Neuregulin-1,a member of the epidermal growth factor family,plays an important role in the neuronal survival,development,migration,myelin formation,and synaptic plasticity and function. This article mainly summarized the structure and function of neuregulin1 and its neuroprotective roles in cerebral ischemia. Tne neuroprotective mechanisms of neuregulin-1 may include the inhibition of the early inflammatory response and apoptosis,and the regulation of the expression the neurotrophic factors.

The present paper is aimedto investigate the effect of basic fibroblast growth factor (bFGF) on proliferation, migration and differentiation of endogenous neural stem cell in rat cerebral cortex with global brain ischemia-reperfusion. A global brain ischemia-reperfusion model was established. Immunohistochemistry was used to observe the pathological changes and the expression of BrdU and Nestin in cerebral cortex. RT-PCR was used to measure the NSE mRNA in brain tissue. The results of measurements indicated that in sham operation group, there was no positive cell in cerebral cortex, and the content of NSE mRNA did not change. In the operation group, the expression of BrdU and Nestin increased significantly at the end of the 3rd day, and peaked on the 7th day. NSE mRNA expression did not significantly increase. In bFGF group, compared with sham operation group and model group, the number of BrdU-positive and Nestin-positive cells increased significantly at each time point (P<0. 05), and peaked at the end of the 11th day, and the content of NSE mRNA increased significantly (P<0. 05). This research demonstrated that the proliferation of endogenous neural stem cells in situ could be induced by global cerebral ischemia and reperfu- sion, and could be promoted and extended by bFGF. In additiion, bFGF might promote endogenous neural stem cells differentiated into neurons.
Animals ; Brain Ischemia ; pathology ; Cell Differentiation ; Cell Movement ; Cell Proliferation ; Cerebral Cortex ; cytology ; metabolism ; pathology ; Fibroblast Growth Factor 2 ; pharmacology ; Nestin ; metabolism ; Neural Stem Cells ; drug effects ; Rats ; Reperfusion Injury

BACKGROUND:Cordyceps polysaccharide is a commonly used adjuvant drug for clinical treatment of nephrotic syndrome. As a classic model of nephrotic syndrome induced by adriamycin, the Sprague-Dawley rat model of nephrotic syndrome exhibits similar clinical manifestations and pathological changes to minimal-change nephropathy in humans. OBJECTIVE:To observe the effect of adipose-derived mesenchymal stem cel s (ADMSCs) transplantation combined with cordyceps polysaccharide on renal function and hypercoagulable state in rats with nephrotic syndrome. METHODS:ADMSCs suspension was made in vitro and labeled using PKH26. Fifty Sprague-Dawley rats were randomized into normal (no intervention), model, ADMSCs, cordyceps polysaccharide and combined treatment groups (n=10/group). Adriamycin administration was performed to make rat models of nephrotic syndrome in the latter three groups. After modeling, model rats were respectively given no treatment, ADMSCs intravenously for 3 days, cordyceps polysaccharide intragastrical y for 12 weeks, or their combined use. Then, 24-hour urinary protein, serum total cholesterol, triglyceride, total protein, albumin, high-density lipoprotein, low-density lipoprotein, creatinine, blood urea nitrogen levels and coagulation changes were detected at 12 weeks. Meanwhile, histopathological changes of renal tissues were observed under light microscope;survival and distribution of PKH26-labeled ADMSCs were observed by fluorescence microscopy;and expression of Hpa gene in renal tissue was detected by RT-PCR. RESULTS AND CONCLUSION:Compared with the model group, the 24-hour urinary protein, serum total cholesterol, triglyceride, low-density lipoprotein, creatinine, and blood urea nitrogen levels were significantly lower, while the serum total protein, albumin and high-density lipoprotein levels were significantly higher in the three treatment groups (P<0.05). These indicators showed significant differences between the combined group and ADMSCs and cordyceps polysaccharide groups (P<0.05). Both ADMSCs transplantation and cordyceps polysaccharide significantly relieved the hypercoagulable state of rats with nephrotic syndrome, and their combined effects were stronger (P<0.05). After treatment, the pathological improvement in the kidney tissues was found in the three treatment groups;moreover, it was better in the combined treatment group than the ADMSCs and cordyceps polysaccharide groups. Better improvement in the number of PKH26-labeled ADMSCs and the expression of Hpa mRNA was observed in the combined treatment group compared with the ADMSCs and cordyceps polysaccharide groups. In conclusion, the combination of ADMSCs transplantation and cordyceps polysaccharide can improve kidney function and hypercoagulable state in rats with nephrotic syndrome, reducing pathological damage to the kidney tissue.

Objective To investigate the MRI features of intracranial solitary fibrous tumors/hemangiopericytomas (SFT/HPC),and to compare these findings with those of intracranial meningiomas.Methods The clinical features and MRI findings in 28 patients of intracranial SFT/HPC (SFT/HPC group)and 68 patients of meningiomas (meningiomas group) confirmed by operation and pathology were retrospectively analyzed.The indicators of two groups were compared.Results Shape of tumor,signal homogeneous,signal voids of vessel in tumor,hypointense signal nodules on T2WI and enhanded,cystic or necrosis in tumor,meningeal tail sign,changes of the nearby bone,sex,Ki-67％ level,blood lose in surgery had significant differences between SFT/HPC group and meningiomas group (all P＜0.05).Conclusion There are some differences between intracranial SFT/HPC and meningiomas.It is helpful in diagnosis and differential diagnosis through the comparative analysis of the imaging signs.

Objective To study the inhibitory effect of arsenic trioxide(As_2O_3) on the tumor growth of breast cancer cell line MCF-7 implanted subcutaneously in nude mice and its mechanism.Methods BALB/C-nu/nu nude mice were subcutaneously injected with MCF-7 breast cancer cell line,and treated with intraperitoneal injection of As_2O_3 and 5-FU in different concentrations.The implanted tumor was weighed,and the tumor inhibition rates were calculated.The apoptosis of the implanted tumor was detected by flow cytometry.The expressions of bcl-2 and Fas induced by As_2O_3 were examined by immunohistochemical method.Routine blood test and bone marrow test were used to observe the function of hematopoietic system after As_2O_3 treatment.Results The growth of implanted tumor was markedly inhibited with 5-FU,low dose and high dose As_2O_3,the inhibitory rates being 38.33%、51.42% and 62.43%,respectively.The inhibitory effect of As_2O_3 was significantly stronger than that of 5-FU(P

AIM: To investigate the effect of telmisartan on intestinal flora and metabolite TMAO in atherosclerosis. METHODS: Seventeen ApoE

Objective To investigate the establishment of a six-gene-edited pig-to-non-human primate kidney xenotransplantation model. Methods The kidney of humanized genetically-edited pig (GTKO/β4GalNT2KO/CMAHKO/hCD55/hCD46/hTBM) was transplanted into a cynomolgus monkey. The survival of the recipient and kidney condition after blood perfusion were observed. The parenchymal echo, blood flow changes, and size of the kidney were monitored on a regular basis. Routine blood test, kidney function test and electrolyte assessment were carried out. Dynamic changes of urine, feces and body mass were monitored. At the end of life, the transplant kidney, heart, liver, spleen, lung, and cecum were collected for pathological examination. Results The recipient died at postoperative 7 d. After blood flow was restored, the kidney was properly perfused, the organ was soft and the color was normal. At the end of the recipient's life, a slight amount of purulent secretion was attached to the ventral side of the kidney, with evident congestion and swelling, showing the appearance of "red kidney". Postoperatively, the echo of renal parenchyma was increased, blood flow was decreased, the cortex was gradually thickened, and a slight amount of effusion surrounded the kidney and abdominal cavity over time. In the recipient, the amount of peripheral red blood cells, hemoglobin, albumin, and platelets was progressively decreased, and serum creatinine level was increased to 308 μmol/L at postoperative 7 d, whereas the K⁺ concentration did not significantly change. Light yellow urine was discharged immediately after surgery, diet and drinking water were resumed within postoperative 3 h, and light yellow and normal-shape stool was discharged. The reddish urine was gradually restored to normal color within postoperative 1 d, which were consistent with the results of the routine urine test. A large amount of brown bloody stool was discharged twice in the morning of 2 d after surgery. Omeprazole was given for acid suppression, and the stool returned to normal at postoperative 4 d. The β₂-microglobulin level was increased to 0.75 mg/L at postoperative 7 d. The body mass was increased by 1.7 kg. Autopsy pathological examination showed interstitial edema and bleeding of the transplant kidney, a large amount of infiltration of lymphocytes and macrophages, infiltration of lymphocytes in the arteriole wall and arterial cavity, accompanied by arteritis changes, lymphocyte infiltration in the cecal stroma and congestion in the spleen tissues. No significant abnormal changes were observed in other organs. Conclusions The humanized genetically-edited pig-to-non-human primate kidney xenotransplantation model is successfully established, and postoperative survival of the recipient is 1 week.

Objective:To analyze the molecular characteristics of hemagglutinin-neuraminidase (HN) gene of human parainfluenza virus type 3 (HPIV3) among the cases with acute respiratory tract infection (ARI) in Henan Province.Methods:Nasal/throat swab samples collected from patients with severe acute respiratory tract infection (SARI) in Luohe and patients with influenza-like illness (ILI) in Zhengzhou were used in this study. HPIV nucleic acids in the samples were detected using real-time fluorescent PCR. HPIV3-positive samples were subjected to RT-PCR for the amplification of HN genes and the sequences were analyzed with Sanger method. CExpress and MEGA7.0 software were used for sequences editing, evolution tree construction and gene sequence analysis.Results:A total of 374 throat swab samples collected form ARI cases in Luohe and Zhengzhou were tested and 20 (5.3%) of them were positive for HPIV3. Eighteen HPIV3 HN gene sequences were successfully amplified and all belonged to C3 subgroups, including 16 sequences of C3f genotype and two sequences of C3a genotype. The 18 HN gene sequences shared the homology of 97.6%-100.0% in nucleotide and 99.3%-100.0% in amino acid, but the differences between them and the prototype strain Wash/47885/57 were significant. There were 12 amino acid mutations shared by them, including four function-related mutations (H295Y, I391V, D556N and I53T). There were no significant differences in the nucleotide or amino acid sequences as compared with the epidemic strain of China/BCH4210A/2014.Conclusions:The C3f and C3a branches of HPIV3 were the epidemic genotypes in Henan Province in recent years and a local circulating prevalence might be established. Continuous and in-depth monitoring of HPIV3 C3 subtype would be of great significance for the prevention and control of HPIV3-associated diseases.

OBJECTIVETo synthesize compounds based on imidazo-fused heterocycles and evaluate their anti-tumor activity against breast cancer.

METHODSThe compounds 1a-1e, 2a and 2b were synthesized by aerobic copper-catalyzed halocyclization of methyl N-heteroaromatics with aliphatic amines; 3a and 3b were generated by sonogashira reaction and Suzuki reaction, respectively; the compounds 4a-4c were obtained by Buchwald-Hartwig reaction of the corresponding amines and 1e. The effects of these compounds against breast cancer cells and their nephrotoxicity were determined using MTT assay. Annexin VFITC/PI apoptosis detection kit was used to assess the apoptosis-inducing effects of these compounds in breast cancer cells. With normal saline as the control, the safety and anti-tumor activity of the compound 2a (daily dose of 10 mg/kg for 14 days) was tested in a mouse model bearing human breast cancer xenografts.

RESULTSThe compounds 2a, 4a, 4b and 4c all showed obvious anti-tumor activities. Among these compounds, 2a showed the most potent anti-tumor effect against breast cancer cells with an IC of 9.77 ± 2.32 μmol/L, similar to that of cisplatin (IC=8.96 ± 2.35 μmol/L); 2a also showed a slightly lower nephrotoxicity than cisplatin, and their CC was 10.79±0.87 μmol/L and 8.45±0.68 μmol/L, respectively. 2a obviously promoted apoptosis of breast cancer cells and caused a moderate suppression of the breast cancer growth in the tumor-bearing mouse models without producing serious adverse effects.

CONCLUSIONSFour compounds synthesized based on imidazo-fused heterocycles have anti-tumor activities against breast cancer. The compound 2a is capable of dose-dependently promoting apoptosis of breast cancer cells and has a good safety and a moderate efficacy for suppressing tumor growth in mouse models bearing human breast cancer xenografts.

Seven new 4-hydroxybenzyl-substituted amino acid derivatives (1-7), together with 11 known compounds, were isolated from an aqueous extract of the rhizomes of Gastrodia elata Blume. Their structures were determined by spectroscopic and chemical methods. Compounds 1-3 are pyroglutamate derivatives containing 4-hydroxybenzyl units at the N atom and 4-7 are the first examples of natural products with the 4-hydroxybenzyl unit linked via a thioether bond to 2-hydroxy-3-mercaptopropanoic acid (4-6) and 2-hydroxy-4-mercaptobutanoic acid (7), which would be biogenetically derived from cysteine and homocysteine, respectively. The structures of 1 and 2 were verified by synthesis, while the absolute configurations of 4, 5 and 7 were assigned using Mosher's method based on the MPA determination rule of Δδ RS values. The known compound 4-(hydroxymethyl)-5-nitrobenzene-1,2-diol (8) exhibited activity against Fe(2+)-cysteine induced rat liver microsomal lipid peroxidation with IC50 values of 9.99×10(-6) mol/L.