Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores ...Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores the potential mechanisms underlying the pathogenesis of CEAS,focusing on the role of SLCO2A1-encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2(PGE2)levels.Studies have suggested that elevated PGE2 levels contribute to mucosal damage,inflammation,and disruption of the intestinal barrier.The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality,as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS.Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel,targeted therapies.展开更多
Parkinsonism by unilateral,intranigralβ-sitosterolβ-D-glucoside administration in rats is distinguished in that theα-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time,...Parkinsonism by unilateral,intranigralβ-sitosterolβ-D-glucoside administration in rats is distinguished in that theα-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time,thus replicating several clinical features of Parkinson’s disease,a typicalα-synucleinopathy.As Nurr1 repressesα-synuclein,we evaluated whether unilateral transfected of rNurr1-V5 transgene via neurotensin-polyplex to the substantia nigra on day 30 after unilateralβ-sitosterolβ-D-glucoside lesion could affect bilateral neuropathology and sensorimotor deficits on day 30 post-transfection.This study found that rNurr1-V5 expression but not that of the green fluorescent protein(the negative control)reducedβ-sitosterolβ-D-glucoside-induced neuropathology.Accordingly,a bilateral increase in tyrosine hydroxylase-positive cells and arborization occurred in the substantia nigra and increased tyrosine hydroxylase-positive ramifications in the striatum.In addition,tyrosine hydroxylase-positive cells displayed less senescence markerβ-galactosidase and more neuron-cytoskeleton markerβIII-tubulin and brain-derived neurotrophic factor.A significant decrease in activated microglia(positive to ionized calcium-binding adaptor molecule 1)and neurotoxic astrocytes(positive to glial fibrillary acidic protein and complement component 3)and increased neurotrophic astrocytes(positive to glial fibrillary acidic protein and S100 calcium-binding protein A10)also occurred in the substantia nigra.These effects followed the bilateral reduction inα-synuclein aggregates in the nigrostriatal system,improving sensorimotor behavior.Our results show that unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neurodegeneration(senescence and loss of neuron-cytoskeleton and tyrosine hydroxylase-positive cells),neuroinflammation(activated microglia,neurotoxic astrocytes),α-synuclein aggregation,and sensorimotor deficits.Increased neurotrophic astrocytes and brain-derived neurotrophic factor can mediate the rNurr1-V5 effect,supporting its potential clinical use in the treatment of Parkinson’s disease.展开更多
BACKGROUND Chronic myelomonocytic leukemia(CMML),a rare clonal hematopoietic stem cell disorder characterized by myelodysplastic syndrome and myeloproliferative neoplasms,has a generally poor prognosis,and easily prog...BACKGROUND Chronic myelomonocytic leukemia(CMML),a rare clonal hematopoietic stem cell disorder characterized by myelodysplastic syndrome and myeloproliferative neoplasms,has a generally poor prognosis,and easily progresses to acute myeloid leukemia.The simultaneous incidence of hematologic malignancies and solid tumors is extremely low,and CMML coinciding with lung malignancies is even rarer.Here,we report a case of CMML,with ASXL1 and EZH2 gene mutations,combined with non-small cell lung cancer(lung squamous cell carcinoma).CASE SUMMARY A 63-year-old male,suffering from toothache accompanied by coughing,sputum,and bloody sputum for three months,was given a blood test after experiencing continuous bleeding resulting from a tooth extraction at a local hospital.Based on morphological results,the patient was diagnosed with CMML and bronchoscopy was performed in situ to confirm the diagnosis of squamous cell carcinoma in the lower lobe of the lung.After receiving azacitidine,programmed cell death protein 1,and platinum-based chemotherapy drugs,the patient developed severe myelosuppression and eventually fatal leukocyte stasis and dyspnea.CONCLUSION During the treatment and observation of CMML and be vigilant of the growth of multiple primary malignant tumors.展开更多
Triggering receptor expressed on myeloid cells-like 2(TREML2)is a newly identified susceptibility gene for Alzheimer's disease(AD).It encodes a microglial inflammation-associated receptor.To date,the potential rol...Triggering receptor expressed on myeloid cells-like 2(TREML2)is a newly identified susceptibility gene for Alzheimer's disease(AD).It encodes a microglial inflammation-associated receptor.To date,the potential role of mic roglial TREML2 in neuroinflammation in the context of AD remains unclear.In this study,APP/PS1 mice were used to investigate the dynamic changes of TREML2 levels in brain during AD progression.In addition,lipopolysaccharide(LPS)stimulation of primary microglia as well as a lentivirus-mediated TREML2 overexpression and knockdown were employed to explore the role of TREML2 in neuroinflammation in the context of AD.Our res ults show that TREML2 levels gradually increased in the brains of AP P/PS1 mice during disease progression.LPS stimulation of primary microglia led to the release of inflammato ry cytokines including interleukin-1β,inte rleukin-6,and tumor necrosis factor-a in the culture medium.The LPS-induced mic roglial release of inflammatory cytokines was enhanced by TREML2 overexpression and was attenuated by TREML2 knoc kdown.LPS increased the levels of mic roglial M1-type polarization marker inducible nitric oxide synthase.This effect was enhanced by TREML2 overexpression and ameliorated by TREML2 knockdown.Furthermore,the levels of microglial M2-type polarization markers CD206 and ARG1 in the primary microglia were reduced by TREML2 overexpression and elevated by TREML2 knockdown.LPS stimulation increased the levels of NLRP3 in primary microglia.The LPS-induced increase in NLRP3 was further elevated by TREML2 overexpression and alleviated by TREML2 knockdown.In summary,this study provides the first evidence that TREML2 modulates inflammation by regulating microglial polarization and NLRP3 inflammasome activation.These findings reveal the mechanisms by which TREML2 regulates microglial inflammation and suggest that TREML2 inhibition may represent a novel therapeutic strategy for AD.展开更多
目的探讨果蝇双翅边缘缺刻同源基因(Notch)信号通路在慢性阻塞性肺疾病(COPD)辅助性T细胞1(Helper T cells 1,Th1)和辅助性T细胞2(Helper T cells 2,Th2)失衡中的作用及芪蛭皱肺颗粒的干预机制。方法70只Wistar大鼠随机挑选10只作为空...目的探讨果蝇双翅边缘缺刻同源基因(Notch)信号通路在慢性阻塞性肺疾病(COPD)辅助性T细胞1(Helper T cells 1,Th1)和辅助性T细胞2(Helper T cells 2,Th2)失衡中的作用及芪蛭皱肺颗粒的干预机制。方法70只Wistar大鼠随机挑选10只作为空白对照组,其余大鼠均采用香烟烟雾(CS)联合气管滴注脂多糖(Lipopolysaccharide,LPS)法建立COPD模型,空白对照组及造模组各随机挑选3只大鼠验证造模是否成功。造模结束进行灌胃给药干预,造模组大鼠随机分为模型对照组、阳性对照组(67.5μg·kg^(-1))及芪蛭皱肺颗粒高中低剂量组(3.24、1.62、0.81 g·kg^(-1)),分别给予生理盐水、醋酸地塞米松混悬液、芪蛭皱肺高、中、低剂量混悬液进行灌胃干预,空白对照组同模型对照组,灌胃等体积生理盐水。经28天造模及28天治疗后,采用动物肺功能测试系统检测吸气峰流速(Peak Inspiratory Flow,PIF)和呼气峰流速(Peak Expiratory Flow,PEF),处死大鼠提取肺脏、脾脏、血清及支气管肺泡灌洗液(BALF),苏木素-伊红(HE)染色评价肺组织病理变化,酶联免疫吸附实验法(ELISA)测定血清及BALF中肿瘤坏死因子-α(TNF-α)含量,流式细胞仪检测脾脏Th1/Th2细胞水平,免疫组织化学法(Immunohistochemistry,IHC)及蛋白免疫印迹法(Western blot)检测肺组织Notch1、Hes家族发状分裂相关增强子1(Hes1)、Hey家族发状分裂相关增强子1(Hey1)蛋白水平,实时荧光定量聚合酶链式反应(Real-time PCR,RT-PCR)检测肺组织Notch1、Hes1、Hey1基因表达水平。结果与空白对照组比较,模型对照组大鼠肺功能显著降低(P<0.05),肺组织出现炎性细胞浸润、支气管结构破坏等病变,血清及BALF中TNF-α含量显著升高(P<0.05),脾Th1细胞百分比显著降低(P<0.05),Th2细胞百分比显著升高(P<0.05),肺组织Notch1、Hes1、Hey1蛋白及mRNA表达显著升高(P<0.05),差异均具有统计学意义;与模型对照组比较,各给药组大鼠肺功能显著升高(P<0.05),肺组织病理损伤均有所减轻,血清及BALF中TNF-α含量显著降低(P<0.05),脾Th1细胞百分比显著升高(P<0.05),Th2细胞百分比显著降低(P<0.05),肺组织Notch1、Hes1、Hey1蛋白及mRNA表达显著降低(P<0.05),差异均具有统计学意义。结论芪蛭皱肺颗粒通过抑制Notch信号通路调节Th1/Th2平衡,从而改善COPD大鼠肺功能及病理损伤,影响其免疫功能。展开更多
Objective:To study the genetic diversity at the msp—1,msp—2,and glurp genes of Plasmodium falciparum(P.falciparum) isolates from 3 endemic areas in Thailand:Tak.Kanchanaburi and Ranong provinces.Methods:A total of 1...Objective:To study the genetic diversity at the msp—1,msp—2,and glurp genes of Plasmodium falciparum(P.falciparum) isolates from 3 endemic areas in Thailand:Tak.Kanchanaburi and Ranong provinces.Methods:A total of 144 P.falciparum isolates collected prior to Irealmenl during January.2012 to June,2013 were genotyped.DNA was extracted:allele frequency and diversity of msp-1.msp-2,and glurp genes were investigated by nested polymerase chain reaction.Results:P.falciparum isolates in this study had high rate of multiple genotypes infection(96.5%)with an overall mean multiplicity of infection of 3.21.The distribution of allelic families of msp-1was significantly different among isolales from Tak.kanchanahnri.and Ranong but not for the msp-2.K1 and MAD20 were the predominant allelic families at the msp-1 gene,whereas alleles belonging to 3D7 were more frequent at the msp-2 gene.The glurp gene had the least diverse alleles.Population structure of P.falciparum isolates from Tak and Ranong was quite similar as revealed by the presence of similar proportions of MAD20 and K1 alleles at msp-1 loci.3D7 and FC27 alleles at msp-2 loci as well as comparable mean MOI.Isolates from Kanchanaburi had different structures;the most prevalent alleles were K1 and RO33.Conclusions:The present study shows that P.falciparum isolates from Tak and Ranong provinces had similar allelic pattern of msp—1 and msp—2 and diversity but different from Kanchanaburi isolates.These allelic variant profiles are valuable baseline data for future epidemiological study of malaria transmission and for continued monitoring of polymorphisms associated with antimalarial drug resistance in these areas.展开更多
[Objective] The paper was to improve the blast resistance of insect-resistant transgenic rice. [Method] The Japonica rice variety Jikang10, a new transgenic variety with exogenous insect-resistant gene Cry1C, was used...[Objective] The paper was to improve the blast resistance of insect-resistant transgenic rice. [Method] The Japonica rice variety Jikang10, a new transgenic variety with exogenous insect-resistant gene Cry1C, was used as the receptor, and Kongyu 131, a traditional breeding variety with broad-spectrum high blast resistance genes Pi1 and Pi2, was used as the donor to breeding new rice varieties. The genes were polymerized by hybridization and multi-generation backcrossing, and the offspring of each generation was screened by molecular marker assisted selection, field identification of multi-resistance against insect pests and diseases and agronomic trait selection. [Result] Four lines SK01, SK02, SK03 and SK04 with better resistances to insect pests and blast and outstanding agronomic traits in field were selected. [Conclusion] The results will lay foundations for breeding new multi-resistance rice varieties in Huanghuai rice region.展开更多
Vitamin D, a fat-soluble vitamin and endocrine horm one, and it impacts various bone and extra-bone health, such as osteoporosis, diabetes, and cancer. The main circulating form of vitamin D is 25-hydroxyvitamin D [25...Vitamin D, a fat-soluble vitamin and endocrine horm one, and it impacts various bone and extra-bone health, such as osteoporosis, diabetes, and cancer. The main circulating form of vitamin D is 25-hydroxyvitamin D [25(OH)D] and it is a useful clinical biomarker of vitamin D status. The Institute of Medicine (IOM) defines as vitamin D deficiency (VDD) when serum 25(OH)D concentration is less than 20 ng/mL⑴.Worldwide, VDD is recognized as a severe public health problem. In 2007, Holick estimated that globally over one billion people suffered from VDD or vitamin D insufficiency (VDI). In China, it has bee n reported that the prevale nee of VDD ranged from 38.8% to 91.2% in different regions.展开更多
BACKGROUND Invasion and migration are the irreversible stages of colorectal cancer(CRC).The key is to find a sensitive,reliable molecular marker that can predict the migration of CRC at an early stage.N-myc downstream...BACKGROUND Invasion and migration are the irreversible stages of colorectal cancer(CRC).The key is to find a sensitive,reliable molecular marker that can predict the migration of CRC at an early stage.N-myc downstream regulated gene 1(NDRG1)is a multifunctional gene that has been tentatively reported to have a strong relationship with tumor invasion and migration,however the current molecular role of NDRG1 in CRC remains unknown.AIM To explore the role of NDRG1 in the development of CRC.METHODS NDRG1 stably over-expressed Caco2 cell line was established by lentiviral infection and NDRG1 knock-out Caco2 cell line was established by CRISPR/Cas9.Furthermore,the mRNA and protein levels of NDRG1 in Caco2 cells after NDRG1 over-expression and knockout were detected by real-time polymerase chain reaction and western blot.The cell proliferation rate was measured by the cell counting kit-8 method;cell cycle and apoptosis were detected by flow cytometry;invasion and migration ability were detected by the 24-transwell method.RESULTS NDRG1 over-expression inhibited Caco2 proliferation and the cell cycle could be arrested at the G1/S phase when NDRG1 was over-expressed,while the number of cells in the G2 phase was significantly increased when NDRG1 was knocked out.This suggests that NDRG1 inhibited the proliferation of Caco2 cells by arresting the cell cycle in the G1/S phase.Our data also demonstrated that NDRG1 promotes early cell apoptosis.Invasion and migration of cells were extensively inhibited when NDRG1 was over-expressed.CONCLUSION NDRG1 inhibits tumor progression in Caco2 cells which may represent a potential novel therapeutic strategy for the treatment of CRC.展开更多
Heterogeneous nuclear ribonucleoprotein （hnRNP） C plays a key role in RNA processing but also exerts a dominant negative effect on responses to 1,25-dihydroxyvitamin D （1,25（OH）2D） by functioning as a vitamin D ...Heterogeneous nuclear ribonucleoprotein （hnRNP） C plays a key role in RNA processing but also exerts a dominant negative effect on responses to 1,25-dihydroxyvitamin D （1,25（OH）2D） by functioning as a vitamin D response element-binding protein （VDRE-BP）. hnRNPC acts a tetramer of hnRNPC1 （huC1） and hnRNPC2 （huC2）, and organization of these subunits is critical to in vivo nucleic acid-binding. Overexpression of either huC1 or huC2 in human osteoblasts is sufficient to confer VDRE-BP suppression of 1,25（OH）2D-mediated transcription. However, huC1 or huC2 alone did not suppress 1,25（OH）2D-induced transcription in mouse osteoblastic cells. By contrast, overexpression of huC1 and huC2 in combination or transfection with a bone-specific polycistronic vector using a ＂self-cleaving＂ 2A peptide to co-express huC1/C2 suppressed 1,25D-mediated induction of osteoblast target gene expression. Structural diversity of hnRNPC between human/NWPs and mouse/rat/rabbit/dog was investigated by analysis of sequence variations within the hnRNP CLZ domain. The predicted loss of distal helical function in hnRNPC from lower species provides an explanation for the altered interaction between huC1/C2 and their mouse counterparts. These data provide new evidence of a role for hnRNPC1/C2 in 1,25（OH）2D-driven gene expression, and further suggest that species-specific tetramerization is a crucial determinant of its actions as a regulator of VDR-directed transactivation.展开更多
Summary： The ATP2C1 gene mutation in one ease of familial benign chronic pemphigus was investigated.One patient was diagnosed as familial benign chronic pemphigus by pathology, ultrastructral examination and clinical...Summary： The ATP2C1 gene mutation in one ease of familial benign chronic pemphigus was investigated.One patient was diagnosed as familial benign chronic pemphigus by pathology, ultrastructral examination and clinical features. Genomic DNA was extracted from blood samples. Mutation of ATP2CI gene was detected by polymerase chain reaction （PCR） and DNA sequencing. The results showed that deletion mutation was detected in ATP2C1 gene in this patient, which was 2374delTTTG. No mutation was found in the family members and normal individuals. It was coneluded that the 2374delTTTG mutation in ATP2C1 gene was the specific mutation for the clinical phenotype for this patient and was a de novo mutation.展开更多
AIM:To investigate hepatitis virus, genetic and environmental factors, and their interactions in predisposing patients to liver diseases in Northeast India. METHODS:A total of 104 jaundice patients and 124 community c...AIM:To investigate hepatitis virus, genetic and environmental factors, and their interactions in predisposing patients to liver diseases in Northeast India. METHODS:A total of 104 jaundice patients and 124 community controls were included. Serological analysis was performed by routine enzyme-linked immunosorbent assay, and nucleic acid testing for hepatitis viruses was done by polymerase chain reaction (PCR), followed by PCR direct sequencing for viral genotyping. Cytochrome P450 2E1 (CYP2E1) polymorphism was studied by PCR-restriction fragment length polymorphism. Nitrite and volatile nitrosamines in indigenous foods consumed routinely by the Northeast Indian ethnic population were estimated by Griess’s reagent and GC-MS, respectively.RESULTS: Hepatitis A virus (HAV) infection was predominantly prevalent (36.5%) in our cohort, followed by hepatitis B virus (HBV), hepatitis E virus (HEV) andhepatitis C virus. HBV genotype D and HEV genotype 1 were the most dominant. CYP2E1 c1/c2 genotype frequency was comparatively higher in alcoholic (P<0.0001,OR =30.5) and cryptogenic (P=0.014, OR=8.714) patients, and was associated with significantly higher hepatitis risk (P=0.0.007,OR=6.489). Mutant C allele of Cyp2E1 DraⅠ frequency was comparatively higher in HAV (P=0.006), alcoholic (P =0.003) and cryptogenic (P=0.014) cases, and was associated with overall hepatitis risk (P=0.026, OR=5.083). Indigenous foods, Gundruk, Kharoli, betel leaf and nuts were found to have the highest nitrite content. CONCLUSION: Apart from viral factors, CYP2E1 polymorphism might be associated with increased risk of liver diseases in Northeast India. Indigenous foods that contain nitrite and nitrosamine might be an associated risk factor.展开更多
Actin is a ubiquitous protein and plays essential roles on cellular structure maintenance and cellular motility in both muscle and non-muscle tissues.Multiple genes encoding muscle actin have been identified from the ...Actin is a ubiquitous protein and plays essential roles on cellular structure maintenance and cellular motility in both muscle and non-muscle tissues.Multiple genes encoding muscle actin have been identified from the ascidians,including those expressed in the larval tail muscle,the adult body-wall muscle,and adult heart muscle.In this study,a novel striated non-tail muscle actin gene was identified from the RNA-seq data of Ciona savignyi embryos.Phylogenetic analysis,alignment of the N-terminal amino acid sequences and comparation of diagnostic residues provided evidence that it had high similarity with vertebrate cardiac and skeletal muscle actin.In situ hybridization and promoter-driven GFP reporter assay revealed that it was specifically expressed in the primordia of the oral and atrial siphon.We hereby defined it as siphon-specific muscle actin coding gene(Cs-SMA).A 201 bp(−1350 bp to−1150 bp)sequence containing T-box and Six1/2 binding motif within the upstream region of Cs-SMA confined the expression of GFP in the siphons of electroporated embryos.Six1/2 binding motif was experimentally confirmed to play indispensable role in controlling the siphon-specific expression of Cs-SMA.The tissue-specific expression of Cs-SMA in the siphon primordia indicated its potential crucial roles in Ciona embryogenesis and organogenesis.展开更多
In recent years,some super hybrid rice varieties were bred with strong culms and large panicles,which are mainly contributed by the ipa1-2D locus.A gain-of-function allele of OsSPL14 is the ipa1-2D and it can greatly ...In recent years,some super hybrid rice varieties were bred with strong culms and large panicles,which are mainly contributed by the ipa1-2D locus.A gain-of-function allele of OsSPL14 is the ipa1-2D and it can greatly increase the panicle primary branch number.However,the key downstream genes mediating this trait variation are not fully explored.In this study,we developed high-quality near-isogenic lines(NILs)with a difference of only 30 kb chromosomal segment covering the ipa1-2D locus.Using the NILs,we explored the impact of ipa1-2D on five sequential stages of early inflorescence development,and found that the locus can greatly enhance the initiation of primary branch meristems.A transcriptomic analysis was performed to unveil the downstream molecular network of ipa1-2D,and 87 genes were found differentially expressed,many of which are involved in metabolism and catalysis processes.In addition,transgenic lines of overexpression and RNA interference were generated to shape different levels of OsSPL14.They were also used to validate the expression variation explored by transcriptome.Based on the gene annotation,twelve potential downstream targets of ipa1-2D were selected,and their expression variation was confirmed by qRT-PCR analysis both in NILs and transgenic lines.This research expands the molecular network underlying ipa1-2D and provides novel gene information which might be involved in the control of panicle branching.We discussed the potential function of identified genes and highlighted their values for future function exploration and breeding application.展开更多
基金Supported by the National High-Level Hospital Clinical Research Fund,No.2022-PUMCH-A-020the Undergraduate Teaching Reform and Innovation Project,No.2022zlgc0108.
文摘Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores the potential mechanisms underlying the pathogenesis of CEAS,focusing on the role of SLCO2A1-encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2(PGE2)levels.Studies have suggested that elevated PGE2 levels contribute to mucosal damage,inflammation,and disruption of the intestinal barrier.The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality,as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS.Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel,targeted therapies.
文摘Parkinsonism by unilateral,intranigralβ-sitosterolβ-D-glucoside administration in rats is distinguished in that theα-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time,thus replicating several clinical features of Parkinson’s disease,a typicalα-synucleinopathy.As Nurr1 repressesα-synuclein,we evaluated whether unilateral transfected of rNurr1-V5 transgene via neurotensin-polyplex to the substantia nigra on day 30 after unilateralβ-sitosterolβ-D-glucoside lesion could affect bilateral neuropathology and sensorimotor deficits on day 30 post-transfection.This study found that rNurr1-V5 expression but not that of the green fluorescent protein(the negative control)reducedβ-sitosterolβ-D-glucoside-induced neuropathology.Accordingly,a bilateral increase in tyrosine hydroxylase-positive cells and arborization occurred in the substantia nigra and increased tyrosine hydroxylase-positive ramifications in the striatum.In addition,tyrosine hydroxylase-positive cells displayed less senescence markerβ-galactosidase and more neuron-cytoskeleton markerβIII-tubulin and brain-derived neurotrophic factor.A significant decrease in activated microglia(positive to ionized calcium-binding adaptor molecule 1)and neurotoxic astrocytes(positive to glial fibrillary acidic protein and complement component 3)and increased neurotrophic astrocytes(positive to glial fibrillary acidic protein and S100 calcium-binding protein A10)also occurred in the substantia nigra.These effects followed the bilateral reduction inα-synuclein aggregates in the nigrostriatal system,improving sensorimotor behavior.Our results show that unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neurodegeneration(senescence and loss of neuron-cytoskeleton and tyrosine hydroxylase-positive cells),neuroinflammation(activated microglia,neurotoxic astrocytes),α-synuclein aggregation,and sensorimotor deficits.Increased neurotrophic astrocytes and brain-derived neurotrophic factor can mediate the rNurr1-V5 effect,supporting its potential clinical use in the treatment of Parkinson’s disease.
文摘BACKGROUND Chronic myelomonocytic leukemia(CMML),a rare clonal hematopoietic stem cell disorder characterized by myelodysplastic syndrome and myeloproliferative neoplasms,has a generally poor prognosis,and easily progresses to acute myeloid leukemia.The simultaneous incidence of hematologic malignancies and solid tumors is extremely low,and CMML coinciding with lung malignancies is even rarer.Here,we report a case of CMML,with ASXL1 and EZH2 gene mutations,combined with non-small cell lung cancer(lung squamous cell carcinoma).CASE SUMMARY A 63-year-old male,suffering from toothache accompanied by coughing,sputum,and bloody sputum for three months,was given a blood test after experiencing continuous bleeding resulting from a tooth extraction at a local hospital.Based on morphological results,the patient was diagnosed with CMML and bronchoscopy was performed in situ to confirm the diagnosis of squamous cell carcinoma in the lower lobe of the lung.After receiving azacitidine,programmed cell death protein 1,and platinum-based chemotherapy drugs,the patient developed severe myelosuppression and eventually fatal leukocyte stasis and dyspnea.CONCLUSION During the treatment and observation of CMML and be vigilant of the growth of multiple primary malignant tumors.
基金supported by the National Natural Science Foundation of china,No.81974156(to TJ)the Natural Science Foundation of Jiangsu Province,No.BK20201117(to YDZ)。
文摘Triggering receptor expressed on myeloid cells-like 2(TREML2)is a newly identified susceptibility gene for Alzheimer's disease(AD).It encodes a microglial inflammation-associated receptor.To date,the potential role of mic roglial TREML2 in neuroinflammation in the context of AD remains unclear.In this study,APP/PS1 mice were used to investigate the dynamic changes of TREML2 levels in brain during AD progression.In addition,lipopolysaccharide(LPS)stimulation of primary microglia as well as a lentivirus-mediated TREML2 overexpression and knockdown were employed to explore the role of TREML2 in neuroinflammation in the context of AD.Our res ults show that TREML2 levels gradually increased in the brains of AP P/PS1 mice during disease progression.LPS stimulation of primary microglia led to the release of inflammato ry cytokines including interleukin-1β,inte rleukin-6,and tumor necrosis factor-a in the culture medium.The LPS-induced mic roglial release of inflammatory cytokines was enhanced by TREML2 overexpression and was attenuated by TREML2 knoc kdown.LPS increased the levels of mic roglial M1-type polarization marker inducible nitric oxide synthase.This effect was enhanced by TREML2 overexpression and ameliorated by TREML2 knockdown.Furthermore,the levels of microglial M2-type polarization markers CD206 and ARG1 in the primary microglia were reduced by TREML2 overexpression and elevated by TREML2 knockdown.LPS stimulation increased the levels of NLRP3 in primary microglia.The LPS-induced increase in NLRP3 was further elevated by TREML2 overexpression and alleviated by TREML2 knockdown.In summary,this study provides the first evidence that TREML2 modulates inflammation by regulating microglial polarization and NLRP3 inflammasome activation.These findings reveal the mechanisms by which TREML2 regulates microglial inflammation and suggest that TREML2 inhibition may represent a novel therapeutic strategy for AD.
基金Supported by a grant from Research Institute,Bansomdejchaopraya Rajabhat University(Grant no.2555)
文摘Objective:To study the genetic diversity at the msp—1,msp—2,and glurp genes of Plasmodium falciparum(P.falciparum) isolates from 3 endemic areas in Thailand:Tak.Kanchanaburi and Ranong provinces.Methods:A total of 144 P.falciparum isolates collected prior to Irealmenl during January.2012 to June,2013 were genotyped.DNA was extracted:allele frequency and diversity of msp-1.msp-2,and glurp genes were investigated by nested polymerase chain reaction.Results:P.falciparum isolates in this study had high rate of multiple genotypes infection(96.5%)with an overall mean multiplicity of infection of 3.21.The distribution of allelic families of msp-1was significantly different among isolales from Tak.kanchanahnri.and Ranong but not for the msp-2.K1 and MAD20 were the predominant allelic families at the msp-1 gene,whereas alleles belonging to 3D7 were more frequent at the msp-2 gene.The glurp gene had the least diverse alleles.Population structure of P.falciparum isolates from Tak and Ranong was quite similar as revealed by the presence of similar proportions of MAD20 and K1 alleles at msp-1 loci.3D7 and FC27 alleles at msp-2 loci as well as comparable mean MOI.Isolates from Kanchanaburi had different structures;the most prevalent alleles were K1 and RO33.Conclusions:The present study shows that P.falciparum isolates from Tak and Ranong provinces had similar allelic pattern of msp—1 and msp—2 and diversity but different from Kanchanaburi isolates.These allelic variant profiles are valuable baseline data for future epidemiological study of malaria transmission and for continued monitoring of polymorphisms associated with antimalarial drug resistance in these areas.
基金Supported by The Agricultural Seed Improvement Project of Shandong (2019LZGC017, 2019LZGC003)Agricultural Industry Research System (Rice) Project of Shandong Province (SDAIT-17-03)The Agricultural and Technology Innovation Project of Shandong Academy of Agricultural Sciences(CXGC2021A30)。
文摘[Objective] The paper was to improve the blast resistance of insect-resistant transgenic rice. [Method] The Japonica rice variety Jikang10, a new transgenic variety with exogenous insect-resistant gene Cry1C, was used as the receptor, and Kongyu 131, a traditional breeding variety with broad-spectrum high blast resistance genes Pi1 and Pi2, was used as the donor to breeding new rice varieties. The genes were polymerized by hybridization and multi-generation backcrossing, and the offspring of each generation was screened by molecular marker assisted selection, field identification of multi-resistance against insect pests and diseases and agronomic trait selection. [Result] Four lines SK01, SK02, SK03 and SK04 with better resistances to insect pests and blast and outstanding agronomic traits in field were selected. [Conclusion] The results will lay foundations for breeding new multi-resistance rice varieties in Huanghuai rice region.
基金supported by the National Nature Science Foundation of China [grants number 81872626,81573151,U1204823,and 81573243]Science and Technology Foundation for Innovation Talent of Henan Province [No.154200510010]
文摘Vitamin D, a fat-soluble vitamin and endocrine horm one, and it impacts various bone and extra-bone health, such as osteoporosis, diabetes, and cancer. The main circulating form of vitamin D is 25-hydroxyvitamin D [25(OH)D] and it is a useful clinical biomarker of vitamin D status. The Institute of Medicine (IOM) defines as vitamin D deficiency (VDD) when serum 25(OH)D concentration is less than 20 ng/mL⑴.Worldwide, VDD is recognized as a severe public health problem. In 2007, Holick estimated that globally over one billion people suffered from VDD or vitamin D insufficiency (VDI). In China, it has bee n reported that the prevale nee of VDD ranged from 38.8% to 91.2% in different regions.
基金the National Natural Science Foundation of China,No.81260361Incubation Project of Mianyang Central Hospital,No.2020FH05.
文摘BACKGROUND Invasion and migration are the irreversible stages of colorectal cancer(CRC).The key is to find a sensitive,reliable molecular marker that can predict the migration of CRC at an early stage.N-myc downstream regulated gene 1(NDRG1)is a multifunctional gene that has been tentatively reported to have a strong relationship with tumor invasion and migration,however the current molecular role of NDRG1 in CRC remains unknown.AIM To explore the role of NDRG1 in the development of CRC.METHODS NDRG1 stably over-expressed Caco2 cell line was established by lentiviral infection and NDRG1 knock-out Caco2 cell line was established by CRISPR/Cas9.Furthermore,the mRNA and protein levels of NDRG1 in Caco2 cells after NDRG1 over-expression and knockout were detected by real-time polymerase chain reaction and western blot.The cell proliferation rate was measured by the cell counting kit-8 method;cell cycle and apoptosis were detected by flow cytometry;invasion and migration ability were detected by the 24-transwell method.RESULTS NDRG1 over-expression inhibited Caco2 proliferation and the cell cycle could be arrested at the G1/S phase when NDRG1 was over-expressed,while the number of cells in the G2 phase was significantly increased when NDRG1 was knocked out.This suggests that NDRG1 inhibited the proliferation of Caco2 cells by arresting the cell cycle in the G1/S phase.Our data also demonstrated that NDRG1 promotes early cell apoptosis.Invasion and migration of cells were extensively inhibited when NDRG1 was over-expressed.CONCLUSION NDRG1 inhibits tumor progression in Caco2 cells which may represent a potential novel therapeutic strategy for the treatment of CRC.
基金supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number 5R01AR037399the UCLA Vector Core (Emmanuelle Faure and Kip Hermann) for vector and viral preparations supported by JCCC/P30 CA016042 and CURE/P30 DK41301
文摘Heterogeneous nuclear ribonucleoprotein （hnRNP） C plays a key role in RNA processing but also exerts a dominant negative effect on responses to 1,25-dihydroxyvitamin D （1,25（OH）2D） by functioning as a vitamin D response element-binding protein （VDRE-BP）. hnRNPC acts a tetramer of hnRNPC1 （huC1） and hnRNPC2 （huC2）, and organization of these subunits is critical to in vivo nucleic acid-binding. Overexpression of either huC1 or huC2 in human osteoblasts is sufficient to confer VDRE-BP suppression of 1,25（OH）2D-mediated transcription. However, huC1 or huC2 alone did not suppress 1,25（OH）2D-induced transcription in mouse osteoblastic cells. By contrast, overexpression of huC1 and huC2 in combination or transfection with a bone-specific polycistronic vector using a ＂self-cleaving＂ 2A peptide to co-express huC1/C2 suppressed 1,25D-mediated induction of osteoblast target gene expression. Structural diversity of hnRNPC between human/NWPs and mouse/rat/rabbit/dog was investigated by analysis of sequence variations within the hnRNP CLZ domain. The predicted loss of distal helical function in hnRNPC from lower species provides an explanation for the altered interaction between huC1/C2 and their mouse counterparts. These data provide new evidence of a role for hnRNPC1/C2 in 1,25（OH）2D-driven gene expression, and further suggest that species-specific tetramerization is a crucial determinant of its actions as a regulator of VDR-directed transactivation.
文摘Summary： The ATP2C1 gene mutation in one ease of familial benign chronic pemphigus was investigated.One patient was diagnosed as familial benign chronic pemphigus by pathology, ultrastructral examination and clinical features. Genomic DNA was extracted from blood samples. Mutation of ATP2CI gene was detected by polymerase chain reaction （PCR） and DNA sequencing. The results showed that deletion mutation was detected in ATP2C1 gene in this patient, which was 2374delTTTG. No mutation was found in the family members and normal individuals. It was coneluded that the 2374delTTTG mutation in ATP2C1 gene was the specific mutation for the clinical phenotype for this patient and was a de novo mutation.
基金Supported by Gauhati University,Guwahati,Assam,India
文摘AIM:To investigate hepatitis virus, genetic and environmental factors, and their interactions in predisposing patients to liver diseases in Northeast India. METHODS:A total of 104 jaundice patients and 124 community controls were included. Serological analysis was performed by routine enzyme-linked immunosorbent assay, and nucleic acid testing for hepatitis viruses was done by polymerase chain reaction (PCR), followed by PCR direct sequencing for viral genotyping. Cytochrome P450 2E1 (CYP2E1) polymorphism was studied by PCR-restriction fragment length polymorphism. Nitrite and volatile nitrosamines in indigenous foods consumed routinely by the Northeast Indian ethnic population were estimated by Griess’s reagent and GC-MS, respectively.RESULTS: Hepatitis A virus (HAV) infection was predominantly prevalent (36.5%) in our cohort, followed by hepatitis B virus (HBV), hepatitis E virus (HEV) andhepatitis C virus. HBV genotype D and HEV genotype 1 were the most dominant. CYP2E1 c1/c2 genotype frequency was comparatively higher in alcoholic (P<0.0001,OR =30.5) and cryptogenic (P=0.014, OR=8.714) patients, and was associated with significantly higher hepatitis risk (P=0.0.007,OR=6.489). Mutant C allele of Cyp2E1 DraⅠ frequency was comparatively higher in HAV (P=0.006), alcoholic (P =0.003) and cryptogenic (P=0.014) cases, and was associated with overall hepatitis risk (P=0.026, OR=5.083). Indigenous foods, Gundruk, Kharoli, betel leaf and nuts were found to have the highest nitrite content. CONCLUSION: Apart from viral factors, CYP2E1 polymorphism might be associated with increased risk of liver diseases in Northeast India. Indigenous foods that contain nitrite and nitrosamine might be an associated risk factor.
基金funded by the National Key Research and Development Program of China(Nos.2019YFE0190900,2018YFD0900705).
文摘Actin is a ubiquitous protein and plays essential roles on cellular structure maintenance and cellular motility in both muscle and non-muscle tissues.Multiple genes encoding muscle actin have been identified from the ascidians,including those expressed in the larval tail muscle,the adult body-wall muscle,and adult heart muscle.In this study,a novel striated non-tail muscle actin gene was identified from the RNA-seq data of Ciona savignyi embryos.Phylogenetic analysis,alignment of the N-terminal amino acid sequences and comparation of diagnostic residues provided evidence that it had high similarity with vertebrate cardiac and skeletal muscle actin.In situ hybridization and promoter-driven GFP reporter assay revealed that it was specifically expressed in the primordia of the oral and atrial siphon.We hereby defined it as siphon-specific muscle actin coding gene(Cs-SMA).A 201 bp(−1350 bp to−1150 bp)sequence containing T-box and Six1/2 binding motif within the upstream region of Cs-SMA confined the expression of GFP in the siphons of electroporated embryos.Six1/2 binding motif was experimentally confirmed to play indispensable role in controlling the siphon-specific expression of Cs-SMA.The tissue-specific expression of Cs-SMA in the siphon primordia indicated its potential crucial roles in Ciona embryogenesis and organogenesis.
基金This work was supported by grants from the National Natural Science Foundation of China(31600990,31871217 and 32072037)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(20KJA210002)+2 种基金Project of Special Funding for Crop Science Discipline Development(yzuxk202006)the open funds of the State Key Laboratory of Crop Genetics and Germplasm Enhancement(ZW202010)the Key Research and Development Program of Jiangsu Province(BE2018357).
文摘In recent years,some super hybrid rice varieties were bred with strong culms and large panicles,which are mainly contributed by the ipa1-2D locus.A gain-of-function allele of OsSPL14 is the ipa1-2D and it can greatly increase the panicle primary branch number.However,the key downstream genes mediating this trait variation are not fully explored.In this study,we developed high-quality near-isogenic lines(NILs)with a difference of only 30 kb chromosomal segment covering the ipa1-2D locus.Using the NILs,we explored the impact of ipa1-2D on five sequential stages of early inflorescence development,and found that the locus can greatly enhance the initiation of primary branch meristems.A transcriptomic analysis was performed to unveil the downstream molecular network of ipa1-2D,and 87 genes were found differentially expressed,many of which are involved in metabolism and catalysis processes.In addition,transgenic lines of overexpression and RNA interference were generated to shape different levels of OsSPL14.They were also used to validate the expression variation explored by transcriptome.Based on the gene annotation,twelve potential downstream targets of ipa1-2D were selected,and their expression variation was confirmed by qRT-PCR analysis both in NILs and transgenic lines.This research expands the molecular network underlying ipa1-2D and provides novel gene information which might be involved in the control of panicle branching.We discussed the potential function of identified genes and highlighted their values for future function exploration and breeding application.
