The family Alaudidae,larks,comprises 93-100 species(depending on taxonomy)that are widely distributed across Africa and Eurasia,with single species extending their ranges to North and northernmost South America and Au...The family Alaudidae,larks,comprises 93-100 species(depending on taxonomy)that are widely distributed across Africa and Eurasia,with single species extending their ranges to North and northernmost South America and Australia.A decade-old molecular phylogeny,comprising~80%of the species,revealed multiple cases of parallel evolution and large variation in rates of morphological evolution,which had misled taxonomists into creating many non-monophyletic genera.Here,we reconstruct the phylogeny of the larks,using a dataset covering one mitochondrial and 16 nuclear loci and comprising all except one of the currently recognised species as well as several recently proposed new species(in total 133 taxa;not all loci available for all species).We provide additional support using genome-wide markers to infer a genus-level phylogeny based on near-complete generic sampling(in total 51 samples of 44 taxa across 40 species).Our results confirm the previous findings of rampant morphological convergence and divergence,and reveal new cases of paraphyletic genera.We propose a new subfamily classification,and also that the genus Mirafra is divided into four genera to produce a more balanced generic classification of the Alaudidae.Our study supports recently proposed species splits as well as some recent lumps,while also questioning some of the latter.This comprehensive phylogeny will form an important basis for future studies,such as comparative studies of lark natural history,ecology,evolution and conservation.展开更多
BACKGROUND It is known that under conditions of tissue tolerance to insulin,observed during type 2 diabetes mellitus(DM2),there is an increased production of reactive oxygen species.Moreover,the free radicals can init...BACKGROUND It is known that under conditions of tissue tolerance to insulin,observed during type 2 diabetes mellitus(DM2),there is an increased production of reactive oxygen species.Moreover,the free radicals can initiate lipid peroxidation(LPO)in lipoprotein particles.The concentration of LPO products can influence the state of insulin receptors,repressing their hormone connection activity,which is expressed as a reduction of the glucose consumption by cells.It is possible that reduction in glucose concentration during administration of 10-(6-plastoquinonyl)decyltriphenylphosphonium(SkQ1)to rats with DM2 may be related to the antioxidant properties of this substance.AIM To establish the influence of SkQ1 on free-radical homeostasis in the heart and blood serum of rats with streptozotocin-induced hyperglycemia.METHODS To induce hyperglycemia,rats were fed a high-fat diet for 1 mo and then administered two intra-abdominal injections of streptozotocin with a 7-d interval at a 30 mg/kg of animal weight dose with citrate buffer equal to pH 4.4.SkQ1 solution was administered intraperitoneally at a 1250 nmol/kg dose per day.Tissue samples were taken from control animals,animals with experimental hyperglycemia,rats with streptozotocin-induced glycemia that were administered SkQ1 solution,animals housed under standard vivarium conditions that were administered SkQ1,rats that were administered intraperitoneally citrate buffer equal to pH 4.4 once a week during 2 wk after 1-mo high-fat diet,and animals that were administered intraperitoneally with appropriate amount of solution without SkQ1(98%ethanol diluted eight times with normal saline solution).To determine the intensity of free radical oxidation and total antioxidant activity,we used the biochemiluminescence method.Aconitate hydratase(AH),superoxide dismutase,and catalase activities were estimated using the Hitachi U-1900 spectrophotometer supplied with software.The amount of citrate was determined by means of the Natelson method.Real-time polymerase chain reaction was carried out using an amplifier ANK-32.RESULTS It was found that the mitochondrial-directed antioxidant elicits decrease of biochemiluminescence parameter values that increase by pathology as well as the levels of primary products of LPO,such as diene conjugates and carbonyl compounds,which indicate intensity of free radical oxidation.At the same time,the activity of AH,considered a crucial target of free radicals,which decreased during experimental hyperglycemia,increased.Apparently,increasing activity of AH influenced the speed of citrate utilization,whose concentration decreased after administering SkQ1 by pathology.Moreover,the previously applied antioxidant during hyperglycemia influenced the rate of antioxidant system mobilization.Thus,superoxide dismutase and catalase activity,as well as the level of gene transcript under influence of SkQ1 at pathology,were changing to the direction of control groups values.CONCLUSION According to the results of performed research,SkQ1 can be considered a promising addition to be included in antioxidant therapy of DM2.展开更多
Campylobacter species are a major cause of foodborne bacterial infections in both developed and developing countries worldwide.Campylobacter jejuni is responsible for the majority of infectio ns.This study was con duc...Campylobacter species are a major cause of foodborne bacterial infections in both developed and developing countries worldwide.Campylobacter jejuni is responsible for the majority of infectio ns.This study was con ducted to identify virule nceassociated genes in Campylobacter species isolated from livestock production systems in South Africa.A total of 250 fecal samples consisting of cattle(n=50),chickens(n=50),goats(n=50),sheep(n=50)and pigs(n=50)were randomly collected from livestock in Eastern Cape and KwaZulu-Natal provinces of South Africa between April and October 2018.The samples were an a lyzed for the presence of virule nee genes in Campylobacter species using molecular PCR-based methods.It was found that 77 and 23%of Campylobacter jejuni and Campylobacter coli respectively were isolated from all the livestock samples.There were positive significant(P<0.05)correlations amongst all the virulenee genes that were investigated.Chisquare and Fisher's exact tests were implemented to test for the effect of livestock species on the presenee or absenee of virule nee gen es.The study dem on strated that most of livestock species can pote ntially cause zoonotic infecti on s and food pois oning due to the high prevale nee of Campylobacter.The high prevale nee of virule nee genes highlights the sign ifica nee of Campylobacter\r\livestock production systems in South Africa.This requires the implementation of one-health approaches to reduce the impact of foodborne and zoonotic diseases for the welfare of human and animal health.展开更多
OBJECTIVE GubenyiliuⅡ(GYⅡ),a traditional Chinese medicine(TCM)formula used in our hospital,has shown beneficial effects in cancer patients.In this study,we investigated the molecular mechanisms underlying the benefi...OBJECTIVE GubenyiliuⅡ(GYⅡ),a traditional Chinese medicine(TCM)formula used in our hospital,has shown beneficial effects in cancer patients.In this study,we investigated the molecular mechanisms underlying the beneficial effects of GYⅡon murine breast cancer models.METHODS Inhibition of tumor growth and metastasis was evaluated by assessment of tumor weight and analysis of bioluminescent signal after a homograft inoculation.Viability of cultured breast cancer cells was determined using MTT assay andreal-time cell analysis(RTCA).Cell migratory ability was evaluated by Transwell?assay and wound healing assay.Subsequently,the potential anti-tumor and anti-metastatic mechanism was investigated by Western blotting and Immunohistochemistry.RESULTS GYⅡshowed significant inhibitory effects on tumor growth and metastasis in the murine breast cancer model.And GYⅡsuppressed theproliferation of 4T1 and MCF-7 cells in a dose-dependent manner.A better inhibitory effect on 4T1 cells proliferation and migration was found in sub-fractions(SF)of GYⅡ.Moreover,heparanase expression and degree of angiogenesis were reduced in tumor tissues.Western blotting analysis showed decreased expression of heparanase and growth factors in the cells treated with GYⅡand its sub-fractions(SF2 and SF3),there by a reduction in phosphorylation of ERK and AKT.CONCLUSION GYⅡexerts anti-tumor growth and anti-metastatic effects on murine breast cancer model.Sub-fractions 2 and 3 exhibits higher potency of the anti-tumor activity that is,at least partly,associated with decreased heparanase and growth factor sexpression,which subsequently sup-pressed activation of ERK and AKT pathways.展开更多
Medulloblastomas(MBs)are the most prevalent brain tumours in children.They are classified as grade IV,the highest in malignancy,with about 30%metastatic tumours at the time of diagnosis.Cancer stem cells(CSCs)are a sm...Medulloblastomas(MBs)are the most prevalent brain tumours in children.They are classified as grade IV,the highest in malignancy,with about 30%metastatic tumours at the time of diagnosis.Cancer stem cells(CSCs)are a small subset of tumour cells that can initiate and support tumour growth.In MB,CSCs contribute to tumour initiation,metastasis,and therapy resistance.Metabolic differences among the different MB groups have started to emerge.Sonic hedgehog tumours show enriched lipid and nucleic acid metabolism pathways,whereas Group 3 MBs upregulate glycolysis,gluconeogenesis,glutamine anabolism,and glutathione-mediated anti-oxidant pathways.Such differences impact the clinical behaviour of MB tumours and can be exploited therapeutically.In this review,we summarise the existing knowledge about metabolic rewiring in MB,with a particular focus on MB-CSCs.Finally,we highlight some of the emerging metabolism-based therapeutic strategies for MB.展开更多
Hepatocellular carcinoma(HCC) is one of the most common and deadly cancers worldwide. In ninety percent of the cases it develops as a result of chronic liver damage and it is thus a typical inflammationrelated cancer ...Hepatocellular carcinoma(HCC) is one of the most common and deadly cancers worldwide. In ninety percent of the cases it develops as a result of chronic liver damage and it is thus a typical inflammationrelated cancer characterized by the close relation between the tumor microenvironment and tumor cells. The stromal environment consists out of several cell types, including hepatic stellate cells, macrophages and endothelial cells. They are not just active bystanders in the pathogenesis of HCC, but play an important and active role in tumor initiation, progression and metastasis. Furthermore, the tumor itself influences these cells to create a background that is beneficial for sustaining tumor growth. One of the key players is the hepatic stellate cell, which is activated during liver damage and differentiates towards a myofibroblast-like cell. Activated stellate cells are responsible for the deposition of extracellular matrix, increase the production of angiogenic factors and stimulate the recruitment of macrophages. The increase of angiogenic factors(which are secreted by macrophages, tumor cells and activated stellate cells) will induce the formation of new blood vessels, thereby supplying the tumor with more oxygen and nutrients, thus supporting tumor growth and offering a passageway in the circulatory system. In addition, the secretion of chemokines by the tumor cells leads to the recruitment of tumor associated macrophages. These tumor associated macrophages are key actors of cancer-related inflammation, being the main type of inflammatory cells infiltrating the tumor environment and exerting a tumor promoting effect by secreting growth factors, stimulating angiogenesis and influ-encing the activation of stellate cells. This complex interplay between the several cell types involved in liver cancer emphasizes the need for targeting the tumor stroma in HCC patients.展开更多
Dear Editor,Coronavirus disease 2019(COVID-19)is a global pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-Co V-2).SARS-Co V-2 infection was first detected in Wuhan,China in late December 2019.T...Dear Editor,Coronavirus disease 2019(COVID-19)is a global pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-Co V-2).SARS-Co V-2 infection was first detected in Wuhan,China in late December 2019.The virus was spreading rapidly to other cities of China and accumulating cases had been reported(Li et al.2020).展开更多
Mast cells are emerging as players in the communication between peripheral nerve endings and cells of the immune system.However,it is not clear the mechanism by which mast cells communicate with peripheral nerves.We p...Mast cells are emerging as players in the communication between peripheral nerve endings and cells of the immune system.However,it is not clear the mechanism by which mast cells communicate with peripheral nerves.We previously found that mast cells located within healing tendons can express glutamate receptors,raising the possibility that mast cells may be sensitive to glutamate signaling.To evaluate this hypothesis,we stimulated primary mast cells with glutamate and showed that glutamate induced the profound upregulation of a panel of glutamate receptors of both the ionotropic type(NMDAR1,NMDAR2A,and NMDAR2B)and the metabotropic type(mGluR2 and mGluR7)at both the mRNA and protein levels.The binding of glutamate to glutamate receptors on the mast cell surface was confirmed.Further,glutamate had extensive effects on gene expression in the mast cells,including the upregulation of proinflammatory components such as IL-6 and CCL2.Glutamate also induced the upregulation of transcription factors,including Egr2,Egr3 and,in particular,FosB.The extensive induction of FosB was confirmed by immunofluorescence assessment.Glutamate receptor antagonists abrogated the responses of the mast cells to glutamate,supporting the supposition of a functional glutamate–glutamate receptor axis in mast cells.Finally,we provide in vivo evidence supporting a functional glutamate–glutamate receptor axis in the mast cells of injured tendons.Together,these findings establish glutamate as an effector of mast cell function,thereby introducing a novel principle for how cells in the immune system can communicate with nerve cells.展开更多
Background:Avian influenza viruses(AIVs)have been identified from more than 100 different species of wild birds around the globe.Wild migratory birds can act as potential spreaders for AIVs to domestic birds between d...Background:Avian influenza viruses(AIVs)have been identified from more than 100 different species of wild birds around the globe.Wild migratory birds can act as potential spreaders for AIVs to domestic birds between different countries.Egypt is situated on important migratory flyways for wild birds between different continents.While much is known about circulation of zoonotic potential H5N1 and H9N2 AIVs in domestic poultry in Egypt,little is known about the pivotal role of migratory birds in the maintenance and transmission of the viruses in Egypt.Methods:Targeted AIV surveillance has been conducted in 2017 in different wetlands areas in Northern and Eastern Egypt.Results:AIV of subtype H5 was detected in two bird species.In addition,a novel reassortant strain of the H6N2 subtype was identified which reveals the continuous risk of new influenza virus(es)introduction into Egypt.This novel virus possesses a reassortant pattern originating from different AIV gene pools.Conclusions:Intervention control strategies should be performed to minimize the possible contact of domestic birds with wild birds to lower the risk of virus transmission at this interface.In addition,constant monitoring of AIVs in migratory birds is essential in the early detection of influenza virus introduction into Egypt.展开更多
OBJECTIVE To investigate the inhibitory effects of Spatholobus Suberectus Column Extract(SSCE)on estrogen receptor positive(ER+)breast cancer cel MCF-7and its possible molecular mechanism.METHODS MCF-7cells were cultu...OBJECTIVE To investigate the inhibitory effects of Spatholobus Suberectus Column Extract(SSCE)on estrogen receptor positive(ER+)breast cancer cel MCF-7and its possible molecular mechanism.METHODS MCF-7cells were cultured without estrogen and with 17-β-estrogen(10-8mol·L-1),respectively,then treated with SSCE(0,40,80,160,320μg·m L-1).MTT assay was employed to evaluate cell viability.Flow cytometry assays were performed to underlying apoptosis and detecting cel cycle of MCF-7 cells treated with SSCE(0,80,160,320μg·mL-1).Wound healing assays was conducted to detect the migration ability.Dual luciferase reporter system was used to detect the activity of p-ERα,p-ERβpresented in intra-nuclear estrogen response element(ERE).Western blotting assay was employed to identify the expression of protein such as Bax,Bcl-2,p-ERα,p-ERβ,ERK1/2,p-ERK1/2,AKT,p-AKT,m TOR,p-m TOR,PI3K,p-PI3K.RESULTS It showed that SSCE(80,160and 320μg·mL-1)significantly decreased the viability of MCF-7.SSCE also triggered apoptosis,arrested cell cycle at G0/G1phase,inhibited migration.Dual luciferase reporter system showed that SSCE suppressed intra-nuclear p-ER activity,Western blotting analysis confirmed that SSCE did repress the expression of phosphorylated-ER alpha(p-ERα),ERK1/2,p-ERK1/2,AKT,p-AKT,pmT OR,PI3K,p-PI3K,which indicate that SSCE suppress MAPK PI3K/AKT signal pathway.CONCLUSION Our result showed that SSCE cause ER+MCF-7 cells apoptosis,G0/G1phase arresting,migration decreasing,via hypo-active of ER,suppress MAPK PI3K/AKT pathway.展开更多
Liver diseases with the central pathogenetic mechanism of oxidative stress are one of the main causes of mortality worldwide.Therefore,dihydroquinoline derivatives,which are precursors of hepatoprotectors and have ant...Liver diseases with the central pathogenetic mechanism of oxidative stress are one of the main causes of mortality worldwide.Therefore,dihydroquinoline derivatives,which are precursors of hepatoprotectors and have antioxidant activity,are of interest.We have previously found that some compounds in this class have the ability to normalize redox homeostasis under experimental conditions.Here,we initially analyzed the hepatoprotective potential of the dihydroquinoline derivative 1-benzoyl-6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline(BHDQ)for carbon tetrachloride(CCl4)-induced liver injury in rats.Results suggested that BHDQ normalized the alanine aminotransferase,aspartate aminotransferase,and gamma-glutamyl transpeptidase in serum.We also observed an improvement in liver tissue morphology related to BHDQ.Animals with CCl4-induced liver injuries treated with BHDQ had less oxidative stress compared to animals with CCl4-induced liver injury.BHDQ promoted activation changes in superoxide dismutase,catalase,glutathione peroxidase,glutathione reductase,and glutathione transferase on control values in animals with CCl4-induced liver injury.BHDQ also activated gene transcription in Sod1 and Gpx1 via nuclear factor erythroid 2-related factor 2 and forkhead box protein O1 factors.Therefore,the compound of concern has a hepatoprotective effect by inhibiting the development of necrotic processes in the liver tissue,through antioxidation.展开更多
The COVID-19 pandemic has caused severe health problems worldwide and unprecedented decimation of the global economy.Moreover,after more than 2 years,many populations are still under pressure of infection.Thus,a broad...The COVID-19 pandemic has caused severe health problems worldwide and unprecedented decimation of the global economy.Moreover,after more than 2 years,many populations are still under pressure of infection.Thus,a broader perspective in developing antiviral strategies is still of great importance.Inspired by the observed multiple benefits of heparin in the treatment of thrombosis,the potential of low molecular weight heparin(LMWH)for the treatment of COVID-19 have been explored.Clinical applications found that LMWH decreased the level of inflammatory cytokines in COVID-19 patients,accordingly reducing lethality.Furthermore,several in vitro studies have demonstrated the important roles of heparan sulfate in SARS-CoV-2 infection and the inhibitory effects of heparin and heparin mimetics in viral infection.These clinical observations and designed studies argue for the potential to develop heparin mimetics as anti-SARS-CoV-2 drug candidates.In this review,we summarize the properties of heparin as an anticoagulant and the pharmaceutical possibilities for the treatment of virus infection,focusing on the perspectives of developing heparin mimetics via chemical synthesis,chemoenzymatic synthesis,and bioengineered production by microbial cell factories.The ultimate goal is to pave the eminent need for exploring novel compounds to treat coronavirus infection-caused diseases.展开更多
A recent publication in Nature by Lan et al.,presented GREM1(gremlin 1)as an important regulatory node of cellular plasticity in pancreatic ductal adenocarcinoma(PDAC).1 Knockout experiments in mice point to an import...A recent publication in Nature by Lan et al.,presented GREM1(gremlin 1)as an important regulatory node of cellular plasticity in pancreatic ductal adenocarcinoma(PDAC).1 Knockout experiments in mice point to an important role of Grem1 in retaining an epithelial,differentiated phenotype of pancreatic cancer cells presumably by inhibiting BMP signalling.展开更多
The World Society for Virology(WSV) was founded and incorporated as a nonprofit organization in the United States in 2017. WSV seeks to strengthen and support both virological research and virologists who conduct rese...The World Society for Virology(WSV) was founded and incorporated as a nonprofit organization in the United States in 2017. WSV seeks to strengthen and support both virological research and virologists who conduct research of viruses that affect humans, other animals, plants, and other organisms. One of the objectives of WSV is to connect virologists worldwide and support collaboration. Fulfilling this objective, virologists from fourteen countries in North America,Europe, Africa, Asia, and the Middle East met on 25–27 th August 2019 in Stockholm, Sweden at the Karolinska University Hospital for the first Committee Meeting of WSV. This meeting included compelling keynote and honorary speeches and a series of 18 scientific talks were given encompassing a diverse array of subjects within virology. Followed by the scientific session, a business session was held where multiple aspects and next steps of the society were discussed and charted out.展开更多
基金the National Swedish Research Council(grants No.2015-04402,2019-04486)the Carl Trygger Foundation(CTS 20:6)+3 种基金the Jornvall FoundationJulian Francis for financial supportthe National Genomics Infrastructure in Stockholm funded by Science for Life Laboratory,the Knut and Alice Wallenberg Foundationthe Research/Scientific Computing teams at The James Hutton Institute and NIAB for providing computational resources and technical support for the"UK's Crop Diversity Bioinformatics HPC"(BBSRC grant BB/S019669/1)。
文摘The family Alaudidae,larks,comprises 93-100 species(depending on taxonomy)that are widely distributed across Africa and Eurasia,with single species extending their ranges to North and northernmost South America and Australia.A decade-old molecular phylogeny,comprising~80%of the species,revealed multiple cases of parallel evolution and large variation in rates of morphological evolution,which had misled taxonomists into creating many non-monophyletic genera.Here,we reconstruct the phylogeny of the larks,using a dataset covering one mitochondrial and 16 nuclear loci and comprising all except one of the currently recognised species as well as several recently proposed new species(in total 133 taxa;not all loci available for all species).We provide additional support using genome-wide markers to infer a genus-level phylogeny based on near-complete generic sampling(in total 51 samples of 44 taxa across 40 species).Our results confirm the previous findings of rampant morphological convergence and divergence,and reveal new cases of paraphyletic genera.We propose a new subfamily classification,and also that the genus Mirafra is divided into four genera to produce a more balanced generic classification of the Alaudidae.Our study supports recently proposed species splits as well as some recent lumps,while also questioning some of the latter.This comprehensive phylogeny will form an important basis for future studies,such as comparative studies of lark natural history,ecology,evolution and conservation.
文摘BACKGROUND It is known that under conditions of tissue tolerance to insulin,observed during type 2 diabetes mellitus(DM2),there is an increased production of reactive oxygen species.Moreover,the free radicals can initiate lipid peroxidation(LPO)in lipoprotein particles.The concentration of LPO products can influence the state of insulin receptors,repressing their hormone connection activity,which is expressed as a reduction of the glucose consumption by cells.It is possible that reduction in glucose concentration during administration of 10-(6-plastoquinonyl)decyltriphenylphosphonium(SkQ1)to rats with DM2 may be related to the antioxidant properties of this substance.AIM To establish the influence of SkQ1 on free-radical homeostasis in the heart and blood serum of rats with streptozotocin-induced hyperglycemia.METHODS To induce hyperglycemia,rats were fed a high-fat diet for 1 mo and then administered two intra-abdominal injections of streptozotocin with a 7-d interval at a 30 mg/kg of animal weight dose with citrate buffer equal to pH 4.4.SkQ1 solution was administered intraperitoneally at a 1250 nmol/kg dose per day.Tissue samples were taken from control animals,animals with experimental hyperglycemia,rats with streptozotocin-induced glycemia that were administered SkQ1 solution,animals housed under standard vivarium conditions that were administered SkQ1,rats that were administered intraperitoneally citrate buffer equal to pH 4.4 once a week during 2 wk after 1-mo high-fat diet,and animals that were administered intraperitoneally with appropriate amount of solution without SkQ1(98%ethanol diluted eight times with normal saline solution).To determine the intensity of free radical oxidation and total antioxidant activity,we used the biochemiluminescence method.Aconitate hydratase(AH),superoxide dismutase,and catalase activities were estimated using the Hitachi U-1900 spectrophotometer supplied with software.The amount of citrate was determined by means of the Natelson method.Real-time polymerase chain reaction was carried out using an amplifier ANK-32.RESULTS It was found that the mitochondrial-directed antioxidant elicits decrease of biochemiluminescence parameter values that increase by pathology as well as the levels of primary products of LPO,such as diene conjugates and carbonyl compounds,which indicate intensity of free radical oxidation.At the same time,the activity of AH,considered a crucial target of free radicals,which decreased during experimental hyperglycemia,increased.Apparently,increasing activity of AH influenced the speed of citrate utilization,whose concentration decreased after administering SkQ1 by pathology.Moreover,the previously applied antioxidant during hyperglycemia influenced the rate of antioxidant system mobilization.Thus,superoxide dismutase and catalase activity,as well as the level of gene transcript under influence of SkQ1 at pathology,were changing to the direction of control groups values.CONCLUSION According to the results of performed research,SkQ1 can be considered a promising addition to be included in antioxidant therapy of DM2.
基金We would like to thank the South African National Research Foundation for supporting this research through the Thuthuka Funding Instrument(TTK170411226583).We would also like to thank the College of Agriculture,Engineering and Science as well as the School of Life Sciences at University of KwaZulu-Natal(Westville Campus),South Africa for their support during the execution of this research.Authors would like to thank the anonymous reviewers for their valuable comments that significantly improved the manuscript.
文摘Campylobacter species are a major cause of foodborne bacterial infections in both developed and developing countries worldwide.Campylobacter jejuni is responsible for the majority of infectio ns.This study was con ducted to identify virule nceassociated genes in Campylobacter species isolated from livestock production systems in South Africa.A total of 250 fecal samples consisting of cattle(n=50),chickens(n=50),goats(n=50),sheep(n=50)and pigs(n=50)were randomly collected from livestock in Eastern Cape and KwaZulu-Natal provinces of South Africa between April and October 2018.The samples were an a lyzed for the presence of virule nee genes in Campylobacter species using molecular PCR-based methods.It was found that 77 and 23%of Campylobacter jejuni and Campylobacter coli respectively were isolated from all the livestock samples.There were positive significant(P<0.05)correlations amongst all the virulenee genes that were investigated.Chisquare and Fisher's exact tests were implemented to test for the effect of livestock species on the presenee or absenee of virule nee gen es.The study dem on strated that most of livestock species can pote ntially cause zoonotic infecti on s and food pois oning due to the high prevale nee of Campylobacter.The high prevale nee of virule nee genes highlights the sign ifica nee of Campylobacter\r\livestock production systems in South Africa.This requires the implementation of one-health approaches to reduce the impact of foodborne and zoonotic diseases for the welfare of human and animal health.
基金The project supported by National Natural Science Foundation of China(81202840,81373815)Specialized Research Fund for the Doctoral Program of Higher Education of China(20131107110014)+1 种基金Beijing Natural Science Foundation(7162084)Swedish Cancer Foundation(150815)
文摘OBJECTIVE GubenyiliuⅡ(GYⅡ),a traditional Chinese medicine(TCM)formula used in our hospital,has shown beneficial effects in cancer patients.In this study,we investigated the molecular mechanisms underlying the beneficial effects of GYⅡon murine breast cancer models.METHODS Inhibition of tumor growth and metastasis was evaluated by assessment of tumor weight and analysis of bioluminescent signal after a homograft inoculation.Viability of cultured breast cancer cells was determined using MTT assay andreal-time cell analysis(RTCA).Cell migratory ability was evaluated by Transwell?assay and wound healing assay.Subsequently,the potential anti-tumor and anti-metastatic mechanism was investigated by Western blotting and Immunohistochemistry.RESULTS GYⅡshowed significant inhibitory effects on tumor growth and metastasis in the murine breast cancer model.And GYⅡsuppressed theproliferation of 4T1 and MCF-7 cells in a dose-dependent manner.A better inhibitory effect on 4T1 cells proliferation and migration was found in sub-fractions(SF)of GYⅡ.Moreover,heparanase expression and degree of angiogenesis were reduced in tumor tissues.Western blotting analysis showed decreased expression of heparanase and growth factors in the cells treated with GYⅡand its sub-fractions(SF2 and SF3),there by a reduction in phosphorylation of ERK and AKT.CONCLUSION GYⅡexerts anti-tumor growth and anti-metastatic effects on murine breast cancer model.Sub-fractions 2 and 3 exhibits higher potency of the anti-tumor activity that is,at least partly,associated with decreased heparanase and growth factor sexpression,which subsequently sup-pressed activation of ERK and AKT pathways.
基金Supported by the Miguel Servet and pFIS fellowships,No.CP16/00121(P.S.) and No.FI21/00031(P.E-R.) from the Instituto de Salud Carlos Ⅲ and cofinanced by European funds(FSE:“el FSE invierte en tu futuro”)Magnus Bergvalls Stiftelse,No.2021-04284(L.C.)the Ⅳ Grant for Childhood Cancer Research from Asociación de Padres de Niños con Cáncer de Aragón(ASPANOA,P.S.).
文摘Medulloblastomas(MBs)are the most prevalent brain tumours in children.They are classified as grade IV,the highest in malignancy,with about 30%metastatic tumours at the time of diagnosis.Cancer stem cells(CSCs)are a small subset of tumour cells that can initiate and support tumour growth.In MB,CSCs contribute to tumour initiation,metastasis,and therapy resistance.Metabolic differences among the different MB groups have started to emerge.Sonic hedgehog tumours show enriched lipid and nucleic acid metabolism pathways,whereas Group 3 MBs upregulate glycolysis,gluconeogenesis,glutamine anabolism,and glutathione-mediated anti-oxidant pathways.Such differences impact the clinical behaviour of MB tumours and can be exploited therapeutically.In this review,we summarise the existing knowledge about metabolic rewiring in MB,with a particular focus on MB-CSCs.Finally,we highlight some of the emerging metabolism-based therapeutic strategies for MB.
文摘Hepatocellular carcinoma(HCC) is one of the most common and deadly cancers worldwide. In ninety percent of the cases it develops as a result of chronic liver damage and it is thus a typical inflammationrelated cancer characterized by the close relation between the tumor microenvironment and tumor cells. The stromal environment consists out of several cell types, including hepatic stellate cells, macrophages and endothelial cells. They are not just active bystanders in the pathogenesis of HCC, but play an important and active role in tumor initiation, progression and metastasis. Furthermore, the tumor itself influences these cells to create a background that is beneficial for sustaining tumor growth. One of the key players is the hepatic stellate cell, which is activated during liver damage and differentiates towards a myofibroblast-like cell. Activated stellate cells are responsible for the deposition of extracellular matrix, increase the production of angiogenic factors and stimulate the recruitment of macrophages. The increase of angiogenic factors(which are secreted by macrophages, tumor cells and activated stellate cells) will induce the formation of new blood vessels, thereby supplying the tumor with more oxygen and nutrients, thus supporting tumor growth and offering a passageway in the circulatory system. In addition, the secretion of chemokines by the tumor cells leads to the recruitment of tumor associated macrophages. These tumor associated macrophages are key actors of cancer-related inflammation, being the main type of inflammatory cells infiltrating the tumor environment and exerting a tumor promoting effect by secreting growth factors, stimulating angiogenesis and influ-encing the activation of stellate cells. This complex interplay between the several cell types involved in liver cancer emphasizes the need for targeting the tumor stroma in HCC patients.
基金funded by the Zhongnan Hospital of Wuhan University Science,Technology and Innovation Seed Fund(Grant No.znpy2018007)。
文摘Dear Editor,Coronavirus disease 2019(COVID-19)is a global pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-Co V-2).SARS-Co V-2 infection was first detected in Wuhan,China in late December 2019.The virus was spreading rapidly to other cities of China and accumulating cases had been reported(Li et al.2020).
基金This study was funded by grants from AFA Forsakring(M.P.).
文摘Mast cells are emerging as players in the communication between peripheral nerve endings and cells of the immune system.However,it is not clear the mechanism by which mast cells communicate with peripheral nerves.We previously found that mast cells located within healing tendons can express glutamate receptors,raising the possibility that mast cells may be sensitive to glutamate signaling.To evaluate this hypothesis,we stimulated primary mast cells with glutamate and showed that glutamate induced the profound upregulation of a panel of glutamate receptors of both the ionotropic type(NMDAR1,NMDAR2A,and NMDAR2B)and the metabotropic type(mGluR2 and mGluR7)at both the mRNA and protein levels.The binding of glutamate to glutamate receptors on the mast cell surface was confirmed.Further,glutamate had extensive effects on gene expression in the mast cells,including the upregulation of proinflammatory components such as IL-6 and CCL2.Glutamate also induced the upregulation of transcription factors,including Egr2,Egr3 and,in particular,FosB.The extensive induction of FosB was confirmed by immunofluorescence assessment.Glutamate receptor antagonists abrogated the responses of the mast cells to glutamate,supporting the supposition of a functional glutamate–glutamate receptor axis in mast cells.Finally,we provide in vivo evidence supporting a functional glutamate–glutamate receptor axis in the mast cells of injured tendons.Together,these findings establish glutamate as an effector of mast cell function,thereby introducing a novel principle for how cells in the immune system can communicate with nerve cells.
基金funded by an internal project of the Reference Laboratory for Veterinary Quality Control on Poultry Production,Animal Health Research Institutesupported in part by the Swedish Research Council VR(Grant Numbers 2016-02596 and 2018-02569)to MMN
文摘Background:Avian influenza viruses(AIVs)have been identified from more than 100 different species of wild birds around the globe.Wild migratory birds can act as potential spreaders for AIVs to domestic birds between different countries.Egypt is situated on important migratory flyways for wild birds between different continents.While much is known about circulation of zoonotic potential H5N1 and H9N2 AIVs in domestic poultry in Egypt,little is known about the pivotal role of migratory birds in the maintenance and transmission of the viruses in Egypt.Methods:Targeted AIV surveillance has been conducted in 2017 in different wetlands areas in Northern and Eastern Egypt.Results:AIV of subtype H5 was detected in two bird species.In addition,a novel reassortant strain of the H6N2 subtype was identified which reveals the continuous risk of new influenza virus(es)introduction into Egypt.This novel virus possesses a reassortant pattern originating from different AIV gene pools.Conclusions:Intervention control strategies should be performed to minimize the possible contact of domestic birds with wild birds to lower the risk of virus transmission at this interface.In addition,constant monitoring of AIVs in migratory birds is essential in the early detection of influenza virus introduction into Egypt.
基金The project supported by Beijing Natural Science Foundation(7122083)Beijing Science and Technology Projec(tD161100005116005)
文摘OBJECTIVE To investigate the inhibitory effects of Spatholobus Suberectus Column Extract(SSCE)on estrogen receptor positive(ER+)breast cancer cel MCF-7and its possible molecular mechanism.METHODS MCF-7cells were cultured without estrogen and with 17-β-estrogen(10-8mol·L-1),respectively,then treated with SSCE(0,40,80,160,320μg·m L-1).MTT assay was employed to evaluate cell viability.Flow cytometry assays were performed to underlying apoptosis and detecting cel cycle of MCF-7 cells treated with SSCE(0,80,160,320μg·mL-1).Wound healing assays was conducted to detect the migration ability.Dual luciferase reporter system was used to detect the activity of p-ERα,p-ERβpresented in intra-nuclear estrogen response element(ERE).Western blotting assay was employed to identify the expression of protein such as Bax,Bcl-2,p-ERα,p-ERβ,ERK1/2,p-ERK1/2,AKT,p-AKT,m TOR,p-m TOR,PI3K,p-PI3K.RESULTS It showed that SSCE(80,160and 320μg·mL-1)significantly decreased the viability of MCF-7.SSCE also triggered apoptosis,arrested cell cycle at G0/G1phase,inhibited migration.Dual luciferase reporter system showed that SSCE suppressed intra-nuclear p-ER activity,Western blotting analysis confirmed that SSCE did repress the expression of phosphorylated-ER alpha(p-ERα),ERK1/2,p-ERK1/2,AKT,p-AKT,pmT OR,PI3K,p-PI3K,which indicate that SSCE suppress MAPK PI3K/AKT signal pathway.CONCLUSION Our result showed that SSCE cause ER+MCF-7 cells apoptosis,G0/G1phase arresting,migration decreasing,via hypo-active of ER,suppress MAPK PI3K/AKT pathway.
基金supported by the Russian Foundation for Basic Research (Grant No. 20-04-00526А)
文摘Liver diseases with the central pathogenetic mechanism of oxidative stress are one of the main causes of mortality worldwide.Therefore,dihydroquinoline derivatives,which are precursors of hepatoprotectors and have antioxidant activity,are of interest.We have previously found that some compounds in this class have the ability to normalize redox homeostasis under experimental conditions.Here,we initially analyzed the hepatoprotective potential of the dihydroquinoline derivative 1-benzoyl-6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline(BHDQ)for carbon tetrachloride(CCl4)-induced liver injury in rats.Results suggested that BHDQ normalized the alanine aminotransferase,aspartate aminotransferase,and gamma-glutamyl transpeptidase in serum.We also observed an improvement in liver tissue morphology related to BHDQ.Animals with CCl4-induced liver injuries treated with BHDQ had less oxidative stress compared to animals with CCl4-induced liver injury.BHDQ promoted activation changes in superoxide dismutase,catalase,glutathione peroxidase,glutathione reductase,and glutathione transferase on control values in animals with CCl4-induced liver injury.BHDQ also activated gene transcription in Sod1 and Gpx1 via nuclear factor erythroid 2-related factor 2 and forkhead box protein O1 factors.Therefore,the compound of concern has a hepatoprotective effect by inhibiting the development of necrotic processes in the liver tissue,through antioxidation.
基金support from the National Key Research and Development Program of China (2021YFF0600700,2020YFA090032 and 2019YFA0906201)the Swedish research council (2020-05759)the National Natural Science Foundation of China (31720103901,31961133004,21907031,21977029,22108266).
文摘The COVID-19 pandemic has caused severe health problems worldwide and unprecedented decimation of the global economy.Moreover,after more than 2 years,many populations are still under pressure of infection.Thus,a broader perspective in developing antiviral strategies is still of great importance.Inspired by the observed multiple benefits of heparin in the treatment of thrombosis,the potential of low molecular weight heparin(LMWH)for the treatment of COVID-19 have been explored.Clinical applications found that LMWH decreased the level of inflammatory cytokines in COVID-19 patients,accordingly reducing lethality.Furthermore,several in vitro studies have demonstrated the important roles of heparan sulfate in SARS-CoV-2 infection and the inhibitory effects of heparin and heparin mimetics in viral infection.These clinical observations and designed studies argue for the potential to develop heparin mimetics as anti-SARS-CoV-2 drug candidates.In this review,we summarize the properties of heparin as an anticoagulant and the pharmaceutical possibilities for the treatment of virus infection,focusing on the perspectives of developing heparin mimetics via chemical synthesis,chemoenzymatic synthesis,and bioengineered production by microbial cell factories.The ultimate goal is to pave the eminent need for exploring novel compounds to treat coronavirus infection-caused diseases.
文摘A recent publication in Nature by Lan et al.,presented GREM1(gremlin 1)as an important regulatory node of cellular plasticity in pancreatic ductal adenocarcinoma(PDAC).1 Knockout experiments in mice point to an important role of Grem1 in retaining an epithelial,differentiated phenotype of pancreatic cancer cells presumably by inhibiting BMP signalling.
文摘The World Society for Virology(WSV) was founded and incorporated as a nonprofit organization in the United States in 2017. WSV seeks to strengthen and support both virological research and virologists who conduct research of viruses that affect humans, other animals, plants, and other organisms. One of the objectives of WSV is to connect virologists worldwide and support collaboration. Fulfilling this objective, virologists from fourteen countries in North America,Europe, Africa, Asia, and the Middle East met on 25–27 th August 2019 in Stockholm, Sweden at the Karolinska University Hospital for the first Committee Meeting of WSV. This meeting included compelling keynote and honorary speeches and a series of 18 scientific talks were given encompassing a diverse array of subjects within virology. Followed by the scientific session, a business session was held where multiple aspects and next steps of the society were discussed and charted out.
