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1.
Cell ; 182(5): 1328-1340.e13, 2020 09 03.
Article in English | MEDLINE | ID: mdl-32814014

ABSTRACT

Among arthropod vectors, ticks transmit the most diverse human and animal pathogens, leading to an increasing number of new challenges worldwide. Here we sequenced and assembled high-quality genomes of six ixodid tick species and further resequenced 678 tick specimens to understand three key aspects of ticks: genetic diversity, population structure, and pathogen distribution. We explored the genetic basis common to ticks, including heme and hemoglobin digestion, iron metabolism, and reactive oxygen species, and unveiled for the first time that genetic structure and pathogen composition in different tick species are mainly shaped by ecological and geographic factors. We further identified species-specific determinants associated with different host ranges, life cycles, and distributions. The findings of this study are an invaluable resource for research and control of ticks and tick-borne diseases.


Subject(s)
Genetic Variation/genetics , Tick-Borne Diseases/microbiology , Ticks/genetics , Animals , Cell Line , Disease Vectors , Host Specificity/genetics
2.
Respir Res ; 25(1): 67, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38317146

ABSTRACT

Chronic obstructive pulmonary disease (COPD) is a leading aging related cause of global mortality. Small airway narrowing is recognized as an early and significant factor for COPD development. Senescent fibroblasts were observed to accumulate in lung of COPD patients and promote COPD progression through aberrant extracellular matrix (ECM) deposition and senescence-associated secretory phenotype (SASP). On the basis of our previous study, we further investigated the the causes for the increased levels of miR-377-3p in the blood of COPD patients, as well as its regulatory function in the pathological progression of COPD. We found that the majority of up-regulated miR-377-3p was localized in lung fibroblasts. Inhibition of miR-377-3p improved chronic smoking-induced COPD in mice. Mechanistically, miR-377-3p promoted senescence of lung fibroblasts, while knockdown of miR-377-3p attenuated bleomycin-induced senescence in lung fibroblasts. We also identified ZFP36L1 as a direct target for miR-377-3p that likely mediated its pro senescence activity in lung fibroblasts. Our data reveal that miR-377-3p is crucial for COPD pathogenesis, and may serve as a potential target for COPD therapy.


Subject(s)
Butyrate Response Factor 1 , MicroRNAs , Pulmonary Disease, Chronic Obstructive , Animals , Humans , Mice , Aging , Butyrate Response Factor 1/metabolism , Cellular Senescence/genetics , Fibroblasts/metabolism , Lung/metabolism , MicroRNAs/metabolism , Pulmonary Disease, Chronic Obstructive/metabolism
3.
Ann Hematol ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38990294

ABSTRACT

The MEF2D rearrangement is a recurrent chromosomal abnormality detected in approximately 2.4-5.3% of patients with acute B-cell lymphoblastic leukemia (B-ALL). Currently, MEF2D-rearranged B-ALL is not classified as an independent subtype in the WHO classification. Consequently, the clinical significance of MEF2D rearrangement in B-ALL remains largely unexplored. In this study, we retrospectively screened 260 B-ALL patients with RNA sequencing data collected between November 2018 and December 2022. Among these, 10 patients were identified with MEF2D rearrangements (4 with MEF2D::HNRNPUL1, 3 with MEF2D::BCL9, 1 with MEF2D::ARID1B, 1 with MEF2D::DAZAP1 and 1 with MEF2D::HNRNPM). Notably, HNRNPM and ARID1B are reported as MEF2D fusion partners for the first time. The patient with the MEF2D::HNRNPM fusion was resistant to chemotherapy and chimeric antigen receptor T-cell therapy and relapsed early after allogenic stem cell transplantation. The patient with MEF2D::ARID1B experienced early extramedullary relapse after diagnosis. All 10 patients achieved complete remission after induction chemotherapy. However, 9/10 (90%) of whom experienced relapse. Three of the 9 patients relapsed with aberrant expression of myeloid antigens. The median overall survival of these patients was only 11 months. This small cohort showed a high incidence of early relapse and short survival in patients with MEF2D rearrangements.

4.
Br J Haematol ; 202(3): 539-549, 2023 08.
Article in English | MEDLINE | ID: mdl-37246158

ABSTRACT

Fms-like tyrosine kinase 3 (FLT3) is frequently mutated in haematological malignancies. Although canonical FLT3 mutations including internal tandem duplications (ITDs) and tyrosine kinase domains (TKDs) have been extensively studied, little is known about the clinical significance of non-canonical FLT3 mutations. Here, we first profiled the spectrum of FLT3 mutations in 869 consecutively newly diagnosed acute myeloid leukaemia (AML), myelodysplastic syndrome and acute lymphoblastic leukaemia patients. Our results showed four types of non-canonical FLT3 mutations depending on the affected protein structure: namely non-canonical point mutations (NCPMs) (19.2%), deletion (0.7%), frameshift (0.8%) and ITD outside the juxtamembrane domain (JMD) and TKD1 regions (0.5%). Furthermore, we found that the survival of patients with high-frequency (>1%) FLT3-NCPM in AML was comparable to those with canonical TKD. In vitro studies using seven representative FLT3-deletion or frameshift mutant constructs showed that the deletion mutants of TKD1 and the FLT3-ITD mutant of TKD2 had significantly higher kinase activity than wild-type FLT3, whereas the deletion mutants of JMD had phosphorylation levels comparable with wild-type FLT3. All tested deletion mutations and ITD were sensitive to AC220 and sorafenib. Collectively, these data enrich our understanding of FLT3 non-canonical mutations in haematological malignancies. Our results may also facilitate prognostic stratification and targeted therapy of AML with FLT3 non-canonical mutations.


Subject(s)
Hematologic Neoplasms , Leukemia, Myeloid, Acute , Humans , fms-Like Tyrosine Kinase 3/genetics , Mutation , Leukemia, Myeloid, Acute/genetics , Point Mutation
5.
Ann Hematol ; 102(9): 2397-2402, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37103615

ABSTRACT

Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype with a poor prognosis under conventional chemotherapy. Ph-like ALL has a similar gene expression profile to Philadelphia chromosome-positive (Ph+) ALL, but is highly heterogeneous in terms of genomic alterations. Approximately 10-20% of patients with Ph-like ALL harbor ABL class (e.g. ABL1, ABL2, PDGFRB, and CSF1R) rearrangements. Additional genes that form fusion genes with ABL class genes are still being researched. These aberrations result from rearrangements including chromosome translocations or deletions and may be targets of tyrosine kinase inhibitors (TKIs). However, due to the heterogeneity and rarity of each fusion gene in clinical practice, there is limited data on the efficacy of tyrosine kinase inhibitors. Here, we report three cases of Ph-like B-ALL with ABL1 rearrangements treated with the dasatinib backbone for the CNTRL::ABL1, LSM14A::ABL1, and FOXP1::ABL1 fusion genes. All three patients achieved rapid and profound remission with no significant adverse events. Our findings suggest that dasatinib is a potent TKI for the treatment of ABL1-rearranged Ph-like ALL and can be used as a first-line treatment option for such patients.


Subject(s)
Philadelphia Chromosome , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Dasatinib/therapeutic use , Fusion Proteins, bcr-abl/genetics , Protein Kinase Inhibitors/therapeutic use , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Repressor Proteins/genetics , Forkhead Transcription Factors
6.
Acta Pharmacol Sin ; 44(8): 1612-1624, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36747104

ABSTRACT

Suprachiasmatic nucleus (SCN) in mammals functions as the master circadian pacemaker that coordinates temporal organization of physiological processes with the environmental light/dark cycles. But the causative links between SCN and cardiovascular diseases, specifically the reparative responses after myocardial infarction (MI), remain largely unknown. In this study we disrupted mouse SCN function to investigate the role of SCN in cardiac dysfunction post-MI. Bilateral ablation of the SCN (SCNx) was generated in mice by electrical lesion; myocardial infarction was induced via ligation of the mid-left anterior descending artery (LAD); cardiac function was assessed using echocardiography. We showed that SCN ablation significantly alleviated MI-induced cardiac dysfunction and cardiac fibrosis, and promoted angiogenesis. RNA sequencing revealed differentially expressed genes in the heart of SCNx mice from D0 to D3 post-MI, which were functionally associated with the inflammatory response and cytokine-cytokine receptor interaction. Notably, the expression levels of insulin-like growth factor 2 (Igf2) in the heart and serum IGF2 concentration were significantly elevated in SCNx mice on D3 post-MI. Stimulation of murine peritoneal macrophages in vitro with serum isolated from SCNx mice on D3 post-MI accelerated the transition of anti-inflammatory macrophages, while antibody-mediated neutralization of IGF2 receptor blocked the macrophage transition toward the anti-inflammatory phenotype in vitro as well as the corresponding cardioprotective effects observed in SCNx mice post-MI. In addition, disruption of mouse SCN function by exposure to a desynchronizing condition (constant light) caused similar protective effects accompanied by elevated IGF2 expression on D3 post-MI. Finally, mice deficient in the circadian core clock genes (Ckm-cre; Bmal1f/f mice or Per1/2 double knockout) did not lead to increased serum IGF2 concentration and showed no protective roles in post-MI, suggesting that the cardioprotective effect observed in this study was mediated particularly by the SCN itself, but not by self-sustained molecular clock. Together, we demonstrate that inhibition of SCN function promotes Igf2 expression, which leads to macrophage transition and improves cardiac repair post-MI.


Subject(s)
Circadian Rhythm , Myocardial Infarction , Animals , Mice , Circadian Rhythm/genetics , Macrophages , Mammals , Mice, Inbred C57BL , Myocardial Infarction/metabolism , Suprachiasmatic Nucleus/metabolism
7.
Exp Cell Res ; 401(1): 112520, 2021 04 01.
Article in English | MEDLINE | ID: mdl-33639177

ABSTRACT

We previously found that ATP synthases localize to male-specific sensory cilia and control the ciliary response by regulating polycystin signalling in Caenorhabditis elegans. Herein, we discovered that the ciliary localization of ATP synthase is evolutionarily conserved in mammals. We showed that the ATP synthase subunit F1ß is colocalized with the cilia marker acetylated α-tubulin in both mammalian renal epithelial cells (MDCK) and normal mouse cholangiocytes (NMCs). Treatment with ATP synthase inhibitor oligomycin impaired ciliogenesis in MDCK cells, and F1ß was co-immunoprecipitated with PKD2 in mammalian cells. Our study provides evidence for the evolutionarily conserved localization of ATP synthase in cilia from worm to mammals. Defects in ATP synthase can lead to ciliary dysfunction, which may be a potential mechanism of polycystic kidney disease.


Subject(s)
Cilia/genetics , Mitochondrial Proton-Translocating ATPases/genetics , Molecular Chaperones/genetics , TRPP Cation Channels/genetics , ATP Synthetase Complexes/chemistry , ATP Synthetase Complexes/genetics , Adenosine Triphosphate/genetics , Animals , Caenorhabditis elegans/genetics , Cilia/metabolism , Dogs , Kinesins/genetics , Madin Darby Canine Kidney Cells , Mammals , Mice , Oligomycins/pharmacology , Polycystic Kidney Diseases/enzymology , Polycystic Kidney Diseases/genetics , Polycystic Kidney Diseases/pathology , Protein Processing, Post-Translational/genetics
8.
BMC Public Health ; 22(1): 2160, 2022 11 24.
Article in English | MEDLINE | ID: mdl-36419020

ABSTRACT

BACKGROUND: Anxiety and depression are two common psychological disorders in patients with pulmonary tuberculosis. We aimed to explore the effects of cognitive-behavioral therapy (CBT) on psychological stress and quality of life in patients with pulmonary tuberculosis. METHODS: From September 2018 to November 2018, 20 communities (461 participants in total) were randomly assigned in an intervention or control group following a two-level cluster random design. The intervention group underwent CBT for 2 months, whereas the control group received routine follow-up. Anxiety, depression, and quality of life were assessed using the Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder questionnaire (GAD-7), and 36-Item Short-Form Health Survey (SF-36) scales, respectively. Comparisons between the two groups were conducted using independent samples t-tests, and differences between the two groups before and after treatment were analyzed using paired samples t-tests. RESULTS: There were a total of 454 participants in the final analysis. After 2 months of CBT intervention, the CBT group had a GAD-7 score that was 1.72 lower than the control group (1.47-1.99, p < 0.001), a PHQ-9 score of the CBT group that was 2.05 lower than that of the control group (1.74-2.37, p < 0.001). The CBT group had a total SF-36 score that was 10.7 lower than that of the control group (95% CI: 7.9-13.5, p < 0.001). In patients with different degrees of anxiety and depression, only those in the intervention group who had mild and moderate anxiety and depression symptoms showed a significant reduction in anxiety and depression scores following the intervention. CONCLUSIONS: CBT can relieve anxiety, and depression symptoms and increase the quality of life in subjects with pulmonary tuberculosis. TRIALS REGISTRATION: ChiCTR-TRC-12001958 Date of Registration: 22/02/2012.


Subject(s)
Cognitive Behavioral Therapy , Tuberculosis, Pulmonary , Humans , Quality of Life , Stress, Psychological/therapy , Anxiety/therapy , Tuberculosis, Pulmonary/therapy
9.
J Cell Mol Med ; 25(18): 8628-8644, 2021 09.
Article in English | MEDLINE | ID: mdl-34309202

ABSTRACT

The relationship between baseline high peritoneal solute transport rate (PSTR) and the prognosis of peritoneal dialysis (PD) patients remains unclear. The present study combined clinical data and basic experiments to investigate the impact of baseline PSTR and the underlying molecular mechanisms. A total of 204 incident CAPD patients from four PD centres in Shanghai between 1 January 2014 and 30 September 2020 were grouped based on a peritoneal equilibration test after the first month of dialysis. Analysed with multivariate Cox and logistic regression models, baseline high PSTR was a significant risk factor for technique failure (AHR 5.70; 95% CI 1.581 to 20.548 p = 0.008). Baseline hyperuricemia was an independent predictor of mortality (AHR 1.006 95%CI 1.003 to 1.008, p < 0.001) and baseline high PSTR (AOR 1.007; 95%CI 1.003 to 1.012; p = 0.020). Since uric acid was closely related to high PSTR and adverse prognosis, the in vitro experiments were performed to explore the underlying mechanisms of which uric acid affected peritoneum. We found hyperuricemia induced epithelial-to-mesenchymal transition (EMT) of cultured human peritoneal mesothelial cells by activating TGF-ß1/Smad3 signalling pathway and nuclear transcription factors. Conclusively, high baseline PSTR induced by hyperuricaemia through EMT was an important reason of poor outcomes in CAPD patients.


Subject(s)
Kidney Failure, Chronic/therapy , Peritoneal Dialysis/adverse effects , Adolescent , Adult , Aged , Dialysis Solutions , Female , Humans , Male , Middle Aged , Prognosis , Risk Factors , Young Adult
10.
Diabet Med ; 38(2): e14491, 2021 02.
Article in English | MEDLINE | ID: mdl-33296541

ABSTRACT

OBJECTIVE: To assess whether group cognitive behavioural therapy (GCBT) delivered by general practitioners reduces anxiety and depression and improves glycaemic levels in adults with type 2 diabetes mellitus. METHODS: We conducted a community-based cluster randomized controlled trial in adults with type 2 diabetes mellitus from 48 communities in China. Participants received either GCBT plus usual care (UC) or UC only. General practitioners were trained in GCBT before intervention in the intervention group. The primary outcome was glycated haemoglobin (HbA1c ) concentration. Outcome data were collected from all participants at baseline, 2 months, 6 months and 1 year. The secondary outcomes were depression (Patient Health Questionnaire-9; PHQ-9) and anxiety (General Anxiety Disorder questionnaire; GAD-7). RESULTS: The GCBT group showed greater improvement in GAD-7 and PHQ-9 scores, respectively, than the UC group after 2 months post-baseline (T = -6.46, p < 0.0001; T = -5.29, p < 0.001), 6 months (T = -4.58, p < 0.001; T = -4.37, p < 0.001) and 1 year post-intervention (T = -3.91, p < 0.001; T = -3.57, p < 0.001). There was no difference in HbA1c values between the GCBT and UC groups at 2 months while the values were lower in the GCBT group at 6 months and 1 year (T = -6.83, p < 0.001; T = -4.93, p < 0.001, respectively). Subgroup analysis indicated a long-term effect of GCBT only for mild and moderate anxiety and mild depression groups. Similarly, HbA1c values reduced only in the mild and moderate anxiety and the mild depression groups. CONCLUSIONS: General practitioners can deliver GCBT interventions. GCBT plus UC is superior to UC for reducing mild/moderate anxiety and depression, and improving glycaemic levels. TRIAL REGISTRATION: Chinese clinical trials registration (ChiCTR-IOP-16008045).


Subject(s)
Anxiety/therapy , Cognitive Behavioral Therapy/methods , Depression/therapy , Diabetes Mellitus, Type 2/metabolism , Glycated Hemoglobin/metabolism , Psychotherapy, Group/methods , Stress, Psychological/therapy , Aged , Anxiety/psychology , China , Depression/psychology , Diabetes Mellitus, Type 2/psychology , Female , General Practitioners , Humans , Linear Models , Male , Middle Aged , Patient Health Questionnaire , Stress, Psychological/psychology , Treatment Outcome
11.
Nutr Metab Cardiovasc Dis ; 30(11): 1980-1988, 2020 10 30.
Article in English | MEDLINE | ID: mdl-32807632

ABSTRACT

BACKGROUND AND AIMS: Cognitive behavioral therapy (CBT) is recommended as the first-line nonpharmacotherapy for sleep complaints. However, there are no studies that tested CBT for improving sleep quality and increasing quality of life (QOL) in patients with type 2 diabetes mellitus (T2DM). Therefore, this study aims to test the effect of CBT on sleep disturbances and QOL in patients with T2DM. METHODS AND RESULTS: In total, 187 participants with T2DM and comorbid poor sleep quality were included in the analysis with the control group of 93 receiving usual care (UC) only and the intervention group of 94 receiving CBT with aerobic exercise plus UC, The Pittsburgh Sleep Quality Index (PSQI), the Diabetes-Specific Quality of Life Scale (DSQLS) and the glycated hemoglobin (HbA1C) values were collected at baseline, after the 2-month intervention, and 6 months of follow-up. The CBT group had 3.03 points lower PSQI scores (95% confidence interval [CI]: 2.07-4.00, P < 0.001) and 7.92 points lower total DSQLS scores (95% CI: 4.98-10.87, P < 0.001) than the control group after 6-month follow-up. No difference was found in HbAlc between the two groups (t = -0.47, P = 0.64) after 2-month intervention, while the CBT group had 0.89 units lower HbAlc (95% CI: 0.49-1.28, P < 0.001) than the control group after 6-month follow-up. CONCLUSION: CBT is effective for sleep disturbances and can also improve sleep quality, increase QOL, and decrease glycemic levels in participants with T2DM. TRIAL REGISTRATION: Chinese Clinical Trials Registration (Practical study of the appropriate technique for improvement of quality of life of the patients with type 2 diabetes in communities: ChiCTR-IOP-16008045).


Subject(s)
Cognitive Behavioral Therapy , Diabetes Mellitus, Type 2/therapy , Quality of Life , Sleep Wake Disorders/therapy , Sleep , Aged , Biomarkers/blood , Blood Glucose/metabolism , China , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/psychology , Female , Glycated Hemoglobin/metabolism , Humans , Male , Middle Aged , Single-Blind Method , Sleep Wake Disorders/complications , Sleep Wake Disorders/physiopathology , Sleep Wake Disorders/psychology , Time Factors , Treatment Outcome
12.
J Fish Dis ; 43(11): 1409-1418, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32880984

ABSTRACT

Clonorchis sinensis, an important fish-borne zoonotic trematode, is widely distributed in South-East Asia, especially in China. Infections from human and animal reservoir hosts occur due to the consumption of raw or undercooked fish with C. sinensis metacercariae. This study aimed to evaluate the prevalence of C. sinensis metacercariae in fish in South-East Asia via systematic review and meta-analysis. We searched PubMed, ScienceDirect, China National Knowledge Infrastructure, Wanfang and Chongqing VIP databases for studies published between 1976 and 2020 that are related to the prevalence of C. sinensis metacercariae in fish. Studies were screened with keywords based on inclusion and exclusion criteria. Seventy-one eligible articles were identified, covering three countries: China, Korea and Vietnam. The pooled prevalence of C. sinensis metacercariae in fish from South-East Asia was 30.5%, with 35.1% in China, 29.7% in Korea and 8.4% in Vietnam. In subgroup analyses of climate, season, water source and publication date, the highest prevalence was identified in the Dwb climate type (43.3%), summer (70.2%), river (34.5%) and pre-2001 publications (38.9%), respectively. In comparison, the lowest prevalence was found in the Dfa climate type (14.5%), winter (19.5%), lake (8.0%) and post-2001 publications (23.8%). Meta-regression results indicated that country (p = .009), the published time (p = .035) and water source subgroups (p = .003) may be the source of heterogeneity. Overall, our study indicates that a high prevalence of C. sinensis infections occurs in fish in China, Korea and Vietnam, illuminating a significant public health concern in these countries.


Subject(s)
Clonorchiasis/veterinary , Clonorchis sinensis/isolation & purification , Fish Diseases/parasitology , Animals , China/epidemiology , Climate , Clonorchiasis/epidemiology , Fish Diseases/epidemiology , Fishes , Republic of Korea/epidemiology , Vietnam/epidemiology
13.
Clin Infect Dis ; 67(7): 1110-1119, 2018 09 14.
Article in English | MEDLINE | ID: mdl-29538646

ABSTRACT

Background: Human babesiosis is an emerging health problem in China. Methods: Babesia were identified in ticks, sheep, and humans in northeastern China using polymerase chain reaction (PCR) followed by genetic sequencing. We enrolled residents who experienced a viral-like illness after recent tick bite or were healthy residents. We defined a case using the definition for babesiosis developed by the US Centers for Disease Control and Prevention. Results: A Babesia crassa-like agent was identified in Ixodes persulcatus and Haemaphysalis concinna ticks using PCR followed by sequencing. The agent was characterized through phylogenetic analyses of the 18S rRNA gene, the ß-tubulin gene, and the internal transcribed spacer region. We tested sheep as a possible reservoir and found that 1.1% were infected with the B. crassa-like agent. We screened 1125 human participants following tick bites using B. crassa-specific PCR and identified 31 confirmed and 27 suspected cases. All the patients were previously healthy except for 1 with an ovarian tumor. Headache (74%), nausea or vomiting (52%), and fever (48%) were the most common clinical manifestations of confirmed cases. Six of 10 cases remained PCR positive for B. crassa-like infection 9 months after initial diagnosis. Asymptomatic infections were detected in 7.5% of 160 local residents. Conclusions: We identified B. crassa-like infection in people in northeastern China that caused mild to moderate symptoms. The possibility of more severe disease in immunocompromised patients and of transmission through the blood supply due to asymptomatic infections justifies further investigation of this reported infection.


Subject(s)
Babesia/genetics , Babesiosis/epidemiology , Babesiosis/microbiology , Adolescent , Adult , Aged , Babesia/classification , Child , Child, Preschool , China/epidemiology , Female , Humans , Male , Middle Aged , Phylogeny , RNA, Bacterial/genetics , RNA, Ribosomal, 18S/genetics , Young Adult
14.
Cancer Sci ; 109(12): 3981-3992, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30320942

ABSTRACT

FMS-like tyrosine kinase 3 (FLT3) is one of the most frequently mutated genes in hematological malignancies. FLT3 internal tandem duplication (FLT3-ITD) mutations located in juxtamembrane domain (JMD) and tyrosine kinase domain 1 (TKD1) regions account for two-thirds of all FLT3 mutations. The outcome of patients remains unsatisfactory, with low survival rates. It is not yet known whether the different mutations within the FLT3 gene are all associated with patient outcome. In addition, the cause of FLT3-ITD in-frame duplication events remains unknown. Although there are some published studies investigating the FLT3-ITD mutation and its clinical implications in Chinese acute myeloid leukemia (AML) patients, sample sizes tend to be small and detailed molecular profiles of FLT3 mutations are lacking in these studies. In our study, 227 FLT3-ITD sequences were analyzed from 227 Chinese de novo AML patients. ITD were next classified into 3 types based on molecular profiles of insertion DNA sequences: DNA complete duplication (type I), DNA partial duplication (type II) and complete random sequence (type III). From the 154 patients, we confirmed that high ITD allelic ratio (≥.5) and allogeneic stem cell transplant treatment under CR1 are independent prognostic factors. We also presented evidence that ITD integration sites in the hinge region or beta1-sheet region are an unfavorable prognostic factor in adult AML patients with FLT3-ITD mutations. These findings may help to decipher the mechanisms of FLT3-ITD in-frame duplication events and stratify patients when considering different therapeutic combinations.


Subject(s)
Leukemia, Myeloid, Acute/therapy , Stem Cell Transplantation/methods , Tandem Repeat Sequences , fms-Like Tyrosine Kinase 3/chemistry , fms-Like Tyrosine Kinase 3/genetics , Adult , China , Female , Humans , Leukemia, Myeloid, Acute/genetics , Male , Middle Aged , Mutagenesis, Insertional , Prognosis , Protein Domains , Remission Induction , Sample Size , Survival Analysis , Transplantation, Homologous , Young Adult
15.
Exp Parasitol ; 184: 90-96, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29225048

ABSTRACT

Metorchis orientalis is a neglected zoonotic parasite, living in the gallbladder and bile duct of poultry and some mammals as well as humans. In spite of its economic and medical importance, the information known about the transcriptome and genome of M. orientalis is limited. In this study, we performed de novo sequencing, transcriptome assembly and functional annotations of the adult M. orientalis, obtained about 77.4 million high-quality clean reads, among which the length of the transcript contigs ranged from 100 to 11,249 nt with mean length of 373 nt and N50 length of 919 nt. We then assembled 31,943 unigenes, of which 20,009 (62.6%) were annotated by BLASTn and BLASTx searches against the available database. Among these unigenes, 19,795 (62.0%), 3407 (10.7%), 10,620 (33.2%) of them had significant similarity in the NR, NT and Swiss-Prot databases, respectively; 5744 (18.0%) and 4678 (14.6%) unigenes were assigned to GO and COG, respectively; and 9099 (28.5%) unigenes were identified and mapped onto 256 pathways in the KEGG Pathway database. Furthermore, we found that 98 (1.08%) unigenes were related to bile secretion and 5 (0.05%) to primary bile acid biosynthesis pathways category. The characterization of these transcriptomic data has implications for the better understanding of the biology of M. orientalis, and will facilitate the development of intervention agents for this and other pathogenic flukes of human and animal health significance.


Subject(s)
Neglected Diseases/parasitology , Opisthorchidae/physiology , Transcriptome , Trematode Infections/parasitology , Zoonoses/parasitology , Animals , Bile Ducts/parasitology , Computational Biology , DNA, Complementary/biosynthesis , Ducks/parasitology , Fish Diseases/parasitology , Fish Diseases/transmission , Fishes , Gallbladder/parasitology , High-Throughput Nucleotide Sequencing , Humans , Opisthorchidae/genetics , Poultry Diseases/parasitology , RNA, Helminth/genetics , RNA, Helminth/isolation & purification , RNA, Messenger/genetics , RNA, Messenger/isolation & purification , Exome Sequencing
16.
Exp Parasitol ; 181: 88-93, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28803904

ABSTRACT

Triodontophorus serratus and Triodontophorus nipponicus are two of the most common nematodes inhabiting in the large intestine of horse. In the present study, the complete mitochondrial (mt) genome sequences of T. serratus and T. nipponicus have been determined. The mt genomes of T. serratus and T. nipponicus are circular molecules with 13,794 bp and 13,701 bp in size, respectively. These circular mt genomes encode 36 genes, including 12 protein-coding genes, two rRNA genes and 22 tRNA genes. All of these genes are transcribed in the same direction and gene arrangements are consistent with that of gene arrangement 3 (GA3-type). T. serratus and T. nipponicus had two non-coding regions, but T. brevicauda had three. Phylogenetic relationships were reconstructed using concatenated amino acid sequences of the 12 protein-coding genes with three methods, indicating that three species of Triodontophorus clustered together with strong statistical support. However, the genera of Strongylus and Triodontophorus belonged to Strongylinae do not cluster together, and Triodontophorus is more closely related to Cylicocyclus insigne, Cylicocyclus nassatus, Cylicostephanus goldi (Cyathostominae) than to Strongylus. The findings from the present study provide useful genetic markers for studying the molecular ecology, systematics, and population genetics of Triodontophorus in equine.


Subject(s)
Genome, Mitochondrial , Horse Diseases/parasitology , Strongylida Infections/veterinary , Strongyloidea/genetics , Animals , Base Composition , Cecum/parasitology , Colon/parasitology , DNA, Helminth/chemistry , DNA, Mitochondrial/chemistry , Gene Order , Genome, Mitochondrial/genetics , Horses , Phylogeny , Strongylida Infections/parasitology , Strongyloidea/classification
17.
Foodborne Pathog Dis ; 14(8): 440-446, 2017 08.
Article in English | MEDLINE | ID: mdl-28737961

ABSTRACT

To investigate the metacercarial infections of fishborne zoonotic trematodes (FZT), a total of 6815 freshwater fish (in representing 13 species of 5 families) were collected from Songhua river (n = 2636), Nenjiang river (n = 1935), Mudanjiang river (n = 301), and other lakes or ponds (n = 1943) in 36 representative regions in Heilongjiang Province, China, from August 2012 to December 2015. Metacercariae of four FZT species, that is, Clonorchis sinensis, Metorchis orientalis, Isthmiophora hortensis, and Metagonimus yokogawai, metacercariae were detected in the examination by the artificial digestion method. As the partial data for C. sinensis were previously reported, the remaining three FZT species are to be treated in this study. The overall prevalence of M. orientalis, I. hortensis, and M. yokogawai, metacercariae was 10.54%, 0.28%, and 1.35%, respectively. Metacercariae of M. orientalis were detected in seven fish species, that is, Pseudorasbora parva, Hemiculter leucisculus, Saurogobio dabryi, Rhynchocypris lagowskii, Carassius auratus, Rhodeus ocellatus and Perccottus glehnii. Their prevalences were the highest in false dace, P. parva (26.81%), and in fish from Songhua river (17.94%). Metacercariae of I. hortensis were detected in only one fish species, Misgurnus anguillicaudatus, from Nenjiang river only. Metacercariae of M. yokogawai were detected in three fish species, that is, P. parva, H. leucisculus and S. dabryi. Their prevalences were the highest in sharpbelly, H. leucisculus (6.05%), and in fish from Mudanjiang river (5.65%). This study first demonstrated the existence of M. orientalis, I. hortensis, and M. yokogawai in freshwater fish from Heilongjiang Province, posing a major public health concern. Eight fish species, namely M. anguillicaudatus, P. parva, H. leucisculus, S. dabryi, R. lagowskii, C. auratus, R. ocellatus, and P. glehnii, cannot be eaten raw. Moreover, the findings of this study not only extended the second intermediate host range of FZT, but also improve the information of the distribution of FZT in China.


Subject(s)
Fish Diseases/parasitology , Trematoda/isolation & purification , Trematode Infections/parasitology , Animals , China/epidemiology , Fish Diseases/epidemiology , Fishes , Fresh Water , Humans , Lakes , Metacercariae , Prevalence , Public Health , Rivers , Trematoda/genetics , Trematode Infections/epidemiology , Zoonoses
18.
Appl Microbiol Biotechnol ; 100(4): 1967-1976, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26515562

ABSTRACT

Arthrobacter sp. strain YC-RL1, capable of utilizing bisphenol A (BPA) as sole carbon source for growth, was isolated from petroleum contaminated soil. YC-RL1 could rapidly degrade BPA in a wide range of pH (5.0-9.0) and temperature (20-40 °C). Substrate analysis found that YC-RL1 could also degrade bisphenol F (BPF) and tetrabromobisphenol A (TBBPA). The maximum and minimum concentrations of BPA (0.2-600 mg/L), BPF (0.2-600 mg/L), and TBBPA (0.2-300 mg/L) for efficient biodegradation were detected. The released bromide ion and metabolic intermediates of BPF and BPA/TBBPA were detected, as well as the degradation pathways for BPF and BPA/TBBPA were deduced tentatively. The present study provides important information for the investigation of BPs degrading mechanism and the application of microbial remediation in BP-contaminated environment. This study is the first report about a genus Arthrobacter bacterium which could simultaneously degrade BPA, BPF, and TBBPA.


Subject(s)
Arthrobacter/metabolism , Benzhydryl Compounds/metabolism , Soil Pollutants/metabolism , Biotransformation , Carbon/metabolism , Hydrogen-Ion Concentration , Temperature
19.
Exp Parasitol ; 169: 22-7, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27423970

ABSTRACT

Ticks are obligate blood-sucking ectoparasites of a wide range of vertebrates. They can transmit a range of pathogens that cause economic losses to livestock production as well as human disease. In the present study, the complete mitochondrial (mt) genome of Dermacentor silvarum was determined. The mt genome is 14,945 bp in length contains 37 genes, including 13 are protein-coding genes (cox1-3, nad1-6, nad4L, cytb, atp6 and atp8), two ribosomal RNA genes and 22 transfer RNA genes. The nucleotide composition of the D. silvarum mt genome was A + T biased at 78.78%; T was the most abundant nucleotide and G the least abundant. The mt genome of D. silvarum was 106 bp longer than that of Dermacentor nitens and the arrangements of two genomes were identical. For the 13 protein-coding genes, comparison between D. silvarum and D. nitens revealed sequence divergence at both the nucleotide (15.46-35.14%) and amino acid (6.05-48.98%) levels. Among them, cox1 was the most conserved gene, while atp8 was the least conserved. The lengths of the 13 protein-coding genes were the same or similar, except for cytb which was significantly longer in D. silvarum than in D. nitens. The mtDNA contained a variable repeat region consisting of a "similar to nad1" motif that was repeated three times, and the "Tick-box" motifs were also found. The overall difference between the nucleotide sequences of the two complete mt genomes was 21.4%. The mtDNA data presented in this study provide a rich resource for further studies on the phylogenetics, population genetics, and molecular epidemiology of ticks.


Subject(s)
DNA, Mitochondrial/chemistry , Dermacentor/genetics , Genome, Mitochondrial/genetics , Animals , Base Composition , Base Sequence/genetics , Cattle , Dermacentor/classification , Minisatellite Repeats , Molecular Sequence Annotation , Polymerase Chain Reaction , Proteins/genetics , RNA, Ribosomal/genetics , RNA, Transfer/genetics
20.
BMC Fam Pract ; 17: 40, 2016 Apr 05.
Article in English | MEDLINE | ID: mdl-27044393

ABSTRACT

BACKGROUND: Poor sleep quality and depression negatively impact the health-related quality of life of patients with type 2 diabetes, but the combined effect of the two factors is unknown. This study aimed to assess the interactive effects of poor sleep quality and depression on the quality of life in patients with type 2 diabetes. METHODS: Patients with type 2 diabetes (n = 944) completed the Diabetes Specificity Quality of Life scale (DSQL) and questionnaires on sleep quality and depression. The products of poor sleep quality and depression were added to the logistic regression model to evaluate their multiplicative interactions, which were expressed as the relative excess risk of interaction (RERI), the attributable proportion (AP) of interaction, and the synergy index (S). RESULTS: Poor sleep quality and depressive symptoms both increased DSQL scores. The co-presence of poor sleep quality and depressive symptoms significantly reduced DSQL scores by a factor of 3.96 on biological interaction measures. The relative excess risk of interaction was 1.08. The combined effect of poor sleep quality and depressive symptoms was observed only in women. CONCLUSIONS: Patients with both depressive symptoms and poor sleep quality are at an increased risk of reduction in diabetes-related quality of life, and this risk is particularly high for women due to the interaction effect. Clinicians should screen for and treat sleep difficulties and depressive symptoms in patients with type 2 diabetes.


Subject(s)
Depression/complications , Diabetes Mellitus, Type 2/psychology , Quality of Life , Sleep Initiation and Maintenance Disorders/complications , Adult , Aged , Cross-Sectional Studies , Depression/diagnosis , Diabetes Mellitus, Type 2/complications , Female , Health Status Indicators , Humans , Logistic Models , Male , Middle Aged , Self Report , Sleep Initiation and Maintenance Disorders/diagnosis , Surveys and Questionnaires
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