作者机构：
[Shi, Zhi Min; Wei, Jia-ming] Hunan Univ Chinese Med, Sch Chinese Med, Changsha 410208, Peoples R China.;[Wang, Zi-yan; Yuan, Hui; Liu, Cheng-xin] Hunan Univ Chinese Med, Clin Coll Chinese Med 1, Changsha 410208, Peoples R China.;[Wang, Zi-yan; Shi, Zhi Min; Yuan, Hui; Wei, Jia-ming; Liu, Cheng-xin] Hunan Univ Chinese Med, Hunan Key Lab Coll & Univ Intelligent Tradit Chine, 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 ; Shi, ZM ] H;Hunan Univ Chinese Med, Hunan Key Lab Coll & Univ Intelligent Tradit Chine, Changsha 410208, Peoples R China.;Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Peoples R China.
关键词：
ApoE(-/-) mice;Atherosclerosis;NOX/ROS/NF-κB signal pathway;Vascular smooth muscle cell;Xin-tong-tai
摘要：
Background: Xin-tong-tai Granule (XTTG), a traditional Chinese medicine, has been used to treat atherosclerosis (AS), but its mechanism is poorly understood. Intriguingly, oxidative stress has been recognized as vital factors in the treatment of atherosclerosis. Purpose: This study aims to explore the potential mechanism of XTTG for treating AS. Methods: An in-vivo model of AS was established by feeding ApoE-/- mice with a high-fat diet (HFD), and the Human Aortic Vascular Smooth Muscle Cells (HAVSMCs) were induced by oxidized low-density lipoprotein (oxLDL) in vitro. After treatment, the blood lipid levels and pathological aortic changes of each group were observed, and the cell proliferation and lipid droplet aggregation in each group were evaluated. The oxidative stress indicators such as malondialdehyde (MDA) and superoxide dismutase (SOD) levels and related NOX/ROS/ NF-.kappa B signaling pathway indicators were observed. Results: XTTG improved blood lipid levels and pathological aortic changes of ApoE / mice with HFD feeding, inhibited HAVSMCs proliferation and lipid droplet aggregation induced by ox-LDL, reduced MDA content, increased SOD content, inhibited NOX4 and p22phox protein expression, downregulated ROS content, inhibited IKK-alpha, IKK-ss, NF-.kappa B protein and mRNA expression and the phosphorylation of NF-.kappa B. Conclusion: XTTG can inhibit NOX/ROS/NF-.kappa B signaling pathway, reduce damages caused by oxidative stress, and exert anti-AS effects.
摘要：
(1) Background: Ginsenoside Rb1-PLGA nanoparticles (GRb1@PLGA@NPs) represent a novel nanotherapeutic system, yet their therapeutic efficacy and underlying mechanisms for treating heart failure (HF) remain unexplored. This study aims to investigate the potential mechanisms underlying the therapeutic effects of GRb1@PLGA@NPs in HF treatment; (2) Methods: The left anterior descending coronary artery ligation was employed to establish a HF model in Sprague-Dawley rats, along with an in vitro oxidative stress model using H9c2 myocardial cells. Following treatment with GRb1@PLGA@NPs, cardiac tissue pathological changes and cell proliferation were observed. Additionally, the serum levels of biomarkers such as NT-proBNP, TNF-alpha, and IL-1 beta were measured, along with the expression of the ROS/PPAR alpha/PGC1 alpha pathway; (3) Results: GRb1@PLGA@NPs effectively ameliorated the pathological status of cardiac tissues in HF rats, mitigated oxidative stress-induced myocardial cell damage, elevated SOD and MMP levels, and reduced LDH, MDA, ROS, NT-proBNP, TNF-alpha, and IL-1 beta levels. Furthermore, the expression of PPAR alpha and PGC1 alpha proteins was upregulated; (4) Conclusions: GRb1@PLGA@NPs may attenuate myocardial cell injury and treat HF through the ROS/PPAR alpha/PGC1 alpha pathway.
摘要：
Improving hepatic glucose and lipid metabolisms is an important strategy to treat type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease (T2DM-NAFLD). Silybin (SLB) has the potential hepatoprotection, while its oral bioavailability is poor. This study aims to investigate the functional role and mechanism of liposomal SLB in modulating glucose/lipid metabolism in T2DM-NAFLD. SLB was prepared by thin film dispersion method and characterized using dynamic light scattering, scanning electron microscope, high performance liquid chromatography and zeta potential analyzer. A rat model of T2DM-NAFLD was used to determine the role of liposomal SLB in regulating glycolipid metabolism and hepatic damage. Rat primary hepatocytes were used to demonstrate the hepatoprotection mechanism of liposomal SLB. The encapsulation efficiency was more than 80%, which showed the average particle size of 119.76 nm. Also, the average Zeta potential was -4.76 mV. These liposomes were spherical. In rats with T2DM-NAFLD, liposomal SLB alleviated insulin resistance and lipid metabolism, thereby improving hepatic lipid accumulation, inflammation and fibrosis. Besides, liposomal SLB elevated AMPK phosphorylation, and decreased collagen I/III, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1) and the phosphorylation of Smad2/3. In hepatocyte model, compound C partially reversed the effects of liposomal SLB on cell viability, glycolipid metabolism and AMPK/TGF-β1/Smad pathway activation. Liposomal SLB ameliorates hepatic glucose and lipid metabolisms in T2DM-NAFLD via activating AMPK/TGF-β1/Smad pathway, providing an efficient strategy for treating T2DM-NAFLD.
摘要：
Liuwei Dihuang Pill (LP) was verified to alleviate postmenopausal osteoporosis (PMOP) development. Nevertheless, the major constituent of LP and the related network pharmacology study remain unexplored. Protein–protein interaction was established to identify the downstream target of LP in PMOP, and the related signaling pathway was investigated by bioinformatics analysis. MC3T3-E1 cells were added to ferric ammonium citrate (FAC) to mimic osteoporosis in vitro. The osteoblasts were identified by Alizarin red staining. Western blot was applied to evaluate protein levels. In addition, Cell Counting Kit-8 (CCK8) assay was applied to assess cell viability, and cell apoptosis was assessed by flow cytometry. Quercetin was the major constituent of LP. In addition, quercetin significantly reversed FAC-induced inhibition of osteogenic differentiation in MC3T3-E1 cells. In addition, quercetin notably abolished the FAC-induced upregulation of Bax, Caspase-3, FOS, JUN, TGFB1 and PPARD. In contrast, Bcl-2, p-mTOR/mTOR, p-AKT/AKT and p-PI3K/PI3K levels in MC3T3-E1 cells were reduced by FAC, which was restored by quercetin. Meanwhile, FAC notably inhibited the viability of MC3T3-E1 cells via inducing apoptosis, but this impact was abolished by quercetin. Furthermore, quercetin could reverse pcDNA3.1-FOS-mediated growth of FAC-treated osteoblasts by mediating PI3K/AKT/mTOR signaling. Quercetin alleviated the progression of PMOP via activation of PI3K/AKT/mTOR signaling. Hence, this study would shed novel insights into discovering new methods against PMOP.
关键词：
atherosclerosis;endothelial cell;endothelial cell senescence;endothelial cell death
摘要：
Endothelial cells (ECs) form the inner linings of blood vessels, and are directly exposed to endogenous hazard signals and metabolites in the circulatory system. The senescence and death of ECs are not only adverse outcomes, but also causal contributors to endothelial dysfunction, an early risk marker of atherosclerosis. The pathophysiological process of EC senescence involves both structural and functional changes and has been linked to various factors, including oxidative stress, dysregulated cell cycle, hyperuricemia, vascular inflammation, and aberrant metabolite sensing and signaling. Multiple forms of EC death have been documented in atherosclerosis, including autophagic cell death, apoptosis, pyroptosis, NETosis, necroptosis, and ferroptosis. Despite this, the molecular mechanisms underlying EC senescence or death in atherogenesis are not fully understood. To provide a comprehensive update on the subject, this review examines the historic and latest findings on the molecular mechanisms and functional alterations associated with EC senescence and death in different stages of atherosclerosis.
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]
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.
期刊：
Journal of Biochemical and Molecular Toxicology,2023年37(6):e23344 ISSN：1095-6670
作者机构：
[Xiao, Guiying; Xiong, Liguang; Li, Yuan; Yuan, Fang; Deng, Yang; Xiang, Debiao; Li, Xin] Third Hosp Changsha, Dept Pharm, Changsha, Hunan, Peoples R China.;[Xiao, Guiying; Xiong, Liguang; Li, Yuan; Yuan, Fang; Deng, Yang; Xiang, Debiao; Li, Xin] Third Hosp Changsha, Inst Clin Applicat Antibiot, Changsha, Hunan, Peoples R China.;[Xiao, Guiying; Xiong, Liguang; Li, Xin] Hunan Univ Chinese Med, Hosp Changsha 3, Dept Pharm, Changsha, Hunan, Peoples R China.;[Li, Yuan; Li, Xin] Third Hosp Changsha, Dept Pharm, 176 Western Laodong Rd, Changsha 410015, Hunan, Peoples R China.
关键词：
Nrf2/NQO1 pathway;apoptosis;nephrotoxicity;oxidative stress;polymyxin B
摘要：
Polymyxin B (PMB) is a polypeptide antibiotic widely used in treating multidrug-resistant Gram-negative bacteria. However, nephrotoxicity is a serious adverse effect that limits its clinical use. Therefore, clarification of the molecular mechanism of PMB-induced renal injury is essential. Our study aimed to explore possible mechanisms of PMB-induced nephrotoxicity in vivo and in vitro. Mice were treated with PMB to construct the kidney injury model. The antioxidant capacity was assessed by measuring the superoxide dismutase (SOD) and catalase (CAT) activities and the glutathione (GSH)and malondialdehyde (MDA) contents. The pathway of the nuclear factor erythroid 2-related factor 2/NADH quinone oxidoreductase 1 (Nrf2/NQO1) was examined after PMB treatment in NRK-52E cells and mice. Finally, the expressions of genes and proteins (Bax, Bcl-2, Caspase-3, Caspase-9) related to apoptosis were evaluated through quantitative polymerasechain reaction and western blot assay. The study verified PMB-induced nephrotoxicity in mice and NRK-52E cells in a dose- and time-dependent manner. PMB treatment significantly decreased the expression of Nrf2 and its downstream target gene NQO1 and increased the apoptosis-related proteins expression. In summary, our results suggested that PMB-induced oxidative stress damage by inhibiting the Nrf2/NQO1 pathway and promoting apoptosis in kidney tissues.
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).
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：
[Fan, Bei; Jin, Nuo; Wang, Feng-Zhong; Liu, Jia-Meng; Fan, B; Lu, Cong; Sun, Jing; Wang, FZ; Sun, Yu-Feng; Li, Shu-Ying; Wang, Shan-Shan] Chinese Acad Agr Sci, China Inst Food Sci & Technol, Key Lab Agroprod Qual & Safety Control Storage & T, Minist Agr & Rural Affairs, Beijing, Peoples R China.;[Liang, Yan-Tian] Hunan Univ Tradit Chinese Med, Coll Pharm, Changsha, Hunan, Peoples R China.
通讯机构：
[Fan, B; Wang, FZ ] C;Chinese Acad Agr Sci, China Inst Food Sci & Technol, Key Lab Agroprod Qual & Safety Control Storage & T, Minist Agr & Rural Affairs, Beijing, Peoples R China.
摘要：
The growth of endophytic bacteria is influenced by the host plants and their secondary metabolites and activities. In this study, P. megaterium P-NA14 and P. megaterium D-HT207 were isolated from potato tuber and dendrobium stem respectively. They were both identified as Priestia megaterium. The antimicrobial activities and metabolites of both strains were explored. For antimicrobial activities, results showed that P. megaterium P-NA14 exhibited a stronger inhibition effect on the pathogen of dendrobium, while P. megaterium D-HT207 exhibited a stronger inhibition effect on the pathogen of potato. The supernatant of P. megaterium P-NA14 showed an inhibition effect only on Staphylococcus aureus, while the sediment of P. megaterium D-HT207 showed an inhibition effect only on Escherichia coli. For metabolomic analysis, the content of L-phenylalanine in P. megaterium P-NA14 was higher than that of P. megaterium D-HT207, and several key downstream metabolites of L-phenylalanine were associated with inhibition of S. aureus including tyrosine, capsaicin, etc. Therefore, we speculated that the different antimicrobial activities between P. megaterium P-NA14 and P. megaterium D-HT207 were possibly related to the content of L-phenylalanine and its metabolites. This study preliminarily explored why the same strains isolated from different hosts exhibit different activities from the perspective of metabolomics.
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：
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.
摘要：
BACKGROUND: Many epidemiological studies have shown that idiopathic pulmonary fibrosis (IPF) is a risk factor for lung cancer (LC), but these studies do not provide direct evidence of a causal association between the two diseases. We investigated the causal association between IPF and different pathological types of LC based on the Mendelian randomization (MR) study. METHODS: The genome-wide association study (GWAS) data of IPF and LC were obtained from the latest published articles, and instrumental variables (IVs) for analysis were obtained after screening and eliminating the confounders. MR Analysis was carried out with the help of random effects inverse variance weighting (re-IVW), MR-egger, and weighted median method, and a comprehensive sensitivity test was conducted. RESULTS: The results of re-IVW analysis showed that IPF may increase the risk of lung squamous cell carcinoma (LUSC) (OR = 1.045, 95% CI 1.011 to 1.080, P = 0.008). In addition, no causal relationship was found between IPF and overall LC (OR = 0.977, 95% CI 0.933 to 1.023, P = 0.32), lung adenocarcinoma (LUAD) (OR = 0.967, 95% CI 0.903 to 1.036, P = 0.345) and small cell lung carcinoma (SCLC) (OR = 1.081, 95% CI 0.992 to 1.177, P = 0.074). A comprehensive sensitivity analysis ensured the reliability of the study. CONCLUSION: In conclusion, from the perspective of genetic association, we found that IPF is an independent risk factor for LUSC and may increase the risk of LUSC, but no such causal relationship was found in LUAD and SCLC.
摘要：
Abstract: In this study, soluble dietary fibers (SDFs) were extracted from rape bee pollen using four methods including acid extraction (AC), alkali extraction (AL), cellulase extraction (CL) and complex enzyme extraction (CE). The effects of different extraction methods on the structure of SDFs and in vitro fermentation characteristics were further investigated. The results showed that the four extraction methods significantly affected the monosaccharide composition molar ratio, molecular weight, surface microstructure and phenolic compounds content, but showed little effect on the typical functional groups and crystal structure. In addition, all SDFs decreased the Firmicutes/Bacteroidota ratio, promoted the growth of beneficial bacteria such as Bacteroides, Parabacteroides and Phascolarctobacterium, inhibited the growth of pathogenic bacteria such as Escherichia-Shigella, and increased the total short-chain fatty acids (SCFAs) concentrations by 1.63–2.45 times, suggesting that the bee pollen SDFs had a positive regulation on gut microbiota. Notably, the SDF obtained by CE exhibited the largest molecular weight, a relatively loose structure, higher extraction yield and phenolic compounds content and the highest SCFA concentration. Overall, our results indicated that CE was an appropriate extraction method of high-quality bee pollen SDF. Keywords: bee pollen; soluble dietary fiber; extraction methods; structure; in vitro fermentation characteristics
期刊：
Journal of Pharmacy and Pharmacology,2023年75(6):784-805 ISSN：0022-3573
通讯作者：
Xili Zhang
作者机构：
[Zhang, Xili; Zhao, Jing; Liu, Wenlong; Li, Shixiong] Hunan Univ Chinese Med, Dept Pharm, Changsha, Peoples R China.;[Hou, Manting; Zhao, Jing; Li, Hui; Bai, Zhaofang; Ding, Kaixin] Chinese Peoples Liberat Army Gen Hosp, Med Ctr 5, Dept Hepatol, Beijing, Peoples R China.;[Hou, Manting; Zhao, Jing; Li, Hui; Bai, Zhaofang; Ding, Kaixin] Chinese Peoples Liberat Army Gen Hosp, Med Ctr 5, China Mil Inst Chinese Mat, Beijing, Peoples R China.
通讯机构：
[Xili Zhang] D;Department of Pharmacy, Hunan University of Chinese Medicine , Changsha , China
关键词：
Jie Geng Tang;cisplatin;Nrf2;lung cancer
摘要：
OBJECTIVES: Jie Geng Tang (JGT) is an ancient traditional Chinese herbal decoction that exhibits various pharmacological activities, however, is poorly understood in the sensitivity of lung cancer to chemotherapy. Here, we explored the effect of JGT on sensitizing cisplatin (DDP)-resistant A549 cells (A549/DDP). METHODS: Cell viability was assessed using cell counting kit-8 assay. Flow cytometry was applied to detected cell apoptosis, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) levels. Western blotting and qRT-PCR were performed to determine protein and mRNA levels. KEY FINDINGS: The results demonstrated that DDP co-treatment with JGT significantly increased the cytotoxicity of A549/DDP cells and exhibited efficacy in suppressing the migration and proliferation. The rate of apoptosis was increased by co-treatment with DDP and JGT, along with a higher rate of Bax/Bcl-2, and increased loss of MMP. Furthermore, the combination promoted ROS accumulation and increased γ-H2AX levels. Moreover, Nrf2 levels were suppressed in a dose- and time-dependent manner, Nrf2 stability was reduced following treatment with JGT. Notably, the combination induced inhibition of the Nrf2/ARE pathway at the mRNA and protein levels. CONCLUSIONS: Collectively, these results indicate that co-treatment with JGT and DDP can be considered a combinational approach to treating DDP resistance.
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Paeoniae Radix Rubra (PRR), the root of Paeonia lactiflora Pall. or Paeonia veitchii Lynch, has been widely used to promote blood circulation and eliminate blood stasis in Chinese clinical practice, but its effect on cerebral ischemia is still rarely reported. AIM OF THE STUDY: The present study aimed to assess the potential therapeutic possibilities of the extract of PRR (PRRE) on cerebral ischemia, further exploring the underlying mechanism, and preliminary screening of the corresponding active components. MATERIALS AND METHODS: The neuroprotective effects of PRRE in Sprague-Dawley (SD) rats with middle cerebral artery occlusion (MCAO) injury and mouse hippocampal neuronal cells (HT22cell line) following oxidative stress were confirmed. The mechanism was investigated using immunohistochemical staining, western blotting, transmission electron microscopy (TEM), and immunofluorescence. The active components of PRRE were analysed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and molecular docking. RESULTS: The in vivo study showed that PRRE reduced infarct volume and improved neurological deficits in rats, and the expression of GPX4, FTH1, Beclin1, LC3 II, and p-Akt was upregulated in the rat hippocampi. In addition, the vitro research indicated that PRRE can also alleviate H(2)O(2)-induced HT22cell damage by regulating cytokines such as malondialdehyde (MDA), reduced glutathione (GSH) and reactive oxygen species (ROS), and the expressions of GPX4 and Beclin1 were observed to be elevated. The PI3K/Akt signalling pathway was inhibited by LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K). Furthermore, the effective components of PRRE in regulating ferroptosis and autophagy are mainly defined as albiflorin, paeoniflorin, benzoyl paeoniflorin, oleanolic acid, and hederagenin. CONCLUSION: PRRE exerts neuroprotective effects against cerebral ischaemic injury by inhibiting ferroptosis and activating autophagy through the PI3K/Akt signalling pathway. This study provides an experimental basis for the potential application of PRRE as a novel therapeutic drug, and PI3K/Akt-associated ferroptosis and autophagy as therapeutic targets for cerebral ischemia.
期刊：
Journal of Liposome Research,2023年33(3):283-299 ISSN：0898-2104
通讯作者：
Lili Zhou<&wdkj&>Xinhua Xia
作者机构：
[Xia, Xinhua; Xu, Yilin; Lin, Peng; Zhou, Lili; Zou, Manshu] Hunan Univ Chinese Med, Sch Pharm, Changsha, Peoples R China.;[Xia, Xinhua; Zhou, Lili] Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Peoples R China.
通讯机构：
[Lili Zhou; Xinhua Xia] S;School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China<&wdkj&>School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
摘要：
In this study, cantharidin(CTD), a bioactive terpenoid in traditional Chinese medicine cantharidin, was selected as a model component to construct novel nano liposome delivery systems for hepatocellular carcinoma therapy. Previous studies have shown that although cantharidin has definite curative effects on primary liver cancer, it is associated with numerous toxic and side effects. Therefore, based on the glycyrrhetinic acid (GA) binding site and the asialoglycoprotein receptor (ASGPR) on the hepatocyte membrane, the surface of CTD liposomes was modified with stearyl alcohol galactoside (SA-Gal) or/and the newly synthesized 3-succinic-30-stearyl deoxyglycyrrhetinic acid (11-DGA-Suc) ligands, and the physicochemical properties, pharmacokinetics, invivo and invitro anti-liver tumor activity and its mechanism of modified liposomes were investigated. Compared to CTD-lip, SA-Gal-CTD-lip, and 11-DGA-Suc + SA-Gal-CTD-lip, 11-DGA-Suc-CTD-lip showed stronger cytotoxicity and increased inhibition of HepG2 cell migration had the highest apoptosis rate. The cell cycle results indicated that HepG2 cells was arrested mainly at G0/G1phase and G2/M phase. The results of invivo pharmacokinetic experiments revealed that the distribution of modified liposomes in the liver was significantly increased compared with that of unmodified liposome. In vivo tumor inhibition experiment showed that 11-DGA-Suc-CTD-lip had excellent tumor inhibition, and the tumor inhibition rates was 80.96%. The 11-DGA-Suc-CTD-lip group also displayed the strongest proliferation inhibition with the lowest proliferation index of 7% in PCNA assay and the highest apoptotic index of 49% in TUNEL assay. Taken together, our findings provide a promising solution for improving the targeting of nano liposomes and further demonstrates the encouraging potential of poor solubility and high toxicity drugs applicable to tumor therapy.
