AIM:To investigate the effect of the neuropeptides bombesin(BBS)and neurotensin(NT)on oval cell proliferation in partially hepatectomized rats not pretreated with a known hepatocyte inhibitor.METHODS:Seventy male Wist...AIM:To investigate the effect of the neuropeptides bombesin(BBS)and neurotensin(NT)on oval cell proliferation in partially hepatectomized rats not pretreated with a known hepatocyte inhibitor.METHODS:Seventy male Wistar rats were randomly divided into five groups:Ⅰ=controls,Ⅱ=sham operated,Ⅲ=partial hepatectomy 70%(PHx),Ⅳ=PHx+ BBS(30μg/kg per day),Ⅴ=PHx+NT(300μg/kg per day).Forty eight hours after liver resection,portal en-dotoxin levels and hepatic glutathione redox state were determined.α-fetoprotein(AFP)mRNA(in situ hybridisation),cytokeratin-19 and Ki67 antigen expression (immunohistochemistry)and apoptosis(TUNEL)were evaluated on liver tissue samples.Cells with morphological features of oval cells that were cytokeratin-19 (+)and AFP mRNA(+)were scored in morphometric analysis and their proliferation was recorded.In addition,the proliferation and apoptotic rates of hepatocytes were determined.RESULTS:In the control and sham operated groups,oval cells were significantly less compared to groups Ⅲ,ⅣandⅤ(P<0.001).The neuropeptides BBS and NT significantly increased the proliferation of oval cells compared to groupⅢ(P<0.001).In addition,BBS and NT induced a significant increase of hepatocyte proliferation(P<0.001),whereas it decreased their apoptotic activity(P<0.001)compared to groupⅢ.BBS and NT significantly decreased portal endotoxemia (P<0.001)and increased the hepatic GSH:GSSG ratio (P<0.05 and P<0.001,respectively)compared to groupⅢ.CONCLUSION:BBS and NT stimulated oval cell proliferation in a model of liver regeneration,without use of concomitant suppression of hepatocyte proliferation as oval cell activation stimuli,and improved the hepatocyte regenerative response.This peptides-induced combined stimulation of oval cell and hepatocyte proliferation might serve as a possible treatment modality for several liver diseases.展开更多
Capsaicin(trans-8-methyl-N-vanillyl-6-nonenamide) is the main component in hot peppers, including red chili peppers, alapenos, and habanero, belonging to the genus Capsicum. Capsaicin is a potent antioxidant that inte...Capsaicin(trans-8-methyl-N-vanillyl-6-nonenamide) is the main component in hot peppers, including red chili peppers, alapenos, and habanero, belonging to the genus Capsicum. Capsaicin is a potent antioxidant that interferes with free radical activities. In the present study, the possible protective effect of capsaicin was studied against methyl methanesulphonate(MMS) induced toxicity in third instar larvae of transgenic Drosophila melanogaster(hsp70-lacZ)Bg^9. The third instar was allowed to feed on the diet having different doses of capsaicin and MMS separately and in combination. The results suggested that the exposure of third instar larvae to the diet having MMS alone showed significant hsp70 expression as well as tissue DNA and oxidative damage, whereas the larvae feed on the diet having MMS and capsaicin showed a decrease in the toxic effects for 48-h of exposure. In conclusion, capsaicin showed a dose-dependent decrease in the toxic effects induced by MMS in the third instar larvae of transgenic Drosophila melanogaster.展开更多
Seedlessness represents a highly appreciated trait in table grapes.Based on an interesting case of seedless fruit production described in the crop species Annona squamosa,we focused on the Vitis vinifera INNER NO OUTE...Seedlessness represents a highly appreciated trait in table grapes.Based on an interesting case of seedless fruit production described in the crop species Annona squamosa,we focused on the Vitis vinifera INNER NO OUTER(INO)gene as a candidate.This gene encodes a transcription factor belonging to the YABBY family involved in the determination of abaxial identity in several organs.In Arabidopsis thaliana,this gene was shown to be essential for the formation and asymmetric growth of the ovule outer integument and its mutation leads to a phenotypic defect of ovules and failure in seed formation.In this study,we identified in silico the V.vinifera orthologue and investigated its phylogenetic relationship to INO genes from other species and its expression in different organs in seeded and seedless varieties.Applying cross-species complementation,we have tested its functionality in the Arabidopsis ino-1 mutant.We show that the V.vinifera INO successfully rescues the ovule outer integument growth and seeds set and also partially complements the outer integument asymmetric growth in the Arabidopsis mutant,differently from orthologues from other species.These data demonstrate that VviINO retains similar activity and protein targets in grapevine as in Arabidopsis.Potential implications for grapevine breeding are discussed.展开更多
In the present study,we studied the effect of Genistein against the hepatotoxicity induced by N-nitrosodiethylamine（NDEA）.NDEA is present in almost all kinds of food stuff and has been reported to be a hepatocarcino...In the present study,we studied the effect of Genistein against the hepatotoxicity induced by N-nitrosodiethylamine（NDEA）.NDEA is present in almost all kinds of food stuff and has been reported to be a hepatocarcinogen.The male rats were exposed to NDEA（0.1 mg/mL） dissolved in drinking water separately and along with 25,50,100 mg/mL of Genistein for 21 days.The activities of serum glutamic oxaloacetic transaminase（SGOT）,serum glutamic pyruvic transaminase（SGPT）.alkaline phosphatase（ALP） and lactate dehydrogenase（LDH） were measured in blood serum.Lipid peroxidation,protein carbonyl content,micronucleus frequency and DNA damage（Comet assay） were performed on rat hepatocytes.The results of the study reveal that the treatment of NDEA along with Genistein showed a significant dose-dependent decrease in the levels of blood serum enzymes i.e.,SGOT,SGPT,ALP and LDH（P〈0.05）.The HE staining of histological sections of the liver also revealed a protective effect of Genistein.A significant dose-dependent reduction in the lipid peroxidation and protein carbonyl content was observed in rats exposed to NDEA（0.1 mg/mL） along with Genistein（P〈0.05）.The results obtained for the comet assay in rat hepatocytes showed a significant dose-dependent decrease in the mean tail length（P〈0.05）.Thus the present study supports the hepatoprotective role of Genistein.展开更多
AIM: To evaluate the effect of Ocimum sanctum leaf extract on the dietary supplementation in the transgenic Drosophila model of Parkinson's disease. METHOD: The effect of Ocimum sanctum leaf extract was studied on...AIM: To evaluate the effect of Ocimum sanctum leaf extract on the dietary supplementation in the transgenic Drosophila model of Parkinson's disease. METHOD: The effect of Ocimum sanctum leaf extract was studied on the transgenic Drosophila model of flies expressing normal human alpha synuclein(h-αs) in the neurons. O. sanctum extract at final concentrations of 0.042 8 × 10-4, 0.87 × 10-4, and 1.85 × 10-4 g·mL-1 of diet were established and the flies were allowed to feed for 21 days. The climbing assay and lipid peroxidation were taken as parameters for the study. RESULTS: The supplementation of O. sanctum extract showed a dose-dependent significant delay in the loss of climbing ability and reduction in oxidative stress in the brain of PD model flies. CONCLUSION: The results of the present study showed that the O. sanctum extract is potent in reducing the PD symptoms in transgenic Drosophila model.展开更多
OBJECTIVE To investigate apoptosis induced by Bax in hepatocellular carcinoma cells and to examine the results of 2 different routes for in vivo gene delivery. METHODS The anti-hepatocellular carcinoma activity of the...OBJECTIVE To investigate apoptosis induced by Bax in hepatocellular carcinoma cells and to examine the results of 2 different routes for in vivo gene delivery. METHODS The anti-hepatocellular carcinoma activity of the Bax gene transferred to the human hepatocellular carcinoma QGY7703 cell line was examined. In addition the Bax gene was transferred in vivo in mice via the caudal vein or hepatic artery to investigate the differences in target organ and non-target organ transfection. RESULTS 1）The Bax gene mediated by a binary adenoviral vector system induced apoptosis in the human hepatic carcinoma QFY7703 cell line. The cell apoptotic rate in the experimental group （Bax） was 50.2±6.9% but only 32.1 ± 9.7% in the Ad/CMV-p53 group, showing that the Bax-apoptotic rate was significantly higher than the control group. 2） LacZ expression was higher in the target organ （liver） when given through the hepatic artery than through the tail vein. In contrast, LacZ expression in the nontarget organs was higher if given through the tail vein compared to the hepatic artery. CONCLUSION Superselective hepatic artery delivery with Bax gene therapy is safe, specific, effective and has low toxicity. This study provided the basis for Bax-gene therapy via the hepatic artery in vivo.展开更多
Every disease treatment is ideally finalized to prevent symptom occurrence,to stop or slow down the progression of disease,to alleviate complications already present and consequently to improve the quality of life for...Every disease treatment is ideally finalized to prevent symptom occurrence,to stop or slow down the progression of disease,to alleviate complications already present and consequently to improve the quality of life for each patient.Unfortunately,in Parkinson’s disease(PD)a treatment able to completely cure the disease is not so far available.Indeed,until now,the current therapies only allow to control the disease symptoms,展开更多
AIM: To study histidine decarboxylase(HDC) expression in normal and neoplastic gastric neuroendocrine cells in relationship to the main histamine metabolite. METHODS: Control tissues from fundus(n = 3) and corpus(n = ...AIM: To study histidine decarboxylase(HDC) expression in normal and neoplastic gastric neuroendocrine cells in relationship to the main histamine metabolite. METHODS: Control tissues from fundus(n = 3) and corpus(n = 3) mucosa of six patients undergoing operations for gastric adenocarcinoma, biopsy and/or gastric surgical specimens from 64 patients with primary gastric neuroendocrine tumours(GNETs), as well as metastases from 22 of these patients, were investigated using conventional immunohistochemistry and double immunofluorescence with commercial antibodies vs vesicular monoamine transporter 2(VMAT-2), HDC and ghrelin. The urinary excretion of the main histamine metabolite methylimidazoleacetic acid(U-Me Im AA) was determined using highperformance liquid chromatography in 27 of the 64 patients.RESULTS: In the gastric mucosa of the control tissues, co-localization studies identified neuroendocrine cells that showed immunoreactivity only to VMAT-2 and others with reactivity only to HDC. A third cellpopulation co-expressed both antigens. There was no co-expression of HDC and ghrelin. Similar results were obtained in the foci of neuroendocrine cell hyperplasia associated with chronic atrophic gastritis type A and also in the tumours. The relative incidence of the three aforementioned markers varied in the tumours that were examined using conventional immunohistochemistry. All of these GNETs revealed both VMAT-2 and HDC immunoreactivity, and their metastases showed an immunohistochemical pattern and frequency similar to that of their primary tumours. In four patients, increased U-Me Im AA excretion was detected, but only two of the patients exhibited related endocrine symptoms. CONCLUSION: Human enterochromaffin-like cells appear to partially co-express VMAT-2 and HDC. Coexpression of VMAT-2 and HDC might be required for increased histamine production in patients with GNETs.展开更多
Over the past few years,it is observed an increased interest for oleaginous microorganisms in the perspective to produce microbial oils of great commercial interest through the consumption of low/zero cost substrates....Over the past few years,it is observed an increased interest for oleaginous microorganisms in the perspective to produce microbial oils of great commercial interest through the consumption of low/zero cost substrates.In this paper,the physiology of the fungus Umbelopsis isabellina growing on blends of glycerol and glucose was investigated.In all experiments the fungus completely consumed glucose and produced satisfactory quantities of biomass containing reserve lipids in high percentages.However,glycerol concentration in the growth medium was negatively correlated to glucose assimilation rate,mainly during the balanced-growth phase.Nevertheless,at high initial concentrations,glycerol was partially consumed and seemed to contribute positively to the suppression of lipid degradation.Following the discovery of this complex regulatory mechanism regarding glucose and glycerol co-assimilation,the activity of three key-enzymes namely aldolase,glycerol kinase and glycerol dehydrogenase,which are implicated in glycerol and glucose assimilation,was investigated.The experiments revealed a clear preference of the fungus for glucose over glycerol.On the other hand,storage polysaccharides are degraded instead of storage lipid at the late oleaginous phase for maintenance purpose.These new biochemical features will enable the design of appropriate growth media for the co-fermentation of these two substrates by U.isabellina with the aim to maximize lipid accumulation.展开更多
The plant hormone jasmonic acid （JA） is essential for stress responses and the formation of reproductive organs, but its role in fruit development and ripening is unclear. Conjugation of JA to isoleucine is a crucia...The plant hormone jasmonic acid （JA） is essential for stress responses and the formation of reproductive organs, but its role in fruit development and ripening is unclear. Conjugation of JA to isoleucine is a crucial step in the JA signaling pathway since only JA-Ile is recognized by the jasmonate receptor. The conjugation reaction is catalyzed by JA-amido synthetases, belonging to the family of Gretchen Hagen3 （GH3） proteins. Here, in vitro studies of two grapevine （Vitis vinifera L. cv Shiraz） GH3 enzymes, VvGH3-7 and VvGH3-9, demonstrated JA-conjugating activ- ities with an overlapping range of amino acid substrates, including isoleucine. Expression studies of the correspond- ing genes in grape berries combined with JA and JA-lle measurements suggested a primary role for JA signaling in fruit set and cell division and did not support an involvement of JA in the ripening process. In response to methyl JA （MeJA） treatment, and in wounded and unwounded （distal）leaves, VvGH3-9 transcripts accumulated, indicating a participation in the JA response. In contrast, VvGH3-7 was unresponsive to MeJA and local wounding, demonstrating a differential transcriptional regulation of VvGH3-7 and VvGH3- 9. The transient induction of VvGH3-7 in unwounded, distal leaves was suggestive of the involvement of an unknown mobile wound signal.展开更多
Asexually reproducing fungi play a significant role in essential processes in managed and wild ecosystems such as nutrients cycling and multitrophic interactions.A large number of such taxa are among the most notoriou...Asexually reproducing fungi play a significant role in essential processes in managed and wild ecosystems such as nutrients cycling and multitrophic interactions.A large number of such taxa are among the most notorious plant and animal pathogens.In addition,they have a key role in food production,biotechnology and medicine.Taxa without or rare sexual reproduction are distinguished based on their sporulating structures and conidiomata in traditional morphology-based taxonomy.The number,variation and diversity of asexually reproducing taxa are insufficiently known,even though fungi capable of asexual reproduction may provide an untapped,rich biological resource for future exploitation.Currently,ca.30,000 asexual species belonging to ca.3800 genera have been reported(including 1388 coelomycetous and 2265 hyphomycetous genera).Recent reports(2017–2020)reiterate that the number of asexually producing fungi is higher than the number of frequently sexually-reproducing fungi.With the advent of molecular tools and the abandonment of the dual nomenclature system for pleomorphic fungi,priority criteria were established and revisited in the latest outline of fungi and fungus-like taxa.However,species numbers and taxonomic boundaries of pleomorphic taxa and their synanamorphs or synasexual morphs have yet to be addressed.The number of species of speciose genera(e.g.Alternaria,Aspergillus,Cercospora,Fusarium,Phoma and Pseudocercospora),cryptic species,species of pleomorphic genera,less studied life modes(such as lichenicolous taxa,taxa from extreme environments)and species from biodiversity-rich areas still need evaluation to achieve more reliable estimates of their diversity.This paper discusses the current knowledge on the matter,with diversity estimates,and potential obstacles in several chapters on(1)speciose genera;(2)pleomorphic genera;(3)cryptic species;(4)well-studied but insufficiently resolved taxa,e.g.leaf inhabiting species,marine fungi,(5)less studied life modes,e.g.lichenicolous,rock-inhabiting fungi,insect-associated and yeast-forming taxa and(6)species from biodiversity-rich areas.展开更多
X-linked redegreen color blindness is the most widespread form of vision impairment.The study aimed to determine the prevalence and gene frequencies of redegreen color vision impairments among children of six differen...X-linked redegreen color blindness is the most widespread form of vision impairment.The study aimed to determine the prevalence and gene frequencies of redegreen color vision impairments among children of six different human populations of Jammu province.A total of 1028 healthy subjects(6e15 years of age)were selected from five Muslim populations and the color vision impairments were determined using the Ishihara’s test of color deficiency.The gene frequency was calculated using HardyeWeinberg equilibrium method.The prevalence of color vision deficiency(CVD)ranged from 5.26%to 11.36%among males and 0.00%e3.03%among females of six different populations.The gender based differences in the frequency of CVD was found to be statistically significant(p<0.0001),with a higher prevalence among male(7.52%)as compared to female(0.83%)children.We observed high frequency of deutan as compared to protan defects.The incidences of deuteranomaly(5.68%)and deuteranopia(2.27%)were higher among male children of Syed population while the frequencies of protanomaly(1.94%),protanopia(1.28%)and achromacy(2.27%)were the highest among male subjects of Khan,Malik and Syed populations,respectively.The allele and genotype frequencies showed cogent differences among six populations.The population based assessment of CVDs help patients to follow adaptive strategies that could minimize the risks of the disease.展开更多
Ubiquitin regulatory X(UBX)domain-containing protein 6(UBXN6)is an essential cofactor for the activity of the valosin-containing protein p97,an adenosine triphosphatase associated with diverse cellular activities.None...Ubiquitin regulatory X(UBX)domain-containing protein 6(UBXN6)is an essential cofactor for the activity of the valosin-containing protein p97,an adenosine triphosphatase associated with diverse cellular activities.Nonetheless,its role in cells of the innate immune system remains largely unexplored.In this study,we report that UBXN6 is upregulated in humans with sepsis and may serve as a pivotal regulator of inflammatory responses via the activation of autophagy.Notably,the upregulation of UBXN6 in sepsis patients was negatively correlated with inflammatory gene profiles but positively correlated with the expression of Forkhead box O3,an autophagy-driving transcription factor.Compared with those of control mice,the macrophages of mice subjected to myeloid cell-specific UBXN6 depletion exhibited exacerbated inflammation,increased mitochondrial oxidative stress,and greater impairment of autophagy and endoplasmic reticulum-associated degradation pathways.UBXN6-deficient macrophages also exhibited immunometabolic remodeling,characterized by a shift to aerobic glycolysis and elevated levels of branched-chain amino acids.These metabolic shifts amplify mammalian target of rapamycin pathway signaling,in turn reducing the nuclear translocation of the transcription factor EB and impairing lysosomal biogenesis.Together,these data reveal that UBXN6 serves as an activator of autophagy and regulates inflammation to maintain immune system suppression during human sepsis.展开更多
Mutations in DNA repair enzymes can cause two neurological clinical manifestations:a developmental impairment and a degenerative disease.Polynucleotide kinase 3′-phosphatase(PNKP)is an enzyme that is actively involve...Mutations in DNA repair enzymes can cause two neurological clinical manifestations:a developmental impairment and a degenerative disease.Polynucleotide kinase 3′-phosphatase(PNKP)is an enzyme that is actively involved in DNA repair in both single and double strand break repair systems.Mutations in this protein or others in the same pathway are responsible for a complex group of diseases with a broad clinical spectrum.Besides,mitochondrial dysfunction also has been consolidated as a hallmark of brain degeneration.Here we provide evidence that supports a shared role between mitochondrial dysfunction and DNA repair defects in the pathogenesis of the nervous system.As models,we analyze PNKP-related disorders,focusing on Charcot-Marie-Tooth disease and ataxia.A better understanding of the molecular dynamics of this relationship could provide improved diagnosis and treatment for neurological diseases.展开更多
文摘AIM:To investigate the effect of the neuropeptides bombesin(BBS)and neurotensin(NT)on oval cell proliferation in partially hepatectomized rats not pretreated with a known hepatocyte inhibitor.METHODS:Seventy male Wistar rats were randomly divided into five groups:Ⅰ=controls,Ⅱ=sham operated,Ⅲ=partial hepatectomy 70%(PHx),Ⅳ=PHx+ BBS(30μg/kg per day),Ⅴ=PHx+NT(300μg/kg per day).Forty eight hours after liver resection,portal en-dotoxin levels and hepatic glutathione redox state were determined.α-fetoprotein(AFP)mRNA(in situ hybridisation),cytokeratin-19 and Ki67 antigen expression (immunohistochemistry)and apoptosis(TUNEL)were evaluated on liver tissue samples.Cells with morphological features of oval cells that were cytokeratin-19 (+)and AFP mRNA(+)were scored in morphometric analysis and their proliferation was recorded.In addition,the proliferation and apoptotic rates of hepatocytes were determined.RESULTS:In the control and sham operated groups,oval cells were significantly less compared to groups Ⅲ,ⅣandⅤ(P<0.001).The neuropeptides BBS and NT significantly increased the proliferation of oval cells compared to groupⅢ(P<0.001).In addition,BBS and NT induced a significant increase of hepatocyte proliferation(P<0.001),whereas it decreased their apoptotic activity(P<0.001)compared to groupⅢ.BBS and NT significantly decreased portal endotoxemia (P<0.001)and increased the hepatic GSH:GSSG ratio (P<0.05 and P<0.001,respectively)compared to groupⅢ.CONCLUSION:BBS and NT stimulated oval cell proliferation in a model of liver regeneration,without use of concomitant suppression of hepatocyte proliferation as oval cell activation stimuli,and improved the hepatocyte regenerative response.This peptides-induced combined stimulation of oval cell and hepatocyte proliferation might serve as a possible treatment modality for several liver diseases.
文摘Capsaicin(trans-8-methyl-N-vanillyl-6-nonenamide) is the main component in hot peppers, including red chili peppers, alapenos, and habanero, belonging to the genus Capsicum. Capsaicin is a potent antioxidant that interferes with free radical activities. In the present study, the possible protective effect of capsaicin was studied against methyl methanesulphonate(MMS) induced toxicity in third instar larvae of transgenic Drosophila melanogaster(hsp70-lacZ)Bg^9. The third instar was allowed to feed on the diet having different doses of capsaicin and MMS separately and in combination. The results suggested that the exposure of third instar larvae to the diet having MMS alone showed significant hsp70 expression as well as tissue DNA and oxidative damage, whereas the larvae feed on the diet having MMS and capsaicin showed a decrease in the toxic effects for 48-h of exposure. In conclusion, capsaicin showed a dose-dependent decrease in the toxic effects induced by MMS in the third instar larvae of transgenic Drosophila melanogaster.
文摘Seedlessness represents a highly appreciated trait in table grapes.Based on an interesting case of seedless fruit production described in the crop species Annona squamosa,we focused on the Vitis vinifera INNER NO OUTER(INO)gene as a candidate.This gene encodes a transcription factor belonging to the YABBY family involved in the determination of abaxial identity in several organs.In Arabidopsis thaliana,this gene was shown to be essential for the formation and asymmetric growth of the ovule outer integument and its mutation leads to a phenotypic defect of ovules and failure in seed formation.In this study,we identified in silico the V.vinifera orthologue and investigated its phylogenetic relationship to INO genes from other species and its expression in different organs in seeded and seedless varieties.Applying cross-species complementation,we have tested its functionality in the Arabidopsis ino-1 mutant.We show that the V.vinifera INO successfully rescues the ovule outer integument growth and seeds set and also partially complements the outer integument asymmetric growth in the Arabidopsis mutant,differently from orthologues from other species.These data demonstrate that VviINO retains similar activity and protein targets in grapevine as in Arabidopsis.Potential implications for grapevine breeding are discussed.
基金Science and Engineering Research Board(SERB),Department of Science & Technology,Technology Bhavan,New Delhi,India,for the sanction of the research project (No.SR/FT/LS-60/2011) to Dr.Yasir Hasan Siddique
文摘In the present study,we studied the effect of Genistein against the hepatotoxicity induced by N-nitrosodiethylamine（NDEA）.NDEA is present in almost all kinds of food stuff and has been reported to be a hepatocarcinogen.The male rats were exposed to NDEA（0.1 mg/mL） dissolved in drinking water separately and along with 25,50,100 mg/mL of Genistein for 21 days.The activities of serum glutamic oxaloacetic transaminase（SGOT）,serum glutamic pyruvic transaminase（SGPT）.alkaline phosphatase（ALP） and lactate dehydrogenase（LDH） were measured in blood serum.Lipid peroxidation,protein carbonyl content,micronucleus frequency and DNA damage（Comet assay） were performed on rat hepatocytes.The results of the study reveal that the treatment of NDEA along with Genistein showed a significant dose-dependent decrease in the levels of blood serum enzymes i.e.,SGOT,SGPT,ALP and LDH（P〈0.05）.The HE staining of histological sections of the liver also revealed a protective effect of Genistein.A significant dose-dependent reduction in the lipid peroxidation and protein carbonyl content was observed in rats exposed to NDEA（0.1 mg/mL） along with Genistein（P〈0.05）.The results obtained for the comet assay in rat hepatocytes showed a significant dose-dependent decrease in the mean tail length（P〈0.05）.Thus the present study supports the hepatoprotective role of Genistein.
文摘AIM: To evaluate the effect of Ocimum sanctum leaf extract on the dietary supplementation in the transgenic Drosophila model of Parkinson's disease. METHOD: The effect of Ocimum sanctum leaf extract was studied on the transgenic Drosophila model of flies expressing normal human alpha synuclein(h-αs) in the neurons. O. sanctum extract at final concentrations of 0.042 8 × 10-4, 0.87 × 10-4, and 1.85 × 10-4 g·mL-1 of diet were established and the flies were allowed to feed for 21 days. The climbing assay and lipid peroxidation were taken as parameters for the study. RESULTS: The supplementation of O. sanctum extract showed a dose-dependent significant delay in the loss of climbing ability and reduction in oxidative stress in the brain of PD model flies. CONCLUSION: The results of the present study showed that the O. sanctum extract is potent in reducing the PD symptoms in transgenic Drosophila model.
文摘OBJECTIVE To investigate apoptosis induced by Bax in hepatocellular carcinoma cells and to examine the results of 2 different routes for in vivo gene delivery. METHODS The anti-hepatocellular carcinoma activity of the Bax gene transferred to the human hepatocellular carcinoma QGY7703 cell line was examined. In addition the Bax gene was transferred in vivo in mice via the caudal vein or hepatic artery to investigate the differences in target organ and non-target organ transfection. RESULTS 1）The Bax gene mediated by a binary adenoviral vector system induced apoptosis in the human hepatic carcinoma QFY7703 cell line. The cell apoptotic rate in the experimental group （Bax） was 50.2±6.9% but only 32.1 ± 9.7% in the Ad/CMV-p53 group, showing that the Bax-apoptotic rate was significantly higher than the control group. 2） LacZ expression was higher in the target organ （liver） when given through the hepatic artery than through the tail vein. In contrast, LacZ expression in the nontarget organs was higher if given through the tail vein compared to the hepatic artery. CONCLUSION Superselective hepatic artery delivery with Bax gene therapy is safe, specific, effective and has low toxicity. This study provided the basis for Bax-gene therapy via the hepatic artery in vivo.
文摘Every disease treatment is ideally finalized to prevent symptom occurrence,to stop or slow down the progression of disease,to alleviate complications already present and consequently to improve the quality of life for each patient.Unfortunately,in Parkinson’s disease(PD)a treatment able to completely cure the disease is not so far available.Indeed,until now,the current therapies only allow to control the disease symptoms,
基金Supported by The Selander Foundation and the Foundation for Clinical Cancer Research in Jönköping
文摘AIM: To study histidine decarboxylase(HDC) expression in normal and neoplastic gastric neuroendocrine cells in relationship to the main histamine metabolite. METHODS: Control tissues from fundus(n = 3) and corpus(n = 3) mucosa of six patients undergoing operations for gastric adenocarcinoma, biopsy and/or gastric surgical specimens from 64 patients with primary gastric neuroendocrine tumours(GNETs), as well as metastases from 22 of these patients, were investigated using conventional immunohistochemistry and double immunofluorescence with commercial antibodies vs vesicular monoamine transporter 2(VMAT-2), HDC and ghrelin. The urinary excretion of the main histamine metabolite methylimidazoleacetic acid(U-Me Im AA) was determined using highperformance liquid chromatography in 27 of the 64 patients.RESULTS: In the gastric mucosa of the control tissues, co-localization studies identified neuroendocrine cells that showed immunoreactivity only to VMAT-2 and others with reactivity only to HDC. A third cellpopulation co-expressed both antigens. There was no co-expression of HDC and ghrelin. Similar results were obtained in the foci of neuroendocrine cell hyperplasia associated with chronic atrophic gastritis type A and also in the tumours. The relative incidence of the three aforementioned markers varied in the tumours that were examined using conventional immunohistochemistry. All of these GNETs revealed both VMAT-2 and HDC immunoreactivity, and their metastases showed an immunohistochemical pattern and frequency similar to that of their primary tumours. In four patients, increased U-Me Im AA excretion was detected, but only two of the patients exhibited related endocrine symptoms. CONCLUSION: Human enterochromaffin-like cells appear to partially co-express VMAT-2 and HDC. Coexpression of VMAT-2 and HDC might be required for increased histamine production in patients with GNETs.
基金financed by the Green Fund of the Hellenic Ministry of Environment and Energy,under the funding program“National Environment and Innovation Activities 2022”,Priority Axis“Research&Application”,Project“Sustainable technology for converting pomegranate residues into bioproducts and bioactive compounds”with the acronym“POMEGRANATE”.
文摘Over the past few years,it is observed an increased interest for oleaginous microorganisms in the perspective to produce microbial oils of great commercial interest through the consumption of low/zero cost substrates.In this paper,the physiology of the fungus Umbelopsis isabellina growing on blends of glycerol and glucose was investigated.In all experiments the fungus completely consumed glucose and produced satisfactory quantities of biomass containing reserve lipids in high percentages.However,glycerol concentration in the growth medium was negatively correlated to glucose assimilation rate,mainly during the balanced-growth phase.Nevertheless,at high initial concentrations,glycerol was partially consumed and seemed to contribute positively to the suppression of lipid degradation.Following the discovery of this complex regulatory mechanism regarding glucose and glycerol co-assimilation,the activity of three key-enzymes namely aldolase,glycerol kinase and glycerol dehydrogenase,which are implicated in glycerol and glucose assimilation,was investigated.The experiments revealed a clear preference of the fungus for glucose over glycerol.On the other hand,storage polysaccharides are degraded instead of storage lipid at the late oleaginous phase for maintenance purpose.These new biochemical features will enable the design of appropriate growth media for the co-fermentation of these two substrates by U.isabellina with the aim to maximize lipid accumulation.
基金funded by Australia's grape growers and winemakers through their investment body the Grape and Wine ResearchDevelopment Corporation(grant no.CSP 09/05) with matching funding from the Australian Federal Government
文摘The plant hormone jasmonic acid （JA） is essential for stress responses and the formation of reproductive organs, but its role in fruit development and ripening is unclear. Conjugation of JA to isoleucine is a crucial step in the JA signaling pathway since only JA-Ile is recognized by the jasmonate receptor. The conjugation reaction is catalyzed by JA-amido synthetases, belonging to the family of Gretchen Hagen3 （GH3） proteins. Here, in vitro studies of two grapevine （Vitis vinifera L. cv Shiraz） GH3 enzymes, VvGH3-7 and VvGH3-9, demonstrated JA-conjugating activ- ities with an overlapping range of amino acid substrates, including isoleucine. Expression studies of the correspond- ing genes in grape berries combined with JA and JA-lle measurements suggested a primary role for JA signaling in fruit set and cell division and did not support an involvement of JA in the ripening process. In response to methyl JA （MeJA） treatment, and in wounded and unwounded （distal）leaves, VvGH3-9 transcripts accumulated, indicating a participation in the JA response. In contrast, VvGH3-7 was unresponsive to MeJA and local wounding, demonstrating a differential transcriptional regulation of VvGH3-7 and VvGH3- 9. The transient induction of VvGH3-7 in unwounded, distal leaves was suggestive of the involvement of an unknown mobile wound signal.
基金supported by the National Natural Science Foundation of China(No.NSFC 31950410558,NSFC 31760013)Department of Science and Technology of Yunnan Province(No.2018FB050)+2 种基金the State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University(No.FAMP201906K)Science and Technology Department of Guizhou Province(QKHRCPT[2017]5101)High-Level Talent Recruitment Plan of Yunnan Provinces("Young Talents"Program and"High-End Foreign Experts"Program).
文摘Asexually reproducing fungi play a significant role in essential processes in managed and wild ecosystems such as nutrients cycling and multitrophic interactions.A large number of such taxa are among the most notorious plant and animal pathogens.In addition,they have a key role in food production,biotechnology and medicine.Taxa without or rare sexual reproduction are distinguished based on their sporulating structures and conidiomata in traditional morphology-based taxonomy.The number,variation and diversity of asexually reproducing taxa are insufficiently known,even though fungi capable of asexual reproduction may provide an untapped,rich biological resource for future exploitation.Currently,ca.30,000 asexual species belonging to ca.3800 genera have been reported(including 1388 coelomycetous and 2265 hyphomycetous genera).Recent reports(2017–2020)reiterate that the number of asexually producing fungi is higher than the number of frequently sexually-reproducing fungi.With the advent of molecular tools and the abandonment of the dual nomenclature system for pleomorphic fungi,priority criteria were established and revisited in the latest outline of fungi and fungus-like taxa.However,species numbers and taxonomic boundaries of pleomorphic taxa and their synanamorphs or synasexual morphs have yet to be addressed.The number of species of speciose genera(e.g.Alternaria,Aspergillus,Cercospora,Fusarium,Phoma and Pseudocercospora),cryptic species,species of pleomorphic genera,less studied life modes(such as lichenicolous taxa,taxa from extreme environments)and species from biodiversity-rich areas still need evaluation to achieve more reliable estimates of their diversity.This paper discusses the current knowledge on the matter,with diversity estimates,and potential obstacles in several chapters on(1)speciose genera;(2)pleomorphic genera;(3)cryptic species;(4)well-studied but insufficiently resolved taxa,e.g.leaf inhabiting species,marine fungi,(5)less studied life modes,e.g.lichenicolous,rock-inhabiting fungi,insect-associated and yeast-forming taxa and(6)species from biodiversity-rich areas.
文摘X-linked redegreen color blindness is the most widespread form of vision impairment.The study aimed to determine the prevalence and gene frequencies of redegreen color vision impairments among children of six different human populations of Jammu province.A total of 1028 healthy subjects(6e15 years of age)were selected from five Muslim populations and the color vision impairments were determined using the Ishihara’s test of color deficiency.The gene frequency was calculated using HardyeWeinberg equilibrium method.The prevalence of color vision deficiency(CVD)ranged from 5.26%to 11.36%among males and 0.00%e3.03%among females of six different populations.The gender based differences in the frequency of CVD was found to be statistically significant(p<0.0001),with a higher prevalence among male(7.52%)as compared to female(0.83%)children.We observed high frequency of deutan as compared to protan defects.The incidences of deuteranomaly(5.68%)and deuteranopia(2.27%)were higher among male children of Syed population while the frequencies of protanomaly(1.94%),protanopia(1.28%)and achromacy(2.27%)were the highest among male subjects of Khan,Malik and Syed populations,respectively.The allele and genotype frequencies showed cogent differences among six populations.The population based assessment of CVDs help patients to follow adaptive strategies that could minimize the risks of the disease.
基金supported by the National Research Foundation of Korea(NRF)grants funded by the Korea government(MSIT)(RS-2023-00255021,RS-2023-00227274,and RS-2024-00406568).
文摘Ubiquitin regulatory X(UBX)domain-containing protein 6(UBXN6)is an essential cofactor for the activity of the valosin-containing protein p97,an adenosine triphosphatase associated with diverse cellular activities.Nonetheless,its role in cells of the innate immune system remains largely unexplored.In this study,we report that UBXN6 is upregulated in humans with sepsis and may serve as a pivotal regulator of inflammatory responses via the activation of autophagy.Notably,the upregulation of UBXN6 in sepsis patients was negatively correlated with inflammatory gene profiles but positively correlated with the expression of Forkhead box O3,an autophagy-driving transcription factor.Compared with those of control mice,the macrophages of mice subjected to myeloid cell-specific UBXN6 depletion exhibited exacerbated inflammation,increased mitochondrial oxidative stress,and greater impairment of autophagy and endoplasmic reticulum-associated degradation pathways.UBXN6-deficient macrophages also exhibited immunometabolic remodeling,characterized by a shift to aerobic glycolysis and elevated levels of branched-chain amino acids.These metabolic shifts amplify mammalian target of rapamycin pathway signaling,in turn reducing the nuclear translocation of the transcription factor EB and impairing lysosomal biogenesis.Together,these data reveal that UBXN6 serves as an activator of autophagy and regulates inflammation to maintain immune system suppression during human sepsis.
基金Support from the University of Costa Rica is gratefully acknowledged(project 111-B2-372).
文摘Mutations in DNA repair enzymes can cause two neurological clinical manifestations:a developmental impairment and a degenerative disease.Polynucleotide kinase 3′-phosphatase(PNKP)is an enzyme that is actively involved in DNA repair in both single and double strand break repair systems.Mutations in this protein or others in the same pathway are responsible for a complex group of diseases with a broad clinical spectrum.Besides,mitochondrial dysfunction also has been consolidated as a hallmark of brain degeneration.Here we provide evidence that supports a shared role between mitochondrial dysfunction and DNA repair defects in the pathogenesis of the nervous system.As models,we analyze PNKP-related disorders,focusing on Charcot-Marie-Tooth disease and ataxia.A better understanding of the molecular dynamics of this relationship could provide improved diagnosis and treatment for neurological diseases.
