine like factor 1 (CKLF1)/ C-C chemokine receptor type 5 (CCR5) axis. METHODS: In this study, the MCAO model was used as an ischemic stroke model, and experimental tests were performed after 6 hours of ischemia. The anti-ischemic effect of Rg1 was examined by TTC staining, nissl-staining and neurobehavioral tests. In the in vitro experiments, PC12 cells were subjected to stimulation with CKLF1's mimetic peptide C27 to assess the potential of CKLF1 to induce focal neuronal cell death. Additionally, the impact of CKLF1 mimetic peptide C27, antagonistic peptide C19, and CCR5 inhibitor MVC on PC12 cells subjected to oxygen-glucose deprivation (OGD) and subsequently treated with Rg1 was investigated. In vivo, Rg1 treatment was examined by quantitative real-time PCR (qPCR), ELISA, immunohistochemistry (IHC), immunofluorescence (IF), western blot (WB), and co-immunoprecipitate (Co-IP) assays to perspective whether Rg1 treatment reduces CKLF1/CCR5 axis-induced pyroptotic neuronal cell death. In addition, to further explore the biological significance of CKLF1 in ischemic stroke, CKLF1-/- rats were used as the observation subjects in this study. RESULTS: The in vitro results suggested that CKLF1 was able to induce neuronal cells to undergo pyroptosis. In vivo pharmacodynamic results showed that Rg1 treatment was able to significantly improve symptoms in ischemic stroke rats. In addition, Rg1 treatment was able to inhibit the interaction between CKLF1 and CCR5 after ischemic stroke and inhibited CKLF1/CCR5 axis-induced pyroptosis. The results of related experiments in CKLF1-/- rats showed that Rg1 lost its therapeutic effect after CKLF1 knockdown. CONCLUSION: Our findings indicate that the activation of the NLRP3 inflammasome is initiated by the CKLF1/CCR5 axis, facilitated through the activation of the NF-κB pathway, ultimately resulting in the pyroptosis of neuronal cells. Conversely, Rg1 demonstrates the capability to mitigate neuronal cell damage following CKLF1-induced effects by suppressing the expression of CKLF1. Thus, CKLF1 represents a crucial target for Rg1 in the context of cerebral ischemia treatment, and it also holds promise as a potential target for drug screening in the management of ischemic stroke.

Higenamine exerts antidepressant effect by improving the astrocytic gap junctions and inflammatory response.

BACKGROUND: Depression is a refractory psychiatric disorder closely associated with dysfunction of the gap junctions (GJs) between astrocytes as well as neuroinflammation. Higenamine (Hig) is a potent cardiotonic ingredient in Fuzi (i.e., Aconitum carmichaeli Debx.) with anti-inflammatory and antioxidant effects, which has a significant protective effect on damaged nerve cells and has great potential for the treatment of neuropsychiatric diseases. METHODS: Rats were stimulated by chronic unpredictable stress (CUS) for 28 days while given Hig (5, 10, 20 mg/kg) and then analyzed behaviorally by the open field test, sucrose preference test, and forced swimming test. Changes in astrocyte GJs function and morphology were observed by dye transfer and transmission electron microscopy, respectively. Expression and phosphorylation of connexin 43 (Cx43) were analyzed by Western blot. Also, considering the close relationship between depression and neuroinflammation, we determined the inflammatory response in serum with ELISA kits and analyzed the expression of inflammation-related proteins with Western blot. RESULTS: Hig ameliorated CUS-induced depression-like behavior in rats. Hig administration improved gap junctional dysfunction in astrocytes, reduced gap junctional gaps and elevated the expression of Cx43 and decreased the phosphorylation of Cx43. Meanwhile, Hig administration was also able to attenuate the inflammatory response that occurs after CUS in rats. LIMITATIONS: For the role of Cx43 in depression, we did not validate it more deeply in animal models with knockout Cx43. In addition, GJs dysfunction might be associated with the inflammatory response seen in depression, but this needs to be further investigated. CONCLUSIONS: Hig ameliorates depression and exerts its antidepressant effect possibly by improving the dysfunctional GJs between astrocytes and the inflammatory response.

CC chemokines Modulate Immune responses in Pulmonary Hypertension.

BACKGROUND: Pulmonary hypertension (PH) represents a progressive condition characterized by the remodeling of pulmonary arteries, ultimately culminating in right heart failure and increased mortality rates. Substantial evidence has elucidated the pivotal role of perivascular inflammatory factors and immune dysregulation in the pathogenesis of PH. Chemokines, a class of small secreted proteins, exert precise control over immune cell recruitment and functionality, particularly with respect to their migration to sites of inflammation. Consequently, chemokines emerge as critical drivers facilitating immune cell infiltration into the pulmonary tissue during inflammatory responses. This review comprehensively examines the significant contributions of CC chemokines in the maintenance of immune cell homeostasis and their pivotal role in regulating inflammatory responses. The central focus of this discussion is directed towards elucidating the precise immunoregulatory actions of CC chemokines concerning various immune cell types, including neutrophils, monocytes, macrophages, lymphocytes, dendritic cells, mast cells, eosinophils, and basophils, particularly in the context of pH processes. Furthermore, this paper delves into an exploration of the underlying pathogenic mechanisms that underpin the development of PH. Specifically, it investigates processes such as cellular pyroptosis, examines the intricate crosstalk between bone morphogenetic protein receptor type 2 (BMPR2) mutations and the immune response, and sheds light on key signaling pathways involved in the inflammatory response. These aspects are deemed critical in enhancing our understanding of the complex pathophysiology of PH. Moreover, this review provides a comprehensive synthesis of findings from experimental investigations targeting immune cells and CC chemokines. AIM OF REVIEW: In summary, the inquiry into the inflammatory responses mediated by CC chemokines and their corresponding receptors, and their potential in modulating immune reactions, holds promise as a prospective avenue for addressing PH. The potential inhibition of CC chemokines and their receptors stands as a viable strategy to attenuate the inflammatory cascade and ameliorate the pathological manifestations of PH. Nonetheless, it is essential to acknowledge the current state of clinical trials and the ensuing progress, which regrettably appears to be less than encouraging. Substantial hurdles exist in the successful translation of research findings into clinical applications. The intention is that such emphasis could potentially foster the advancement of potent therapeutic agents presently in the process of clinical evaluation. This, in turn, may further bolster the potential for effective management of PH.

Novel antidepressant mechanism of hypericin: Role of connexin 43-based gap junctions.

Hypericin is widely utilized for its precise antidepressant properties, but its exact antidepressant mechanism remains unclear. Gap junctions, which were predominantly expressed in astrocytes in the central nervous system, are concerned with the pathogenesis of depression. However, the role of hypericin in gap junctional dysfunction in depression has rarely been investigated. Here, we found that gap junctions were ultra-structurally broadened in the chronic unpredictable stress (CUS) rat model of depression, while hypericin repaired the dysfunction of gap junctions. Suppression of gap junctions by bilateral injection of carbenoxolone (CBX) in the prefrontal cortex of rats significantly inhibited the restoration of gap junctional dysfunction in depression by hypericin. Meanwhile, hypericin failed to show antidepressant benefits. Furthermore, in corticosterone (CORT)-stimulated primary astrocytes derived from neonatal rats, hypericin dramatically reversed the phosphorylation of connexin 43 (Cx43), normalizing the expression of Cx43 and thereby ameliorating gap junctional dysfunction. Comparatively, CBX inhibited the remission of hypericin on gap junctional intercellular communication function. Gap junctional function might be a novel therapeutic target for hypericin in the treatment of depression and provide potential novel insights into the antidepressant mechanism of other herbal ingredients.

Targeting oxidative stress as a preventive and therapeutic approach for cardiovascular disease.

Cardiovascular diseases (CVDs) continue to exert a significant impact on global mortality rates, encompassing conditions like pulmonary arterial hypertension (PAH), atherosclerosis (AS), and myocardial infarction (MI). Oxidative stress (OS) plays a crucial role in the pathogenesis and advancement of CVDs, highlighting its significance as a contributing factor. Maintaining an equilibrium between reactive oxygen species (ROS) and antioxidant systems not only aids in mitigating oxidative stress but also confers protective benefits on cardiac health. Herbal monomers can inhibit OS in CVDs by activating multiple signaling pathways, such as increasing the activity of endogenous antioxidant systems and decreasing the level of ROS expression. Given the actions of herbal monomers to significantly protect the normal function of the heart and reduce the damage caused by OS to the organism. Hence, it is imperative to recognize the significance of herbal monomers as prospective therapeutic interventions for mitigating oxidative damage in CVDs. This paper aims to comprehensively review the origins and mechanisms underlying OS, elucidate the intricate association between CVDs and OS, and explore the therapeutic potential of antioxidant treatment utilizing herbal monomers. Furthermore, particular emphasis will be placed on examining the cardioprotective effects of herbal monomers by evaluating their impact on cardiac signaling pathways subsequent to treatment.

Mechanisms of dihydromyricetin against hepatocellular carcinoma elucidated by network pharmacology combined with experimental validation.

CONTEXT: Dihydromyricetin (DMY) is extracted from vine tea, a traditional Chinese herbal medicine with anti-cancer, liver protection, and cholesterol-lowering effects. OBJECTIVE: This study investigated the mechanism of DMY against hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Potential DMY, HCC, and cholesterol targets were collected from relevant databases. PPI networks were created by STRING. Then, the hub genes of co-targets, screened using CytoHubba. GO and KEGG pathway enrichment, were performed by Metascape. Based on the above results, a series of in vitro experiments were conducted by using 40-160 µM DMY for 24 h, including transwell migration/invasion assay, western blotting, and Bodipy stain assay. RESULTS: Network pharmacology identified 98 common targets and 10 hub genes of DMY, HCC, and cholesterol, and revealed that the anti-HCC effect of DMY may be related to the positive regulation of lipid rafts. Further experiments confirmed that DMY inhibits the proliferation, migration, and invasion of HCC cells and reduces their cholesterol levels in vitro. The IC50 is 894.4, 814.4, 467.8, 1,878.8, 151.8, and 156.9 µM for 97H, Hep3B, Sk-Hep1, SMMC-7721, HepG2, and Huh7 cells, respectively. In addition, DMY downregulates the expression of lipid raft markers (CAV1, FLOT1), as well as EGFR, PI3K, Akt, STAT3, and Erk. DISCUSSION AND CONCLUSION: The present study reveals that DMY suppresses EGFR and its downstream pathways by reducing cholesterol to disrupt lipid rafts, thereby inhibiting HCC, which provides a promising candidate drug with low toxicity for the treatment of HCC.

Targeting pyroptosis as a preventive and therapeutic approach for stroke.

Stroke has caused tremendous social stress worldwide, yet despite decades of research and development of new stroke drugs, most have failed and rt-PA (Recombinant tissue plasminogen activator) is still the accepted treatment for ischemic stroke. the complexity of the stroke mechanism has led to unsatisfactory efficacy of most drugs in clinical trials, indicating that there are still many gaps in our understanding of stroke. Pyroptosis is a programmed cell death (PCD) with inflammatory properties and are thought to be closely associated with stroke. Pyroptosis is regulated by the GSDMD of the gasdermin family, which when cleaved by Caspase-1/Caspase-11 into N-GSDMD with pore-forming activity can bind to the plasma membrane to form small 10-20 nm pores, which would allow the release of inflammatory factors IL-18 and IL-1ß before cell rupture, greatly exacerbating the inflammatory response. The pyroptosis occurs mainly in the border zone of cerebral infarction, and glial cells, neuronal cells and brain microvascular endothelial cells (BMECs) all undergo pyroptosis after stroke, which largely exacerbates the breakdown of the blood-brain barrier (BBB) and thus aggravates brain injury. Therefore, pyroptosis may be a good direction for the treatment of stroke. In this review, we focus on the latest mechanisms of action of pyroptosis and the process by which pyroptosis regulates stroke development. We also suggest potential therapeutic stroke drugs that target the pyroptosis pathway, providing additional therapeutic strategies for the clinical management of stroke. The role of pyroptosis after stroke. After stroke, microglia first rush to the damaged area and polarize into M1 and M2 types. Under the influence of various stimuli, microglia undergo pyroptosis, release pro-inflammatory factors, and are converted to the M1 type; astrocytes and neuronal cells also undergo pyroptosis under the stimulation of various pro-inflammatory factors, leading to astrocyte death due to increased osmotic pressure in the membrane, resulting in water absorption and swelling until rupture. BMECs, the main structural component of the BBB, also undergo pyroptosis when stimulated by pro-inflammatory factors released from microglia and astrocytes, leading to the destruction of the structural integrity of the BBB, ultimately causing more severe brain damage. In addition, GSDMD in neutrophils mainly mediate the release of NETs rather than pyroptosis, which also aggravates brain injury. IL-10=interleukin-10; TGF-ß = transforming growth factor-ß; IL-18=interleukin-18; IL-1ß = interleukin-1ß; TNF-α = tumor necrosis factor-α; iNOS=induced nitrogen monoxide synthase; MMPs=Matrix metalloproteinases; GSDMD = gasdermin D; BMECs=brain microvascular endothelial cells; BBB = blood-brain barrier.

Paeoniae Radix Rubra extract attenuates cerebral ischemia injury by inhibiting ferroptosis and activating autophagy through the PI3K/Akt signalling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Paeoniae Radix Rubra (PRR), the root of Paeonia lactiflora Pall. or Paeonia veitchii Lynch, has been widely used to promote blood circulation and eliminate blood stasis in Chinese clinical practice, but its effect on cerebral ischemia is still rarely reported. AIM OF THE STUDY: The present study aimed to assess the potential therapeutic possibilities of the extract of PRR (PRRE) on cerebral ischemia, further exploring the underlying mechanism, and preliminary screening of the corresponding active components. MATERIALS AND METHODS: The neuroprotective effects of PRRE in Sprague-Dawley (SD) rats with middle cerebral artery occlusion (MCAO) injury and mouse hippocampal neuronal cells (HT22 cell line) following oxidative stress were confirmed. The mechanism was investigated using immunohistochemical staining, western blotting, transmission electron microscopy (TEM), and immunofluorescence. The active components of PRRE were analysed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and molecular docking. RESULTS: The in vivo study showed that PRRE reduced infarct volume and improved neurological deficits in rats, and the expression of GPX4, FTH1, Beclin1, LC3 II, and p-Akt was upregulated in the rat hippocampi. In addition, the vitro research indicated that PRRE can also alleviate H2O2-induced HT22 cell damage by regulating cytokines such as malondialdehyde (MDA), reduced glutathione (GSH) and reactive oxygen species (ROS), and the expressions of GPX4 and Beclin1 were observed to be elevated. The PI3K/Akt signalling pathway was inhibited by LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K). Furthermore, the effective components of PRRE in regulating ferroptosis and autophagy are mainly defined as albiflorin, paeoniflorin, benzoyl paeoniflorin, oleanolic acid, and hederagenin. CONCLUSION: PRRE exerts neuroprotective effects against cerebral ischaemic injury by inhibiting ferroptosis and activating autophagy through the PI3K/Akt signalling pathway. This study provides an experimental basis for the potential application of PRRE as a novel therapeutic drug, and PI3K/Akt-associated ferroptosis and autophagy as therapeutic targets for cerebral ischemia.

A Review of Research on the Association between Neuron-Astrocyte Signaling Processes and Depressive Symptoms.

Depression is a mental illness that has a serious negative impact on physical and mental health. The pathophysiology of depression is still unknown, and therapeutic medications have drawbacks, such as poor effectiveness, strong dependence, adverse drug withdrawal symptoms, and harmful side effects. Therefore, the primary purpose of contemporary research is to understand the exact pathophysiology of depression. The connection between astrocytes, neurons, and their interactions with depression has recently become the focus of great research interest. This review summarizes the pathological changes of neurons and astrocytes, and their interactions in depression, including the alterations of mid-spiny neurons and pyramidal neurons, the alterations of astrocyte-related biomarkers, and the alterations of gliotransmitters between astrocytes and neurons. In addition to providing the subjects of this research and suggestions for the pathogenesis and treatment techniques of depression, the intention of this article is to more clearly identify links between neuronal-astrocyte signaling processes and depressive symptoms.

CZK, a novel alkaloid derivative from Clausena lansium, alleviates ischemic stroke injury through Nrf2-mediated antioxidant effects.

Anti-oxidant stress is a potential strategy for the treatment of ischemic stroke. Here, we found a novel free radical scavenger termed as CZK, which is derived from alkaloids contained in Clausena lansium. In this study, we first compared cytotoxicity and biological activity between CZK and its parent's compound Claulansine F. It was found that CZK had lower cytotoxicity and improved anti-oxygen-glucose deprivation/reoxygenation (OGD/R) injury than its parent's compound. Free radical scavenging test showed that CZK had a strong inhibitory effect on hydroxyl free radicals with the IC50 of 77.08 nM. Intravenous injection of CZK (50 mg/kg) significantly alleviated ischemia-reperfusion injury, manifested by reduced neuronal damage and decreased oxidative stress. Consistent with the findings, the activities of superoxide dismutase (SOD) and reduced glutathione (GSH) were increased. Molecular docking predicted that CZK might be combined with nuclear factor erythroid 2-related factor 2 (Nrf2) complex. Our results also confirmed that CZK upregulated the contents of Nrf2 and its target gene products Heme Oxygenase-1 (HO-1), and NAD(P)H: Quinone Oxidoreductase 1 (NQO1). In conclusion, CZK had a potential therapeutic effect for ischemic stroke by activating Nrf2-mediated antioxidant system.

The mechanism of programmed death and endoplasmic reticulum stress in pulmonary hypertension.

Pulmonary hypertension (PH) was a cardiovascular disease with high morbidity and mortality. PH was a chronic disease with complicated pathogenesis and uncontrollable factors. PH was divided into five groups according to its pathogenesis and clinical manifestations. Although the treatment and diagnosis of PH has made great progress in the past ten years. However, the diagnosis and prognosis of the PAH had a great contrast, which was not conducive to the diagnosis and treatment of PH. If not treated properly, it will lead to right ventricular failure or even death. Therefore, it was necessary to explore the pathogenesis of PH. The problem we urgently need to solve was to find and develop drugs for the treatment of PH. We reviewed the PH articles in the past 10 years or so as well as systematically summarized the recent advance. We summarized the latest research on the key regulatory factors (pyroptosis, apoptosis, necroptosis, ferroptosis, and endoplasmic reticulum stress) involved in PH. To provide theoretical basis and basis for finding new therapeutic targets and research directions of PH.

Characteristics and pathogenesis of chemokines in the post-stroke stage.

Chemokines, as small molecular proteins, play a crucial role in the immune and inflammatory responses after stroke. A large amount of evidence showed chemokines and their receptors were increasingly recognized as potential targets for stroke treatment, which were involved in the processing of neovascularization, neurogenesis, and neural network reconstruction. In this review, we summarized the characteristics of chemokine alterations throughout the post-stroke nerve repair phase to gain insight into the pathological mechanisms of chemokines and find effective therapeutic targets for stroke.