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1.
J Virol ; 97(11): e0110123, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-37916835

RESUMO

IMPORTANCE: Clade 2.3.4.4 H5Nx avian influenza viruses (AIVs) have circulated globally and caused substantial economic loss. Increasing numbers of humans have been infected with Clade 2.3.4.4 H5N6 AIVs in recent years. Only a few human influenza vaccines have been licensed to date. However, the licensed live attenuated influenza virus vaccine exhibited the potential of being recombinant with the wild-type influenza A virus (IAV). Therefore, we developed a chimeric cold-adapted attenuated influenza vaccine based on the Clade 2.3.4.4 H5 AIVs. These H5 vaccines demonstrate the advantage of being non-recombinant with circulated IAVs in the future influenza vaccine study. The findings of our current study reveal that these H5 vaccines can induce cross-reactive protective efficacy in mice and ferrets. Our H5 vaccines may provide a novel option for developing human-infected Clade 2.3.4.4 H5 AIV vaccines.


Assuntos
Proteção Cruzada , Vírus da Influenza A , Vacinas contra Influenza , Infecções por Orthomyxoviridae , Animais , Camundongos , Anticorpos Antivirais , Furões , Influenza Aviária , Vacinas contra Influenza/genética , Vacinas Atenuadas , Infecções por Orthomyxoviridae/prevenção & controle
2.
BMC Womens Health ; 23(1): 394, 2023 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-37496042

RESUMO

BACKGROUND: Uterine sarcomas are uncommon mesenchymal tumors of the uterus. The clinical problem is that the features of uterine sarcomas can sometimes mimic uterine fibroids. This study aims to investigate the clinical characteristics of patients with uterine sarcomas who were preoperative presenting mainly with uterine masses. METHODS: A retrospective analysis of patients who underwent gynecological surgery for uterine sarcomas at the Obstetrics & Gynecology Hospital of Fudan University, between January 2016 and December 2021. RESULTS: Over the 5-year period, 277 patients were final diagnosed of uterine sarcomas. A total of 162 patients were preoperatively diagnosed as uterine fibroids for surgical treatment, the majority of whom were diagnosed of uterine leiomyosarcoma (uLMS) (49/162) and low-grade endometrial stromal sarcoma (LG-ESS) (100/162). Ninety people underwent total hysterectomy and bilateral salpingo-oophorectomy (TH + BSO), while 72 underwent myomectomy followed by supplemental TH + BSO. The group with direct hysterectomy had a higher average age than the group with prior myomectomy (47.20 ± 8.94 vs. 40.86 ± 5.88, p < 0.001). Among patients preoperatively diagnosed as uterine fibroids, patients with uLMS had a higher proportion of previous myomectomy (26.53% vs. 5.00%, p < 0.001), a larger uterine mass diameter on ultrasound (8.38 ± 3.39 cm vs. 6.41 ± 1.92 cm, p < 0.001), and richer hypervascularity (34.69% vs. 18%, p = 0.024) compared with LG-ESS. CONCLUSIONS: Analysis of our data showed that a large proportion of uterine sarcomas, especially uLMS and LG-ESS, present mainly with uterine masses. Ultrasound features including a large uterine mass diameter and rich hypervascularity, and with a history of myomectomy may alert clinicians in suspicion of uLMS when compared with LG-ESS.


Assuntos
Neoplasias do Endométrio , Leiomioma , Leiomiossarcoma , Neoplasias Pélvicas , Sarcoma do Estroma Endometrial , Sarcoma , Neoplasias Uterinas , Feminino , Humanos , Estudos Retrospectivos , Sarcoma do Estroma Endometrial/diagnóstico , Sarcoma do Estroma Endometrial/cirurgia , Sarcoma do Estroma Endometrial/patologia , Neoplasias Uterinas/diagnóstico por imagem , Neoplasias Uterinas/cirurgia , Sarcoma/diagnóstico por imagem , Sarcoma/cirurgia , Leiomiossarcoma/diagnóstico por imagem , Leiomiossarcoma/cirurgia , Leiomioma/cirurgia , Histerectomia , Neoplasias do Endométrio/patologia
3.
J Transl Med ; 19(1): 51, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536036

RESUMO

BACKGROUND: Currently, there is no reliable blood-based marker to track tumor recurrence in endometrial cancer (EC) patients. Liquid biopsies, specifically, circulating tumor DNA (ctDNA) analysis emerged as a way to monitor tumor metastasis. The objective of this study was to examine the feasibility of ctDNA in recurrence surveillance and prognostic evaluation of high-risk EC. METHODS: Tumor tissues from nine high-risk EC patients were collected during primary surgery and tumor DNA was subjected to next generation sequencing to obtain the initial mutation spectrum using a 78 cancer-associated gene panel. Baseline and serial post-operative plasma samples were collected and droplet digital PCR (ddPCR) assays for patient-specific mutations were developed to track the mutations in the ctDNA in serial plasma samples. Log-rank test was used to assess the association between detection of ctDNA before or after surgery and disease-free survival. RESULTS: Somatic mutations were identified in all of the cases. The most frequent mutated genes were PTEN, FAT4, ARID1A, TP53, ZFHX3, ATM, and FBXW7. For each patient, personalized ddPCR assays were designed for one-to-three high-frequent mutations. DdPCR analysis and tumor panel sequencing had a high level of agreement in the assessment of the mutant allele fractions in baseline tumor tissue DNA. CtDNA was detected in 67% (6 of 9) of baseline plasma samples, which was not predictive of disease-free survival (DFS). CtDNA was detected in serial post-operative plasma samples (ctDNA tracking) of 44% (4 of 9) of the patients, which predicted tumor relapse. The DFS was a median of 9 months (ctDNA detected) versus median DFS undefined (ctDNA not detected), with a hazard ratio of 17.43 (95% CI, 1.616-188.3). The sensitivity of post-operative ctDNA detection in estimating tumor relapse was 100% and specificity was 83.3%, which was superior to CA125 or HE4. CONCLUSIONS: Personalized ctDNA detection was effective and stable for high-risk EC. CtDNA tracking in post-operative plasma is valuable for predicting tumor recurrence.


Assuntos
DNA Tumoral Circulante , Neoplasias do Endométrio , Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Feminino , Humanos , Mutação/genética , Recidiva Local de Neoplasia/genética , Prognóstico
4.
Gynecol Oncol ; 162(3): 788-796, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34183163

RESUMO

OBJECTIVES: Our study aims to investigate whether PI3K/mTOR dual inhibitor LY3023414 has synergistic effects with carboplatin in suppressing endometrial cancer (EC), and explore the mechanisms and toxicity of combined therapy. METHODS: The effects of combined therapy of LY3023414 and carboplatin on cell viability, long-term survival and cell apoptosis were studied in vitro, and on subcutaneous xenograft model of HEC-1A cells and patient derived xenograft (PDX) models with different PI3K pathway mutational patterns in vivo. The synergistic mechanisms were explored on ATM/Chk2 and PI3K signaling pathway. The toxicity of combined therapy was also observed. RESULTS: Combined treatment of LY3023414 and carboplatin synergistically inhibited proliferation, colony formation, promoted apoptosis of EC cells, and significantly activated ATM/Chk2 signaling pathway. LY3023414 had synergistic anti-tumor effects with carboplatin in HEC-1A subcutaneous xenograft which harbors PIK3CA mutation. The sensitivity to LY3023414 and carboplatin differed in PDX of EC cases with different mutational patterns of PI3K pathway, and combined therapy exhibited distinct synergistic anti-tumor effects in those harboring different PI3K pathway mutations. No increased drug toxicity in nude mice was seen in combined groups. CONCLUSIONS: Combined therapy of PI3K/mTOR dual inhibitor LY3023414 and carboplatin had synergistic anti-tumor effects in EC cell line and some of the PDX EC models, without increasing the toxicity of single drug. Enhanced carboplatin-induced DNA damage response (DDR) and cell apoptosis may be the mechanisms of synergistic effects. The anti-tumor effects may correlate with the mutational pattern of PI3K pathway, which provides experimental basis of individual treatments of ECs in the future.


Assuntos
Antineoplásicos/administração & dosagem , Carboplatina/administração & dosagem , Neoplasias do Endométrio/tratamento farmacológico , Piridinas/administração & dosagem , Quinolonas/administração & dosagem , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Camundongos Nus
5.
Int J Mol Sci ; 22(14)2021 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-34299294

RESUMO

Nitrogen (N) is an essential nutrient for plant growth and development. The root system architecture is a highly regulated morphological system, which is sensitive to the availability of nutrients, such as N. Phenotypic characterization of roots from LY9348 (a rice variety with high nitrogen use efficiency (NUE)) treated with 0.725 mM NH4NO3 (1/4N) was remarkable, especially primary root (PR) elongation, which was the highest. A comprehensive analysis was performed for transcriptome and proteome profiling of LY9348 roots between 1/4N and 2.9 mM NH4NO3 (1N) treatments. The results indicated 3908 differential expression genes (DEGs; 2569 upregulated and 1339 downregulated) and 411 differential abundance proteins (DAPs; 192 upregulated and 219 downregulated). Among all DAPs in the proteome, glutamine synthetase (GS2), a chloroplastic ammonium assimilation protein, was the most upregulated protein identified. The unexpected concentration of GS2 from the shoot to the root in the 1/4N treatment indicated that the presence of an alternative pathway of N assimilation regulated by GS2 in LY9348 corresponded to the low N signal, which was supported by GS enzyme activity and glutamine/glutamate (Gln/Glu) contents analysis. In addition, N transporters (NRT2.1, NRT2.2, NRT2.3, NRT2.4, NAR2.1, AMT1.3, AMT1.2, and putative AMT3.3) and N assimilators (NR2, GS1;1, GS1;2, GS1;3, NADH-GOGAT2, and AS2) were significantly induced during the long-term N-deficiency response at the transcription level (14 days). Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated that phenylpropanoid biosynthesis and glutathione metabolism were significantly modulated by N deficiency. Notably, many transcription factors and plant hormones were found to participate in root morphological adaptation. In conclusion, our study provides valuable information to further understand the response of rice roots to N-deficiency stress.


Assuntos
Glutamato-Amônia Ligase/metabolismo , Nitrogênio/deficiência , Oryza/genética , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes/genética , Glutamato-Amônia Ligase/genética , Nitrogênio/metabolismo , Oryza/enzimologia , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Folhas de Planta/genética , Proteínas de Plantas/genética , Raízes de Plantas/genética , Proteômica/métodos , Estresse Fisiológico/genética , Fatores de Transcrição/metabolismo , Transcriptoma/genética
6.
Artigo em Inglês | MEDLINE | ID: mdl-31139268

RESUMO

BACKGROUND: Inguinal metastasis of endometrial cancer (EC) is rare. The aims of the study were to identify whether the inguinal metastatic tumor was originated from EC and to present the management of the disease. METHODS: The clinical data of a case of endometrioid EC "recurring" as serous adenocarcinoma in the inguinal lymph nodes were collected and analyzed. Paired samples of primary and metastatic tumors were used for exome sequencing to determine whether the tumors are same origination and to identify potential gene mutations associated with the relapse. RESULTS: The patient presented with right inguinal lymphadenopathy and histopathology revealed metastatic serous adenocarcinoma. A germline MLH1 mutation was identified. A combination of bioinformatical methods and cancer-related gene exome sequencing assay identified that only 17 (0.1%) somatic gene mutations were shared by the primary EC and the metastatic inguinal tumor, suggesting that the metastasis did not originate from the primary EC. Postoperative radiation therapy followed by a combination of chemotherapy were performed. Thirty-four months after that, the patient was doing well without any evidence of recurrence. CONCLUSIONS: This is the first case of metastatic inguinal serous adenocarcinoma in a woman with Lynch syndrome shortly after surgical treatment of stage I endometrioid EC.

9.
Int J Gynecol Cancer ; 28(9): 1812-1820, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30358704

RESUMO

OBJECTIVE: High-risk endometrial cancers (ECs), including high-grade EC, serous carcinoma (SC), clear cell carcinoma, and carcinosarcoma, account for 50% of deaths due to ECs. Therapies for these cancers are limited, and patient-derived tumor xenograft (PDTX) models are useful tools for preclinical drug evaluation, biomarker identification, and personalized medicine strategies. Here, we used and compared 2 methods to establish PDTX models. METHODS: Fresh tumor tissues collected from 18 primary high-risk EC patients (10 high-grade ECs, 6 SCs, 1 clear cell carcinoma, and 1 carcinosarcoma) were engrafted subcutaneously and in the subrenal capsule in NOD/SCID for establishment and Balb/c-nu/nu mice for expansion. Histology and cytokeratin, estrogen receptor, progesterone receptor, and P53 expression were evaluated to assess the similarity of primary tumors and different generations of PDTX tumors. Whole-exome sequencing (WES) and RNA sequencing were used in 2 high-grade EC models to verify whether the genetic mutation profiles and gene expression were similar between primary and PDTX tumors. RESULTS: The total tumor engraftment rate was 77.8% (14/18) regardless of the engraft method. The tumor engraftment rate was increased in subrenal capsule models compared with subcutaneous models (62.5% vs 50%, P = 0.464). The time to tumor formation varied significantly from 2 to 11 weeks. After subrenal capsular grafting, grafted tumors could be successfully transplanted to subcutaneous sites. We observed good similarity between primary tumors and corresponding different passages of xenografts. CONCLUSIONS: The combination of 2 engrafting methods increases the tumor engraftment rate. The high tumor engraftment rate ensures the establishment of a high-risk EC biobank, which is a powerful resource for performing preclinical drug-sensitivity tests and identifying biomarkers for response or resistance.


Assuntos
Neoplasias do Endométrio/patologia , Animais , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Feminino , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos NOD , Camundongos Nus , Camundongos SCID , Gradação de Tumores , Transplante de Neoplasias
10.
BMC Cancer ; 17(1): 696, 2017 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-29061125

RESUMO

BACKGROUND: Our research aimed to investigate whether lymphadenectomy was required in patients with intermediate-risk endometrioid endometrial cancer (EEC). METHODS: Between 1989 and 2015, 1009 patients with intermediate-risk EEC: grade 1 or 2 tumor, <50% myometrial invasion, and a tumor diameter ≥ 2 cm and 818 low-risk patients with grade 1 or 2 tumor, <50% myometrial invasion, and a tumor diameter < 2 cm were enrolled in this study. The rate and risk factors of node metastasis were evaluated and compared between the two risk groups. Survival data were analyzed in patients with intermediate-risk EEC with or without lymphadenectomy. RESULTS: In all, 624 of 1009 (61.8%) patients with intermediate-risk EEC underwent pelvic ± para-aortic lymphadenectomy with a nodal metastasis rate of 1.9% (12/624), whereas 394 of 818 (48.2%) patients with low-risk EEC underwent pelvic ± para-aortic lymphadenectomy with a nodal metastasis rate of 0.3% (1/394) (p = 0.021). Notably, intermediate-risk EEC patients with a microcystic, elongated and fragmented (MELF) pattern of invasion, lymphatic vascular space invasion (LVSI), diffuse lesions, or lesions located in the cornua were more likely to have node metastasis. The 5-year overall cancer-related survival and the recurrence-free survival rates of the 742 intermediate-risk EEC patients who were followed for more than 3 years were 99.4% and 94.7%, respectively. In intermediate-risk group, 6 patients (6/443, 1.4%) with lymphadenectomy and 9 patients (9/299, 3.0%) without lymphadenectomy recurred, with a mean recurrence time of 38.3 and 18.7 months respectively. The five-year overall and recurrence-free survival rates of intermediate-risk patients with and without lymphadenectomy were similar (100% vs 98.9%, p = 0.351; 95.2% vs 93.3%, p = 0.464). CONCLUSION: Patients with intermediate-risk EEC have low nodal metastasis rate and a favorable outcome whether lymphadenectomy is performed or not. Omission of lymphadenectomy may be a reasonable option in the surgical management of patients with intermediate-risk EEC.


Assuntos
Carcinoma Endometrioide/diagnóstico , Neoplasias do Endométrio/diagnóstico , Excisão de Linfonodo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Endometrioide/cirurgia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Risco
11.
Int J Gynecol Cancer ; 27(6): 1206-1215, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28448305

RESUMO

OBJECTIVE: Limited data have been obtained in regard to pulmonary metastasis (PM) in patients with stage I endometrial cancer. The aims of the study were (1) to present the clinical and pathological characteristics of patients with PM in the setting of stage I endometrioid-type endometrial cancer (EEC) and (2) to define possible factors that may be used to predict PM. METHODS: Six hundred thirty patients with stage I EEC, including 12 with PM, 19 with extra-PM (EPM), and 599 with no recurrence, were observed. Paired samples of primary and metastatic tumors from a patient were used for exome sequencing to identify potential gene mutations associated with PM. RESULTS: There was no significant difference in the age, Ki-67, lymphatic vascular space invasion, and grade 3 among the 3 groups (P > 0.05). More squamous epithelial differentiation was observed in PM (7/12), as compared with patients with EPM (1/19) (P < 0.05) and no recurrence (20/599) (P < 0.05). The tumor size of the patients with PM was bigger than that of nonrecurrent patients (29.8 ± 16.6 vs 18.5 ± 16.3 mm, P < 0.05). More percentage of patients with deep myometrial invasion (IB) were found in PM (6/12) (P < 0.05) as compared with patients with EPM (3/19) (P < 0.05) and no recurrence (76/599). CDH10, ARID1A, and EMT-associated gene mutations were identified in metastatic tumor tissue but not in primary tumors from a patient with EEC and lung metastases. CONCLUSIONS: Squamous epithelial differentiation, large tumor size, and deep myometrial invasion might be risk factors for PM in patients with stage I EEC. CDH10, ARID1A, and EMT-associated gene mutation may promote the initiation of lung recurrence. However, further studies are needed to determine the precise mechanisms associated with lung metastasis in these patients.


Assuntos
Carcinoma Endometrioide/patologia , Neoplasias do Endométrio/patologia , Neoplasias Pulmonares/secundário , Idoso , Idoso de 80 Anos ou mais , Carcinoma Endometrioide/genética , Neoplasias do Endométrio/genética , Feminino , Humanos , Neoplasias Pulmonares/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de Risco
12.
BMC Cancer ; 15: 744, 2015 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-26486312

RESUMO

BACKGROUND: In 5-20 % of patients with cervical high-grade squamous intraepithelial lesion (HSIL), a positive margin after the loop electrosurgical excision procedure (LEEP) is associated with persistence/recurrence, but the prognostic value of other clinico-pathological factors is less clear. METHODS: Among 4336 patients with HSIL who underwent an initial LEEP, 275 (6 %) had HSIL-positive margins, 37 of whom were lost to follow-up. We evaluated the remaining 238 patients. Persistence/recurrence was defined as histopathological HSIL during follow-up. RESULTS: The age of the patients ranged from 21 to 69 years (median: 40). The median follow-up period was 25 months (range: 6-43). Of the 238 patients, 211 (88.7 %) patients remained free of persistence/recurrence, while 27 (11.3 %) experienced persistence/recurrence. According to a univariate analysis, age (P = 0.03) and maximum specimen diameter (P = 0.043) were associated with persistence/recurrence, but number/location of involved margin sections and the pathology of the endocervical curettage were not (P > 0.10). The relative risk of the subjects (greater than or equal to 35 years ages) was 4.6 times of the subject less than 35 years, the difference was statistically significant (14 % vs. 3 %, P < 0.05). A multivariate analysis indicated that an age of 35 years or older was the only independent risk factor (OR 4.97, 95 % CI 1.14-21.62, P = 0.03). CONCLUSION: In patients with HSIL and HSIL-involved margins after an initial LEEP, age is a strong independent predictor of persistence/recurrence. Follow-up with screening cytology and/or biopsy may be considered in younger patients, whereas a secondary LEEP/hysterectomy may be considered in older patients.


Assuntos
Lesões Intraepiteliais Escamosas Cervicais/epidemiologia , Lesões Intraepiteliais Escamosas Cervicais/patologia , Adulto , Idoso , Eletrocirurgia/métodos , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Lesões Intraepiteliais Escamosas Cervicais/cirurgia , Adulto Jovem
13.
J Cancer Res Ther ; 20(4): 1300-1305, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39206992

RESUMO

OBJECTIVE: This study aimed to evaluate the incidence and predict the risk factors of lymph node (LN) metastasis among patients with grossly apparent early-stage epithelial ovarian cancer (EOC). METHODS: We retrospectively reviewed the clinicopathologic data and follow-up information of 266 patients who underwent LN dissection for apparent early-stage EOC between January 2018 and September 2022 at the Obstetrics and Gynecology Hospital of Fudan University. RESULTS: Among 266 patients, 44 (16.5%) showed LN metastasis, of which 65.9% and 59.1% presented in the pelvic region and para-aortic region, respectively. Univariate analysis revealed higher LN positivity in patients with high-grade serous carcinoma (HGSC), preoperative imaging suggestive of LN metastasis, bilateral adnexal involvement, lymphovascular space invasion (LVSI), positive peritoneal cytology, and clinical stage IIA. LN metastases were identified in 7.9%, 10.2%, and 39.7% of clinical stage IA/B, IC, and IIA disease cases, respectively. Multivariate analysis confirmed significantly higher LN positivity rates in patients with HGSC, LVSI, and clinical stage IIA. In clinical stage IIA EOC, the 3-year progression-free survival (PFS) rates were 65.8% and 77.4% (P = 0.360) for LN-negative and LN-positive groups, respectively. In clinical stage I EOC, the 3-year PFS rates were 93.5% and 59.4% (P < 0.001) for LN-negative and LN-positive groups, respectively. CONCLUSIONS: High-grade serous histology, LVSI, and clinical stage IIA disease are predictive factors for LN involvement in early-stage EOC. In addition, LN metastasis appears to be associated with worse PFS in clinical stage I EOC compared with clinical stage IIA EOC.


Assuntos
Carcinoma Epitelial do Ovário , Metástase Linfática , Estadiamento de Neoplasias , Neoplasias Ovarianas , Centros de Atenção Terciária , Humanos , Feminino , Estudos Retrospectivos , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/cirurgia , Pessoa de Meia-Idade , Metástase Linfática/patologia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/cirurgia , Adulto , Idoso , Linfonodos/patologia , Linfonodos/cirurgia , Excisão de Linfonodo , Prognóstico , Seguimentos , Fatores de Risco , Taxa de Sobrevida
14.
Data Brief ; 55: 110576, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39006349

RESUMO

HnRNPK, a prominent member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family, is widely expressed in mammalian tissues and plays a crucial role in animal development. Despite its well-established functions, limited information is available regarding its role in skeletal muscle development and regeneration. To elucidate the functional role of hnRNPK in skeletal muscle, we utilized Pax7CreER; HnrnpkLoxP/LoxP (Hnrnpk pKO) mice as a model, isolated primary mouse skeletal muscle satellite cells (MuSCs), and induced hnRNPK knockout using 4-OTH. Transcriptome sequencing was performed on four distinct groups: Hnrnpk pKO MuSCs undergoing proliferation for 24 h (ethanol 24 h) and 48 h (ethanol 48 h) after treatment with ethanol as the control, as well as Hnrnpk pKO MuSCs undergoing proliferation for 24 h (4-OHT 24 h) and 48 h (4-OHT 48 h) after treatment with 4-OHT as the hnRNPK-induced knockout group. The RNA sequencing data was generated using the Illumina HiSeq 2000/2500 sequencing platform. The raw data files have been archived in the Sequence Read Archive at the China National Center for Bioinformation (CNCB) under the accession number CRA015864. This data article is related to the research paper "Deletion of heterogeneous nuclear ribonucleoprotein K in satellite cells leads to inhibited skeletal muscle regeneration in mice, Genes & Diseases 11: 101,062, DOI: 10.1016/j.gendis.2023.06.031".

15.
Front Vet Sci ; 11: 1427966, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39263678

RESUMO

The contagious respiratory pathogen, Avibacterium paragallinarum, contributes to infectious coryza in poultry. However, commercial vaccines have not shown perfect protection against infectious coryza. To search for an alternative approach, this research aimed to investigate whether the quorum-sensing system of pathogens plays a crucial role in their survival and pathogenicity. The LuxS/AI-2 quorum-sensing system in many Gram-negative and Gram-positive bacteria senses environmental changes to regulate physiological traits and virulent properties, and the role of the luxS gene in Av. paragallinarum remains unclear. To investigate the effect of the luxS gene in the quorum-sensing system of Av. paragallinarum, we constructed a luxS mutant. Bioluminescence analysis indicated that the luxS gene plays a vital role in the LuxS/AI-2 quorum-sensing system. The analysis of the LuxS/AI-2 system-related genes showed the level of pfs mRNA to be significantly increased in the mutant strain; however, lsrR, lsrK, and lsrB mRNA levels were not significantly different compared with the wild type. The ability of the luxS mutant strain to invade HD11 and DF-1 cells was significantly decreased compared with the wild-type strain. In addition, all chickens challenged with various doses of the luxS mutant strain developed infections and symptoms, and those challenged with the lowest dose exhibited only minor differences compared to chickens challenged with the wild-type strain. Thus, the deletion of the luxS gene reduces the invasion, but the luxS gene does not play an essential role in the pathogenesis of A. paragallinarum.

16.
Curr Drug Targets ; 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39171461

RESUMO

BACKGROUND: Nitazoxanide not only exhibits a broad spectrum of activities against various pathogens infecting animals and humans but also induces cellular autophagy. Currently, the pattern of action and subcellular targets of nitazoxanide-induced cellular autophagy are still unclear. METHODS: To identify potential targets of nitazoxanide in mammalian cells, we developed an af-finity chromatography system using tizoxanide, a deacetyl derivative of nitazoxanide, as a ligand. Affinity chromatography was performed using VERO cell extracts on tizoxanide-biotin, and the isolated binding proteins were identified by mass spectrometry. Candidate target proteins ob-tained using affinity chromatography were co-analysed with the drug affinity response target sta-bility method. Fluorescent probes obtained by coupling rhodamine B to nitazoxanide were used for intracellular localisation of the binding targets. Solvent-induced protein precipitation profiling and thermal proteome profiling were used to further validate the binding proteins. RESULTS: The joint analysis of the drug affinity response target stability method and affinity chro-matography resulted in the screening of six possible candidate target proteins. Fluorescent probes localised the nitazoxanide-binding protein around the nuclear membrane. Molecular docking re-vealed that the binding proteins mainly formed hydrogen bonds with the nitro group of nitazoxa-nide. Solvent-induced protein precipitation profiling and thermal proteome profiling further vali-dated SEC61A, PSMD12, and PRKAG1 as potential target proteins of nitazoxanide. CONCLUSION: The data supports the idea that nitazoxanide is a multifunctional compound with multiple targets.

17.
Virus Res ; 345: 199378, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38643857

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant threat to human health globally. It is crucial to develop a vaccine to reduce the effect of the virus on public health, economy, and society and regulate the transmission of SARS-CoV-2. Influenza B virus (IBV) can be used as a vector that does not rely on the current circulating influenza A strains. In this study, we constructed an IBV-based vector vaccine by inserting a receptor-binding domain (RBD) into a non-structural protein 1 (NS1)-truncated gene (rIBV-NS110-RBD). Subsequently, we assessed its safety, immunogenicity, and protective efficacy against SARS-CoV-2 in mice, and observed that it was safe in a mouse model. Intranasal administration of a recombinant rIBV-NS110-RBD vaccine induced high levels of SARS-CoV-2-specific IgA and IgG antibodies and T cell-mediated immunity in mice. Administering two doses of the intranasal rIBV-NS110-RBD vaccine significantly reduced the viral load and lung damage in mice. This novel IBV-based vaccine offers a novel approach for controlling the SARS-CoV-2 pandemic.


Assuntos
Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Vírus da Influenza B , Camundongos Endogâmicos BALB C , SARS-CoV-2 , Vacinas Atenuadas , Animais , Camundongos , Vírus da Influenza B/imunologia , Vírus da Influenza B/genética , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , SARS-CoV-2/imunologia , SARS-CoV-2/genética , COVID-19/prevenção & controle , COVID-19/imunologia , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/genética , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Feminino , Administração Intranasal , Humanos , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/genética , Imunoglobulina A/sangue , Modelos Animais de Doenças , Imunoglobulina G/sangue , Carga Viral , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia
18.
Adv Mater ; : e2408192, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39155803

RESUMO

Mechanochromic light control technology that can dynamically regulate solar irradiation is recognized as one of the leading candidates for energy-saving windows. However, the lack of spectrally selective modulation ability still hinders its application for different scenarios or individual needs. Here, inspired by the generation of structure color and color change of living organisms, a simple layer-by-layer assembly approach toward large-area fabricating mechanically responsive film for visible and near-infrared multiwavelength spectral modulation smart windows is reported here. The assembled SiO2 nanoparticles and W18O49 nanowires enable the film with an optical modulation rate of up to 42.4% at the wavelength of 550 nm and 18.4% for the near-infrared region, separately, and the typical composite film under 50% stretching shows ≈41.6% modulation rate at the wavelength of 550 nm with NIR modulation rate less than 2.7%. More importantly, the introduction of the multilayer assembly structure not only optimizes the film's optical modulation but also enables the film with high stability during 100 000 stretching cycles. A cooling effect of 21.3 and 6.9 °C for the blackbody and air inside a model house in the real environmental application is achieved. This approach provides theoretical and technical support for the new mechanochromic energy-saving windows.

19.
Diagn Pathol ; 18(1): 118, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37907964

RESUMO

BACKGROUND: Nevoid basal cell carcinoma syndrome (NBCCS, Gorlin syndrome) is a rare autosomal dominantly inherited disorder that is characterized by multisystem disorder such as basal cell carcinomas, keratocystic odontogenic tumors and skeletal abnormalities. Bilateral and/or unilateral ovarian fibromas have been reported in individuals diagnosed with NBCCS. CASE PRESENTATION: A 22-year-old female, presented with low back pain, and was found to have bilateral giant adnexal masses on pelvic ultrasonography, which had been suspected to be malignant ovarian tumors. Positron emission tomography/computed tomography showed multiple intracranial calcification and skeletal abnormalities. The left adnexa and right ovarian tumor were resected with laparotomy, and pathology revealed bilateral ovarian fibromas with marked calcification. We recommended the patient to receive genetic testing and dermatological examination. No skin lesion was detected. Germline testing identified pathogenic heterozygous mutation in PTCH1 (Patched1). CONCLUSIONS: The possibility of NBCCS needs to be considered in patients with ovarian fibromas diagnosed in an early age. Skin lesions are not necessary for the diagnosis of NBCCS. Ovarian fibromas are managed with surgical excision with an attempt at preserving ovarian function. Follow-up regime and counseling on options for future fertility should be offered to patients.


Assuntos
Síndrome do Nevo Basocelular , Fibroma , Cistos Odontogênicos , Neoplasias Ovarianas , Feminino , Humanos , Adulto Jovem , Adulto , Síndrome do Nevo Basocelular/diagnóstico , Síndrome do Nevo Basocelular/genética , Síndrome do Nevo Basocelular/cirurgia , Fibroma/diagnóstico , Fibroma/genética , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética
20.
RSC Adv ; 13(10): 6619-6629, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36860542

RESUMO

Next-generation wearable electromagnetic interference (EMI) materials need to be provided with oxidation resistance, lightness, and flexibility. In this study, a high-performance EMI film with synergistic enhancement of Zn2+@Ti3C2T x MXene/cellulose nanofibers (CNF) was found. The unique Zn@Ti3C2T x MXene/CNF heterogeneous interface facilitates the loss of interface polarization, making the total electromagnetic shielding effectiveness (EMI SET) and shielding effectiveness per unit thickness (SE/d) of the films reach 60.3 dB and 5025 dB mm-1, respectively, in the X-band at the thickness of 12 µm ± 2 µm, significantly exceeding that of other MXene-based shielding materials. In addition, the coefficient of absorption gradually increases with the increasing CNF content. Moreover, under the synergistic effect of Zn2+, the film shows excellent oxidation resistance (maintaining stable performance after 30 days), greatly exceeding the previous test cycle. Furthermore, the mechanical performance and flexibility of the film are greatly enhanced (tensile strength at 60 MPa, and maintaining stable performance after 100 times bending tests) due to the CNF and hot-pressing process. Therefore, with the enhancement of the EMI performance, high flexibility and oxidation resistance under high temperature and high humidity conditions, the as-prepared films have wide practical significance and broad application prospects in a series of complex applications, such as flexible wearable fields, ocean engineering fields and high-power device packaging fields.

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