Chemodynamic therapy(CDT),using Fenton agents to generate highly cytotoxic•OH from H_(2)O_(2)has been demonstrated as a powerful anticancer method.However,the insufficient endogenous H_(2)O_(2)in tumor cells greatly l...Chemodynamic therapy(CDT),using Fenton agents to generate highly cytotoxic•OH from H_(2)O_(2)has been demonstrated as a powerful anticancer method.However,the insufficient endogenous H_(2)O_(2)in tumor cells greatly limited its therapeutic effect.Herein,we prepared a pH-responsiveβ-lapachone-loaded ironpolyphenol nanocomplex(LIPN)through a one-pot method.β-Lapachone in LIPN selectively enhanced H_(2)O_(2)concentration in tumor cells,and ferrous ions cascadely generated abundant cytotoxic•OH.Therefore,LIPN with cascade amplification of reactive oxygen species(ROS)showed high chemodynamic cytotoxicity in tumor cells,efficiently improving the expression of damage-associated molecular patterns(DAMPs),and exerting strong immunogenic cell death(ICD).As a result,LIPN exhibited efficient tumor inhibition ability in 4T1 subcutaneous tumor model in vivo with great biocompatibility.Additionally,the infiltration of cytotoxic CD8^(+)T lymphocytes and inhibition of regulatory CD4^(+)FoxP3^(+)T lymphocytes in tumors demonstrated the activation of immunosuppressive tumor microenvironment by LIPN-induced ICD.Therefore,this work provided a new approach to enhance ICD of chemodynamic therapy through selective cascade amplification of ROS in cancer cells.展开更多
Vascular-targeted photodynamic therapy(V-PDT)is an effective treatment for port wine stains(PWS).However,repeated treatment is usually needed to achieve optimal treatment outcomes,possibly due to the limited treatment...Vascular-targeted photodynamic therapy(V-PDT)is an effective treatment for port wine stains(PWS).However,repeated treatment is usually needed to achieve optimal treatment outcomes,possibly due to the limited treatment light penetration depth in the PWS lesion.The optical clearing technique can increase light penetration in depth by reducing light scattering.This study aimed to investigate the V-PDT in combination with an optical clearing agent(OCA)for the therapeutic enhancement of V-PDT in the rodent skinfold window chamber model.Vascular responses were closely monitored with laser speckle contrast imaging(LSCI),optical coherence tomography angiography,and stereo microscope before,during,and after the treatment.We further quantitatively demonstrated the effects of V-PDT in combination with OCA on the blood flow and blood vessel size of skin microvasculature.The combination of OCA and V-PDT resulted in significant vascular damage,including vasoconstriction and the reduction of blood flow.Our results indicate the promising potential of OCA for enhancing V-PDT for treating vascular-related diseases,including PWS.展开更多
ALKBH1 was recently discovered as a demethylase for DNA N6-methyladenine （N6-mA）, a new epigenetic modification, and interacts with the core transcriptional pluripotency network of embryonic stem cells. However, the...ALKBH1 was recently discovered as a demethylase for DNA N6-methyladenine （N6-mA）, a new epigenetic modification, and interacts with the core transcriptional pluripotency network of embryonic stem cells. However, the role of ALKBH1 and DNA N6-mA in regulating osteogenic differentiation is largely unknown. In this study, we demonstrated that the expression of ALKBH1 in human mesenchymal stem cells （MSCs） was upregulated during osteogenic induction. Knockdown of ALKBH1 increased the genomic DNA N6-mA levels and significantly reduced the expression of osteogenic-related genes, alkaline phosphatase activity, and mineralization. ALKBHl-depleted MSCs also exhibited a restricted capacity for bone formation in vivo. By contrast, the ectopic overexpression of ALKBH1 enhanced osteoblastic differentiation. Mechanically, we found that the depletion of ALKBH1 resulted in the accumulation of N6-mA on the promoter region of ATF4, which subsequently silenced ATF4 transcription. In addition, restoring the expression of ATP by adenovirus-mediated transduction successfully rescued osteogenic differentiation. Taken together, our results demonstrate that ALKBH1 is indispensable for the osteogenic differentiation of MSCs and indicate that DNA N6-mA modifications area new mechanism for the epigenetic regulation of stem cell differentiation.展开更多
Osteoarthritis （OA） is a degenerative joint disease and a major cause of pain and disability in older adults. We have previously identified epidermal growth factor receptor （EGFR） signaling as an important regulat...Osteoarthritis （OA） is a degenerative joint disease and a major cause of pain and disability in older adults. We have previously identified epidermal growth factor receptor （EGFR） signaling as an important regulator of cartilage matrix degradation during epiphyseal cartilage development. To study its function in OA progression, we performed surgical destabilization of the medial meniscus （DMM） to induce OA in two mouse models with reduced EGFR activity, one with genetic modification （, was/＋ mice） and the other one with pharmacological inhibition （gefitinib treatment）. Histological analyses and scoring at 3 months post-surgery revealed increased cartilage destruction and accelerated OA progression in both mouse models. TUNEL staining demonstrated that EGFR signaling protects chondrocytes from OA-induced apoptosis, which was further confirmed in primary chondrocyte culture. Immunohistochemistry showed increased aggrecan degradation in these mouse models, which coincides with elevated amounts of ADAMTS5 and matrix metalloproteinase 13 （MMP13）, the principle proteinases responsible for aggrecan degradation, in the articular cartilage after DMM surgery. Furthermore, hypoxia-inducible factor 2α （HIF2α）, a critical catabolic transcription factor stimulating MMP13 expression during OA, was also upregulated in mice with reduced EGFR signaling. Taken together, our findings demonstrate a primarily protective role of EGFR during OA progression by regulating chondrocyte survival and cartilage degradation.展开更多
Copper （Cu） is an essential trace mineral element for all forms of life, and is an important structural component and co-factor for a variety of metalloenzymes （Pefia et al., 1999; Bertinato and L＇Abbe, 2004）. In...Copper （Cu） is an essential trace mineral element for all forms of life, and is an important structural component and co-factor for a variety of metalloenzymes （Pefia et al., 1999; Bertinato and L＇Abbe, 2004）. In humans, Cu deficiency is not common because of the ubiquitous occurrence of Cu and ease of gastrointestinal absorption （Zidar et al., 1977; Uauy et al., 1998）.展开更多
Depression refers to a series of mental health issues characterized by loss of interest and enjoyment in everyday life,low mood and selected emotional,cognitive,physical and behavioral symptoms.Depression is a common ...Depression refers to a series of mental health issues characterized by loss of interest and enjoyment in everyday life,low mood and selected emotional,cognitive,physical and behavioral symptoms.Depression is a common disorder,affecting 5–15%of the general population.When diagnosed as major depressive disorder（MDD）,patients are currentlytreated with pharmacological agents such as serotonin or noradren- aline uptake inhibitors （SSRI or SNRI） or tricyclics.展开更多
Toll-like receptor （TLR）-mediated inflammatory response could negatively affect bone metabolism. In this study, we determined how osteogenesis is regulated during inflammatory responses that are downstream of TLR si...Toll-like receptor （TLR）-mediated inflammatory response could negatively affect bone metabolism. In this study, we determined how osteogenesis is regulated during inflammatory responses that are downstream of TLR signaling. Human primary osteoblasts were cultured in collagen gels. Pam3CSK4 （P3C） and Escherichia coli lipopolysaccharide （EcLPS） were used as TLR2 and TLR4 ligand respectively. Porphyromonas gingivalis LPS having TLR2 activity with either TLR4 agonism （Pg1690） or TLR4 antagonism （Pg1449） and mutant E. coli LPS （LPxE/LPxF/WSK） were used. IL-lp, SH2-containing inositol phosphatase-1 （SHIP1） that has regulatory roles in osteogenesis, alkaline phosphatase and mineralization were analyzed. 3α-Aminocholestane （3AC） was used to inhibit SHIP1. Our results suggest that osteoblasts stimulated by P3C, poorly induced IL-1β but strongly upregulated SHIP1 and enhanced osteogenic mediators. On the contrary, EcLPS significantly induced IL-1β and osteogenic mediators were not induced. While Pg1690 downmodulated osteogenic mediators, Pg1449 enhanced osteogenic responses, suggesting that TLR4 signaling annuls osteogenesis even with TLR2 activity. Interestingly, mutant E. coli LPS that induces weak inflammation upregulated osteogenesis, but SHIP1 was not induced. Moreover, inhibiting SHIP1 significantly upregulated TLR2-mediated inflammatory response and downmodulated osteogenesis. In conclusion, these results suggest that induction of weak inflammatory response through TLR2 （with SHIP1 activity） and mutant TLR4 ligands could enhance osteogenesis.展开更多
Burkitt lymphoma is a highly aggressive B-cell neoplasm. New therapeutic methods are needed to overcome the adverse effect of intensive chemotherapy regimens. Valproic acid and （-）-gossypol are two kinds of chemical...Burkitt lymphoma is a highly aggressive B-cell neoplasm. New therapeutic methods are needed to overcome the adverse effect of intensive chemotherapy regimens. Valproic acid and （-）-gossypol are two kinds of chemical compounds used as new anti-tumor drugs in recent years.展开更多
Objective:The tumor necrosis factor receptor-associated factor 7(TRAF7)is one of the components of the tumor necrosis factor alpha(TNF-α)/nuclear factor kappa B(NF-κB)pathway and a putative E3-ubiquitin ligase.This ...Objective:The tumor necrosis factor receptor-associated factor 7(TRAF7)is one of the components of the tumor necrosis factor alpha(TNF-α)/nuclear factor kappa B(NF-κB)pathway and a putative E3-ubiquitin ligase.This study aims to explore the biologic effects and the molecular mechanisms of deregulated TRAF7 signaling in hepatocellular carcinoma(HCC)progression.展开更多
Johnson et al. (1993) showed that coexposure to UV-A between 300-400 nm enhanced the toxicity of nitrotoluenes to Phoiobacterium phosphoreum, a marine bioluminescent bacteria used in the Microtox test (Microbics Inc.)...Johnson et al. (1993) showed that coexposure to UV-A between 300-400 nm enhanced the toxicity of nitrotoluenes to Phoiobacterium phosphoreum, a marine bioluminescent bacteria used in the Microtox test (Microbics Inc.). This paper reports that UV-A photoenhanced the toxicity of polynuclear aromatic hydrocarbons, other types of organic compounds, and some transition metals to P. phosphoreum. Coexposure to 400 μw/cm2 for 15 min increased the toxicity of psoralen, α-terthienyl, anthracene, acridine, fluoranthene,TNT, Cu2+, As3+, Ni2, and Cd2+. Phenanthrene was photoenhanced after 30 min coexposure at 400 μw/cm2+, and Mn2+ at 800 μw/cm2 aftef 15 min. Naphthalene was not enhanced at 800 μw/cm2 for 30 min展开更多
Sigma-1 receptors are unique receptors that are postulated to act as intracellular amplifiers for signal transduction within cells of the nervous system. The present paper studied the
BACKGROUND： Interstitial stem cell is charactenzed by multiple differentiations, and retinoic acid （RA） can induce differentiation of stromal cells into nerve tissue cells in fetal liver of mice, so, its signal tra...BACKGROUND： Interstitial stem cell is charactenzed by multiple differentiations, and retinoic acid （RA） can induce differentiation of stromal cells into nerve tissue cells in fetal liver of mice, so, its signal transduction pathway should be discussed to trigger differentiation. OBJECTIVE ： To study the effect of RA on expression of neural specific gene and its signal transduction in fetal liver of mice.DESIGN ： Paired controlled study on the basis of cell.SETTING ： Institute of Hematology, Medical College of Jinan University.MATERIALS： The experiment was completed in the Institute of Hematology, Medical College of Jinan University from April to December 2005. C57BL/6 mice, of clean grade, aged 8-10 weeks, weighting 20-35 g, 10 females and 4 males, were selected in this study.METHODS： Sca-1^＋ cells in fetal liver were prepared with MACS kit and cultured with DMEM ＋ 10% fetal bovine serum （FBS）. On the fourth day, it was added with or without protein kinase C （PKC） inhibitor chelerythrine chloride （3μmol/L） and 5×10^-7 mol/L RA for 24 hours, and then incubated in serum-free medium for 5 days. Expressions of genes were assayed by Westem blotting and semi-quantitative RT-PCR.MAIN OUTCOME MEASURES ： Expression of neural specific gene NF-L, NF-H, BF-1 and TH.RESULTS： Expression of neural specific gene NF-L, NF-H, BF-1 and TH was significantly increased after treatment with RA and they were increased 5.06, 5.15, 4.63 and 3.33 times, respectively. However, chelerythrine chloride could inhibit expression of neural specific gene NF-L, NF-H, BF-1 and TH induced by RA.CONCLUSION ： RA can promote the expression of neural specific genes in Sca-1^＋ cells of fetal liver, and its pathway may be related to PKC.展开更多
Multiple links between miRNA activity and cancer have been established. Several miRNAs have been describedas oncogenes while others act as tumour suppressors[1]. MiR-449a is a member of miR-34 family which locates onh...Multiple links between miRNA activity and cancer have been established. Several miRNAs have been describedas oncogenes while others act as tumour suppressors[1]. MiR-449a is a member of miR-34 family which locates onhuman chromosome 5q11.2, a region identified as a susceptibility locus in a variety of malignancies, includingprostate cancer[2]. In line with the tumor-suppressive role of miR-34, miR-449a was shown to be significantly downregulatedin prostate cancer cell lines and tissue relative to normal tissues and plays a critical role in growth ofprostate cancer cells [3;4].展开更多
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial transcription factor regulating the expression ofantioxidant genes. Under oxidative stress conditions or other stimulus, Nrf2 translocating from the cyto...Nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial transcription factor regulating the expression ofantioxidant genes. Under oxidative stress conditions or other stimulus, Nrf2 translocating from the cytoplasminto the nucleus, binds to antioxidant response elements, and increases the expression of antioxidant enzymes[1;2].Constitutive Nrf2 activation in many tumors enhances cell survival and resistance. For instance, high level of Nrf2 isobserved in non-small cell lung cancer A549 cells[3;4]. The gain of Nrf2 function has been implicated in the resistanceof cancer cells to radiation therapy.展开更多
c-Myc was one of the first oncogenes to be identified and its overexpression at the RNA and protein levels has subsequently been linked to a wide variety of human cancers[1]. Overexpression of the c-Myc protein or c-M...c-Myc was one of the first oncogenes to be identified and its overexpression at the RNA and protein levels has subsequently been linked to a wide variety of human cancers[1]. Overexpression of the c-Myc protein or c-Myc gene has been shown in 80% of breast cancers, 70% of colon cancers, 90% of gynecological cancers, 50% of hepatocellular carcinomas and a variety of hematological tumors.展开更多
Transient receptor potential vanilloid 1(TRPVl) that is known as capsaicin receptor is a non-selective cationion channel[1]. TRPV1 can regulate Ca2+ influx, participate in a variety of physiological and pathological p...Transient receptor potential vanilloid 1(TRPVl) that is known as capsaicin receptor is a non-selective cationion channel[1]. TRPV1 can regulate Ca2+ influx, participate in a variety of physiological and pathological processof tumor[2]. One such agent is Capsazepine (CPZ) that is now widely used as a selective vanilloid type 1 receptor(TRPV1) antagonist. CPZ can be directly actived on the capsaicin receptor, blocked its biological effects, and abolishedosteosarcoma-induced hyperalgesia when administered subcutaneously at doses ranging from 3 to 10 mg/kg,blocked calcium channels[3]. However, the mechanisms underlying the anticancer effects of CPZ have not fully beenunderstood. Whether CPZ can induce apoptosis of human hepatocellular carcinoma cell line HepG2 is not known.Therefore, the objective of the study reported here was to determine whether CPZ can enhance radiation sensitivityin HepG2 cell, and impact on cell proliferation.展开更多
From October 10 to 17,the Festival of China 2009 was held in Kathmandu,capital of Nepal.This one-week biennial celebration,initiated in 2003,aims to"promote
Background: Enhanced recovery after surgery(ERAS) protocol is a multimodal, multidisciplinary and evidence-based approach to reduce surgical stress and enhance recovery in the postoperative period. This study aimed to...Background: Enhanced recovery after surgery(ERAS) protocol is a multimodal, multidisciplinary and evidence-based approach to reduce surgical stress and enhance recovery in the postoperative period. This study aimed to analyze the outcome of ERAS protocol in patients after pancreaticoduodenectomy(PD). Methods: A total of 50 consecutive patients with pancreatic/periampullary cancer who underwent PD between January 2016 to August 2017 were included in the study. As per the institute ERAS protocol, nasogastric tube(NGT) was removed on postoperative day(POD) 1 if output was less than 200 mL and oral sips were allowed; oral liquids were allowed on POD2; semisolid diet by POD3; abdominal drain was removed on POD 4 if output was less than 100 mL with no evidence of postoperative pancreatic fistula(POPF); normal diet was allowed on POD5. Discharge criteria on POD6 were afebrile, tolerating oral normal diet, pain free and no surgery related complications(defined as per the ISGPS definitions). Results: NGT was removed on POD1 in 45(90%) patients, abdominal drain removed by POD4 in 41(82%) and 43(86%) patients were discharged on POD6. There was no 30-day postoperative mortality. Three(6%) patients had delayed gastric emptying(DGE). None had postoperative hemorrhage and POPF. Readmission rate was 8%. A significant relation was found between the length of hospital stay(LOS) with age( P < 0.05) and a marginal relation between LOS and postoperative albumin( P = 0.05). Conclusions: ERAS protocol can be safely followed in the perioperative care of patients who undergo PD. Early removal of NGT and allowing oral diet restore bowel function early. ERAS decreases the LOS and postoperative complications.展开更多
Cry toxins produced by Bacillus thuringiensis（Bt） are effective biological insecticides against certain insect species.In this study,bioassay results indicated that Cry1B and Cry1C were toxic to Spodoptera exigua.We...Cry toxins produced by Bacillus thuringiensis（Bt） are effective biological insecticides against certain insect species.In this study,bioassay results indicated that Cry1B and Cry1C were toxic to Spodoptera exigua.We also identified a cadherin-like gene in S.exigua that could enhance the toxicity of Cry1B and Cry1C.The cadherin-like gene identified from the larvae midgut tissue was cloned by reverse transcription polymerase chain reaction（RT-PCR） and rapid amplification of cDNA ends（RACE）.The full-length cDNA of the gene consisted of 5 220 bp encoding 1 740 amino acid with a predicted molecular mass of 196 kD.BLAST search analysis showed that the predicted amino acid sequence had a high sequence identity to the published sequences of cadherin-like proteins from other Lepidoptera insects.Spatial expression of the cadherin-like gene detected by qRT-PCR analysis revealed that the cadherin-like gene was mainly present in the gut of 4th instar larvae and during different life stages.The results suggested that the commercial development of this synergist has the potential to enhance Cry1B and Cry1C toxicity against Lepidoptera insects.展开更多
基金supported by the National Natural Science Foundation of China(Nos.T2293753,52203194)the National Key R&D Program of China(No.2021YFA1201200)+1 种基金the Natural Science Foundation of Zhejiang Province(No.LR18E030002)2023 Hangzhou West Lake Pearl Project Leading Innovative Youth Team Project.
文摘Chemodynamic therapy(CDT),using Fenton agents to generate highly cytotoxic•OH from H_(2)O_(2)has been demonstrated as a powerful anticancer method.However,the insufficient endogenous H_(2)O_(2)in tumor cells greatly limited its therapeutic effect.Herein,we prepared a pH-responsiveβ-lapachone-loaded ironpolyphenol nanocomplex(LIPN)through a one-pot method.β-Lapachone in LIPN selectively enhanced H_(2)O_(2)concentration in tumor cells,and ferrous ions cascadely generated abundant cytotoxic•OH.Therefore,LIPN with cascade amplification of reactive oxygen species(ROS)showed high chemodynamic cytotoxicity in tumor cells,efficiently improving the expression of damage-associated molecular patterns(DAMPs),and exerting strong immunogenic cell death(ICD).As a result,LIPN exhibited efficient tumor inhibition ability in 4T1 subcutaneous tumor model in vivo with great biocompatibility.Additionally,the infiltration of cytotoxic CD8^(+)T lymphocytes and inhibition of regulatory CD4^(+)FoxP3^(+)T lymphocytes in tumors demonstrated the activation of immunosuppressive tumor microenvironment by LIPN-induced ICD.Therefore,this work provided a new approach to enhance ICD of chemodynamic therapy through selective cascade amplification of ROS in cancer cells.
基金supported by the National Natural Science Foundation of China(Grant Numbers 62205025 and 61835015)Beijing Natural Science Foundation(7222309)+2 种基金the Open Project Program of Wuhan National Laboratory for Optoelectronics(2020WNLOKF025)CAMS Innovation Fund for Medical Sciences(CIFMS)(2019-I2M-5-061)Beijing Institute of Technology Research Fund Program for Young Scholars(XSQD-202123001).
文摘Vascular-targeted photodynamic therapy(V-PDT)is an effective treatment for port wine stains(PWS).However,repeated treatment is usually needed to achieve optimal treatment outcomes,possibly due to the limited treatment light penetration depth in the PWS lesion.The optical clearing technique can increase light penetration in depth by reducing light scattering.This study aimed to investigate the V-PDT in combination with an optical clearing agent(OCA)for the therapeutic enhancement of V-PDT in the rodent skinfold window chamber model.Vascular responses were closely monitored with laser speckle contrast imaging(LSCI),optical coherence tomography angiography,and stereo microscope before,during,and after the treatment.We further quantitatively demonstrated the effects of V-PDT in combination with OCA on the blood flow and blood vessel size of skin microvasculature.The combination of OCA and V-PDT resulted in significant vascular damage,including vasoconstriction and the reduction of blood flow.Our results indicate the promising potential of OCA for enhancing V-PDT for treating vascular-related diseases,including PWS.
基金supported by grants from the National Natural Science Foundation of China (No.81271178 and 81470777)
文摘ALKBH1 was recently discovered as a demethylase for DNA N6-methyladenine （N6-mA）, a new epigenetic modification, and interacts with the core transcriptional pluripotency network of embryonic stem cells. However, the role of ALKBH1 and DNA N6-mA in regulating osteogenic differentiation is largely unknown. In this study, we demonstrated that the expression of ALKBH1 in human mesenchymal stem cells （MSCs） was upregulated during osteogenic induction. Knockdown of ALKBH1 increased the genomic DNA N6-mA levels and significantly reduced the expression of osteogenic-related genes, alkaline phosphatase activity, and mineralization. ALKBHl-depleted MSCs also exhibited a restricted capacity for bone formation in vivo. By contrast, the ectopic overexpression of ALKBH1 enhanced osteoblastic differentiation. Mechanically, we found that the depletion of ALKBH1 resulted in the accumulation of N6-mA on the promoter region of ATF4, which subsequently silenced ATF4 transcription. In addition, restoring the expression of ATP by adenovirus-mediated transduction successfully rescued osteogenic differentiation. Taken together, our results demonstrate that ALKBH1 is indispensable for the osteogenic differentiation of MSCs and indicate that DNA N6-mA modifications area new mechanism for the epigenetic regulation of stem cell differentiation.
基金supported by ASBMR Research Career Enhancement Award (to LQ)NIH grants AR060991 (to LQ)AR062908 (to ME-I)
文摘Osteoarthritis （OA） is a degenerative joint disease and a major cause of pain and disability in older adults. We have previously identified epidermal growth factor receptor （EGFR） signaling as an important regulator of cartilage matrix degradation during epiphyseal cartilage development. To study its function in OA progression, we performed surgical destabilization of the medial meniscus （DMM） to induce OA in two mouse models with reduced EGFR activity, one with genetic modification （, was/＋ mice） and the other one with pharmacological inhibition （gefitinib treatment）. Histological analyses and scoring at 3 months post-surgery revealed increased cartilage destruction and accelerated OA progression in both mouse models. TUNEL staining demonstrated that EGFR signaling protects chondrocytes from OA-induced apoptosis, which was further confirmed in primary chondrocyte culture. Immunohistochemistry showed increased aggrecan degradation in these mouse models, which coincides with elevated amounts of ADAMTS5 and matrix metalloproteinase 13 （MMP13）, the principle proteinases responsible for aggrecan degradation, in the articular cartilage after DMM surgery. Furthermore, hypoxia-inducible factor 2α （HIF2α）, a critical catabolic transcription factor stimulating MMP13 expression during OA, was also upregulated in mice with reduced EGFR signaling. Taken together, our findings demonstrate a primarily protective role of EGFR during OA progression by regulating chondrocyte survival and cartilage degradation.
基金jointly supported by the National Key Technology Support Program(No.2015BAD05B02)the National Natural Science Foundation of China(Nos.31270426,31470443 and 31371596)
文摘Copper （Cu） is an essential trace mineral element for all forms of life, and is an important structural component and co-factor for a variety of metalloenzymes （Pefia et al., 1999; Bertinato and L＇Abbe, 2004）. In humans, Cu deficiency is not common because of the ubiquitous occurrence of Cu and ease of gastrointestinal absorption （Zidar et al., 1977; Uauy et al., 1998）.
基金funded by Ministry of Education,University and Research(MIUR)ex-60% research fund University of Brescia,Italy
文摘Depression refers to a series of mental health issues characterized by loss of interest and enjoyment in everyday life,low mood and selected emotional,cognitive,physical and behavioral symptoms.Depression is a common disorder,affecting 5–15%of the general population.When diagnosed as major depressive disorder（MDD）,patients are currentlytreated with pharmacological agents such as serotonin or noradren- aline uptake inhibitors （SSRI or SNRI） or tricyclics.
基金supported by Elam M. and Georgina E.Hack Memorial Research Funds,Department of Periodontics,University of Washington,Seattle,WA,USAsupported by WVCTSI funds,West Virginia University,Morgantown,WV,USA
文摘Toll-like receptor （TLR）-mediated inflammatory response could negatively affect bone metabolism. In this study, we determined how osteogenesis is regulated during inflammatory responses that are downstream of TLR signaling. Human primary osteoblasts were cultured in collagen gels. Pam3CSK4 （P3C） and Escherichia coli lipopolysaccharide （EcLPS） were used as TLR2 and TLR4 ligand respectively. Porphyromonas gingivalis LPS having TLR2 activity with either TLR4 agonism （Pg1690） or TLR4 antagonism （Pg1449） and mutant E. coli LPS （LPxE/LPxF/WSK） were used. IL-lp, SH2-containing inositol phosphatase-1 （SHIP1） that has regulatory roles in osteogenesis, alkaline phosphatase and mineralization were analyzed. 3α-Aminocholestane （3AC） was used to inhibit SHIP1. Our results suggest that osteoblasts stimulated by P3C, poorly induced IL-1β but strongly upregulated SHIP1 and enhanced osteogenic mediators. On the contrary, EcLPS significantly induced IL-1β and osteogenic mediators were not induced. While Pg1690 downmodulated osteogenic mediators, Pg1449 enhanced osteogenic responses, suggesting that TLR4 signaling annuls osteogenesis even with TLR2 activity. Interestingly, mutant E. coli LPS that induces weak inflammation upregulated osteogenesis, but SHIP1 was not induced. Moreover, inhibiting SHIP1 significantly upregulated TLR2-mediated inflammatory response and downmodulated osteogenesis. In conclusion, these results suggest that induction of weak inflammatory response through TLR2 （with SHIP1 activity） and mutant TLR4 ligands could enhance osteogenesis.
基金supported by the National Natural Science Foundation of China(81170467 and 81270569)Major Project of PLA Medical S&T foundation(AWS11C004)Medical Science Research Foundation of Chongqing Health and Family Planning Committee(2015MSXM224)
文摘Burkitt lymphoma is a highly aggressive B-cell neoplasm. New therapeutic methods are needed to overcome the adverse effect of intensive chemotherapy regimens. Valproic acid and （-）-gossypol are two kinds of chemical compounds used as new anti-tumor drugs in recent years.
文摘Objective:The tumor necrosis factor receptor-associated factor 7(TRAF7)is one of the components of the tumor necrosis factor alpha(TNF-α)/nuclear factor kappa B(NF-κB)pathway and a putative E3-ubiquitin ligase.This study aims to explore the biologic effects and the molecular mechanisms of deregulated TRAF7 signaling in hepatocellular carcinoma(HCC)progression.
文摘Johnson et al. (1993) showed that coexposure to UV-A between 300-400 nm enhanced the toxicity of nitrotoluenes to Phoiobacterium phosphoreum, a marine bioluminescent bacteria used in the Microtox test (Microbics Inc.). This paper reports that UV-A photoenhanced the toxicity of polynuclear aromatic hydrocarbons, other types of organic compounds, and some transition metals to P. phosphoreum. Coexposure to 400 μw/cm2 for 15 min increased the toxicity of psoralen, α-terthienyl, anthracene, acridine, fluoranthene,TNT, Cu2+, As3+, Ni2, and Cd2+. Phenanthrene was photoenhanced after 30 min coexposure at 400 μw/cm2+, and Mn2+ at 800 μw/cm2 aftef 15 min. Naphthalene was not enhanced at 800 μw/cm2 for 30 min
文摘Sigma-1 receptors are unique receptors that are postulated to act as intracellular amplifiers for signal transduction within cells of the nervous system. The present paper studied the
文摘BACKGROUND： Interstitial stem cell is charactenzed by multiple differentiations, and retinoic acid （RA） can induce differentiation of stromal cells into nerve tissue cells in fetal liver of mice, so, its signal transduction pathway should be discussed to trigger differentiation. OBJECTIVE ： To study the effect of RA on expression of neural specific gene and its signal transduction in fetal liver of mice.DESIGN ： Paired controlled study on the basis of cell.SETTING ： Institute of Hematology, Medical College of Jinan University.MATERIALS： The experiment was completed in the Institute of Hematology, Medical College of Jinan University from April to December 2005. C57BL/6 mice, of clean grade, aged 8-10 weeks, weighting 20-35 g, 10 females and 4 males, were selected in this study.METHODS： Sca-1^＋ cells in fetal liver were prepared with MACS kit and cultured with DMEM ＋ 10% fetal bovine serum （FBS）. On the fourth day, it was added with or without protein kinase C （PKC） inhibitor chelerythrine chloride （3μmol/L） and 5×10^-7 mol/L RA for 24 hours, and then incubated in serum-free medium for 5 days. Expressions of genes were assayed by Westem blotting and semi-quantitative RT-PCR.MAIN OUTCOME MEASURES ： Expression of neural specific gene NF-L, NF-H, BF-1 and TH.RESULTS： Expression of neural specific gene NF-L, NF-H, BF-1 and TH was significantly increased after treatment with RA and they were increased 5.06, 5.15, 4.63 and 3.33 times, respectively. However, chelerythrine chloride could inhibit expression of neural specific gene NF-L, NF-H, BF-1 and TH induced by RA.CONCLUSION ： RA can promote the expression of neural specific genes in Sca-1^＋ cells of fetal liver, and its pathway may be related to PKC.
基金Key Program of National Natural Science Foundation of China (U1432248), National Natural Science Foundationof China (10835011, 11205219), Western Talent Program of Chinese Academy of Sciences(Y260230XB0).
文摘Multiple links between miRNA activity and cancer have been established. Several miRNAs have been describedas oncogenes while others act as tumour suppressors[1]. MiR-449a is a member of miR-34 family which locates onhuman chromosome 5q11.2, a region identified as a susceptibility locus in a variety of malignancies, includingprostate cancer[2]. In line with the tumor-suppressive role of miR-34, miR-449a was shown to be significantly downregulatedin prostate cancer cell lines and tissue relative to normal tissues and plays a critical role in growth ofprostate cancer cells [3;4].
基金Key Program of National Natural Science Foundation of China (U1432248), National Natural Science Foundationof China (11205219), Western Talent Program of Chinese Academy of Sciences(Y260230XB0).
文摘Nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial transcription factor regulating the expression ofantioxidant genes. Under oxidative stress conditions or other stimulus, Nrf2 translocating from the cytoplasminto the nucleus, binds to antioxidant response elements, and increases the expression of antioxidant enzymes[1;2].Constitutive Nrf2 activation in many tumors enhances cell survival and resistance. For instance, high level of Nrf2 isobserved in non-small cell lung cancer A549 cells[3;4]. The gain of Nrf2 function has been implicated in the resistanceof cancer cells to radiation therapy.
基金Key Program of National Natural Science Foundation of China (U1432248), National Natural Science Foundation of China (11305226)
文摘c-Myc was one of the first oncogenes to be identified and its overexpression at the RNA and protein levels has subsequently been linked to a wide variety of human cancers[1]. Overexpression of the c-Myc protein or c-Myc gene has been shown in 80% of breast cancers, 70% of colon cancers, 90% of gynecological cancers, 50% of hepatocellular carcinomas and a variety of hematological tumors.
基金Key Program of National Natural Science Foundation of China (U1432248), National Natural Science Foundationof China (11175222, 11205219) , Western Talent Program of Chinese Academy of Sciences (Y260230XB0).
文摘Transient receptor potential vanilloid 1(TRPVl) that is known as capsaicin receptor is a non-selective cationion channel[1]. TRPV1 can regulate Ca2+ influx, participate in a variety of physiological and pathological processof tumor[2]. One such agent is Capsazepine (CPZ) that is now widely used as a selective vanilloid type 1 receptor(TRPV1) antagonist. CPZ can be directly actived on the capsaicin receptor, blocked its biological effects, and abolishedosteosarcoma-induced hyperalgesia when administered subcutaneously at doses ranging from 3 to 10 mg/kg,blocked calcium channels[3]. However, the mechanisms underlying the anticancer effects of CPZ have not fully beenunderstood. Whether CPZ can induce apoptosis of human hepatocellular carcinoma cell line HepG2 is not known.Therefore, the objective of the study reported here was to determine whether CPZ can enhance radiation sensitivityin HepG2 cell, and impact on cell proliferation.
文摘From October 10 to 17,the Festival of China 2009 was held in Kathmandu,capital of Nepal.This one-week biennial celebration,initiated in 2003,aims to"promote
文摘Background: Enhanced recovery after surgery(ERAS) protocol is a multimodal, multidisciplinary and evidence-based approach to reduce surgical stress and enhance recovery in the postoperative period. This study aimed to analyze the outcome of ERAS protocol in patients after pancreaticoduodenectomy(PD). Methods: A total of 50 consecutive patients with pancreatic/periampullary cancer who underwent PD between January 2016 to August 2017 were included in the study. As per the institute ERAS protocol, nasogastric tube(NGT) was removed on postoperative day(POD) 1 if output was less than 200 mL and oral sips were allowed; oral liquids were allowed on POD2; semisolid diet by POD3; abdominal drain was removed on POD 4 if output was less than 100 mL with no evidence of postoperative pancreatic fistula(POPF); normal diet was allowed on POD5. Discharge criteria on POD6 were afebrile, tolerating oral normal diet, pain free and no surgery related complications(defined as per the ISGPS definitions). Results: NGT was removed on POD1 in 45(90%) patients, abdominal drain removed by POD4 in 41(82%) and 43(86%) patients were discharged on POD6. There was no 30-day postoperative mortality. Three(6%) patients had delayed gastric emptying(DGE). None had postoperative hemorrhage and POPF. Readmission rate was 8%. A significant relation was found between the length of hospital stay(LOS) with age( P < 0.05) and a marginal relation between LOS and postoperative albumin( P = 0.05). Conclusions: ERAS protocol can be safely followed in the perioperative care of patients who undergo PD. Early removal of NGT and allowing oral diet restore bowel function early. ERAS decreases the LOS and postoperative complications.
基金supported by the National Basic Research Program of China(2012CB114104)the National Natural Science Foundation of China (31071694 and 31171858)
文摘Cry toxins produced by Bacillus thuringiensis（Bt） are effective biological insecticides against certain insect species.In this study,bioassay results indicated that Cry1B and Cry1C were toxic to Spodoptera exigua.We also identified a cadherin-like gene in S.exigua that could enhance the toxicity of Cry1B and Cry1C.The cadherin-like gene identified from the larvae midgut tissue was cloned by reverse transcription polymerase chain reaction（RT-PCR） and rapid amplification of cDNA ends（RACE）.The full-length cDNA of the gene consisted of 5 220 bp encoding 1 740 amino acid with a predicted molecular mass of 196 kD.BLAST search analysis showed that the predicted amino acid sequence had a high sequence identity to the published sequences of cadherin-like proteins from other Lepidoptera insects.Spatial expression of the cadherin-like gene detected by qRT-PCR analysis revealed that the cadherin-like gene was mainly present in the gut of 4th instar larvae and during different life stages.The results suggested that the commercial development of this synergist has the potential to enhance Cry1B and Cry1C toxicity against Lepidoptera insects.
