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Colorectal cancer is one of the most common malignant cancers. Pseudogenes have been identified as oncogenes or tumor suppressor genes in the development of various cancers. However, the function of pseudogene CSPG4P12 in colorectal cancer remains unclear. Therefore, the aim of this study was to investigate the potential role of CSPG4P12 in colorectal cancer and explore the possible underlying mechanism. The difference of CSPG4P12 expression between colorectal cancer tissues and adjacent normal tissues was analyzed using the online Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database. Cell viability and colony formation assays were conducted to evaluate cell viability. Transwell and wound healing assays were performed to assess cell migration and invasion capacities. Western blot was used to measure the expression levels of epithelial-mesenchymal transition-related proteins. Colorectal cancer tissues had lower CSPG4P12 expression than adjacent normal tissues. The overexpression of CSPG4P12 inhibited cell proliferation, invasion, and migration in colorectal cancer cells. Overexpressed CSPG4P12 promoted the expression of E-cadherin, whereas it inhibited the expression of vimentin, N-cadherin, and MMP9. These findings suggested that CSPG4P12 inhibits colorectal cancer development and may serve as a new potential target for colorectal cancer.
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Bladder cancer （BCa） is the most common malignant tumor of the urinary system， and its incidence is increasing year by year. At present， for all patients with resectable non-metastatic muscle-invasive BCa， radical cystectomy + bilateral pelvic lymph node dissection is strongly recommended， but they still face the risk of recurrence， metastasis and death. In recent years， the proportion of patients with advanced and metastatic BCa is increasing among patients with newly diagnosed BCa. Although current treatment models are diverse， they often struggle to achieve significant efficacy due to their low effectiveness and adverse effects， resulting in low survival rates for patients with advanced and metastatic BCa. Therefore， the treatment of BCa still faces great challenges， and there is an urgent need to discover an effective new antitumor drug. With the improvement of medical standards， traditional Chinese medicine has shown great advantages in the treatment of BCa. Traditional Chinese medicine is mild and easy to accept， and can inhibit tumor progression through a multi-pathway， multi-way and multi-target manner， so as to exert its anticancer effect. Taraxaci Herba is a medicinal and food homologous plant， which has many biological activities， such as antibacterial， anti-inflammatory， anti-oxidation， anti-tumor， protecting liver and gallbladder， reducing blood sugar and enhancing immunity， and it has shown a clear anticancer effect in breast cancer， liver cancer， gastric cancer， tongue cancer and lung cancer. By reviewing previous studies worldwide， this article summarizes the mechanism of Taraxaci Herba extract in inducing autophagy and apoptosis， inhibiting cell migration and invasion， regulating cell cycle and proliferation， regulating cell metabolism， inhibiting tumor angiogenesis， combining the effects of chemotherapeutic drugs， and regulating the transduction of related signal pathways. On this basis， this study systematically elaborates on the potential mechanism of Taraxaci Herba against BCa， in order to provide a theoretical basis for the research and treatment of BCa.
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Liver failure （LF） is a great trouble to the majority of patients due to its severe onset， many complications， difficult treatment， poor prognosis and other characteristics. This disease is liver injury caused by infection， hepatotoxic substances， autoimmunity， circulation disorders and other factors. It is a group of common clinical symptoms mainly manifested by coagulation disorders， jaundice， hepatic encephalopathy， ascites， and so on. In traditional Chinese medicine， it falls under the categories of "tympanites"， "jaundice" and other diseases. At present， the research progress of Western medicine in the treatment of LF is slow， and its clinical application effect is still not ideal. In contrast， traditional Chinese medicine has a long history in the treatment of this disease， with over thousands of years of clinical practice and verification. It is characterized by exact efficacy and fewer side effects. The pathological mechanism of LF is extremely complex， involves a variety of signaling pathways， and is mainly related to inflammation， oxidative stress， liver fibrosis， cell apoptosis and other processes. In recent years， many studies have shown that traditional Chinese medicine can intervene in the occurrence and development of LF by mediating relevant signaling pathways in vivo， but there is still a lack of relevant summary. Therefore， this review summarized several signaling pathways related to the intervention of traditional Chinese medicine in LF by referring to and sorting out relevant literature worldwide， including nuclear factor kappa B （NF-κB）， mitogen-activated protein kinase （MAPK）， phosphatidylin-ositol-3-kinase/protein kinase B （PI3K/Akt）， transforming growth factor-β/ drosophila mothers against decapentaplegic proteins （TGF-β/Smads）， and nuclear factor erythroid 2-related factor 2/heme oxygenase-1 （Nrf2/HO-1）， and elaborated the specific mechanism of their intervention in LF. This paper aims to provide practical and effective pathways and corresponding mechanisms for the treatment of LF by traditional Chinese medicine， and to provide new ideas and a theoretical basis for the clinical treatment of LF and further scientific research.
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ObjectiveTo investigate the therapeutic effect of Scutellariae Radix-Coptidis Rhizoma （SRCR） on atherosclerosis （AS） in mice and the effect of SRCR on macrophage pyroptosis in plaques via NOD-like receptor thermal protein domain-associated protein 3 （NLRP3） inflammasomes. MethodApoE-/- mice were fed with a high-fat diet for the modeling of AS and randomized into model， atorvastatin （5 mg·kg-1）， and low-， medium-， and high-dose （1.95， 3.9， 7.8 g·kg-1， respectively） SRCR groups. Normal C57BL/6J mice were selected as the control group. After 8 weeks of administration， hematoxylin-eosin staining was used to observe the pathological status of the aortic plaque. The lipid accumulation in aortic plaque was observed by oil red O staining. The serum levels of total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） in mice were measured. Immunofluorescence double staining was employed to detect the co-localized expression of EGF-like module-containing mucin-like hormone receptor-like 1 （EMR1）/NLRP3 and EMR1/gasdermin D （GSDMD）. The serum levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） were determined by enzyme-linked immunosorbent assay （ELISA）. The protein levels of NLRP3， apoptosis-associated speck-like protein （ASC）， Caspase-1， cleaved Caspase-1， GSDMD， N-terminus of GSDMD （GSDMD-NT）， pro-IL-1β， IL-1β， and IL-18 were determined by Western blot， and the mRNA levels of NLRP3， ASC， Caspase-1， GSDMD， IL-1β， and IL-18 were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the control group， the model group showed obvious plaques， elevated serum levels of TG， TC， LDL-C， IL-1β， and IL-18 （P<0.01）， lowered serum level of HDL-C （P<0.01）， and up-regulated expression of NLRP3 inflammasomes and molecules related to pyroptosis in the aortic plaques （P<0.01）. Compared with the model group， SRCR， especially at the medium and high doses， alleviated the plaque pathology， reduced the lipid content in plaques （P<0.05， P<0.01）， recovered the serum lipid levels （P<0.05）， reduced the macrophage recruitment （P<0.01）， activation of NLRP3 inflammasomes， and pyroptosis in aortic root plaques （P<0.05）， lowered the serum IL-1β and IL-18 levels （P<0.01）， and down-regulated the protein levels of NLRP3， ASC， Caspase-1， cleaved Caspase-1， GSDMD， GSDMD-NT， pro-IL-1β， IL-1β， and IL-18 （P<0.05） and the mRNA levels of NLRP3， ASC， Caspase-1， GSDMD， IL-1β， and IL-18 in the aortic tissue （P<0.05）. ConclusionSRCR exerts a therapeutic effect on high-fat diet-induced AS in mice by inhibiting the activation NLRP3 inflammasomes and reducing the pyroptosis of macrophages in plaques.
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ObjectiveThis study aimed at conducting retrospective analysis of the clinical symptoms and genetic mutations in 20 children with Gitelman syndrome treated at the Affiliated Children′s Hospital of Nanjing Medical University from August 2015 to November 2022 and also explored the molecular mechanism of the pathogenic high-frequency mutation D486N in the Chinese population.MethodsWe collected the clinical manifestations, growth and development status, laboratory examination results, and SLC12A3 gene variations of the patients. We distinguished the wild-type and mutant SLC12A3 genes overexpressed in human embryonic kidney 293T cells (HEK293T). We used protein immunoblotting to detect the expression level of NCC, and used immunofluorescence techniques to examine the subcellular localization of NCC. In addition, we investigated the impact of the high-frequency SLC12A3 gene mutation D486N on NCC protein expression and localization.ResultsIn the 20 patients with Gitelman syndrome, all of them had hypokalemia. We indemnified twenty-six SLC12A3 gene mutations, 13 of which are missense mutation, 1 of which synonymous mutation, 1 nonsense mutation, 4 frameshift mutation, and 7 splicing site mutation. Among them, four mutations (p.T235K, c.1096-1G > A, p.A464A, and c.2660+1_2660+2insT) were novel mutations.ConclusionsWe found the preliminary evidence that the high-frequency mutation D486N in the Chinese population affected the expression of total and membrane-bound NCC protein and influenced the membrane localization of NCC protein. The findings of this study provides experimental evidence for genetic counseling, diagnosis, and treatment of Gitelman syndrome.
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OBJECTIVE To study the antifungal activity of Huangqin decoction （HQD） against Trichophyton mentagrophytes and explore its mechanism. METHODS Minimal inhibitory concentration （MIC）， minimal fungicidal concentration （MFC）， mycelial length， spore germination rate， biomass and mycelium ultrastructure observation were performed to evaluate the antifungal activity of HQD against T. mentagrophytes. The effects of HQD on the cell wall of T. mentagrophytes were detected through sorbitol protection experiment. By measuring the content of ergosterol and the activities of squalene epoxide （SE） and lanosterol 14α-demethylase （CYP51）， the activity of HQD on the cell membrane of T. mentagrophytes was investigated. The effects of HQD on T. mentagrophytes mitochondria were investigated by determining the activities of malate dehydrogenase （MDH）， succinate dehydrogenase （SDH）， and ATPases （including sodium potassium ATPase， calcium magnesium ATPase， and total ATPase）. RESULTS HQD exhibited significant antifungal activity against T. mentagrophytes with MIC of 3.13 mg/mL and MFC of 25 mg/mL. After intervention with HQD， the mycelial length of T. mentagrophytes was significantly shortened （P＜0.05）； spore germination rate， biomass， the content of ergosterol in the cell membrane， the activities of SE and CYP51 in the cell membrane and MDH， SDH and ATPase in mitochondria were all decreased significantly （P＜0.05）； cell structure had been ；damaged to a certain extent， but the integrity of the cell wall had not been affected. CONCLUSIONS HQD shows significant antifungal activity against T. mentagrophytes， the mechanism of which may be associated with reducing the 0791- content of ergosterol in the cell membrane and the activities of SE， CYP51， and mitochondria-related enzymes.
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Diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia caused by absolute or relative insufficiency of insulin secretion. As the disease progresses， patients begin to suffer from diabetic nephropathy， diabetic cardiomyopathy， non-alcoholic fatty liver disease or other complications， which increase the burden on the patients. Moreover， the number of patients is increasing， which brings a heavy burden to the society. Ferroptosis is a new type of programmed cell death which has attracted wide attention in recent years. It refers to the cell death caused by the excessive accumulation of lipid peroxide under the overload of iron ions. Studies have discovered that ferroptosis exists in diabetes mellitus and its complications. Inhibiting ferroptosis can greatly slow down the occurrence and progression of diabetes mellitus and its complications. Chinese medicine， the unique medical treasure in China， acts in a multi-pathway， multi-target manner and is praised for the cheap price， low toxicity， and mild side effects. It has been widely used in the treatment of diabetes mellitus and its complications and has demonstrated definite therapeutic effects， bringing the good news for the majority of patients. The regulation of ferroptosis by Chinese medicine may be a new direction for the treatment of diabetes mellitus and its complications in the future. This paper briefly describes the mechanism of ferroptosis， explores the relationship of ferroptosis with diabetes mellitus and its complications， summarizes the research status of Chinese medicine interventions， and puts forward suggestions， aiming to provide a reference for further research on the treatment of diabetes mellitus and its complications with Chinese medicine.
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Colorectal cancer （CRC） is a malignant tumor of the intestinal tract with changes in bowel habits， blood in the stool， and pain as the main clinical manifestations. With the change in lifestyle and diet structure in recent years， the incidence of CRC has been increasing year by year. The pathogenesis of CRC is closely related to abnormal immune response and chronic inflammation， intestinal microbial dysbiosis， and the production of oncogenic metabolites. There is a two-way communication between the intestinal microbiota and the body's immunity， which not only plays a key role in maintaining the body's health but also has a close relationship with the development of diseases. An increasing number of studies have shown that abnormal immune responses accelerate the disease process by producing inflammatory factors， causing chronic inflammation in the body， disrupting the intestinal mucosal barrier， and increasing mucosal permeability， thus resulting in dysbiosis of the intestinal microbial ecology and a large number of pathogenic microorganisms and their metabolites. In addition， dysbiosis of intestinal microbes， by suppressing the normal immune response， leads to the disruption of multiple metabolic pathways in the body， affecting the internal and external stress response of the intestine， inducing inflammation， and thus producing disease. Therefore， the complex crosstalk mechanism between the immune response and intestinal microbial axis is closely related to the development of CRC. Based on traditional Chinese medicine theory and clinical research， it was found that dietary factors are an important causative factor in the development of CRC. The deficiency of positive energy is the root cause of the disease， and damp-heat accumulation is the key pathogenesis. Through modern medical and biological research， it is believed that abnormal immune response is the microscopic manifestation of damp-heat entrapment， while intestinal microbial dysbiosis is the biological basis of toxic injection into the large intestine， and in the pathogenesis of CRC， the imbalance of immune response-intestinal microbial axis is compatible with damp-heat accumulation in traditional Chinese medicine. This study aims to explore the biological connotation of CRC due to damp-heat accumulation from the immune response-intestinal microbial axis， so as to interpret the pathogenesis of CRC due to damp-heat accumulation with objective data and provide new ideas and theoretical basis for the pathogenesis and treatment strategies of CRC due to damp-heat accumulation.
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As a commonly used traditional Chinese medicine in clinical practice， Tripterygium wilfordii has the functions of dispelling wind and removing dampness， detoxicating and destroying parasites， detumescence， pain relief， promoting blood circulation， and dredging collateral. Modern pharmacological studies show that it also has other functions such as anticancer， anti-inflammation， and immunosuppression. It has been widely used to treat autoimmune diseases， renal diseases， and tumors. T. wilfordii contains a variety of chemical components， among which triptolide （TP） can cause varying degrees of damage to human digestive， circulatory， reproductive， and other systems， with liver injury being the most common one， which greatly limits the development of TP in new drug research and industrial application. Therefore， the authors focused on the research hotspot of TP-induced liver injury and summarized relevant Chinese and international literature regarding the clinical manifestations， injury mechanisms， and detoxification strategies of TP-induced liver injury. This helps to provide a scientific basis for the clinical drug safety and scientific drug supervision of TP. The clinical manifestations of TP-induced liver injury are mostly abnormal transaminases， loss of appetite， nausea and vomiting， anorexia， yellow staining of skin and sclera， and yellow urine. The mechanisms of the above clinical manifestations involve apoptosis， oxidative stress， influence on cytochrome P450 superfamily， macrophage polarization， regulation of biological clock gene Clock， etc. Among them， cell apoptosis is related to neurogenic locus notch homolog protein 1 （Notch1）， dynamin-related protein 1 （Drp1）-cytochrome C （Cyt C）， phosphatidylinositide 3-kinases （PI3K）/protein kinase B （Akt）， mitogen-activated protein kinase （MAPK）， tumor suppressor protein 53 （p53）， Fas cell surface death receptor （Fas）/Caspase-8， and other signaling pathways. Oxidative stress is related to inhibition of nuclear factor-erythroid 2-related factor 2 （NRF2） signaling pathway， promotion of cytochrome P450 2E1 （CYP2E1） expression， and excessive accumulation of reactive oxygen （ROS）. The influence of the cytochrome P450 superfamily is manifested as reducing the substrate affinity， activity， and expression of cytochrome P450 3A （CYP3A）， cytochrome P450 2C9 （CYP2C9）， cytochrome P450 2C19 （CYP2C19）， and cytochrome P450 1A2 （CYP1A2）. Promoting the transformation of macrophages into the M1 type is related to the secretion of inflammatory factors and the accumulation of endotoxin， and the internal rhythmic regulation of the biological clock gene Clock， is related to the expression of cytochrome P450 3A11 （CYP3A11） metabolic enzyme. The detoxification strategies in the clinical application include herbs-processing detoxification strategy and drug-pairing detoxification. The traditional Chinese medicines and monomers that are helpful for detoxification include Glycyrrhiza uralensis， Paeonia lactiflora， Lysimachia christinae， Rehmannia glutinosa， saffron， and paeoniflorin. The reviews and discussion about these topics can help to provide more references for related research and clinical application of TP.
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ObjectiveTo explore the comprehensive effects of Qingxin Zishen decoction on the symptom score and neuroendocrine indexes and the mechanism of the decoction in regulating KNDy neurons in the patients with menopausal syndrome. MethodA total of 60 patients with menopausal syndrome due to yin deficiency with effulgent fire who attended the menopausal outpatient of Jiangsu Province Hospital of Chinese Medicine were randomized into an experimental （Qingxin Zishen decoction） group （30 cases） and a control （femoston） group （30 cases）. The treatment lasted for 12 weeks in both groups. The two groups were compared in terms of the comprehensive efficacy， frequency and degree of hot flashes and sweating， modified Kupperman score， and the serum levels of hypothalamic peptide kisspeptin， neurokinin B （NKB）， dynorphin （Dyn）， follicle-stimulating hormone （FSH）， and estradiol （E2）. Result① Comprehensive efficacy： The comprehensive efficacy of the two groups was comparable. ② Frequency and degrees of hot flashes and sweating： After treatment， the frequency and degrees of hot flashes and sweating in the two groups were reduced （P<0.05） and the control group outperformed the experimental group （P<0.05）. ③ Modified Kupperman score and menopausal symptoms： After treatment， the modified Kupperman score decreased in both groups （P<0.05）. After 4 weeks of treatment， the experimental group was superior to the control group in terms of the scores of dizziness and headache （P<0.05）. ④ Serum levels of sex hormones： After treatment， the serum E2 level elevated and the FSH level lowered in both groups （P<0.05）， and the changes were more obvious in the control group （P<0.05）. ⑤ Neuroendocrine indexes： After treatment， the serum levels of kisspeptin and NKB in the two groups decreased （P<0.05）， and the serum Dyn level in the experimental group increased （P<0.05）. Moreover， the experimental group had higher Dyn level than the control group after treatment （P<0.05）. ConclusionQingxin Zishen decoction can alleviate hot flashes， sweating， and other symptoms in the women with menopausal syndrome by acting on the KNDy neurons to lower the kisspeptin and NKB levels and elevate the Dyn level. The findings provide new ideas for the clinical treatment of hot flashes in menopause.
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ObjectiveTo investigate the effect of Yunkang oral liquid on postpartum kidney deficiency in mice. MethodPostpartum mice were randomized into model and low-dose （6 mL·kg-1）， medium-dose （9 mL·kg-1）， and high-dose （12 mL·kg-1） Yunkang oral liquid groups. The mouse model of postpartum kidney deficiency was established by sleep deprivation combined with forced swimming. Another 9 female ICR mice were selected as the normal control group. The mice were administrated with Yunkang oral liquid during the period of modeling. The levels of estradiol （E2）， progesterone （P）， follicle-stimulating hormone （FSH）， and luteinizing hormone （LH） in the serum were measured by the enzyme-linked immunosorbent assay. The morphological changes of ovaries and uterus were observed by hematoxylin-eosin （HE） staining， and the expression of transforming growth factor （TGF）-β and Smad2/3 was determined by immunohistochemistry and Western blotting. ResultThe mice in the model group showed prolonged estrous cycle， reduced voluntary activity， dorsal temperature， grip strength， and bone strength， and whitening tongue coating. Compared with the model group， Yunkang oral liquid shortened the estrous cycle， increased the voluntary activity， dorsal temperature， grip strength， and bone strength， and alleviated the whitening of tongue coating. Moreover， it elevated the E2 and P levels and lowered the FSH and LH levels in the serum， decreased ovarian follicular atresia rate， promoted uterine repair， and down-regulated the expression of TGF-β and Smad2/3 in the ovarian and uterine tissues. ConclusionYunkang oral liquid can ameliorate postpartum kidney deficiency in mice by regulating the TGF-β/Smads signaling pathway.
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Pollinosis is one of the common allergic diseases, and its morbidity continues to increase. Studies have demonstrated that air pollution is a key environmental factor that leads to the increased prevalence of pollinosis. Air pollutants and pollen allergens exert synergistic effects in stimulating allergic responses in susceptible individuals. In this article, we analyzed the relationship between air pollution and pollinosis based on the latest studies, and elaborated potential mechanisms on how air pollution increases the incidence of pollinosis and aggravates allergic reactions. Air pollutants can increase both pollen production and the levels of allergenic proteins, and enhance allergenicity of pollen allergens through structural alterations or chemical modifications. The potential mechanisms of air pollutants exacerbating pollen allergies are as follows: Air pollutants may disrupt the barrier function of the respiratory epithelium and facilitate the penetration of pollen allergens into deeper tissues. Additionally, they may accelerate the process of the release of pollen allergy-related cytokines, promoting T helper 2 (Th2) cell differentiation and exacerbating inflammatory responses in the airways. Given the limitations of existing research, future prospective studies are needed to explore the effects of mixed pollutants and different types of pollutants on pollen, and the response mechanisms of allergy-related cells and cytokines to different pollutant categories. The findings would provide a comprehensive understanding of the impacts of air pollution on pollen allergies and scientific evidence for effective protection of the heath of pollinosis patients.
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Sesquiterpenoids are natural compounds composed of 15 carbon atoms， which can be divided into sesquiterpene alcohols， ketones， lactones， aldehydes， and carboxylic acids according to oxygen groups. These compounds are widely distributed in nature， and their physiological activities are diverse. For example， many sesquiterpenes with potential anticancer effects have been found for anti-tumor effects， including cytotoxicity， antioxidant， immune regulation， cell proliferation， and so on. In addition， some sesquiterpenoids have good application prospects in antibacterial， anti-inflammatory， and anti-cardiovascular diseases. Malignant tumors， inflammation， bacterial diseases， and cardiovascular diseases are the main diseases that cause human death， and natural products have unique advantages in the treatment of these diseases. Therefore， the development of new drugs that are easy to promote has become a new research hotspot. In this paper， the sesquiterpenes extracted from the natural components of Chinese herbs and plants with anti-tumor， anti-inflammatory， antibacterial， and anti-cardiovascular activities， such as Xanthium， Atractylodes， Convolvulus， Acanthium， Ligularia， Artemisia， Ligularia， Ligularia， Labiaceae Mint， Acanthophyllum， Turmeria， Ginger， and other Chinese herbs and plants， were discussed. The biological activities and related mechanisms of this compound were reviewed， which provided a reference for further research and clinical application of sesquiterpenes.
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Gancao Fuzitang originates from the Treatise on Febrile Diseases and Miscellaneous Diseases （《伤寒杂病论》） and is mainly used to treat pain in the bones and joints and symptoms such as no flexion or extension. It has the effect of tonifying the spleen and kidney and removing dampness and turbidity， so it is widely used in the clinical treatment of various bone and joint diseases. This article reviewed the clinical research and mechanism of Gancao Fuzitang in the treatment of bone and joint diseases. The research has found that this prescription has good efficacy in treating bone and joint diseases such as rheumatoid arthritis， rheumatoid arthritis， ankylosing spondylitis， gout， and intervertebral disc herniation. Its mechanism of action may be related to regulating the level of inflammatory factors， antioxidation， and the protein expression of inflammatory and apoptotic cell-related pathways， improving bone and joint diseases， and alleviating related symptoms. This study can provide a reference for further deepening the research on the prevention and treatment of bone and joint diseases with Gancao Fuzitang.
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Diabetic retinopathy（DR） and coronary heart disease（CHD） are both major chronic vascular complications that seriously jeopardize the health of the population and often occur together in clinical practice， it is of great clinical value to actively explore the association between the two in the process of disease development and methods of prevention and treatment of modern medicine and traditional Chinese medicine（TCM）. According to TCM， the heart and eyes physiologically communicate with each other by taking Qi， blood and veins as bridges， blood stasis obstructing collaterals is the common TCM etiology of DR and CHD， whose mechanism involves inflammation， oxidative stress and endothelial dysfunction. Promoting blood circulation and removing blood stasis plays an important role in the same treatment for different diseases and prevention and treatment of comorbidities， possibly by inhibiting the expression of interleukin-1β（IL-1β）， endothelin-1（ET-1） and hypoxia inducible factor-1α/vascular endothelial growth factor（HIF-1α/VEGF）， regulating phosphatidylinositol 3-kinases/protein kinase B/mammalian target of rapamycin（PI3K/Akt/mTOR） pathway， initiating adenosine monophosphate（AMP）-activated protein kinase/silent information regulator 1（AMPK/SIRT1） and nuclear transcription factor erythroid 2-related factor 2/heme oxygenase-1（Nrf2/HO-1） signaling pathways， inhibiting Hippo/Yes-associated protein（Hippo/YAP） signaling pathway， inhibiting mitochondrial permeability transition pore and anti-platelet agglutination for treating DR and CHD， which provides a multi-component， multi-pathway and multi-target selection strategies and ideas for the prevention and treatment of DR and CHD by TCM from a biological perspective. Based on this， subsequent studies should focus on constructing clinically relevant comorbidity models， conducting multicenter prospective studies， and fully utilizing artificial intelligence technology to gain a deeper understanding of the relationship between the two diseases， so as to elucidate the mechanism of promoting blood circulation and removing blood stasis in preventing and treating panvascular diseases.
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ObjectiveThis study observes the intervention effect of Longmu Piyan prescription on oxidative stress in BALB/c mice with atopic dermatitis （AD） induced by 2，4-dinitrochlorobenzene （DNCB） and explores its mechanism. MethodThe AD model was established using the method of DNCB sensitization on the back skin of BALB/c mice. Forty male BALB/c mice were randomly divided into a blank group， a model group， a vitamin C control group （0.5×10-3 mg·kg-1）， and a Longmu Piyan prescription group （26 g·kg-1）. Except for the blank group， other groups were sensitized with different concentrations of DNCB on the back to induce AD， and the blank group was treated with matrix coating. The gastric administration was started on the seventh day after sensitization with 2% DNCB and on the 24th day after sensitization with 0.2% DNCB continuously for 21 days. The changes in skin lesions of each group were directly observed after the experiment. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of interleukin （IL）-4， tumor necrosis factor （TNF）-α， immunoglobulin E （IgE）， and reactive oxygen species （ROS） in the serum of each group. The total antioxidant capacity determination kit-trace method (ABTS method) was used to measure the level of total antioxidant capacity （TAOC） in serum. The Hematoxylin eosin （HE） staining method was used to observe the pathological and morphological changes of the skin lesion site. The immunohistochemical method was used to detect the expression of thymic stromal lymphopoietin （TSLP） in the skin lesion site. Western blot was used to detect the expression of filaggrin （FLG） in the dorsal skin lesions. ResultThe results showed that compared with the blank group， the skin lesion score of the model group mice was significantly increased （P<0.01）， and HE staining showed characteristic pathological changes of AD in the skin lesion site. At the same time， the expression of TSLP in the skin lesion was significantly increased， and that of FLG was reduced （P<0.05）. The levels of TNF-α， IL-4， IgE， and ROS in serum increased， while the activity of TAOC decreased （P<0.01）. Compared with the model group， the Longmu Piyan prescription group showed a significant decrease in skin lesion scores and a significant improvement in skin lesion pathology. At the same time， the expression of TSLP decreased， and the expression of FLG increased in the skin lesions （P<0.05）. In addition， compared with the model group， the serum levels of TNF-α， IL-4， IgE， and ROS also decreased to varying degrees （P<0.05，P<0.01）， and TAOC activity increased in the Longmu Piyan prescription group （P<0.01）. ConclusionThere is a significant correlation among the degree of oxidative stress， the severity of skin lesions in AD， and the levels of inflammatory cytokines. Longmu Piyandu prescription can improve AD-like skin lesions in BALB/c mice by promoting ROS clearance， enhancing TAOC， and inhibiting oxidative stress， thus protecting the skin barrier and reducing inflammation.
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@#Herpes simplex virus(HSV)is a ubiquitous enveloped virus containing double-stranded DNA. HSV-1 infection can cause inflammation of the lips,conjunctivitis and encephalitis,HSV-2 infection can cause genital herpes at many ages,and both viruses can establish lifelong latent infection in the body. Membrane fusion triggered by the interaction of various HSV membrane proteins is an important way for viruses to enter host cells. This review introduced the conserved core fusion mechanism of HSV composed of four viral glycoproteins gD,gH,gL and gB by analyzing the structure of glycoproteins and their interaction modes. Since there is currently no HSV vaccine approved for marketing in the world,it is of great significance to study the mode of action of HSV and host cells for the development of vaccines
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Osteoporosis （OP） is a common bone disease affecting the quality of life and causing huge medical burden to the patients and society. The occurrence of OP is mainly caused by excessive bone resorption and insufficient bone formation， which are directly influenced by external calcium ion balance. Calcium imbalance can impair bone integrity， reduce the calcium supply to the bone， and lower the calcium content in the bone， thus triggering OP. Drugs are the main anti-OP therapy in modern medicine， which， however， may cause adverse reactions and drug dependence. Chinese medicines have good clinical effects and high safety in treating OP， being suitable for long-term use. Recent studies have shown that Chinese medicines can alleviate estrogen deficiency， regulate bone cell and calcium metabolism， which is crucial for the formation and development of OP. The transient receptor potential cation channel superfamily V members 5 and 6 （TRPV5 and TRPV6， respectively） affect bone homeostasis by mediating the transmembrane calcium ion transport in the intestine （TRPV6） and kidney （TRPV5）. Therefore， TRPV5/6 is one of the key targets to understand the anti-OP mechanisms of the effective parts of Chinese medicines， which is worthy of further study. This paper summarizes the research results about the anti-OP effects of Chinese medicines in the last two decades， especially the mechanism of regulating calcium metabolism， aiming to provide new ideas for the basic research， clinical application， and drug development of OP treatment.
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Ulcerative colitis （UC） is a chronic inflammatory bowel disease with complex etiology. The pathogenesis of this disease， due to a combination of factors， is complex and has not yet been elucidated. Among them， intestinal mucosal barrier damage is the basic pathological change of UC. As a non-destructive response of cells， autophagy regulates intestinal mucosal immunity， inflammation， oxidative stress， and bacterial homeostasis through degradation and reabsorption to actively repair damaged intestinal mucosal barrier， exerting a key role in the occurrence and development of UC. The disease is mainly treated clinically with aminosalicylic acid preparations， glucocorticoids， and immunosuppressants. Western medicine treatment of the disease has a fast onset of effect， and the short-term efficacy is definite， but the long-term application is easy to be accompanied by more adverse reactions. Moreover， some drugs are expensive， bringing great physical and mental pain and economic burden to patients. Therefore， it is urgent to explore new therapies with stable efficacy and mild adverse effects. In recent years， a large number of studies have shown that Chinese medicine can regulate autophagy of the intestinal mucosa with multiple targets and effects and repair the intestinal mucosal barrier function， thereby inhibiting the development of UC. Many experiments have shown that the active ingredient or monomers and compound formulas of Chinese medicine can improve the immunity of the intestinal mucosa， inflammation， oxidative stress， and flora by regulating the level of autophagy to maintain the normal function of the intestinal mucosal barrier to effectively intervene in UC， providing a new measure for the prevention and treatment of UC. However， there is a lack of systematic review of Chinese medicine in regulating the level of autophagy in the intestinal mucosa for the prevention and treatment of UC. Therefore， based on the current research on UC， autophagy process， and Chinese medicine treatment， this article reviewed the relationship of autophagy and its key target proteins with UC to clarify the key role of autophagy in UC production and systematically summarized Chinese medicines targeting the regulation of autophagy to treat UC in recent years to provide new ideas for the treatment and drug development of UC.
ABSTRACT
Chronic obstructive pulmonary disease （COPD） is one of the most common chronic diseases of the respiratory system in the clinic. The disease has a long course and is difficult to cure， which seriously threatens human health. Airway mucus hypersecretion （AMH） is an independent risk factor for COPD and has a significant impact on the development and prognosis of the disease. The review finds that the abnormal proliferation of goblet cells and the excessive secretion of mucin are the direct causes of AMH. The pathogenesis of AMH may be closely related to the inhalation of heterogeneous particles， airway inflammation， the imbalance of mucin/water salt ratio， and the regulation of related signaling pathways. Traditional Chinese medicine （TCM） believes that AMH of COPD belongs to the category of lung distension with phlegm-fluid retention syndrome， and the disease is mainly treated from phlegm on the basis of lung distension. This article summarizes the relevant research in the field of TCM in recent years and finds that the single TCM that effectively intervened AMH of COPD is mainly phlegm-resolving TCM， and the main active ingredients of TCM are flavonoids， terpenoids， phenols， and alkaloids. The main TCM compounds are mainly designed to remove heat-phlegm， warmly resolve cold-phlegm， dry dampness to eliminate phlegm， invigorate Qi， promote blood circulation and dispel phlegm， and invigorate lung， spleen， and kidney. Its mechanism of action may be direct inhibition or indirect inhibition of airway epithelial goblet cell metaplasia and mucin expression by inhibiting airway inflammation， regulating aquaporins to correct the imbalance of mucin/water salt ratio， and regulating signaling pathways， so as to reduce mucus oversecretion in COPD. However， there are still some problems. For example， the research mainly focuses on TCM compounds instead of the single TCM or its effective components. The research on the mechanism of action is not thorough enough， and the research results are not interoperable. The clinical transformation rate of basic research is insufficient. This article systematically reviews the research status of AMH in the treatment of COPD with TCM and puts forward some thoughts on the existing problems， so as to provide a reference for clinical rational medication and in-depth research.