Inhibitory effect of flavonoids from Glycyrrhiza uralensis on expressions of TGF-β1 and Caspase-3 in thioacetamide-induced hepatic fibrosis in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To study the inhibitory effect of flavonoids from Glycyrrhiza uralensis on thioacetamide-induced chonic hepatic fibrosis in rats and the effect on the protein expressions of transforming growth factor-β1 (TGF-β1) and Caspase-3 in livers.</p><p><b>METHOD</b>Male Sprague-Dawley rats were randomly divided into totally seven groups: the normal control group, the model group, LF groups s (400, 200, 100, 50 mg · kg(-1) · d(-1)) and the silymarin positive control group (30 mg · kg(-1) · d(-1)). The hepatic fibrosis model was induced in the rats through intraperitoneal injection with 3% thioacetamide (TAA) at a dose of 150 mg · kg(-1) body weight twice a week for 12 weeks. During the course, the control group and the model group were orally administered with saline (1 mL · kg(-1) · d(-1)). After the modeling and drug intervention, the pathologic changes and fibrosis in liver tissues were observed by HE staining and Masson's Trichrome staining. The serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and liver hydroxyproline (HYP) contents were assayed by biochemical process. The serum hyaluronic acid (HA) was assessed by radioimmunoassay. In addition, the protein expressions of liver TGF-β1 and Caspase-3 were examined by immunohistochemical method. The mRNA expression of TGF-β1 in hepatic tissues was examined by quantitative Real-time PCR analysis.</p><p><b>RESULT</b>Compared with the model group, flavonoids can protect the integrity of the structure of liver tissues, significantly reduce the hepatic cell degeneration and necrosis and the proliferation of fibrous tissues, notably reduce the serum AST, ALT, ALP and HA and HYP in hepatic tissues and down-regulate the protein expressions of liver TGF-β1 and Caspase-3 and the mRNA expression of TGF-β1 in hepatic tissues.</p><p><b>CONCLUSION</b>The licorice flavonoids can resist the thioacetamide-induced hepatic fibrosis in rats. Its mechanism may be related to the down-regulation of the protein expressions of TGF-β1 and Caspase-3.</p>

Hypothalamic-pituitary-thyroid axis in patients with Alzheimer disease (AD).

OBJECTIVE: We observed the function of hypothalamic-pituitary-thyroid axis in patients with Alzheimer disease (AD) using a case-control study. METHODS: The case was a cohort that included 50 patients with AD. For each case subject, 1 control who was of similar age, sex, daily activities (scale of Lawton), sleep quality (Pittsburgh Sleep Quality Index), and depression (15-item Geriatrics Depression Scale) was recruited. Thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), total tetraiodothyronine (TT4), free triiodothyronine (FT3), and free tetraiodothyronine (FT4) were detected using radioimmunity. RESULTS: Compared with the healthy controls, the patients with AD had significantly lower levels of TRH (67.72 ± 18.44 vs 78.64 ± 14.31 pmol/L; t = 2.078; P = 0.036), TSH (3.89 ± 1.22 vs 4.31 ± 1.07 mIU/L; t = 2.331; P = 0.024), TT3 (1.44 ± 0.21 vs 1.63 ± 0.19 nmol/L; t = 3.761; P = 0.018), TT4 (119.71 ± 18.64 nmol/L vs 129.54 ± 23.17 nmol/L; t = 1.328; P = 0.044), FT3 (4.01 ± 1.27 vs 5.41 ± 0.99 pmol/L; t = 4.976; P = 0.008), and FT4 (9.84 ± 1.56 vs 12.96 ± 2.20 pmol/L; t = 5.381; P = 0.006). In the AD cases, none of the correlations between TRH and TSH, TT3, TT4, FT3, and FT4, and between TSH and TT3, TT4, FT3, FT4 was significant. However, in the healthy controls, TRH was significantly correlated with TSH (R = 0.020; P = 0.042) and FT4 (R = 0.015; P = 0.018), and TSH was significantly correlated with TT4 (R = 0.209; P = 0.017) and FT4 (R = 0.215; P = 0.009). CONCLUSION: Alzheimer disease was associated with abnormal function of the hypothalamic-pituitary-thyroid axis.

Living arrangements and risk for late life depression: a meta-analysis of published literature.

OBJECTIVE: The goal of this study was to determine the relationship between living arrangements and risk for depression among older people. METHOD: MEDLINE, EMBASE, The Cochrane Library database was used to identify potential studies. The studies were divided into cross-sectional and longitudinal subsets. Qualitative meta-analysis of the cross-sectional studies and longitudinal studies was performed, respectively. For prevalence and incidence rates of depression, odds ratio (OR) and relative risk (RR) were calculated, respectively. RESULTS: The qualitative meta-analysis showed that older people living alone had a higher risk of depression than those not living alone (OR: 1.44; 95% confidence interval [95% CI]: 1.04-1.99); Relative risk (RR: 1.27, 95% CI: 0.89-1.80) and those living with families (OR: 2.59, 95% CI: 1.60-4.20). Older people living in a nursing home (OR: 2.90, 95% CI: 0.94-8.94; RR: 1.94, 95% CI: 1.18-3.20) or institutionalized setting (OR: 1.86, 95% CI: 1.37-2.52; RR: 2.03, 95% CI: 1.12-3.70) had a higher risk of depression than those living in home. CONCLUSIONS: Despite the methodological limitations of this meta-analysis, living arrangements appear related to the risk for depression in the older population. Older persons living alone, in a nursing home, or in an institutionalized setting have higher risk for depression.

Antidepressant activities of flavonoids from Glycyrrhiza uralensis and its neurogenesis protective effect in rats / 药学学报

Adult rats chronic unpredictable stress model of depression (CUS) was adopted to elucidate the antidepressant pharmacological activity and related neurogenesis protective effect of the total flavonoids extract (licorice flavonoids, LF) from the Glycyrrhiza uralensis Fisch. cultivated locally in Ningxia. The rats were exposed to 9 kinds of unpredictable sequence of stressors and were given flavonoids (300 mg x kg(-1), 100 mg x kg(-1) and 30 mg x kg(-1)) for 28 days. The antidepressant effect was elucidated by open field test, forced swimming test and tail suspension test. The level of serum corticosterone was detected by radioimmunoassay. 5'-Bromo-2'-deoxyuridine (BrdU) labeling experiments was employed to study the neurogenesis protective activities. The flavonoids can increase the sum of line crosses and number of rears, and decrease the number of fecal boli produced in the open field test of the CUS rats. Also the flavonoids can decrease the immobility time in forced swim test as well as in the tail suspension test. In addition, the flavonoids (300 mg x kg(-1)) can decrease the serum corticosterone level of the CUS rats, and increase the number of the new born BrdU positive progenitor cells at the subgranular zone (SGZ) of dentate gyrus (DG) region in hippocampus. The results demonstrated that the total flavonoids extract from the cultivated Glycyrrhiza uralensis Fisch. could produce the anti-depressive effect on chronic unpredictable stress of depression model rats and its mechanism may be associated with its neurogenesis protective effect.

Effects of valsartan on diabetic cardiomyopathy in rats with type 2 diabetes mellitus / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The development of diabetic cardiomyopathy is multifactorial. Insulin resistance (IR) and excessive activity of the renin-angiotensin system are confirmed reasons for diabetic cardiomyopathy. Renin-angiotensin system (RAS) inhibitors can reduce tissue Ang II levels, with beneficial effects on cardiovascular function. Therefore, in type-2 diabetes mellitus (T2DM), blockade of the RAS may have the function of protecting against diabetic cardiomyopathy through increasing insulin sensitivity and inhibiting excessive activity of RAS. However, this has not been confirmed.</p><p><b>METHODS</b>The effect of valsartan, an angiotensin receptor blocker (ARB), on diabetic cardiomyopathy in the presence of T2DM was studied. Wistar rats with T2DM and T2DM treated with valsartan were studied. Glucose infusion rates (GIR), index of IR, heart weight, the heart weight-to-body weight ratio (HW/BW), myocardial apoptotic index, cardiac hydroxyprolin content, and cardiac tissue collagen type I and collagen type III content were measured.</p><p><b>RESULTS</b>GIR in T2DM rats and T2DM rats treated with valsartan decreased (P < 0.01). In T2DM rats treated with valsartan, heart weight, myocardial apoptotic index, cardiac hydroxyprolin content, and cardiac tissue collagen type I and collagen type III content were higher than in control rats, but lower than in T2DM rats. In rats with T2DM, GIR was negatively and significantly correlated with all the variables. However, in T2DM rats treated with valsartan or normal control rats, none of the correlations was significant.</p><p><b>CONCLUSIONS</b>In the presence of T2DM, diabetic cardiomyopathy is related with IR. Valsartan can not alleviate IR, but can protect against diabetic cardiomyopathy and remove the correlation between IR and diabetic cardiomyopathy.</p>

Renal injury, abnormal vitamin D metabolism and bone homeostasis in aged rats with insulin resistance or type 2 diabetes mellitus.

OBJECTIVE: The study aimed to explore the relationship among renal injury, abnormal vitamin D metabolism, and bone homeostasis in insulin resistance (IR) or type 2 diabetes mellitus (T2DM). DESIGN AND METHODS: The animal models of IR, T2DM, and T2DM treated with 1-alpha hydroxyvitamin D (1-alphaOHD) were established on 18-month-old male Wistar rats. Glucose infusion rates (GIR) and levels of urinary albumin (UA), serum 25-hydroxyvitamin D (25-(OH)D), serum 1,25-dihydroxyvitamin D (1,25-OH2D), and bone mineral density (BMD) in lumbar vertebrae and femoral bone were measured. RESULTS: Urinary albumin level in the rats with T2DM significantly increased, and there existed a significant and negative correlation between GIR and UA level in the rats with T2DM or IR. The levels of serum 25-OHD in all models were similar. The levels of serum 1,25-OH2D and BMD in the rats with IR were significantly higher than those in the rats with T2DM and were lower than those in normal control rats. In the aged rats with T2DM, administration of 1-alphaOHD had no effect on serum 25-OHD level although significantly increased the levels of serum 1,25-O2D and BMD. There existed a negative correlation between the levels of serum 1,25-(OH)2D and UA in the rats with T2DM or IR. CONCLUSIONS: In IR or T2DM, abnormal vitamin D metabolism is characterized by 1,25-OH2D deficiency and is related to renal injury, and there also existed bone loss. In T2DM, both 1,25-(OH)2D deficiency and bone loss can be reversed by 1-alphaOHD.

Insulin resistance, renal injury, renal 1-alpha hydroxylase, and bone homeostasis in aged obese rats.

BACKGROUND: This study aimed to explore the relationship among insulin resistance (IR), renal injury, renal 1-alpha hydroxylase activity (RHA), and bone homeostasis in the presence of obesity. METHODS: Obesity, obesity treated with vitamin D, and obesity treated with 1-alpha hydroxyvitamin D [1-alpha(OH)D] were studied in animal models using aged Wistar rats. Glucose infusion rates (GIR), levels of urinary albumin (UA), serum 25-hydroxyvitamin D [25-(OH)D], serum 1,25-dihydroxyvitamin D [1,25(OH)(2)D], and bone mineral density (BMD) in lumbar vertebrae and femoral bone were measured. RESULTS: GIR in obese rats decreased. A negative correlation existed between UA level and GIR in the aged obese rats, which did not exist in the normal control rats. Levels of serum 25(OH)D in all models were similar. Obese rats had lower levels of serum 1,25(OH)(2)D and BMD than normal control rats. Treating obese rats with vitamin D had no effect on levels of serum 25-(OH)D, serum 1,25(OH)(2)D, and BMD. Administration of 1alpha-(OH)D to obese rats significantly increased serum 1,25(OH)(2)D to above-normal levels and BMD to normal level. In obese rats, levels of serum 1,25(OH)(2)D and BMD in lumbar vertebrae and femoral bone were positively correlated with GIR, and the level of serum 1,25(OH)(2)D was negatively correlated with the UA level. CONCLUSIONS: In the presence of obesity, IR, renal injury, decrease in RHA and bone loss exist. IR-injured kidney accounts for a decrease in RHA, which is a precipitating factor for bone loss.

Inhibiting effects of denshensu, baicalin, astragalus and Panax notoginseng saponins on hepatic fibrosis and their possible mechanisms / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the anti-fibrotic effects of danshensu, baicalin, astragalus and Panax notoginseng saponins (PNS) and their possible mechanisms.</p><p><b>METHODS</b>The four Chinese herb products mentioned above were given intraperitoneally to experimental rats with hepatic fibrosis. Colchicine was administered to a control group. Comparisons were made in four aspects: (1) Degrees of liver fibrosis; (2) Serum levels of hyaluronic acid (HA) and type IV collagen (CIV), using radioimmunoassay; (3) Densities of malondialdehyde (MDA), superoxide dismutase (SOD) and hydroxyproline (Hyp), using chromatometry, to detect the expression of tissue inhibitors of matrix metalloproteinase-1 (TIMP-1), matrix metalloproteinase-1(MMP-1) and transforming growth factor beta 1 (TGF beta 1) in liver tissues, using immunohistochemical techniques; and (4) For hepatic stellate cells (HSCs): proliferation using MMT calorimetric assay, the cell cycles using flow cytometry, apoptosis using AO/EB fluorescence staining and type I and type III collagens using immunocytochemical stainings.</p><p><b>RESULTS</b>(1) Compared with the model group, the serum levels of HA and CIV decreased significantly in all four drug-treated groups, especially in the danshensu-treated group. Astragalus and baicalin had better effects over PNS (P<0.05 or 0.01). (2) In contrast to the model group, all four drugs dramatically reduced the amount of Hyp and MDA, increased SOD activity and reduced the degrees of liver fibrosis and the expressions of TIMP-1 and TGFbeta1 in liver tissues (P<0.05 or 0.01). Danshensu had the best effect, astragalus and baicalin had similar effects which were stronger than PNS. (3) All four drugs inhibited HSCs proliferation, induced HSCs apoptosis and decreased type I, III collagen synthesis of HSC.</p><p><b>CONCLUSIONS</b>The four drugs could minimize the hepatic fibrosis of rats in different degrees. Danshensu had the best effect, astragalus and baicalin had similar effects. The possible mechanisms of these effects might be related to inhibiting actions on activation and proliferation, promoting apoptosis and lowering the expression of type I and type III collagen of HSCs by down-regulating the expression of TGFbeta1; the decrease in the amount of MDA and the increase of SOD activity; and the reduction of extracellular matrix by down-regulation of TIMP-1/MMP-1.</p>

Hypnotic effect of Chinese materia medica Cynanchum chinese in mice / 中国中药杂志

<p><b>OBJECTIVE</b>To study the central pharmacological effect of the water and chloroform-extract compounds from C. chinese in mice.</p><p><b>METHOD</b>The independent activity test and the hypnotic synergism test by sub-threshold hypnotic dosage of pentobarbital were employed to evaluate the central pharmacological effect of the extract-compounds, and the minimal neurotoxicity was evaluated by the rotorod test.</p><p><b>RESULT</b>the extract-compounds exhibited significant dose-related inhibition effect of the spontaneous motor activity in mice after intraperitoneal administration. And the two extract-compounds promoted the hypnotic effect by sub-threshold hypnotic dosage administration of pentobarbital, and produced ED50 value of 2.36 g kg (-1) and 0.75 g kg(-1), respectively. Also, both extract-compounds showed no neurotoxicity in the experiment.</p><p><b>CONCLUSION</b>The extract compounds from C. chinese showed inhibitional effect on CNS.</p>

Clinical study and pathological examination on the treatment of deep partial thickness burn wound with negative charge aerosol / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the effect of negative charge aerosol (NCA) on the treatment of burn wound.</p><p><b>METHODS</b>Patients with superficial or deep partial thickness burn only were enrolled in the study, and they were randomly divided into trial group (T, including 180 cases of superficial thickness burn and 100 cases of deep partial thickness burn), control group (C, including 30 cases with superficial thickness burn and 30 with deep partial thickness burn), and self control group (SC, including 10 cases with superficial thickness burn and 10 with deep partial thickness burn). The patients in T and SC groups were treated with NCA for 1.5 hours, 1-2 times a day, from 6 postburn hour (PBH) to 2 postburn day (PBD), while those in C group received conventional treatment. For those in SC group, some of the wounds were covered with sterile schissel, while other wounds without schissel covering. The general changes in the wounds during NCA treatment were observed, and bacterial culture before and after NCA treatment was performed. The healing time was recorded and the blood biochemical parameters were determined. Rat model with deep partial thickness scald was established, and the rats were also divided into T and C groups, and received treatment as in human. Tissue samples were harvested from the wounds of rats in the 2 groups before and 1, 2, 3 weeks after treatment for pathological examination.</p><p><b>RESULTS</b>There was no infection and little exudation in the patients in T group. No bacteria were found in the wound before and after NCA treatment. The healing time of the wounds of patients with superficial and deep partial thickness burn in T group was 6.3 +/- 1.6 d and 15.1 +/- 3.1 d, respectively, which was obviously shorter than those in C group (11.3 +/- 1.4 d and 21.2 +/- 1.4 d, P < 0.01). In SC group, the healing time of those with sterile schissel coverage was also significantly shorter than those without covering (P < 0.01). There was no obvious change in the liver and kidney functions and blood biochemical parameters among the patients. Pathological examination showed that the skin structure was almost recovered in the rats in T group 3 weeks after treatment, while those in C group was not.</p><p><b>CONCLUSION</b>Negative charge aerosol is safe and effective in promoting wound healing of the patients with partial thickness burns.</p>

Cloning, ligation and expression of the variable region genes of the monoclonal antibody against human HnRNPA2/B1 / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To clone the variable region genes of the monoclonal antibody (McAb) against human heterogeneous nuclear ribonucleoprotein A2/B1 (HnRNPA2/B1), ligate them to assemble single chain Fv (ScFv) gene and express in Escherichia coli.</p><p><b>METHODS</b>The specificity of the anti-HnRNPA2/B1 McAb 3E8 to synthetic HnRNPA2/B1 peptide, HnRNPA2/B1 protein in lung cancer cells were examined by dot-immunobinding assay, Western blot and immunohistochemistry. The variable region genes of heavy chain (VH) and light chain (VL) were amplified from hybridoma cell by reverse transcription-polymerase chain reaction(RT-PCR), and then were linked by a linker peptide using SOE-PCR (splicing by overlap extension-PCR) to construct recombination ScFv gene. The latter was cloned into the expression vector pET28 (a+) and expressed in E coli BL21. The expressed product was identified by SDS-PAGE and competitive ELISA inhibition test.</p><p><b>RESULTS</b>It was shown that the McAb combined specifically with synthetic HnRNPA2/B1 peptide and HnRNPA2/B1 protein in three lung cancer cells. The cloned VH gene and VL gene were 345 bp and 309 bp respectively and were linked successfully to obtain ScFv gene. The ScFv protein was expressed in the form of inclusion body, with molecular weight of 28,000 and immunoreactivity to HnRNPA2/B1.</p><p><b>CONCLUSION</b>VH gene, VL gene and ScFv gene of anti-HnRNPA2/B1 antibody were cloned, constructed and functionally expressed in E coli. These results provide the experimental basis for elucidating the role of HnRNPA2/B1 in lung cancer.</p>