Terpine-4-ol on inhibiting vascular smooth muscle cell calcification by improving mitochondrial dynamics / 药学学报

The aim of this study was to investigate the role and mechanism of terpinen-4-ol (T4O) on high glucose (HG) -induced calcification in vascular smooth muscle cell (VSMC). To investigate the role of T4O on HG-induced calcium deposition, osteogenic phenotypic transformation and mitochondrial dynamics in VSMC, Mdivi-1, a mitochondrial dynamin-related protein 1 (Drp-1) inhibitor, was used to analyze the correlation between mitochondrial dynamics and VSMC calcification and the role of T4O. Alizarin red S staining was used to observe calcium salt deposition and flow cytometry to detect intracellular Ca2+ content; Western blot and immunofluorescence were used to detect the expression of phenotypic switching-related markers α-smooth muscle actin (α-SMA), bone morphogenetic protein 2 (BMP2) and Runt related transcription factor 2 (Runx2), and mitochondrial dynamics-related markers mitofusin 1 (MFN1), mitofusin 2 (MFN2) and Drp-1. The results showed that low and high doses of T4O could inhibit HG-induced down-regulation of α-SMA, MFN1 and MFN2 expression levels, and up-regulation of BMP2, Runx2 and Drp-1 expression levels, reduce intracellular Ca2+ content and calcium salt deposition, and effectively inhibit HG-induced VSMC calcification and mitochondrial dynamics disorders. The T4O group, Mdivi-1 group and T4O+Mdivi-1 group were able to up-regulate the expression levels of HG-induced α-SMA, MFN1 and MFN2, down-regulate the protein expression levels of BMP2, Runx2 and Drp-1, and inhibit calcium salt deposition, and there was no significant difference between the above indexes in the T4O and T4O+Mdivi-1 groups. The above findings suggest that T4O can inhibit the expression level of Drp-1, regulate the disturbance of mitochondrial dynamics, and suppress HG-induced VSMC calcification.

Dysideanones F-G and dysiherbols D-E, unusual sesquiterpene quinones with rearranged skeletons from the marine sponge Dysidea avara / 中国天然药物

Four new sesquiterpene quinone meroterpenoids, dysideanones F-G (1-2) and dysiherbols D-E (3-4), were isolated from the marine sponge Dysidea avara collected from the South China Sea. The new structures were elucidated by extensive analysis of spectroscopic data including HR-MS and 1D and 2D NMR spectra, and their absolute configurations were assigned by single-crystal X-ray diffraction and ECD calculations. Anti-inflammatory evaluation showed that dysiherbols D-E (3-4) exhibited moderate inhibitory activity on TNF-α-induced NF-κB activation in human HEK-293T cells with IC50 values of 10.2 and 8.6 μmol·L-1, respectively.

Morphological and molecular characterization of Fusarium spp. associated with Fusarium wilt disease of Piper nigrum L. in Northwestern region of Sarawak

Aims@#Piper nigrum L. (black pepper) is an economically important commodity plant in Malaysia, which generated RM 200.95 million from pepper export in the year of 2018. However, the increase in pepper production is restricted by diseases. Fusarium wilt is one of the major diseases of P. nigrum L. The objectives for this study were to isolate Fusarium spp. associated with Fusarium wilt of P. nigrum L. from selected pepper farms in the northwestern region of Sarawak and to characterize the Fusarium spp. isolated morphologically and molecularly.@*Methodology and results@#Fusarium spp. were isolated from diseased root samples. The pathogen was grown on potato dextrose agar (PDA) under dark condition at circa (ca.) 25 °C for morphological characterisation. Molecular characterisation was done by using internal transcribed spacer (ITS). Phylogenetic tree was constructed to study the genetic relationship of the isolates. Fusarium solani, F. oxysporum, F. proliferatum were the three Fusarium species identified. There were variations in morphological characters observed between and among the species, including the colony form, margin, elevation, surface appearance and pigmentation. No distinctive morphological characteristic was specific to a location. In addition, growth rate, macroconidia sporulation rate, and microconidia sporulation rate of the isolates were not correlated. In molecular phylogeny, the three Fusarium species were separated into three distinct clades representing the three identified species. The genetic relatedness between isolates within each species was depicted in the tree. @*Conclusion, significance and impact of study@#Variations were observed among isolates in this study based on morphological and molecular characterization. This study would contribute information on the variations of Fusarium spp. associated with Fusarium wilt of P. nigrum L. from the northwestern region of Sarawak.

Analysis on related factors of myocardial fibrosis in patients with hypertrophic cardiomyopathy / 中华心血管病杂志

Objective: To investigate the related factors of myocardial fibrosis in patients with hypertrophic cardiomyopathy. Methods: Patients with hypertrophic cardiomyopathy, hospitalized in the First People's Hospital of Yunnan Province from January 2016 to May 2020, were included in this cross-sectional study. Patients were divided into delayed enhancement positive group (fibrosis group) and non-delayed enhancement group (non-fibrosis group). According to the maximum left ventricular end diastolic wall thickness (LVMWT), patients in the fibrosis group was further divided into mild hypertrophy group, moderate hypertrophy group and severe hypertrophy group. The baseline clinical data of patients were collected by medical record management system. All enrolled patients underwent cardiac magnetic resonance imaging (CMR). The presence and location of myocardial fibrosis were identified by CMR gadolinium contrast delayed enhancement (LGE). The range of LGE (LGE%) was calculated by visual analysis. The levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) in peripheral blood were measured . Results: A total of 48 patients ( age (46.4±14.3) years, 42 (87.5%) males) were enrolled. There were 34 LGE positive cases (fibrosis group) and 14 LGE negative cases (non-fibrosis group). Compared with non-fibrosis group, patients in fibrosis group were younger (P=0.038) and prevalence of NYHA grade Ⅲ/Ⅳ was higher (P=0.00). Compared with non-fibrosis group, patients in fibrosis group had thicker LVMWT (P= 0.008), higher left ventricular mass index(LVMI) (P=0.001), higher left ventricular end diastolic volume (LVEDV) (P=0.043), lower left ventricular ejection fraction (LVEF) and cardiac index (CI) (all P <0.05). The levels of NT-proBNP and cTnI were significantly higher in fibrosis group than in non-fibrosis group (2 760.5 (1 503.4, 3 783.6) ng / L vs. 861.3 (552.2, 1 092.8) ng / L, P=0.002; 0.970 (0.448, 1.684)μg / L vs. 0.147 (0.033, 0.251)μg / L, P=0.041).In fibrosis group, there were 15 cases of mild hypertrophy (mild hypertrophy group), 10 cases of moderate hypertrophy (moderate hypertrophy group), and 9 cases of severe hypertrophy (severe hypertrophy group). The LGE% and NT-proBNP and cTnI increased in proportion with increasing myocardial hypertrophy (P<0.05). LGE% was negatively correlated with age (r=-0.618, P=0.011), and positively correlated with NT-proBNP and cTnI levels (r=0.271, P=0.010; r=0.111,P=0.013, respectively), and positively correlated with LVEDV, LVMWT and LVMI (r=0.438, P=0.09; r=0.735, P=0.001; r=0.532, P=0.034, respectively). Conclusions: In patients with hypertrophic cardiomyopathy, the extent of myocardial fibrosis increases with the increase of myocardial hypertrophy. Myocardial fibrosis is negatively correlated with age, and positively correlated with NT-proBNP and cTnI, as well as LVEDV, LVMWT and LVMI in this patient cohort.

Effect of resveratrol on the expression of peroxisome proliferator activated receptor γ coactivator-1αin skeletal muscle of rats with chronic obstructive pulmonary disease / 新乡医学院学报

Objective To investigate the effect of resveratrol on the expression of peroxisome proliferator activated re-ceptor γ coactivator-1α(PGC-1α)in skeletal muscle of rats with chronic obstructive pulmonary disease(COPD). Methods A total of 45 male Sprague Dawley rats were randomly divided into control group,model group and resveratrol group,15 rats in each group. The rats in the model group and resveratrol group were made COPD model through the intratracheal instillation of lipopolysaccharide and repeated smoke exposure,except the rats in the control group. From the 29th day of smoke exposure,the rats in the control group and model group were given 2 mL saline by gavage,once a day for 30 days;and the rats in the resvera-trol group were given 2 mL resveratrol solution by gavage(100 mg·kg - 1 ·d - 1 ),once a day for 30 days. After 30 days of con-tinuous gavage,the rats were sacrificed,then arterial blood and skeletal muscles were harvested. The level of tumor necrosis factor-α(TNF-α)in serum and skeletal muscle of rats was detected by enzyme linked immunosorbent assay. The expression of PGC-1α,nuclear respiratory factor 1(NRF1),mitochondrial transcription factor A(Tfam)and cytochrome C oxidase Ⅳ(COXⅣ)mRNA in skeletal muscle tissues of rats was determined by quantitative real-time polymerase chain reaction. The expres-sion of PGC-1α,NRF1,Tfam and COX Ⅳ protein was detected by Western blot. Results The level of TNF-α in serum and skeletal muscle tissues of rats in the model group and resveratrol group was significantly higher than that in the control group (P < 0. 01). The level of TNF-α in serum and skeletal muscle tissues of rats in the resveratrol group was significantly lower than that in the model group(P < 0. 01). The expression of PGC-1α,NRF1,Tfam,COX Ⅳ protein and mRNA in skeletal mus-cle tissues of rats in the resveratrol group and model group was significantly lower than that in the control group(P < 0. 01). The expression of PGC-1α,NRF1,Tfam,COX Ⅳ protein and mRNA in skeletal muscle tissues of rats in the resveratrol group was significantly higher than that in the model group(P < 0. 01,P < 0. 05). Conclusion Resveratrol can reduce the level of TNF-α in serum and skeletal muscle tissues of COPD rats,increase the expression of PGC-1α,thereby improving the mitochon-drial biosynthesis function.

Bioinformatics analysis of Stenotrophomonas maltophilia outer membrane protein OmpA / 军事医学

Objective To predict and analyze the structure and function of Stenotrophomonas maltophilia OmpA. Methods Bioinformatics software and biological databases were used to analyze the physicochemical properties, signal peptides,and transmembrane structures of the OmpA protein and to predict the subcellular localization, secondary and tertiary structures,sequence homology and conserved domains,and epitopes of OmpA.Results OmpA protein had strong hydrophilicity but without transmembrane helices in mature protein,and positions 1-22 of the sequence were predicted as signal peptide.In the second structure random coil helix,αlpha-helix,beta-turn and extended strand made up 50.27%, 24.59%,9.29%and 15.85%,respectively.The three-dimensional structure was β-barrel.OmpA was highly conserved among S.maltophilia strains but shared minimal homology with human and mouse proteins.The N-terminal domain of OmpA was OM-channels superfamily and the C-terminal domain of OmpA was OmpA_C-like superfamily.OmpA protein contained 11 dominant antigen epitopes.Conclusion The characteristics of OmpA identified by bioinformatics analysis can not only provide reference for the study of the structure and novel function of OmpA,but also theoretically contribute to the research on related new subunit vaccines.

A Multi-stage Carcinogenesis Model to Investigate Caloric Restriction as a Potential Tool for Post-irradiation Mitigation of Cancer Risk

The risk of radiation-induced cancer adds to anxiety in low-dose exposed populations. Safe and effective lifestyle changes which can help mitigate excess cancer risk might provide exposed individuals the opportunity to pro-actively reduce their cancer risk, and improve mental health and well-being. Here, we applied a mathematical multi-stage carcinogenesis model to the mouse lifespan data using adult-onset caloric restriction following irradiation in early life. We re-evaluated autopsy records with a veterinary pathologist to determine which tumors were the probable causes of death in order to calculate age-specific mortality. The model revealed that in both irradiated and unirradiated mice, caloric restriction reduced the age-specific mortality of all solid tumors and hepatocellular carcinomas across most of the lifespan, with the mortality rate dependent more on age owing to an increase in the number of predicted rate-limiting steps. Conversely, irradiation did not significantly alter the number of steps, but did increase the overall transition rate between the steps. We show that the extent of the protective effect of caloric restriction is independent of the induction of cancer from radiation exposure, and discuss future avenues of research to explore the utility of caloric restriction as an example of a potential post-irradiation mitigation strategy.

Effects of early intensive and moderate insulin therapy on the prognosis of patients with severe acute pancreatitis / 中华消化外科杂志

Objective To compare the efficacies of early intensive and moderate insulin therapy on the prognosis of patients with severe acute pancreatitis (SAP).Methods The clinical data of 78 patients with SAP complicated by hyperglycemia who were admitted to the Second Hospital of Lanzhou University from January 2005 to December 2009 were retrospectively analyzed.All patients were divided into the intensive insulin therapy (IIT)group (31 patients) and moderate insulin therapy (MIT) group (47 patients).The target levels of blood glucose were 0.80-1.10 g/L(4.4-6.1 mmol/L) in the IIT group and 1.44-1.80 g/L(8.0-10.0 mmol/L) in the MIT group,respectively.The effects of the 2 therapies on the prognosis of the patients were compared.All data were analyzed by the t test or chi-square test.Results The daily intravenous insulin dosage,fasting glucose level and incidence of severe hypoglycemia were ( 35 ± 11 ) u,( 1.02 ± 0.13 ) g/L[ (5.7 ± 0.7 ) mmol/L] and 10％ (3/31 )in the IIT group,and ( 24 ± 15 ) u,( 1.58 ± 0.21 ) g/L[ ( 8.8 ± 1.2 ) mmol/L] and 2％ ( 1/47 ) in the MIT group.A significant difference was detected in the daily intravenous insulin dosage between the 2 groups( t =12.76,P ＜=0.05),but no significant difference was detected in the incidence of severe hypoglycemia between the 2 groups (x2 =0.91,P ＞ 0.05 ).The levels of albumin and prealbumin on the 14th day were ( 34 ± 6) g/L and (231 ± 31 ) mg/L in the IIT group,and (35 ± 5)g/L and (241 ± 29)mg/L in the MIT group,respectively,with no significant difference between the 2 groups( t =-1.94,-1.68,P ＞ 0.05).The incidences of abdominal infection,circulatory dysfunction,respiratory dysfunction and acquired kidney injury were 23％ (7/31),32％ (10/31),26％ (8/31)and 13％ (4/31) in the lIT group,and 26％ (12/47),36％ ( 17/47),30％ (14/47) and 23％ (11/47) in the MIT group,with no significant difference between the 2 groups(x2 =0.09,0.13,0.15,1.33,P ＞ 0.05).The scores of APPACHE Ⅱ on the 14th day were 9 ± 4 in the IIT group and 9 ± 3 in the MIT group,respectively,with no significant difference between the 2 groups ( t =- 0.60,P ＞ 0.05 ).There were 4 ( 13％ ) patients in the IIT group and 7( 15％ ) patients in the MIT group died of multi-organ dysfunction syndrome,including 2 patients in the IIT group and 6 patients in the MIT group complicated with sepsis.There was no significant difference in the mortality between the 2 groups ( x2 =0,P ＞ 0.05 ).Conclusions Compared with MIT,early IIT could not improve the prognosis of the patients with SAP.MIT is appropriate for SAP patients complicated with hyperglycemia.

Iodoacetamide-induced aquaporin 1 expression in fibroblasts is energy-dependent / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the impact of energy metabolism at the cellular level on the expression of the water channel protein aquaporin 1 (AQP1).</p><p><b>METHODS</b>Balb/c mouse fibroblasts were incubated with iodoacetamide (IA) in vitro, and the changes in AQP1 expression were detected by immunoblotting and immunohistochemistry at 0, 4, and 6 h.</p><p><b>RESULTS</b>IA induced the expression of AQP1 at 4 and 6 h accompanied with cell death. Reverse transcription PCR showed an increased expression of AQP1 mRNA in the cells. AQP1 expression was also upregulated by the inhibitor of microtubule and cytochrome C oxidase.</p><p><b>CONCLUSION</b>A pretranslational regulation occurs in IA-induced AQP1 expression in mouse fibroblasts, and the up-regulated AQP1 accumulation is characterized by mitochondria-related energy dependence.</p>

Preparation of galactosylated hyaluronic acid/chitosan scaffold for liver tissue engineering / 生物医学工程学杂志

The purpose of this research is to construct a kind of 3D-Scaffold with galactose-carrying polysaccharide for improving the function of hepatocytes in vitro. Galactose moieties were covalently coupled with hyaluronic acid through ethylenediamine. Galactosylated hyaluronic acid/chitosan scaffolds were prepared by lyophilization. The characteristics of the scaffolds such as morphology, hydrophilicity, and mechanical properties were investigated. The results indicated that the porosity and the pore size of the scaffolds made in -20 degrees C were useful used for culturing hepatocytes. And, the incorporating of hyaluronic acid in chitosan network improved the hydrophilicity and mechanical properties of the scaffolds. Rat primary hepatocytes growing in the scaffolds observed by phase-contrast microscope showed the multicellular spheroid morphologies. Therefore, galactosylated hyaluronic acid/chitosan scaffolds could be used as a promising scaffold for liver tissue engineering.

Effect of vasectomy via inguinal canal on spermatogenesis in rabbits / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To determine whether vasectomy away from the epididymal tail (via the inguinal canal) in rabbits can reduce the early postoperative effects on spermatogenesis.</p><p><b>METHODS</b>Twenty-nine normal male Japanese white rabbits (aged 4-6 months) were subjected to unilateral close-ended (conventional) or open-ended (the cut end of the juxta-epididymal vas deferens not ligated) vasectomy via the inguinal canal. Ten days and 3 months after operation, testes, epididymides and vasa deferentia were removed and methacrylate resin-embedded sections prepared. The histology of the testis, epididymis and vas deferens was examined under light microscope, and the volume and diameter of the seminiferous tubules were quantitatively studied using stereological methods.</p><p><b>RESULTS</b>Neither of the methods of vasectomy led to apparent damage to spermatogenesis on the vasectomized side in comparison with the contralateral sham-operated side, but the juxta-epididymal vas deferens on the vasectomized side was highly distended and contained numerous sperm 3 months after operation.</p><p><b>CONCLUSION</b>Vasectomy away from the cauda epididymis has no significant early postoperative effects on spermatogenesis in rabbits.</p>

Injecting Kanseran into Tumor Mass via Fibrobronchoscope in Combination with Chemotherapy for Treatment of Advanced Non-small-cell Lung Cancer / 医药导报

Objective:To observe the therapeutic effect and toxicity of local Kanseran injection in combination with chemotherapy in advanced NSCLC patients.Methods:A total of 18 cases was recruited in this study. After desensitization,Kanseran injection was injected into tumor mass through fibrobronchoscope,2 mg every time,once per week. Meanwhile,MVP regimen was administered.Results:Of the 18 patients,1 was completely relieved,7 cases were partially relieved. The response rate was 44.4%. After treatment,when examined by fibrobronchoscope the tumor masses of 15 patients became smaller. The main side effects were fever,alopecia and gastrointestinal reaction,which were mild and tolerable.Conclusion:Local Kanseran injection into tumor mass in conjunction with chemotherapy is effective and safe in the treatment of advanced NSCLC patients with bronchus obstruction.