DIAGNOSTIC VALUE OF SERUM INSULIN- LIKE GROWTH FACTOR BINDING PROTEIN- 3 IN CHILDREN WITH OR WITHOUT GROWTH HORMONE DEFICIENCY

OBJECTIVE: To study the value of serum insulin-like growth factor binding protein-3 (IGFBP-3) levels in differential diagnosis of growth hormone deficiency (GHD). METHODS: To measure serum IGFBP-3 levels by RIA in normal children and adolescents, GHD children and short-stature children without GHD. RESULTS: Serum level of IGFBP-3 in 129 children with untreated GHD and with no pubertal development was 1.6 +/- 0.9 mg/L, which was less than that in normal group of the same age, but overlapped with the normal children in Tanner stage I. After six-month treatment with recombinant human growth hormone (rhGH), serum level of IGFBP-3 in 59 GHD significantly increased from 1.3 +/- 0.7 mg/L to 2.7 +/- 0.9 mg/L, accompanied by an increase of body heights, growth velocities and serum level of IGF-1. Serum level of IGFBP-3 in 55 short-stature children without GHD was 3.3 +/- 2.2 mg/L, which was not significantly different from that in normal group. CONCLUSION: Serum IGFBP-3 level can reflect the status of GH secretion in children with GHD and is a useful marker for differential diagnosis of GHD.

Omega-3 fatty acids for the treatment of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease （NAFLD） has been recognized as a major health burden. It is the most important cause of chronic liver disease and a major in- dependent cardiovascular risk factor. Lacking a definite treatment for NAFLD, a specific diet and an increase in physical activity represent the most commonly used therapeutic approaches. In this review, major literature data about the use of omega-3 polyunsaturated fatty ac- ids （n-3 PUFAs） as a potential treatment of NAFLD have been described, n-3 PUFAs, besides having a beneficial impact on most of the cardio-metabolic risk factors （hy- pertension, hyperlipidemia, endothelial dysfunction and atherosclerosis） by regulating gene transcription factors [i.e., peroxisome proliferator-activated receptor （PPAR） cz, PPARy, sterol regulatory element-binding protein-i, carbohydrate responsive element-binding protein], im- pacts both lipid metabolism and on insulin sensitivity. In addition to an enhancement of hepatic beta oxidation and a decrease of the endogenous lipid production, n-3 PUFAs are able to determine a significant reduction of the expression of pro-inflammatory molecules （tumor necrosis factor-~ and interleukin-6） and of oxygen reac- tive species. Further strengthening the results of the in vitro studies, both animal models and human interven- tion trials, showed a beneficial effect of n-3 PUFAs on the severity of NAFLD as expressed by laboratory pa- rameters and imaging measurements. Despite available results provided encouraging data about the efficacy of n-3 PUFAs as a treatment of NAFLD in humans, well- designed randomized controlled trials of adequate size and duration, with histological endpoints, are needed to assess the long-term safety and efficacy of PUFA, as well as other therapies, for the treatment of NAFLD and non-alcoholic steatohepatitis patients. It is worthwhile to consider that n-3 PUFAs cannot be synthesized by the human body and must be derived from exogenous sources （fish oil, flaxseeds, olive oil） which are typical foods of the Mediterranean diet, known for its beneficial effects in preventing obesity, diabetes and, in turn, cardiovascular events. According to these data, it is important to consider that most of the beneficial effects of n-3 PUFAs can also be obtained by an equilibrate nutrition program.

Regulated expression of TATA-binding protein-related factor 3(TRF3)during early embryogenesis

RNA polymerase （Pol） Ⅱ transcription persists in TATA-box-binding protein （TBP）^-/- mutant mouse embryos, indicating TBP-independent mechanisms for Pol Ⅱ transcription in early development. TBP-related factor 3 （TRF3） has been proposed to substitute for TBP in TBP^-/- mouse embryos. We examined the expression of TRF3 in maturing oocytes and early embryos and found that TRF3 was co-expressed with TBP in the meiotic oocytes and early embryos from the late one-cell stage onward. The amounts of TBP and TRF3 changed dynamically and correlated well with transcriptional activity. Chromatin immunoprecipitation （CHIP） assay revealed that different gene promoters in mouse embryonic stem （ES） cells recruited TRF3 and TBP selectively. Comparative analyses of TRF3 and TBP during cell cycle showed that both factors proceeded through cell cycle in a similar pace, except that TRF3 was slightly delayed than TBP in entering the nucleus when cells were exiting the M-phase. Data from expression and biochemical analyses therefore support the hypothesis that TRF3 plays a role in early mouse development. In addition, results from co-localization study suggest that TRF3 may be also involved in Pol Ⅰ transcription.

硫代乙酰胺诱导的肝硬化大鼠生长激素/胰岛素样生长因子-1轴的变化(英文)

目的 探讨硫代乙酰胺诱导的肝硬化大鼠GH/IGF - 1轴的变化。方法 设正常组大鼠 6只、肝硬化组大鼠 6只 ,测大鼠肝功能、血糖和血清GH、IGF - 1、IGFBP - 3水平 ,用RT -PCR法检测肝ALBmRNA、IGF- 1mRNA、IGFBP - 3mRNA表达。肝组织行HE染色和Ki6 7免疫组化染色。结果 肝硬化组大鼠血清AST、ALT、ALP明显高于正常组 ,血清TBIL、ALB、血糖两组间无明显差别 ,血清GH水平明显高于正常组 ,而血清IGF - 1、IGFBP - 3水平明显低于正常组 ,肝ALBmRNA、IGF - 1mRNA、IGFBP - 3mRNA表达水平明显低于正常组。肝硬化组大鼠镜下见假小叶形成 ,肝Ki6 7指数明显高于正常组。结论 肝硬化大鼠存在GH/IGF -

血液透析患者生长激素-胰岛素样生长因子轴与营养状态关系的研究

目的 本研究观察透析患者生长激素(GH)、胰岛素样生长因子(IGF-Ⅰ)及其结合蛋白-1(IGFBP 1)、结合蛋白-3(IGFBP 3)与主要营养指标如血浆白蛋白、前白蛋白、转铁蛋白水平的关系,探索透析患者营养不良的原因。方法 ELISA法检测60例血液透析稳定患者血GH、IGF—Ⅰ及IGFBP 1、IGFBP3。同时检测血前白蛋白、转铁蛋白、白蛋白、总蛋白;另设15例健康对照组,年龄、性别与上匹配。分别用GH、IGF—Ⅰ、IGFBP 1、IGFBP 3与上述营养指标进行相关分析。结果 60例透析患者IGF—Ⅰ及IGFBP 3显著低于正常对照组,GH及IGFBP1显著增高,有统计学意义。GH与血浆白蛋白及氮平衡呈正相关关系;IGF—Ⅰ、IGFBP 3与血浆白蛋白、前白蛋白、转铁蛋白及氮平衡呈正相关,而IGFBP1与白蛋白呈负相关关系,P<0.05。结论 本研究证实,血液透析患者存在GH—IGF轴的紊乱,这些患者平均前白蛋白、转铁蛋白低于正常对照组,热量及蛋白摄入量低于推荐量。GH—IGF轴中的GH、IGF—Ⅰ、IGFBP 1、IGFBP 3与营养有一定的相关关系。

Regulatory effects of moxibustion on ubiquitin and NLRP3 proteins in colon of ulcerative colitis rats

Objective:To observe the effects of moxibustion on colonic inflammation,and the expressions of ubiquitin and nucleotide-binding oligomerization domain(Nod)-Iike receptor protein 3(NLRP3)proteins in rats with ulcerative colitis(UC),and to explore the anti-inflammatory mechanism of moxibustion in the UC treatment.Methods:Clean grade male Sprague-Dawley(SD)rats were randomly divided into a normal group(NG),a model group(MG),a moxa-stick moxibustion group(MSMG)and a Western medicine group(WMG).UC model was prepared by freely drinking 35 g/L d ext ran sulfate sodium(DSS)solution.Bilateral Tianshu(ST 25)were selected for mild moxibustion treatment in the MSMG;mesalazine solution was intragastrically administrated in the WMG.Rats in the NG and MG were only grasped and fixed as in the MSMG without any treatment.After treatment,hematoxylin-eosin(HE)staining was performed to observe and score the colonic pathological damage under light microscope;immunofluorescence method was used to determine the expression of colonic ubiquitin protein;immunohistochemical method was used to detect the expressions of colonic interleukin(IL)-1β and NLRP3 proteins.Results:The colon tissue was severely injured,and the pathological score was significantly increased in the MG than in the NG(P<0.01),and the protein expressions of ubiquitin,NLRP3 and IL-1β in the colon were significantly increased(all P<0.01).Compared with the MG,the colonic damage was repaired,the inflammation and pathological scores were reduced,and the ubiquitin,NLRP3 and IL-1β protein expressions were decreased in the MSMG and WMG(all P<0.01).Correlation analysis revealed that the ubiquitin protein expression was correlated with the colonic pathological score and the NLRP3 protein expression(r=0.677,P<0.01;r=0.536,P<0.05).Conclusion:Moxibustion can down-regulate the protein expressions of ubiquitin,NLRP3 and IL-1β in the colon of UC rats,which may be one of the mechanisms to promote the repair of colonic inflammatory lesions and exert anti-inflammatory effects.

Discussion of the promising effect of electroacupuncture on cognitive improvement in D-galactose-induced aging rats based on NLRP3-ASC-Caspase-1 signaling pathway

Objective:To investigate the effect of electroacupuncture(EA)on cognitive function in D-galactose(D-gal)-induced aging rats,and the correlation between the effect and nucleotide-binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)-ASC-Caspase-1 signaling pathway.Methods:Forty-six male Sprague-Dawley(SD)rats were randomly divided into a control group(n=10),a model group(n=12),an EA-7 d group(n=12)and an EA-21 d group(n=12).Except the control group,the other three groups received 42 consecutive days of intraperitoneal injection of D-gal to establish aging rat models with cognitive dysfunction.The control group received the same amount of normal saline via intraperitoneal injection.Two EA groups were given EA therapy for 21 consecutive days(began from the 22nd day of modeling)or 7 consecutive days(began from the 36th day of modeling)accordingly at Dazhui(GV 14),Baihui(GV 20),Shenshu(BL 23)and Zusanli(ST 36).After modeling/intervention,all four groups received behavioral evaluations by Morris water maze(MWM)test,novel object recognition(NOR)test and step-down passive avoidance(SDPA)test followed by the Western blot(WB)detection of the expression levels of hippocampal NLRP3 inflammasome-associated proteins NLRP3,ASC and Caspase-1.Results:MWM(place navigation test,PNT)results showed that the escape latency in the model group was significantly longer than that in the other three groups(P<0.05),and there was no significant difference among the other three groups on the 1st day of the test(P>0.05).From the 2nd day to the 4th day of the test,there was no significant difference between the EA-21 d group and the control group(P>0.05)in the escape latency;the escape latency was significantly shorter in the EA-21 d group than in the model group and the EA-7 d group(P<0.05).MWM(spatial probe test,SPT)results showed that the time spent in the target quadrant was significantly shorter and platform crossover number was significantly lower in the model group than in the other three groups(P<0.05).The time spent in the target quadrant was longer in the EA-7 d group than in the model group(P<0.05),but was shorter than that in the control group and the EA-21 d group(P<0.05).There was no significant difference in the swimming speed among the four groups(P>0.05).NOR results showed that there was no significant difference in the recognition ratio between the EA-7 d group and the EA-21 d group(P>0.05),and the recognition ratio was significantly higher in the two EA groups than in the model group(P<0.05),but was lower than in the control group(P<0.05).SDPA results showed that the electric shock number was higher in the model group than in the other three groups(P<0.05),and the differences among the other three groups were statistically insignificant(P>0.05).The model group had the shortest step-down latency,followed by the EA-7 d group,the EA-21 d group and the control group in order(P<0.05).The WB results indicated that the expression level of NLRP3 was significantly lower in the control group and the EA-21 d group than in the model group and the EA-7 d group(P<0.05).The expression levels of ASC and Caspase-1 were significantly higher in the model group than in the other three groups(P<0.05),and there was no significant difference among these three groups(P>0.05).Conclusion:NLRP3 inflammasome may be involved in the development of cognitive decline in aging rats;7 consecutive days of EA intervention can partially improve the cognitive impairment in aging rats though the effect is rather limited;21 consecutive days of EA intervention may improve the learning and memory abilities in aging rats via downregulating the expression levels of NLRP3 inflammasome-associated proteins in hippocampus.

Effect of electroacupuncture on NF-κB and NLRP3 inflammasome in uterine tissues of rats with primary dysmenorrhea

Objective: To observe the effect of electroacupuncture (EA) on nuclear factor kappa B (NF-κB) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in uterine tissues of rats with primary dysmenorrhea (PD), thus to explore the possible mechanism of EA for PD. Methods: Fifty female Sprague-Dawley (SD) rats were randomly divided into a normal group, a model group, an EA at non-acupoint group, an EA at acupoint group and a Western medicine group, with 10 rats in each group. Except for the normal group, rats in the other four groups were treated with estradiol benzoate combined with oxytocin for 11 d to establish PD rat models. From day 1 of the modeling, rats in the normal group and the model group were only properly grasped without any intervention;Guanyuan (CV 4) and Sanyinjiao (SP 6) were selected for EA treatment in the EA at acupoint group;rats in the EA at non-acupoint group were treated with EA at 5 mm away from the acupoints selected above;rats in the Western medicine group were treated with ibuprofen via gavage. Rats in each group were treated for 10-day successively. On the 11th day, except for the normal group, rats in the other groups were intraperitoneally injected with oxytocin (2 U/rat), and the writhing number within 30 min in each group was compared;the pathological changes in rat uteruses were observed by hematoxylin-eosin (HE) staining, and the pathological damage scores were evaluated. Protein expression levels of NF-κB p65, phospho-NF-κB p65, NLRP3, cysteine aspastic acid-specific protease 1 (caspase-1), interleukin (IL)-1β and IL-18 were detected by Western blot. Results: Compared with the normal group, the writhing number increased significantly (P<0.05), and the extensive exfoliation of the endometrium, severe edema, and histopathological score all increased significantly in the model group (P<0.05) as well as the protein levels of NLRP3, caspase-1, IL-1β and IL-18, and the ratio of phospho-NF-κB p65/NF-κB p65 in rat uterine tissues (all P<0.05);compared with the model group, the numbers of writhing reaction decreased within 30 min (P<0.05), the endometrial exfoliation was rare, the edema degree was mild, and the histopathological scores decreased significantly (all P<0.05) in the EA at acupoint group and the Western medicine group;compared with the model group, the phospho-NF-κB p65/NF-κB p65 ratio and the NLRP3, caspase-1, IL-1β and IL-18 protein levels of rat uterine tissues in the EA at acupoint group were significantly lower (P<0.05);compared with the model group, the caspase-1, IL-1β and IL-18 protein levels of the rat uterine tissues decreased significantly (all P<0.05), and the differences in the NLRP3 and phospho-NF-κB p65/NF-κB p65 levels were statistically insignificant (all P>0.05) in the Western medicine group;compared with the Western medicine group, the phospho-NF-κB p65/NF-κB p65 ratio, also the NLRP3, IL-1β and IL-18 protein levels of the uterine tissues decreased significantly in the EA at acupoint group (all P<0.05), while the difference in the caspase-1 level was statistically insignificant (P>0.05);there were no significant differences between the EA at non-acupoint group and the model group in any indicators (all P>0.05). Conclusion: EA at acupoints significantly improves the pain and pathological damages of PD rats. The mechanism may be related to the reduced uterine inflammation via inhibiting NF-κB phosphorylation and NLRP3 activation in uteruses of PD rats.