1.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.
2.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.
3.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.
4.Research Progress of Macrophages in Development of Radiation Pneumonitis and Pulmonary Fibrosis
Yaping XU ; Jiamei FU ; Yujie YAN
Cancer Research on Prevention and Treatment 2023;50(7):647-651
Radiation pneumonitis and pulmonary fibrosis are important dose-limiting side effects of radiotherapy that influence the prognosis and quality of life of patients with thoracic cancer. The disorder of the immune system plays a key role, especially macrophages. With the discovery of underlying molecular mechanisms, including the chemotaxis and polarization of macrophages, the infiltration of inflammatory cells, the release of inflammatory and pro-fibrotic factors, extracellular matrix deposition and the remodeling of lung structure, increasing strategies are under investigation to facilitate the prevention or treatment of lung injury via targeting macrophages. In this paper, the role of macrophages in the development of radiation pneumonitis, pulmonary fibrosis, and potential drug use strategies were reviewed.
5.Diagnosis and treatment recommendations of dialysis patients with SARS-CoV-2 infection for primary care clinicians
Rongguo FU ; Zhao CHEN ; Lining JIA ; Li WANG ; Jin HAN ; Lifang TIAN ; Xianghui CHEN ; Linting WEI ; Fuqian LEI ; Jiamei LU ; Xiaoqin MA ; Li ZHAO ; Shizhuo WEI ; Jing LIU ; Zhaoyang DUAN ; Jie GAO
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(3):353-360
End-stage renal disease (ESRD) patients undergoing outpatient hemodialysis (HD) and home peritoneal dialysis (PD) are high risk population of severe and critical types caused by SARS-CoV-2 infection. In order to improve the quality of diagnosis and treatment in dialysis patients with SARS-CoV-2 infection, we wrote this recommendation for primary care clinicians. During the epidemic period of SARS-CoV-2 infection, all patients should be instructed to strengthen self-management. Once the SARS-CoV-2 infection was found in dialysis patients, early stratified management should be carried out within 72 hours after the first positive nucleic acid or antigen test results, which includes early antiviral therapy, early recognition, and transferring severe patients from community or primary hospital to a referral hospital promptly. Guidance for dietary and sports rehabilitation after SARS-CoV-2 infection should also be started as soon as possible.
6.Role of GDC-0449 in a rat model of liver fibrosis induced by carbon tetrachloride combined with 2-acetylaminofluorene
Yonghong HU ; Zhun XIAO ; Yadong FU ; Yue LIANG ; Linzhang ZHANG ; Wei LIU ; Yongping MU ; Chenghai LIU ; Ping LIU ; Jiamei CHEN
Journal of Clinical Hepatology 2022;38(2):334-341
Objective To investigate the intervention effect of GDC-0449, a hedgehog signaling pathway inhibitor, on rats with liver fibrosis induced by carbon tetrachloride (CCl 4 ) combined with 2-acetylaminofluorene (2-AAF). Methods A total of 18 female Fisher344 rats were randomly divided into normal group, CCl 4 /2-AAF group, and GDC-0449 group, with 6 rats in each group. The rats in the CCl 4 /2-AAF group and the GDC-0449 group were given subcutaneously injected 30% CCl 4 -olive oil solution at a dose of 2 mL/kg twice a week for 6 weeks to induce liver fibrosis; since week 7, in addition to the injection of CCl 4 -olive oil solution, the rats in these two groups were given 2-AAF (100 mg/kg/d) by gavage, and the rats in the GDC-0449 group were given GDC-0449 (25 mg/kg/d) by gavage, while those in the normal group were given an equal volume of olive oil solution by injection and normal saline by gavage. All rats were sacrificed at the end of week 9, and related samples were collected. HE staining and sirius red (SR) staining were used to observe the changes in liver histopathology and collagen deposition, and the semi-quantitative analysis of SR-positive area and Ishak score were used to evaluate fibrosis degree; the alkaline hydrolysis method was used to measure the level of hydroxyproline (Hyp) in liver tissue; immunohistochemistry, Western blot, and qRT-PCR were used to measure the expression of α-smooth muscle actin (α-SMA), type Ⅰ collagen (Col-Ⅰ), type Ⅳ collagen (Col-Ⅳ), cytokeratin 19 (CK19), cytokeratin 7 (CK7), the epithelial cell adhesion molecule Epcam, and the hedgehog signaling pathway in liver tissue; double immunofluorescence staining was used to observe the colocalization of CK19 and the oval cell marker OV6. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the normal group, the CCl 4 /2-AAF group had marked inflammatory cell aggregation and collagen deposition in liver tissue, with the formation of a pseudolobular structure, as well as significant increases in Hyp level and collagen positive area ratio in liver tissue ( P < 0.05), Ishak score ( P < 0.05), and the expression of α-SMA, Col-Ⅰ, Col-Ⅳ, Epcam, CK19, CK7, the transmembrane transporter Smoothened (Smo), Hedgehog ligand Desert Hedgehog (Dhh), the Indian Hedgehog membrane-binding receptor Patched (Ptch2), and glioma-related oncogenes Gli1, Gli2, and Gli3 (all P < 0.05); double immunofluorescence staining showed that CK19-positive cells also expressed OV6 in the liver tissue of rats in the CCl 4 /2-AAF group, with a significant increase compared with the normal group. Compared with the CCl 4 /2-AAF group, the GDC-0449 group had significant reductions in inflammatory cell aggregation and collagen deposition in liver tissue, Hyp level and collagen positive area ratio in liver tissue ( P < 0.05), Ishak score ( P < 0.05), and the expression of α-SMA, Epcam, CK19, CK7, Smo, Ptch2, Gli1, Gli2, and Gli3 (all P < 0.05); double immunofluorescence staining showed a significant reduction in the number of cells with co-expression of OV6 and CK19 in liver tissue. Conclusion The Hedgehog signaling pathway inhibitor GDC-0449 can significantly inhibit the progression of liver fibrosis induced by CCl 4 /2-AAF in rats, possibly by inhibiting hepatic stellate cell activation, collagen deposition, activation and proliferation of hepatic progenitor cells, and differentiation of hepatic progenitor cells into biliary epithelial cells.
7. Risk factors analysis and prognosis of renal pelvis dilatation in high-risk infants in monocenter
Qian FU ; Lirong FAN ; Ying SHEN ; Gaojun ZHOU ; Huizhen YI ; Ning SUN ; Jiamei WANG ; Liqun JIA ; Xiaoman WANG ; Hui WANG
Chinese Journal of Pediatrics 2018;56(1):53-57
Objective:
To explore the prognosis and risk factors of pyelectasis in high-risk infants.
Methods:
This was a retrospective study. Totally 960 high-risk infants, who accepted type B ultrasonic examination for fetus at 28th week of gestation and for newborns in 48 hours after birth, were included in the study in departments of obstetrics and eonatology, Shunyi Maternal and Children's Hospital of Beijing Children's Hospital during May 2012 to April 2013. The degree of pyelectasis was classified using Grignon grade and the paients were followed up for 3 years. The factors of epidemiology, high risk pregnant women, fetus and high-risk newborns that relate to pyelectasis were summarized. High-risk factors were analyzed by using logistic multivariate regression analysis.
Results:
Of 960 high-risk infants, 103 had abnormal urinary ultrasound results, 87 (9.1% of high-risk infants) were diagnosed with pyelectasis, 16 (1.7% of high-risk infants) were diagnosed with congenital anomalies of the kidney and urinary tract. According to the degree of pyelectasis, 68 infants were Grignon grade Ⅰ, male:female ratio=5.8∶1, left side:right side ratio=1.91∶1; 19 infants were Grignon grade Ⅱ, male:female ratio=5.33∶1, left side:right side ratio=2.12∶1. Postnatal follow-up results showed that pyelectasis disappeared in 48 cases (55% of pyelectasis cae), 40 infants were Grignon grade Ⅰ (59% of all Grignon grade Ⅰ patients), 8 infants were Grignon grade Ⅱ (42% of all Grignon grade Ⅱ patients); The result of risk factors analysis showed that the risk of pyelectasis in males was 4.368 times that of females (95%

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