An extensively drug-resistant(XDR)Escherichia coli strain 258E was isolated from an anal swab sample of a chicken farm of Anhui province in China.Genomic analyses indicated that the strain 258E harbors an incompatibil...An extensively drug-resistant(XDR)Escherichia coli strain 258E was isolated from an anal swab sample of a chicken farm of Anhui province in China.Genomic analyses indicated that the strain 258E harbors an incompatibility group N(IncN)plasmid pEC258-3,which co-produces bla_(CTX-M-3),bla_(KPC-2),bla_(TEM-1B),qnrS1,aac(6')-Ib-cr,dfrA14,arr-3,and aac(6')-Ib3.Multiple genome arrangement analyses indicated that pEC258-3 is highly homologous with pCRKP-1-KPC discovered in Klebsiella pneumoniae from a patient.Furthermore,conjugation experiments proved that plasmid pEC258-3 can be transferred horizontally and may pose a significant potential threat in animals,community and hospital settings.展开更多
AIM:To investigate whether the apoptotic activities of 8-bromo-7-methoxychrysin(BrMC) involve reactive oxygen species(ROS) generation and c-Jun N-terminal kinase(JNK) activation in human hepatocellular carcinoma cells...AIM:To investigate whether the apoptotic activities of 8-bromo-7-methoxychrysin(BrMC) involve reactive oxygen species(ROS) generation and c-Jun N-terminal kinase(JNK) activation in human hepatocellular carcinoma cells(HCC).METHODS:HepG2,Bel-7402 and L-02 cell lines were cultured in vitro and the apoptotic effects of BrMC were evaluated by flow cytometry(FCM) after propidium iodide(PI) staining,caspase-3 activity using enzymelinked immunosorbent assay(ELISA),and DNA agarose gel electrophoresis.ROS production was evaluated by FCM after dichlorodihydrofluorescein diacetate(DCHFDA) probe labeling.The phosphorylation level of JNK and c-Jun protein was analyzed by Western blotting.RESULTS:FCM after PI staining showed a dose-dependent increase in the percentage of the sub-G1 cell pop-ulation(P < 0.05),reaching 39.0% ± 2.8% of HepG2 cells after 48 h of treatment with BrMC at 10 μmol/L.The potency of BrMC to HepG2 and Bel-7402(32.1% ± 2.6%) cells was found to be more effective than the lead compound,chrysin(16.2% ± 1.6% for HepG2 cells and 11.0% ± 1.3% for Bel-7402 cell) at 40 μmol/L and similar to 5-flurouracil(33.0% ± 2.1% for HepG2 cells and 29.3% ± 2.3% for Bel-7402 cells) at 10 μmol/L.BrMC had little effect on human embryo liver L-02 cells,with the percentage of sub-G1 cell population 5.4% ± 1.8%.Treatment of HepG2 cells with BrMC for 48 h also increased the levels of active caspase-3,in a concentration-dependent manner.z-DEVD-fmk,a caspase-3specific inhibitor,prevented the activation of caspase-3.Treatment with BrMC at 10 μmol/L for 48 h resulted in the formation of a DNA ladder.Treatment of cells with BrMC(10 μmol/L) increased mean fluorescence intensity of DCHF-DA in HepG2 cells from 7.2 ± 1.12 at 0 h to 79.8 ± 3.9 at 3 h and 89.7 ± 4.7 at 6 h.BrMC did not affect ROS generation in L-02 cells.BrMC treatment failed to induce cell death and caspase-3 activation in HepG2 cells pretreated with N-acetylcysteine(10 mmol/L).In addition,in HepG2 cells treated with BrMC(2.5,5.0,10.0 μmol/L) for 12 h,JNK activation was observed.Peak JNK activation occurred at 12 h post-treatment and this activation persisted for up to 24 h.The expression of phosphorylated JNK and c-Jun protein after 12 h with BrMC-treated cells was inhibited by N-acetylcysteine and SP600125 pre-treatment,but GW9662 had no effect.SP600125 substantially reduced BrMC-induced cell death and caspase-3 activation of HepG2 cells.N-acetylcysteine and GW9662 also attenuated induction of cell death and caspase-3 activation in HepG2 cells treated with BrMC.CONCLUSION:BrMC induces apoptosis of HCC cells by ROS generation and sustained JNK activation.展开更多
Curcumin has been reported to possess multifunctional bioactivities with low toxicity. However, the clinical application of curcumin has been significantly limited by its instability and poor metabolic property. Up to...Curcumin has been reported to possess multifunctional bioactivities with low toxicity. However, the clinical application of curcumin has been significantly limited by its instability and poor metabolic property. Up to now, multiple approaches are being sought to overcome these limitations to obtaining “super curcumin”, and many analogues of curcumin have been designed and synthesized. In all of those analogues, a series of mono-carbonyl curcumin analogues deleting the β-diketone draw our attention. Since the seven-carbon β-diketone linker in curcumin may be responsible for its instability, the series of mono-carbonyl curcumin analogues deleting the β-diketone may be potential prodrug with improved pharmacokinetic and pharmacodynamic properties. This review just focuses on these more stable mono-carbonyl analogues of curcumin, and shows the new class of active structure by introducing the synthesis and anticancer activity of them.展开更多
AIM:To investigate the effects of macrophage migration inhibitory factor (MIF) on proliferation of human gastric cancer MGC-803 cells and expression of cyclin D1 and p27Kip1 in them,and further determine whether the e...AIM:To investigate the effects of macrophage migration inhibitory factor (MIF) on proliferation of human gastric cancer MGC-803 cells and expression of cyclin D1 and p27Kip1 in them,and further determine whether the effects are related to the PI3K/Akt signal transduction pathway. METHODS:Gastric cancer MGC-803 cells were cultured and then treated with 50 μg/L recombinant human MIF (rhMIF) with and without a PI3K inhibitor,LY294002 (25 μmol/L). MTT assay was used to detect the prolifer-ation of MGC-803 cells. Cell cycle was detected by flow cytometry. Expression of cyclin D1 and p27Kip1 mRNA was by reverse transcription-polymerase chain reaction. Protein expression of phosphorylated Akt (p-Akt),Akt,cyclin D1 and p27Kip1 was examined by immunocyto-chemistry and Western blotting. RESULTS:rhMIF signifi cantly stimulated the prolifera-tion of MGC-803 cells and cell cycle progression from G1 phase to S phase in a concentration-and time-de-pendent manner. After the MGC-803 cells were treated with rhMIF for 24 h,the expression of cyclin D1 was signifi cantly up-regulated compared with the cells not treated with rhMIF at both mRNA and protein levels(0.97 ± 0.02 vs 0.74 ± 0.01,P = 0.002; 0.98 ± 0.05 vs 0.69 ± 0.04,P = 0.003). The p27Kip1 was down-regulated but only statistically significant at the protein level. rhMIF significantly increased the expression of p-Akt,which reached the peak at 30 min,but did not affect the expression of Akt. However,LY294002 inhibited all the effects of rhMIF.CONCLUSION:Macrophage MIF increases the proliferation of gastric cancer cells,induces the expression of cyclin D1 at the transcriptional level and inhibits the expression of p27Kip1 at the post-transcriptional level via the PI3K/Akt pathway.展开更多
Objective:This study aimed to explore the effects of our rational emotive behavior therapy(REBT)program on symptoms,anxiety,depression,and sleep state in patients with colorectal cancer(CRC)undergoing chemotherapy.Met...Objective:This study aimed to explore the effects of our rational emotive behavior therapy(REBT)program on symptoms,anxiety,depression,and sleep state in patients with colorectal cancer(CRC)undergoing chemotherapy.Methods:From October 2020 to May 2021,fifty-six patients with CRC in a hospital in the Hunan Province were randomly divided into an intervention group(n=28)and a control group(n=28).The patients in the intervention group completed a 6-week REBT program based on routine nursing care,including four courses:1)establish a relationship and formulate health files;2)group communications and study symptom management;3)continuously provide health knowledge and strengthen healthy behavior;and 4)review the treatment and summary.The control group maintained routine nursing care.The simplified Chinese version of the Memorial Symptom Assessment Scale Short Form(MSASeSFeSC),the Hospital Anxiety and Depression Scale(HADS),and the Pittsburgh Sleep Quality Index(PSQI)scale were used to investigate and compare the intervention effects of the two groups at baseline(T1,before the intervention),four weeks(T2),and six weeks(T3)after the intervention.Results:The intervention group was significantly improved in symptoms,anxiety,depression,and sleep state,compared with the control group.At T2,MSASeSFeSC(24.43±4.26 vs.28.07±3.91),symptom distress(17.29±4.04 vs.19.39±3.59),symptom frequency(7.14±1.51 vs.8.68±1.42),HADS(13.68±3.38 vs.15.86±3.79),anxiety(3.89±1.85 vs.5.18±2.18),and depression(9.79±2.06 vs.10.68±2.23),showed that the difference between the two groups was statistically significant(P<0.05).At T3,MSASeSFeSC(23.89±3.54 vs.30.14±3.94),symptom distress(17.61±3.52 vs.21.32±3.57),symptom frequency(6.29±1.49 vs.8.82±1.47),HADS(11.82±2.57 vs.16.29±3.13),anxiety(3.21±1.64 vs.5.61±1.77),and depression(8.61±1.52 vs.10.68±1.81),showed that the difference between the two groups was statistically significant(P<0.05).The sleep state of the intervention group was better than the control group at T3,with decreased score of PSQI[4.00(3.00,8.00)vs.9.00(7.00,12.50),Z=-3.706,P<0.001].Conclusion:The 6-week REBT program can effectively improve the symptom,anxiety,depression,and sleep state of patients with CRC undergoing chemotherapy,which could as a care plan for patients with CRC who are repeatedly admitted to the hospital for chemotherapy.展开更多
Apelin is an endogenous ligand of the apelin receptor(APJ),a seven-transmembrane G protein-coupled receptor.Apelin and APJ exist in a variety of tissues,with special status in the heart,lung and tumors.Furthermore,man...Apelin is an endogenous ligand of the apelin receptor(APJ),a seven-transmembrane G protein-coupled receptor.Apelin and APJ exist in a variety of tissues,with special status in the heart,lung and tumors.Furthermore,many research shows that the apelin/APJ system exerts a broad range of activities that affect kidney systems.This review we summarize the role of apelin/APJ system on renal fibrosis,renal ischemia/reperfusion injury and diabetic nephropathy,polycystic kidney disease,hemodialysis.It was found that the level expression of apelin m RNA in the inner stripe of kidney outer medulla was the highest,and the region is significantly correlated with water and sodium balance.In UUO mice model,intraperitoneal injection of Apelin can reduceα-SMA,the expression of TGF-1 and its receptor,and between renal stromal components also significantly decreased.These results show that Apelin can reduce the deposition of ECM and improve renal interstitial fibrosis.In renal ischemia/reperfusion injury studies show that apelin-13 can significantly reduce the damage induced by renal tubularlesions,renal cell death and the normal renal function is not completely lead to large damage.But in diabetic nephropathy,Apelin-APJ system can promote or slow DN disease progression is controversial,still needs further research.Analysis the receiver operating characteristic curve found that in the process of identifying ADPKD disease apelin and copeptin shows good receiver operating characteristic curve(ROC),cox proportional hazards regression model also showed apelin can predict on the progress of kidney disease.In hemodialysis patients the apelin levels and PTH levels were positively correlated,it could prompt apelin can protect bone dialysis patients.Apelin also can reduce Pit-1 inhibition of vascular smooth muscle cell osteoblast calcification and thus improve the aortic calcification,so Apelin may have a potential role in the treatment of vascular calcification in CKD.In kidney disease conditions,Apelin/APJ system plays a variety of biological functions,because of the Apelin protective on kidney,Apelin/APJ may be a potential material for the treatment of chronic kidney disease.展开更多
Along with its wide anatomical distribution, somatostatin (SST) acts on multiple targets via a family of 5 receptors to produce a broad spectrum of biological effects. Therefore, a variety of peptide analogs have been...Along with its wide anatomical distribution, somatostatin (SST) acts on multiple targets via a family of 5 receptors to produce a broad spectrum of biological effects. Therefore, a variety of peptide analogs have been produced and are widely used in clinical treatment. However, because of their flaws in the structure of peptide, the clinical efficacy is limited. In this review, we summarize the structure, pharmacological effects and the potential clinical value of non-peptide SST analogs. We focus on the research and development of non-peptide SST analogs since 1998, and discuss the problems and potential prospects for non-peptide SST analogs. We believe that as more non-peptide somatostatin analogs are successfully developed, the extensive clinical application of SSTs will contribute a great deal to medical science.展开更多
Mammalian adipose tissues can be broadly divided into white adipose tissue(WAT),beige adipose tissue,and brown adipose tissue(BAT)[1].The function of WAT is to store superfluous energy and is characterized by unilamel...Mammalian adipose tissues can be broadly divided into white adipose tissue(WAT),beige adipose tissue,and brown adipose tissue(BAT)[1].The function of WAT is to store superfluous energy and is characterized by unilamellar lipid droplets.WAT,as a prominent endocrine organ,regulates feeding and satiety by producing hormones.展开更多
To the Editor:Pathological cardiac hypertrophy is commonly stimulated by stress or induced by cardiovascular diseases,such as hypertension and myocardial infarction.A sustained pathological hypertrophic response can l...To the Editor:Pathological cardiac hypertrophy is commonly stimulated by stress or induced by cardiovascular diseases,such as hypertension and myocardial infarction.A sustained pathological hypertrophic response can lead to declines in diastolic and systolic functions and eventually develop heart failure.Angiotensin II(Ang II)can mediate cardiac hypertrophy through the angiotensin II type 1 receptor(AT1R).^([1])展开更多
Prolonged activation of adenosine A1 receptor likely leads to damage of dopaminergic neurons and subsequent development of neurodegenerative diseases.However,the pathogenesis underlying long-term adenosine A1 receptor...Prolonged activation of adenosine A1 receptor likely leads to damage of dopaminergic neurons and subsequent development of neurodegenerative diseases.However,the pathogenesis underlying long-term adenosine A1 receptor activation-induced neurodegeneration remains unclear.In this study,rats were intraperitoneally injected with 5 mg/kg of the adenosine A1 receptor agonist N6-cyclopentyladenosine(CPA)for five weeks.The mobility of rats was evaluated by forced swimming test,while their cognitive capabilities were evaluated by Y-maze test.Expression of sortilin,α-synuclein,p-JUN,and c-JUN proteins in the substantia nigra were detected by western blot analysis.In addition,immunofluorescence staining of sortilin andα-synuclein was performed to detect expression in the substantia nigra.The results showed that,compared with adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine(5 mg/kg)+CPA co-treated rats,motor and memory abilities were reduced,surface expression of sortin andα-synuclein in dopaminergic neurons was reduced,and total sortilin and totalα-synuclein were increased in CPA-treated rats.MN9D cells were incubated with 500 nM CPA alone or in combination with 10μM SP600125(JNK inhibitor)for 48 hours.Quantitative real-time polymerase chain reaction analysis of sortilin andα-synuclein mRNA levels in MN9D cells revealed upregulated sortilin expression in MN9D cells cultured with CPA alone,but the combination of CPA and SP600125 could inhibit this expression.Predictions made using Jasper,PROMO,and Alibaba online databases identified a highly conserved sequence in the sortilin promoter that was predicted to bind JUN in both humans and rodents.A luciferase reporter assay of sortilin promoter plasmid-transfected HEK293T cells confirmed this prediction.After sortilin expression was inhibited by sh-SORT1,expression of p-JUN and c-JUN was detected by western blot analysis.Long-term adenosine A1 receptor activation levels upregulatedα-synuclein expression at the post-transcriptional level by affecting sortilin expression.The online tool Raptor-X-Binding and Discovery Studio 4.5 prediction software predicted that sortilin can bind toα-synuclein.Co-immunoprecipitation revealed an interaction between sortilin andα-synuclein in MN9D cells.Our findings indicate that suppression of prolonged adenosine A1 receptor activation potently inhibited sortilin expression andα-synuclein accumulation,and dramatically improved host cognition and kineticism.This study was approved by the University Committee of Animal Care and Supply at the University of Saskatchewan(approval No.AUP#20070090)in March 2007 and the Animals Ethics Committee of University of South China(approval No.LL0387-USC)in June 2017.展开更多
Objective To prepare, characterize and evaluate the antioxidant activity of rutin-liposome（RL）. Methods Liposomes of rutin were prepared by film dispersion method and the encapsulation efficiency（EE） was determine...Objective To prepare, characterize and evaluate the antioxidant activity of rutin-liposome（RL）. Methods Liposomes of rutin were prepared by film dispersion method and the encapsulation efficiency（EE） was determined by RP-HPLC. Human umbilical vein endothelial cells（HUVECs） were injuried by H_2O_2 and treated with either free aqueous rutin or the RL delivery systems. The viability of HUVECs was determined by MTT and ELISA. Results The drug delivery system showed uniform rutin loaded nanoparticles with average particle size of（147.20 ± 1.42） nm, polydispersity index of（0.191 ± 0.003） nm, Zeta potential of（-20.0 ± 1.0） mV, and the drug EE was closed to 90.0%. The antioxidant effect of the drug delivery system to H_2O_2-damaged HUVECs showed that RL could increase injury cells viability compared to free aqueous rutin, which was accompanied with an obvious decrease in malondialdehyde（MDA）, lactate dehydrogenase（LDH） while increase the level of nitrogen oxide（NOS）. Conclusion The nanostructured RL is improved on the antioxidant effect and may be treating the different diseases caused by free radicals.展开更多
Recently, Prieto-Godino et al.[1] found that the olfactory receptor 75a （Ir75a） gene is a functional pseudo-pseudogene in Drosophila sechellia. For a long time, Ir75a has been regarded as an acetic acid receptor tha...Recently, Prieto-Godino et al.[1] found that the olfactory receptor 75a （Ir75a） gene is a functional pseudo-pseudogene in Drosophila sechellia. For a long time, Ir75a has been regarded as an acetic acid receptor that detects acetic acid and induces obvious olfactory responses in olfactory sensory neurons （OSNs）f2J. Nonetheless, Prieto-Godino et al. confirmed that Ir75a lost its sensitivity to acetic acid in D. sechellia. Thus, the D. sechelfia Ir75a gene is generally recognized as a pseudogene in OSNs.展开更多
PRIMARY pulmonary sarcomatoid carcinoma （PSC）is a rare condition, approximately accounting for0.1%-0.4% of all lung malignancies.1 PSCsconsist of 5 major histological variants accordingto 2004 WHO classification： p...PRIMARY pulmonary sarcomatoid carcinoma （PSC）is a rare condition, approximately accounting for0.1%-0.4% of all lung malignancies.1 PSCsconsist of 5 major histological variants accordingto 2004 WHO classification： pleomorphic carcinoma,spindle cell carcinoma, giant cell carcinoma, carcinosarcoma.展开更多
As trifluoromethylthiolation has received increasing attention recently, many CF_3S-reagents and trifluoromethylthiolation methods have been developed. Herein we describe trifluoromethylthiolation of alkyl halides by ...As trifluoromethylthiolation has received increasing attention recently, many CF_3S-reagents and trifluoromethylthiolation methods have been developed. Herein we describe trifluoromethylthiolation of alkyl halides by using Ph_3 P^+CF_2CO_2 as a fluoride and difluorocarbene source. Difluorocarbene is a versatile intermediate, but its side reactions are usually ignored and the by-products would therefore be discarded. In this work, a side reaction of difluorocarbene, the generation of a fluoride anion from difluorocarbene, was developed into a synthetic tool. Although the trifluoromethylthiolation reaction involved multi-sequential steps, the cleavage of C-F bond, the formation of CF_2=S bond, F-C(S)F_2 bond,and C-SCF_3 bond, the conversion proceeded fast and was completed within 10 min.展开更多
Truttmann MC et al.[1] recently reported that AMPylation of heat shock protein 70 (HSP70) family of chaperones participates in altering the aggregation properties and maintaining protein homeostasis (proteostasis), th...Truttmann MC et al.[1] recently reported that AMPylation of heat shock protein 70 (HSP70) family of chaperones participates in altering the aggregation properties and maintaining protein homeostasis (proteostasis), thereby playing a vital role in the development of neurodegenerative diseases (NDs). NDs are commonly manifested by protein aggregates, which exert harmful effects on proteostasis. Interestingly, it has been observed that AMPylation of heat shock proteins (HSPs) can maintain proteostasis by inhibiting the formation of protein aggregates. As previous studies only indicate that HSPs could regulate proteostasis, such a novel discovery further demonstrates the involvement of HSP70 AMPylation in the regulation of protein aggregation and the maintenance of proteostasis. Therefore, AMPylation can be considered to possess a therapeutic potential to target certain physiological processes related to proteostasis, such as age-related diseases.展开更多
A novel turn-on fluorescent probe for the detection of palladium has been designed. The probe can selectively and sensitively detect palladium in solution, and the limit of detection was calculated to be 11.4 nmol...A novel turn-on fluorescent probe for the detection of palladium has been designed. The probe can selectively and sensitively detect palladium in solution, and the limit of detection was calculated to be 11.4 nmol·L-1. Furthermore, the probe was successfully used for fluorescence imaging of palladium in living cells.展开更多
Background:Cuprotosis is a newly discovered Copper-dependence form of cell death.Cuprotosis-related genes(CRGs)regulating mitochondrial metabolism and protein lipoylation suggest the critical roles cuprotosis for in c...Background:Cuprotosis is a newly discovered Copper-dependence form of cell death.Cuprotosis-related genes(CRGs)regulating mitochondrial metabolism and protein lipoylation suggest the critical roles cuprotosis for in cancer.However,the prognostic value of CRGs in the highly immunogenic cancer type,kidney renal clear cell carcinoma(KIRC)needs to be further studied.Herein,we aim to identify novel prognostic genes and construct a CRGs prognostic signature for KIRC.Methods:We downloaded the mRNA sequencing data from the Cancer Genome Atlas,differentially expressed CRGs were screened out and their bio-function was elucidated.Then we used Cox regression analysis to establish a prediction model of CRGs.Subsequently,a prognostic scoring model based on the regression coefficients of the screened out CRGs and their corresponding mRNA expressions were constructed and validated.Results:Seven differentially expressed CRGs were screened.A two-gene model was built to separate samples into high-risk and low-risk groups.Overall survival was lower in the high-risk group than in the low-risk group(p<0.05).The receiver operating characteristic curve showed a good diagnostic efficiency of the signature.We verified this prognostic model in the Cancer Genome Atlas test cohorts.The risk score was identified as an independent prognostic factor via multivariate Cox regression.Moreover,the nomogram was used to predict 1-/3-/5-year OS of KIRC patients.Furthermore,risk score has a very significant effect on the infiltration of immune cells and the expression of immune checkpoints.Conclusions:To conclude,we constructed a novel prognostic signature based on CRGs.Targeting cuprotosis may represent a promising approach for the treatment of KIRC.展开更多
It is well known that sleep is one of the inevitable activities of daily living and it is one of the most important factors contributing to human health.Sleep in mammals is a cyclic occurrence of two distinct states,r...It is well known that sleep is one of the inevitable activities of daily living and it is one of the most important factors contributing to human health.Sleep in mammals is a cyclic occurrence of two distinct states,rapid eye movement(REM)and non-rapid eye movement(NREM)[1].展开更多
Bacterial small RNAs （sRNAs） are an emerging class of regulatory RNAs of about 40-500 nucleotides in length and, by binding to their target mRNAs or proteins, get involved in many biological processes such as sensin...Bacterial small RNAs （sRNAs） are an emerging class of regulatory RNAs of about 40-500 nucleotides in length and, by binding to their target mRNAs or proteins, get involved in many biological processes such as sensing environmental changes and regulating gene expres- sion. Thus, identification of bacterial sRNAs and their targets has become an important part of sRNA biology. Current strategies for discovery of sRNAs and their targets usually involve bioinformatics prediction followed by experimental validation, emphasizing a key role for bioinformatics prediction. Here, therefore, we provided an overview on prediction methods, focusing on the merits and limita- tions of each class of models. Finally, we will present our thinking on developing related bioinformafics models in future.展开更多
基金the National Key Research and Development Program of China(2018YFE0192600)the Shanghai Agriculture Applied Technology Development Program,China(T20200104)+1 种基金the Fundamental Research Funds for the Central Universities,China(2020JB05)the Agricultural Science and Technology Innovation Program of Chinese Academy of Agricultural Sciences(CAAS-ZDRW202203).
文摘An extensively drug-resistant(XDR)Escherichia coli strain 258E was isolated from an anal swab sample of a chicken farm of Anhui province in China.Genomic analyses indicated that the strain 258E harbors an incompatibility group N(IncN)plasmid pEC258-3,which co-produces bla_(CTX-M-3),bla_(KPC-2),bla_(TEM-1B),qnrS1,aac(6')-Ib-cr,dfrA14,arr-3,and aac(6')-Ib3.Multiple genome arrangement analyses indicated that pEC258-3 is highly homologous with pCRKP-1-KPC discovered in Klebsiella pneumoniae from a patient.Furthermore,conjugation experiments proved that plasmid pEC258-3 can be transferred horizontally and may pose a significant potential threat in animals,community and hospital settings.
基金Supported by Hunan Provincial Natural Science Foundation of China,No.03JJY5009
文摘AIM:To investigate whether the apoptotic activities of 8-bromo-7-methoxychrysin(BrMC) involve reactive oxygen species(ROS) generation and c-Jun N-terminal kinase(JNK) activation in human hepatocellular carcinoma cells(HCC).METHODS:HepG2,Bel-7402 and L-02 cell lines were cultured in vitro and the apoptotic effects of BrMC were evaluated by flow cytometry(FCM) after propidium iodide(PI) staining,caspase-3 activity using enzymelinked immunosorbent assay(ELISA),and DNA agarose gel electrophoresis.ROS production was evaluated by FCM after dichlorodihydrofluorescein diacetate(DCHFDA) probe labeling.The phosphorylation level of JNK and c-Jun protein was analyzed by Western blotting.RESULTS:FCM after PI staining showed a dose-dependent increase in the percentage of the sub-G1 cell pop-ulation(P < 0.05),reaching 39.0% ± 2.8% of HepG2 cells after 48 h of treatment with BrMC at 10 μmol/L.The potency of BrMC to HepG2 and Bel-7402(32.1% ± 2.6%) cells was found to be more effective than the lead compound,chrysin(16.2% ± 1.6% for HepG2 cells and 11.0% ± 1.3% for Bel-7402 cell) at 40 μmol/L and similar to 5-flurouracil(33.0% ± 2.1% for HepG2 cells and 29.3% ± 2.3% for Bel-7402 cells) at 10 μmol/L.BrMC had little effect on human embryo liver L-02 cells,with the percentage of sub-G1 cell population 5.4% ± 1.8%.Treatment of HepG2 cells with BrMC for 48 h also increased the levels of active caspase-3,in a concentration-dependent manner.z-DEVD-fmk,a caspase-3specific inhibitor,prevented the activation of caspase-3.Treatment with BrMC at 10 μmol/L for 48 h resulted in the formation of a DNA ladder.Treatment of cells with BrMC(10 μmol/L) increased mean fluorescence intensity of DCHF-DA in HepG2 cells from 7.2 ± 1.12 at 0 h to 79.8 ± 3.9 at 3 h and 89.7 ± 4.7 at 6 h.BrMC did not affect ROS generation in L-02 cells.BrMC treatment failed to induce cell death and caspase-3 activation in HepG2 cells pretreated with N-acetylcysteine(10 mmol/L).In addition,in HepG2 cells treated with BrMC(2.5,5.0,10.0 μmol/L) for 12 h,JNK activation was observed.Peak JNK activation occurred at 12 h post-treatment and this activation persisted for up to 24 h.The expression of phosphorylated JNK and c-Jun protein after 12 h with BrMC-treated cells was inhibited by N-acetylcysteine and SP600125 pre-treatment,but GW9662 had no effect.SP600125 substantially reduced BrMC-induced cell death and caspase-3 activation of HepG2 cells.N-acetylcysteine and GW9662 also attenuated induction of cell death and caspase-3 activation in HepG2 cells treated with BrMC.CONCLUSION:BrMC induces apoptosis of HCC cells by ROS generation and sustained JNK activation.
文摘Curcumin has been reported to possess multifunctional bioactivities with low toxicity. However, the clinical application of curcumin has been significantly limited by its instability and poor metabolic property. Up to now, multiple approaches are being sought to overcome these limitations to obtaining “super curcumin”, and many analogues of curcumin have been designed and synthesized. In all of those analogues, a series of mono-carbonyl curcumin analogues deleting the β-diketone draw our attention. Since the seven-carbon β-diketone linker in curcumin may be responsible for its instability, the series of mono-carbonyl curcumin analogues deleting the β-diketone may be potential prodrug with improved pharmacokinetic and pharmacodynamic properties. This review just focuses on these more stable mono-carbonyl analogues of curcumin, and shows the new class of active structure by introducing the synthesis and anticancer activity of them.
基金Supported by Grant from Hunan Provincial Science and Technology Department (2008 FJ 3088), China
文摘AIM:To investigate the effects of macrophage migration inhibitory factor (MIF) on proliferation of human gastric cancer MGC-803 cells and expression of cyclin D1 and p27Kip1 in them,and further determine whether the effects are related to the PI3K/Akt signal transduction pathway. METHODS:Gastric cancer MGC-803 cells were cultured and then treated with 50 μg/L recombinant human MIF (rhMIF) with and without a PI3K inhibitor,LY294002 (25 μmol/L). MTT assay was used to detect the prolifer-ation of MGC-803 cells. Cell cycle was detected by flow cytometry. Expression of cyclin D1 and p27Kip1 mRNA was by reverse transcription-polymerase chain reaction. Protein expression of phosphorylated Akt (p-Akt),Akt,cyclin D1 and p27Kip1 was examined by immunocyto-chemistry and Western blotting. RESULTS:rhMIF signifi cantly stimulated the prolifera-tion of MGC-803 cells and cell cycle progression from G1 phase to S phase in a concentration-and time-de-pendent manner. After the MGC-803 cells were treated with rhMIF for 24 h,the expression of cyclin D1 was signifi cantly up-regulated compared with the cells not treated with rhMIF at both mRNA and protein levels(0.97 ± 0.02 vs 0.74 ± 0.01,P = 0.002; 0.98 ± 0.05 vs 0.69 ± 0.04,P = 0.003). The p27Kip1 was down-regulated but only statistically significant at the protein level. rhMIF significantly increased the expression of p-Akt,which reached the peak at 30 min,but did not affect the expression of Akt. However,LY294002 inhibited all the effects of rhMIF.CONCLUSION:Macrophage MIF increases the proliferation of gastric cancer cells,induces the expression of cyclin D1 at the transcriptional level and inhibits the expression of p27Kip1 at the post-transcriptional level via the PI3K/Akt pathway.
基金support from the Education Department of Hunan Province(No.19A419).
文摘Objective:This study aimed to explore the effects of our rational emotive behavior therapy(REBT)program on symptoms,anxiety,depression,and sleep state in patients with colorectal cancer(CRC)undergoing chemotherapy.Methods:From October 2020 to May 2021,fifty-six patients with CRC in a hospital in the Hunan Province were randomly divided into an intervention group(n=28)and a control group(n=28).The patients in the intervention group completed a 6-week REBT program based on routine nursing care,including four courses:1)establish a relationship and formulate health files;2)group communications and study symptom management;3)continuously provide health knowledge and strengthen healthy behavior;and 4)review the treatment and summary.The control group maintained routine nursing care.The simplified Chinese version of the Memorial Symptom Assessment Scale Short Form(MSASeSFeSC),the Hospital Anxiety and Depression Scale(HADS),and the Pittsburgh Sleep Quality Index(PSQI)scale were used to investigate and compare the intervention effects of the two groups at baseline(T1,before the intervention),four weeks(T2),and six weeks(T3)after the intervention.Results:The intervention group was significantly improved in symptoms,anxiety,depression,and sleep state,compared with the control group.At T2,MSASeSFeSC(24.43±4.26 vs.28.07±3.91),symptom distress(17.29±4.04 vs.19.39±3.59),symptom frequency(7.14±1.51 vs.8.68±1.42),HADS(13.68±3.38 vs.15.86±3.79),anxiety(3.89±1.85 vs.5.18±2.18),and depression(9.79±2.06 vs.10.68±2.23),showed that the difference between the two groups was statistically significant(P<0.05).At T3,MSASeSFeSC(23.89±3.54 vs.30.14±3.94),symptom distress(17.61±3.52 vs.21.32±3.57),symptom frequency(6.29±1.49 vs.8.82±1.47),HADS(11.82±2.57 vs.16.29±3.13),anxiety(3.21±1.64 vs.5.61±1.77),and depression(8.61±1.52 vs.10.68±1.81),showed that the difference between the two groups was statistically significant(P<0.05).The sleep state of the intervention group was better than the control group at T3,with decreased score of PSQI[4.00(3.00,8.00)vs.9.00(7.00,12.50),Z=-3.706,P<0.001].Conclusion:The 6-week REBT program can effectively improve the symptom,anxiety,depression,and sleep state of patients with CRC undergoing chemotherapy,which could as a care plan for patients with CRC who are repeatedly admitted to the hospital for chemotherapy.
文摘Apelin is an endogenous ligand of the apelin receptor(APJ),a seven-transmembrane G protein-coupled receptor.Apelin and APJ exist in a variety of tissues,with special status in the heart,lung and tumors.Furthermore,many research shows that the apelin/APJ system exerts a broad range of activities that affect kidney systems.This review we summarize the role of apelin/APJ system on renal fibrosis,renal ischemia/reperfusion injury and diabetic nephropathy,polycystic kidney disease,hemodialysis.It was found that the level expression of apelin m RNA in the inner stripe of kidney outer medulla was the highest,and the region is significantly correlated with water and sodium balance.In UUO mice model,intraperitoneal injection of Apelin can reduceα-SMA,the expression of TGF-1 and its receptor,and between renal stromal components also significantly decreased.These results show that Apelin can reduce the deposition of ECM and improve renal interstitial fibrosis.In renal ischemia/reperfusion injury studies show that apelin-13 can significantly reduce the damage induced by renal tubularlesions,renal cell death and the normal renal function is not completely lead to large damage.But in diabetic nephropathy,Apelin-APJ system can promote or slow DN disease progression is controversial,still needs further research.Analysis the receiver operating characteristic curve found that in the process of identifying ADPKD disease apelin and copeptin shows good receiver operating characteristic curve(ROC),cox proportional hazards regression model also showed apelin can predict on the progress of kidney disease.In hemodialysis patients the apelin levels and PTH levels were positively correlated,it could prompt apelin can protect bone dialysis patients.Apelin also can reduce Pit-1 inhibition of vascular smooth muscle cell osteoblast calcification and thus improve the aortic calcification,so Apelin may have a potential role in the treatment of vascular calcification in CKD.In kidney disease conditions,Apelin/APJ system plays a variety of biological functions,because of the Apelin protective on kidney,Apelin/APJ may be a potential material for the treatment of chronic kidney disease.
文摘Along with its wide anatomical distribution, somatostatin (SST) acts on multiple targets via a family of 5 receptors to produce a broad spectrum of biological effects. Therefore, a variety of peptide analogs have been produced and are widely used in clinical treatment. However, because of their flaws in the structure of peptide, the clinical efficacy is limited. In this review, we summarize the structure, pharmacological effects and the potential clinical value of non-peptide SST analogs. We focus on the research and development of non-peptide SST analogs since 1998, and discuss the problems and potential prospects for non-peptide SST analogs. We believe that as more non-peptide somatostatin analogs are successfully developed, the extensive clinical application of SSTs will contribute a great deal to medical science.
基金the grants from the National Natural Science Foundation of China[No.81903615]Natural Science Foundation of Hunan Province[No.2018JJ2339,2018JJ6122]。
文摘Mammalian adipose tissues can be broadly divided into white adipose tissue(WAT),beige adipose tissue,and brown adipose tissue(BAT)[1].The function of WAT is to store superfluous energy and is characterized by unilamellar lipid droplets.WAT,as a prominent endocrine organ,regulates feeding and satiety by producing hormones.
基金supported by grants from the National Natural Science Foundation of China(No.81970431)the Hunan Provincial Natural Science Foundation of China(No.2023JJ50136)
文摘To the Editor:Pathological cardiac hypertrophy is commonly stimulated by stress or induced by cardiovascular diseases,such as hypertension and myocardial infarction.A sustained pathological hypertrophic response can lead to declines in diastolic and systolic functions and eventually develop heart failure.Angiotensin II(Ang II)can mediate cardiac hypertrophy through the angiotensin II type 1 receptor(AT1R).^([1])
基金supported by the National Natural Sciences Foundation of China,No.81770460(to YCL)the Postdoctoral Research Fellowship of the Saskatchewan Health Research Foundation,No.SHRF,4144(to YCL)+2 种基金the third level of the Chuanshan Talent project of the University of South China,No.2017CST20(to YCL)the Aid Program,No.2017KJ268 and the Key Lab for Clinical Anatomy&Reproductive Medicine,No.2017KJ182 from the Science and Technology Bureau of Hengyang City,China(to YCL and XC)the Postgraduate Student Research Innovation Projects of Hunan Province,China,No.CX2018B62(to ABG)
文摘Prolonged activation of adenosine A1 receptor likely leads to damage of dopaminergic neurons and subsequent development of neurodegenerative diseases.However,the pathogenesis underlying long-term adenosine A1 receptor activation-induced neurodegeneration remains unclear.In this study,rats were intraperitoneally injected with 5 mg/kg of the adenosine A1 receptor agonist N6-cyclopentyladenosine(CPA)for five weeks.The mobility of rats was evaluated by forced swimming test,while their cognitive capabilities were evaluated by Y-maze test.Expression of sortilin,α-synuclein,p-JUN,and c-JUN proteins in the substantia nigra were detected by western blot analysis.In addition,immunofluorescence staining of sortilin andα-synuclein was performed to detect expression in the substantia nigra.The results showed that,compared with adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine(5 mg/kg)+CPA co-treated rats,motor and memory abilities were reduced,surface expression of sortin andα-synuclein in dopaminergic neurons was reduced,and total sortilin and totalα-synuclein were increased in CPA-treated rats.MN9D cells were incubated with 500 nM CPA alone or in combination with 10μM SP600125(JNK inhibitor)for 48 hours.Quantitative real-time polymerase chain reaction analysis of sortilin andα-synuclein mRNA levels in MN9D cells revealed upregulated sortilin expression in MN9D cells cultured with CPA alone,but the combination of CPA and SP600125 could inhibit this expression.Predictions made using Jasper,PROMO,and Alibaba online databases identified a highly conserved sequence in the sortilin promoter that was predicted to bind JUN in both humans and rodents.A luciferase reporter assay of sortilin promoter plasmid-transfected HEK293T cells confirmed this prediction.After sortilin expression was inhibited by sh-SORT1,expression of p-JUN and c-JUN was detected by western blot analysis.Long-term adenosine A1 receptor activation levels upregulatedα-synuclein expression at the post-transcriptional level by affecting sortilin expression.The online tool Raptor-X-Binding and Discovery Studio 4.5 prediction software predicted that sortilin can bind toα-synuclein.Co-immunoprecipitation revealed an interaction between sortilin andα-synuclein in MN9D cells.Our findings indicate that suppression of prolonged adenosine A1 receptor activation potently inhibited sortilin expression andα-synuclein accumulation,and dramatically improved host cognition and kineticism.This study was approved by the University Committee of Animal Care and Supply at the University of Saskatchewan(approval No.AUP#20070090)in March 2007 and the Animals Ethics Committee of University of South China(approval No.LL0387-USC)in June 2017.
基金National Natural Science Foundation of China(81372579,81273537)the Construct Program of the Key Discipline in Hunan Province
文摘Objective To prepare, characterize and evaluate the antioxidant activity of rutin-liposome（RL）. Methods Liposomes of rutin were prepared by film dispersion method and the encapsulation efficiency（EE） was determined by RP-HPLC. Human umbilical vein endothelial cells（HUVECs） were injuried by H_2O_2 and treated with either free aqueous rutin or the RL delivery systems. The viability of HUVECs was determined by MTT and ELISA. Results The drug delivery system showed uniform rutin loaded nanoparticles with average particle size of（147.20 ± 1.42） nm, polydispersity index of（0.191 ± 0.003） nm, Zeta potential of（-20.0 ± 1.0） mV, and the drug EE was closed to 90.0%. The antioxidant effect of the drug delivery system to H_2O_2-damaged HUVECs showed that RL could increase injury cells viability compared to free aqueous rutin, which was accompanied with an obvious decrease in malondialdehyde（MDA）, lactate dehydrogenase（LDH） while increase the level of nitrogen oxide（NOS）. Conclusion The nanostructured RL is improved on the antioxidant effect and may be treating the different diseases caused by free radicals.
基金funded by grants from the National Natural Science Foundation of China[81470434,81503074,81670265]Hunan Province Cooperative Innovation Center for Molecular Target New Drugs Study(Hunan Provincial Education Department document)[Approval number:2014-405]
文摘Recently, Prieto-Godino et al.[1] found that the olfactory receptor 75a （Ir75a） gene is a functional pseudo-pseudogene in Drosophila sechellia. For a long time, Ir75a has been regarded as an acetic acid receptor that detects acetic acid and induces obvious olfactory responses in olfactory sensory neurons （OSNs）f2J. Nonetheless, Prieto-Godino et al. confirmed that Ir75a lost its sensitivity to acetic acid in D. sechellia. Thus, the D. sechelfia Ir75a gene is generally recognized as a pseudogene in OSNs.
文摘PRIMARY pulmonary sarcomatoid carcinoma （PSC）is a rare condition, approximately accounting for0.1%-0.4% of all lung malignancies.1 PSCsconsist of 5 major histological variants accordingto 2004 WHO classification： pleomorphic carcinoma,spindle cell carcinoma, giant cell carcinoma, carcinosarcoma.
基金the National Basic Research Program of China (No. 2015CB931903)the National Natural Science Foundation of China (Nos. 21421002, 21472222, 21502214, 21672242, 81273537)+7 种基金the Chinese Academy of Sciences (Nos. XDA02020105, XDA02020106)the Key Research Program of Frontier Sciences(CAS)(No. QYZDJSSW-SLH049)the Key Project of Hunan Provincial Education Department(No. 17A190)the Zhengxiang Scholar Program of the University of South China, Hunan Provincial Hengyang City Joint Fund(No. 2017JJ4050)Hunan Graduate Science and Technology Innovation Projects (No. 2018-400)Program for Innovative Talent Team of Hengyang(No. 2017-1)the Key Project of Hengyang Science and Technology Department(No. 2017KJ166)Shanghai Research Institute of Chemical Industry Co., LTD.(No. SKL-LCTP-201802)for financial support
文摘As trifluoromethylthiolation has received increasing attention recently, many CF_3S-reagents and trifluoromethylthiolation methods have been developed. Herein we describe trifluoromethylthiolation of alkyl halides by using Ph_3 P^+CF_2CO_2 as a fluoride and difluorocarbene source. Difluorocarbene is a versatile intermediate, but its side reactions are usually ignored and the by-products would therefore be discarded. In this work, a side reaction of difluorocarbene, the generation of a fluoride anion from difluorocarbene, was developed into a synthetic tool. Although the trifluoromethylthiolation reaction involved multi-sequential steps, the cleavage of C-F bond, the formation of CF_2=S bond, F-C(S)F_2 bond,and C-SCF_3 bond, the conversion proceeded fast and was completed within 10 min.
基金supported by the grants from the National Natural Science Foundation of China [81470434]
文摘Truttmann MC et al.[1] recently reported that AMPylation of heat shock protein 70 (HSP70) family of chaperones participates in altering the aggregation properties and maintaining protein homeostasis (proteostasis), thereby playing a vital role in the development of neurodegenerative diseases (NDs). NDs are commonly manifested by protein aggregates, which exert harmful effects on proteostasis. Interestingly, it has been observed that AMPylation of heat shock proteins (HSPs) can maintain proteostasis by inhibiting the formation of protein aggregates. As previous studies only indicate that HSPs could regulate proteostasis, such a novel discovery further demonstrates the involvement of HSP70 AMPylation in the regulation of protein aggregation and the maintenance of proteostasis. Therefore, AMPylation can be considered to possess a therapeutic potential to target certain physiological processes related to proteostasis, such as age-related diseases.
文摘A novel turn-on fluorescent probe for the detection of palladium has been designed. The probe can selectively and sensitively detect palladium in solution, and the limit of detection was calculated to be 11.4 nmol·L-1. Furthermore, the probe was successfully used for fluorescence imaging of palladium in living cells.
基金financially supported by Hunan Provincial Natural Science Foundation of China 2022JJ40405(X.L).
文摘Background:Cuprotosis is a newly discovered Copper-dependence form of cell death.Cuprotosis-related genes(CRGs)regulating mitochondrial metabolism and protein lipoylation suggest the critical roles cuprotosis for in cancer.However,the prognostic value of CRGs in the highly immunogenic cancer type,kidney renal clear cell carcinoma(KIRC)needs to be further studied.Herein,we aim to identify novel prognostic genes and construct a CRGs prognostic signature for KIRC.Methods:We downloaded the mRNA sequencing data from the Cancer Genome Atlas,differentially expressed CRGs were screened out and their bio-function was elucidated.Then we used Cox regression analysis to establish a prediction model of CRGs.Subsequently,a prognostic scoring model based on the regression coefficients of the screened out CRGs and their corresponding mRNA expressions were constructed and validated.Results:Seven differentially expressed CRGs were screened.A two-gene model was built to separate samples into high-risk and low-risk groups.Overall survival was lower in the high-risk group than in the low-risk group(p<0.05).The receiver operating characteristic curve showed a good diagnostic efficiency of the signature.We verified this prognostic model in the Cancer Genome Atlas test cohorts.The risk score was identified as an independent prognostic factor via multivariate Cox regression.Moreover,the nomogram was used to predict 1-/3-/5-year OS of KIRC patients.Furthermore,risk score has a very significant effect on the infiltration of immune cells and the expression of immune checkpoints.Conclusions:To conclude,we constructed a novel prognostic signature based on CRGs.Targeting cuprotosis may represent a promising approach for the treatment of KIRC.
基金supported by grants from the National Natural Science Foundation of China(81970431)the Hunan Provincial Natural Science Foundation(2023JJ50136).
文摘It is well known that sleep is one of the inevitable activities of daily living and it is one of the most important factors contributing to human health.Sleep in mammals is a cyclic occurrence of two distinct states,rapid eye movement(REM)and non-rapid eye movement(NREM)[1].
基金supported by grants from National Key Basic Research and Development Program (Grant No.2010CB912801)National Natural Science Foundation of China (Grant No. 31071157 and 31271404)
文摘Bacterial small RNAs （sRNAs） are an emerging class of regulatory RNAs of about 40-500 nucleotides in length and, by binding to their target mRNAs or proteins, get involved in many biological processes such as sensing environmental changes and regulating gene expres- sion. Thus, identification of bacterial sRNAs and their targets has become an important part of sRNA biology. Current strategies for discovery of sRNAs and their targets usually involve bioinformatics prediction followed by experimental validation, emphasizing a key role for bioinformatics prediction. Here, therefore, we provided an overview on prediction methods, focusing on the merits and limita- tions of each class of models. Finally, we will present our thinking on developing related bioinformafics models in future.
