Mammalian mitochondria have small genomes encoding very limited numbers of proteins.Over one thousand proteins and noncoding RNAs encoded by the nuclear genome must be imported from the cytosol into the mitochondria.H...Mammalian mitochondria have small genomes encoding very limited numbers of proteins.Over one thousand proteins and noncoding RNAs encoded by the nuclear genome must be imported from the cytosol into the mitochondria.Here,we report the identification of hundreds of circular RNAs(mecciRNAs)encoded by the mitochondrial genome.We provide both in vitro and in vivo evidence to show that mecciRNAs facilitate the mitochondrial entry of nuclear-encoded proteins by serving as molecular chaperones in the folding of imported proteins.Known components involved in mitochondrial protein and RNA importation,such as TOM40 and PNPASE,interact with mecciRNAs and regulate protein entry.The expression of mecciRNAs is regulated,and these transcripts are critical for the adaption of mitochondria to physiological conditions and diseases such as stresses and cancers by modulating mitochondrial protein importation.mecciRNAs and their associated physiological roles add categories and functions to the known eukaryotic circular RNAs and shed novel light on the communication between mitochondria and the nucleus.展开更多
Neuroinflammation and neurodegeneration are key processes that mediate the development and progression of neurological diseases.However,the mechanisms modulating these processes in different diseases remain incomplete...Neuroinflammation and neurodegeneration are key processes that mediate the development and progression of neurological diseases.However,the mechanisms modulating these processes in different diseases remain incompletely understood.Advances in single cell based multi-omic analyses have helped to identify distinct molecular signatures such as Lgals3 that is associated with neuroinflammation and neurodegeneration in the central nervous system(CNS).Lgals3 encodes galectin-3(Gal3),aβ-galactoside and glycan binding glycoprotein that is frequently upregulated by reactive microglia/macrophages in the CNS during various neurological diseases.While Gal3 has previously been associated with non-CNS inflammatory and fibrotic diseases,recent studies highlight Gal3 as a prominent regulator of inflammation and neuroaxonal damage in the CNS during diseases such as multiple sclerosis,Alzheimer’s disease,and Parkinson’s disease.In this review,we summarize the pleiotropic functions of Gal3 and discuss evidence that demonstrates its detrimental role in neuroinflammation and neurodegeneration during different neurological diseases.We also consider the challenges of translating preclinical observations into targeting Gal3 in the human CNS.展开更多
Despite recent progress in crop genomics studies,the genomic changes brought about by modern breeding selection are still poorly understood,thus hampering genomics-assisted breeding,especially in polyploid crops with ...Despite recent progress in crop genomics studies,the genomic changes brought about by modern breeding selection are still poorly understood,thus hampering genomics-assisted breeding,especially in polyploid crops with compound genomes such as common wheat(Triticum aestivum).In this work,we constructed genome resources for the modern elite common wheat variety Aikang 58(AK58).Comparative genomics between AK58 and the landrace cultivar Chinese Spring(CS)shed light on genomic changes that occurred through recent varietal improvement.We also explored subgenome diploidization and divergence in common wheat and developed a homoeologous locus-based genome-wide association study(HGWAS)approach,which was more effective than single homoeolog-based GWAS in unraveling agronomic trait-associated loci.A total of 123 major HGWAs loci were detected using a genetic population derived from AK58 and cs.Elite homoeologous haplotypes(HHs),formed by combinations of subgenomic homoeologs of the associated loci,were found in both parents and progeny,and many could substantially improve wheat yield and related traits.We built a website where users can download genome assembly sequence and annotation data for AK58,perform blast analysis,and run JBrowse.Our work enriches genome resources for wheat,provides new insights into genomic changes during modern wheat improve-.ment,and suggests that efficientmining of elite HHs can make a substantial contribuutionto genomics-assisted breeding in common wheat and other polyploid crops.展开更多
Cafeteria diet is known to induce excessive endoplasmic reticulum stress(ERS),oxidative stress(OS),and inflammation that could cause metabolic changes and liver diseases.Bergamottin(BGM)is a natural furanocoumarin tha...Cafeteria diet is known to induce excessive endoplasmic reticulum stress(ERS),oxidative stress(OS),and inflammation that could cause metabolic changes and liver diseases.Bergamottin(BGM)is a natural furanocoumarin that is known to have various biological activities.The present study,for the first time,assessed the reducing effect of BGM on the development of liver damage in cafeteria diet fed mice.48 male C57BL/6 mice were fed an experimental diets diet for 16 weeks and BGM(0.05 mg/kg and 0.22 mg/kg)was administered for the last four weeks.The serum samples and liver homogenates were assessed for markers of ERS,OS,and inflammation.Also,histopathological analyzes were performed.This study demonstrated that the CAF diet caused metabolic changes,ERS,OS,and inflammation in serum and liver tissue.However,BGM exerts anti-oxidant,anti-ER stress anti-inflammatory effects in CAF-induced liver damage.Therefore,BGM may potentially be a novel therapeutic compound to ameliorate liver damage.展开更多
Objective:To investigate the loxic implications of ethanolic stem bark extract of Azadirachta indica(A-indica)at 50,100,200 and 300 mg/kg body weight in Wistar rats.Methods:Fifty male rats of Wistar strains were rando...Objective:To investigate the loxic implications of ethanolic stem bark extract of Azadirachta indica(A-indica)at 50,100,200 and 300 mg/kg body weight in Wistar rats.Methods:Fifty male rats of Wistar strains were randomly grouped into five(A-F.)of ten animals each.Animals in Group A(control)were orally administered 1 mL of distilled water on daily basis for 21 days while those in Groups B-E received same volume of the extract corresponding to 50,100,200 and 300mg/kg body weight.Results:The extract did not significantly(P>0.05)alter the levels of albumin,total protein,red blood cells and factors relating to it whereas the white blood cell,platelets,serum triacylglycerol and high-density lipoprotein cholesterol decreased significantly(P<0.05).In contrast,the final body weights,absolute weights of the liver,kidney,lungs and heart as well as their organ-body weight ratios,serum globulins,total and conjugated bilirubin,serum cholesterol,low-density lipoprotein cholesterol and computed atherogenic index increased significantly.The spleen-body weight ratio,alkaline phosphatase,alanine and aspartate transaminases,sodium,potassium,calcium,feed and water intake were altered at specific doses.Conclusions:Overall,the alterations in the biochemical parameters of toxicity have consequential effects on the normal functioning of the organs of the animals.Therefore,the ethanolic extract of A.indica stem bark at the doses of 50,100,200 and 300 mg/kg body weight may not be completely safe as an oral remedy and should be taken with caution if absolutely necessary.展开更多
Objective: To examine the in vitro and in vivo anti-inflammatory effects of the alkaloid enriched extract(ELA) from the roots of Eurycoma longifolia. Methods: The in vitro antiinflammatory effects of ELA were evaluate...Objective: To examine the in vitro and in vivo anti-inflammatory effects of the alkaloid enriched extract(ELA) from the roots of Eurycoma longifolia. Methods: The in vitro antiinflammatory effects of ELA were evaluated by examining its inhibitory activities against nitric oxide(NO) production and inducible nitric oxide synthase(iN OS) and cyclooxygenase2(COX-2) expressions in lipopolysaccharide(LPS)-stimulated RAW264.7 cells. The level of NO produced in the culture media was determined by Griess method. The i NOS and COX-2 protein expressions were analyzed by Western blot. The in vivo effect of ELA was evaluated on LPS-induced septic shock in mice model. Mice mortality was monitored for5 days after injection of LPS. The chemical contents of the ELA were determined by using various chromatographic and spectroscopic techniques. Results: The ELA was found to exhibit a significant anti-inflammatory effect in both in vitro and in vivo models. The results demonstrated that ELA dose-dependently inhibited LPS-induced NO production as well as the protein iN OS and COX-2 expressions. In the septic shock model, ELA dose-dependently protected mice from LPS-induced mortality. Further study on the isolated components of ELA indicated that 9,10-dimethoxycanthin-6-one may contribute significantly to the antiinflammatory effects of the extract. Conclusions: These results suggest that ELA exhibits the anti-inflammatory activity via suppression of pro-inflammatory mediators such as NO, iN OS,and COX-2 and protects mice from LPS-induced mortality in septic shock model.展开更多
Purpose: We evaluated biochemical analysis results with the aim of discovering serum levels that have possible effects on the development of retinopathy of prematurity (ROP). Methods: A retrospective study was conduct...Purpose: We evaluated biochemical analysis results with the aim of discovering serum levels that have possible effects on the development of retinopathy of prematurity (ROP). Methods: A retrospective study was conducted between January 2017 and January 2018 on a total of 110 infants with 35 or less gestational weeks. The sample included 78 infants who had been diagnosed with different stages of ROP and 32 infants without ROP. Results from routine serum biochemical analyses, performed at birth and at one month after birth, were evaluated. The Independent Sample t-test and Mann-Whitney U test were performed to compare the data. Results: The infants with ROP were born at a mean of 28.0 (±2.1) weeks of gestation, weighing a mean of 1066 (±314) g, and the mean duration of stay in the incubator was 38.2 (±19) days. The infants without ROP were born at a mean of 29.6 (±2.6) weeks of gestation, weighing a mean of 1265 (±372) g. 59 infants (53.6%) were females, and 51 (46.4%) were males. Between infants with and without ROP, differences in the following levels were not statistically significant: glucose, blood urine nitrogen, creatinine, alanine aminotransferase, aspartate aminotransferase, albumin, total protein, direct bilirubin, indirect bilirubin, uric acid, and phosphorus. Serum magnesium (Mg) levels at birth in infants with ROP were significantly higher than infants without ROP (p = 0.014). Conclusions: Serum Mg levels at birth were found to be higher in infants with ROP than in those without ROP. The levels may be dependent on the mothers’ treatment of Mg for different medical reasons.展开更多
Effects of two doses of the anti-diabetic drug, metformin (MF), on hormonal and metabolic levels of serum of non-diabetic male Wistar rats with 1,2-dimethylhydrazine (DMH)-induced colon tumor adenocarcinomas were ...Effects of two doses of the anti-diabetic drug, metformin (MF), on hormonal and metabolic levels of serum of non-diabetic male Wistar rats with 1,2-dimethylhydrazine (DMH)-induced colon tumor adenocarcinomas were studied. Carcinogenesis in the animals was also observed. Rats with DMH-induced colon adenocarcinomas had elevated levels of serum glucose, insulin, insulin- like growth factor-l, total cholesterol, triglycerides, catalase, malonic dialdehyde, glycated hemoglobin, aspartate aminotransferase, and alanine aminotransferase and decreased hemoglobin. Treatment with two doses of MF normalized maiority of these changes in DMH-treated rats, whereas the drug was ineffective in rats without DMH treatment. The only exception was the decreased triglyceride levels in MF-treated rats. A 100 mg/kg dose of MF increased DMH-induced exophytic colon carcinomas and decreased endophytic tumors compared with untreated rats. Moreover, both MF doses increased DMH-induced and highly differentiated tumors and decreased the invasiveness of colon carcinomas compared with rats provided with DMH and water. Therefore, effects of MF on metabolic homeostasis are critical for preventing colon cancer.展开更多
AIM: To assess the prognostic significance of cathepsin L, a cysteine protease that degrades the peri-tumoral tissue, in patients with pancreatic cancer.
OBJECTIVE To observe the effect of curcumin on proliferation and apop-tosis in the prostate cancer LNCaP cell line. METHODS The AXSYMTM system luciferase method was used to examine the effect of various concentratious...OBJECTIVE To observe the effect of curcumin on proliferation and apop-tosis in the prostate cancer LNCaP cell line. METHODS The AXSYMTM system luciferase method was used to examine the effect of various concentratious of curcumin on the content of prostate specific antigen (PSA) in prostate cancer LNCaP cells. A pGL3-PSA luciferase expression vector, containing 640 bp DNA of the PSA gene 5' -promoter region was constructed and transfected into the LNCaP cells with lipofectin. By measuring luciferase activity, the effect of 10 μmol/L, 20 μmol/L, 30 and 40 μmol/L curcumin on the promoter was studied. Effects on cell growth and apoptosis were analyzed by microscopy, the MTT colorimetric assay and flow cytometry. Western-blotting was used to measure expression of the androgen receptor (AR) in the LNCaP cells treated with different concentrations of curcumin. RESULTS The results showed that the expression of PSA was inhibited as curcumin reduced the activity of luciferase. Curcumin also caused a sigificant concentration-dependent decrease in AR expession measured by Western -blotting. Cell growth was inhibited and apoptosis was induced. CONCLUSION By inhibiting AR expression, curcumin reduced the function of the PSA promoter and inhibited PSA protein expression. Curcumin decreased the cellular proliferation and induced apoptosis in LNCaP cells in a concention-dependent manner.展开更多
Diabetes mellitus (DM) is associated with platelet dysfunction. In diabetic patients, alterations in platelet functions, especially increased platelet agregation, have been suggested to cause increasing in cardiovascu...Diabetes mellitus (DM) is associated with platelet dysfunction. In diabetic patients, alterations in platelet functions, especially increased platelet agregation, have been suggested to cause increasing in cardiovascular morbidity and mortality or in accelaretion of athersclerotic process. In this study, we aimed to investigate the platelet aggregation response alterations and the effects of DM duration, HbA1c, treatment options among the patients with Type 2 DM. Fortyfive patients (case group;21 male, 24 female) with Type 2 DM and forty-eight healthy individuals (control group;22 male, 26 female) were included in this study. Platelet aggregation was determinated with Chorono-log 500 (USA) named device by using Chorono-log/ADP, Chorono-log/ collagen and Chorono-log/epinephrine kits. ADP-induced platelet aggregation was significantly higher in the case group compared with control group (p 【0.05). Epinephrine induced platelet aggregation were significant in negatively correlation with the diabetes duration (P 【0.05). Platelet aggregation responses did not differ according to their treatment type (sulphonylurea or insulin) was statistically insignificiant among the case groups (p 】0.05). In conclusion, our findings supported that type 2 diabetes may interfere with platelet functions without any relationship age, gender, the treatment types and the regulation levels. These findings supports that existence potential new factors or mechanism affecting platelet agregation. The subject requires more detailed studies in the future.展开更多
Purpose: Retinopathy of prematurity (ROP), an abnormal proliferation of retinal vessels in premature infants with low birth weight, develops due to many factors. This study investigated a possible correlation between ...Purpose: Retinopathy of prematurity (ROP), an abnormal proliferation of retinal vessels in premature infants with low birth weight, develops due to many factors. This study investigated a possible correlation between haematological parameters and ROP development. Method: This study included 189 infants without ROP and 128 with ROP. All were born at 35 weeks’ gestation or earlier, had a CBC drawn within 72 hours of birth, and had haemogram data for the first month. Haemoglobin (Hb), haematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), red cell distribution width (RDW), platelet counts (PLT), mean platelet volume (MPV) and platelet distribution width (PDW) values were obtained from hospital data and retrospectively analysed. Results: The mean gestational age was 31 weeks and 29 weeks for the control and ROP groups, respectively;the mean birth weights were 1757 g and 1332 g, respectively. The ROP group’s birth Hb, MCV and RDW were significantly lower than the control group (p p p p Conclusion: Premature infants with ROP had lower Hb and increased platelet, MPV and PDW in early postnatal life than infants without ROP. In the first month, when ROP develops, low PLT, PDW and Hb and high MPV could be indicators for ROP diagnosis, follow-up and treatment.展开更多
Objective: BCR/ABL oncoprotein-expression is associated with uncontrolled cell growth. Sphingosine kinase 1 (SPK1) regulates the production of sphingosine 1-phosphate (S1P), a key lipid signal molecular in cell p...Objective: BCR/ABL oncoprotein-expression is associated with uncontrolled cell growth. Sphingosine kinase 1 (SPK1) regulates the production of sphingosine 1-phosphate (S1P), a key lipid signal molecular in cell proliferation and survival. The objective of this study was to elucidate the roles of S1P and its receptors in bcr/abl positive chronic myeloid leukemia (CML) cells. Methods: The expressions of SIP receptors: S1P1, S1P2 and S1P3 in CML cells were detected by RT-PCR. SPK1 expression, activity and extracellular S1P were determined in ECV304 and HL-60 cells which were transfected with bcr/abl gene. To elucidate the relationship between the BCR/ABL, ERK/MAPK (extracellular signal-regulated kinase/mitogen-activated protein kinase), SPK/S 1P and S 1P/S 1 P2 signal pathways, bcr/abl positive CML cell line K562 was treated with STI571, PD98059, N,N-dimethyl sphingosine (DMS) and JTE-013. Results: Retrovirus-mediated overexpression of bcr/abl gene in ECV304 and HL-60 cells resulted in upregulation of the expression, activity of SPK1 and increase of the secretion of SIP, whereas treatment of STI571 and PD98059 decreased the BCR/ABL-induced S1P secretion. Treatment of DMS reduced S1P secretion and P42/44MAPK phosphorylation. S1P2-selective antagonist JTE-013 could also decrease P42/44MAPK phosphorylation. Conclusion: These results suggest that BCR/ABL up-regulates extracellular sphingosine 1-phosphate through sphingosine kinase 1 and there is cross-talk between SPK1/S1P/S1P2 and P42/44MAPK in bcr/abl positive CML cells.展开更多
基金Supported by grants to G. S.: the National Key R&D Program of China (2019YFA0802600 and 2018YFC1004500)the National Natural Science Foundation of China (31725016, 31930019, and 91940303)and the Strategic Priority Research Program (Pilot Study) “Biological basis of aging and therapeutic strategies” of the Chinese Academy of Sciences (XDPB10).
文摘Mammalian mitochondria have small genomes encoding very limited numbers of proteins.Over one thousand proteins and noncoding RNAs encoded by the nuclear genome must be imported from the cytosol into the mitochondria.Here,we report the identification of hundreds of circular RNAs(mecciRNAs)encoded by the mitochondrial genome.We provide both in vitro and in vivo evidence to show that mecciRNAs facilitate the mitochondrial entry of nuclear-encoded proteins by serving as molecular chaperones in the folding of imported proteins.Known components involved in mitochondrial protein and RNA importation,such as TOM40 and PNPASE,interact with mecciRNAs and regulate protein entry.The expression of mecciRNAs is regulated,and these transcripts are critical for the adaption of mitochondria to physiological conditions and diseases such as stresses and cancers by modulating mitochondrial protein importation.mecciRNAs and their associated physiological roles add categories and functions to the known eukaryotic circular RNAs and shed novel light on the communication between mitochondria and the nucleus.
文摘Neuroinflammation and neurodegeneration are key processes that mediate the development and progression of neurological diseases.However,the mechanisms modulating these processes in different diseases remain incompletely understood.Advances in single cell based multi-omic analyses have helped to identify distinct molecular signatures such as Lgals3 that is associated with neuroinflammation and neurodegeneration in the central nervous system(CNS).Lgals3 encodes galectin-3(Gal3),aβ-galactoside and glycan binding glycoprotein that is frequently upregulated by reactive microglia/macrophages in the CNS during various neurological diseases.While Gal3 has previously been associated with non-CNS inflammatory and fibrotic diseases,recent studies highlight Gal3 as a prominent regulator of inflammation and neuroaxonal damage in the CNS during diseases such as multiple sclerosis,Alzheimer’s disease,and Parkinson’s disease.In this review,we summarize the pleiotropic functions of Gal3 and discuss evidence that demonstrates its detrimental role in neuroinflammation and neurodegeneration during different neurological diseases.We also consider the challenges of translating preclinical observations into targeting Gal3 in the human CNS.
基金the Collaborative Innovation Center for Henan Grain Crops,the Ministry of Science and Technology of the People's Republic of China(2021YFF1000200)the National Natural Science Foundation of China(Major Program,31991213)+4 种基金the Central Publicinterest Scientific Institution Basal Research Fund(Y2021YJ01)the Major Public Welfare Projects of Henan Province(201300110800)the Key Research and Development Program of China(2016YFD0100102)the CAAS Agricultural Science and Technology Innovation Program(CAASZDRW202002)the seed innovation program of the Ministry of Agriculture and Rural Affairs of China,and the Henan Provincial R&D Projects of Interregional Cooperation for Local Scientific and Technological Development Guided by the Central Government(YDZX20214100004191).
文摘Despite recent progress in crop genomics studies,the genomic changes brought about by modern breeding selection are still poorly understood,thus hampering genomics-assisted breeding,especially in polyploid crops with compound genomes such as common wheat(Triticum aestivum).In this work,we constructed genome resources for the modern elite common wheat variety Aikang 58(AK58).Comparative genomics between AK58 and the landrace cultivar Chinese Spring(CS)shed light on genomic changes that occurred through recent varietal improvement.We also explored subgenome diploidization and divergence in common wheat and developed a homoeologous locus-based genome-wide association study(HGWAS)approach,which was more effective than single homoeolog-based GWAS in unraveling agronomic trait-associated loci.A total of 123 major HGWAs loci were detected using a genetic population derived from AK58 and cs.Elite homoeologous haplotypes(HHs),formed by combinations of subgenomic homoeologs of the associated loci,were found in both parents and progeny,and many could substantially improve wheat yield and related traits.We built a website where users can download genome assembly sequence and annotation data for AK58,perform blast analysis,and run JBrowse.Our work enriches genome resources for wheat,provides new insights into genomic changes during modern wheat improve-.ment,and suggests that efficientmining of elite HHs can make a substantial contribuutionto genomics-assisted breeding in common wheat and other polyploid crops.
基金This work was supported by Office of Scientific Research Projects of Karadeniz Technical University under Project number:TDK-2021-9315.
文摘Cafeteria diet is known to induce excessive endoplasmic reticulum stress(ERS),oxidative stress(OS),and inflammation that could cause metabolic changes and liver diseases.Bergamottin(BGM)is a natural furanocoumarin that is known to have various biological activities.The present study,for the first time,assessed the reducing effect of BGM on the development of liver damage in cafeteria diet fed mice.48 male C57BL/6 mice were fed an experimental diets diet for 16 weeks and BGM(0.05 mg/kg and 0.22 mg/kg)was administered for the last four weeks.The serum samples and liver homogenates were assessed for markers of ERS,OS,and inflammation.Also,histopathological analyzes were performed.This study demonstrated that the CAF diet caused metabolic changes,ERS,OS,and inflammation in serum and liver tissue.However,BGM exerts anti-oxidant,anti-ER stress anti-inflammatory effects in CAF-induced liver damage.Therefore,BGM may potentially be a novel therapeutic compound to ameliorate liver damage.
文摘Objective:To investigate the loxic implications of ethanolic stem bark extract of Azadirachta indica(A-indica)at 50,100,200 and 300 mg/kg body weight in Wistar rats.Methods:Fifty male rats of Wistar strains were randomly grouped into five(A-F.)of ten animals each.Animals in Group A(control)were orally administered 1 mL of distilled water on daily basis for 21 days while those in Groups B-E received same volume of the extract corresponding to 50,100,200 and 300mg/kg body weight.Results:The extract did not significantly(P>0.05)alter the levels of albumin,total protein,red blood cells and factors relating to it whereas the white blood cell,platelets,serum triacylglycerol and high-density lipoprotein cholesterol decreased significantly(P<0.05).In contrast,the final body weights,absolute weights of the liver,kidney,lungs and heart as well as their organ-body weight ratios,serum globulins,total and conjugated bilirubin,serum cholesterol,low-density lipoprotein cholesterol and computed atherogenic index increased significantly.The spleen-body weight ratio,alkaline phosphatase,alanine and aspartate transaminases,sodium,potassium,calcium,feed and water intake were altered at specific doses.Conclusions:Overall,the alterations in the biochemical parameters of toxicity have consequential effects on the normal functioning of the organs of the animals.Therefore,the ethanolic extract of A.indica stem bark at the doses of 50,100,200 and 300 mg/kg body weight may not be completely safe as an oral remedy and should be taken with caution if absolutely necessary.
基金funded by Vietnam Academy of Science and Technology under grant number VAST04.03/17-18
文摘Objective: To examine the in vitro and in vivo anti-inflammatory effects of the alkaloid enriched extract(ELA) from the roots of Eurycoma longifolia. Methods: The in vitro antiinflammatory effects of ELA were evaluated by examining its inhibitory activities against nitric oxide(NO) production and inducible nitric oxide synthase(iN OS) and cyclooxygenase2(COX-2) expressions in lipopolysaccharide(LPS)-stimulated RAW264.7 cells. The level of NO produced in the culture media was determined by Griess method. The i NOS and COX-2 protein expressions were analyzed by Western blot. The in vivo effect of ELA was evaluated on LPS-induced septic shock in mice model. Mice mortality was monitored for5 days after injection of LPS. The chemical contents of the ELA were determined by using various chromatographic and spectroscopic techniques. Results: The ELA was found to exhibit a significant anti-inflammatory effect in both in vitro and in vivo models. The results demonstrated that ELA dose-dependently inhibited LPS-induced NO production as well as the protein iN OS and COX-2 expressions. In the septic shock model, ELA dose-dependently protected mice from LPS-induced mortality. Further study on the isolated components of ELA indicated that 9,10-dimethoxycanthin-6-one may contribute significantly to the antiinflammatory effects of the extract. Conclusions: These results suggest that ELA exhibits the anti-inflammatory activity via suppression of pro-inflammatory mediators such as NO, iN OS,and COX-2 and protects mice from LPS-induced mortality in septic shock model.
文摘Purpose: We evaluated biochemical analysis results with the aim of discovering serum levels that have possible effects on the development of retinopathy of prematurity (ROP). Methods: A retrospective study was conducted between January 2017 and January 2018 on a total of 110 infants with 35 or less gestational weeks. The sample included 78 infants who had been diagnosed with different stages of ROP and 32 infants without ROP. Results from routine serum biochemical analyses, performed at birth and at one month after birth, were evaluated. The Independent Sample t-test and Mann-Whitney U test were performed to compare the data. Results: The infants with ROP were born at a mean of 28.0 (±2.1) weeks of gestation, weighing a mean of 1066 (±314) g, and the mean duration of stay in the incubator was 38.2 (±19) days. The infants without ROP were born at a mean of 29.6 (±2.6) weeks of gestation, weighing a mean of 1265 (±372) g. 59 infants (53.6%) were females, and 51 (46.4%) were males. Between infants with and without ROP, differences in the following levels were not statistically significant: glucose, blood urine nitrogen, creatinine, alanine aminotransferase, aspartate aminotransferase, albumin, total protein, direct bilirubin, indirect bilirubin, uric acid, and phosphorus. Serum magnesium (Mg) levels at birth in infants with ROP were significantly higher than infants without ROP (p = 0.014). Conclusions: Serum Mg levels at birth were found to be higher in infants with ROP than in those without ROP. The levels may be dependent on the mothers’ treatment of Mg for different medical reasons.
基金supported in part by a grant from the Russian Foundation for Basic Research(Grant No.14-04-01653)
文摘Effects of two doses of the anti-diabetic drug, metformin (MF), on hormonal and metabolic levels of serum of non-diabetic male Wistar rats with 1,2-dimethylhydrazine (DMH)-induced colon tumor adenocarcinomas were studied. Carcinogenesis in the animals was also observed. Rats with DMH-induced colon adenocarcinomas had elevated levels of serum glucose, insulin, insulin- like growth factor-l, total cholesterol, triglycerides, catalase, malonic dialdehyde, glycated hemoglobin, aspartate aminotransferase, and alanine aminotransferase and decreased hemoglobin. Treatment with two doses of MF normalized maiority of these changes in DMH-treated rats, whereas the drug was ineffective in rats without DMH treatment. The only exception was the decreased triglyceride levels in MF-treated rats. A 100 mg/kg dose of MF increased DMH-induced exophytic colon carcinomas and decreased endophytic tumors compared with untreated rats. Moreover, both MF doses increased DMH-induced and highly differentiated tumors and decreased the invasiveness of colon carcinomas compared with rats provided with DMH and water. Therefore, effects of MF on metabolic homeostasis are critical for preventing colon cancer.
基金Supported by Grants from Indian Council of Medical Research,New Delhi and Council of Scientific and Industrial Research,New Delhi
文摘AIM: To assess the prognostic significance of cathepsin L, a cysteine protease that degrades the peri-tumoral tissue, in patients with pancreatic cancer.
文摘OBJECTIVE To observe the effect of curcumin on proliferation and apop-tosis in the prostate cancer LNCaP cell line. METHODS The AXSYMTM system luciferase method was used to examine the effect of various concentratious of curcumin on the content of prostate specific antigen (PSA) in prostate cancer LNCaP cells. A pGL3-PSA luciferase expression vector, containing 640 bp DNA of the PSA gene 5' -promoter region was constructed and transfected into the LNCaP cells with lipofectin. By measuring luciferase activity, the effect of 10 μmol/L, 20 μmol/L, 30 and 40 μmol/L curcumin on the promoter was studied. Effects on cell growth and apoptosis were analyzed by microscopy, the MTT colorimetric assay and flow cytometry. Western-blotting was used to measure expression of the androgen receptor (AR) in the LNCaP cells treated with different concentrations of curcumin. RESULTS The results showed that the expression of PSA was inhibited as curcumin reduced the activity of luciferase. Curcumin also caused a sigificant concentration-dependent decrease in AR expession measured by Western -blotting. Cell growth was inhibited and apoptosis was induced. CONCLUSION By inhibiting AR expression, curcumin reduced the function of the PSA promoter and inhibited PSA protein expression. Curcumin decreased the cellular proliferation and induced apoptosis in LNCaP cells in a concention-dependent manner.
文摘Diabetes mellitus (DM) is associated with platelet dysfunction. In diabetic patients, alterations in platelet functions, especially increased platelet agregation, have been suggested to cause increasing in cardiovascular morbidity and mortality or in accelaretion of athersclerotic process. In this study, we aimed to investigate the platelet aggregation response alterations and the effects of DM duration, HbA1c, treatment options among the patients with Type 2 DM. Fortyfive patients (case group;21 male, 24 female) with Type 2 DM and forty-eight healthy individuals (control group;22 male, 26 female) were included in this study. Platelet aggregation was determinated with Chorono-log 500 (USA) named device by using Chorono-log/ADP, Chorono-log/ collagen and Chorono-log/epinephrine kits. ADP-induced platelet aggregation was significantly higher in the case group compared with control group (p 【0.05). Epinephrine induced platelet aggregation were significant in negatively correlation with the diabetes duration (P 【0.05). Platelet aggregation responses did not differ according to their treatment type (sulphonylurea or insulin) was statistically insignificiant among the case groups (p 】0.05). In conclusion, our findings supported that type 2 diabetes may interfere with platelet functions without any relationship age, gender, the treatment types and the regulation levels. These findings supports that existence potential new factors or mechanism affecting platelet agregation. The subject requires more detailed studies in the future.
文摘Purpose: Retinopathy of prematurity (ROP), an abnormal proliferation of retinal vessels in premature infants with low birth weight, develops due to many factors. This study investigated a possible correlation between haematological parameters and ROP development. Method: This study included 189 infants without ROP and 128 with ROP. All were born at 35 weeks’ gestation or earlier, had a CBC drawn within 72 hours of birth, and had haemogram data for the first month. Haemoglobin (Hb), haematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), red cell distribution width (RDW), platelet counts (PLT), mean platelet volume (MPV) and platelet distribution width (PDW) values were obtained from hospital data and retrospectively analysed. Results: The mean gestational age was 31 weeks and 29 weeks for the control and ROP groups, respectively;the mean birth weights were 1757 g and 1332 g, respectively. The ROP group’s birth Hb, MCV and RDW were significantly lower than the control group (p p p p Conclusion: Premature infants with ROP had lower Hb and increased platelet, MPV and PDW in early postnatal life than infants without ROP. In the first month, when ROP develops, low PLT, PDW and Hb and high MPV could be indicators for ROP diagnosis, follow-up and treatment.
基金supported by the National Natural Science Foundation of China (No. 30570782).
文摘Objective: BCR/ABL oncoprotein-expression is associated with uncontrolled cell growth. Sphingosine kinase 1 (SPK1) regulates the production of sphingosine 1-phosphate (S1P), a key lipid signal molecular in cell proliferation and survival. The objective of this study was to elucidate the roles of S1P and its receptors in bcr/abl positive chronic myeloid leukemia (CML) cells. Methods: The expressions of SIP receptors: S1P1, S1P2 and S1P3 in CML cells were detected by RT-PCR. SPK1 expression, activity and extracellular S1P were determined in ECV304 and HL-60 cells which were transfected with bcr/abl gene. To elucidate the relationship between the BCR/ABL, ERK/MAPK (extracellular signal-regulated kinase/mitogen-activated protein kinase), SPK/S 1P and S 1P/S 1 P2 signal pathways, bcr/abl positive CML cell line K562 was treated with STI571, PD98059, N,N-dimethyl sphingosine (DMS) and JTE-013. Results: Retrovirus-mediated overexpression of bcr/abl gene in ECV304 and HL-60 cells resulted in upregulation of the expression, activity of SPK1 and increase of the secretion of SIP, whereas treatment of STI571 and PD98059 decreased the BCR/ABL-induced S1P secretion. Treatment of DMS reduced S1P secretion and P42/44MAPK phosphorylation. S1P2-selective antagonist JTE-013 could also decrease P42/44MAPK phosphorylation. Conclusion: These results suggest that BCR/ABL up-regulates extracellular sphingosine 1-phosphate through sphingosine kinase 1 and there is cross-talk between SPK1/S1P/S1P2 and P42/44MAPK in bcr/abl positive CML cells.