BACKGROUND Centromere protein A(CENPA)exhibits an increased expression level in primary human rectal cancer tissues,but its role has not been investigated.AIM To clarify the specific role and mechanism of CENPA in rec...BACKGROUND Centromere protein A(CENPA)exhibits an increased expression level in primary human rectal cancer tissues,but its role has not been investigated.AIM To clarify the specific role and mechanism of CENPA in rectal cancer progression.METHODS CENPA protein expression in rectal cancer tissues and cell lines were detected.CENPA was overexpressed and knocked down in SW837 and SW480 cells,and proliferation,invasion,apoptosis and epithelial-mesenchymal transition(EMT)marker protein levels were examined.O6-methylguanine DNA methyltransferase(MGMT)promoter methylation was assessed with methylation-specific poly-merase chain reaction.Co-immunoprecipitation assay verified the interaction between MGMT and protein tyrosine phosphatase nonreceptor type 4(PTPN4).SW837 cells with CENPA knockdown were injected subcutaneously into mice,and tumor growth was examined.RESULTS CENPA was upregulated in rectal cancer tissues and cell lines.CENPA overex-pression promoted proliferation,invasion and EMT,and inhibited apoptosis in rectal cancer cells.Whereas CENPA knockdown showed the opposite results.Moreover,CENPA inhibited MGMT expression by promoting DNA methyltrans-ferase 1-mediated MGMT promoter methylation.MGMT knockdown abolished the CENPA knockdown-mediated inhibition of rectal cancer cell progression.MGMT increased PTPN4 protein stability by inhibiting PTPN4 ubiquitination degradation via competing with ubiquitin-conjugating enzyme E2O for interacting with PTPN4.PTPN4 knockdown abolished the inhibitory effects of MGMT overexpression on rectal cancer cell progression.Moreover,CENPA knockdown inhibited xenograft tumor growth in vivo.CONCLUSION CENPA knockdown inhibited rectal cancer cell growth and attenuated xenograft tumor growth through regulating the MGMT/PTPN4 axis.展开更多
Irritable bowel syndrome(IBS) is a highly prevalent medical condition that adversely affects patient quality of life and constitutes a significant economic burden on healthcare resources. A large proportion of patient...Irritable bowel syndrome(IBS) is a highly prevalent medical condition that adversely affects patient quality of life and constitutes a significant economic burden on healthcare resources. A large proportion of patients suffer from the constipation subtype of IBS(IBS-C), most commonly afflicting older individuals and those with a lower socioeconomic status. Conventional pharmacologic and nonpharmacologic treatment options have limited efficacies and/or significant adverse events, which lead to increased long-term health care expenditures. Failure to effectively treat IBS-C patients over the past decades has largely been due to a poor understanding of disease pathophysiology, lack of a global view of the patient, and an inappropriate selection of patients and treatment endpoints in clinical trials. In recent years, however, more effective and safer drugs have been developed for the treatment of IBS-C. The advancement in the area of pharmacologic treatment is based on new knowledge of the pathophysiologic basis of IBS-C and the development of drugs with increased selectivity within pharmacologic classes with recognized efficacies. This narrative review covers the spectrum of available drugs and their mechanisms of action, as well as the efficacy and safety profiles of each as determined in relevant clinical trials that have investigated treatment options for IBS-C and chronic constipation. A brief summary of laxative-based treatment options is presented, followed by up-to-date assessments for three classes of drugs: prokinetics, prosecretory agents, and bile acid modulators.展开更多
AIM：To investigate the effect of the overexpression of C-X-C chemokine receptor type 4（CXCR4） on homing of mesenchymal stem cells（MSCs） in vitro and therapeutic effects of diabetic retinopathy（DR） in vivo.METH...AIM：To investigate the effect of the overexpression of C-X-C chemokine receptor type 4（CXCR4） on homing of mesenchymal stem cells（MSCs） in vitro and therapeutic effects of diabetic retinopathy（DR） in vivo.METHODS：MSCs were infected by lentivirus constructed with CXCR4.The expression of CXCR4 was examined by immunofluorescence,Western blot,and quantitative polymerase chain reaction.CXCR4-overexpressing MSCs were cultured in vitro to evaluate their chemotaxis,migration,and apoptotic activities.CXCR4-overexpressing MSCs were intravitreally injected to observe and compare their effects in a mouse model of DR.The histological structure of DR in rats was inspected by hematoxylin and eosin staining.The expression of rhodopsin,neuron-specific enolase（NSE）,and inflammatory cytokines interleukin（IL）-6 and tumor necrosis factor（TNF）-α was examined by Western blot and immunohistochemical analyses.RESULTS：The transduction of MSCs by lentivirus was effective,and the transduced MSCs had high expression levels of CXCR4 gene and protein.Improved migration activities were observed in CXCR4-overexpressing MSCs.Further,reduced retinal damage,upregulation of rhodopsin and NSE protein,and downregulation of inflammatory cytokines IL-6 and TNF-α were observed in CXCR4-overexpressing MSCs in vivo.CONCLUSION：The homing of MSCs can be enhanced by upregulating CXCR4 levels,possibly improving histological structures of DR.CXCR4-overexpressing MSCs can be a novel strategy for treating DR.展开更多
Objective and background： Although p21 ras has been reported to be upregulated in hepatocellular carcinoma complicating chronic hepatitis C type I, p21 ras has a different role in advanced stages, as it has been foun...Objective and background： Although p21 ras has been reported to be upregulated in hepatocellular carcinoma complicating chronic hepatitis C type I, p21 ras has a different role in advanced stages, as it has been found to be downregulated. The goal of this study was to investigate the status of p21 ras in early-stage/low-grade and late-stage/high-grade hepatocellular carcinoma and its possible link to apoptosis. Material and methods： Thirty-five cases each of chronic HCV hepatitis type 4 （group I） and cirrhosis with hepatocellular carcinoma （HCC） complicating chronic HCV hepatitis （groups Ⅱ and Ⅲ） were immunohistochemically evaluated using a p21 ras polyclonal antibody. The apoptotic index was determined in histologic sections using the terminal deoxynncleotidyl transferase-mediated d-UTP biotin nick end labeling （TUNEL） assay. Results： Significant differences （P=0.001） were detected in p21 ras protein expression between the three groups. A near 2-fold increase in p21 ras staining was observed in the cirrhotic cases compared to the hepatitis cases, and p21 ras expression was decreased in the HCC group, p21 ras expression correlated with stage （r=0.64, P--0.001） and grade （r=-0.65, P=0.001） in the HCC group and grade in the HCV group （r=0.44, P=0.008）. Both p21 ras expression and TUNEL-LI were significantly lower in large HCCs compared to small HCCs （P=0.01 each）. The TUNEL values were negatively correlated with stage in the HCC group （r=-0.85, P=0.001）. The TUNEL values were also negatively correlated with grade in both the HCV and HCC groups （r=0.89, P=0.001 and r=0.53, P=0.001, respectively）. The p21 ras scores were significantly correlated with the TUNEL-LI values in the HCC group （r=0.63, P=0.001） and HCV group （r=0.88, P=0.001）. Conclusions： p21 ras acts as an initiator in HCC complicating type 4 chronic HCV and is downregulated with HCC progression, which most likely promotes tumor cell survival because it facilitates the downregulation of apoptosis with tumor progression.展开更多
The existence of cancer stem cells has been wellestablished in acute myeloid leukemia. Initial proof of the existence of leukemia stem cells(LSCs) was accomplished by functional studies in xenograft models making use ...The existence of cancer stem cells has been wellestablished in acute myeloid leukemia. Initial proof of the existence of leukemia stem cells(LSCs) was accomplished by functional studies in xenograft models making use of the key features shared with normal hematopoietic stem cells(HSCs) such as the capacity of self-renewal and the ability to initiate and sustain growth of progenitors in vivo. Significant progress has also been made in identifying the phenotype and signaling pathways specific for LSCs. Therapeutically, a multitude of drugs targeting LSCs are in different phases of preclinical and clinical development. This review focuses on recent discoveries which have advanced our understanding of LSC biology and provided rational targets for development of novel therapeutic agents. One of the major challenges is how to target the selfrenewal pathways of LSCs without affecting normal HSCs significantly therefore providing an acceptable therapeutic window. Important issues pertinent to the successful design and conduct of clinical trials evaluating drugs targeting LSCs will be discussed as well.展开更多
OBJECTIVE: To determine the efficacy of a fermented buckwheat flower and leaf extract(EFBFL) for the reduction of blood glucose and lipid dysregulation in spontaneously obese type 2 diabetic db/db mice, and to explore...OBJECTIVE: To determine the efficacy of a fermented buckwheat flower and leaf extract(EFBFL) for the reduction of blood glucose and lipid dysregulation in spontaneously obese type 2 diabetic db/db mice, and to explore the possible mechanisms involved.METHODS: Forty 9-week-old male db/db mice were randomly allocated to a high-dose EFBFL group(EFBFL-H), a low-dose EFBFL group(EFBFL-L),a metformin hydrochloride positive control group(MEG), and a db/db control group(MG), and there was also a db/m negative control group(NCG)(n =10). Oral glucose tolerance tests(OGTT) were performed after 7 weeks of treatment. At the end of 8 weeks of treatment, random blood glucose(RBG),glycosylated hemoglobin(Hb Alc), fasting plasma glucose(FPG), fasting serum insulin(FINS), triglyceride(TG), serum total cholesterol(TC), free fatty acids(FFA), high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol(LDL-c) were measured, the homeostasis model assessment-insulin resistance(HOMA-IR) was calculated. Immunohistochemistry and western blotting measured the expression of glucose transporter4(GLUT4) and peroxisome proliferator-activated receptor γ(PPAR-γ) by in skeletal muscle.RESULTS: The MG mice had a significantly increased in RBG, Hb Alc, the HOMA-IR level, the serum of TG, TC, LDL-c, but a decreased in glucose tolerance and the protein expression of GLUT4 and PPAR-γ compared with the NCG. Compared with the MG, EFBFL groups significantly decreased RBG, Hb Alc, and the HOMA-IR level, increased glucose tolerance. Meanwhile EFBFL groups reduced the serum TG, TC, and LDL-c in a dose-dependent manner. In addition, EFBFL increased the protein expression of GLUT4 and PPAR-γ in the skeletal muscle of db/db mice.There was significant difference between the MG group and EFBFL groups.CONCLUSION: These findings suggest that EFBFL has anti-diabetic effects in db/db mice, ameliorating glucose intolerance, lipid dysregulation, and insulin resistance.展开更多
Objective： The aim of the research was to study peptidylarginine deiminase type 4 （PAD4/PADI4） expression and its tumodgenic mechanism in hepatocellular carcinomas. Methods： Expressions of PADI4 and p53 were inves...Objective： The aim of the research was to study peptidylarginine deiminase type 4 （PAD4/PADI4） expression and its tumodgenic mechanism in hepatocellular carcinomas. Methods： Expressions of PADI4 and p53 were investigated in tumors and non-tumor tissues by Western blot in patients with hepatocellular carcinomas. We constructed plasmid of PADI4-Flag and transfected it in Hela cells to investigate the mechanism. Results： Western blot analysis showed higher PADI4 expression in hepatocellular carcinomas than in the surrounding healthy tissues. Furthermore, by Western blot, we detected decreased p53 levels in the tumor tissues of patients with hepatocellular carcinomas compared to surrounding healthy tissues. In Hela cells transfected with PcDNA3.0-Flag-PADI4 plasmid, the expression of p53 decreased obviously. Conclusion： Our results suggest that PADI4 elevated in the tissues of hepatocellular carcinomas and induced tumorigenic by down-regulating p53 expression.展开更多
We report the fabrication and photocatalytic property of a composite of C/CaFe2O4nanorods(NRs)in an effort to reveal the influence of carbon modification.It is demonstrated that the photocatalytic degradation activity...We report the fabrication and photocatalytic property of a composite of C/CaFe2O4nanorods(NRs)in an effort to reveal the influence of carbon modification.It is demonstrated that the photocatalytic degradation activity is dependent on the mass ratio of C to CaFe2O4.The optimal carbon content is determined to be58wt%to yield a methylene blue(MB)degradation rate of0.0058min.1,which is4.8times higher than that of the pristine CaFe2O4NRs.The decoration of carbon on the surface of CaFe2O4NRs improves its adsorption capacity of the MB dye,which is specifically adsorbed on the surface as a monolayer according to the adsorption isotherm analysis.The trapping experiments of the reactive species indicate that superoxide radicals(.O2)are the main active species responsible for the removal of MB under visible‐light irradiation.Overall,the unique feature of carbon coating enables the efficient separation and transfer of photogenerated electrons and holes,strengthens the adsorption capacity of MB,and improves the light harvesting capability,hence enhancing the overall photocatalytic degradation of MB.展开更多
Sodium-ion batteries are considered as promising alternatives to lithium-ion batteries,owing to their low cost and abundant raw materials.Among the several candidate materials for the anode,spinel-type Li_(4)Ti_(5)O_(...Sodium-ion batteries are considered as promising alternatives to lithium-ion batteries,owing to their low cost and abundant raw materials.Among the several candidate materials for the anode,spinel-type Li_(4)Ti_(5)O_(12)has potential owing to its superior safety originating from an appropriate operating voltage and the reversible Na^(+)intercalation properties.However,a low diffusion coefficient for Na^(+)and the insulating nature of LTO remains challenging for practical sodium-ion battery systems.Herein,we present a strategy for integrating physical and chemical approaches to achieve superior electrochemical properties in LTO.We demonstrate that carefully controlling the amount of Cr doping is crucial to enhance the electrochemical properties of nanostructured LTO.Optimized Cr doped LTO shows a superior reversible capacity of 110 m Ah g^(-1) after 400 cycles at 1 C,with a three-fold higher capacity(75 m Ah g^(-1))at 10 C compared with undoped LTO material.This suggests that appropriately Cr doped nanostructured LTO is a promising anode material for sodium-ion batteries.展开更多
AIM： To delineate the mechanisms of renal vasoconstriction in hepatorenal syndrome （HRS）, we investigated the expression of type I inositol 1, 4, 5-triphosphate receptors （IP3R I） of kidney in mice with fulminant...AIM： To delineate the mechanisms of renal vasoconstriction in hepatorenal syndrome （HRS）, we investigated the expression of type I inositol 1, 4, 5-triphosphate receptors （IP3R I） of kidney in mice with fulminant hepatic failure （FHF）. METHODS： FHF was induced by lipopolysaccharide （LPS） in D-galactosamine （GAIN） sensitized BALB/c mice. There were 20 mice in normal saline （NS）-treated group, 20 mice in LPS-treated group, 20 mice in GaIN- treated group, and 60 mice in GalN/LPS-treated group （FHF group）. Liver and kidney tissues were obtained at 2, 6, and 9 h after administration. The liver and kidney specimens were stained with hematoxylin-eosin for studying morphological changes under light microscope. The expression of IP3R I in kidney tissue was tested by immunohistochemistry, Western blot and reverse transcription （RT）-PCR. RESULTS： Kidney tissues were morphologically normal at all time points in all groups. IP3R I proteins were found localized in the plasma region of glomerular mesangial cells （GMC） and vascular smooth muscle cells （VSMC） in kidney by immunohistochemical staining. In kidney of mice with FHF at 6 h and 9 h IP3R I staining was upregulated. Results from Western blot demonstrated consistent and significant increment of IP3R I expression in mice with FHF at 6 h and 9 h （t = 3.16, P 〈 0.05; t = 5.43, P 〈 0.01）. Furthermore, we evaluated IP3R I mRNA expression by RT-PCR and observed marked upregulation of IP3R I mRNA in FHF samples at 2 h, 6 h and 9 h compared to controls （t = 2.97, P 〈 0.05; t = 4.42, P 〈 0.01; t = 3.81, P 〈 0.01）. CONCLUSION： The expression of IP3R I protein increased in GMC and renal VSMC of mice with FHF, possibly caused by up-regulation of IP3R I mRNA.展开更多
Type 1 autoimmune pancreatitis (AIP) or chronic sclerosing sialadenitis (Küttner’s tumour) is an uncommon disorder that has recently been confirmed as an IgG4-related disease. Here, we describe...Type 1 autoimmune pancreatitis (AIP) or chronic sclerosing sialadenitis (Küttner’s tumour) is an uncommon disorder that has recently been confirmed as an IgG4-related disease. Here, we describe a rare case of a 53-year-old male patient who primarily presented with pancreatic body mass, left neck mass and several lumps in his lower lip mimicking pancreatic cancer (PC) and neck metastasis. The patient underwent pancreatic body mass and labial gland lumps resection as well as an ultrasound-guided biopsy of the left neck mass. He was diagnosed with IgG4-related focal type of AIP (f-AIP) and Küttner’s tumour by immunohistochemistry. The patient responded well to corticosteroid therapy and remains healthy with no signs of recurrence at one year follow-up. The differentiation of f-AIP from PC is very important to avoid unnecessary pancreatic resection.展开更多
BACKGROUND Pituitary apoplexy represents one of the most serious,life threatening endocrine emergencies that requires immediate management.Gonadotropin-releasing hormone agonist(GnRHa)can induce pituitary apoplexy in ...BACKGROUND Pituitary apoplexy represents one of the most serious,life threatening endocrine emergencies that requires immediate management.Gonadotropin-releasing hormone agonist(GnRHa)can induce pituitary apoplexy in those patients who have insidious pituitary adenoma coincidentally.CASE SUMMARY A 46-year-old woman,with a history of hypertension and menorrhagia was transferred to our hospital from a secondary care hospital after complaints of headache and vomiting,with loss of consciousness 5 min after an injection of GnRHa.The drug was prescribed by her gynecologist due to the presence of uterine myomas.The clinical neurological examination revealed right cranial nerve III palsy,ptosis and movement limitation of the right eye.Our first clinical consideration was a pituitary apoplexy.Blood hormonal analysis revealed mild hyperprolactinemia and high follicle stimulating hormone level;PTH and calcium was high with glomerular filtration rate mildly to moderately decrease.A computed tomography scan,revealed an enlarged pituitary gland(3.5 cm)impinging upon the optic chiasm with bone involvement of the sella.Following contrast media administration,the lesion showed homogeneous enhancement with high-density focus that suggests hemorrhagic infarction of the tumor.Transsphenoidal endoscopic surgery was perfomed and adenomatous tissue was removed.Immunohistochemistry was positive for luteinizing hormone(LH)and follicular-stimulating hormone(FSH).A solid hypoechoic nodule(14 mm x 13 mm x 16 mm)was found in the caudal portion of the right thyroid lobe after a parathyroid ultrasound.A genetic test of Multiple Endocrine Neoplasia type 1(MEN1)was negative.A right lower parathyroidectomy was performed and the pathologic study showed the presence of an encapsulated parathyroid carcinoma of 1.5 cm.A MEN type 4 genetic test was performed result was negative.CONCLUSION This case demonstrates an uncommon complication of GnRH agonist therapy in the setting of a pituitary macroadenoma and the casual finding of parathyroid carcinoma.It also highlights the importance of suspecting the presence of a multiple endocrine neoplasia syndrome and to carry out relevant genetic studies.展开更多
Background: This study investigated serum Glucose transporter (GLUT) 4 levels and examined the relationship between serum GLUT4 levels and sepsis in critically ill children. Methods: This was a retrospective study of ...Background: This study investigated serum Glucose transporter (GLUT) 4 levels and examined the relationship between serum GLUT4 levels and sepsis in critically ill children. Methods: This was a retrospective study of 77 critically ill children and 33 non-diabetic healthy children (controls) who were admitted between 07/2015 and 05/2016. Patient data, clinical information, and blood samples were collected on admission, alongside a large number of laboratory parameters that were routinely assessed. Critically ill patients were divided into sepsis and non-sepsis/systemic inflammatory response syndrome (SIRS). Serum GLUT4 was measured using western blotting and enzyme-linked immunosorbent assays. Insulin resistance indexes, clinical data, laboratory parameters, and inflammatory cytokines were assessed. Results: GLUT4 serum levels were higher in critically ill children than in healthy children (90.5 vs. 30.3 μg/L, P 0.05). Compared to healthy children, hyperglycemic patients (n = 48) had elevated GLUT4 serum levels (30.3 vs. 103.7 g/L, P Conclusions: GLUT4 serum levels might be significantly increased in critically ill children compared with healthy children, particularly those in septic shock. Serum GLUT4 could predict disease severity.展开更多
基金This study was reviewed and approved by the Ethic Committee of Medical College of Henan Vocational University of Science and Technology(Approval No.HVUYL414101416920231017001)all participants signed a written informed consent.
文摘BACKGROUND Centromere protein A(CENPA)exhibits an increased expression level in primary human rectal cancer tissues,but its role has not been investigated.AIM To clarify the specific role and mechanism of CENPA in rectal cancer progression.METHODS CENPA protein expression in rectal cancer tissues and cell lines were detected.CENPA was overexpressed and knocked down in SW837 and SW480 cells,and proliferation,invasion,apoptosis and epithelial-mesenchymal transition(EMT)marker protein levels were examined.O6-methylguanine DNA methyltransferase(MGMT)promoter methylation was assessed with methylation-specific poly-merase chain reaction.Co-immunoprecipitation assay verified the interaction between MGMT and protein tyrosine phosphatase nonreceptor type 4(PTPN4).SW837 cells with CENPA knockdown were injected subcutaneously into mice,and tumor growth was examined.RESULTS CENPA was upregulated in rectal cancer tissues and cell lines.CENPA overex-pression promoted proliferation,invasion and EMT,and inhibited apoptosis in rectal cancer cells.Whereas CENPA knockdown showed the opposite results.Moreover,CENPA inhibited MGMT expression by promoting DNA methyltrans-ferase 1-mediated MGMT promoter methylation.MGMT knockdown abolished the CENPA knockdown-mediated inhibition of rectal cancer cell progression.MGMT increased PTPN4 protein stability by inhibiting PTPN4 ubiquitination degradation via competing with ubiquitin-conjugating enzyme E2O for interacting with PTPN4.PTPN4 knockdown abolished the inhibitory effects of MGMT overexpression on rectal cancer cell progression.Moreover,CENPA knockdown inhibited xenograft tumor growth in vivo.CONCLUSION CENPA knockdown inhibited rectal cancer cell growth and attenuated xenograft tumor growth through regulating the MGMT/PTPN4 axis.
文摘Irritable bowel syndrome(IBS) is a highly prevalent medical condition that adversely affects patient quality of life and constitutes a significant economic burden on healthcare resources. A large proportion of patients suffer from the constipation subtype of IBS(IBS-C), most commonly afflicting older individuals and those with a lower socioeconomic status. Conventional pharmacologic and nonpharmacologic treatment options have limited efficacies and/or significant adverse events, which lead to increased long-term health care expenditures. Failure to effectively treat IBS-C patients over the past decades has largely been due to a poor understanding of disease pathophysiology, lack of a global view of the patient, and an inappropriate selection of patients and treatment endpoints in clinical trials. In recent years, however, more effective and safer drugs have been developed for the treatment of IBS-C. The advancement in the area of pharmacologic treatment is based on new knowledge of the pathophysiologic basis of IBS-C and the development of drugs with increased selectivity within pharmacologic classes with recognized efficacies. This narrative review covers the spectrum of available drugs and their mechanisms of action, as well as the efficacy and safety profiles of each as determined in relevant clinical trials that have investigated treatment options for IBS-C and chronic constipation. A brief summary of laxative-based treatment options is presented, followed by up-to-date assessments for three classes of drugs: prokinetics, prosecretory agents, and bile acid modulators.
基金Supported by the National Natural Science Foundation of China(No.81700846)Tianjin Science and Technology Project of China(No.13ZCZDSY01500)
文摘AIM：To investigate the effect of the overexpression of C-X-C chemokine receptor type 4（CXCR4） on homing of mesenchymal stem cells（MSCs） in vitro and therapeutic effects of diabetic retinopathy（DR） in vivo.METHODS：MSCs were infected by lentivirus constructed with CXCR4.The expression of CXCR4 was examined by immunofluorescence,Western blot,and quantitative polymerase chain reaction.CXCR4-overexpressing MSCs were cultured in vitro to evaluate their chemotaxis,migration,and apoptotic activities.CXCR4-overexpressing MSCs were intravitreally injected to observe and compare their effects in a mouse model of DR.The histological structure of DR in rats was inspected by hematoxylin and eosin staining.The expression of rhodopsin,neuron-specific enolase（NSE）,and inflammatory cytokines interleukin（IL）-6 and tumor necrosis factor（TNF）-α was examined by Western blot and immunohistochemical analyses.RESULTS：The transduction of MSCs by lentivirus was effective,and the transduced MSCs had high expression levels of CXCR4 gene and protein.Improved migration activities were observed in CXCR4-overexpressing MSCs.Further,reduced retinal damage,upregulation of rhodopsin and NSE protein,and downregulation of inflammatory cytokines IL-6 and TNF-α were observed in CXCR4-overexpressing MSCs in vivo.CONCLUSION：The homing of MSCs can be enhanced by upregulating CXCR4 levels,possibly improving histological structures of DR.CXCR4-overexpressing MSCs can be a novel strategy for treating DR.
文摘Objective and background： Although p21 ras has been reported to be upregulated in hepatocellular carcinoma complicating chronic hepatitis C type I, p21 ras has a different role in advanced stages, as it has been found to be downregulated. The goal of this study was to investigate the status of p21 ras in early-stage/low-grade and late-stage/high-grade hepatocellular carcinoma and its possible link to apoptosis. Material and methods： Thirty-five cases each of chronic HCV hepatitis type 4 （group I） and cirrhosis with hepatocellular carcinoma （HCC） complicating chronic HCV hepatitis （groups Ⅱ and Ⅲ） were immunohistochemically evaluated using a p21 ras polyclonal antibody. The apoptotic index was determined in histologic sections using the terminal deoxynncleotidyl transferase-mediated d-UTP biotin nick end labeling （TUNEL） assay. Results： Significant differences （P=0.001） were detected in p21 ras protein expression between the three groups. A near 2-fold increase in p21 ras staining was observed in the cirrhotic cases compared to the hepatitis cases, and p21 ras expression was decreased in the HCC group, p21 ras expression correlated with stage （r=0.64, P--0.001） and grade （r=-0.65, P=0.001） in the HCC group and grade in the HCV group （r=0.44, P=0.008）. Both p21 ras expression and TUNEL-LI were significantly lower in large HCCs compared to small HCCs （P=0.01 each）. The TUNEL values were negatively correlated with stage in the HCC group （r=-0.85, P=0.001）. The TUNEL values were also negatively correlated with grade in both the HCV and HCC groups （r=0.89, P=0.001 and r=0.53, P=0.001, respectively）. The p21 ras scores were significantly correlated with the TUNEL-LI values in the HCC group （r=0.63, P=0.001） and HCV group （r=0.88, P=0.001）. Conclusions： p21 ras acts as an initiator in HCC complicating type 4 chronic HCV and is downregulated with HCC progression, which most likely promotes tumor cell survival because it facilitates the downregulation of apoptosis with tumor progression.
文摘The existence of cancer stem cells has been wellestablished in acute myeloid leukemia. Initial proof of the existence of leukemia stem cells(LSCs) was accomplished by functional studies in xenograft models making use of the key features shared with normal hematopoietic stem cells(HSCs) such as the capacity of self-renewal and the ability to initiate and sustain growth of progenitors in vivo. Significant progress has also been made in identifying the phenotype and signaling pathways specific for LSCs. Therapeutically, a multitude of drugs targeting LSCs are in different phases of preclinical and clinical development. This review focuses on recent discoveries which have advanced our understanding of LSC biology and provided rational targets for development of novel therapeutic agents. One of the major challenges is how to target the selfrenewal pathways of LSCs without affecting normal HSCs significantly therefore providing an acceptable therapeutic window. Important issues pertinent to the successful design and conduct of clinical trials evaluating drugs targeting LSCs will be discussed as well.
基金Supported by a Grant from the Scientific Research Project of Hebei Provincial Administration for Traditional Chinese Medicine(Protective Effects and Mechanism of Extract from Fermented Buckwheat Flower and Leaf on Kidney in TypeⅡDiabetic db/db Mice,No.2017083)the Key Project Plan of Medical Science Research in Hebei Province in 2018(Protective Effects and Mechanism of Extract From Fermented Buckwheat Flower and Leaf on IsletβCells,No.201810736)。
文摘OBJECTIVE: To determine the efficacy of a fermented buckwheat flower and leaf extract(EFBFL) for the reduction of blood glucose and lipid dysregulation in spontaneously obese type 2 diabetic db/db mice, and to explore the possible mechanisms involved.METHODS: Forty 9-week-old male db/db mice were randomly allocated to a high-dose EFBFL group(EFBFL-H), a low-dose EFBFL group(EFBFL-L),a metformin hydrochloride positive control group(MEG), and a db/db control group(MG), and there was also a db/m negative control group(NCG)(n =10). Oral glucose tolerance tests(OGTT) were performed after 7 weeks of treatment. At the end of 8 weeks of treatment, random blood glucose(RBG),glycosylated hemoglobin(Hb Alc), fasting plasma glucose(FPG), fasting serum insulin(FINS), triglyceride(TG), serum total cholesterol(TC), free fatty acids(FFA), high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol(LDL-c) were measured, the homeostasis model assessment-insulin resistance(HOMA-IR) was calculated. Immunohistochemistry and western blotting measured the expression of glucose transporter4(GLUT4) and peroxisome proliferator-activated receptor γ(PPAR-γ) by in skeletal muscle.RESULTS: The MG mice had a significantly increased in RBG, Hb Alc, the HOMA-IR level, the serum of TG, TC, LDL-c, but a decreased in glucose tolerance and the protein expression of GLUT4 and PPAR-γ compared with the NCG. Compared with the MG, EFBFL groups significantly decreased RBG, Hb Alc, and the HOMA-IR level, increased glucose tolerance. Meanwhile EFBFL groups reduced the serum TG, TC, and LDL-c in a dose-dependent manner. In addition, EFBFL increased the protein expression of GLUT4 and PPAR-γ in the skeletal muscle of db/db mice.There was significant difference between the MG group and EFBFL groups.CONCLUSION: These findings suggest that EFBFL has anti-diabetic effects in db/db mice, ameliorating glucose intolerance, lipid dysregulation, and insulin resistance.
文摘Objective： The aim of the research was to study peptidylarginine deiminase type 4 （PAD4/PADI4） expression and its tumodgenic mechanism in hepatocellular carcinomas. Methods： Expressions of PADI4 and p53 were investigated in tumors and non-tumor tissues by Western blot in patients with hepatocellular carcinomas. We constructed plasmid of PADI4-Flag and transfected it in Hela cells to investigate the mechanism. Results： Western blot analysis showed higher PADI4 expression in hepatocellular carcinomas than in the surrounding healthy tissues. Furthermore, by Western blot, we detected decreased p53 levels in the tumor tissues of patients with hepatocellular carcinomas compared to surrounding healthy tissues. In Hela cells transfected with PcDNA3.0-Flag-PADI4 plasmid, the expression of p53 decreased obviously. Conclusion： Our results suggest that PADI4 elevated in the tissues of hepatocellular carcinomas and induced tumorigenic by down-regulating p53 expression.
基金supported by the National Natural Science Foundation of China(21503100)Natural Science Foundation of Jiangxi Province(20161BAB213071,20151BAB213010)+1 种基金Project of Education Department of Jiangxi Province(GJJ150325)Sponsored Program for Cultivating Youths of Outstanding Ability in Jiangxi Normal University~~
文摘We report the fabrication and photocatalytic property of a composite of C/CaFe2O4nanorods(NRs)in an effort to reveal the influence of carbon modification.It is demonstrated that the photocatalytic degradation activity is dependent on the mass ratio of C to CaFe2O4.The optimal carbon content is determined to be58wt%to yield a methylene blue(MB)degradation rate of0.0058min.1,which is4.8times higher than that of the pristine CaFe2O4NRs.The decoration of carbon on the surface of CaFe2O4NRs improves its adsorption capacity of the MB dye,which is specifically adsorbed on the surface as a monolayer according to the adsorption isotherm analysis.The trapping experiments of the reactive species indicate that superoxide radicals(.O2)are the main active species responsible for the removal of MB under visible‐light irradiation.Overall,the unique feature of carbon coating enables the efficient separation and transfer of photogenerated electrons and holes,strengthens the adsorption capacity of MB,and improves the light harvesting capability,hence enhancing the overall photocatalytic degradation of MB.
基金supported by the Korea Institute of Science and Technology(KIST)Institutional Program(Project No.2E30212)the National Research Foundation of Korea(NRF)(NRF-2020M3H4A1A0308297811)。
文摘Sodium-ion batteries are considered as promising alternatives to lithium-ion batteries,owing to their low cost and abundant raw materials.Among the several candidate materials for the anode,spinel-type Li_(4)Ti_(5)O_(12)has potential owing to its superior safety originating from an appropriate operating voltage and the reversible Na^(+)intercalation properties.However,a low diffusion coefficient for Na^(+)and the insulating nature of LTO remains challenging for practical sodium-ion battery systems.Herein,we present a strategy for integrating physical and chemical approaches to achieve superior electrochemical properties in LTO.We demonstrate that carefully controlling the amount of Cr doping is crucial to enhance the electrochemical properties of nanostructured LTO.Optimized Cr doped LTO shows a superior reversible capacity of 110 m Ah g^(-1) after 400 cycles at 1 C,with a three-fold higher capacity(75 m Ah g^(-1))at 10 C compared with undoped LTO material.This suggests that appropriately Cr doped nanostructured LTO is a promising anode material for sodium-ion batteries.
基金Supported by National Natural Science Foundation of China, No. 30270607
文摘AIM： To delineate the mechanisms of renal vasoconstriction in hepatorenal syndrome （HRS）, we investigated the expression of type I inositol 1, 4, 5-triphosphate receptors （IP3R I） of kidney in mice with fulminant hepatic failure （FHF）. METHODS： FHF was induced by lipopolysaccharide （LPS） in D-galactosamine （GAIN） sensitized BALB/c mice. There were 20 mice in normal saline （NS）-treated group, 20 mice in LPS-treated group, 20 mice in GaIN- treated group, and 60 mice in GalN/LPS-treated group （FHF group）. Liver and kidney tissues were obtained at 2, 6, and 9 h after administration. The liver and kidney specimens were stained with hematoxylin-eosin for studying morphological changes under light microscope. The expression of IP3R I in kidney tissue was tested by immunohistochemistry, Western blot and reverse transcription （RT）-PCR. RESULTS： Kidney tissues were morphologically normal at all time points in all groups. IP3R I proteins were found localized in the plasma region of glomerular mesangial cells （GMC） and vascular smooth muscle cells （VSMC） in kidney by immunohistochemical staining. In kidney of mice with FHF at 6 h and 9 h IP3R I staining was upregulated. Results from Western blot demonstrated consistent and significant increment of IP3R I expression in mice with FHF at 6 h and 9 h （t = 3.16, P 〈 0.05; t = 5.43, P 〈 0.01）. Furthermore, we evaluated IP3R I mRNA expression by RT-PCR and observed marked upregulation of IP3R I mRNA in FHF samples at 2 h, 6 h and 9 h compared to controls （t = 2.97, P 〈 0.05; t = 4.42, P 〈 0.01; t = 3.81, P 〈 0.01）. CONCLUSION： The expression of IP3R I protein increased in GMC and renal VSMC of mice with FHF, possibly caused by up-regulation of IP3R I mRNA.
基金Supported by National Natural Scientific Foundation,No.81070370,and No.81270544 to Gao RPNational Institutes of Health,No.5R01AA016003 to Brigstock DR
文摘Type 1 autoimmune pancreatitis (AIP) or chronic sclerosing sialadenitis (Küttner’s tumour) is an uncommon disorder that has recently been confirmed as an IgG4-related disease. Here, we describe a rare case of a 53-year-old male patient who primarily presented with pancreatic body mass, left neck mass and several lumps in his lower lip mimicking pancreatic cancer (PC) and neck metastasis. The patient underwent pancreatic body mass and labial gland lumps resection as well as an ultrasound-guided biopsy of the left neck mass. He was diagnosed with IgG4-related focal type of AIP (f-AIP) and Küttner’s tumour by immunohistochemistry. The patient responded well to corticosteroid therapy and remains healthy with no signs of recurrence at one year follow-up. The differentiation of f-AIP from PC is very important to avoid unnecessary pancreatic resection.
基金Supported by FIS del Instituto de Salud Carlos Ⅲ(FEDER from E.U.),Spain,No.PI13/00322 and PI16/00884
文摘BACKGROUND Pituitary apoplexy represents one of the most serious,life threatening endocrine emergencies that requires immediate management.Gonadotropin-releasing hormone agonist(GnRHa)can induce pituitary apoplexy in those patients who have insidious pituitary adenoma coincidentally.CASE SUMMARY A 46-year-old woman,with a history of hypertension and menorrhagia was transferred to our hospital from a secondary care hospital after complaints of headache and vomiting,with loss of consciousness 5 min after an injection of GnRHa.The drug was prescribed by her gynecologist due to the presence of uterine myomas.The clinical neurological examination revealed right cranial nerve III palsy,ptosis and movement limitation of the right eye.Our first clinical consideration was a pituitary apoplexy.Blood hormonal analysis revealed mild hyperprolactinemia and high follicle stimulating hormone level;PTH and calcium was high with glomerular filtration rate mildly to moderately decrease.A computed tomography scan,revealed an enlarged pituitary gland(3.5 cm)impinging upon the optic chiasm with bone involvement of the sella.Following contrast media administration,the lesion showed homogeneous enhancement with high-density focus that suggests hemorrhagic infarction of the tumor.Transsphenoidal endoscopic surgery was perfomed and adenomatous tissue was removed.Immunohistochemistry was positive for luteinizing hormone(LH)and follicular-stimulating hormone(FSH).A solid hypoechoic nodule(14 mm x 13 mm x 16 mm)was found in the caudal portion of the right thyroid lobe after a parathyroid ultrasound.A genetic test of Multiple Endocrine Neoplasia type 1(MEN1)was negative.A right lower parathyroidectomy was performed and the pathologic study showed the presence of an encapsulated parathyroid carcinoma of 1.5 cm.A MEN type 4 genetic test was performed result was negative.CONCLUSION This case demonstrates an uncommon complication of GnRH agonist therapy in the setting of a pituitary macroadenoma and the casual finding of parathyroid carcinoma.It also highlights the importance of suspecting the presence of a multiple endocrine neoplasia syndrome and to carry out relevant genetic studies.
文摘Background: This study investigated serum Glucose transporter (GLUT) 4 levels and examined the relationship between serum GLUT4 levels and sepsis in critically ill children. Methods: This was a retrospective study of 77 critically ill children and 33 non-diabetic healthy children (controls) who were admitted between 07/2015 and 05/2016. Patient data, clinical information, and blood samples were collected on admission, alongside a large number of laboratory parameters that were routinely assessed. Critically ill patients were divided into sepsis and non-sepsis/systemic inflammatory response syndrome (SIRS). Serum GLUT4 was measured using western blotting and enzyme-linked immunosorbent assays. Insulin resistance indexes, clinical data, laboratory parameters, and inflammatory cytokines were assessed. Results: GLUT4 serum levels were higher in critically ill children than in healthy children (90.5 vs. 30.3 μg/L, P 0.05). Compared to healthy children, hyperglycemic patients (n = 48) had elevated GLUT4 serum levels (30.3 vs. 103.7 g/L, P Conclusions: GLUT4 serum levels might be significantly increased in critically ill children compared with healthy children, particularly those in septic shock. Serum GLUT4 could predict disease severity.
