Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 210
Filtrar
1.
Clin Genet ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32017041

RESUMO

Severe oligozoospermia (SO) is an important cause of male infertility. Its etiology and pathogenesis are associated with genetic abnormalities; however, the genetic causes of the majority of idiopathic human SO remain unclear. Here, we report a homozygous splice-site mutation in M1AP (meiosis 1 associated protein; NM_138804, c.1435-1G>A) observed in a patient with SO from a consanguineous Han Chinese family. His parents and fertile brother were heterozygous for the mutation. The splice variant led to a lack of M1AP protein in the patient's spermatozoa. Ultrastructural and immunostaining analyses of patient's spermatozoa showed highly aberrant swollen mitochondrial sheaths with normal axonemal structures. Subsequent mutation screening identified three additional heterozygous M1AP variants in 4/243 subjects with idiopathic SO, but no M1AP variants among 223 fertile subjects. Additionally, a previously study reported that M1ap knock-out mice exhibited SO due to meiotic arrest. Hence, our findings indicate that M1AP mutation might represent novel genetic alteration responsible for human SO.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31909850

RESUMO

OBJECTIVES: To examine whether moral hazard may exist under unsupervised home-based online applications, leading to more assistive technology devices (ATDs) and larger per capita expenditures on ATDs than under supervised community center-based online applications. METHODS: Using the data from the Assistive Devices Resource Centre in Shanghai, descriptive statistics were estimated for the sociodemographics of applicants. Multiple linear regression and logistic regression were used to test the effect of the introduction of home-based online applications. RESULTS: In 2015-2016, there were marked increases of 22.3% in the total number of ATDs and 27.2% in the total expenditure on ATDs compared with 2013-2014. The per capita number and expenditure also demonstrated an increasing trend. More devices were applied for in 2015-2016 than in 2013-2014, yielding a higher expenditure per capita (P < .001). Interestingly, with an invisible price, more devices were applied for at home than in community centers (P < .001), but the expenditure per capita was smaller (P < .001). CONCLUSIONS: The introduction of online applications increased the number of ATDs per capita. The home-based applications induced the purchase of more ATDs but not higher expenditures on ATDs. Individuals with disabilities tend to request the maximum number of ATDs allowed by the application rules, which is an indicator of moral hazard. The prices of ATDs were not visible for individuals with disabilities, which may cause individuals to order costlier ATDs when applying at home. Stricter review may be needed to reign in the potential moral hazard among online applicants with disabilities.

3.
Hum Genet ; 139(2): 257-271, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31942643

RESUMO

Severe asthenozoospermia is a common cause of male infertility. Recent studies have revealed that SPEF2 mutations lead to multiple morphological abnormalities of the sperm flagella (MMAF) without primary ciliary dyskinesia (PCD) symptoms in males, but PCD phenotype was also found in one female individual. Therefore, whether there is a phenotypic continuum ranging from infertile patients with PCD to MMAF patients with no or low noise PCD manifestations remains elusive. Here, we performed whole-exome sequencing in 47 patients with severe asthenozoospermia from 45 unrelated Chinese families. We identified four novel biallelic mutations in SPEF2 (8.9%, 4/45) in six affected individuals (12.8%, 6/47), while no deleterious biallelic variants in SPEF2 were detected in 637 controls, including 219 with oligoasthenospermia, 195 with non-obstructive azoospermia, and 223 fertile controls. Notably, all six patients exhibited PCD-like symptoms, including recurrent airway infections, bronchitis, and rhinosinusitis. Ultrastructural analysis revealed normal 9 + 2 axonemes of respiratory cilia but consistently abnormal 9 + 0 axoneme or disordered accessory structures of sperm flagella, indicating different roles of SPEF2 in sperm flagella and respiratory cilia. Subsequently, a Spef2 knockout mouse model was used to validate the PCD-like phenotype and male infertility, where the subfertility of female Spef2-/- mice was found unexpectedly. Overall, our data bridge the link between MMAF and PCD based on the association of SPEF2 mutations with both infertility and PCD in males and provide basis for further exploring the molecular mechanism of SPEF2 during spermiogenesis and ciliogenesis.


Assuntos
Anormalidades Múltiplas/patologia , Proteínas de Ciclo Celular/genética , Cílios/patologia , Transtornos da Motilidade Ciliar/patologia , Infertilidade Masculina/patologia , Proteínas/fisiologia , Cauda do Espermatozoide/patologia , Anormalidades Múltiplas/genética , Animais , Cílios/genética , Transtornos da Motilidade Ciliar/genética , Feminino , Humanos , Infertilidade Masculina/genética , Masculino , Camundongos , Camundongos Knockout , Fenótipo , Motilidade Espermática , Cauda do Espermatozoide/metabolismo
4.
Anticancer Drugs ; 31(2): 158-168, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31584454

RESUMO

Although arsenic trioxide (ATO) treatment has transformed acute promyelocytic leukemia (APL) from the most fatal to the most curable hematological cancer, many high-risk APL patients who fail to achieve a complete molecular remission or relapse become resistant to ATO. Herein, we report that 7-(4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide (CUDC-101) exhibits specific anticancer effects on APL and ATO-resistant APL in vitro and in vivo, while showing negligible cytotoxic effect on the noncancerous cells including normal CD34 cells and bone marrow mesenchymal stem cells from APL patients. Further mechanistic studies show that CUDC-101 triggers caspase-dependent degradation of the promyelocytic leukemia-retinoic acid receptor alpha fusion protein. As a result, APL and ATO-resistant APL cells undergo apoptosis upon CUDC-101 treatment and this apoptosis-inducing effect is even stronger than that of ATO. Finally, using a xenograft mouse model, we demonstrated that CUDC-101 significantly represses leukemia development in vivo. In conclusion, these results suggested that CUDC-101 can serve as a potential candidate drug for APL, particularly for ATO-resistant APL.

5.
Clin Cancer Res ; 26(1): 282-289, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31471311

RESUMO

PURPOSE: We recently reported that indoleamine 2, 3-dioxygenase (IDO) activity is significantly correlated with more distant metastasis and worse survival. The present study examined whether radiotherapy (RT) dose fractionation correlates with IDO-mediated immune activity in patients with early-stage NSCLC.Methods: Patients with newly diagnosed stage I-II NSCLC treated with either conventionally fractionated 3-dimensional conformal radiotherapy (3DCRT) or stereotactic body radiotherapy (SBRT) were analyzed. Levels of two key molecules associated with the IDO immune checkpoint, serum kynurenine and the kynurenine:tryptophan ratio (K:T ratio), were measured at pre-RT, during-RT, and 3-month post-RT. The relationship between disease control outcomes [overall survival (OS), progression free survival, and local/regional/distant failure rates] and absolute levels of these markers, as well as dynamic changes in their levels during RT, was studied. RESULTS: Fifty-six patients (SBRT = 28, 3DCRT = 28) with early-stage NSCLC were studied. In all patients, higher kynurenine post-RT was significantly associated with worse OS ([HR, 1.25; 95% confidence interval (CI), 1.01-1.55; P = 0.044). No statistically significant differences in absolute kynurenine levels or the K:T ratio were observed in patients treated with 3DCRT or SBRT at any of the three time points. However, the absolute kynurenine levels rose significantly more post-RT in the 3DCRT patients with a median increase 0.721 ng/mL, compared to that of SBRT patients (0.115 ng/mL); P = 0.022. CONCLUSIONS: This study validated that elevated IDO activity correlated with worse survival outcomes in patients with early-stage NSCLC treated with definitive RT. Hypofractionated SBRT may have less immunosuppressive effect than 3DCRT, as measured by IDO.

6.
Radiother Oncol ; 144: 105-113, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31794944

RESUMO

INTRODUCTION: Associations between radiation-induced lymphopenia (RIL) and survival have been extensively reported. However, the immune system is not considered as an organ-at-risk (OAR) in radiotherapy. This study aimed to develop the framework of an immune OAR model that may be utilized to predict and minimize RIL. METHODS: A dynamic model was first developed for lymphocyte trafficking among 5 compartments of the immune system. Radiation dose to the circulating lymphocytes in each compartment was calculated based on the doses to fixed structures of each immune compartment and blood flow patterns. A RIL model was developed based on lymphocyte dynamics, lymphocyte radiosensitivity and reproductivity, and the dose to the lymphocytes. The model was tested in 51 patients by fitting it to weekly-measured absolute lymphocyte counts (ALC) for each patient, considering lymphocyte radiosensitivity and reproductivity as patient-dependent fitting parameters. RESULTS: The fitting was almost perfect for 20 patients, with sum of square of errors (SSE) between measured and predicted ALCs < 0.5. It was acceptable for another 27 patients, with SSE = 0.5~4.0. Only 4 patients had SSE > 4.0. The fitting also provided a method of in vivo estimation of radiosensitivity (α) for each patient. The median α was 0.40 Gy-1 for the 51 patients, consistent with in vitro measured data of 0.41 Gy-1 in the literature. CONCLUSION: We have presented a framework of developing an immune OAR model that has the potential to predict and minimize RIL in radiotherapy.

7.
J Cancer ; 10(27): 6767-6778, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31839811

RESUMO

OBJECTIVE: Fenretinide is reported to induce NR4A1-associated apoptosis in several types of cancer cells. However, it remains unclear about its specific role and the underlying mechanism in acute myeloid leukemia (AML). Therefore, this study aimed to explore the role and mechanism of fenretinide-induced apoptosis in AML. METHOD: Firstly, the NR4A1 mRNA level in the newly diagnosed AML patients was measured, then AML cells were treated with fenretinide at various time points and doses, and cell viability was investigated by using the cell-counting kit-8 (CCK-8) assay. Additionally, apoptosis and cell cycles were analyzed by using flow cytometry. Moreover, siNR4A1 was utilized to knockdown NR4A1 expression, and leptomycin B (LMB) was adopted to inhibit the nuclear export; afterwards, the apoptosis rate and expression of apoptotic proteins in AML cells were detected. In addition, the expression levels of NR4A1 in the nuclei and mitochondria of fenretinide-treated AML cells were also measured. Meanwhile, the interaction between NR4A1 and Bcl-2, as well as the Bcl-2 transformation, was also examined. The anti-leukemic effect of fenretinide on NOD/SCID mice was also determined through subcutaneous injection of HL-60 cells. RESULTS: NR4A1 expression in AML patients was markedly down-regulated compared with that in normal donors. Fenretinide induced the expression of NR4A1 and mitochondria-mediated apoptotic pathway-associated proteins in a time- and concentration-dependent manner. Importantly, both siNR4A1 alone or the combination of fenretinide with LMB could attenuate the fenretinide-induced apoptosis and expression of apoptotic proteins. Under the action of fenretinide, the NR4A1 protein expression was down-regulated in nuclear extracts whereas up-regulated in mitochondrial extracts. At the same time, fenretinide promoted NR4A1 translocation from nuclei into mitochondria, and enhanced the interaction between NR4A1 and Bcl-2, thereby exposing the BH3 domain of Bcl-2 to exert the anti-apoptotic effect. Moreover, fenretinide also exhibited an anti-leukemic effect and induced NR4A1 expression in the AML mouse model. CONCLUSIONS: Fenretinide exerts an obvious effect on AML cells both in vitro and in vivo. Besides, the NR4A1-mediated signaling pathway is highly involved in the fenretinide-induced apoptosis of AML cells.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31828919

RESUMO

While dehydrogenases play crucial roles in tricarboxylic acid (TCA) cycle of cell metabolism, which are extensively explored for biomedical and chemical engineering uses, it's a big challenge to overcome the shortcomings (low stability and high costs) of recombinant dehydrogenases. Herein, we made an interesting finding that two-dimension (2D) SnSe is capable of mimicking native dehydrogenases to efficiently catalyze hydrogen transfer from 1-(R)-2-(R')-ethanol groups. In contrary to susceptible native dehydrogenases, lactic dehydrogenase (LDH) for instance, SnSe is extremely tolerant to reaction condition changes ( e.g. pH, temperature and organic solvents) and displays extraordinary reusable capability. Structure-activity analysis indicates that the single-atom structure, Sn vacancy and hydrogen binding affinity of SnSe may be responsible for their catalytic activity. Overall, our findings define the first report of a 2D SnSe nanozyme to mimic key dehydrogenases in cell metabolism.

9.
Medicine (Baltimore) ; 98(49): e18247, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31804353

RESUMO

RATIONALE: Patients with chronic Strongyloides stercoralis infection are usually asymptomatic; therefore, their condition is easily overlooked. In immunosuppressed patients, mortality is high because of disseminated infection and hyperinfection. This report describes a fatal S stercoralis hyperinfection in a patient with nephrotic syndrome after treatment with steroids. PATIENT CONCERNS: A 70-year-old male presented with a history of progressive edema, skin infection, persistent fever, cough, intermittent abdominal pain, and progressive respiratory failure after steroid treatment. DIAGNOSIS: Nephrotic syndrome; cellulitis; S stercoralis hyperinfection; Klebsiella pneumonia. INTERVENTIONS: During the first hospital admission, the patient was administered full-dose glucocorticoid and antibiotic therapy after suffering from cellulitis. During the second admission, he was diagnosed and treated for normal digestive discomfort and a bacterial infection. The patient had progressive respiratory failure and was placed on a ventilator. He was immediately treated with albendazole when S stercoralis was found in samples of his sputum and feces. OUTCOMES: The patient died despite treatment with albendazole and antibiotic therapy. LESSONS: It is essential to consider the possibility of S stercoralis infection in immunosuppressed patients with nephrotic syndrome. Given the lack of classic manifestations and high mortality rate of advanced disease, continuous monitoring, early diagnosis, and proper treatment are imperative.


Assuntos
Infecções por Klebsiella/diagnóstico , Síndrome Nefrótica/diagnóstico , Estrongiloidíase/diagnóstico , Idoso , Animais , Doença Crônica , Coinfecção , Diagnóstico Diferencial , Evolução Fatal , Humanos , Hospedeiro Imunocomprometido , Infecções por Klebsiella/tratamento farmacológico , Masculino , Síndrome Nefrótica/tratamento farmacológico , Strongyloides stercoralis , Estrongiloidíase/tratamento farmacológico
10.
Vet Microbiol ; 237: 108397, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31585638

RESUMO

Aves polyomavirus 1 (APV) causes inflammatory disease in psittacine birds, especially in young budgerigar. In this study, an APV virus (SD18 strain) was isolated from a diseased psittacine birds breeding facility. The full genome (4981 bp) of SD18 was determined and analyzed. Phylogenetic analysis of full genome sequences indicated all the APV strains form two groups. The SD18 strain showed close relationship with APV isolated from Poland, however, the other Chinese strains are located in group II, which suggested different genotypes APVs are co-circulating in China. Compared with the consensus sequence of APV full genome, the SD18 strain contains 13 nucleotide mutations, and 2 unique amino acid substitutions (R179M and Q382K) located in VP2/3 and Large T proteins. To explore the pathogenicity of the virus, the SD18 strain was used to challenge 2-week-old budgerigars. All infected birds died no later than 5 days post infection, and virus was detected in multiple organs including brain, heart, ingluvies, liver, and intestine, which indicated that SD18 is fatal and causes systemic infection in young budgerigar. In vitro studies showed that SD18 replicated efficiently in CEF cells and reached the highest viral titers at 9 days post infection. Notably, replication of SD18 stimulated IFN-ß response in CEF cells and overexpression of the VP4 or VP4Delta proteins significantly inhibited IFN-ß promoter activation, which could be the strategy of APV to escape from the host innate immunity.


Assuntos
Doenças das Aves/virologia , Melopsittacus/virologia , Infecções por Polyomavirus/veterinária , Polyomavirus/isolamento & purificação , Animais , Doenças das Aves/epidemiologia , Surtos de Doenças/veterinária , Genoma Viral , Filogenia , Polyomavirus/genética , Infecções por Polyomavirus/epidemiologia , Infecções por Polyomavirus/virologia
11.
Int J Biol Macromol ; 141: 738-746, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31499105

RESUMO

Dextran-chitosan (DC) macromolecule resin was synthesized by ultrasonic heating and applied to adsorb various heavy metal ions (Cu2+, Co2+, Ni2+, Pb2+, Cd2+). The morphology and structure of the samples were characterized by various testing methods. The effects of five factors on the adsorption properties were studied. The adsorption kinetics, thermodynamics and isotherm models were discussed theoretically. The results show that the adsorption of heavy metal ions by DC resin is a spontaneous single molecule chemical adsorption, and the adsorption capacities of DC resin for Cu2+, Co2+, Ni2+, Pb2+ and Cd2+ were 342 mg g-1, 232 mg g-1, 184 mg g-1, 395 mg g-1, and 269 mg g-1, respectively at 20 °C, pH = 7 and adsorbent dose is 0.01 g. In addition, DC resin adsorbent has good reusability.

12.
J Med Genet ; 56(11): 750-757, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31413122

RESUMO

BACKGROUND: The genetic causes for most male infertility due to severe asthenozoospermia remain unclear. OBJECTIVE: Our objective was to identify unknown genetic factors in 47 patients with severe asthenozoospermia from 45 unrelated Chinese families. METHODS: We performed whole exome sequencing of 47 individuals with severe asthenozoospermia from 45 unrelated families. Mutation screening was performed in a control cohort of 637 individuals, including 219 with oligoasthenospermia, 195 with non-obstructive azoospermia and 223 fertile controls. Ultrastructural and immunostaining analyses of patients' spermatozoa were performed to characterise the effect of variants. RESULTS: One homozygous non-sense mutation (NM_194302, c.G5341T:p.E1781X), two compound heterozygous mutations (c.C2284T:p.R762X and c.1751delC:p.P584fs) and two compound heterozygous mutations (c.5714_5721del:p.L1905fs and c.C3021A:p.N1007K) were identified in CFAP65 of three individuals with completely immotile spermatozoa, respectively. No biallelic deleterious variants of CFAP65 were detected in the control cohort of 637 individuals. Ultrastructural and immunostaining analyses of spermatozoa from two patients showed highly aberrant sperm morphology with severe defects such as acrosome hypoplasia, disruption of the mitochondrial sheath and absence of the central pair complex. CONCLUSION: To the best of our knowledge, we are the first to report that CFAP65 mutations may cause spermatozoa to be completely immotile.

13.
Am J Nephrol ; 50(3): 196-203, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31416077

RESUMO

BACKGROUND: Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite involved in various diseases. S1P also plays significant roles in the differentiation of fibroblasts into myofibroblasts, being implicated in fibrotic diseases. S1P is produced by the phosphorylation of sphingosine catalyzed by sphingosine kinases (SphK1 and SphK2). It remains unclear if the activation of endogenous SphK1 contributes to fibrogenesis in kidneys. The present study determined the effect of SphK1 gene knockout (KO) on fibrotic markers in kidneys. METHODS: The renal fibrosis was produced using the unilateral ureteral obstruction (UUO) model in wild-type (WT) and SphK1 gene KO mice. Renal mRNA levels of SphK1 and S1P receptors (S1PR) were measured by real-time RT-PCR. Fibrotic and immune cell markers in kidneys were measured by Western blot analysis and immunostaining, respectively. Renal morphological damage was examined by Periodic-Acid Schiff staining. RESULTS: The mRNA levels of SphK1 and S1PRs were dramatically increased in renal tissues of WT-UUO mice, whereas the increase in renal SphK1 mRNA was blocked in KO-UUO mice. Interestingly, the increased levels of fibrotic markers, collagen and α-smooth muscle actin, in kidneys were significantly attenuated in KO-UUO versus WT-UUO mice. Meanwhile, kidney damage indices were remarkably attenuated in KO-UUO mice compared with WT-UUO mice. However, increased numbers of CD43+ and CD48+ cells, markers for T cell and macrophage, respectively, showed no significant difference between -WT-UUO and KO-UUO kidneys. CONCLUSION: The activation of the SphK1-S1P pathway may contribute to tubulointerstitial fibrosis in UUO kidneys by affecting fibrotic signaling within renal cells independent of immune modulation.

14.
Chemosphere ; 237: 124422, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31352104

RESUMO

Environmental estrogenic compounds are important pollutants, which are widely distributed in natural water bodies. They produce various adverse effects on fish, but their concentration-dependent toxicities in fish metabolism and health are not fully understood. This study investigated the effects of 17ß-estradiol (E2) and bisphenol A (BPA) at low and high concentrations on lipid deposition, inflammation and antioxidant response in male zebrafish. We measured fish growth parameters, gonad development, lipid contents and the activities of inflammatory and antioxidant enzymes, as well as their mRNA expressions. All E2 and BPA concentrations used increased body weight, damaged gonad structure and induced feminization in male zebrafish. The exposure of zebrafish to E2 and BPA promoted lipid accumulation by increasing total fat, liver triglycerides and free fatty acid contents, and also upregulated lipogenic genes expression, although they decreased total cholesterol content. Notably, zebrafish exposed to low concentrations of E2 (200 ng/L) and BPA (100 µg/L) had higher lipid synthesis and deposition compared to high concentrations (2000 ng/L and 2000 µg/L, respectively). However, the high concentrations of E2 and BPA increased inflammation and antioxidant response. Furthermore, BPA caused greater damage to fish gonad development and more severe lipid peroxidation compared to E2. Overall, the results suggest that the toxic effects of E2 and BPA on zebrafish are concentration-dependent such that, the relative low concentrations used induced lipid deposition, whereas the high ones caused adverse effects on inflammation and antioxidant response.


Assuntos
Antioxidantes/metabolismo , Compostos Benzidrílicos/farmacologia , Estradiol/farmacologia , Inflamação/induzido quimicamente , Metabolismo dos Lipídeos/efeitos dos fármacos , Fenóis/farmacologia , Poluentes Químicos da Água/toxicidade , Animais , Compostos Benzidrílicos/metabolismo , Relação Dose-Resposta a Droga , Estradiol/metabolismo , Estrogênios/farmacologia , Gônadas/efeitos dos fármacos , Inflamação/metabolismo , Masculino , Fenóis/metabolismo , Diferenciação Sexual , Peixe-Zebra/metabolismo
15.
J Clin Med ; 8(7)2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31277466

RESUMO

Virtual reality (VR) has the potential to help clinical medicine manage generalized anxiety disorder (GAD). However, patients with GAD who use traditional head-mounted VR to cycle may cause them to feel motion sickness and fatigue. To solve this problem, a projection-based virtual environment (VE) system was built to provide GAD patients with a sense of immersion while they are cycling. This projection-based VE system allows patients with GAD to interact with the virtual environment and produce experiences similar to cycling in the outdoors. Sixty GAD patients met several screening criteria and were selected as participants. All participants were randomly assigned to one of the two 20-min conditions: (1) Observing watercolor paintings projected by the projector while engaged in cycling with a stationary bicycle; or (2) observing the scenes (i.e., forest or park) projected by the VE system and engaging in cycling with a stationary bicycle. Finally, this study confirmed that patients with GAD in the projection-based VE group exhibited higher alpha values and lower galvanic skin responses (GSR) after cycling than those cycling in the control group. These results showed that cycling in the projection-based VE group allowed the patient with GAD to achieve higher exercise intensity and lower perceived emotional stress.

16.
J Cell Biochem ; 120(10): 17791-17810, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31264739

RESUMO

Chemoresistance often causes treatment failure of B-cell acute lymphoblastic leukemia (B-ALL). However, the mechanism remains unclear at present. Herein, overexpression of heme oxygenase-1 (HO-1) was found in the bone marrow stromal cells (BMSCs) from B-ALL patients developing resistance to vincristine (VCR), a chemotherapeutic agent. Two B-ALL cell lines Super B15 and CCRF-SB were cocultured with BMSCs transfected with lentivirus to regulate the expression of HO-1. Silencing HO-1 expression in BMSCs increased the apoptotic rates of B-ALL cell lines induced by VCR, whereas upregulating HO-1 expression reduced the rate. Cell cycle can be arrested in the G2/M phase by VCR. In contrast, B-ALL cells were arrested in the G0/G1 phase due to HO-1 overexpression in BMSCs, which avoided damage from the G2/M phase. Vascular endothelial growth factor (VEGF) in BMSCs, as a key factor in the microenvironment-associated chemoresistance, was also positively coexpressed with HO-1. VEGF secretion was markedly increased in BMSCs with HO-1 upregulation but decreased in BMSCs with HO-1 silencing. B-ALL cell lines became resistant to VCR when cultured with VEGF recombinant protein, so VEGF secretion induced by HO-1 expression may promote the VCR resistance of B-ALL cells. As to the molecular mechanism, the PI3K/AKT pathway mediated regulation of VEGF by HO-1. In conclusion, this study clarifies a mechanism by which B-ALL is induced to resist VCR through HO-1 overexpression in BMSCs, and provides a novel strategy for overcoming VCR resistance in clinical practice.

17.
J Periodontol ; 90(11): 1297-1306, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31161648

RESUMO

BACKGROUND: The relationship between chronic periodontitis and pulpal/cemental changes is seldom reported. This study aimed to report on the microstructural changes of cementum and histopathological features of the dental pulp in teeth with severe chronic periodontitis. METHODS: Eighty molar teeth with severe chronic periodontitis and 50 extracted third molars (as normal controls) were collected. The microstructure of cementum was evaluated by scanning electron microscopy, and the pulp was stained with hematoxylin and eosin. Interleukin (IL)-17 and IL-1ß levels were examined by immunohistochemistry/western blotting. Reactive oxygen species (ROS) and superoxide dismutase 1 (SOD 1) levels were also checked. Caspase 3 expression and terminal-deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining were used as apoptotic indices, and LC3B and P62 were detected to demonstrate the level of autophagy. RESULTS: The surface of cementum showed irregularities; the dental pulp was inflamed and under oxidative stress. IL-17 and IL-1ß levels were increased in the pulp of teeth with periodontitis. ROS and apoptosis levels were higher than in normal dental pulp, while SOD 1 level was reduced. Intriguingly, autophagy markers LC3B and P62 were upregulated in the pulp obtained from teeth with periodontitis. CONCLUSIONS: Severe chronic periodontitis influenced the microstructure of both cementum and dental pulp. The dental pulp collected from teeth with periodontitis was inflamed, under oxidative stress, and presented increased levels of apoptosis and autophagy relative to normal dental pulp.

18.
Transbound Emerg Dis ; 66(5): 1827-1833, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31237100

RESUMO

Psittacine beak and feather disease (PBFD) is a common disease in psittacine bird that caused by beak and feather disease virus (BFDV). BFDV is widely spread and threatening psittacine birds worldwide. However, the BFDV infection in China remains largely unknown. In this study, a surveillance study of BFDV was conducted in three budgerigar breeding facilities, which showed that 66.6% of collected faeces samples were positive for BFDV. Full genomes of nine BFDV circulating in the three budgerigar breeding facilities (three for each facility) were determined and analysed. The full genomes shared 75.9% to 87.5% identity with the known genotype BFDV. Phylogenetic analysis of the full genome indicated that the BFDV circulating in China formed a separated group, and the nine isolates fell into three subgroups, suggesting that different unique BFDV genotypes are circulating in China. Notably, the Cap genes of three strains (SD3, SD5 and SD9) showed low identity (67.9% to 70%) to all the known genotypes of BFDV. Phylogenetic analysis showed that these three Cap genes formed a unique lineage that is different from all known genotypes, which suggested that the SD3, SD5 and SD9 strains identified in this study belong to a novel genotype that has not been reported. However, the origin of this genotype remains unclear. All the data indicated that the different unique genotypes of BFDV are co-circulating in China, and active surveillance of BFDV is warranted.


Assuntos
Doenças das Aves/virologia , Infecções por Circoviridae/veterinária , Circovirus/genética , Genoma Viral/genética , Melopsittacus/virologia , Animais , Bico/virologia , Doenças das Aves/epidemiologia , Cruzamento , China/epidemiologia , Infecções por Circoviridae/epidemiologia , Infecções por Circoviridae/virologia , Circovirus/isolamento & purificação , Plumas/virologia , Genótipo , Filogenia
19.
Asian J Androl ; 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31210147

RESUMO

The syndrome of multiple morphological abnormalities of the sperm flagella (MMAF) is a specific kind of asthenoteratozoospermia with a mosaic of flagellar morphological abnormalities (absent, short, bent, coiled, and irregular flagella). MMAF was proposed in 2014 and has attracted increasing attention; however, it has not been clearly understood. In this review, we elucidate the definition of MMAF from a systematical view, the difference between MMAF and other conditions with asthenoteratozoospermia or asthenozoospermia (such as primary mitochondrial sheath defects and primary ciliary dyskinesia), the knowledge regarding its etiological mechanism and related genetic findings, and the clinical significance of MMAF for intracytoplasmic sperm injection and genetic counseling. This review provides the basic knowledge for MMAF and puts forward some suggestions for further investigations.

20.
Plant Physiol ; 180(4): 2142-2151, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31227618

RESUMO

Small nuclear RNAs (snRNAs) play essential roles in spliceosome assembly and splicing. Most snRNAs are transcribed by the DNA-dependent RNA polymerase II (Pol II) and require 3'-end endonucleolytic cleavage. We have previously shown that the Arabidopsis (Arabidopsis thaliana) Defective in snRNA Processing 1 (DSP1) complex, composed of at least five subunits, is responsible for snRNA 3' maturation and is essential for plant development. Yet it remains unclear how DSP1 complex subunits act together to process snRNAs. Here, we show that DSP4, a member of the metallo-ß-lactamase family, physically interacts with DSP1 through its ß-Casp domain. Null dsp4-1 mutants have pleiotropic developmental defects, including impaired pollen development and reduced pre-snRNA transcription and 3' maturation, resembling the phenotype of the dsp1-1 mutant. Interestingly, dsp1-1 dsp4-1 double mutants exhibit complete male sterility and reduced pre-snRNA transcription and 3'-end maturation, unlike dsp1-1 or dsp4-1 In addition, Pol II occupancy at snRNA loci is lower in dsp1-1 dsp4-1 than in either single mutant. We also detected miscleaved pre-snRNAs in dsp1-1 dsp4-1, but not in dsp1-1 or dsp4-1 Taken together, these data reveal that DSP1 and DSP4 function is essential for pollen development, and that the two cooperatively promote pre-snRNA transcription and 3'-end processing efficiency and accuracy.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA