Microscopic growth mechanism and edge states of monolayer 1T'-MoTe_(2)

Transition metal ditellurides(TMTDs)have versatile physical properties,including non-trivial topology,Weyl semimetal states and unique spin texture.Controlled growth of high-quality and large-scale monolayer TMTDs with preferred crystal phases is crucial for their applications.Here,we demonstrate the epitaxial growth of 1T'-MoTe_(2) on Au(111)and graphitized silicon carbide(Gr/SiC)by molecular beam epitaxy(MBE).We investigate the morphology of the grown1T'-MoTe_(2) at the atomic level by scanning tunnelling microscopy(STM)and reveal the corresponding microscopic growth mechanism.It is found that the unique ordered Te structures preferentially deposited on Au(111)regulate the growth of monolayer single crystal 1T'-MoTe_(2),while the Mo clusters were preferentially deposited on the Gr/SiC substrate,which impedes the ordered growth of monolayer MoTe_(2).We confirm that the size of single crystal 1T'-MoTe_(2) grown on Au(111)is nearly two orders of magnitude larger than that on Gr/SiC.By scanning tunnelling spectroscopy(STS),we observe that the STS spectrum of the monolayer 1T'-MoTe_(2) nano-island at the edge is different from that at the interior,which exhibits enhanced conductivity.

帕金森病患者免疫球蛋白、Th9亚群水平变化及其与IGF-1、S-100B蛋白的相关性

目的:研究帕金森病(PD)患者免疫球蛋白(IgG、IgA和IgM)、辅助性T细胞亚群Th9水平变化及其与胰岛素生长因子-1(IGF-1)、S-100B蛋白的相关性。方法:选取2020年12月至2022年12月期间在河北省中医院确诊的108例PD患者,将其作为研究组,并根据患者病变程度分为轻度组(35例)、中度组(44例)和重度组(29例);另选108例健康成人作为对照组。对比研究组和对照组免疫球蛋白和Th9亚群水平,以及轻度组、中度组及重度组免疫球蛋白、Th9亚群、IGF-1和S-100B蛋白水平,采用Pearson相关性分析免疫球蛋白、Th9亚群和IGF-1、S-100B蛋白的相关性。采用Spearman相关性分析PD患者疾病程度和所有差异指标间的相关性。结果:研究组IgM水平较对照组低,且重度组低于中度组,中度组低于轻度组(P<0.05);研究组IgG、IgA、IL-9和Th9亚群水平较对照组高,且重度组高于中度组,中度组高于轻度组(P<0.05)。重度组IGF-1水平低于中度组,中度组低于轻度组;重度组S-100B蛋白水平高于中度组,中度组高于轻度组(P<0.05)。Pearson相关性分析结果显示,PD患者IgM水平与IGF-1水平呈正相关,与S-100B蛋白水平呈负相关;IgG、IgA、IL-9和Th9亚群水平均与IGF-1水平呈负相关,与S-100B蛋白水平呈正相关(P<0.05)。Spearman相关性分析结果显示,PD患者疾病程度与IgM、IGF-1水平呈负相关,与S-100B蛋白、IgG、IgA、IL-9和Th9亚群水平呈正相关(P<0.05)。结论:PD患者IgM水平降低,IgG、IgA、Th9亚群水平升高,且其水平变化与IGF-1、S-100B明显相关,可以用于评估病情的严重程度。

Neuroprotective effects of insulin-like growth factor-2 in 6-hydroxydopamine-induced cellular and mouse models of Parkinson’s disease

Skin-derived precursor Schwann cells have been reported to play a protective role in the central nervous system. The neuroprotective effects of skin-derived precursor Schwann cells may be attributable to the release of growth factors that nourish host cells. In this study, we first established a cellular model of Parkinson’s disease using 6-hydroxydopamine. When SH-SY5 Y cells were pretreated with conditioned medium from skin-derived precursor Schwann cells, their activity was greatly increased. The addition of insulin-like growth factor-2 neutralizing antibody markedly attenuated the neuroprotective effects of skin-derived precursor Schwann cells. We also found that insulin-like growth factor-2 levels in the peripheral blood were greatly increased in patients with Parkinson’s disease and in a mouse model of Parkinson’s disease. Next, we pretreated cell models of Parkinson’s disease with insulin-like growth factor-2 and administered insulin-like growth factor-2 intranasally to a mouse model of Parkinson’s disease induced by 6-hydroxydopamine and found that the level of tyrosine hydroxylase, a marker of dopamine neurons, was markedly restored, α-synuclein aggregation decreased, and insulin-like growth factor-2 receptor downregulation was alleviated. Finally, in vitro experiments showed that insulin-like growth factor-2 activated the phosphatidylinositol 3 kinase(PI3 K)/AKT pathway. These findings suggest that the neuroprotective effects of skin-derived precursor Schwann cells on the central nervous system were achieved through insulinlike growth factor-2, and that insulin-like growth factor-2 may play a neuroprotective role through the insulin-like growth factor-2 receptor/PI3 K/AKT pathway. Therefore, insulin-like growth factor-2 may be an useful target for Parkinson’s disease treatment.

Optimization of growth medium for microbially induced calcium carbonate precipitation(MICP) treatment of desert sand

Wind-induced sand erosion is a natural process, and can have several negative impacts on human health, environment, and economy. To mitigate the wind-induced sand erosion, an environmental friendly technique that helps to bind soil particles is desirable. The microbially induced calcium carbonate precipitation(MICP) treatment has lately become renowned and a viable alternative to enhance the binding of sand particles(especially against wind erosion). The efficiency of Sporosarcina pasteurii bacteria in inducing calcite formation can be influenced by various factors, including the type of growth media used for bacterial culture. Most of the studies have mainly validated the efficiency of S. pasteurii bacteria usually under single growth media for the MICP treatment. However, the efficiency of S. pasteurii under different growth media on calcite formation is rarely explored. The current study explores the effect of S.pasteurii bacteria on calcite formation under the presence of three different growth media, namely,molasses(MS), tryptic soy broth(TB), and nutrient broth(NB). The three growth media have been applied in the laboratory with and without bacterial solution(control samples). Altered cementation media concentrations(0.5 and 1.0 M) with different pore volumes(PVs), namely, 0.25, 0.50, and 1.00 PV were used in sand-filled tubes for 7 and 14 treatment cycles(1 cycle=24 h). The pH and EC were measured for 12-h period in every 2 h interval, to monitor values at the time of treatment at room temperature. The calcite precipitation was confirmed using SEM(scanning electron microscope), PXRD(powder X-ray diffraction), and calcimeter tests. It was observed that MS generates lower calcite precipitation as compared with NB and TB. However, MS has the advantage of being more economical and abundant(waste product from sugar mills and refineries) as compared with other growth media(NB and TB). It was observed that the minimum and the maximum calcite precipitation using MS is 5% and 12%, respectively.The findings using MS in the present study was compared with the literature and found that precipitation of calcite using MS is effective to stabilize soil against wind erosion.

Overexpression of fibroblast growth factor 13 ameliorates amyloid-β-induced neuronal damage

Previous studies have shown that fibroblast growth factor 13 is downregulated in the brain of both Alzheimer’s disease mouse models and patients,and that it plays a vital role in the learning and memory.However,the underlying mechanisms of fibroblast growth factor 13 in Alzheimer’s disease remain unclear.In this study,we established rat models of Alzheimer’s disease by stereotaxic injection of amyloid-β(Aβ_(1-42))-induced into bilateral hippocampus.We also injected lentivirus containing fibroblast growth factor 13 into bilateral hippocampus to overexpress fibroblast growth factor 13.The expression of fibroblast growth factor 13 was downregulated in the brain of the Alzheimer’s disease model rats.After overexpression of fibroblast growth factor 13,learning and memory abilities of the Alzheimer’s disease model rats were remarkably improved.Fibroblast growth factor 13 overexpression increased brain expression levels of oxidative stress-related markers glutathione,superoxide dismutase,phosphatidylinositol-3-kinase,AKT and glycogen synthase kinase 3β,and anti-apoptotic factor BCL.Furthermore,fibroblast growth factor 13 overexpression decreased the number of apoptotic cells,expression of pro-apoptotic factor BAX,cleaved-caspase 3 and amyloid-βexpression,and levels of tau phosphorylation,malondialdehyde,reactive oxygen species and acetylcholinesterase in the brain of Alzheimer’s disease model rats.The changes were reversed by the phosphatidylinositol-3-kinase inhibitor LY294002.These findings suggest that overexpression of fibroblast growth factor 13 improved neuronal damage in a rat model of Alzheimer’s disease through activation of the phosphatidylinositol-3-kinase/AKT/glycogen synthase kinase 3βsignaling pathway.

On the Mechanism of Evolution for Enterprise＇s Sustainable Growth Based on the Theory of Self-organization

The capabilities of industry, technology, institution and market power form the model of four-capability structure for enterprise＇s sustainable growth. The firm＇s system has the characteristics of dissipative structure. The process of the formation for the sustainable growth capability is one of self-organization operations. The evolution and development of sustainable growth capability is the result of inter-functions and inter-operations among all the sub-systems. On the whole, the current level of sustainable growth capability, the four-capability structure and the random rise-and-fall elements of the external environment determine the direction, speed and level of transition of sustainable growth capability. The self-organization mechanism of the enterprise＇s sustainable growth can be illustrated by the instability of system evolution, the sequence parameter, the potential function and the nonequilibrium phase transition. Chinese firms must pay attention to industry selecting and positioning, technology innovation, institution reform and cultivation of market power, and accelerate the formation of self-organization and effective operation through the dynamic integration and inter-operation of industry, technology, institution and market power. Only in this way can firms cultivate and develop their sustainable growth capability and realize enterprises＇ sustainable growth finally.

Prognostic significance and relationship of SMAD3 phosphoisoforms and VEGFR-1 in gastric cancer:A clinicopathological study

BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer.METHODS This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years(median age 65)between July 2006 and April 2007.Patients were followed up until death or the study ended(median follow-up duration of 28.5 mo).The samples were used to generate tissue microarrays(TMAs)for immunohistochemical(IHC)staining.The expressions of TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 in gastric cancer(GC)tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients.Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015.The relationship between TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient.The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test.A survival curve was generated using the Kaplan-Meier survival analysis.RESULTS TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent noncancerous tissue.The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site[pSMAD3C(S423/425):51.0%and pSMAD3L(S204):31.6%].High expression of pSMAD-3L(S204)was significantly correlated with larger tumors(P=0.038)and later N stages(P=0.035).Additionally,high expression of VEGFR-1 was closely correlated with tumor size(P=0.015)and pathological grading(P=0.013).High expression of both pSMAD3L(S204)and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival(OS).Multivariate analysis indicated that high expression of pSMAD3L(S204)and VEGFR-1 were independent risk factors for prognosis in GC patients.VEGFR-1 protein expression was correlated with TGF-β1(r=0.220,P=0.029),pSMAD3C(S423/425)(r=0.302,P=0.002),and pSMAD3L(S204)(r=0.201,P=0.047),respectively.Simultaneous overexpression of pSMAD3L(S204)and VEGFR-1 was associated with poor OS in gastric cancer patients.CONCLUSION Co-upregulation of pSMAD3L(S204)and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis,and pSMAD3L(204)may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner.

Potential plausible role of Wharton’s jelly mesenchymal stem cells for diabetic bone regeneration

This letter addresses the review titled“Wharton’s jelly mesenchymal stem cells:Future regenerative medicine for clinical applications in mitigation of radiation injury”.The review highlights the regenerative potential of Wharton’s jelly mesenchymal stem cells(WJ-MSCs)and describes why WJ-MSCs will become one of the most probable stem cells for future regenerative medicine.The potential plausible role of WJ-MSCs for diabetic bone regeneration should be noticeable,which will provide a new strategy for improving bone regeneration under diabetic conditions.

Soluble p75 neurotrophic receptor as a reliable biomarker in neurodegenerative diseases: what is the evidence?

Neurodegenerative diseases are often misdiagnosed,especially when the diagnosis is based solely on clinical symptoms.The p75 neurotrophic receptor(p75^(NTR))has been studied as an index of sensory and motor nerve development and maturation.Its cleavable extracellular domain(ECD)is readily detectable in various biological fluids including plasma,serum and urine.There is evidence for increased p75NTR ECD levels in neurodegenerative diseases such as Alzheimer’s disease,amyotrophic lateral sclerosis,age-related dementia,schizophrenia,and diabetic neuropathy.Whether p75^(NTR) ECD could be used as a biomarker for diagnosis and/or prognosis in these disorders,and whether it could potentially lead to the development of targeted therapies,remains an open question.In this review,we present and discuss published studies that have evaluated the relevance of this emerging biomarker in the context of various neurodegenerative diseases.We also highlight areas that require further investigation to better understand the role of p75^(NTR) ECD in the clinical diagnosis and management of neurodegenerative disorders.

CO_(2)和H_(2)S对镍基合金028点蚀敏感性及点蚀生长动力学的影响

目的探明CO_(2)和H_(2)S对镍基合金028钝化膜性能和点蚀敏感性的影响。方法采用循环动电位极化(CPP)、电化学阻抗谱(EIS)、莫特-肖特基(M-S)等测试方法,研究Cl-环境、CO_(2)-Cl-环境和H_(2)S-Cl-环境中镍基合金028的钝化膜性能。通过制备一维人工凹坑电极模拟点蚀坑的稳态生长,采用向负向电位扫描法,研究镍基合金028在局部点蚀环境中的金属溶解动力学,明确CO_(2)和H_(2)S对点蚀生长动力学的影响。结果CO_(2)和H_(2)S都会使镍基合金028钝化膜性能变差,而H_(2)S的影响更为显著,具体表现为:在H_(2)S-Cl-环境中具有更高的钝化电流密度jp、更低的点蚀电位Eb和再钝化电位Erp。H_(2)S-Cl-环境中的钝化膜电阻Rf、电荷转移电阻Rt和钝化膜厚度均低于CO_(2)-Cl-环境中的,此外,钝化膜在H_(2)S-Cl-环境中具有更高的点缺陷密度。在最大点蚀坑溶解电流密度jdiss,max相同的条件下,H_(2)S-Cl-环境中点蚀稳态生长所需的驱动力Emax明显低于CO_(2)-Cl-环境中的;在相同Emax下,H_(2)S-Cl-环境中的jdiss,max高于CO_(2)-Cl-环境中的。结论CO_(2)和H_(2)S通过增加钝化膜溶解速率、降低钝化膜电阻和增加点缺陷密度,不同程度地增加了镍基合金028的点蚀敏感性,而H_(2)S更容易造成钝化膜损伤。在点蚀稳态生长阶段,镍基合金028点蚀的稳态生长遵循塔菲尔规律,相比于CO_(2),H_(2)S更容易促进点蚀从亚稳态向稳态发展,并且在H_(2)S环境中具有更高的点蚀生长稳定性。

多奈哌齐联合丁苯酞治疗老年阿尔茨海默病的效果及对患者Hcy、CysC、VEGF的影响

目的观察多奈哌齐联合丁苯酞治疗老年阿尔茨海默病(AD)的效果及对患者血清同型半胱氨酸(Hcy)、胱抑素C(CysC)、血管内皮生长因子(VEGF)的影响。方法选取2021年1月—2022年6月福州市中医院收治的老年AD患者90例作为观察组,选择同期进行健康体检的90例健康老年人作为健康对照组,将观察组患者按随机数字表法分为Ⅰ亚组、Ⅱ亚组、Ⅲ亚组各30例,分别给予多奈哌齐、丁苯酞及多奈哌齐+丁苯酞治疗,3组均治疗24周。治疗前、治疗24周结束时对2组受试者进行血清Hcy、CysC、VEGF检测及记录简易精神状态检查量表(MMSE)、日常生活活动能力量表(ADL)评分,根据MMSE评分将患者分为轻度、中度、重度,比较不同病情程度患者治疗前血清Hcy、CysC、VEGF水平,采用Pearson相关分析探讨Hcy、CysC、VEGF与病情程度的相关性,治疗24周结束时评价临床疗效。结果观察组血清Hcy、CysC水平明显高于健康对照组,血清VEGF水平明显低于健康对照组(P均<0.01)。轻度、中度、重度患者血清Hcy、CysC、VEGF水平比较,差异有统计学意义(F/P=20.917/<0.001、37.397/<0.001、60.507/<0.001);Pearson相关分析显示,Hcy、CysC与病情程度呈正相关(r=0.853、0.864,P<0.01),VEGF与病情程度呈负相关(r=-0.901,P<0.01)。3亚组治疗总有效率比较,差异有统计学意义(χ^(2)=6.477,P=0.039);Ⅲ亚组治疗总有效率高于Ⅰ亚组、Ⅱ亚组(χ^(2)/P=5.963/0.015、4.812/0.028),但Ⅰ亚组、Ⅱ亚组治疗总有效率比较,差异无统计学意义(P>0.05)。3亚组治疗24周后MMSE评分与血清VEGF水平较治疗前升高,ADL评分与血清Hcy、CysC水平较治疗前降低,且治疗后3亚组间MMSE、ADL评分与血清Hcy、CysC、VEGF水平比较,差异有统计学意义(P<0.01),Ⅲ亚组治疗后相应指标与Ⅰ亚组、Ⅱ亚组比较差异有统计学意义(P<0.01),但Ⅰ亚组、Ⅱ亚组比较差异无统计学意义(P>0.05)。结论Hcy、CysC、VEGF参与老年AD的形成过程,Hcy、CysC与病情程度呈正相关,VEGF与病情程度呈负相关,多奈哌齐联合丁苯酞治疗老年AD能更有效降低Hcy、CysC水平,升高VEGF水平,进而提高临床治疗效果。

Dwarfing effects of plant growth regulators on narcissi

The effects of four kinds of plant growth regulators with different concentrations on narcissi were studied in 2001. The results showed that the regulators could inhibit the growths of height and leaves of narcissi. Of the four regulators, the dwarfing effects of paclobatrazol (PP333) and uniconazole (S3307) on narcissi were better than those of chlorocholine (CCC) and dimethyl amino-sussinamic acid (B9). All of the regulators did not have significant effect on the root length. Moreover, the time of flowering was later for the narcissi treated with regulators than that of the control to a certain extent, and the range delayed was from 2 days to 19 days. The correlation analysis results showed that there was a significant correlation between the time of flowering and the concentrations of regulators. The ornament value of narcissi was obviously improved by using the regulators.

Chinese and US S&T Innovation Policies and Their Effects on Economic Growth Potentials

Since the eruption of the recent global financial crisis, major countries have been pushing forward structural reforms with science and technology （S＆T） innovation at the heart. Since taking office, US President Donald Trump has adopted an ＂America First＂ strategy but has yet to specify a clear S＆T innovation policy. However, Trump＇s current policies have already affected S＆T innovation and his planned budget cuts will impact US growth potentials. Compared with the US, China is steadily implementing its innovation-driven development strategy with significant improvement in S＆ T innovation that increasingly supports economic growth. To spur future economic growth, China should steadfastly follow its S＆T innovation strategy, promote the utilization of S＆T innovation results, boost its economic growth potentials and make the most of global innovation resources.

China’s Potential Economic Growths during 2015-2025 under Different Scenarios~

China has entered a crucial period of further growth and restructuring that will last until 2025. Based on a review of the major factors affecting China＇s potential economic growth, this paper has created an integrated economic system model consisting of system dynamics, econometrics, and input-output for the forecast of China＇s economic size and structure by 2025. Analysis shows that prior to 2025, China will be able to maintain a potential annual economic growth rate of 5.7%-7.2%. Faced with an international environment of a possible slowdown of advanced economies and diminishing demographic dividends, China needs to further expedite its urbanization process, enhance R＆D and education spending, increase total factor productivity （TFP）, vigorously develop the tertiary sector, and expand consumption in order to achieve the optimistically estimated growth of 6.6%-7.4% during the period of 2015-2025. Economic growth should be accompanied by the upgrade of industry structure and improvement of investment and consumption structures.

Prognostic significance of S100A4 and vascular endothelial growth factor expression in pancreatic cancer

AIM: To investigate the expression of vascular endothelial growth factor (VEGF) and calcium-binding protein S100A4 in pancreatic cancer and their relationship to the clinicopathological parameters and prognosis of pancreatic cancer. METHODS: Expression status of VEGF and S100A4 was examined in 62 surgical specimens of primary pancreatic cancer by immunohistochemistry. Correlation between the expression of VEGF and S100A4 and clinicopathological parameters was analyzed. RESULTS: Thirty-eight of 62 (61.3%) specimens of primary pancreatic cancer were positive for S100A4. Thirty-seven (59.7%) specimens showed positive expression of VEGF. The positive correlation between S100A4 and VEGF expression was significant in cancer tissues (P < 0.001). S100A4 expression was significantly correlated with tumor size, TNM stage and poorer prognosis. VEGF expression had a significant correlation with poorer prognosis. The prognosis of 17 S100A4-and VEGF-negative cancer patients was significantly better than that of other patients (P < 0.05). Distant metastasis (P = 0.001), S100A4-(P = 0.008) and VEGF-positive expression (P = 0.016) were significantly independent prognostic predictors (P < 0.05). CONCLUSION: Over-expression of S100A4 and VEGF plays an important role in the development of pancreatic cancer. Combined examination of the two molecules might be useful in evaluating the outcome of patients with pancreatic cancer.

Cyclooxygenase-2 and epithelial growth factor receptor up-regulation during progression of Barrett's esophagus to adenocarcinoma

AIM： To investigate the expression of cyclooxygenase-2 （COX-2） and epithelial growth factor receptor （EGFR） throughout the progression of Barrett＇s esophagus （BE）. METHODS： COX-2 and EGFR protein expressions were detected by using immunohistochemical method. A detailed cytomorphological changes were determined. Areas of COX-2 and EGFR expression were quantified by using computer Imaging System. RESULTS： The expressions of both COX-2 and EGFR increased along with the progression from BE to esophagus adenocarcinoma （EAC）. A positive correlation was found between COX-2 expression and EGFR expression. CONCLUSION： COX-2 and EGFR may be cooperative in the stepwise progression from BE to EAC, thereby leading to carcinogenesis.

Comparison of six statistical approaches in the selection of appropriate fish growth models

The performance of six statistical approaches,which can be used for selection of the best model to describe the growth of individual fish,was analyzed using simulated and real length-at-age data.The six approaches include coefficient of determination(R2),adjusted coefficient of determination(adj.-R2),root mean squared error(RMSE),Akaike's information criterion(AIC),bias correction of AIC(AICc) and Bayesian information criterion(BIC).The simulation data were generated by five growth models with different numbers of parameters.Four sets of real data were taken from the literature.The parameters in each of the five growth models were estimated using the maximum likelihood method under the assumption of the additive error structure for the data.The best supported model by the data was identified using each of the six approaches.The results show that R2 and RMSE have the same properties and perform worst.The sample size has an effect on the performance of adj.-R2,AIC,AICc and BIC.Adj.-R2 does better in small samples than in large samples.AIC is not suitable to use in small samples and tends to select more complex model when the sample size becomes large.AICc and BIC have best performance in small and large sample cases,respectively.Use of AICc or BIC is recommended for selection of fish growth model according to the size of the length-at-age data.

The role of endotoxin,TNF-α,and IL-6 in inducing the state of growth hormone insensitivity

AIM: Critical illnesses such as sepsis, trauma, and burns cause a growth hormone insensitivity, which leads to an increased negative nitrogen balance. Endotoxin is generously released into blood under these conditions and stimulates the production of proinflammatory cytokines such as TNF-alpha, IL-6, and IL-1, which may play a very important role in inducing the growth hormone insensitivity. The objective of this current study was to investigate the role of endotoxin, TNF-alpha and IL-6 in inducing the growth hormone insensitivity at the receptor and post-receptor levels. METHODS: Spague-Dawley rats were injected with endotoxin, TNF-alpha, and IL-6, respectively and part of rats injected with endotoxin was treated with exogenous somatotropin simultaneously. All rats were killed at different time points. The expression of IGF-I, GHR, SOCS-3 and beta-actin mRNA in the liver was detected by RT-PCR and the GH levels were measured by radioimmunoassay, the levels of TNF-alpha and IL-6 were detected by ELISA. RESULTS: There was no significant difference in serous GH levels between experimental group and control rats after endotoxin injection, however, liver IGF-I mRNA expression had been obviously down-regulated in endotoxemic rats. Liver GHR mRNA expression also had a predominant down-regulation after endotoxin injection. The lowest regulation of liver IGF-I mRNA expression occurred at 12h after LPS injection, being decreased by 53% compared with control rats. For GHR mRNA expression, the lowest expression occurred at 8h and had a 81% decrease. Although SOCS-3 mRNA was weakly expressed in control rats, it was strongly up-regulated after LPS injection and had a 7.84 times increase compared with control rats. Exogenous GH could enhance IGF-I mRNA expression in control rats, but it did fail to prevent the decline in IGF-I mRNA expression in endotoxemic rats. Endotoxin stimulated the production of TNF-alpha and IL-6, and the elevated IL-6 levels was shown a positive correlation with increased SOCS-3 mRNA expression. The liver GHR mRNA expression was obviously down-regulated after TNF-alpha iv injection and had a 40% decrease at 8h, but the liver SOCS-3 mRNA expression was the 4.94 times up-regulation occurred at 40 min after IL-6 injection. CONCLUSION: The growth hormone insensitivity could be induced by LPS injection, which was associated with down-regulated GHR mRNA expression at receptor level and with up-regulated SOCS-3 mRNA expression at post-receptor level. The in vivo biological activities of LPS were mediated by TNF-alpha and IL-6 indirectly, and TNF-alpha and IL-6 may exert their effects on the receptor and post-receptor levels respectively.

Total flavone of Abelmoschus manihot suppresses epithelial-mesenchymal transition via interfering transforming growth factor-β1 signaling in Crohn's disease intestinal fibrosis

AIM To explore the role and mechanism of total flavone of Abelmoschus manihot(TFA) on epithelial-mesenchymal transition(EMT) progress of Crohn's disease(CD) intestinal fibrosis.METHODS First,CCK-8 assay was performed to assess TFA on the viability of intestinal epithelial(IEC-6) cells and select the optimal concentrations of TFA for our further studies.Then cell morphology,wound healing and transwell assays were performed to examine the effect of TFA on morphology,migration and invasion of IEC-6 cells treated with TGF-β1.In addition,immunofluorescence,real-time PCR analysis(q RT-PCR) and western blotting assays were carried out to detect the impact of TFA on EMT progress.Moreover,western blotting assay was performed to evaluate the function of TFA on the Smad and MAPK signaling pathways.Further,the role of co-treatment of TFA and si-Smad or MAPK inhibitors has been examined by q RTPCR,western blotting,morphology,wound healing andtranswell assays.RESULTS In this study,TFA promoted transforming growth factor-β1(TGF-β1)-induced(IEC-6) morphological change,migration and invasion,and increased the expression of epithelial markers and reduced the levels of mesenchymal markers,along with the inactivation of Smad and MAPK signaling pathways.Moreover,we revealed that si-Smad and MAPK inhibitors effectively attenuated TGF-β1-induced EMT in IEC-6 cells.Importantly,co-treatment of TFA and si-Smad or MAPK inhibitors had better inhibitory effects on TGF-β1-induced EMT in IEC-6 cells than either one of them.CONCLUSION These findings could provide new insight into the molecular mechanisms of TFA on TGF-β1-induced EMT in IEC-6 cells and TFA is expected to advance as a new therapy to treat CD intestinal fibrosis.

Reduction of tumorigenicity of SMMC-7721 hepatoma cells by vascular endothelial growth factor antisense gene therapy

AIM: To test the hypothesis to block VEGF expression of SMMC-7721 hepatoma cells may inhibit tumor growth using the rat hepatoma model. METHODS: Amplify the 200 VEGF cDNA fragment and insert it into human U6 gene cassette in the reverse orientation transcribing small antisense RNA which could specifically interact with VEGF165, and VEGF121 mRNA. Construct the retroviral vector containing this antisense VEGF U6 cassette and package the replication-deficient recombinant retrovirus. SMMC-7721 cells were transduced with these virus and positive clones were selected with G418. PCR and Southern blot analysis were performed to determine if U6 cassette integrated into the genomic DNA of positive clone. Transfected tumor cells were evaluated for RNA expression by ribonuclease protection assays. The VEGF protein in the supernatant of parental tumor cells and genetically modified tumor cells was determined with ELISA. In vitro and in vivo growth properties of antisense VEGF cell clone in nude mice were analyzed. RESULTS: Restriction enzyme digestion and PCR sequencing verified that the antisense VEGF RNA retroviral vector was successfully constructed.After G418 selection, resistant SMMC-7721 cell clone was picked up. PCR and Southern blot analysis suggested that U6 cassette was integrated into the cell genomic DNA. Stable SMMC-7721 cell clone transduced with U6 antisense RNA cassette could express 200 bp small antisense VEGF RNA and secrete reduced levels of VEGF in culture condition. Production of VEGF by antisense transgene-expressing cells was 65+/-10 ng/L per 10(6) cells, 42045 ng/L per 10(6) cells in sense group and 485+/-30 ng/L per 10(6) cells in the negative control group, (P【 0.05). The antisense-VEGF cell clone appeared phenotypically indistinguishable from SMMC-7721 cells and SMMC-7721 cells transfected sense VEGF. The growth rate of the antisense-VEGF cell clone was the same as the control cells. When S.C. was implanted into nude mice, growth of antisense-VEGF cell lines was greatly inhibited compared with control cells. CONCLUSION: Expression of antisense VEGF RNA in SMMC-7721 cells could decrease the tumorigenicity, and antisense-VEGF gene therapy may be an adjuvant treatment for hepatoma.