1.The neuroprotective effect of curcumin by inhibiting the aggregation of α-synuclein on lipopolysaccharide-induced Parkinson's disease model
Xiaokui GAN ; Xiaowei SONG ; Ming ZHANG ; Yiming FANG ; Longbiao MA ; Baosheng HUANG
China Pharmacist 2024;27(5):779-787
Objective To explore the neuroprotective effect of curcumin(Cur)on Parkinson's disease model and its mechanism.Methods Sprague-Dawley rats were randomly divided into the control(CON)group,the model(PD)group,and the low-,medium-,and highdose curcumin(Cur)groups,with ten rats in each group.Lipopolysaccharide was injected into the substantia nigra to establish a Parkinson's disease model.Rats in the Cur groups were administered Cur intraperitoneally at doses of 20 mg/kg,40 mg/kg,and 60 mg/kg daily for 21 days.α-synuclein(α-syn),nuclear transcription factor κB proteins(NF-κB,IKBα,p-NF-κB,p-IKBα)and the activation levels of astrocytes were detected in rat brain tissues by immunohistochemistry(IHC).mRNA levels of pro-inflammatory cytokines(TNF-α,IL-β,IFN-γ,IL-6),inducible nitric oxide synthase(iNOS),cyclooxygenase-2(COX-2),NADPH oxidase complex(gp47phox,gp91phox,gp67phox),and apoptosis-related factors(Bax,Bcl-2,Caspase-3,and Caspase-9)were measured by quantitative reverse transcription polymerase chain reaction(qRT-PCR).The rotarod and pole climbing tests were used to evaluate the motor coordination of the rats.Results Compared to the CON group,PD rats showed significantly increased levels of α-syn,p-NF-κB,p-IKBα proteins,activation of astrocytes,TNF-α,IL-β,IFN-γ,IL-6,iNOS,COX-2,Bax,Caspase-3,Caspase-9,gp47phox,gp91phox and gp67phox mRNA levels(P<0.05);while the Bcl-2 level was significantly decreased(P<0.05).Compared with the PD group,the medium-and high-dose Cur treatment groups inhibited the aggregation of α-syn protein,reduced the activation of the NF-κB pathway,and the expression of inflammatory and apoptosis-related factors(P<0.05).Moreover,medium and high doses of Cur significantly improved the motor coordination in rats,and compared with the PD group,the performance of rotarod and pole climbing tests was significantly improved(P<0.05).Conclusion cur may inhibit the aggregation of α-syn by suppressing neuroinflammation and oxidative stress responses,thereby improving motor coordination in Parkinson's disease rats and exerting neuroprotective effects.
2.Evaluation and influencing factors of early residual myocardial ischemia on myocardial perfusion imaging after percutaneous coronary intervention for coronary artery disease
Zhimin YANG ; Xiaoyu YANG ; Yuetao WANG ; Wenji YU ; Ke LI ; Chun QIU ; Feifei ZHANG ; Xiao-Liang SHAO ; Baosheng MENG ; Jianfeng WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(9):539-544
Objective:To evaluate early residual myocardial ischemia after successful percutaneous coronary intervention (PCI) in patients with coronary artery disease by using myocardial perfusion imaging (MPI) and investigate independent influencing factors of early residual myocardial ischemia.Methods:From January 2020 to December 2022, 127 patients (107 males, 20 females; age (60.3±9.6) years) with coronary artery disease who underwent PCI complete revascularization at the First People′s Hospital of Changzhou were consecutively enrolled prospectively. All patients underwent rest and stress MPI within 1-3 months after PCI. Reversible myocardial perfusion defect in the blood supply area of the culprit vessels in stress and rest MPI was defined as early residual myocardial ischemia after PCI. Accordingly, the culprit vessels undergoing PCI were divided into residual ischemic group and non-ischemic group. Differences of cardiovascular examination between two groups were compared ( χ2 test), such as proportion of culprit vessels with severe stenosis (≥90%), proportion of bifurcation lesions, and proportion of diffuse coronary disease. Logistic regression analyses were performed to identify influencing factors for early residual myocardial ischemia. Results:Among 148 culprit vessels undergoing PCI in 127 patients, early residual myocardial ischemia was present in 49 vessels (33.1%, 49/148). The proportion of culprit vessels with severe stenosis before PCI in residual ischemia group was higher than that in non-ischemia group (69.4%(34/49) and 49.5%(49/99); χ2=5.27, P=0.022). The proportion of bifurcation lesions in residual ischemic group was also higher than that in non-ischemic group (28.6%(14/49) and 10.1%(10/99); χ2=8.23, P=0.004), with a slightly higher proportion of diffuse coronary disease compared to non-ischemic group (14.3%(7/49) and 4.0%(4/99); χ2=3.62, P=0.057). Multivariate logistic regression analysis showed that bifurcation lesion (odds ratio ( OR)=4.087, 95% CI: 1.615-10.344, P=0.003) and diffuse coronary disease ( OR=4.208, 95% CI: 1.115-15.878, P=0.034) were independent influencing factors for early residual myocardial ischemia. Conclusions:Early residual myocardial ischemia is still present in about 1/3 of the culprit vessels after PCI complete revascularization. Bifurcation lesion and diffuse coronary disease are independent influencing factors for early residual myocardial ischemia in culprit vessels.
3.Dynamic evaluation of inflammation in infarct area after acute myocardial infarction and its relationship with left ventricular remodeling by 18F-FDG PET imaging
Feifei ZHANG ; Xiaoliang SHAO ; Jianfeng WANG ; Xiaoyu YANG ; Min XU ; Peng WAN ; Shengdeng FAN ; Yunmei SHI ; Wenji YU ; Bao LIU ; Xiaoxia LI ; Xiaoyun WANG ; Baosheng MENG ; Yong WANG ; Yuetao WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(11):661-667
Objective:To evaluate inflammation early in the infarct zone and its dynamic changes after acute myocardial infarction (AMI) using 18F-FDG PET imaging, and analyze its relationship with left ventricular remodeling progression (LVRP). Methods:Sixteen Bama miniature pigs (4-6 months old, 8 females) were selected. AMI models were established by balloon occlusion of the left anterior descending artery. 18F-FDG PET imaging was performed before AMI and at days 1, 5, 8, and 14 post-AMI to evaluate the regional inflammation response. 18F-FDG SUV ratio (SUVR) and the percentage of uptake area of left ventricle (F-extent) in the infarct zone, and the SUVRs of the spleen and bone marrow, were measured. Echocardiography and 99Tc m-methoxyisobutylisonitrile(MIBI) SPECT myocardial perfusion imaging (MPI) were performed at the above time points and on day 28 post-AMI to assess left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and myocardial perfusion defect extent. The degree of LVRP at day 28 post-AMI was defined as ΔLVESV(%)=(LVESV AMI 28 d-LVESV AMI 1 d)/LVESV AMI 1 d×100%. Data were analyzed using repeated measures analysis of variance, Kruskal-Wallis rank sum test and Pearson correlation analysis. Results:Twelve pigs were successfully modeled and completed the study. Inflammation in the infarct zone persisted until day 14 post-AMI. The SUVR of the infarct zone pre-AMI and at days 1, 5, 8, and 14 post-AMI were 1.03±0.08, 3.49±1.06, 2.93±0.90, 2.38±0.76, and 1.63±0.62, respectively ( F=49.31, P<0.001). The F-extent values in the infarct zone pre-AMI and at days 1, 5, 8, and 14 post-AMI were 0, (40.08±12.46)%, (40.00±12.76)%, (31.08±12.82)%, and 16.50%(7.25%, 22.00%), respectively ( H=37.61, P=0.001). There were no significant differences in the SUVRs of bone marrow and spleen before and after AMI ( F values: 0.69 and 0.77, both P>0.05). At day 1 post-AMI, both SUVR and F-extent in the infarct zone were significantly correlated with LVRP ( r values: 0.82 and 0.70, P values: 0.001 and 0.035). Conclusions:18F-FDG PET imaging can be used to evaluate inflammation in the infarct area and its dynamic changes after AMI. Inflammation in the infarct area is severe at day 1, and then gradually decreases. The extent and severity of inflammation visible on 18F-FDG PET imaging 1 d after AMI are closely related to LVRP.
4.Effect and Mechanism of Uric Acid in Regulating Larval Growth and Development of Drosophila Melanogaster
Ruidi ZHANG ; Hongbin QIU ; Jingtao WANG ; Baosheng GUAN ; Xue BAI ; Xianglin YIN
Acta Academiae Medicinae Sinicae 2024;46(5):653-658
Objective To explore the effect and mechanism of uric acid(UA)in regulating the larval growth and development of Drosophila melanogaster.Methods A total of 1350 newly hatched first-instar larvae of wild-type Drosophila melanogaster(W11 18)were collected,and the Drosophila melanogaster model of hyperurice-mia was constructed with a high purine diet.The larvae were assigned into three groups(n=150):control(stand-ard corn meal medium),low-dose adenine(corn meal medium containing 0.05%adenine),and high-dose ad-enine(corn meal medium containing 0.10%adenine),and two parallel groups were set up.The growth and de-velopment of larvae in each group was observed,and the UA and hormone levels were measured.In addition,the expression levels of genes involved in growth and development were determined.Results Compared with the con-trol group,the low-and high-dose adenine groups showed elevated UA levels(both P<0.001)and prolonged de-velopmental period(P=0.024,P<0.001).The high-dose adenine group showed decreased survival rate,pupa-tion rate,and eclosion rate and elevated levels of juvenile hormone(JH)and 20-hydroxyecdysone(20E)(all P<0.001).The PCR results showed that compared with the control group,high-dose adenine upregulated the mRNA levels of reactive oxygen species(ROS),forkhead box O(FOXO),and mammalian target of rapamycin(mTOR)while downregulating the mRNA levels of Sestrin,mTOR complex 1(mTORC1),and AMP-activated protein kinase(all P<0.001).Conclusion High concentrations of UA may promote the expression of ROS/FOXO/mTORC1/mTOR signaling pathway by regulating the levels of JH and 20E,thereby inhibiting the larval growth and development of Drosophila melanogaster.
5.Chinese expert consensus on targeted and immunotherapy combined with concurrent chemoradiotherapy in the treatment of locally advanced cervical cancer
Ping JIANG ; Zi LIU ; Lichun WEI ; Yunyan ZHANG ; Fengju ZHAO ; Xiangkun YUAN ; Yipeng SONG ; Jing BAI ; Xiaofan LI ; Baosheng SUN ; Lijuan ZOU ; Sha LI ; Yuhua GAO ; Yanhong ZHUO ; Song GAO ; Qin XU ; Xiaohong ZHOU ; Hong ZHU ; Junjie WANG
Chinese Journal of Radiation Oncology 2024;33(10):893-901
Concurrent chemoradiotherapy (CCRT) refers to the simultaneous treatment of chemotherapy and radiotherapy, and the effect of radiotherapy is enhanced with low-dose chemotherapy, which can reduce tumor recurrence and metastasis and improve clinical prognosis of patients. At present, the main factors for the increase of radiosensitivity of concurrent chemotherapy is that concurrent chemotherapy prevents the repair of tumor cells, and chemotherapy and radiotherapy act on different cell cycles and have synergistic effects. However, even for patients with locally advanced cervical cancer (LACC) who have undergone CCRT, the 5-year survival rate is only 60%, which is still not ideal. In order to improve the efficacy, researchers have conducted a series of exploratory studies, which consist of the combination of targeted drugs and immunodrugs, and neoadjuvant regimens before CCRT, etc. Although targeted or immunologic drugs are effective treatment of LACC, in view of the lack of large-scale evidence-based medical evidence, multi-center prospective and randomized phase III clinical trials and high-level articles are needed to improve the level of evidence-based medicine. This consensus summarizes several key evidence-based medical studies published recently, especially the clinical research progress in targeted and immunological therapies, providing reference for domestic peers.
6.Effect and Mechanism of Water Extract of Mori Folium on Oxidative Stress in Adipose Tissue of T2DM Mice
Huilin ZHANG ; Yongcheng AN ; Changhao HE ; Yan HUANG ; Wanxin FU ; Menglu WANG ; Ziyi SHAN ; Yuhang DU ; Jiamei XIE ; Zhanhong JIA ; Baosheng ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(11):43-50
ObjectiveTo observe the effect of water extract of Mori Folium (MLE) on oxidative stress in adipose tissue of type 2 diabetes mellitus (T2DM) mice and explore its mechanism. MethodTwenty-four male db/db mice were randomly divided into model group, metformin group, low-dose MLE (MLE-L) group, and high-dose MLE (MLE-H) group according to their body weight and blood glucose, with six mice in each group, and other six C57BLKS/JGpt wild littermate mice were selected as normal group. The mice in the metformin group were given 200 mg·kg-1 metformin suspension, and the mice in the MLE-L and MLE-H groups were respectively given 2 g·kg-1 and 4 g·kg-1 MLE, while the mice in the normal group and model group were given the same dose of deionized water by daily gavage for eight weeks. Body weight, subcutaneous fat index, fasting blood glucose (FBG), and oral glucose tolerance level (OGTT) of the mice were detected, and serum superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) were measured. The expression levels of silent information regulator 1 (SIRT1) and NADPH oxidase type 4 (NOX4) protein in subcutaneous adipose tissue of the mice were detected by Western blot. ResultThe FBG level, OGTT, and subcutaneous fat index of T2DM mice were significantly decreased (P<0.05, P<0.01) after administration of MLE compared with the blank group. The contents of serum SOD and GSH were significantly increased, while the level of oxidative stress damage marker MDA was significantly decreased (P<0.05, P<0.01). The expression of SIRT1 protein in adipose tissue was significantly increased, while the expression of NOX4 protein was significantly decreased (P<0.05, P<0.01). ConclusionMLE can ameliorate T2DM by alleviating oxidative stress in adipose tissue of T2DM mice and reducing blood glucose.
7.Protective Effect and Mechanism of Mori Folium Extract on Kidney of db/db Diabetic Mice
Yan HUANG ; Huilin ZHANG ; Changhao HE ; Yongcheng AN ; Wanxin FU ; Menglu WANG ; Ziyi SHAN ; Yuhang DU ; Jiamei XIE ; Zhanhong JIA ; Baosheng ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(11):51-59
ObjectiveTo investigate the protective effects of Mori Folium extract (MLE) on the kidney of db/db diabetic mice and its mechanism. MethodTwenty-four male C57BLKS/JGpt-Leprdb/Leprdb (db/db) mice were randomly divided into model group, metformin group, low-dose group of MLE (MLE-L), and high-dose group of MLE (MLE-H) according to their fasting blood glucose (FBG), with six mice in each group, and other six C57BLKS/JGpt wild littermate (m/m) mice were selected as normal group. The mice in the drug administration groups were given corresponding drugs by gavage, and the mice in the normal group and model group were given the same dose of deionized water by gavage once a day for continuous eight weeks. Body weight, bilateral kidney weight, and FBG were measured, and an oral glucose tolerance test (OGTT) was performed. The pathological changes in the kidney tissue of mice were observed by hematoxylin-eosin (HE) and periodic acid-silver (PAS) staining, and serum creatinine (SCr) and blood urea nitrogen (BUN) levels were detected. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in serum and urinary microalbumin (U-mAlb) of mice. The expression levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor-kappa B p65 (NF-κB p65) protein in kidney tissue of mice were tested by Western blot. ResultCompared with the normal group, the body weight, absolute renal weight, FBG, and the area under the curve (AUC) of OGTT of mice in the model group were significantly increased (P<0.01), and the levels of SCr, BUN, and U-mAlb, as well as TNF-α and IL-6 in serum were significantly increased (P<0.01). The glomerular basement membrane in the kidney tissue of mice was thicker, with obvious inflammatory cell infiltration. The protein expression levels of TLR4, MyD88, and NF-κB p65 in the kidney tissue of mice were increased significantly (P<0.01). Compared with the model group, there was no statistical difference in the body weight of mice in each drug administration group. The absolute renal weight of mice in the MLE-H and metformin groups was significantly reduced (P<0.05, P<0.01). The FBG levels of mice in the metformin, MLE-L, and MLE-H groups started to decrease after treatment for four to eight weeks (P<0.05, P<0.01). The AUC of mice in the MLE-H and metformin groups was significantly decreased (P<0.01). The levels of SCr, BUN, and U-mAlb of mice in the MLE-H and metformin groups were significantly decreased (P<0.01), and those of SCr and U-mAlb of mice in the MLE-L group were significantly decreased (P<0.01). The levels of TNF-α and IL-6 in the serum of mice in the MLE-H and metformin groups were significantly decreased (P<0.01). The renal tissue pathology of mice in each drug administration group was improved to varying degrees, and the protein expression levels of TLR4, MyD88, and NF-κB p65 in the MLE-H group were decreased significantly (P<0.05, P<0.01). ConclusionMLE can improve the renal structure and function of db/db diabetic mice, and its mechanism may be related to the inhibition of the TLR4/MyD88/NF-κB signaling pathway.
8.Extraction Process and Mechanism of Active Ingredients of Mori Folium for Lowering Blood Glucose: A Review
Jiamei XIE ; Huilin ZHANG ; Yan HUANG ; Menglu WANG ; Yuhang DU ; Changhao HE ; Yongcheng AN ; Wanxin FU ; Ziyi SHAN ; Baosheng ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(11):60-69
Mori Folium, the dried leaves of Morus alba, is widely used in clinical practice for dispersing wind and heat, clearing the lung and moistening dryness, soothing the liver and improving vision, and cooling blood and stopping bleeding. It has been used to regulate blood glucose since ancient times, and modern studies have shown that the active components of Mori Folium for lowering blood glucose mainly include flavonoids, alkaloids, polysaccharides, and phenols. These components are mainly extracted by solvents such as water and alcohols with the assistance of ultrasound and microwave. In addition, new extraction methods are emerging, such as CO2 supercritical fluid extraction, enzymatic hydrolysis, and cloud point extraction. Mori Folium lowers blood glucose via multiple components, pathways, and targets. Specifically, it can improve glucose and lipid metabolism, protect pancreatic β cells, and alleviate insulin resistance to reduce the damage caused by hyperglycemia and restore normal physiological functions. Although a large number of studies have been carried out on diabetes, the causes and radical treatment methods remain to be explored, and diabetes is still a major disease that endangers human health and needs to be solved urgently. The articles about extraction process and mechanism of active components in Mori Folium for lowering blood glucose were retrieved from the China National Knowledge Infrastructure (CNKI), Web of Science, and PubMed. We analyzed the applicable extraction methods for the blood glucose-lowering components such as flavonoids, polysaccharides, and alkaloids in Mori Folium, and compared the conventional and emerging methods. Furthermore, we summarized our research achievements in the extraction of active components from Mori Folium and the blood glucose-lowering effect and mechanisms. This review aims to provide theoretical support for the optimization of the extraction process, the research on the blood glucose-lowering components and mechanism, and the development of new drugs and clinical application of Mori Folium.
9.Imaging diagnosis, pathological upgrade, and imaging technology progress of ductal carcinoma in situ of the breast
Lili ZHANG ; Ru TAN ; Xueli FANG ; Yu YANG ; Zheng SANG ; Baosheng LI
Journal of International Oncology 2024;51(3):166-169
Ductal carcinoma in situ of the breast (DCIS) most commonly manifests as asymptomatic calcifications at mammography. The most common manifestation of MRI is nonmass enhancement. The ultrasound mainly presents as a hypoechoic irregular hypervascular mass without posterior features. Core-needle biopsy is a commonly used method for preoperative diagnosis of DCIS. Due to differences in needle type and sample size, there is a certain degree of pathological upgrading of the lesion. In recent years, there has been controversy over the diagnosis and treatment of DCIS. With the development of breast disease diagnostic technology, advances in digital breast tomography, artificial intelligence, and radiomics are expected to help DCIS management and address issues such as overdiagnosis.
10.Pathological Mechanism of Diabetes Based on NF-κB Signaling Pathway and Traditional Chinese Medicine Intervention: A Review
Menglu WANG ; Lu SHI ; Changhao HE ; Yongcheng AN ; Yinglan LYU ; Chen WANG ; Huimin LI ; Huilin ZHANG ; Yan HUANG ; Wanxin FU ; Ziyi SHAN ; Baosheng ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):246-255
As people's living standards improve, the development trend of diabetes has gradually become severe. Diabetes is a chronic inflammatory disease associated with abnormal expression of nuclear factor-kappa B (NF-κB) in patients. NF-κB exists in various tissue cells and participates in the regulation of a variety of genes related to immune function and inflammation. Varieties of factors can activate NF-κB when the body is stimulated by external factors, so as to produce inflammation and other reactions. Previous studies on NF-κB mainly focus on cancer, and the pathological mechanism of the treatment of diabetes by related signaling pathways and the progress of traditional Chinese medicine (TCM) treatment have not been systematically elaborated on. By referring to the relevant literature in China and abroad, it was found that NF-κB is not isolated in the development and progression of diabetes but is associated with signal molecules related to inflammation, oxidative stress, and energy metabolism, and it is involved in mediating inflammation, pancreatic β cell apoptosis, insulin signal transduction, and other physiological functions. Therefore, blocking the transmission of NF-κB signaling pathway is beneficial to the treatment of diabetes. At present, Western medicine for the treatment of diabetes mainly includes oral hypoglycemic drugs and insulin injections, but the adverse reactions are obvious. TCM has been characterized by multi-target, extensive action, and excellent curative effects in the treatment of diabetes. TCM and its compounds with functions of tonifying Qi and promoting blood circulation, regulating qi and eliminating phlegm, clearing heat and detoxifying, and nourishing Yin and moistening dryness can effectively intervene in the abnormal expression of NF-κB signaling pathway in vivo through anti-inflammatory effects. In this paper, the association between NF-κB signaling pathway and diabetes was summarized, and the modern research progress of TCM intervention of NF-κB signaling pathway in the treatment of diabetes in the past five years was reviewed, so as to lay a laboratory foundation for the study of a new pathological mechanism of diabetes based on NF-κB signaling pathway and provide new targets and research direction for the prevention and treatment of diabetes and development of related TCM.

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