Buyang Huanwu decoction ameliorates myocardial injury and attenuates platelet activation by regulating the PI3 kinase/Rap1/integrin α(IIb)ß(3) pathway.

BACKGROUND: Buyang Huanwu Decoction (BYHWD) is a traditional Chinese medicine to treat the syndrome of qi deficiency and blood stasis. Platelets play an important role in regulating thrombus and inflammation after ischemic injury, studies have shown that BYHWD regulate myocardial fibrosis and exert anti-inflammatory effects through IL-17 and TLR4 pathways, but the mechanism of platelet activation by BYHWD in stable coronary heart disease is still unknown. In the present study, model of left anterior descending coronary artery ligation was applied to investigate the mechanisms of BYHWD on modulating platelets hyperreactivity and heart function after fibrosis of ischemic myocardial infarction (MI). METHODS: Myocardial infarction model was constructed by ligation of the left anterior descending coronary artery. The rats were randomly divided into five groups: sham, model, MI with aspirin (positive), MI with a low dosage of BYHWD (BYHWD-ld) and MI with a high dosage of BYHWD (BYHWD-hd) for 28 days. RESULTS: Coronary artery ligation prominently induced left ventricle dysfunction, increased cardiomyocyte fibrosis, which was accompanied by platelets with hyperreactivity, and high levels of inflammatory factors. BYHWD obviously reversed cardiac dysfunction and fibrosis, increased the thickness of the left ventricular wall, and inhibited aggregation ratio and CD62p expression. BYHWD restored the mitochondrial respiration of platelets after MI, concomitant with an increased telomere expression and decreased inflammation. According to the result of transcriptome sequencing, we found that 106 differentially expressed genes compared model with BYHWD treatment. Enrichment analysis screened out the Ras-related protein Rap-1 (Rap1) signaling pathway and platelet activation biological function. Quantitative real-time PCR and Western blotting were applied to found that BYHWD reduced the expression of Rap1/PI3K-Akt/Src-CDC42 genes and attenuated the overactivity of PI3 kinase/Rap1/integrin α(IIb)ß(3) pathway. CONCLUSION: BYHWD reduced inflammation and platelet activation via the PI3 kinase/Rap1/integrin α(IIb)ß(3) pathway and improved heart function after MI.

Cytokine Storm in COVID-19: Insight into Pathological Mechanisms and Therapeutic Benefits of Chinese Herbal Medicines.

Cytokine storm (CS) is the main driver of SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) in severe coronavirus disease-19 (COVID-19). The pathological mechanisms of CS are quite complex and involve multiple critical molecular targets that turn self-limited and mild COVID-19 into a severe and life-threatening concern. At present, vaccines are strongly recommended as safe and effective treatments for preventing serious illness or death from COVID-19. However, effective treatment options are still lacking for people who are at the most risk or hospitalized with severe disease. Chinese herbal medicines have been shown to improve the clinical outcomes of mild to severe COVID-19 as an adjunct therapy, particular preventing the development of mild to severe ARDS. This review illustrates in detail the pathogenesis of CS-involved ARDS and its associated key molecular targets, cytokines and signalling pathways. The therapeutic targets were identified particularly in relation to the turning points of the development of COVID-19, from mild symptoms to severe ARDS. Preclinical and clinical studies were reviewed for the effects of Chinese herbal medicines together with conventional therapies in reducing ARDS symptoms and addressing critical therapeutic targets associated with CS. Multiple herbal formulations, herbal extracts and single bioactive phytochemicals with or without conventional therapies demonstrated strong anti-CS effects through multiple mechanisms. However, evidence from larger, well-designed clinical trials is lacking and their detailed mechanisms of action are yet to be well elucidated. More research is warranted to further evaluate the therapeutic value of Chinese herbal medicine for CS in COVID-19-induced ARDS.

Chirally Selective and Switchable Luminescence from Achiral Quantum Emitters on Suspended Twisted Stacking Metasurfaces.

Dynamic control of circularly polarized photoluminescence has aroused great interest in quantum optics and nanophotonics. Chiral plasmonic metasurfaces enable the manipulation of the polarization state via plasmon-photon coupling. However, current plasmonic light-emitting metasurfaces for effective deterministic modulation of spin-dependent emission at near-infrared wavelengths are underexplored in terms of dissymmetry and tunability. Here, we demonstrate a microfluidic hybrid emitting system of a suspended twisted stacking metasurface coated with PbS quantum dots. The suspended metasurface is fabricated with a single step of electron beam exposure, exhibiting a strong optical chirality of 309° µm-1 with a thickness of less than λ/10 at key spectral locations. With significant chiral-selective interactions, enhanced photoluminescence is achieved with strong dissymmetry in circular polarization. The dissymmetry factor of the induced circularly polarized emission can reach 1.54. More importantly, altering the refractive index of the surrounding medium at the bottom surface of the metasurface can effectively manipulate the chiroptical responses of the hybrid system, hence leading to chirality-reversed emission. This active hybrid emitting system could be a resultful platform for chirality-switchable light emission from achiral quantum emitters, holding great potential for anticounterfeiting, biosensing, light sources, imaging, and displays.

[Mechanisms of oxidative stress in myocardial ischemia-reperfusion injury and protective effects of traditional Chinese medicines].

Myocardial ischemia is a disease characterized by high morbidity and mortality rates, restoring blood supply to the ischemic area through reperfusion is an effective intervention method. However, numerous studies have shown that reperfusion may cause severe myocardial damage, resulting in myocardial systolic and diastolic dysfunction and seriously affecting myocardial function. This phenomenon is called myocardial ischemia reperfusion injury(MIRI). The physiological and pathological mechanisms of MIRI include oxidative stress, calcium overload, autophagy, pyrolysis, endoplasmic reticulum stress, apoptosis, etc. Oxidative stress plays an important role in MIRI-related cell death and is considered to be the main mechanism of MIRI. The occurrence of oxidative stress is mainly due to the excessive production of reactive oxygen species(ROS), which disrupts the balance of the redox system of the body or tissue. A large number of highly reactive ROS exceed the antioxidant defense capacity of cardiomyocytes, causing modifications in biological macromolecules such as DNA and proteins and resulting in severe reactions like DNA damage, protein dysfunction, cell damage or death, and local inflammation. Oxidative stress mediates apoptosis, autophagy, and inflammatory injury through various pathways, resulting in irreversible cardiomyocyte injury and myocardial dysfunction, which brings significant challenges for clinical treatment and prognosis. In recent years, remarkable progress has been made in understanding oxidative stress in ischemia reperfusion(I/R) injury of different organs and tissue. However, the injury mechanism caused by oxidative stress in restoring blood supply to the ischemic area and the protective effect of TCM remain largely unexplored. This article reviewed the role of oxidative stress in MIRI, the main production pathways of ROS, and the protective effects of TCM on oxidative stress injury during ischemic myocardial reperfusion, so as to provide a reference for future research and clinical treatment in this field.

Effect of Specific mode electroacupuncture stimulation combined with NGF during the ischaemic stroke: Study protocol for a randomized controlled trial.

BACKGROUND: The emergence of the Nerve Growth Factor (NGF) has promoted the development of neuroprotective therapy; however, it has little effect on cerebral ischemia because of its poor Blood-Brain Barrier (BBB) permeability. Specific Mode Electroacupuncture Stimulation (SMES) can open BBB safely and effectively; however, it has shown inconclusive clinical effects and indirect clinical evidence in the recovery phase. Hence, the authors conducted a multicentre, randomized, placebo-controlled, assessor-blinded clinical trial to assess the effectiveness and safety of SMES combined with NGF treatment used during ischaemic stroke recovery. METHODS: A total of 288 stroke patients from three hospitals will be recruited and randomly allocated to four groups: acupuncture + placebo, acupuncture + NGF, SMES + placebo, and SMES + NGF, in a 1:1:1:1 ratio. Assessment data will be collected at baseline, 2-weeks, and 4-weeks during the treatment period, as well as at the 4-week and 8-week follow-up after treatment completion. The primary outcome measure will be the basic cure rate. The secondary outcome measures include the simplified Modified Barthel Index, Timed Up and Go Test, Fugl-Meyer Assessment of Motor Function Score, Tinetti Performance Oriented Mobility Assessment, Montreal Cognitive Assessment, and Loewenstein Occupational Therapy Cognitive Assessment. Moreover, resting-state functional magnetic resonance imaging and Functional near-infrared spectroscopy can detect changes in cerebral blood flow and brain function and investigate the relationship between the clinical efficacy and mechanism of the prescribed interventions. CONCLUSION: This study will provide clinical evidence for the efficacy and safety of SMES combined with NGF in the treatment of stroke patients.

480†nm InGaN-based cyan laser diode grown on Si by interface engineering of active region.

InGaN-based long wavelength laser diodes (LDs) grown on Si are highly desirable for expanding the applications in laser display and lighting. Proper interface engineering of high In-content InGaN multi-quantum wells (MQWs) is urgently required for the epitaxial growth of InGaN-based long wavelength LD on Si, because the deteriorated interfaces and crystalline quality of InGaN MQWs can severely increase the photon scattering and further exacerbate the internal absorption loss of LDs, which prevents the lasing wavelength of InGaN-based LDs from extending. In this work, a significantly improved morphology and sharp interface of the InGaN active region are obtained by using a graded-compositional InGaN lower waveguide (LWG) capped with a 10-nm-thick Al0.1Ga0.9N layer. The V-pits density of the InGaN LWG was one order of magnitude reduction from 4.8 × 108 to 3.6 × 107 cm-2 along with the root-mean-square surface roughness decreasing from 0.3 to 0.1 nm. Therefore, a room-temperature electrically injected 480 nm InGaN-based cyan LD grown on Si under pulsed current operation was successfully achieved with a threshold current density of 18.3 kA/cm2.

Qilong capsule prevents myocardial ischemia/reperfusion injury by inhibiting platelet activation via the platelet CD36 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Qilong capsule (QC) is developed from the traditional Chinese medicine formula Buyang Huanwu Decoction, which has been clinically used to invigorate Qi and promote blood circulation to eliminate blood stasis. Myocardial ischemia‒reperfusion injury (MIRI) can be attributed to Qi deficiency and blood stasis. However, the effects of QC on MIRI remain unclear. AIM OF THE STUDY: This study aimed to investigate the protective effect and possible mechanism of QC on platelet function in MIRI rats. MATERIALS AND METHODS: The left anterior descending artery of adult Sprague‒Dawley rats was ligated for 30 min and then reperfused for 120 min with or without QC treatment. Then, the whole blood viscosity, plasma viscosity, coagulation, platelet adhesion rate, platelet aggregation, and platelet release factors were evaluated. Platelet CD36 and its downstream signaling pathway-related proteins were detected by western blotting. Furthermore, the active components of QC and the molecular mechanism by which QC regulates platelet function were assessed via molecular docking, platelet aggregation tests in vitro and BLI analysis. RESULTS: We found that QC significantly reduced the whole blood viscosity, plasma viscosity, platelet adhesion rate, and platelet aggregation induced by ADP or AA in rats with MIRI. The inhibition of platelet activation by QC was associated with reduced levels of ß-TG, PF-4, P-selectin and PAF. Mechanistically, QC effectively attenuated the expression of platelet CD36 and thus inhibited the activation of Src, ERK5, and p38. The active components of QC apparently suppressed platelet aggregation in vitro and regulated the CD36 signaling pathway. CONCLUSIONS: QC improves MIRI-induced hemorheological disorders, which might be partly attributed to the inhibition of platelet activation via CD36-mediated platelet signaling pathways.

[Ginsenoside Re regulates mitochondrial biogenesis through Nrf2/HO-1/PGC-1α pathway to reduce hypoxia/reoxygenation injury in H9c2 cells].

This article explored the mechanism by which ginsenoside Re reduces hypoxia/reoxygenation(H/R) injury in H9c2 cells by regulating mitochondrial biogenesis through nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/peroxisome prolife-rator-activated receptor gamma coactivator-1α(PGC-1α) pathway. In this study, H9c2 cells were cultured in hypoxia for 4 hours and then reoxygenated for 2 hours to construct a cardiomyocyte H/R injury model. After ginsenoside Re pre-administration intervention, cell activity, superoxide dismutase(SOD) activity, malondialdehyde(MDA) content, intracellular reactive oxygen species(Cyto-ROS), and intramitochondrial reactive oxygen species(Mito-ROS) levels were detected to evaluate the protective effect of ginsenoside Re on H/R injury of H9c2 cells by resisting oxidative stress. Secondly, fluorescent probes were used to detect changes in mitochondrial membrane potential(ΔΨ_m) and mitochondrial membrane permeability open pore(mPTP), and immunofluorescence was used to detect the expression level of TOM20 to study the protective effect of ginsenoside Re on mitochondria. Western blot was further used to detect the protein expression levels of caspase-3, cleaved caspase-3, Cyto C, Nrf2, HO-1, and PGC-1α to explore the specific mechanism by which ginsenoside Re protected mitochondria against oxidative stress and reduced H/R injury. Compared with the model group, ginse-noside Re effectively reduced the H/R injury oxidative stress response of H9c2 cells, increased SOD activity, reduced MDA content, and decreased Cyto-ROS and Mito-ROS levels in cells. Ginsenoside Re showed a good protective effect on mitochondria by increasing ΔΨ_m, reducing mPTP, and increasing TOM20 expression. Further studies showed that ginsenoside Re promoted the expression of Nrf2, HO-1, and PGC-1α proteins, and reduced the activation of the apoptosis-related regulatory factor caspase-3 to cleaved caspase-3 and the expression of Cyto C protein. In summary, ginsenoside Re can significantly reduce I/R injury in H9c2 cells. The specific mechanism is related to the promotion of mitochondrial biogenesis through the Nrf2/HO-1/PGC-1α pathway, thereby increasing the number of mitochondria, improving mitochondrial function, enhancing the ability of cells to resist oxidative stress, and alleviating cell apoptosis.

[Tetrahydropalmatine inhibiting mitophagy through ULK1/FUNDC1 pathway to alleviate hypoxia/reoxygenation injury in H9c2 cells].

This study explored the specific mechanism by which tetrahydropalmatine(THP) inhibited mitophagy through the UNC-51-like kinase 1(ULK1)/FUN14 domain containing 1(FUNDC1) pathway to reduce hypoxia/reoxygenation(H/R) injury in H9c2 cells. This study used H9c2 cells as the research object to construct a cardiomyocyte H/R injury model. First, a cell viability detection kit was used to detect cell viability, and a micro-method was used to detect lactate dehydrogenase(LDH) leakage to evaluate the protective effect of THP on H/R injury of H9c2 cells. In order to evaluate the protective effect of THP on mitochondria, the chemical fluorescence method was used to detect intracellular reactive oxygen species, intramitochondrial reactive oxygen species, mitochondrial membrane potential, and autophagosomes, and the luciferin method was used to detect intracellular adenosine 5'-triphosphate(ATP) content. Western blot was further used to detect the ratio of microtubule-associated protein 1 light chain 3(LC3) membrane type(LC3-Ⅱ) and slurry type(LC3-Ⅰ) and activated cleaved caspase-3 expression level. In addition, ULK1 expression level and its phosphorylation degree at Ser555 site, as well as the FUNDC1 expression level and its phosphorylation degree of Ser17 site were detected to explore its specific mechanism. The results showed that THP effectively reduced mitochondrial damage in H9c2 cells after H/R. THP protected mitochondria by reducing the level of reactive oxygen species in cells and mitochondria, increasing mitochondrial membrane potential, thereby increasing cellular ATP production, enhancing cellular activity, reducing cellular LDH leakage, and finally alleviating H/R damage in H9c2 cells. Further studies have found that THP could reduce the production of autophagosomes, reduce the LC3-Ⅱ/LC3-Ⅰ ratio, and lower the expression of the apoptosis-related protein, namely cleaved caspase-3, indicating that THP could reduce apoptosis by inhibiting autophagy. In-depth studies have found that THP could inhibit the activation of the ULK1/FUNDC1 pathway of mitophagy and the occurrence of mitophagy by reducing the phosphorylation degree of ULK1 at Ser555 and FUNDC1 at Ser17. The application of ULK1 agonist BL-918 reversely verified the effect of THP on reducing the phosphorylation of ULK1 and FUNDC1. In summary, THP inhibited mitophagy through the ULK1/FUNDC1 pathway to reduce H/R injury in H9c2 cells.

Light-driven phase transition of diffractive optical elements based on liquid crystal elastomers.

Diffractive optical element is advantageous for miniaturization, arraying and integration of optical systems. They have been widely used in beam shaping, diffractive imaging, generating beam arrays, spectral optimization and other aspects. Currently, the vast majority of diffractive optics are not tunable. This limits the applicability and functionality of these devices. Here we report a tunable diffractive optical element controlled by light in the visible band. The diffractive optical element consists of a square gold microarray deposited on a deformable substrate. The substrate is made of a liquid crystal elastomer. When pumped by a 532 nm laser, the substrate is deformed to change the crystal lattice. This changes the far-field diffraction pattern of the device. The proposed concept establishes a light-controlled soft platform with great potential for tunable/reconfigurable photonic devices, such as filters, couplers, holograms and structural color displays.

Metabolomics-Based Effects of a Natural Product on Remyelination After Cerebral Ischemia Injury Via GABABR-pCREB-BDNF Pathway.

BACKGROUND: Yi-Qi-Tong-Luo Granules (YQTLs) is a natural compound of Traditional Chinese Medicine authorized by China Food and Drug Administration (CFDA). These granules are employed in the convalescent stage of cerebral infarction and render notable clinical efficacy. This study aims to uncover the underlying mechanisms of YQTLs on remyelination after cerebral ischemia injury. MATERIALS AND METHODS: We established cerebral ischemia model in rats using microsphere-induced multiple cerebral infarction (MCI). We evaluated the pharmacological effects of YQTLs on MCI rats, through Morri's water maze test, open field test, hematoxylin and eosin staining, and glycine silver immersion. We employed liquid chromatography mass spectrometry metabolomics to identify differential metabolites. Enzyme-linked immunosorbent assay was utilized to measure the release of neurotrophins, while immunofluorescence staining was used to assess oligodendrocyte precursor cells differences and myelin regeneration. We used Western blotting to validate the protein expression of remyelination-associated signaling pathways. RESULTS: YQTLs significantly improves cognitive function following cerebral ischemia injury. Pathological tissue staining revealed that YQTLs administration inhibits neuronal denaturation and neurofibrillary tangles. We identified 141 differential metabolites among the sham, MCI, and YQTLs-treated MCI groups. Among these metabolites, neurotransmitters were identified, and notably, gamma-aminobutyric acid (GABA) showed marked improvement in the YQTLs group. The induction of neurotrophins, such as brain-derived neurotrophic factor (BDNF) and PDGFAA, upregulation of olig2 and MBP expression, and promotion of remyelination were evident in YQTLs-treated MCI groups. Gamma-aminobutyric acid B receptors (GABABR), pERK/extracellular regulated MAP kinase, pAKT/protein kinase B, and pCREB/cAMP response element-binding were upregulated following YQTLs treatment. CONCLUSION: YQTLs enhance the binding of GABA to GABABR, thereby activating the pCREB/BDNF signaling pathway, which in turn increases the expression of downstream myelin-associated proteins and promotes remyelination and cognitive function.

Panax notoginseng saponins stimulates the differentiation and neurite development of C17.2 neural stem cells against OGD/R injuries via mTOR signaling.

Ischemic stroke remains a major disease worldwide, and most stroke patients often suffer from serious sequelae. Endogenous neurogenesis matters in the repair and regeneration of impaired neural cells after stroke. We have previously reported in vivo that PNS could strengthen the proliferation and differentiation of neural stem cells (NSCs), modulate synaptic plasticity and protect against ischemic brain injuries in cerebral ischemia rats, which could be attributed to mTOR signaling activation. Next, to obtain further insights into the function mechanism of PNS, we evaluated the direct influence of PNS on the survival, differentiation and synaptic development of C17.2 NSCs in vitro. The oxygen glucose deprivation/reperfusion (OGD/R) model was established to mimic ischemic brain injuries. We found that after OGD/R injuries, PNS improved the survival of C17.2 cells. Moreover, PNS enhanced the differentiation of C17.2 cells into neurons and astrocytes, and further promoted synaptic plasticity by significantly increasing the expressions of synapse-related proteins BDNF, SYP and PSD95. Meanwhile, PNS markedly activated the Akt/mTOR/p70S6K pathway. Notably, the mTOR inhibitor rapamycin pretreatment could reverse these desirable results. In conclusion, PNS possessed neural differentiation-inducing properties in mouse C17.2 NSCs after OGD/R injuries, and Akt/mTOR/p70S6K signaling pathway was proved to be involved in the differentiation and synaptic development of C17.2 cells induced by PNS treatment under the in vitro ischemic condition. Our findings offer new insights into the mechanisms that PNS regulate neural plasticity and repair triggered by NSCs, and highlight the potential of mTOR signaling as a therapeutic target for neural restoration after ischemic stroke.

[Role of macrophage polarization in pulmonary diseases and intervention of traditional Chinese medicines].

As important immune cells, macrophages are a key factor involved in maintaining the homeostasis of the pulmonary microenvironment. Under different conditions, macrophages with high plasticity can be polarized into classically activated(M1) and selectively activated(M2) macrophages, which have pro-inflammatory and anti-inflammatory effects, respectively. M1/M2 phenotype is associated with the occurrence and development of pulmonary diseases. A variety of information molecules and cytokines involved in the polarization of macrophages play a role in regulating phenotypes in pulmonary diseases, and the phenotype transformation varies significantly in different diseases. This paper introduces the biological characteristics of macrophage polarization and expounds the roles of macrophage polarization in bronchial asthma, chronic obstructive pulmonary disease, acute lung injury, and pulmonary fibrosis. Moreover, the research progress in the regulation of macrophage polarization by the active components in traditional Chinese medicine(TCM) and the TCM compound prescriptions in the treatment of pulmonary diseases was reviewed. This review aims to explore the potential of macrophage polarization in regulating pulmonary inflammation and provide new ideas for related clinical research.

Shuangshen ningxin formula attenuates cardiac microvascular ischemia/reperfusion injury through improving mitochondrial function.

ETHNOPHARMACOLOGICAL RELEVANCE: Shuangshen Ningxin Formula (SSNX) is a traditional Chinese medicine formula used to treat myocardial ischemia-reperfusion injury (MIRI). A randomized controlled trial previously showed that SSNX reduced cardiovascular events, and experiments have also verified that SSNX attenuated ischemia-reperfusion (I/R) injury. However, the mechanism of SSNX in the treatment of microvascular I/R injury is still unclear. AIM OF THE STUDY: To determine whether SSNX protects the microvasculature by regulating I/R induction in rats and whether this effect depends on the regulation of NR4A1/Mff/Drp1 pathway. METHODS: The anterior descending coronary artery was ligated to establish a rat MIRI model with 45 min of ischemia and 24 h of reperfusion. The rats were subjected to a 7-day pretreatment with SSNX and nicorandil, after which their cardiac function and microvascular functional morphology were evaluated through diverse methods, including hematoxylin and eosin (HE) staining, wheat germ agglutinin (WGA) staining, and transmission electron microscopy. Cell apoptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Additionally, serum levels of ET-1 and eNOS were determined through an enzyme-linked immunosorbent assay (ELISA). The expression levels of NR4A1, Mff, and proteins related to mitochondrial fission were examined by Western blot (WB). Cardiac microcirculation endothelial cells (CMECs) were cultured and the oxygen-glucose deprivation/reoxygenation (OGD/R) model was duplicated. Following treatment with SSNX and DIM-C-pPhOH, an NR4A1 inhibitor, cell viability was assessed. Fluorescence was used to evaluate mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (MPTP) opening. Moreover, vascular endothelial function was evaluated through transendothelial electrical resistance (TEER), Transwell assays and tube formation assays. RESULTS: The results showed that SSNX reduced the infarction area and no-flow area, improved cardiac function, mitigated pathological alterations, increased endothelial nitric oxide synthase expression, protected endothelial function, and attenuated microvascular damage after I/R injury. I/R triggered mitochondrial fission and apoptotic signaling in CMECs, while SSNX restored mitochondrial fission to normal levels and inhibited mitochondrial apoptosis. A study using CMECs revealed that SSNX protected endothelial function after OGD/R, attenuating the increase in NR4A1/Mff/Drp1 protein and inactivating VDAC1, HK2, cytochrome c (cyt-c) and caspase-9. Research also shows that SSNX can affect CMEC cell migration and angiogenesis, reduce mitochondrial membrane potential damage, and inhibit membrane opening. Moreover, DIM-C-pPhOH, an NR4A1 inhibitor, partially imitated the effect of SSNX. CONCLUSION: SSNX has a protective effect on the cardiac microvasculature by inhibiting the NR4A1/Mff/Drp1 pathway both in vivo and in vitro.

Investigation of the active ingredients of Shuangshen Ningxin Fomula and the mechanism underlying their protective effects against myocardial ischemia-reperfusion injury by mass spectrometric imaging.

BACKGROUND: Traditional Chinese medicine, particularly Shuangshen Ningxin Capsule (SSNX), has been studied intensely. SSNX includes total ginseng saponins (from Panax ginseng Meyer), total phenolic acids from Salvia miltiorrhiza Bunge, and total alkaloids from Corydalis yanhusuo W. T. Wang. It has been suggested to protect against myocardial ischemia by a mechanism that has not been fully elucidated. METHODS: The composition and content of SSNX were determined by UHPLC-Q-TOFQ-TOF / MS. Then, a rat model of myocardial ischemia-reperfusion injury was established, and the protective effect of SSNX was measured. The protective mechanism was investigated using spatial metabolomics. RESULTS: We found that SSNX significantly improved left ventricular function and ameliorated pathological damages in rats with myocardial ischemia-reperfusion injury. Using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), the protective mechanism of SSNX was examined by comparing the monomer components of drugs targeted in myocardial tissue with the distribution of myocardial energy metabolism-related molecules and phospholipids. Interestingly, some lipids display inconsistent content distribution in the myocardial ischemia risk and non-risk zones. These discrepancies reflect the degree of myocardial injury in different regions. CONCLUSION: These findings suggest that SSNX protects against myocardial ischemia-reperfusion injury by correcting abnormal myocardial energy metabolism, changing the levels and distribution patterns of phospholipids, and stabilizing the structure of the myocardial cell membrane. MALDI-TOF MS can detect the spatial distribution of small molecule metabolites in the myocardium and can be used in pharmacological research.

[Baicalin improves inflammatory response of human microglia by regulating cAMP-PKA-NF-κB/CREB pathway].

This study aims to investigate the effects of baicalein(BAI) on lipopolysaccharide(LPS)-induced human microglial clone 3(HMC3) cells, with a focus on suppressing inflammatory responses and elucidating the potential mechanism underlying the therapeutic effects of BAI on ischemic stroke via modulating the cAMP-PKA-NF-κB/CREB pathway. The findings have significant implications for the application of traditional Chinese medicine in treating cerebral ischemic diseases. First, the safe dosage of BAI was screened, and then an inflammation model was established with HMC3 cells by induction with LPS for 24 h. The cells were assigned into a control group, a model group, and high-, medium-, and low-dose(5, 2.5, and 1.25 µmol·L~(-1), respectively) BAI groups. The levels of superoxide dismutase(SOD) and malondialdehyde(MDA) in cell extracts, as well as the levels of interleukin-1ß(IL-1ß), IL-6, tumor necrosis factor-α(TNF-α), and cyclic adenosine monophosphate(cAMP) in the cell supernatant, were measured. Western blot was performed to determine the expression of protein kinase A(PKA), phosphorylated cAMP-response element binding protein(p-CREB), and nuclear factor-kappa B p65(NF-κB p65). Hoechst 33342/PI staining was employed to assess cell apoptosis. High and low doses of BAI were used for treatment in the research on the mechanism. The results revealed that BAI at the concentrations of 10 µmol·L~(-1) and below had no impact on normally cultured HMC3 cells. LPS induction at 200 ng·mL~(-1) for 24 h reduced the SOD activity and increased the MDA content in HMC3 cells. However, 5, 2.5, and 1.25 µmol·L~(-1) BAI significantly increased the SOD activity and 5 µmol·L~(-1) BAI significantly decreased the MDA content. In addition, BAI ameliorated the M1 polarization of HMC3 cells induced by LPS, as indicated by cellular morphology. The results of ELISA demonstrated that BAI significantly lowered the levels of TNF-α, IL-1ß, IL-6, and cAMP in the cell supernatant. Western blot revealed that BAI up-regulated the protein levels of PKA and p-CREB while down-regulating the expression of NF-κB p65. Hoechst 33342/PI staining results indicated that BAI mitigated the apoptosis of HMC3 cells. Overall, the results indicated that BAI had protective effects on the HMC3 cells induced by LPS, and could inhi-bit inflammatory response and improve cell apoptosis, which might be related to the regulation of the cAMP-PKA-NF-κB/CREB pathway.

Nkx2.5: a crucial regulator of cardiac development, regeneration and diseases.

Cardiomyocytes fail to regenerate after birth and respond to mitotic signals through cellular hypertrophy rather than cellular proliferation. Necrotic cardiomyocytes in the infarcted ventricular tissue are eventually replaced by fibroblasts, generating scar tissue. Cardiomyocyte loss causes localized systolic dysfunction. Therefore, achieving the regeneration of cardiomyocytes is of great significance for cardiac function and development. Heart development is a complex biological process. An integral cardiac developmental network plays a decisive role in the regeneration of cardiomyocytes. During this process, genetic epigenetic factors, transcription factors, signaling pathways and small RNAs are involved in regulating the developmental process of the heart. Cardiomyocyte-specific genes largely promote myocardial regeneration, among which the Nkx2.5 transcription factor is one of the earliest markers of cardiac progenitor cells, and the loss or overexpression of Nkx2.5 affects cardiac development and is a promising candidate factor. Nkx2.5 affects the development and function of the heart through its multiple functional domains. However, until now, the specific mechanism of Nkx2.5 in cardiac development and regeneration is not been fully understood. Therefore, this article will review the molecular structure, function and interaction regulation of Nkx2.5 to provide a new direction for cardiac development and the treatment of heart regeneration.

A randomized, double-blind, placebo-controlled, parallel-group 12-week pilot phase II trial of SaiLuoTong (SLT) for cognitive function in older adults with mild cognitive impairment.

INTRODUCTION: This study primarily aimed to evaluate the efficacy and safety of SaiLuoTong (SLT) on cognition in mild cognitive impairment (MCI). METHODS: Community-dwelling people with MCI aged ≥60 years were randomly assigned to 180 mg/day SLT or placebo for 12 weeks. RESULTS: Thirty-nine participants were randomized to each group (N = 78); 65 were included in the final analysis. After 12 weeks, the between-groups difference in Logical Memory delayed recall scores was 1.40 (95% confidence interval [CI]: 0.22 to 2.58; P = 0.010); Delis-Kaplan Executive Function System Trail Making Test Condition 4 switching and contrast scaled scores were 1.42 (95% CI: -0.15 to 2.99; P = 0.038) and 1.56 (95% CI: -0.09 to 3.20; P = 0.032), respectively; Rey Auditory Verbal Learning Test delayed recall was 1.37 (95% CI: -0.10 to 2.84; P = 0.034); and Functional Activities Questionnaire was 1.21 (95% CI: -0.21 to 2.63; P = 0.047; P < 0.001 after controlling for baseline scores). DISCUSSION: SLT is well tolerated and may be useful in supporting aspects of memory retrieval and executive function in people with MCI. Highlights: SaiLuoTong (SLT) improves delayed memory retrieval and executive function in people with mild cognitive impairment (MCI).SLT is well tolerated in people ≥ 60 years.The sample of community dwellers with MCI was well characterized and homogeneous.

Role of senkyunolide I in the promotion of neural stem/progenitor cell proliferation via the Akt/ß-catenin pathway.

Following brain injury, neural stem cells (NSCs) can generate mature neurons and replace damaged cells. However, the capacity of endogenous NSCs to self-repair from injured brain is limited as most NSCs die before becoming mature neurons. Therefore, a boosting endogenous NSCs by pharmacological support offers the potential to repair the damaged brain. Recently, small molecules have hold considerable promise for neuron regeneration and repair as they can penetrate the blood-brain barrier easily. Senkyunolide I (SEI) is a bioactive constituent derived from traditional Chinese medicines Ligusticum chuanxiong Hort. and Angelica sinensis (Oliv.) Diels, and was found to able to prevent ischemic stroke. This study examined the effects of SEI on the proliferation and neuronal lineage differentiation of prepared neural stem/progenitor cells (NS/PCs). The NS/PC proliferation was determined by 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt, and neurosphere formation assays. The NS/PC differentiation was also investigated by immunocytochemistry, and western blotting was employed to measure phosphorylated Akt (pAkt) and GSK-3ß (pGSK-3ß), and active-ß-catenin protein levels. We showed that the NS/PC proliferation was enhanced after SEI exposure. Elevated cell numbers were also observed in neurospheres, which were incubated with SEI for 3 days, whereas the NS/PC differentiation was decreased after SEI exposure for 5 days. Furthermore, SEI upregulated pAkt/Akt and active-ß-catenin levels and increased NS/PC proliferation after SEI treatment was reversed by phosphatidylinositol 3-kinase inhibitor LY294002. downregulated differentiated processes. Thus, SEI promoted the NS/PC proliferation and suppressed NS/PC differentiation into neurons and/or astrocytes, therefore SEI could be an interesting and promising candidate for stimulating NSCs.

Efficacy of traditional Chinese medicine on diabetic cardiomyopathy in animal models: a systematic review and meta-analysis.

Background: Diabetic cardiomyopathy (DCM) is a severe complication of diabetes that can diminish the quality of life in patients and is a leading cause of death. Research has demonstrated the effectiveness of Traditional Chinese Medicine (TCM) in reducing blood sugar levels and protecting cardiovascular function in both animal models and clinical research studies. Nevertheless, the efficacy of TCM in animal models of DCM has not been analyzed systematically. Method: We searched the following electronic bibliographic databases: Web of Science, PubMed, Cochrane Library, and CNKI(China National Knowledge Infrastructure). Studies that reported the efficacy of TCM in animals with DCM were included. The literature search was conducted using the terms. The data will be restricted from the year 2013 to 24 April 2023, 24 studies were included in the meta-analysis. Result: A total of 24 Traditional Chinese Medicine interventions and 2157 animals met the inclusion criteria. The pooled data revealed that TCM interventions resulted in significant improvements in body weight (BW), heart weight (HW) to body weight ratio (HW/BW), triglyceride (TG) and cholesterol (TC) levels, ejection fraction (EF), fractional shortening (FS) and E/A ratio. Subgroup analysis and meta-regression revealed that the type of TCM, duration of intervention, method of modeling, and animal species were potential sources of heterogeneity. Conclusion: TCM interventions were associated with significant improvements in body weight, heart weight to body weight ratio, triglyceride and cholesterol levels, left ventricular internal dimension in systole, ejection fraction, fractional shortening and E/A ratio. The heterogeneity in the results was found to be potentially due to the type of TCM, duration of intervention, method of modeling, and animal species, as shown in subgroup analysis and meta-regression. Systematic Review Registration: identifier CRD42023402908.