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1.
Zhonghua Yi Xue Za Zhi ; 104(12): 944-949, 2024 Mar 26.
Artigo em Chinês | MEDLINE | ID: mdl-38514343

RESUMO

Objective: To evaluate the mid-term efficacy of ABO incompatible living donor kidney transplantation (ABOi-KT) based on the results of routine renal biopsy for transplantation. Methods: Retrospective collection of clinical data from 23 pairs of ABOi-KT donors and recipients at the First Affiliated Hospital of Sun Yat-sen University from July 2015 to November 2021. ABOi-KT was performed on recipients after desensitization treatment, and the results of routine kidney transplant biopsy at 1 week, 1 month, 3 months, 6 months, and 12 months after surgery were analyzed. Combined with blood type antibody levels and renal function recovery, the mid-term efficacy of ABOi-KT was evaluated. Results: Among the 23 recipients, there were 19 males and 4 females; age range from 19 to 47 years old [(29.6±6.7) years old], all underwent ABOi-KT successfully after receiving desensitization treatment. The follow-up time was (44.6±22.4) months, of which 22 cases were followed up for more than 1 year. The incidence rates of rejection reactions at 1 week, 1 month, 3 months, 6 months, and 12 months after surgery were 15.0% (3/20), 11.1% (1/9), 7.7% (1/13), 25.0% (3/12), and 12.5% (1/8), respectively. For receptors with rejection reactions, targeted anti-rejection therapy was performed based on clinical symptoms and various indicators. Borderline T cell mediated rejection (TCMR) can be converted to mild tubular inflammation after anti-rejection treatment. The positive rate of complement C4d in peritubular capillaries was 95.0% (19/20) one week after surgery, and the positive rate of complement C4d was 100% at 3 and 12 months after surgery. The cumulative survival rates at 1, 3, 5, and 7 years after surgery were all 100%. The cumulative survival rates at 1, 3, 5, and 7 years after kidney transplantation were 100%, 93.3%, 84.0%, and 84.0%, respectively. Except for 2 recipients who underwent transplantation in 2017 and experienced kidney failure at 30 and 49 months after surgery, all other transplanted kidneys survived. Conclusions: The results of routine renal transplant biopsy show that ABOi-KT has a good mid-term therapeutic effect. The pathological changes of ABOi-KT can be dynamically observed through routine renal transplant biopsy and targeted treatment for rejection reactions can be provided accordingly.


Assuntos
Transplante de Rim , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Incompatibilidade de Grupos Sanguíneos , Rim , Doadores Vivos , Biópsia , Sistema ABO de Grupos Sanguíneos , Sobrevivência de Enxerto , Rejeição de Enxerto/epidemiologia
2.
Zhonghua Liu Xing Bing Xue Za Zhi ; 45(2): 250-256, 2024 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-38413065

RESUMO

Objective: To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults. Methods: A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test. Results: A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95%CI: 2.23-3.88) points (P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95%CI: 4.03-5.37) points (P<0.001). Ba Duan Jin showed significant improvement (P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions: This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.


Assuntos
Exercício Físico , Vida Independente , Masculino , Humanos , Feminino , Idoso , Educação em Saúde , China
3.
Br Poult Sci ; 64(2): 268-274, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36416611

RESUMO

1. Fertilisation rate is closely related to the reproductive performance and economic status of chicken laying breeders. In this study, two flocks (n = 1,029 in population I and n = 358 in population II) in the later laying period were used for investigating the individual differences among population fertilisation rates (FRs).2. The funnel and distal parts of the infundibulum were collected from nine individuals (five with low FR and four with high FR from population II) and RNA-sequencing (RNA-seq) method was used to investigate the transcriptome differences in fertilisation. Differences in fertilisation regulation were investigated by comparing the different parts (funnel and distal) of the infundibulum between the low FR and high FR groups.3. There were notable individual FR differences in both categories. Some individuals had a relative high FR (≥90%) for a long time (>5 days after AI), contrarily, some individuals lost the ability to fertilise eggs in a very short time.4. Differentially expressed genes (DEGs), such as DUSP7, PPP1R3B, FYB, OVA, OVALX and OVALY may be associated with sperm functional regulation, fertilisation and early-stage fertilised ovum development processes. DEGs such as AVBD1, AVBD2, AVBD6, NFATC2 and BANK1 indicated a severe immune response to sperm survival and fertilisation in the oviduct.5. The results suggested that individual differences should be considered in the breeding and reproduction process. The DEGs identified in this study may promote our understanding of different fertilisation regulation in laying breeders.


Assuntos
Galinhas , Individualidade , Animais , Masculino , Feminino , Galinhas/genética , Sêmen , Óvulo , Perfilação da Expressão Gênica/veterinária , Hipófise , Fertilização/genética , Transcriptoma
4.
Nan Fang Yi Ke Da Xue Xue Bao ; 43(12): 1998-2005, 2023 Dec 20.
Artigo em Chinês | MEDLINE | ID: mdl-38189384

RESUMO

OBJECTIVE: To explore the role of epigenetic signal molecule bromodomain protein 4 (BRD4) in mediating the therapeutic effect of Liuwei Dihuang (LWDH) Pills on postmenopausal osteoporosis (PMOP) and fatigue. METHODS: Thirty rat models of PMOP induced by bilateral ovariectomy were randomized equally into two groups for treatment with normal saline (model group) or LWDH Pills (385.7 mg/kg), with another 15 sham-operated rats as the sham operation group. After 12 weeks of treatment, femoral samples were taken to determine the bone density and BRD4 protein expression. The weight-bearing exhaustive swimming time of the rat models was recorded, and serum levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were measured using enzyme-linked immunosorbent assay. In cultured primary osteoblasts the changes in the expressions of BRD4, MAPK and NF-κB proteins were detected by immunofluorescence staining following treatment with LWDH Pills. RESULTS: The rat models of PMOP showed significantly up-regulated expression of BRD4 protein in the femoral tissue (P < 0.05), which was obviously lowered by treatment with LWDH Pills. The rats treated with LWDH Pills also showed significant improvement of fatigue. Immunofluorescent staining of the osteoblasts showed that treatment with LWDH Pills significantly decreased the protein expressions of BRD4, MAPK and NF-κB. Analysis of the GSE56116 dataset revealed that that patients with kidney-yin deficiency had significantly higher BRD4 expression than those in the kidney-yang-deficiency group and non-kidney-deficiency group (P < 0.05). The upregulation of BRD4 expression involved multiple signaling pathways including neural ligand receptor response, cytoskeleton rearrangement, cytokine interaction, and granulocyte colony-stimulating factor chemotaxis pathways. CONCLUSION: LWDH can alleviate PMOP and fatigue by decreasing BRD4 signaling pathway, suggesting that potential of BRD4 as a promising therapeutic target for PMOP.


Assuntos
NF-kappa B , Osteoporose Pós-Menopausa , Humanos , Feminino , Animais , Ratos , Proteínas Nucleares , Osteoporose Pós-Menopausa/tratamento farmacológico , Fatores de Transcrição , Fadiga/tratamento farmacológico , Epigênese Genética , Proteínas que Contêm Bromodomínio , Proteínas de Ciclo Celular
6.
Zhonghua Bing Li Xue Za Zhi ; 50(7): 791-795, 2021 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-34405616

RESUMO

Objective: To investigate and compare the histologic characteristics of adenocarcinomas with mesonephric features located in different parts of the gynecologic tract. Methods: Two cases of mesonephric adenocarcinomas (MA) of the cervix and 5 cases of mesonephric-like adenocarcinomas (MLA) of the uterus and ovary were collected in Women's Hospital, School of Medicine, Zhejiang University from January 2018 to October 2020. Hematoxylin-eosin staining, immunohistochemistry and KRAS mutation testing were performed together with review of literature. Results: MA of the cervix as well as MLA of the uterus and ovary had similar morphologic features, showing an admixture of glandular, tubular, papillary and solid growth patterns. However, both MA cases were located in cervical stroma, which demonstrated residual mesonephric ducts present at the periphery. All four uterine MLA cases extensively involved the endometrium and myometrium. The ovarian MLA case was associated with endometriosis. No residual mesonephric ducts were present in the MLA cases. Immunohistochemically, GATA3 was positive in all seven MA/MLA cases. TTF1 was expressed only in 4/5 MLA cases. ER and PR were negative and p53 was wild-type in all cases. KRAS mutation was detected in all five cases. During the 6-32 months of follow-up, one patient developed recurrence and the others were tumor-free. Conclusions: In the gynecologic tract, both MA in cervix and MLA in uterus and ovary have similar morphologic features, immunohistochemical expression and KRAS mutation. However, distinct from MA that originates from mesonephric remnant, MLA is closely related to Mullerian epithelium.


Assuntos
Adenocarcinoma , Neoplasias Uterinas , Adenocarcinoma/genética , Biomarcadores Tumorais , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Uterinas/genética , Ductos Mesonéfricos
7.
Zhonghua Er Ke Za Zhi ; 59(4): 305-310, 2021 Apr 02.
Artigo em Chinês | MEDLINE | ID: mdl-33775050

RESUMO

Objective: To preliminarily establish the multidisciplinary cooperative vaccination management model for pediatric patients with hematological and oncological diseases, and to explore its feasibility. Methods: In this prospective study a total of 150 children with hematological and oncological diseases visited immunization clinic of Shanghai Children's Medical Center from March 2017 to August 2018 were enrolled in this study. After establishing the multidisciplinary team, designing vaccination plan, staff training, implementation and quality control, a multidisciplinary immunization clinic was set up and the vaccination plan were implemented. The implementation rate of vaccination immunization, the HBsAb level and serum hepatitis B surface antibody (HBsAb) level before and after treatment, the HBsAb level and serum immunoglobulin G antibody (IgG) levels of measles, mumps, rubella (MMR) before and 6 months after immunization, the vaccine-related adverse reactions were assessed prospectively. Chi-square test or Fisher exact test was used to compare the differences of antibody level. Results: A total of 124 cases had been vaccinated as planned, with a coverage rate of 82.7%. Among these cases, the difference of HBsAb positive rate before and after treatment was significant (62.9% (78/124) vs.13.7% (17/124), χ²= 63.489, P<0.01). In 64 cases that completed three doses of hepatitis B immunization, there was a significant difference in HBsAb positive rate before and 6 months after immunization (6.3% (4/64) vs. 98.4% (63/64), P<0.01). In 40 cases that completed MMR immunization, the IgG antibody positive rate for measles (22.5% (9/40) vs. 82.5% (33/40), χ²=31.746,P<0.01), mumps (22.5% (9/40) vs.82.5% (33/40), χ²=28.872,P<0.01), rubella (25.0% (10/40) vs.62.5% (25/40), χ²=11.429, P<0.01) before and 6 months after immunization were significantly different. Of the 421 doses of immunization, 25 (5.9%) doses reported controlled systemic or local adverse event. Conclusions: The immunization of pediatric patients with hematological and oncological diseases is of great importance. The newly-developed multidisciplinary cooperation immunization model for Chinese children with hematological and oncological diseases is feasible, and the immunization protocol is safe and has a certain effect.


Assuntos
Sarampo , Caxumba , Anticorpos Antivirais , Criança , China , Humanos , Lactente , Vacina contra Sarampo-Caxumba-Rubéola , Estudos Prospectivos , Vacinação
8.
Cryo Letters ; 41(1): 26-30, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33973981

RESUMO

BACKGROUND: Successful cryopreservation of organs and/or tissues of large dimension is challenging due to damages by solute concentration and thermal stress caused by crystallization during cooling and devitrification/recrystallization during rewarming. The key to reduce thermal stresses in cryopreserved biomaterials during rewarming is fast and uniform heating. OBJECTIVE: To explore a hybrid warming process using two heat sources (microwave and water bath) simultaneously to achieve faster and more uniform heating. MATERIALS AND METHODS: Rewarming of frozen cryoprotectants (CPA) using microwave and 37ºC water bath at the same time was experimentally studied. A helical antenna was installed at the center of a 1.8 mL cryovial. Microwave (2.4 GHz) was generated, amplified and transported to the helical antenna through the matched coaxial cables. Frozen CPA solution in the cryovial at an initial temperature of -196ºC was rewarmed by microwave and water bath. The temperature of two selected points in the sample with the maximum temperature difference was measured by thermocouples during rewarming. RESULTS: During rewarming of the frozen sample in 37ºC water bath without microwave, the warming rate was 70.2ºC min-1 with the maximum temperature gradient of 1.07ºC mm-1 in the sample. With microwave added to form a hybrid warming process, the warming rate was increased to be 100.5ºC min-1 with a smaller temperature gradient of 0.68ºC mm-1. CONCLUSION: The study indicated that warming rate and temperature uniformity increased with the microwave-water bath hybrid heating process.


Assuntos
Criopreservação , Crioprotetores , Micro-Ondas , Temperatura , Água
10.
Eur J Pharm Biopharm ; 139: 47-58, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30872012

RESUMO

Enteric coatings have shown in vivo dissolution rates that are poorly predicted by traditional in vitro tests, with the in vivo dissolution being considerably slower than in vitro. To provide a more mechanistic understanding of this, the dependence of the release properties of various enteric-coated (EC) products on bulk pH and bicarbonate molarity was investigated. It was found that, at presumably in vivo-relevant values, the bicarbonate molarity is a more significant determinant of the dissolution profile than the bulk pH. The findings also indicate that this steep relationship between the dissolution of enteric coatings and bicarbonate molarity limits those coatings' performance in vivo. This is attributed to the relatively low bicarbonate molarities in human intestinal fluids. Further, the hydration and dehydrations kinetics of carbonic acid and carbon dioxide are not sufficiently rapid to reach equilibrium in the diffusion layer surrounding a dissolving ionizable solid. This results in the effective pKa of bicarbonate in the diffusion layer being lower than that determined potentiometrically at equilibrium in the bulk surrounding fluid. These results demonstrate the importance of thoroughly investigating the intestinal bicarbonate concentrations and using bicarbonate buffers or properly designed surrogates (if possible) when evaluating enteric drug products during product development and quality control.


Assuntos
Bicarbonatos/química , Liberação Controlada de Fármacos , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , Modelos Químicos , Acetaminofen/química , Acetaminofen/farmacocinética , Soluções Tampão , Cápsulas , Química Farmacêutica/métodos , Excipientes/química , Humanos , Concentração de Íons de Hidrogênio , Derivados da Hipromelose/química , Mucosa Intestinal/química , Intestino Delgado/química , Mesalamina/química , Mesalamina/farmacocinética , Solubilidade
11.
Eur Rev Med Pharmacol Sci ; 22(19): 6268-6273, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30338795

RESUMO

OBJECTIVE: As a gynecological malignant tumor, cervical cancer tends to occur in younger patients. Furin is an important member of precursor protein convertase that may affect malignant tumor metastasis and neovascularization. Pancreatic duodenal homeobox (PDX), as a transcription factor, can inhibit Furin. This study intends to explore the impact of PDX on cervical cancer HeLa cell proliferation and mechanism. PATIENTS AND METHODS: PDX plasmid was transfected to cervical cancer HeLa cells. Cell proliferation, invasion, and migration were tested. HeLa cells were injected to Balb/c nude mice to observe the change of general status, tumor formation rate, tumor weight, and volume. RESULTS: PDX expression was gradually increased after PDX transfection following time extension. Cell proliferation, invasion, and migration in experimental group were significantly lower than those in normal control (p < 0.05). The nude mice injected with PDX transfected HeLa cells showed markedly better general status, with reducing rate of tumor formation, tumor weight and volume compared with control. CONCLUSIONS: PDX can suppress cervical cancer HeLa cell proliferation, cell invasion and migration, improve general status of tumor-bearing nude mice and reduce tumor weight and volume. Our data highlight the clinical benefits of PDX in inhibiting cervical cancer proliferation, invasion, and metastasis.


Assuntos
Proteínas de Homeodomínio/genética , Transativadores/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Adulto , Idoso , Animais , Movimento Celular , Proliferação de Células , Feminino , Células HeLa , Humanos , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Transplante de Neoplasias , Transfecção , Carga Tumoral
12.
Artigo em Chinês | MEDLINE | ID: mdl-29771089

RESUMO

Objective:To investigate the values of electrocochleograph(ECochG)in patients with OSAHS. Method:ECochG was performed in 31 (62 ears) OSAHS patients (moderately 5 cases, severely 26 cases) and 28 healthy adults (56 ears). AP latency ,AP amplitude and SP/AP were measured and analyzed. Result:There was no difference between the two groups in SP/AP amplitude ratio(P>0.05) while both AP latency(P<0.05) and AP amplitude(P<0.05) were significantly different. Conclusion:ECochG can confirm the damage of cochlear and auditory nerve near the cochlear segment in patients with moderate to severe OSAHS.


Assuntos
Audiometria de Resposta Evocada , Apneia Obstrutiva do Sono/fisiopatologia , Adulto , Estudos de Casos e Controles , Cóclea , Nervo Coclear/fisiopatologia , Humanos , Apneia Obstrutiva do Sono/diagnóstico
13.
Zhonghua Yi Xue Za Zhi ; 98(9): 678-681, 2018 Mar 06.
Artigo em Chinês | MEDLINE | ID: mdl-29534403

RESUMO

Objective: To compare the acute hemodynamic effects of intravenous fasudil with different dosage on patients with congenital heart defects (CHD) and severe pulmonary arterial hypertension (PAH). Methods: Sixty patients (37±17 years old) with CHD and PAH were consecutively enrolled. All patients underwent heart catheterization. The patients were randomly divided into two groups: the regular dosage group and the large dosage group. At initiation and 30 min after intravenous fasudil(30 mg and 60 mg respectively), the following hemodynamic parameters were measured and calculated: right atrial pressure(RAP), pulmonary arterypressure(PAP) , systemic artery pressure (SAP), pulmonary capillary wedge pressure(PCWP) , pulmonary vascular resistance(PVR) and systemic vascular resistance( SVR), cardiac index (CI) and artery oxygen saturation (SaO(2)). Results: Compared with pre-medication, both mPAP and PVR tended to reduce significantly in the regular dosage group and the large dosage group: mPAP from (63.7±8.6)to (58.3±8.5)mmHg(P<0.01) and from (62.9±8.8) to(55.1±7.8)mmHg (P<0.01), respectively; PVR from(9.9±4.3)to (7.7±3.9) Wood(P<0. 01) and from (9.5±4.9)to(6.1±4.8)Wood(P<0.01); CI tended to increase significantly in the two groups: from (2.9±0.9) to (3.1±1.1) L·min(-1)·m(-2)( P<0.05) and from(3.0±0.8) to (3.5±1.6) L·min(-1)·m(-2)( P<0.05), respectively . Compared with the regular dosage group, both mPAP and PVR tended to reduce significantly in the large dosage group: mPAP (8.2±1.8) vs (4.2±1. 0)mmHg (P<0.05); PVR(3.7±1.1) vs (2.1±0.8 ) Wood (P<0.05) .Meanwhile , there was no significant difference in CI, SAP, SVR and SaO(2) between the two groups. Conclusion: Fasudil could improve the acute hemodynamic effects of patients with CHD and severe PAH, especially in the large dosage group.


Assuntos
Cardiopatias Congênitas , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , Adulto , Hipertensão Pulmonar Primária Familiar , Hemodinâmica , Humanos , Hipertensão Pulmonar , Pessoa de Meia-Idade , Adulto Jovem
14.
Pharmacogenomics J ; 18(3): 460-466, 2018 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-28762371

RESUMO

Imatinib-induced ophthalmological side-effects, including conjunctiva hemorrhage and periorbital oedema, although very common and still remain relatively little understood. The present study investigated the effects of genetic polymorphisms of drug targets and membrane transporters on these side effects. We found that the minor allele of EGFR rs10258429 and SLC22A1 rs683369 were significant risk determinants of conjunctival hemorrhage with OR of 7.061 (95%CI=1.791-27.837, P=0.005 for EGFR rs10258429 CT+TT vs CC), and 4.809 (95%CI=1.267-18.431, P=0.021 for SLC22A1 rs683369 GG+CG vs CC). The minor allele of SLC22A5 rs274558 and ABCB1 rs2235040 were protective factors to periorbital oedema with OR of 0.313 (95%CI=0.149-0.656, P=0.002 for SLC22A5 rs274558 AA+AG vs GG), and 0.253 (95%CI=0.079-0.805, P=0.020 for ABCB1 rs2235040 CT vs CC). These results indicated that variants in EGFR, SLC22A1, SLC22A5 and ABCB1 influenced the incidence of Imatinib-induced ophthalmological toxicities, and polymorphism analyses in associated genes might be beneficial to optimize Imatinib treatment.


Assuntos
Oftalmopatias/genética , Predisposição Genética para Doença , Mesilato de Imatinib/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Alelos , Receptores ErbB/genética , Oftalmopatias/induzido quimicamente , Oftalmopatias/patologia , Feminino , Frequência do Gene , Genótipo , Humanos , Mesilato de Imatinib/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Transportador 1 de Cátions Orgânicos/genética , Polimorfismo de Nucleotídeo Único , Membro 5 da Família 22 de Carreadores de Soluto/genética
15.
J Stomatol Oral Maxillofac Surg ; 119(2): 158-160, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29246753

RESUMO

Laugier-Hunziker syndrome (LHS) is a rare, benign, acquired pigmentary condition mainly affecting lips, oral mucosa and acral area, frequently associated with longitudinal melanonychia. Herein, we reported a 45-year-old female case with LHS. The clinical, dermoscopic, histopathologic features of LHS were reviewed and the important differential diagnosis was discussed.


Assuntos
Hiperpigmentação , Doenças Labiais , Doenças da Unha , Feminino , Humanos , Pessoa de Meia-Idade , Mucosa Bucal , Síndrome
16.
Leukemia ; 32(1): 149-158, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28626217

RESUMO

Interferon regulatory factor (IRF)-8 is a critical transcription factor involved in the pathogenesis of myeloid neoplasia. However, the underlying mechanisms in vivo are not well known. Investigation of irf8-mutant zebrafish in this study indicated that Irf8 is evolutionarily conserved as an essential neoplastic suppressor through tight control of the proliferation and longevity of myeloid cells. Surviving irf8 mutants quickly developed a myeloproliferative neoplasm (MPN)-like disease with enhanced output of the myeloid precursors, which recurred after transplantation. Multiple molecules presented notable alteration and Mertk signaling was aberrantly activated in the hematopoietic cells in irf8 mutants. Transgenic mertk overexpression in Tg(coro1a:mertk) zebrafish recapitulated the myeloid neoplasia-like syndrome in irf8 mutants. Moreover, functional interference with Mertk, via morpholino knockdown or genetic disruption, attenuated the myeloid expansion phenotype caused by Irf8 deficiency. Therefore, Mertk signaling is a critical downstream player in the Irf8-mediated regulation of the progression of myeloid neoplasia. Our study extends the understanding of the mechanisms underlying leukemogenesis.


Assuntos
Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/patologia , Transdução de Sinais/genética , Peixe-Zebra/genética , c-Mer Tirosina Quinase/genética , Animais , Animais Geneticamente Modificados/genética , Proliferação de Células/genética , Progressão da Doença , Regulação da Expressão Gênica/genética , Fatores Reguladores de Interferon , Células Mieloides/patologia , Mielopoese/genética
17.
Zhonghua Bing Li Xue Za Zhi ; 46(8): 573-574, 2017 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-28810302
18.
Oncogene ; 36(50): 6906-6918, 2017 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-28846104

RESUMO

Berberine, an isoquinoline alkaloid, is a traditional oriental medicine used to treat diarrhea and gastroenteritis. Recently, we reported that it could inhibit the growth of intestinal polyp in animals and in patients with the familial adenomatous polyposis by downregulating ß-catenin signaling. However, the intracellular target mediating the effects of berberine remains elusive. Here, we provide evidence that berberine inhibits ß-catenin function via directly binding to a unique region comprising residues Gln275, Arg316 and Arg371 in nuclear receptor retinoid X receptor alpha (RXRα), where berberine concomitantly binding to and synergistically activating RXRα with 9-cis-retinoic acid (9-cis-RA), a natural ligand binding to the classical ligand-binding pocket of RXRα. Berberine binding promotes RXRα interaction with nuclear ß-catenin, leading to c-Cbl mediated degradation of ß-catenin, and consequently inhibits the proliferation of colon cancer cells. Furthermore, berberine suppresses the growth of human colon carcinoma xenograft in nude mice in an RXRα-dependent manner. Together, our study not only identifies RXRα as a direct protein target for berberine but also dissects their binding mode and validates that berberine indeed suppresses ß-catenin signaling and cell growth in colon cancer via binding RXRα, which provide new strategies for the design of new RXRα-based antitumor agents and drug combinations.


Assuntos
Berberina/farmacologia , Neoplasias do Colo/patologia , Receptor X Retinoide alfa/metabolismo , Transdução de Sinais/fisiologia , beta Catenina/fisiologia , Animais , Berberina/metabolismo , Berberina/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Aliment Pharmacol Ther ; 44(9): 967-975, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27604507

RESUMO

BACKGROUND: Thiopurine-induced leukopenia is the most common dangerous adverse event in Asians. NUDT15 R139C was recently proposed to be a promising biomarker for leukopenia with thiopurine therapy in Asians, but this has not been replicated in the Chinese population. AIM: To investigate the influence of NUDT15 R139C, thiopurine S-methyltransferase (TPMT), 6-TGN and 6-MMPR on thiopurine-induced leukopenia in Chinese patients with Crohn's disease. METHODS: Clinical and epidemiological characteristics were reviewed from medical records. NUDT15 R139C and TPMT were genotyped. 6-TGN/6-MMPR concentrations were measured with high-performance liquid chromatography (HPLC). RESULTS: A total of 253 patients were included, 65 (25.7%) of whom experienced leukopenia. The median follow-up with thiopurine treatment was 38.0 weeks (range, 1-192 weeks). NUDT15 R139C was strongly associated with the incidence of leukopenia (70.2% mutation vs. 12.8% wild type; P=8.61×10-19 ; odds ratio, 10.80; 95% CI, 5.89-19.83). However, TPMT genotype was not found to be correlated with the incidence of leukopenia (P = 0.44). In subgroup of NUDT15 wild type, there was significant difference of 6TGN concentration between patients with and without leukopenia (413.0 (174.2-831.4) vs. 279.7 (77.3-666.9) pmol/8 × 108 RBC, P = 0.0055). In contrast, no association was found in patients with NUDT15 R139C variant alleles (P = 0.26). 6-MMPR was not correlated with leukopenia (P = 0.84). CONCLUSIONS: In Chinese patients, it is strongly recommended to detect NUDT15 genotype rather than TPMT before initiating thiopurine drugs. 6TGN concentration should be routinely monitored in CD patients with NUDT15 wild type. As for CT genotype, starting at low dose and careful monitoring for leukopenia and 6TGN levels is recommended.


Assuntos
Povo Asiático/genética , Doença de Crohn/genética , Leucopenia/genética , Metiltransferases/genética , Polimorfismo Genético/genética , Pirofosfatases/genética , Adolescente , Adulto , Doença de Crohn/sangue , Doença de Crohn/tratamento farmacológico , Feminino , Seguimentos , Humanos , Leucopenia/sangue , Leucopenia/induzido quimicamente , Masculino , Metiltransferases/sangue , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Adulto Jovem
20.
Zhonghua Bing Li Xue Za Zhi ; 45(4): 248-51, 2016 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-27033388

RESUMO

OBJECTIVE: To study the clinicopathologic features and differential diagnosis of solitary fibrous tumor (SFT) in the urogenital system. METHODS: The clinical data and pathologic characteristics of eight cases of SFT in the urogenital system were analyzed, and the relevant literature was reviewed. RESULTS: The cohort included six male and two female patients, with age of onset ranging from 25 to 80 years. Five occurred in the kidney (three in the right kidney), one case each occurred in the bladder, the prostate and the spermatic cord. Most patients showed no obvious clinical symptoms or only had low back pain and swelling. The diameter of the tumor was ranged from 2.5 to 11.8 cm (median 5.2 cm). Microscopy showed at low magnification, the tumor cells were spindle-shaped and arranged in bundles or helicoid pattern. The regional mesenchymal fibroblasts showed hyperplasia, with obvious collagenization and formed hemangiopericytoma-like structure. One case showed increased mitotic figures (>5 cells/10 HPF) and focal necrosis. By immunohistochemistry, the tumor cells were positive for CD34 and STAT6 in all eight cases, CD99 and vimentin in six cases, bcl-2 in four cases and SMA in one case. All seven cases with follow-up did not show any tumor recurrence or metastasis. CONCLUSIONS: SFT is rare in the urogenital system and most patients show good prognosis. SFT expresses CD34 and STAT6 and needs to be distinguished from other spindle cell tumors.


Assuntos
Neoplasias dos Genitais Masculinos/patologia , Neoplasias Renais/patologia , Neoplasias da Próstata/patologia , Tumores Fibrosos Solitários/patologia , Cordão Espermático , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Neoplasias dos Genitais Masculinos/química , Hemangiopericitoma/patologia , Humanos , Imuno-Histoquímica , Neoplasias Renais/química , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/química , Fator de Transcrição STAT6/análise , Tumores Fibrosos Solitários/química , Cordão Espermático/química , Cordão Espermático/patologia , Neoplasias da Bexiga Urinária/química , Vimentina/análise
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