Studies have found that metformin is not only the preferred drug for lowering blood sugar, but also shows lipid-lowering and weight-loss effects. The purpose of this study was to use a hyperlipidemia hamster model to investigate the lipid-lowering effect of metformin and its effect on important metabolic pathways in lipid metabolism disorders. Fifty golden hamsters were divided into a control group, a model group, metformin high- and low-dose groups, and a simvastatin group. A high-fat diet was fed for 1 week to create the model, and then drug was administered for 11 weeks with the high-fat diet. Serum was taken for measurement of blood lipid and blood glucose at 2, 6, and 9 weeks after administration, and at weeks 3, 5, and 9 feces and urine were collected for ¹H NMR metabolomics tests. After 11 weeks of intravenous injection of [U-¹³C₆] glucose, serum was collected for a ¹³C NMR metabolic flux test. The results showed that the administration of metformin can significantly reduce blood lipids and glucose levels and can significantly affect metabolic pathways such as sugar metabolism, lipid metabolism, ketone metabolism, amino acid metabolism, and intestinal flora metabolism. The results of the metabolic flux analysis showed that the high-fat diet reduced the metabolism of tricarboxylic acids by 37.48%. After administration of low and high doses of metformin the metabolism of tricarboxylic acid increased by 98.14% and 143.10%, respectively. After administration of simvastatin tricarboxylic acid metabolism increased by 33.18%. The results indicate that metformin has a significant effect on promoting energy metabolism. This study used a combination of metabolomics and metabolic flow to explore the effect of metformin on lipid metabolism disorders and quantifies changes in the key pathway of energy metabolism-the tricarboxylic acid cycle. This study provides useful information for the study of the efficacy and mechanism of metformin, as well as a practical technical method for the screening of lipid-lowering drugs based on a hamster model.

OBJECTIVETo study the antiproliferation effect on HepG2 cells and its underlying mechanism of the active chemical composition of the Viburnum Odoratissimum.

METHODS3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction assay and trypan blue dye exclusion assay were used to assess the effect of vibsane-type diterpenoids on the proliferation of various tumor cells. Alterations in cell cycle and apoptosis were determined by flowcytometry. The enzymatic activity of caspase-3/7 was measured by Apo-ONE homogeneous Caspase-3/7 Assay kit.

RESULTSCompound 1 #, a vibsane-type diterpenoid, was found to significantly inhibit the growth of HepG2 cells by anticancer proliferation activity screening. It was demonstrated that the modified groups on side chain coupled to C11 site affected the cell growth-inhibition activity of compounds by structure-activity analysis. In addition, HepG2 cell line was most sensitive to compound 1 #, which induced growth arrest of HepG2 cells in a dose- and time-dependent manner. Study on the mechanisms underlying these effects indicated that compound 1 # induced significant G0/G1 phase arrest of HepG2 cells in a time- and concentration-dependent manner. Meanwhile, It was found that higher concentrations of compound (5-10 micromol/L) caused evident increase in the unmber of apoptotic cells and dose-dependent activation of caspase-3/7.

CONCLUSIONVibsane-type diterpenoids could significantly inhibit the growth of HCC HepG2 cells. Induction of cell cycle arrest and apoptosis may play important roles in their anticancer effects.

Apoptosis ; drug effects ; Cell Cycle Checkpoints ; drug effects ; Cell Proliferation ; drug effects ; Diterpenes ; pharmacology ; Hep G2 Cells ; Humans ; Viburnum ; chemistry

OBJECTIVETo investigate the effect of lead exposure on the gene expression of fibroblast growth factor 3 (Fgf3) in zebrafish embryonic development and the mechanism of lead-induced embryonic developmental toxicity.

METHODSThe embryos of zebrafish (wild types A and B) were exposed to lead acetate (PbAc) at the doses of 0, 0.1, 0.5, 2.5, and 12.5 µmol/L separately. Total RNA was extracted from each treatment group of zebrafish embryos at 8, 12, 16, 24, 36, 48, and 72 hours post fertilization (hpf). The total mRNA expression of Fgf3 was measured by real-time quantitative PCR. The spatial expression of Fgf3 in zebrafish embryos was determined by whole-mount in situ hybridization using synthesized Fgf3 RNA probe.

RESULTSThe mRNA expression of Fgf3 in each group peaked at 12 hpf (P < 0.01). With the increase in PbAc concentration, the mRNA expression of Fgf3 rose. Compared with the mRNA expression level of Fgf3 in the control group, the relative mRNA expression levels of Fgf3 in the 0.1, 0.5, 2.5, and 12.5 µmol/L PbAc exposure groups were 1.02 ± 0.24, 1.05 ± 0.26, 1.22 ± 0.46, and 1.25 ± 0.38, respectively, and the 2.5 and 12.5 µmol/L PbAc exposure groups showed significantly higher Fgf3 expression than the control group (P < 0.05). The whole-mount in situ hybridization results showed that Fgf3 expression occurred mainly in the head and tail in the early stage of embryonic development and in the midbrain, fin bud, and pharyngeal arch in the middle/late stage of embryonic development; there were the most significant regions and intensities of positive hybridization signals at 12 hpf; but no significant differences were found between the control group and exposure groups in the location and intensity of Fgf3 expression

CONCLUSIONLead exposure can result in the upregulation of Fgf3 expression in zebrafish embryonic development, which might contribute to lead-induced embryonic developmental toxicity.

Animals ; Embryonic Development ; drug effects ; Fibroblast Growth Factor 3 ; genetics ; metabolism ; Gene Expression ; Organometallic Compounds ; adverse effects ; Signal Transduction ; Zebrafish ; embryology ; genetics ; metabolism ; Zebrafish Proteins ; genetics ; metabolism

Objectiveβ‑Site APP cleaving enzyme 1 (BACE1) is a rate-limiting enzyme involved in the formation of amyloid plaques in Alzheimer’s disease (AD), and its expression and activity play a crucial role in the development of AD. The interacting protein of BACE1 can directly or indirectly regulate BACE1 in the transcription, translation, modification, intracellular transport and other links of BACE1 by directly binding, indirectly binding, and participating in various cell signal transduction pathways, so as to participate in the occurrence of AD and the process of disease. This study aimed to screen and validate the interacting proteins of BACE1, providing new insights into the mechanisms of amyloid plaque formation. MethodsCo-immunoprecipitation (Co-IP) and mass spectrometry (MS) were used to enrich and identify BACE1 interacting proteins in the hippocampus of wild type (WT) mice and AD model mice. For candidate BACE1 interacting proteins, GO enrichment analysis and KEGG pathway enrichment analysis were used to explore the subcellular localization, molecular function, participating biological processes and participating signaling pathways of BACE1 interacting proteins. The protein-protein interaction (PPI) network of BACE1 was further constructed to explore the potential proteins interacting with BACE1. By searching the mouse genomeinformation (MGI) website and NCBI database, the more reliable proteins among the potential BACE1 interacting proteins were screened. Co-IP assay and immunofluorescence confocal technology were used to preliminarily verify the interaction between the proteins, and the changes in protein expression levels of the interacting proteins in AD cell models were explored. ResultsA total of 614 differentially expressed proteins interacting with BACE1 were identified in AD group. GO enrichment analysis showed that the BACE1 interacting proteins in the AD group were mainly located in membrane organelles such as Golgi apparatus, endoplasmic reticulum, endosome, lysosome and vesicles, which had molecular functions such as ion channel regulation, protein kinase activity, transcription factor binding and passive transmembrane transporter activity. It is mainly involved in the biological processes of immune response regulation cell surface receptor signaling pathway, targeting Golgi vesicles transport, circadian rhythm regulation, Purkinje cell layer development, etc. KEGG analysis showed that BACE1 interacting proteins in AD were mainly involved in the PI3K-Akt signaling pathway, mTOR signaling pathway and other neurodegenerative disease-related pathways. The PPI network of BACE1 showed that a total of 12 proteins were identified as high confidence binding proteins, including PRNP, APOE, SYP, NSF, NUMB, SNAP91, HSP90aa1, UCHL1, BIN1, SNX27, Rheb, Ap2m1, of which, NSF, NUMB, SNAP91, HSP90aa1 were newly identified candidate proteins. After further verification, we found that NSF not only interacts with BACE1, but also interacts with amyloid precursor protein (APP), the substrate of BACE1, and the expression level of NSF is up-regulated in the AD cell model constructed by Aβ₄₂ induction. ConclusionBACE1 binding proteins participate in multiple AD-associated biological processes and signal pathways. NSF is a newly identified BACE1 binding protein that interacts with BACE1, and the protein expression level of NSF is up-regulated in the AD cell model. It is predicted that the interaction between NSF and BACE1 is involved in regulating the course of AD, providing a new target and direction for the study of the mechanism of AD.

Familial isolated pituitary adenoma (FIPA) is an autosomal dominant disease, characterized by low penetrance, early-onset disease, more invasive tumor growth, as well as somatotroph and lactotroph adenomas in most cases. It has been indicated that the aryl hydrocarbon receptor interacting protein (AIP) gene is a tumor suppressor gene. Many heterozygous mutations have been discovered in AIP in about 20% of FIPA families. However, the exact molecular mechanism by which its disfunction promotes tumorigenesis of pituitary is unclear.
Growth Hormone-Secreting Pituitary Adenoma ; genetics ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; Mutation ; Pituitary Neoplasms ; genetics

Objective To summarize the diagnostic and therapeutic experiences for multiple insulinoma. Methods Clinical data of 34 cKsefl of multiple insulinoma treated in Peking Union Medical College Hospital between 1984 and 2007 were analyzed retrospectively. Results Multiple insulinoma was identified in these 34 cases for 37 instances.Malignant insulinoma was found in 2 cases.Three cases suffered from postoperative recurrent multipie tumors.35.3% cases belonged to MEN1;13.5% cases were of insulinoma combined with islet hyperplasia;43.2% cases had 3 or more than 3 insulinomas;Fifteen cases (40.5%)had had a misdiagnosis.45.2%tumors were smaller than 1 cm in diameter:88.9%multiple insulinonla located at the body and tail of the pancreas.Enucleation of multiple tumors was performed for 48.7 percent of cases. Conclusions Most multiple insulinomas were small,it was difficult for preoperative examination to locate all the tumors therefore.Being on the alert against multiple insulinoma and such measures as careful exploration,intraoperative blood glucose determination.fine needle aspiration biopsy,frozen sections helps to avoid missing multiple imuhnoma.

The research advances based on the related references were summarized in the last thirty years. Bauhinia contained many kinds of chemical constituents, primarily including flavanoids, steroids, terpenoid and so on, some of them were firstly obtained from the nature. Many plants of the Bauhinia are used in traditional medicine for their interesting biological activities such as antidiabetic, antiinflammatory, antimicrobial, analgesic, astringent and diuretic effects. This paper gives an overview of phytochemical and pharmacological research in Bauhinia, and it has been classified accordding to the chemical structure characteristics. To provide more material to draw on for further development and utilization resources of Bauhinia.
Bauhinia ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Phytotherapy

Background Infective keratopathy is a key cause of corneal blindness in China,and fungal keratitis is proved to have a higher incidence and bigger threats in infective keratitis.Researches showed that topical immunology plays an important effect during the development of fungal keratitis,but its mechanism is still studying.Objective This experiment was to explore the critical immunocyte during the process of fungal keratitis.Methods Forty-eight SPF 12-week-old male C57BL/6J mice were included and randomized into the control group and model group.The fungal keratitis model closely mimicking human cornea infections was established in the mouse using scratch followed by incubation of fusarium solani on the cornea,and the mice in the control group scratched on the cornea only.Cornea was examined under the slit lamp at 0,6,9,12,24,72 and 120 hours after operation.The severity of keratomycosis was clinically scored based on the literature criteria.The inflammatory cells were identified using immnofluorescence label,and the number of the inflammatory cells was calculated and compared among different groups and time points.This study complied with the Statement of ARVO in the use of experimental animal.Both Experimental Animal Ethic Commission in Zhengzhou University and Life Science Management Commission approved this study proposal.Results After inoculation of fusarium solani,typical fungul keratitis signs were seen on the cornea.Severe corneal opacifieation occurred within 24 hours and peaked at 72 hours.However,only mild edema of cornea was exhibited and gradually recovered normal in the control group within 24 hours.The clinical score of inflammation was higher in the model group in various time points than that in the control group,and it was seen that 24-72 hours after operation,the score attached peak in the model group with a significant difference in comparison with the control group(P＜0.01).In 9,12,24,72 and 120 hours after operation,the number of neutrophil cells was significantly increased in the model group compared with control group (P＜0.05),and that in 12,24,72 hours after operation was significantly higher than the 6 hours(P=0.004,0.000,0.001).However,no significant differences were seen in the number of neutrophil cells between 9 or 120 hours and 6 hours after operation(P=0.772,0.323).The number of T lymphocytes in cornea was significantly increased in 72 and 120 hours in comparison with 6 hours in the model group(P=0.000,0.000),and from 72 to 120 hours after operation,the number of T lymphocytes was significantly higher than that of the contral group (P＜0.01).The neutrophil cell number was positive correlated with the inflammatory score in the early phase (r =0.593,P =0.000).T limphocyte emerged in late phase but no significant correlation with the clinical score (r＝0.315,P=0.062).Conclusions Neutrophil cells play a critical role in the development of fungal keratitis in early stage.

OBJECTIVE: To study the effect of low-dose dopamine adjuvant therapy on inflammatory factors and prognosis in preterm infants with necrotizing enterocolitis (NEC). METHODS: A total of 100 preterm infants with NEC from June 2017 to June 2019 were enrolled and divided into a dopamine treatment group and a conventional treatment group using a random number table, with 50 infants in each group. The infants in the conventional treatment group were given symptomatic treatment, and those in the dopamine treatment group were given low-dose dopamine adjuvant therapy in addition to the conventional treatment. ELISA was used to measure the levels of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-8 (IL-8). The two groups were compared in terms of time to relief of clinical symptoms, fasting time, treatment outcome, prognosis, and adverse reactions. RESULTS: Both groups had significant reductions in the levels of CRP, TNF-α, and IL-8 after treatment, and the dopamine treatment group had significantly lower levels of these markers than the conventional treatment group after treatment (P<0.05). Compared with the conventional treatment group, the dopamine treatment group had significantly shorter time to defecation improvement, time to relief of abdominal distension and diarrhea, and fasting time (P<0.05), a significantly higher response rate (P<0.05), and a significantly lower surgery rate (P<0.05). There were no significant differences in the mortality rate and incidence of adverse events between the two groups (P>0.05). CONCLUSIONS Low-dose dopamine adjuvant therapy can effectively improve the levels of inflammatory factors and clinical symptoms in preterm infants with NEC and has good safety, and therefore, it holds promise for clinical application.

Objective:To evaluate the clinical application value of MR amide proton transfer weighted imaging (APTWI) in predicting the pathological grade of brainstem glioma (BSG).Methods:The data of 41 BSG patients in Beijing Tiantan Hospital, Capital Medical University from August 2019 to June 2020 who underwent both MRI and APTWI 2 weeks before surgery and had pathological grading results were retrospectively analyzed. According to the pathological results, 41 patients were classified into high-grade BSG (20 patients) and low-grade BSG (21 patients). Combined with conventional MR images, the signal intensity (%) of amide proton transfer (APT) in the parenchymal area of the tumor was obtained on APTWI images. χ 2 test or independent sample t-test was used to analyze the differences in gender distribution, age and APT signal intensity between patients with high and low grade BSG. Receiver operating characteristic (ROC) curve was drawn to predict the efficacy of APT signal intensity in the differential diagnosis of high and low grade BSG, and Youden index was calculated to obtain the optimal diagnostic threshold; the predictive ability of APT signal intensity was analyzed in combination with Hosmer-Lemeshow goodness of fit test. Results:There was no significant difference in age [(23±18) years, (20±17) years, t=0.97, P=0.340] and gender distribution (9/11, 9/12 for males/females, χ 2=0.02, P=0.890) between high-grade and low-grade BSG patients. The APT signal intensity of high-grade BSG [(3.9±0.9)%] was significantly higher than that of low-grade BSG [(2.8±0.9)%], and the difference had statistical significance ( t=4.16, P<0.001). The area under the ROC curve of APT signal intensity to distinguish high-grade and low grade BSG was 0.836, and with 2.85% as the optimal diagnostic threshold of APT signal intensity, its sensitivity for the diagnosis of high-grade BSG was 90.0% and specificity was 71.4%. The Hosmer-Lemeshow test showed that APTWI had a good predictive ability for BSG grade (χ 2=13.33, P=0.101). Conclusion:APTWI can be applied in distinguishing high grade BSG from low grade BSG, and has clinical value in predicting glioma grading.