通讯机构：
[Liu, HY; Zuo, YJ ] H;Hunan Univ Chinese Med, Dept Pharm, Hosp 1, Changsha, Peoples R China.
关键词：
4-hydroxylonchocarpin;Corylifol A;Hepatotoxicity;Network analysis;Oxidative stress;Psoralea corylifolia L.
摘要：
Psoralea corylifolia L. (P. corylifolia) has attracted increasing attention because of its potential hepatotoxicity. In this study, we used network analysis (toxic component and hepatotoxic target prediction, proteinprotein interaction, GO enrichment analysis, KEGG pathway analysis, and molecular docking) to predict the components and mechanism of P. corylifolia-induced hepatotoxicity and then selected 4-hydroxylonchocarpin and corylifol A for experimental verification. HepG2 cells were treated with low, medium, and high concentrations of 4-hydroxylonchocarpin or corylifol A. The activities of ALT, AST, and LDH in cell culture media and the MDA level, SOD activity, and GSH level in cell extracts were measured. Moreover, apoptosis, ROS levels, and mitochondrial membrane potential were evaluated. The results showed that the activities of ALT, AST, and LDH in the culture medium increased, and hepatocyte apoptosis increased. The level of MDA increased, and the activity of SOD and level of GSH decreased, and the ROS level increased with 4-hydroxylonchocarpin and corylifol A intervention. Furthermore, the mitochondrial membrane potential decreased in the 4-hydroxylonchocarpin and corylifol A groups. This study suggests that 4-hydroxylonchocarpin and corylifol A cause hepatocyte injury and apoptosis by inducing oxidative stress and mitochondrial dysfunction, suggesting that these compounds may be the potential hepatotoxic components of P. corylifolia.
作者机构：
[Bai, Yuxin; Wang, Wei; Guo, De-an] Changchun Univ Chinese Med, Coll Pharmaceut Sci, Changchun 130117, Peoples R China.;[Guo, De-an; Wei, Wenlong; Yao, Changliang; Wu, Shifei] Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Res Ctr Modernizat Tradit Chinese Med, Natl Engn Res Ctr TCM Standardizat Technol, Shanghai 201203, Peoples R China.;[Wang, Wei] Hunan Univ Chinese Med, Innovat Mat Med Res Inst, Sch Pharm, TCM & Ethnomed Innovat & Dev Int Lab, Changsha 410208, Peoples R China.
通讯机构：
[De-an Guo] C;College of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun 130117, China<&wdkj&>Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
关键词：
Chemical constituent;Clinical application;Pharmacology;TCM formula;Yupingfeng san
摘要：
Yupingfeng San (YPFS) is a famous and commonly used traditional Chinese medicine (TCM) formula for the treatment of chronic obstructive pulmonary disease, asthma, respiratory tract infections, and pneumonia in China. It is composed of three Chinese herbs, including Astragali Radix, Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix. In this review, the relevant references on YPFS were searched in the Web of Science, PubMed, China National Knowledge Infrastructure (CNKI), and other databases. Literatures published from 2000 to 2022 were screened and summarized. The constituents in YPFS could be classified into nine groups according to their structures, including flavonoids, saponins, essential oils, coumarins, lactones, amino acids, organic acids, saccharides, chromones and others. The importance of chemical constituents in YPFS were demonstrated for specific pathological processes including immunoregulatory, anti-inflammatory, anti-tumor and pulmonary diseases. This article systematically reviewed the up-to-date information on its chemical compositions, pharmacology and safety, that could be used as essential data and reference for clinical applications of YPFS.
摘要：
Cardiovascular diseases (CVDs) continue to exert a significant impact on global mortality rates, encompassing conditions like pulmonary arterial hypertension (PAH), atherosclerosis (AS), and myocardial infarction (MI). Oxidative stress (OS) plays a crucial role in the pathogenesis and advancement of CVDs, highlighting its significance as a contributing factor. Maintaining an equilibrium between reactive oxygen species (ROS) and antioxidant systems not only aids in mitigating oxidative stress but also confers protective benefits on cardiac health. Herbal monomers can inhibit OS in CVDs by activating multiple signaling pathways, such as increasing the activity of endogenous antioxidant systems and decreasing the level of ROS expression. Given the actions of herbal monomers to significantly protect the normal function of the heart and reduce the damage caused by OS to the organism. Hence, it is imperative to recognize the significance of herbal monomers as prospective therapeutic interventions for mitigating oxidative damage in CVDs. This paper aims to comprehensively review the origins and mechanisms underlying OS, elucidate the intricate association between CVDs and OS, and explore the therapeutic potential of antioxidant treatment utilizing herbal monomers. Furthermore, particular emphasis will be placed on examining the cardioprotective effects of herbal monomers by evaluating their impact on cardiac signaling pathways subsequent to treatment.
摘要：
High level of intracellular glutathione (GSH) has been identified as a major barrier for cancer therapy. Therefore, effective regulation of GSH can be regarded as a novel approach for cancer therapy. In this study, an off-on fluorescent probe (NBD-P) is developed for selective and sensitive sensing GSH. NBD-P has a good cell membrane permeability that can be applied in bioimaging endogenous GSH in living cells. Moreover, the NBD-P probe is used to visualize GSH in animal models. In addition, a rapid drug screening method is successfully established using the fluorescent probe NBD-P. A potent natural inhibitor of GSH is identified as Celastrol from Tripterygium wilfordii Hook F, which effectively triggers mitochondrial apoptosis in clear cell renal cell carcinoma (ccRCC). More importantly, NBD-P can selectively respond to GSH fluctuations to distinguish cancer tissues from normal tissues. Thus, the present study provides insights into fluorescence probes for the screening GSH inhibitors and cancer diagnosis, as well as in-depth exploration of the anti-cancer effects of Traditional Chinese Medicine (TCM).
作者机构：
[Lei, Chang; Huang, Dan; Xiang, Yun; Zhou, Wei; Hu, Ge] Hunan Univ Chinese Med, Sci & Technol Innovat Ctr, State Key Lab Chinese Med Powder & Med Innovat Hun, Changsha 410208, Peoples R China.;[Li, Y; Li, Ya] Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Peoples R China.
通讯机构：
[Li, Y ; Huang, D ] H;Hunan Univ Chinese Med, Sci & Technol Innovat Ctr, State Key Lab Chinese Med Powder & Med Innovat Hun, Changsha 410208, Peoples R China.;Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Peoples R China.
摘要：
In recent years, as the desire for a healthy lifestyle has become more widespread, consumers are gaining an increasing appreciation for safe, high-quality food. Researchers are constantly seeking new ways to protect foods from insect pests and fungi. This study used GC-IMS to analyze the volatile organic compounds and flavor characteristics of Finger Citron in response to different doses of Co-60 irradiation. The principal component analysis method was used to explore the overall differences in flavor spectra, and a total of 60 compounds were identified. The fingerprints of volatile organic compounds in the samples showed that the volatile organic compounds with doses of Co-60 irradiation in about 0 kGy and 5 kGy are similar, while the 10 kGy samples are quite different. The PCA results showed that the similarity between 0 kGy and 5 kGy was slightly higher, and the difference between 10 kGy and other samples was greater. Therefore, it was determined that Co-60 irradiation with a 10 kGy intensity has a significant influence on the content of volatile oils components, while Co-60 irradiation with a 5 kGy intensity has little effect. Irradiation technology is demonstrated as a promising method of food sterilization, but the irradiation dose and chemical composition must be taken into consideration.
摘要：
Background: Psoralidin (PL) could affect the differentiation of bone marrow mesenchymal stem cells (BMSCs). The role of PL is still unclear in adipose-derived stem cells (ADSCs). Aims: This study aimed to investigate the effects of PL on ADSCs differentiation into nucleus pulposus-like cells and the TGF-beta/Smad signaling pathway. Methods: The proliferation and apoptosis of ADSCs were detected. The nucleus pulposus cell-related markers (CD24, BASP1, KRT19, and Aggrecan) and TGF-beta/Smad signaling pathway indexes were analyzed. Results: The results showed that compared to the control group, the cell activity was increased in the PL group, and the apoptosis rate was decreased. The mRNA and protein levels of nucleus pulposus cells markers (CD24, BASP1, KRT19, Aggrecan, and Collagen Type II) and TGF-beta/Smad signaling pathway-related indexes (TGF-beta, SMAD2, and SMAD3) were increased in PL group. After treatment with PL and TGF-beta silencing, the TGF- beta/Smad signaling pathway-related indicators (TGF-beta, SMAD2, and SMAD3) and nucleus pulposus cells markers (CD24, BASP1, KRT19, Aggrecan, and Collagen Type II) were found to be higher in the sh-TGF-beta +PL group than in the sh-TGF-beta group. Conclusion: In conclusion, our study showed that PL might induce the differentiation of ADSCs to nucleus pulposus cells through the TGF-beta/Smad signaling pathway. It might have the potential application value in the treatment of intervertebral disc degeneration.
作者机构：
[Wu, Zixuan; Xia, Xinhua; Yang, J; Xia, XH; Yang, Jing] Hunan Univ Chinese Med, Sch Pharm, Changsha, Peoples R China.;[Gu, Zhenchang; Li, Xiaohuan] Guangzhou Univ Chinese Med, Affiliated Hosp 2, Guangzhou, Peoples R China.
通讯机构：
[Yang, J ; Xia, XH] H;Hunan Univ Chinese Med, Sch Pharm, Changsha, Peoples R China.
关键词：
BLCA;PyMGs;Immunity, m 6 A and immune checkpoint;Drug prediction;CNV;SNP
摘要：
Background Bladder cancer (BLCA) is a common urinary system malignancy with a significant morbidity and death rate worldwide. Non-muscle invasive BLCA accounts for over 75% of all BLCA cases. The imbalance of tumor metabolic pathways is associated with tumor formation and proliferation. Pyrimidine metabolism (PyM) is a complex enzyme network that incorporates nucleoside salvage, de novo nucleotide synthesis, and catalytic pyrimidine degradation. Metabolic reprogramming is linked to clinical prognosis in several types of cancer. However, the role of pyrimidine metabolism Genes (PyMGs) in the BLCA-fighting process remains poorly understood.Methods Predictive PyMGs were quantified in BLCA samples from the TCGA and GEO datasets. TCGA and GEO provided information on stemness indices (mRNAsi), gene mutations, CNV, TMB, and corresponding clinical features. The prediction model was built using Lasso regression. Co-expression analysis was conducted to investigate the relationship between gene expression and PyM.Results PyMGs were overexpressed in the high-risk sample in the absence of other clinical symptoms, demonstrating their predictive potential for BLCA outcome. Immunological and tumor-related pathways were identified in the high-risk group by GSWA. Immune function and m6a gene expression varied significantly between the risk groups. In BLCA patients, DSG1, C6orf15, SOST, SPRR2A, SERPINB7, MYBPH, and KRT1 may participate in the oncology process. Immunological function and m6a gene expression differed significantly between the two groups. The prognostic model, CNVs, single nucleotide polymorphism (SNP), and drug sensitivity all showed significant gene connections.Conclusions BLCA-associated PyMGs are available to provide guidance in the prognostic and immunological setting and give evidence for the formulation of PyM-related molecularly targeted treatments. PyMGs and their interactions with immune cells in BLCA may serve as therapeutic targets.
摘要：
Lotus (Nelumbo) leaves are rich in polyphenols and dietary fiber, which have the potential as a high-quality fiber material in functional food. However, lotus leaves exhibit dense structure and poor taste, it is vital to develop appropriate modification methods to improve the properties of lotus leaves dietary fiber. In this study, the effects of three modification methods with shear emulsifying (SE), ball milling (BM), and autoclave treatment (AT) on structure, physicochemical properties, phenolic compounds, and antioxidant capacity of lotus leave dietary fiber (LDF) were evaluated. SEM indicated that there were significant differences in the microstructure of modified LDFs. FT-IR spectra and X-ray diffraction pattern of modified LDFs revealed similar shapes, while the peak intensity and crystalline region changed by modification. SE showed the greatest effect on crystallization index. SE-LDF had the highest water holding capacity, water swelling capacity, and bound phenolic content in LDFs, which increased by 15.69, 12.02, and 31.81%, respectively, compared with the unmodified LDF. BM exhibited the most dramatic effect on particle size. BM-LDF had the highest free phenolic and total phenolic contents in LDFs, which increased by 32.20 and 29.05% respectively, compared with the unmodified LDF. Phenolic compounds in LDFs were mainly free phenolic, and modifications altered the concents of flavonoids. The BM-LDF and SE-LDF exhibited higher antioxidant capacity than that of AT-LDF. Overall, SE-LDF showed better physical properties, and BM-LDF showed better bioactive components. SE and BM were considered to be appropriate modification methods to enhance the properties of LDF with their own advantages.
摘要：
Ginsenoside Rg1, a traditional Chinese medicine monomer, has been shown to have antidepressant effects. We previously found that Rg1 exerts antidepressant effects by improving the gap junction channels (GJCs) dysfunction; however, the downstream mechanisms through which Rg1 ameliorates GJC dysfunction remain unclear. Since hemichannels directly release glutamate, GJC dysfunction decreases the expression levels of glutamate transporters in astrocytes, and glutamatergic system dysfunction plays an essential role in the pathogenesis of depression. The glutamatergic system may be a potential downstream target of Rg1 that exerts antidepressant effects. Therefore, in this study, we aimed to determine the downstream mechanisms by which Rg1 ameliorated GJC dysfunction and exerted its antidepressant effects. Corticosterone (CORT) is used to mimic high glucocorticoid levels in patients with depression in vitro. Primary cortical astrocytes were isolated and phosphorylation of connexin43 (Cx43) as well as the functions of hemichannels, GJCs, and the glutamatergic system were evaluated after drug treatment. Rg1 pretreatment reversed the anomalous activation of Cx43 phosphorylation as well as the dysfunction of hemichannels, GJCs, and the glutamatergic system induced by CORT. These results suggest that Rg1 can ameliorate CORT-induced dysfunction of the glutamatergic system in astrocytes by potentially reducing Cx43 phosphorylation and inhibiting opening of hemichannels, thereby improving GJC dysfunction.
作者机构：
[Yin, Lu; Lei, Chang; Huang, Dan; Wan, Hongyan; Li, Shunxiang; Zhou, Wei; He, Ye] Hunan Univ Chinese Med, Sci & Technol Innovat Ctr, State Key Lab Chinese Med Powder & Med Innovat Hun, Changsha 410208, Peoples R China.;[Yin, Lu; Huang, Dan; Wan, Hongyan; Li, Shunxiang; He, Ye] Hunan Univ Chinese Med, Hunan Engn Technol Res Ctr Bioact Subst Discovery, Sch Pharm, Changsha 410208, Peoples R China.;[Huang, Dan; Li, Shunxiang] Hunan Prov Sino US Int Joint Res Ctr Therapeut Dru, Changsha 410208, Peoples R China.
通讯机构：
[Huang, D ; Li, SX] H;Hunan Univ Chinese Med, Sci & Technol Innovat Ctr, State Key Lab Chinese Med Powder & Med Innovat Hun, Changsha 410208, Peoples R China.;Hunan Univ Chinese Med, Hunan Engn Technol Res Ctr Bioact Subst Discovery, Sch Pharm, Changsha 410208, Peoples R China.;Hunan Prov Sino US Int Joint Res Ctr Therapeut Dru, Changsha 410208, Peoples R China.
摘要：
Brain disorders such as neurodegenerative diseases and neuropsychiatric diseases have become serious threatens to human health and quality of life. Oleanolic acid (OA) and ursolic acid (UA) are pentacyclic triterpenoid isomers widely distributed in various plant foods and Chinese herbal medicines. Accumulating evidence indicates that OA and UA exhibit neuroprotective effects on multiple brain disorders. Therefore, this paper reviews researches of OA and UA on neurodegenerative diseases, neuropsychiatric diseases and other brain disorders including ischemic stroke, epilepsy, etc, as well as the potential underlying molecular mechanisms. [GRAPHICS]
摘要：
Ampelopsis grossedentata is a valuable medicinal and edible plant, which is often used as a traditional tea by the Tujia people in China. A. grossedentata has numerous biological activities and is now widely used in the pharmaceutical and food industries. In this study, two new flavonoids (1-2) and seventeen known compounds (3-19) were isolated and identified from the dried stems and leaves of A. grossedentata. These isolated compounds were characterized by various spectroscopic data including mass spectrometry and nuclear magnetic resonance spectroscopy. All isolates were assessed for their alpha-glucosidase inhibitory, antioxidant, and hepatoprotective activities, and their structure-activity relationships were further discussed. The results indicated that compound 1 exhibited effective inhibitory activity against alpha-glucosidase, with an IC50 value of 0.21 mu M. In addition, compounds 1-2 demonstrated not only potent antioxidant activities but also superior hepatoprotective properties. The findings of this study could serve as a reference for the development of A. grossedentata-derived products or drugs aimed at realizing their antidiabetic, antioxidant, and hepatoprotective functions.
作者机构：
[Li, Li; Yuan, Zhiying; Huang, Shiyi; Huang, Chencun; Xu, Guangming; Zhao, Yuan] Hunan Univ Chinese Med, Coll Pharm, Changsha, Hunan, Peoples R China.;[Xu, Guangming] Hunan Univ Chinese Med, Coll Pharm, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Guangming Xu] C;College of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, China
关键词：
affinity ultrafiltration mass spectrometry (AUF-MS);Ligusticum chuanxiong;molecular docking;screening of active compounds;thrombin
摘要：
INTRODUCTION: Ligusticum chuanxiong ('chuanxiong') is a traditional Chinese medicine for promoting blood circulation and removing blood stasis, which is often used to treat thrombotic diseases. However, its potential anticoagulant active ingredients have been unexplored. OBJECTIVES: The study aims to establish an affinity ultrafiltration mass spectrometry (AUF-MS) method for rapid screening of anti-thrombin active components of chuanxiong and to verify it in vitro. METHOD: In this study, the chemical constituents of different parts of chuanxiong were determined. A method for rapid screening of anticoagulant active ingredients by AUF-MS was established using thrombin as an affinity receptor target. Subsequently, the anticoagulant effect of such ligands was verified by in vitro anticoagulation experiments such as chromogenic substrate method and in vitro coagulation assay. Then the possible interaction mechanism between these ligands and thrombin was further studied by molecular docking. RESULTS: Twenty-one components were detected from different parts of chuanxiong. And three potential anti-thrombin active components were screened: ferulic acid, chlorogenic acid, isochlorogenic acid A by AUF coupled with high-performance liquid chromatography-quadrupole-Orbitrap mass spectrometry (HPLC-Q-Orbitrap-MS(n) ). The in vitro activity experiments and molecular docking revealed that these potential ligands exhibited strong binding ability and inhibitory activities on thrombin. CONCLUSION: The present study revealed that chuanxiong is a traditional Chinese medicine with excellent anticoagulation effects. Meanwhile, the integrated strategy based on AUF-MS, in vitro experiments and molecular docking also provided a powerful tool for further exploration of active ingredients responsible for the anticoagulant activity in chuanxiong.
摘要：
OBJECTIVE: Trimethoprim sulfamethoxazole (TMP-SMX) is related to aseptic meningitis. However, a detailed description of its phenotype is lacking, which easily leads to misdiagnosis. The purpose of this article is to explore the clinical characteristics of TMP-SMX-induced aseptic meningitis (TSIAM). METHODS: We collected literature related to TSIAM published before July 31, 2023, by searching Chinese and English databases. Data were extracted and analyzed descriptively. RESULTS: The 55 patients were mostly female (60.0%), with a median age of 43 years (range: 2.5-90 years). The first onset time was from a few minutes to 3 months after administration, and the time of reonset was within 12 hours. Fever (98.2%), headache (78.2%), altered mental status (42.3%), nausea and vomiting (41.8%), and neck pain (34.5%) were the most common symptoms. In severe cases, patients presented with low blood pressure, seizures, unconsciousness, or coma. Typical cerebrospinal fluid analysis showed elevated white blood cell counts, with polymorphonuclear leukocytes predominating, elevated protein levels, and normal glucose levels. Brain imaging usually showed no abnormalities. Symptoms resolved rapidly after the discontinuation of TMP-SMX, within a median time of 2 days (range: 1, 60). Readministration of TMP-SMX led to another relapse of aseptic meningitis. Aseptic meningitis usually culminated in a full recovery, although one patient experienced permanent paraplegia. CONCLUSION: Clinicians should be aware that aseptic meningitis is a rare adverse effect of TMP-SMX. TMP-SMX should be discontinued in patients with TSIAM to reduce unnecessary testing and treatment, and readministration of TMP-SMX should be avoided.
摘要：
Sweet syndrome is a rare complication of azathioprine treatment with unelucidated clinical features. The purpose of this study was to investigate the clinical characteristics of azathioprine-induced Sweet syndrome (AISS) and provide a reference for diagnosis, treatment and prognosis. We collected relevant case reports of AISS by searching Chinese and English databases from 1960 to December 31, 2022, extracted the data and carried out a retrospective analysis. The median age of the 44 patients was 50 (range 9-89) years, and they included 32 males (72.7%). Fever (86.4%) and arthralgia (31.8%) were the most common clinical symptoms. The skin lesions were mainly pustules (54.5%), papules (40.9%), plaques (40.9%) and nodules (31.8%), which were mainly distributed on the extremities (54.5%), face (38.6%) and hands (36.4%). Laboratory examination revealed neutropenia (65.9%) as well as elevated C-reactive protein (63.6%) and erythrocyte sedimentation (40.9%) rates. Histopathology of the lesioned skin showed neutrophil infiltration (93.2%) and dermal edema (38.6%). Symptom relief was achieved at a median time of 7days (range 2-28days) after azathioprine discontinuation in all patients. Nine patients (20.5%) had skin lesions that recurred within 24h after taking azathioprine again. Clinicians and pharmacists should grasp the regularity and characteristics of AISS and should not recommend the readministration of azathioprine, to avoid the recurrence of Sweet syndrome.
摘要：
Fruits are consumed as foods or medicines to supply people with nutrition or treat dis-eases. Zhishi, the dried young fruit of Citrus aurantium L. or Citrus sinensis Osbeck, is one of the most representative health food from the fruit of the Citrus genus. It is widely used in flavorings, canned food, beverages, and medicines because of its outstanding curative effects. The bidirectional regulating effect of Zhishi on the gastrointestinal tract for treating food stagnation or diarrhea has been confirmed. Its active ingredients, including synephrine and N-methyltyramine, have been used clinically as blood pressure boosting and anti-shock drugs. Flavonoids and alkaloids of Zhishi also make it potential weight loss and beauty products due to their definite effectiveness and safety. This paper intends to review the different therapeutic applications of Zhishi and the phytochemicals associated with its medicinal values. Besides, up-to-date information on its botany and analytical methods for the quality control of the medicine is supplied. To conclude, numerous independent research on Zhishi have been conducted in the past decades, but most of them are not deep enough in elucidating its scientific evidence of its health benefits. Further studies may unveil additional pharmacological activities and is beneficial to the mankind. (c) 2023 The Authors. Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
摘要：
Prolonged exposure of the peritoneum to high glucose dialysate leads to the development of peritoneal fibrosis (PF), and apoptosis of peritoneal mesothelial cells (PMCs) is a major cause of PF. The aim of this study is to investigate whether Astragaloside IV could protect PMCs from apoptosis and alleviate PF. PMCs and rats PF models were induced by high glucose peritoneal fluid. We examined the pathology of rat peritoneal tissue by HE staining, the thickness of rat peritoneal tissue by Masson's staining, the number of mitochondria and oxidative stress levels in peritoneal tissue by JC-1 and DHE fluorescence staining, and mitochondria-related proteins and apoptosis-related proteins such as PGC-1α, NRF1, TFAM, Caspase3, Bcl2 smad2 were measured. We used hoechst staining and flow cytometry to assess the apoptotic rate of PMCs in the PF model, and further validated the observed changes in the expressions of PGC-1α, NRF1, TFAM, Caspase3, Bcl2 smad2 in PMCs. We further incubated PMCs with MG-132 (proteasome inhibitor) and Cyclohexylamine (protein synthesis inhibitor). The results demonstrated that Astragaloside IV increased the expression of PGC-1α by reducing the ubiquitination of PGC-1α. It was further found that the protective effects of Astragaloside IV on PMCs were blocked when PGC-1α was inhibited. In conclusion, Astragaloside IV effectively alleviated PF both in vitro and in vivo, possibly by promoting PGC-1α to enhance mitochondrial synthesis to reduce apoptotic effects.
期刊：
Frontiers in Microbiology,2023年14:1476 ISSN：1664-302X
通讯作者：
Peng, YM
作者机构：
[Liang, Xuejuan; Peng, Yanmei; Li, Penghui; Wan, Dan; Peng, YM] Hunan Acad Chinese Med, Innovat Med Inst Tradit Chinese Med, Changsha, Peoples R China.;[Zhou, Kang; Yi, Xin] Hunan Univ Chinese Med, Coll Pharm, Changsha, Peoples R China.;[Liu, Jing] Hunan Univ Chinese Med, Coll Chinese Med, Changsha, Peoples R China.
通讯机构：
[Peng, YM ] H;Hunan Acad Chinese Med, Innovat Med Inst Tradit Chinese Med, Changsha, Peoples R China.
关键词：
E. ulmoides;Eucommiae Cortex;endophytic bacteria;origin;active ingredient
摘要：
ObjectiveThis study aimed to explore the differences between Eucommiae cortex (EC) endophytic bacteria from different origins and their effects on the active ingredients of EC. MethodsA total of 10 samples of Eucommia ulmoides Oliv. (E. ulmoides) bark were collected from each of the following four regions, namely, Zunyi in Guizhou (GZ), Baokang in Hubei (HUB), Cili in Hunan (HUN), and Loyang in Shaanxi (SX). Subsequently, the contents of the main active ingredients of EC were determined by ultra-performance liquid chromatography (UPLC), and the endophytic bacteria of EC were detected by 16S rRNA sequencing. The relationship between the dominant endophytic bacteria and the active ingredients was investigated by correlation analysis. ResultsA total of 4,551 different operational taxonomic units (OTUs) were delineated in the four groups of samples, of which 585, 439, 957, and 684 genera were annotated from GZ, HUB, HUN, and SX, respectively. The richness and diversity of endophytic bacteria from different origins were ranked as HUN > SX > GZ or HUB. The analysis demonstrated that there was no significant correlation between the diversity and richness of endophytic bacteria in EC and its active ingredients. Nevertheless, notable variations in the community structures of endophytic bacteria were observed across different origins, and they had a considerable impact on certain active ingredients in EC. Comamonas and Cedecea were the dominant genera. Characteristic bacteria of different origins could be clearly distinguished. Simultaneous, significant correlations had been identified between some characteristic endophytic bacteria derived from different origins and active ingredients of EC. For example, Delftia, a characteristic bacterium from GZ, showed a significant positive correlation with pinoresinol diglucoside. Paenibacillus and Klebsiella, two characteristic bacteria from HUB, exhibited significant positive correlations with geniposidic acid. Thauera, a characteristic bacterium from HUN, demonstrated a significant positive correlation with geniposide. Brevundimonas, a characteristic bacterium from SX, displayed a significant positive correlation with pinoresinol diglucoside. ConclusionThere was a complex correlation between EC endophytic bacteria and active ingredient content, while EC endophytic bacteria from different origins had significant differences at the genus level.
期刊：
Frontiers in Immunology,2023年14:939 ISSN：1664-3224
作者机构：
[Cai, DQ.; Cai, Diankui] Sun Yat Sen Mem Hosp, Dept Gen Surg, Guangzhou, Peoples R China.;[Cai, DQ.; Jian, Zhixiang; Lin, Ye; Zou, Yiping] Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Dept Gen Surg, Guangzhou, Guangdong, Peoples R China.;[Chen, Xumeng] Hunan Univ Chinese Med, Sch Pharmaceut Sci, Dept Pharmacol, Changsha, Peoples R China.;[Shi, Mude] Guangdong ACXEL Micro & Nano Tech Co Ltd, Foshan, Peoples R China.;[Chen, Jueming] South China Univ Technol, Med Coll, Guangzhou, Peoples R China.
关键词：
prognosis;chemoresistance;Immunotherapy;Signature;tumor-infiltrating CD8+ T cell
摘要：
BackgroundAccumulating evidence has revealed that CD8+ T cell exhaustion (Tex) results in worse immunotherapy outcomes. However, the molecular functions and mechanisms of action of Tex in chemoresistance needed to be elucidated. MethodsThe populations of tumor-infiltrating CD8+ T cells (TILCD8Ts) in chemoresistant and chemosensitive groups of the GSE25066 dataset were calculated using CIBERSORT. Differentially expressed genes (DEGs) between TILCD8Ts and other immune cells were explored by integrating 16 immune cell datasets downloaded from the gene expression omnibus (GEO) database. Gene ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, univariate and multivariate Cox regression, and least absolute shrinkage and selection operator (LASSO) regression of TILCD8T-specific upregulated genes were used to construct a chemoresistant TILCD8T signature (cr-TILCD8TSig). Clinical prognostic data, genomic alterations, chemotherapy response, and immunotherapy response were compared between the different cr-TILCD8TSig subgroups in the GSE25066 and the cancer genome atlas breast cancer (TCGA-BRCA) cohorts. ResultsA cr-TILCD8TSig with exhausted features was identified, consisting of seven genes (TCF7, RARRES3, ARL4C, ITK, CDH3, GZMB, and KLRD1), which were identified from 104 TILCD8Ts-specific DEGs. Our results showed that compared to the cr-TILCD8TSig-low subgroup, the -high subgroup had a poorer distant relapse-free survival (DRFS) in the GSE25066 cohort and worse progression-free survival (PFS) in the TCGA-BRCA cohort. Univariate and multivariate Cox regression analyses also demonstrated that cr-TILCD8TSig was an independent prognostic factor in the two independent cohorts. Furthermore, cr-TILCD8TSig-low patients benefited more from chemotherapy and immunotherapy than cr-TILCD8TSig-high patients. Besides, we found cell transmembrane signal transduction and the ECM may provide the molecular basis for resistance to antitumor agents in the cr-TILCD8Sig-high subgroup. For genomic alterations, we revealed that mutations in PIK3CA, DMD, and APOB were more common in the cr-TILCD8Sig-high subgroup than in the cr-TILCD8Sig-low subgroup. A nomogram was finally constructed with good discrimination and calibration. Conclusionscr-TILCD8TSig is a useful tool to independently predict prognosis, chemotherapy response, and immunotherapy outcomes in patients with breast cancer.
期刊：
Frontiers in Pharmacology,2023年14:1173747 ISSN：1663-9812
通讯作者：
Long, HP
作者机构：
[Zhou, Siqian; Long, HP; Liu, Jian; Long, Hongping] Hunan Univ Chinese Med, Ctr Med Res & Innovat, Hosp 1, Changsha, Peoples R China.;[Ding, Changsong; Zhou, Siqian; Wang, Yajing; Long, HP; Long, Hongping] Hunan Univ Chinese Med, Changsha, Peoples R China.;[Tan, Leihong] Hunan Univ Chinese Med, Dept Pharm, Hosp 2, Changsha, Peoples R China.;[Wang, Yikun] Cent South Univ, Xiangya Hosp 2, Dept Pharm, Changsha, Peoples R China.;[Li, Jing] Cent South Univ, Xiangya Hosp, Dept Pharm, Changsha, Peoples R China.
通讯机构：
[Long, HP ] H;Hunan Univ Chinese Med, Ctr Med Res & Innovat, Hosp 1, Changsha, Peoples R China.;Hunan Univ Chinese Med, Changsha, Peoples R China.
摘要：
Introduction: Corni Fructus (CF) is a Chinese herbal medicine used for medicinal and dietary purposes. It is available commercially in two main forms: raw CF (unprocessed CF) and wine-processed CF. Clinical observations have indicated that wine-processed CF exhibits superior hypoglycemic activity compared to its raw counterpart. However, the mechanisms responsible for this improvement are not well understood. Methods: To address this gap in knowledge, we conducted metabolomics analysis using ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-QTOF-MS) to compare the chemical composition of raw CF and wine-processed CF. Subsequently, network analysis, along with immunofluorescence assays, was employed to elucidate the potential targets and mechanisms underlying the hypoglycemic effects of metabolites in CF. Results: Our results revealed significant compositional differences between raw CF and wine-processed CF, identifying 34 potential markers for distinguishing between the two forms of CF. Notably, wine processing led to a marked decrease in iridoid glycosides and flavonoid glycosides, which are abundant in raw CF. Network analysis predictions provided clues that eight compounds might serve as hypoglycemic metabolites of CF, and glucokinase (GCK) and adenylate cyclase (ADCYs) were speculated as possible key targets responsible for the hypoglycemic effects of CF. Immunofluorescence assays confirmed that oleanolic acid and ursolic acid, two bioactive compounds present in CF, significantly upregulated the expression of GCK and ADCYs in the HepG2 cell model. Discussion: These findings support the notion that CF exerted hypoglycemic activity via multiple components and targets, shedding light on the impact of processing methods on the chemical composition and hypoglycemic activity of Chinese herbal medicine.
