摘要：
Tumor vaccines, a crucial immunotherapy, have gained growing interest because of their unique capability to initiate precise anti-tumor immune responses and establish enduring immune memory. Injected tumor vaccines passively diffuse to the adjacent draining lymph nodes, where the residing antigen-presenting cells capture and present tumor antigens to T cells. This process represents the initial phase of the immune response to the tumor vaccines and constitutes a pivotal determinant of their effectiveness. Nevertheless, the granularity paradox, arising from the different requirements between the passive targeting delivery of tumor vaccines to lymph nodes and the uptake by antigen-presenting cells, diminishes the efficacy of lymph node-targeting tumor vaccines. This study addressed this challenge by employing a vaccine formulation with a tunable, controlled particle size. Manganese dioxide (MnO2) nanoparticles were synthesized, loaded with ovalbumin (OVA), and modified with A50 or T20 DNA single strands to obtain MnO2/OVA/A50 and MnO2/OVA/T20, respectively. Administering the vaccines sequentially, upon reaching the lymph nodes, the two vaccines converge and simultaneously aggregate into MnO2/OVA/A50-T20 particles through base pairing. This process enhances both vaccine uptake and antigen delivery. In vitro and in vivo studies demonstrated that, the combined vaccine, comprising MnO2/OVA/A50 and MnO2/OVA/T20, exhibited robust immunization effects and remarkable anti-tumor efficacy in the melanoma animal models. The strategy of controlling tumor vaccine size and consequently improving tumor antigen presentation efficiency and vaccine efficacy via the DNA base-pairing principle, provides novel concepts for the development of efficient tumor vaccines.
摘要：
Hyperuricemia is a metabolic disease characterized by elevated blood uric acid,clinically most patients are in asymptomatic sub-healthy state,a few people can be caused by urate deposition in the joints or kidneys causing gout.According to TCM,hyperuricemia can be attributed to the category of Xuezhuo(血浊),which is evidence of deficiency and solidity,and the core pathology is the malfunction of the spleen and stomach in elevating and lowering the turbidity,and the blockage of veins by phlegm,dampness,stasis and turbidity,and the accumulation of turbidity and toxins within the body.Clinical treatment is based on the basic idea of solidifying the root of the disease,eliminating evils and restoring normal lifting and lowering,and the basic rule of ascending clearness and lowering turbidity and facilitating the flow of Qi(气)is to solidify and protect the spleen and stomach,and to restore the function of ascending clearness and lowering turbidity,which will be carried out throughout the treatment.At the same time,the treatment is staged at different stages of the onset of hyperuricemia,with flexible addition and subtraction of drugs.In the asymptomatic stage,it is used to transport the spleen and eliminate dampness,focusing on Qi.In the acute stage,it is used to clear away heat and relieve dampness,remove blood stasis and drain turbidity.In the chronic stage,it is used to strengthen the spleen and tonify the kidneys,and eliminate blood stasis and clear the channels.In clinical diagnosis and treatment,sweet,bitter and pungent flavors of medicines are used,and the attributing meridian is based on the spleen and stomach,so as to elevate clearness and lower turbidity,and to regulate Qi and blood,with special emphasis on restoring the body's Qi to be smooth,eliminating blood stasis and seeping away dampness and directing the drainage of turbid evils,strengthening the spleen and tonifying the kidneys,and regulating the five viscera.The combination of disease identification and evidence identification,tonifying the spleen and stomach,and restoring its elevation are the main focuses of the prescription and medication,especially in strengthening the spleen and stomach,restoring the spleen and stomach pivotal function,ascending the clear Yang(阳)and descending the turbid Yin(阴),and making use of Tufuling(Rhizoma Smilacis Glabrae)-Bixie(Rhizoma Dioscoreae Hypoglaucae),Yiyiren(Semen Coicis)-Cangzhu(Rhizoma Atractylodis),Heye(Folium Nelumbinis)-Shanzha(Fructus Crataegi),Cheqiancao(Herba Plantaginis)-Yumixu(Stigma Maydis),Chuanxiong(Rhizoma Chuanxiong)-Danshen(Radix et Rhizoma Salviae Miltiorrhizae)pairs of drugs,which embodies the characteristics of solidifying the root of the body to eliminate the evils,elevating and descending the same cause,and taking into consideration the characteristics of the medicines of Qi and blood,so as to enable the Qi and energy to flow smoothly,and to raise the turbidity and lower the turbidity and blood to restore its state of purity and purity is restored.The author found in the clinic that it showed good efficacy in reducing patients'blood uric acid and improving symptoms.
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Anxiety disorders leads to a decline in quality of life and increased risk of morbidity and mortality. The Baihe Dihuang decoction (BDD) is a classic Chinese medical formula that has been widely used to treat anxiety disorders for thousands of years in China. However, the pharmacodynamic material that is responsible for the antianxiety of BDD remains unclear. AIM OF THE STUDY: To screen the main ingredients of anti-anxiety in BDD based on the establishment of spectrum-effect relationship and verified experiment. METHODS: The UPLC-Q-TOF/MS technique was utilized to establish fingerprints of various fractions of BDD and identify the main compounds. The anti-anxiety effects of BDD were comprehensively evaluated through multiple assessments, including the open field test, elevated plus maze test, and neurotransmitters tests. Then, the spectrum-effect relationship was established through Pearson correlation analysis, gray correlation analysis, orthogonal partial least squares regression analysis. The spectrum-effect relationship results were confirmed through various measures on an anxiety condition cell model, induced by a corticosterone and lipopolysaccharide intervention. These measures included assessing neuronal cell viability, morphology, apoptosis, synaptic damage, and the expression of neurotransmitters and inflammatory factors. RESULTS: In the UPLC-Q-TOF-MS fingerprint, 46 common peaks were identified. The pharmacological results indicated that different fractions of BDD have strong effects on improving anxiety-like behavior and regulating neurotransmitters. Among them, butanol fraction has the highest comprehensive evaluation score of anti-anxiety efficacy, which is main active fraction of BDD for anti-anxiety. The analysis of the spectrum-effect relationship revealed that the 46 peaks exhibited varying degrees of correlation with the anti-anxiety efficacy indicators of BDD. Among them, 14 components have a high correlation with the anti-anxiety efficacy indicators, which may be the potential anti-anxiety efficacy components of BDD. The in vitro activity verification of active components verified our prediction, regaloside A, B, C, D, H, acteoside, and isoacteoside improved neuronal cell viability, cell morphology, apoptosis, and synaptic damage. Additionally, regaloside A, B, C, D, H and acteoside regulated the neurotransmitter levels, while regaloside A, B, C, D, acteoside and isoacteoside inhibited the levels of inflammatory cytokines. CONCLUSION: The butanol fraction was found to be the main active fraction of BDD, and 14 compounds were the major anxiolytic active components. The results of verifying the major active components were consistent with the predicted results of the spectrum-effect analysis. The developed spectrum-effect analysis in this study demonstrates high accuracy and reliability for screening active components in TCMs.
摘要：
BACKGROUND: Diabetes mellitus (DM) is frequently associated with the occurrence and development of depression, and the co-occurrence of diabetes mellitus with depression (DD) may further reduce patients' quality of life. Recent research indicates that dopamine receptors (DRs) play a crucial role in immune and metabolic regulation. Pramipexole (PPX), a D2/3R agonist, has demonstrated promising neuroprotective and immunomodulatory effects. Nevertheless, the therapeutic effects and mechanisms of action of PPX on DM-induced depression are not clear at present. METHODS: Depression, DM, and DD were induced in a rat model through a combination of a high-fat diet (HFD) supplemented with streptozotocin (STZ) and chronic unpredictable mild stress (CUMS) combined with solitary cage rearing. The pathogenesis of DD and the neuroprotective effects of DRs agonists were investigated using behavioral assays, enzyme-linked immunosorbent assay (ELISA), hematoxylin-eosin (HE) staining, Nissl staining, Western blotting (WB) and immunofluorescence (IF). RESULTS: DD rats exhibited more severe dopaminergic, neuroinflammatory, and neuroplastic impairments and more pronounced depressive behaviors than rats with depression alone or DM. Our findings suggest that DRs agonists have significant therapeutic effects on DD rats and that PPX improved neuroplasticity and decreased neuroinflammation in the hippocampus of DD rats while also promoting DG cell growth and differentiation, ultimately mitigating depression-like behaviors. LIMITATION: Our study is based on a rat model. Further evidence is needed to determine whether the therapeutic effects of PPX apply to patients suffering from DD. CONCLUSIONS: Neuroinflammation mediated by damage to the dopaminergic system is one of the key pathogenic mechanisms of DD. We provide evidence that PPX has a neuroprotective effect on the hippocampus in DD rats and the mechanism may involve the inhibition of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation by DRs to attenuate the neuroinflammatory response and neuroplasticity damage.
摘要：
Sepsis-associated encephalopathy (SAE) is the main cause of cognitive impairment in patients with sepsis. The infiltration of inflammatory signals into the central nervous system (CNS) via the compromised blood-brain barrier (BBB) represents a crucial step in the pathological progression of SAE. In particular, T-helper 17 cell (Th17 cells) has been suggested to be highly correlated with the activation of central immune responses. Thus, preventing Th17 cell infiltration into the CNS may be a possible strategy to alleviate cognitive decline in SAE. Dipsacoside B (DB) is one of the primary active components in Chuan Xu Duan (Dipsacus asper Wall). We speculate that DB may be a potential candidate for the treatment of SAE-related cognitive deficits. In the present study, we demonstrated that DB could effectively alleviate cognitive impairment in SAE mice. DB significantly suppressed the central inflammatory response induced by repeated lipopolysaccharide (LPS) injection. The mechanism underlying its therapeutic effect should be attributed to the reduction of BBB impairment and pathogenic Th17 cell infiltration into the CNS by inhibition of vascular endothelial growth factor A (VEGFA)/ Vascular endothelial growth factor receptor 2(VEGFR2)/ Endothelial nitric oxide synthase (eNOS) signaling. Our findings suggest that DB is a potential candidate for the treatment of SAE-related cognitive dysfunction.
通讯机构：
[Lin, LM ] H;Hunan Univ Chinese Med, Coll Pharm, Changsha 410208, Peoples R China.
关键词：
Acute mastitis;Blood-milk barrier;Lipopolysaccharides;Prunella vulgaris L.
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: According to ancient literature, Prunella vulgaris L. (P vulgaris) alleviates mastitis and has been used in China for many years; however, there are no relevant reports that confirm this or the mechanism of its efficacy. AIM OF THE STUDY: To explore the anti-acute mastitis effect and potential mechanism of P vulgaris extract. MATERIALS AND METHODS: First, the active ingredients and targets of P vulgaris against mastitis were predicted using network pharmacology. Next, the relevant active ingredients were enriched using macroporous resins and verified using UV and UPLC-Q-TOF-MS/MS. Lastly, a mouse model of acute mastitis was established by injecting lipopolysaccharides into the mammary gland and administering P vulgaris extract by oral gavage. The pathological changes in mammary tissue were observed by HE staining. Serum and tissue inflammatory factors were measured by ELISA method. MPO activity in mammary tissue was measured using colorimetry and MPO expression was detected by immunohistochemistry. The expression of tight junction proteins (ZO-1, claudin-3, and occludin) in mammary tissue was detected by immunofluorescence and Western blot. iNOS and COX-2 in mammary tissue were detected by Western blot. MAPK pathway and NF-κB pathway related proteins were also detected by Western blot. RESULTS: Network pharmacology predicted that phenolic acids and flavonoids in P vulgaris had anti-mastitis effects. The contents of total flavonoids and total phenolic acids in P vulgaris extract were 64.5% and 29.4%, respectively. UPLC-Q-TOF-MS/MS confirmed that P vulgaris extract contained phenolic acids and flavonoids. The results of animal experiments showed that P vulgaris extract reduced lipopolysaccharide-induced inflammatory edema, inflammatory cell infiltration, and interstitial congestion of mammary tissue. It also reduced the levels of serum and tissue inflammatory factors TNF-α, IL-6, and IL-1β, and inhibited the activation of MPO. Furthermore, it downregulated the expression of MAPK and NF-κB pathway-related proteins. The expressions of ZO-1, occludin, and claudin-3 in mammary gland tissues were upregulated. CONCLUSIONS: P vulgaris extract can maintain the integrity of mammary connective tissue and reduce its inflammatory response to prevent acute mastitis. Its mechanism probably involves regulating NF-κB and MAPK pathways.
期刊：
BALKAN MEDICAL JOURNAL,2024年41(2):130-138 ISSN：2146-3123
通讯作者：
Peng, Wei;Zeng, PH
作者机构：
[Yang, Renyi; Zeng, Puhua; Chen, Hongyao; Li, Kexiong; Yu, Xiaopeng; Peng, Wei; Peng, W] Hunan Acad Chinese Med, Hunan Acad Tradit Chinese Med, Canc Res Inst, Hunan Prov Hosp Integrated Tradit Chinese & Weste, Changsha, Hunan, Peoples R China.;[Yang, Renyi; Chen, Hongyao; Xue, Peisen] Hunan Univ Chinese Med, Changsha, Hunan, Peoples R China.
通讯机构：
[Zeng, PH ; Peng, W] H;Hunan Acad Chinese Med, Hunan Acad Tradit Chinese Med, Canc Res Inst, Hunan Prov Hosp Integrated Tradit Chinese & Weste, Changsha, Hunan, Peoples R China.
摘要：
BACKGROUND: The changes in risk scores of inflammatory markers among patients diagnosed with hepatocellular carcinoma (HCC) remain unknown. AIMS: To investigate the relationship between the inflammation risk score and other contributing factors and the prognostic outcomes in patients with moderate and advanced hepatitis B virus (HBV)-related HCC. STUDY DESIGN: A retrospective cohort study. METHODS: A total of 174 patients with moderate and advanced HBV related HCC were recruited to investigate the impact of stratified inflammatory risk scores and other associated risk factors on disease prognosis. Based on the optimal cut-off values calculated by the Youden index, the patients were divided into high-risk and low-risk groups based on their inflammation risk scores. RESULTS: The study found a significant difference in median survival time between the low-risk and high-risk groups based on the inflammation risk score. Furthermore, the inflammation risk score, alpha-fetoprotein levels, transarterial chemoembolization treatment, and Barcelona Clinic Liver Cancer stage were identified as independent prognostic factors. The four variables were used to construct a prognostic nomogram for HCC. Subsequent evaluations using time-dependent receiver operating characteristic analysis and calibration curve tests revealed the nomogram's commendable discriminatory ability. As a result, the nomogram proved to be an effective tool for predicting survival at 2- to 4-years. CONCLUSION: The inflammation risk score has been identified as a significant prognostic factor for HBV-related HCC. The development of nomogram models has provided a practical and effective tool for determining the prognosis of patients affected by HBV-related HCC.
作者机构：
[Zeng, Puhua; Zhang, Jingting; Li, Kexiong; Peng, Wei] Hunan Acad Tradit Chinese Med, Affiliated Hosp, Changsha 410006, Hunan, Peoples R China.;[Yang, Renyi; Chen, Hongyao; Yang, RY] Hunan Univ Chinese Med, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Zeng, PH ; Yang, RY ] H;Hunan Acad Tradit Chinese Med, Affiliated Hosp, Changsha 410006, Hunan, Peoples R China.;Hunan Univ Chinese Med, Changsha 410208, Hunan, Peoples R China.
关键词：
Hepatocellular carcinoma;nomogram;prognostic model;Traditional Chinese medicine;natural herbs
摘要：
<jats:sec><jats:title>Objective</jats:title><jats:p> This study aimed to screen and identify central genes associated with the progression of non-alcoholic fatty liver disease (NAFLD) to hepatocellular carcinoma (HCC), to establish prognostic and clinical prediction models based on the expression of these genes, and to evaluate the intervention of a traditional Chinese medicine (TCM) formula—SPXJF—on the development of NAFLD into HCC through network pharmacology analysis and in vitro and in vivo validation. </jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p> Datasets for analysis were retrieved from multiple public databases using bioinformatics techniques. Through network pharmacology analysis, SPXJF's active components and their related targets were assessed, while in vitro experiments validated the inhibitory effects of SPXJF on the growth and migration of HepG2 cells. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> The results revealed that the expression levels of the two central genes, regulator of cell cycle gene (RGCC) and atypical chemokine receptor 3 (ACKR3), were closely tied to the survival prognosis of HCC patients. Furthermore, SPXJF significantly inhibited the proliferation and migration of HepG2 cells. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> RGCC and ACKR3, as hub genes, significantly influence HCC patient survival during “NAFLD-HCC” progression. The risk scoring system and prediction model perform well. In vitro experiments showed that SPXJF could inhibit the proliferation and invasion of hepG2 cells. These findings support the discovery of molecular targets for early diagnosis and drug intervention in HCC. They also underscore TCM's potential in anti-HCC strategies and clinical application. </jats:p></jats:sec>
摘要：
Anelectrochemical aptasensor was used for the fast and sensitive detection of zearalenone (ZEN) based on the combination of Co(3)O(4)/MoS(2)/Au nanocomposites and the hybrid chain reaction (HCR). The glassy carbon electrode was coated with Co(3)O(4)/MoS(2)/Au nanomaterials to immobilize the ZEN-cDNA that had been bound with ZEN-Apt by the principle of base complementary pairing. In the absence of ZEN, the HCR could not be triggered because the ZEN-cDNA could not be exposed. After ZEN was added to the surface of the electrode, a complex structure was produced on the modified electrode by the combination of ZEN and ZEN-Apt. Therefore, the ZEN-cDNA can raise the HCR to produce the long-strand dsDNA structure. Due to the formation of dsDNA, the methylene blue (MB) could be inserted into the superstructure of branched DNA and the peak currents of the MB redox signal dramatically increased. So the concentration of ZEN could be detected by the change of signal intensity. Under optimized conditions, the developed electrochemical biosensing strategy showed an outstanding linear detection range of 1.0×10(-10) mol/L to 1.0×10(-6) mol/L, a low detection limit (LOD) of 8.5×10(-11) mol/L with desirable selectivity and stability. Therefore, the fabricated platform possessed a great application potential in fields of food safety, medical detection, and drug analysis.
作者机构：
[Zhou, Tongyi; Yang, Shiyao; Liu, Xiu; Li, Hong; Zou, Junju; Li, Liu; Zhou, Min; Yu, Rong; Xiang, Qin; Huang, Qiuqing] School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;[Zhou, Tongyi; Yang, Shiyao; Liu, Xiu; Li, Hong; Zou, Junju; Li, Liu; Zhou, Min; Xiang, Qin; Huang, Qiuqing] Hunan Key Laboratory of Traditional Chinese Medicine Prescription and Syndromes Translational Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;[Yu, Rong] Hunan Key Laboratory of Traditional Chinese Medicine Prescription and Syndromes Translational Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China. Electronic address: yurong8072@qq.com
关键词：
Astragaloside IV;Diabetic nephropathy;Mitochondrial dysfunction;Oxidative stress;Phenyl sulfate;Reactive oxygen species
摘要：
Astragaloside IV (AS-IV) exhibits diverse biological activities. Despite this, the detailed molecular mechanisms by which AS-IV ameliorates diabetic nephropathy (DN) and shields podocytes from oxidative stress (OS) and mitochondrial dysfunction remain poorly understood. In this study, we used biochemical assays, histopathological analysis, Doppler ultrasound, transmission electron microscopy，flow cytometry, fluorescence staining, and Western blotting and other methods. AS-IV was administered to db/db mice for in vivo experimentation. Our findings indicated that AS-IV treatment significantly reduced diabetes-associated markers, proteinuria, and kidney damage. It also diminished ROS levels in the kidney, enhanced the expression of endogenous antioxidant enzymes, and improved mitochondrial health. Phenyl sulfate (PS), a protein-bound uremic solute of enteric origin, has been closely linked with DN and represents a promising avenue for further research. In vitro, PS exposure induced OS and mitochondrial dysfunction in podocytes, increasing ROS levels while decreasing antioxidant enzyme activity (Catalase, Heme Oxygenase-1, Superoxide Dismutase, and Glutathione Peroxidase). ROS inhibitors (N-acetyl-L-cysteine, NAC) as the positive control group can significantly reduce the levels of ROS and restore antioxidant enzymes protein levels. Additionally, PS reduced markers associated with mitochondrial biosynthesis and function (SIRT1, PGC1α, Nrf1, and TFAM). These adverse effects were partially reversed by AS-IV treatment. However, co-treatment with AS-IV and the SIRT1 inhibitor EX527 failed to restore these indicators. Overall, our study demonstrates that AS-IV effectively attenuates DN and mitigates PS-induced OS and mitochondrial dysfunction in podocytes via the SIRT1/PGC1α/Nrf1 pathway.
