ObjectiveTo investigate the mechanism of topical treatment of allergic contact dermatitis （ACD） mice with Portulacae Herba based on the nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/nuclear factor-κB （NF-κB） signaling pathway. MethodsA total of 70 6-week-old specific pathogen free （SPF） female Kunming mice were adaptively fed for 1 week and randomly divided into blank group， model group， compound dexamethasone acetate cream group （2.075×10^-2 g·g^-1）， blank matrix cream group， low-dose Portulacae Herba cream group （0.1 g·g^-1）， high-dose Portulacae Herba cream group （0.2 g·g^-1）， and Portulacae Herba + inhibitor group （0.2 g·g^-1 + 30 mg·kg^-1 ML385）， with 10 mice in each group. One day before the experiment， the mice were shaved on the neck and back. Except for the blank group， the mice in the other groups were treated with 2，4-dinitrochlorobenzene （DNCB） to establish an ACD model. After respective administration， the skin lesion of the mice was scored， and the histopathological changes of the skin were stained with hematoxylin-eosin （HE）. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， reactive oxygen species （ROS）， superoxide dismutase （SOD） activity， and malondialdehyde （MDA） in serum of mice. The expression of Nrf2/HO-1/NF-κB signaling pathway-related proteins in mouse skin tissue was detected by immunohistochemistry （IHC）， Western blot， and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， the mice in the model group had an increased skin lesion score （P<0.01）， severe pathological damage to skin tissue， increased content of IL-1β， IL-6， ROS， and MDA in their serum （P<0.01）， and decreased content of SOD （P<0.01）. In addition， the mRNA and protein expression levels of Nrf2， HO-1， and nuclear factor-κB inhibitor α （IκBα） in skin tissue were up-regulated （P<0.01）， while the protein expression levels of phosphorylated （p）-IκBα and p-NF-κB p65 and the mRNA expression of NF-κB p65 were down-regulated （P<0.01）. Compared with the model group and the blank matrix cream group， the mice treated with Portulacae Herba had a decreased skin lesion score （P<0.01）， reduced pathological damage to skin tissue， decreased content of IL-1β， IL-6， ROS， and MDA in their serum （P<0.01）， and increased content of SOD （P<0.01）. Additionally， the mRNA and protein expression levels of Nrf2， HO-1， and IκBα in skin tissue were down-regulated （P<0.05，P<0.01）， and the protein expression levels of p-IκBα and p-NF-κB p65 and the mRNA expression of NF-κB p65 were up-regulated （P<0.05，P<0.01）. Compared with the Portulacae Herba + inhibitor group， the high-dose Portulacae Herba cream group had a decreased skin lesion score （P<0.01）， alleviated pathological damage to skin tissue， decreased content of IL-1β， IL-6， ROS， and MDA in the serum of mice （P<0.05，P<0.01）， and increased content of SOD （P<0.01）. The protein expression levels of Nrf2， HO-1， and IκBα and the mRNA expression of Nrf2 and HO-1 in skin tissue were up-regulated （P<0.05，P<0.01）， and the protein expression levels of p-IκBα and p-NF-κB p65 and the mRNA expression of NF-κB p65 were down-regulated （P<0.05）. ConclusionPortulacae Herba can improve DNCB-induced ACD skin damage in mice by regulating the Nrf2/HO-1/NF-κB signaling pathway.

OBJECTIVE To study the effects and mechanism of Portulaca oleracea cream on skin pruritus and barrier function in allergic contact dermatitis （ACD） mice. METHODS Low-concentration and high-concentration P. oleracea creams were prepared， with the P. oleracea extract solution （1 g/mL， calculated by crude drug） concentrations of 10% and 20%. Sixty BALB/c mice were randomly allocated into blank group， model group， Mometasone furoate cream group （positive control）， blank matrix cream group， P. oleracea low-concentration and high-concentration cream groups. Except for blank group， ACD model was induced in each group using 2，4-dinitrochlorobenzene solution. The blank group and model groups received normal saline， while the remaining groups were treated with their respective creams， once a day， at a dose of approximately 0.5 g per application， continuously for 14 days. At 24 h post-final administration， skin lesions of mice were observed and scored； pathological changes of skin tissue were observed； serum levels of immunoglobulin E（IgE） and tumor necrosis factor-α （TNF-α） were quantified. mRNA expression of MAS-related G protein-coupled receptors （including MrgprA3， MrgprC11， and MrgprD） in dorsal root ganglion （DRG） was assessed； while protein expressions of skin barrier function-related proteins Claudin-1 and Occludin in skin tissues were determined. RESULTS Compared with blank group， mice in the model group exhibited severe skin damage， characterized by loss of epidermal architecture， hyperkeratosis of the skin tissue， and the infiltration of a large number of inflammatory cells. The skin injury scores， as well as the serum levels of IgE and TNF-α， and the mRNA expression levels of MrgprA3， MrgprC11， and MrgprD in DRG， were all significantly elevated compared to the blank group （P＜0.05 or P＜0.01）； in contrast， the protein expression levels of Claudin-1 and Occludin in the skin tissue were markedly reduced （P＜0.05）. Compared with model group， mice in P. oleracea low-concentration and high- concentration cream groups demonstrated significant alleviation of skin damage， as evidenced by reduced epidermal hyperplasia， mitigated spongiosis in the dermis， and decreased infiltration of inflammatory cells； these quantitative indicators were almost significantly reversed （P＜0.05 or P＜0.01）. No significant differences were observed in the aforementioned skin injuries， pathological alterations， or quantitative indicators between the blank matrix cream group and the model group. CONCLUSIONS P. oleracea may ameliorate skin lesions and restore skin barrier function of ACD mice， the mechanism of which may be associated with downregulating mRNA expressions of MrgprA3， MrgprC11 and MrgprD in DRG， and up-regulating the protein expressions of Claudin-1 and Occludin in skin tissue.

Objective To analyze the medication law of core prescriptions and categorized prescriptions of TCM for the treatment of heart failure with preserved ejection fraction(HFpEF);To provide references for clinical prescriptions of HFpEF.Methods The clinical research literature on TCM for HFpEF was retrieved from CNKI,Wanfang Data,VIP,CBM,PubMed,Web of Science,Embase and Cochrane Library from establishment of the databases to November 1,2023.Data mining methods,such as complex network,prescription similarity network and community detection method were used to explore the prescription medication law of HFpEF.Results Totally 142 articles related to TCM treatment of HFpEF were included,containing 146 prescriptions and involving 162 kinds of Chinese materia medica.The most frequently used drugs were represented by Astragali Radix,Salviae Miltiorrhizae Radix et Rhizoma and Poria.The core prescription and the commonly used modified law of HFpEF treatment were obtained by complex network analysis.The core prescription consisted of Astragali Radix,Poria,Salviae Miltiorrhizae Radix et Rhizoma,Glycyrrhizae Radix et Rhizoma,Chuanxiong Rhizoma,Cinnamomi Ramulus,Descurainiae Semen Lepidii Semen,Atractylodis Macrocephalae Rhizoma,Paeoniae Radix Rubra,Ophiopogonis Radix and Angelicae Sinensis Radix.Further based on the prescription similarity network and community detection method,the basic prescriptions of the 3 major community of categorized prescription corresponding to the HFpEF staging and syndrome types were obtained,and the staged diagnosis and treatment medication law with the development of the HFpEF disease course were found.Conclusion Invigorating qi and activating blood circulation,warming yang and promoting diuresis are the main therapeutic principles of HFpEF.Data mining technology provides a feasible method for the analysis of core prescriptions and categorized prescriptions for HFpEF,which can provide a basis for the diagnosis and treatment law and medication experience of HFpEF in TCM.

Objective To clarify the predominant symptoms of PH and their correlation with clinical indicators by collecting Chinese medicine clinical syndromic data of patients with pulmonary hypertension(PH).To provide a basis for the clinical diagnosis and treatment of Chinese medicine.Methods Adopting a cross-sectional study method,from January 2020 to July 2021,the cardiovascular ward of Guang'an men Hospital of the China Academy of Traditional Chinese Medicine was in line with the patients with the diagnosis of PH.A total of 298 patients'data were collected,and 236 patients were included in this study by excluding factors such as incomplete data and repeated hospitalization.The clinical data of the patients were organized,analyzed and counted.The distribution pattern of symptoms and syndrome types of PH was derived,and the correlation between syndrome elements and hemodynamics,cardiac function,and coagulation function was explored.Results The eight syndrome elements of PH in this study were,in descending order,blood stasis>Qi deficiency>water stagnation>phlegm turbidity>blood deficiency>yang deficiency>yin deficiency>qi stagnation;The eight syndrome types were in the order of high to low:Qi deficiency and blood stasis,spleen and lung deficiency,blood stasis and water stagnation,phlegm and water stagnation,phlegm and blood stasis stagnation,phlegm and water stagnation,yang deficiency and water stagnation,phlegm and turbid obstruction of lungs,and deficiency of both qi and yin;Qi deficiency was negatively correlated with Systolic pulmonary artery pressure(SPAP),and water stagnation was positively correlated with SPAP;Qi deficiency was negatively correlated with cardiac function grading,and water stagnation and phlegm turbidity evidence were positively correlated with cardiac function grading.Conclusion Blood stasis is the core pathogenesis of PH,and the clinical manifestations and symptoms of PH patients gradually transformed from qi deficiency through blood stasis to phlegm turbidity and water stagnation."Stasis"is present throughout the course of PH disease and has a significant impact on the progression of PH.

Objective To investigate the core drugs of traditional Chinese medicine(TCM)for the treatment of hypoxic pulmonary hypertension(HPH),and to verify the drug efficacy by hypoxia combined with Su5416(Hypoxia+Su5416,HySu)-induced PH mouse model.Methods Relevant literatures on TCM treatment of HPH in China Knowledge Network,Wanfang,Weipu were collected,screened and set up a database through the nerf criteria,and inputted into the software of traditional Chinese medicine inheritance assistance platform(V2.5)for the excavation of medication law.The HySu-PH mouse model was established,and the core drugs were evaluated for drug efficacy through force exhaustion exercise running table,blood oxygen saturation,right ventricular pressure,and right heart hypertrophy index test.Results The 102 relevant formulas for the treatment of HPH were screened,involving a total of 158 traditional Chinese medicines,and the top 5 drug frequencies were Salvia miltiorrhiza,Rhizoma Chuanxiong,Astragalus membranaceus,Draba hebecarpa,and Angelica sinensis,with the highest use of blood-activating and blood-stasis removing drugs,and deficiency-tonifying drugs in the categories of drugs used,and Salvia miltiorrhiza was the core drug used.HySu-PH mouse models were constructed and given 2 weeks of treatment with the danshen preparation Danshen injection.Danshen injection significantly elevated body weight(P<0.01),oxygen saturation(P<0.05),displacement of exhaustion(P<0.01),and duration of exhaustion(P<0.05),and lowered the right ventricular systolic blood pressure(P<0.01)and the right cardiac hypertrophy index(P<0.01).Conclusion Salvia miltiorrhiza is a core drug for the treatment of HPH,and the danshen preparation Danshen injection can effectively treat HySu-PH.

Objective Based on the pre-existing basis of effective treatment of hypoxia combined with Su5416-induced hypoxic pulmonary hypertension(HPH)by Salvia miltiorrhiza,to investigate the mechanism of Salvia miltiorrhiza in the treatment of HPH.Methods Using a network pharmacology approach to obtain the key pathways of Salvia miltiorrhiza for the treatment of HPH.The active ingredients of Salvia miltiorrhiza were collected to obtain the targets of the active ingredients.HPH disease targets were collected to obtain the intersection of Salvia miltiorrhiza component targets and HPH disease targets.Protein-Protein Interaction Networks(PPIs)were constructed and KEGG analysis was performed to obtain the key pathways of Salvia miltiorrhiza for HPH.Then used molecular biology to validate the key pathways.Results The 81 targets of Salvia miltiorrhiza for the treatment of HPH were obtained by network pharmacology,and PPI showed that drug component-disease common core targets included ATK1,TNF,EGFR,IL6,ESR1,and KEGG-enriched Pathway mainly included PI3K-AKT signaling pathway,HIF-1 signaling pathway,MAKP signaling pathway,TNF signaling pathway,JAK-STAT signaling pathway and so on.Molecular biological assays showed that Salvia miltiorrhiza had the effect of reducing lung tissue fibrosis and inhibiting the PI3K/AKT signalling pathway in HySu-PH mice.Conclusion Salvia miltiorrhiza has the effect of attenuating pulmonary fibrosis,and its mechanism of action is related to the inhibition of the PI3K/Akt signalling pathway.

Plant-derived nanovesicles have gained attention given their similarity to mammalian exosomes and advantages such as low cost, sustainability, and tissue targeting. Thus, they hold promise for disease treatment and drug delivery. In this study, we proposed a time-efficient method, PEG 8000 combined with sucrose density gradient centrifugation to prepare ginger-derived nanovesicles (GDNVs). Subsequently, curcumin (CUR) was loaded onto GDNV by ultrasonic incubation. The optimum conditions for ginger-derived nanovesicles loaded with curcumin (CG) were ultrasound time of 3 min, a carrier-to-drug ratio (GDNV:CUR) of 1:1. The study achieved a high loading capacity (94.027% ± 0.094%) and encapsulation efficiency (89.300% ± 0.344%). Finally, the drugs' in vivo distribution and anti-colitis activity were investigated in mice. CG was primarily distributed in the colon after oral administration. Compared to CUR and GDNV, CG was superior in improving disease activity, colon length, liver and spleen coefficients, myeloperoxidase activity, and biochemical factor levels in ulcerative colitis (UC) mice. In addition, CG plays a protective role against UC by modulating serum metabolite levels and gut flora. In summary, our study demonstrated that GDNV can be used for CUR delivery with enhanced therapeutic potential.

Small ubiquitin-related modifier(SUMOylation)is a dynamic post-translational modification that maintains cardiac function and can protect against a hypertrophic response to cardiac pressure overload.However,the function of SUMOylation after myocardial infarction(MI)and the molecular details of heart cell responses to SUMO1 deficiency have not been determined.In this study,we demonstrated that SUMO1 protein was inconsistently abundant in different cell types and heart regions after MI.However,SUMO1 knockout significantly exacerbated systolic dysfunction and infarct size after myocardial injury.Single-nucleus RNA sequencing revealed the differential role of SUMO1 in regulating heart cells.Among cardiomyocytes,SUMO1 deletion increased the Nppa+Nppb+Ankrd1+cardiomyocyte subcluster pro-portion after MI.In addition,the conversion of fibroblasts to myofibroblasts subclusters was inhibited in SUMO1 knockout mice.Importantly,SUMO1 loss promoted proliferation of endothelial cell subsets with the ability to reconstitute neovascularization and expressed angiogenesis-related genes.Computational analysis of ligand/receptor interactions suggested putative pathways that mediate cardiomyocytes to endothelial cell communication in the myocardium.Mice preinjected with cardiomyocyte-specific AAV-SUMO1,but not the endothelial cell-specific form,and exhibited ameliorated cardiac remodeling following MI.Collectively,our results identified the role of SUMO1 in cardiomyocytes,fibroblasts,and endothelial cells after Ml.These findings provide new insights into SUMO1 involvement in the patho-genesis of MI and reveal novel therapeutic targets.

Sodium calcium exchanger (NCX) is encoded by the SCL8 family genes and belongs to the cation/Ca

COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread across the globe, posing an enormous threat to public health and safety. Traditional Chinese medicine (TCM), in combination with Western medicine (WM), has made important and lasting contributions in the battle against COVID-19. In this review, updated clinical effects and potential mechanisms of TCM, presented in newly recognized three distinct phases of the disease, are summarized and discussed. By integrating the available clinical and preclinical evidence, the efficacies and underlying mechanisms of TCM on COVID-19, including the highly recommended three Chinese patent medicines and three Chinese medicine formulas, are described in a panorama. We hope that this comprehensive review not only provides a reference for health care professionals and the public to recognize the significant contributions of TCM for COVID-19, but also serves as an evidence-based in-depth summary and analysis to facilitate understanding the true scientific value of TCM.