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1.
Cancer Lett ; 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34767927

RESUMO

Nuclear pore complex (NPC) embedded in the nuclear envelope, is the only channel for macromolecule nucleocytoplasmic transportation and has important biological functions. However, the deregulation of specific nucleoporins (Nups) and NPC-Nup-based mechanisms and their function in tumour progression remain poorly understood. Here, we aimed to identify the Nups that contribute to HCC progression and metastasis in 729 primary hepatocellular carcinoma (HCC) cases using molecular, cytological, and biochemical techniques. Our results revealed elevated Nup93 expression in HCC tissues, especially in cases with metastasis, and was linked to worse prognosis. Furthermore, Nup93 knockdown suppressed HCC cell metastasis and proliferation, while Nup93 overexpression promoted these activities. We observed that Nup93 promotes HCC metastasis and proliferation by regulating ß-catenin translocation. In addition, we found that Nup93 interacted with ß-catenin directly, independent of importin. Furthermore, LEF1 and ß-catenin facilitated the Nup93-mediated metastasis and proliferation in HCC via a positive feedback loop. Thus, our findings provide novel insights into the mechanisms underlying the Nup93-induced promotion of HCC metastasis and suggest potential therapeutic targets in the LEF1-Nup93-ß-catenin pathway for HCC therapeutics.

2.
J Inflamm Res ; 14: 5489-5500, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34720597

RESUMO

Introduction: Chronic hepatitis B (CHB) virus (HBV) infection has emerged as a global health burden affecting nearly 292 million people. Tenofovir alafenamide (TAF) is an effective treatment for CHB patients. However, the detailed mechanism underlying the antiviral activity of TAF remains unclear. Methods: In this study, we investigated the antiviral effect of exosomes derived from the serum of CHB patients treated with TAF (Exo-serum) and TAF-treated macrophages (MP) (Exo-MP(TAF)). Results: RNAseq analysis was also performed to determine the associated long non-coding RNAs (lncRNAs). The results demonstrated that both Exo-serum and Exo-MP(TAF) could be taken up by HepAD38 cells and exhibited potent antiviral activities, as manifested by significantly downregulating the levels of hepatitis B surface antigen, hepatitis B e antigen, HBV DNA, and covalently closed circular DNA. The antiviral effect of Exo-serum was more potent than those of TAF treatment alone. RNAseq analysis revealed that lncRNA HOTTIP was upregulated significantly in Exo-serum. Further, lncRNA HOTTIP knockdown reversed the antiviral effect of Exo-MP(TAF) on HepAD38 cells, whereas lncRNA HOTTIP knockdown exerted the opposite roles. Discussion: Taken together, these results suggest that exosomal lncRNA HOTTIP is essential for the antiviral activity of TAF and provide a novel understanding of the exosome-mediated mechanism underlying HBV infection.

3.
Am J Surg Pathol ; 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34753864

RESUMO

The metastatic or recurrent potential of localized human papillomavirus-associated endocervical adenocarcinoma (HPVA EAC) is difficult to predict, especially based upon biopsy alone. Recent analyses of small cohorts indicate that high tumor nuclear grade (TNG) and the presence of necrotic tumor debris (NTD) from HPVA EACs in cervical biopsy specimens are highly predictive of nodal metastasis (NM). In the present study, we aimed to investigate how reliably tumoral morphologic features from cervical biopsy specimens predict NM or tumor recurrence (TR) and patient outcomes in a large cohort of endocervical adenocarcinoma patients. A cohort comprised of 397 patients with HPVA EAC treated at 18 institutions was identified, and cervical biopsies were paired with their associated complete tumor resections for a total of 794 specimens. A variety of tumoral histologic features were examined for each paired specimen, including TNG (assessed on a 3-tiered scale of increasing abnormalities-TNG1, TNG2, TNG3) and NTD (defined by the presence of necrotic and apoptotic tumor cells within tumor glandular lumens admixed with granular and eosinophilic amorphous material and inflammatory cells), which were correlated with outcomes. The distribution of TNG in biopsies was as follows: 86 (21.7%) TNG1, 223 (56.2%) TNG2, and 88 (22.2%) TNG3. NTD was identified in 176 (44%) of the biopsy specimens. The sensitivity, specificity, positive predictive value, and negative predictive value of a TNG1 assignment in the biopsy being predictive of the same assignment in the full resection were 0.82 (95% confidence interval [CI]: 0.7-0.9), 0.895 (0.86-0.93), 0.593 (0.48-0.696), and 0.96 (0.94-0.98), respectively. Respective values for an NTD-negative status were 0.89 (95% CI: 0.83-0.92), 0.715 (0.64-0.77), 0.72 (0.65-0.77), and 0.89 (0.83-0.93), respectively. Compared with the other cases in each category, both TNG1 and an NTD-negative status were each significantly associated with lower rates of NM (odds ratio for TNG1=0.245, 95% CI: 0.070-0.857, P=0.0277; for NTD=0.199, 95% CI: 0.094-0.421, P<0.0001) and TR (odds ratio for TNG1=0.225, 95% CI: 0.051-0.987, P=0.0479; for NTD=0.367, 95% CI: 0.171-0.786, P=0.0099) independent of depth of stromal invasion, lymphovascular invasion, tumor size, FIGO stage, and Silva pattern. Overall, 73/379 (19%) cases were both TNG1 and NTD-negative on the biopsy, and none of these 73 cases showed NM (0%), but a single case (1.4%) showed TR. In contrast, among the 324 biopsies with TNG2/3 and/or presence of NTD, 62 (19.1%) had NM, and 41 (12.9%) had TR. In summary, 2 variables in combination (ie, TNG1 and NTD-negative) identified a subset of HPVA EAC patients-∼19%-with a 0% frequency of nodal metastases and only 1.4% frequency of recurrence. Biopsies highly but imperfectly predicted these features. Nonetheless, these findings may potentially be of clinical utility in the risk stratification of patients with HPVA EACs. This may allow some patients with a minimal risk of nodal metastases and TR to be identified at the biopsy phase, thereby facilitating more personalized, possibly less aggressive treatment.

4.
SAGE Open Med Case Rep ; 9: 2050313X211057704, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777811

RESUMO

Alpha-fetoprotein hardly increased due to nasopharyngeal cancer. In this article, we reported a 57-year-old male nasopharyngeal carcinoma patient who had posttreatment subscapular metastasis with high serum alpha-fetoprotein but negative plasma Epstein-Barr virus DNA. Pathology results indicated that the scapular mass was undifferentiated non-keratinizing carcinoma originated in the nasopharynx. Moreover, no liver lesion was detected by imaging examination. In view of the positive alpha-fetoprotein and alpha-fetoprotein messenger RNA staining result in the right scapular mass fine needle aspiration biopsy sample, we considered the diagnosis of alpha-fetoprotein-producing nasopharyngeal carcinoma that had never been reported before.

5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1478-1484, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627427

RESUMO

OBJECTIVE: To investigate the toxic damage and possible mechanism of chronic exposure of ambient particulate matter (PM2.5) to the marrow micro-environment of the mice, and the protective effect of chitooligosaccharides. METHODS: Mice were treated with different doses (150, 300, 600 mg/kg) of chitosan after exposure to PM2.5, and then the mice were divided into: high dose group, medium dose group, low dose group according to the given dose, and the model group and the drug group were set as well. The productions of inflammatory cytokines IL-2, IL-8, TPO and VCAM-1 in marrow tissues were detected by ELISA, the expression of CXCL12 and CXCR4 protein in bone marrow tissues were measured by Western blot. RESULTS: Compared with the mice in control group, IL-2 secretion and CXCL12 expression were decreased in the bone marrow of PM2.5 infected mice, while the secretion of IL-8, TPO and VCAM-1 were significantly increased, and CXCR4 expression was significantly up-regulated (P<0.05). Compared with the mice in control group, drug group and other dose groups, IL-2 secretion in the bone marrow of the mice in high-dose group was significantly increased, and IL-8, TPO and VCAM-1 secretion were significantly decreased (P<0.05). CONCLUSION: Chronic exposure of PM2.5 shows some toxicity effect on marrow micro-environment. Chitosan oligosaccharide can reduce the pathologic damage of bone marrow and the toxicity to bone marrow microenvironment caused by PM2.5 at a certain extent.


Assuntos
Quitosana , Transplante de Células-Tronco Hematopoéticas , Sistema Hematopoético , Animais , Medula Óssea , Camundongos , Material Particulado/toxicidade
6.
Inorg Chem ; 60(22): 17303-17314, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34699193

RESUMO

It remains a challenge to exploit dual-functional metal-organic frameworks (MOFs) for applications, including luminescence detection and proton conduction. With the deliberate selection of the bifunctional organic ligand 5-sulfoisophthalic acid monosodium salt (NaH2bts), and the phosphonic acid ligand N,N'-piperazine (bismethylenephosphonic acid; H4L), a robust three-dimensional (3D) noninterpenetrating dual-functional MOF, [Tb(H2L)(H2bts)(H2O)]·H2O (1), has been synthesized hydrothermally. On the basis of the excellent thermal and chemical as well as superior luminescence stabilities in water and solutions with different pHs, 1 can serve as the simple, rapid, and highly selective and sensitive luminescence detection of the carcinoid biomarkers 5-hydroxytryptamine (HT) and its metabolite 5-hydroxyindole-3-acetic acid (HIAA) with detection limits of nanomolar magnitude in water and in simulated blood plasma and urine systems. Due to the change in the signals that could be readily differentiated by the naked eye under a UV lamp, a portable test paper has been developed. The probable quenching mechanisms are discussed in detail. In addition, a great number of hydrogen-bonding networks are formed among the uncoordinated carboxylic oxygen atoms, sulfonate oxygen atoms, protonated nitrogen atoms, and water molecules, which provide potential proton-hopping sites for proton conduction, leading to a maximum proton conductivity of 2.3 × 10-4 S cm-1 at 368 K and 95% relative humidity. The above results suggest that rationally designed dual-functional MOFs can open an avenue for the development of occupational diagnostic tools and alternative energy technology.

7.
MycoKeys ; 83: 39-67, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539206

RESUMO

During an investigation of Xylariaceae from 2019 to 2020, isolates representing eight Nemania (Xylariacese) species were collected from Yunnan, Guizhou and Hainan Provinces in China. Morphological and multi-gene phylogenetic analyses, based on combined ITS, α-actin, rpb2 and ß-tubulin sequences, confirmed that six of them are new to science, viz. Nemaniacamelliae, N.changningensis, N.cyclobalanopsina, N.feicuiensis, N.lishuicola and N.rubi; one is a new record (N.caries) for China and one is a known species (N.diffusa). Morphological descriptions and illustrations of all species are detailed. In addition, the characteristics of Nemania are summarised and prevailing contradictions in generic concepts are discussed.

8.
Future Microbiol ; 16: 1041-1051, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34493087

RESUMO

Aim: To screen novel biomarkers in serum of syphilis patients using a mass spectrometry-based method. Materials & methods: Sera were collected from 18 syphilis patients and divided into three groups. Every six serum samples (before and after treatment) in each group were pooled and detected by mass spectrometry. Results: Twenty-five unique peptides corresponding to 15 Treponema pallidum proteins were discovered. Among them, Tp0369 was discovered as a promising biomarker candidate in this study. Tp0524 and Tp0984 levels decreased 0.38-fold and 0.51-fold after BPG treatment, respectively, which may be related to disease outcomes of syphilis. Conclusion: These findings confirmed the presence of detectable T. pallidum protein in patients' serum, which could promote the development of syphilis diagnostics.

9.
Int J Clin Oncol ; 26(10): 1847-1855, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34398362

RESUMO

RNA-binding proteins (RBPs) play crucial roles in the post-transcriptional regulation of mRNA during numerous physiological and pathological processes, including tumor genesis and development. However, the role of RNA-binding motif protein 43 (RBM43) in esophageal squamous cell carcinoma (ESCC) has not been reported so far. The current study was the first to evaluate RBM43 protein expression by immunohistochemistry (IHC) in an independent cohort of 207 patients with ESCC, to explore its potential prognostic value and clinical relevance in ESCC. The results indicated that RBM43 protein levels were significantly elevated in ESCC tissues and increased RBM43 expression was associated with age and N categories. In addition, ESCC patients with high expression of RBM43 had shorter overall survival (OS) and disease-free survival (DFS) than those with low RBM43 expression. Furthermore, when survival analyses were conducted at different clinical stages, overexpression of RBM43 was significantly correlated with shortened survival in patients with ESCC at early stages (TNM stage I-II and N0 stage). Cox regression analysis further proved that high RBM43 expression was an independent predictor of poor prognosis in ESCC patients. In conclusion, increased expression of RBM43 is correlated with malignant attributes to ESCC and predicts unfavorable prognosis, suggesting an effective prognostic biomarker and potential therapeutic target for ESCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Neoplasias de Cabeça e Pescoço , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Prognóstico , Motivos de Ligação ao RNA
10.
Epigenomics ; 13(15): 1187-1203, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34382410

RESUMO

Aim: Neurosyphilis patients exhibited significant expression of long noncoding RNA (lncRNA) in peripheral blood T lymphocytes. In this study, we further clarified the role of lncRNA-ENST00000421645 in the pathogenic mechanism of neurosyphilis. Methods: lncRNA-ENST00000421645 was transfected into Jurkat-E6-1 cells, namely lentivirus (Lv)-1645 cells. RNA pull-down assay, flow cytometry, RT-qPCR, ELISA (Neobioscience Technology Co Ltd, Shenzhen, China) and RNA immunoprecipitation chip assay were used to analyze the function of lncRNA-ENST00000421645. Results: The expression of IFN-γ in Lv-1645 cells was significantly increased compared to that in Jurkat-E6-1 cells stimulated by phorbol-12-myristate-13-acetate (PMA). Then, it was suggested that lncRNA-ENST00000421645 interacts with PCM1 protein. Silencing PCM1 significantly increased the level of IFN-γ in Lv-1645 cells stimulated by PMA. Conclusion: This study revealed that lncRNA-ENST00000421645 mediates the production of IFN-γ by sponging PCM1 protein after PMA stimulation.

11.
Anticancer Drugs ; 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34321418

RESUMO

Berbamine is a bisbenzylisoquinoline alkaloid extracted from Berberis poiretii of Berberis of Berberidaceae. It has been reported that it can significantly inhibit the proliferation of a variety of malignant tumor cells, including liver cancer. However, the effect of berbamine on the invasion and metastasis of liver cancer has not been reported. The present study demonstrated that berbamine inhibited the migration and invasion of SMMC-7721 cells in a concentration-dependent manner and obviously increased the gap junction function and the expression of Cx32 in SMMC-7721 cells compared with control group. However, after silencing Cx32, berbamine had no significant effect on cell invasion and metastasis. Before silencing Cx32, the expression of PI3K and P-AKT were decreased after berbamine treated on SMMC-7721 cells for 24 h. After silencing Cx32, the expression of PI3K and P-AKT were increased in SMMC-7721 cells. The expression of PI3K and P-AKT had no significant effect after berbamine treated on SMMC-7721 cells for 24 h with silencing Cx32. In conclusion, the results of the present study suggest that berbamine could inhibit the SMMC-7721 cell migration and invasion, and its mechanism may be related to the regulation of PI3K/AKT signaling pathway by enhancing the expression of Cx32.

12.
Mol Med ; 27(1): 60, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34134633

RESUMO

BACKGROUND: Endocervical adenocarcinoma (ECA) is further classified as human papillomavirus (HPV)-associated (HPVA) or non-HPVA (NHPVA), per the International Endocervical Adenocarcinoma Criteria and Classification (IECC). HPVA is a glandular tumor with stromal invasion and/or exophytic expansile-type invasion, associated with the typical molecular characteristics of high-risk HPV (HR-HPV) infection. Transforming acidic coiled-coil protein-3 (TACC3),an oncogene that is frequently abnormally expressed,represents a vital biomarker for multiple human malignancies. This study aimed to examine the role of TACC3 in the diagnosis and prognosis of ECA. METHODS: We analyzed 264 patients with ECA who underwent surgical resection, classifying their tumors into HPVA and NHPVA subtypes. The expression levels of TACC3, P16, MLH1, PMS2, MSH2, MSH6 and Ki-67 in tumors were evaluated by tissue microarray using immunohistochemistry (IHC). HPV subtypes were identified in formalin-fixed paraffin-embedded (FFPE) ECA tissues by the polymerase chain reaction (PCR). RESULTS: ECA samples showed increased TACC3 expression relative to adjacent non-carcinoma samples. TACC3 expression was higher in HPVA than in NHPA. In the HPVA subtype, high TACC3 expression was significantly correlated with P16-positive, Ki-67-high expression. Furthermore, TACC3 levels were significantly related to tumor histological type (P = 0.006), nerve invasion (P = 0.003), differentiation (P = 0.004), surgical margin (P = 0.012), parametrium invasion (P = 0.040), P16 expression (P < 0.001), and Ki-67 (P = 0.004). Additionally, Kaplan-Meier analysis showed that TACC3 upregulation was associated with poor overall survival (OS, P = 0.001), disease-free survival (DFS, P < 0.001), and recurrence survival (P < 0.001). Multivariate analysis indicated that elevated TACC3 expression served as a marker to independently predict ECA prognosis. ROC curve analyses indicated that TACC3, P16, and HPV subtypes showed similar utility for distinguishing HPVA from NHPVA, with areas under the ROC curves of 0.640, 0.649, and 0.675, respectively. The combination of TACC3 and HPV subtypes improved the diagnostic performance of ECA compared with TACC3, P16, and HPV subtypes alone. CONCLUSIONS: Taken together, our findings identify that TACC3 is a promising complementary biomarker for diagnosis and prognosis for patients with ECA.

13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(3): 853-859, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34105483

RESUMO

OBJECTIVE: To observe and compare the therapeutic effects of hydroxypropyl chitosan ferrous ion complex solution and ferrous sulfate solution in iron deficiency anemia rats and their effects on gastric mucosa. METHODS: Seven rats were randomly selected from thirty five SPF grade SD rats as control group, and were fed with normal diet, distilled water (E). The rest of SD rats were fed with low iron feed and distilled water plus continuous tail vein bloodletting to establish the iron deficiency anemia model. After the model was established successfully, the rats were randomly divided into four groups: blank control group (A), iron deficiency anemia control group (B), ferrous sulfate group (C), hydroxypropyl chitosan ferrous ion complex (HPCTS-Fe2+) group (D). Group A was killed and the gastric tissue was taken to make the pathological section. Group E was fed with normal feed and distilled water continually. Group B, C and D were fed with low iron feed and distilled water. Moreover, Group C and group D were treated with ferrous sulfate solution and HPCTS-Fe2+ solution respectively to made the blood recover treatment (4 mg / kg of iron each time, twice a day). During the treatment period, Ret%, SF and blood routine were checked regularly. After 6 weeks of treatment, the rats were killed, and the gastric tissue was taken to make the pathological section, and the condition of gastric mucosa was observed by the light microscope. RESULTS: After modeling, except the normal control group, the hair color of the rats in the four groups showed dark yellow and the belly of the toes became white gradually. HGB, HCT, Ret%, MCV, MCH, MCHC and SF decreased significantly (P < 0.05). After treatment, the rats with dark yellow hair in group C and D were improved, and the toe abdomen turned pink gradually. RBC, HGB, HCT, Ret%, MCV, MCH, MCHC and SF in rats in group C and D increased, which were higher than those in group B (P < 0.05). The HGB of the rats in group D was higher than that of group C in day 28th during treatment and the Ret% was higher than that in group C at day 10th (P<0.05).After treatment, the liver and spleen of the rats in group C and D were lighter than those in group B (P<0.05).The gastric mucosa in group A, B, D and E was not damaged obviously, while it was slightly irritated and damaged in group C. CONCLUSION: Hydroxypropyl chitosan ferrous complex solution can improve the hemoglobin level of SD rats with iron deficiency anemia, which is stronger than ferrous sulfate solution and shows no damage to gastric mucosa.


Assuntos
Anemia Ferropriva , Quitosana , Anemia Ferropriva/tratamento farmacológico , Animais , Compostos Ferrosos , Hemoglobinas , Ferro , Ratos , Ratos Sprague-Dawley
14.
Br J Cancer ; 124(12): 1988-1996, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33824478

RESUMO

BACKGROUND: Pathologic diagnosis of hepatocellular carcinoma (HCC) can be challenging in differentiating from benign and non-hepatocytic malignancy lesions. The aim of this study was to investigate the potential utility of α-fetoprotein (AFP) mRNA RNAscope, a sensitive and specific method, in the diagnosis of HCC. METHODS: Three independent retrospective cohorts containing 2216 patients with HCC, benign liver lesions, and non-hepatocytic tumours were examined. AFP was detected using ELISA, IHC (Immunohistochemistry), and RNAscope. Glypican3 (GPC3), hepatocyte paraffin-1 (HepPar-1), and arginase-1 (Arg-1) proteins were detected using IHC. RESULTS: AFP RNAscope improved the HCC detection sensitivity by 24.7-32.7% compared with IHC. In two surgical cohorts, a panel of AFP RNAscope and GPC3 provided the best diagnostic value in differentiating HCC from benign hepatocytic lesions (AUC = 0.905 and 0.811), and a panel including AFP RNAscope, GPC3, HepPar-1, and Arg-1 yielded the best AUC (0.971 and 0.977) when distinguishing HCC from non-hepatocytic malignancies. The results from the liver biopsy cohort were similar, and additional application of AFP RNAscope improved the sensitivity by 18% when distinguishing HCC from benign hepatocytic lesions. CONCLUSIONS: AFP mRNA detected by RNAscope is highly specific for hepatocytic malignancy and may serve as a novel diagnostic biomarker for HCC.

16.
BMC Cancer ; 21(1): 332, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33789601

RESUMO

BACKGROUND: Small cell neuroendocrine carcinoma of the uterine cervix (SCNEC) is a rare cancer involving the human papilloma virus (HPV), and has few available treatments. The present work aimed to assess the feasibility of SOX2 and HPV statuses as predictive indicators of SCNEC prognosis. METHODS: The associations of SOX2 and/or high-risk (HR)-HPV RNA in situ hybridization (RISH) levels with clinicopathological characteristics and prognostic outcomes for 88 neuroendocrine carcinoma (NEC) cases were analyzed. RESULTS: Among these patients with SCNEC, SOX2, P16INK4A and HR-HPV RISH expression and SOX2/HR-HPV RISH co-expression were detected in 68(77.3%), 76(86.4%), 73(83.0%), and 48(54.5%), respectively. SOX2-positive and HR-HPV RISH-positive SCNEC cases were associated with poorer overall survival (OS, P = 0.0170, P = 0.0451) and disease-free survival (DFS, P = 0.0334, P = 0.0309) compared with those expressing low SOX2 and negative HR-HPV RISH. Alternatively, univariate analysis revealed that SOX2 and HR-HPV RISH expression, either separately or in combination, predicted the poor prognosis of SCNEC patients. Multivariate analysis revealed that the co-expression of SOX2 with HR-HPV RISH may be an independent factor of OS [hazard ratio = 3.597; 95% confidence interval (CI): 1.085-11.928; P = 0.036] and DFS [hazard ratio = 2.880; 95% CI: 1.199-6.919; P = 0.018] prediction in SCNEC. CONCLUSIONS: Overall, the results of the present study suggest that the co-expression of SOX2 with HR-HPV RISH in SCNEC may represent a specific subgroup exhibiting remarkably poorer prognostic outcomes compared with the expression of any one marker alone.


Assuntos
Carcinoma Neuroendócrino/metabolismo , Carcinoma Neuroendócrino/virologia , Carcinoma de Células Pequenas/genética , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/metabolismo , Fatores de Transcrição SOXB1/biossíntese , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/virologia , Adulto , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/patologia , Carcinoma de Células Pequenas/patologia , Feminino , Humanos , Hibridização In Situ , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nomogramas , Papillomaviridae/genética , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Prognóstico , RNA Viral/genética , Estudos Retrospectivos , Fatores de Transcrição SOXB1/metabolismo , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia
17.
Metallomics ; 13(3)2021 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-33693771

RESUMO

Selenoprotein N (SEPN1) is critical to the normal muscular physiology. Mutation of SEPN1 can raise congenital muscular disorder in human. It is also central to maturation and structure of skeletal muscle in chicken. However, human SEPN1 contained an EF-hand motif, which was not found in chicken. And the biochemical and molecular characterization of chicken SEPN1 remains unclear. Hence, protein domains, transcription factors, and interactions of Ca2+ in SEPN1 were analyzed in silico to provide the divergence and homology between chicken and human in this work. The results showed that vertebrates' SEPN1 evolved from a common ancestor. Human and chicken's SEPN1 shared a conserved CUGS-helix domain with function in antioxidant protection. SEPN1 might be a downstream target of JNK pathway, and it could respond to multiple stresses. Human's SEPN1 might not combine with Ca2+ with a single EF-hand motif in calcium homeostasis, and chicken SEPN1 did not have the EF-hand motif in the prediction, indicating the EF-hand motif malfunctioned in chicken SEPN1.


Assuntos
Antioxidantes/metabolismo , Cálcio/metabolismo , Simulação por Computador , Músculo Esquelético/metabolismo , Selenoproteínas/metabolismo , Fatores de Transcrição/metabolismo , Sequência de Aminoácidos , Animais , Galinhas , Humanos , Mutação , Filogenia , Conformação Proteica , Domínios Proteicos , Selenoproteínas/química , Selenoproteínas/genética , Homologia de Sequência
18.
Ecotoxicol Environ Saf ; 215: 112135, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33780782

RESUMO

Cadmium (Cd) is a ubiquitous environmental pollutant, which mainly input to the aquatic environment through discharge of industrial and agricultural waste, can be a threat to human and animal health. Selenium (Se) possesses a beneficial role in protecting animals and ameliorating the toxic effects of Cd. However, the comparative antagonistic effects of different Se sources such as inorganic, organic Se and nano-form Se on Cd toxicity are still under-investigated. Hence, the purpose of this study was to evaluate the comparative of Se sources antagonism on Cd-induced nephrotoxicity via oxidative stress and selenoproteome transcription. In the present study, Cd-diet disturbed in the system balance of 5 trace elements (Zinc (Zn), copper (Cu), Iron (Fe), Se, Cd) and impaired renal function. Se sources, including nano- Se (NS), Se- yeast (SY), sodium selenite (SS) and mixed selenium (MS) significantly recovered the balance of 4 trace elements (Zn, Cu, Cd, Se) and renal impaired indexes (blood urea nitrogen (BUN) and creatinine (CREA)). Histological appearance of Cd-treated kidney indicated renal tubular epithelial vacuoles, particle degeneration and enlarged capsular space. Ultrastructure observation results illustrated that Cd-induced mitochondrial cristae reduction, membrane disappearance, and nuclear deformation. Treatment with Se sources, NS appeared a better impact on improving kidney tissues against the pathological alterations resulting from Cd administration. Meanwhile, NS reflected a significant impact on relieving Cd-induced kidney oxidative damage, and significantly restored the antioxidant defense system of the body. Our findings also showed NS ameliorated the Cd-induced downtrends expression of selenoproteome and selenoprotein synthesis related transcription factors. Overall, NS was the most effective Se source in avoiding of Cd cumulative toxicity, improving antioxidant capacity and regulating of selenoproteome transcriptome and selenoprotein synthesis related transcription factors expression, which contributes to ameliorate Cd-induced nephrotoxicity in chickens. These results demonstrated diet supplement with NS may prove to be an effective approach for alleviating Cd toxicity and minimizing Cd -induced health risk.


Assuntos
Cádmio/toxicidade , Substâncias Protetoras/metabolismo , Selênio/metabolismo , Animais , Antioxidantes/metabolismo , Galinhas/metabolismo , Cobre/metabolismo , Suplementos Nutricionais , Humanos , Ferro/metabolismo , Rim/efeitos dos fármacos , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Selenoproteínas/metabolismo , Selenito de Sódio , Oligoelementos/metabolismo , Fermento Seco , Zinco/metabolismo
19.
Front Cell Dev Biol ; 9: 616835, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33748106

RESUMO

Alternative polyadenylation (APA) is an important post-transcriptional regulatory mechanism required for cleavage and polyadenylation (CPA) of the 3' untranslated region (3' UTR) of mRNAs. Several aberrant APA events have been reported in hepatocellular carcinoma (HCC). However, the regulatory mechanisms underlying APA remain unclear. In this study, we found that the expression of cleavage and polyadenylation specific factor 1 (CPSF1), a major component of the CPA complex, was significantly increased in HCC tissues and correlated with unfavorable survival outcomes. Knockdown of CPSF1 inhibited HCC cell proliferation and migration, whereas overexpression of CPSF1 caused the opposite effect. Based on integrative analysis of Iso-Seq and RNA-seq data from HepG2.2.15 cells, we identified a series of transcripts with differential 3' UTR lengths following the knockdown of CPSF1. These transcripts were related to the biological functions of gene transcription, cytoskeleton maintenance, and endomembrane system transportation. Moreover, knockdown of CPSF1 induced an increase in alternative splicing (AS) events in addition to APA. Taken together, this study provides new insights into our understanding of the post-transcriptional regulatory mechanisms in HCC and implies that CPSF1 may be a potential prognostic biomarker and therapeutic target for HCC.

20.
Zhen Ci Yan Jiu ; 46(2): 111-6, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33788431

RESUMO

OBJECTIVE: To observe the effect of intranasal acupuncture on allergic rhinitis (AR), and expression of substance P (SP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) proteins in the nasal mucosa and contents of serum immunoglobulin E (IgE), interleukin 4 (IL-4) and interferon-γ (IFN-γ) in AR rabbits, so as to explore its mechanisms underlying improvement of AR. METHODS: New Zealand rabbits were randomly divided into normal control, AR model, non-acupuoint acupuncture (NAA) and intranasal acupuncture (INA) groups, with 8 rabbits in each group. The AR model was established by intra-peritoneal injection of egg protein and nasal mucosal stimulation. In the INA group, bilateral "Neiyingxiang" (EX-HN9) within the nasal cavity (the anterior attachment area of the inferior turbinate, about 1 cm away from the nasal limen) were acupunctured by mani-pulating the filiform needles for a while with uniform reinforcing and reducing methods, followed by keeping the needles for 20 min. In the NAA group, shallow acupuncture was applied to the skin of the outer margin of the cheeks, followed by keeping the needle for 20 min. The acupuncture treatment was conducted once every other day for 7 days. The symptoms of sneezing frequency, nasal secretion amount and nasal itching were scored. The expression levels of SP, VIP and NPY in the nasal mucosa tissue were detected by immunohistochemistry, and the serum IgE, IL-4, and IFN-γ contents were detected by ELISA. RESULTS: After modelling, the symptom score, expression of SP and VIP, and serum IgE and IL-4 contents were significantly higher (P<0.01,P<0.05), NPY expression and serum IFN-γ content significantly lower (P<0.05, P<0.01) in the model group than in the normal control group. Following the intervention, the symptom scores, expressions of SP and VIP, and serum IgE and IL-4 contents were remarkably decreased (P<0.05, P<0.01), while the NPY expression and serum IFN-γ content were significantly up-regulated (P<0.05, P<0.01) in the INA group than in the model group. The effects of INA group were significantly superior to those of NAA group in reducing symptom score, SP and VIP expression, and serum IgE and IL-4 contents and up-regulating NPY expression and IFN-γcontent (P<0.05, P<0.01). There were a positive correlation between the expressions of SP and VIP and contents of serum IgE and IL-4 (P<0.05), and a negative correlation between the expressions of SP and VIP and IFN-γ content (P<0.05). CONCLUSION: INA treatment can relieve symptoms of AR in AR rabbits, which may be associated with its effects in regulating the expression of SP, VIP and NPY of the nasal mucosa, and contents of serum IgE, IL-4 and IFN-γ to improve neurogenic inflammation.


Assuntos
Terapia por Acupuntura , Rinite Alérgica , Animais , Imunoglobulina E , Mucosa Nasal , Inflamação Neurogênica , Coelhos , Rinite Alérgica/genética , Rinite Alérgica/terapia
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