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BACKGROUND: The aim is to establish and verify reference intervals (RIs) for serum tumor markers for an apparently healthy elderly population in Southwestern China using an indirect method. METHODS: Data from 35,635 apparently healthy elderly individuals aged 60 years and above were obtained in West China Hospital from April 2020 to December 2021. We utilized the Box-Cox conversion combined with the Tukey method to normalize the data and eliminate outliers. Subgroups are divided according to gender and age to examine the division of RIs. The Z-test was used to compare differences between groups, and 95% distribution RIs were calculated using a nonparametric method. RESULTS: In the study, we observed that the RIs for serum ferritin and Des-γ-carboxy prothrombin (DCP) were wider for men, ranging from 64.18 to 865.80 ng/ml and 14.00 to 33.00 mAU/ml, respectively, compared to women, whose ranges were 52.58 to 585.88 ng/ml and 13.00 to 29.00 mAU/ml. For other biomarkers, the overall RIs were established as follows: alpha-fetoprotein (AFP) 0-6.75 ng/ml, carcinoembryonic antigen (CEA) 0-4.85 ng/ml, carbohydrate antigen15-3 (CA15-3) for females 0-22.00 U/ml, carbohydrate antigen19-9 (CA19-9) 0-28.10 U/ml, carbohydrate antigen125 (CA125) 0-20.96 U/ml, cytokeratin 19 fragment (CYFRA21-1) 0-4.66 U/ml, neuron-specific enolase (NSE) 0-19.41 ng/ml, total and free prostate-specific antigens (tPSA and fPSA) for males 0-5.26 ng/ml and 0-1.09 ng/ml. The RIs for all these biomarkers have been validated through our rigorous processes. CONCLUSION: This study preliminarily established 95% RIs for an apparently healthy elderly population in Southwestern China. Using real-world data and an indirect method, simple and reliable RIs for an elderly population can be both established and verified, which are suitable for application in various clinical laboratories.
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Biomarcadores Tumorais , Protrombina , Humanos , Masculino , Feminino , Idoso , Biomarcadores Tumorais/sangue , China/epidemiologia , Valores de Referência , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Neoplasias/sangue , Neoplasias/epidemiologia , alfa-Fetoproteínas/análise , Ferritinas/sangue , Antígeno CA-19-9/sangue , Antígeno Carcinoembrionário/sangue , Antígeno Ca-125/sangue , Fosfopiruvato Hidratase/sangue , Queratina-19/sangue , Precursores de Proteínas , BiomarcadoresRESUMO
Birefringent crystals play a crucial role in modulating and controlling the polarization of light in the optical communication and laser industries. Recently, adopting appropriate strategies to enhance the birefringence of crystals has become a prominent area of research focus. Herein, four UV antimony oxalate birefringent crystals, namely, K5Sb2(C2O4)5.5·3H2O, BaSb(C2O4)2.5·3H2O, Na4Sb2O(C2O4)4·6H2O, and Na3Sb(C2O4)2F2·2H2O, have been successfully synthesized. These compounds feature a similar zero-dimensional (0D) cluster structure and share the same functional groups, including π-conjugated [C2O4]2- groups and Sb3+-based distorted polyhedra with stereochemically active lone pairs (SCALPs). Interestingly, we achieved a stepwise increase in birefringence by precisely controlling the Sb3+/[C2O4]2- ratio, ultimately resulting in the compound Na3Sb(C2O4)2F2·2H2O exhibiting a large birefringence (0.21@546 nm). Additionally, we confirmed that the synergistic effects between the π-conjugated [C2O4]2- groups and the distorted polyhedra based on Sb3+ are responsible for the excellent optical properties observed in the reported compounds.
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In the present work, we have successfully obtained two new UV antimony-based sulfates, NH4Sb(SO4)2 and Ca2Sb2O(SO4)4, by a conventional hydrothermal method. Interestingly, both compounds share similar structural building blocks, such as SbO4 seesaws and SO4 tetrahedra, yet they endow discrepant birefringence values measured at 546 nm with values of 0.150 and 0.114, respectively, owing to the different distortions of the SbO4 groups with SCALP electrons. Moreover, both compounds display large band gaps (4.32 and 4.43 eV, respectively), so they can be used as short-wavelength UV birefringent materials. Moreover, NH4Sb(SO4)2 is a noncentrosymmetric compound, showing a frequency doubling effect of 0.2 × KDP. Detailed structural analyses and calculations confirm the source of superior optical performance and the reasons for the different birefringence of the two compounds. This work provides ideas for the following discovery of antimony-based optical materials with excellent properties.
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Two antimony selenites, Sb2O2SeO3 and Sb2O(SeO3)2, were synthesized by simultaneously incorporating stereochemically active lone pair electrons containing SeO32- and Sb3+. These compounds are structured with [SbOx] polyhedra and [SeO3] units within a two-dimensional framework. Both of them exhibit cutoffs at 300 and 330 nm within the ultraviolet (UV) range and demonstrate significant birefringence, with indices of 0.069 and 0.126 at 546 nm, respectively. These properties highlight their potential as UV birefringent materials. Structural analyses and theoretical calculations reveal that their exceptional birefringence results from the synergistic interactions between SeO32- anions and Sb3+ cations.
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In this work, two tin(II)-based sulfates, Sn2OSO4 and Sn3O2(OH)(HSO4), were synthesized via the mild hydrothermal method. Both compounds employ the Sn2+ cation with stereochemically active lone pair (SCALP) electrons and non-π-conjugated tetrahedral anionic groups SO4 as the functional structural blocks. Interestingly, the experimental birefringence of Sn3O2(OH)(HSO4) is 0.169@546 nm, approximately 42 times larger than that of Sn2OSO4, which is 0.004@546 nm. Detailed structural analysis and theoretical calculations suggest that this significant birefringence difference arises from the optimization of functional building blocks in coordination environments and spatial arrangements. Furthermore, both compounds exhibit ultraviolet absorption edges at 308 and 307 nm, respectively. This indicates that Sn3O2(OH)(HSO4) has the potential to be a candidate for an ultraviolet (UV) birefringent crystal. This study offers inspiration for further exploration of tin(II)-based compounds with excellent comprehensive properties.
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PURPOSE: To address this evidence gap and validate short-term OS at less than 5 years as a reliable surrogate endpoint for 5-year OS. METHODS: We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database, focusing on non-metastatic NPC patients diagnosed between 2010 and 2015. Patients were categorized into radiotherapy and chemoradiotherapy groups. RESULTS: This retrospective study examined 2,047 non-metastatic NPC patients. Among them, 217 received radiotherapy, and 1,830 received chemoradiotherapy. Our analysis results indicated that the 4-year OS may serve as a reliable surrogate endpoint for patients with AJCC clinical stage I (80 vs. 78%, P = 0.250), regardless of the treatment received. Specifically, in the radiotherapy group, patients with stage I, T0-T1, and N0 NPC showed similar OS rates at 4 and 5 years (83 vs. 82%, P = 1.000; 78 vs. 76%, P = 0.250; 78 vs. 77%, P = 0.500, respectively). Similarly, patients with stage II-IV, T2-T4, and N1-3 NPC showed no significant difference in OS rates between 3 and 5 years (57 vs. 51%, P = 0.063; 52 vs. 46%, P = 0.250; 54 vs. 46%, P = 0.125, respectively) in the radiotherapy group. In the chemoradiotherapy group, only the 3-year OS rate did not significantly differ from that at 5 years in stage I patients (79vs. 72%, P = 0.063). CONCLUSIONS: Our study suggests that short-term surrogate endpoints may be valuable for evaluating 5-year OS outcomes in NPC patients in non-endemic areas.
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Quimiorradioterapia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Estadiamento de Neoplasias , Humanos , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/mortalidade , Taxa de Sobrevida , Quimiorradioterapia/métodos , Quimiorradioterapia/mortalidade , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/mortalidade , Seguimentos , Prognóstico , Adulto , Programa de SEER/estatística & dados numéricos , Idoso , Adulto JovemRESUMO
Objective To study the expression of SWI/SNF-related,matrix-associated,actin-dependent regulator of chromatin,subfamily A,member 4(SMARCA4)/Brahma-related gene 1,V-raf murine sarcoma viral oncogene homolog B(BRAF),P53,programmed cell death protein-1(PD-1),and programmed death-ligand 1(PD-L1),and changes in the expression of BRAF and neurotrophic tyrosine receptor kinase(NTRK) in the patients with colorectal cancer in Tibet,thereby providing a basis for targeted therapy and immunotherapy for this disease in Tibet. Methods A total of 64 patients with colorectal cancer resected in the Tibet Autonomous Region People's Hospital from January 2015 to July 2021 were enrolled in this study.The expression of SMARCA4,BRAF,P53,PD-1,and PD-L1 was detected by immunohistochemical staining.The gene fusion involving NTRK1,NTRK2,and NTRK3 was detected by fluorescence in situ hybridization,and the BRAF V600E gene mutation by polymerase chain reaction. Results The 64 patients with colorectal cancer were at a male-to-female ratio of 1.21â¶1,with the mean age of (56.59±13.27) years.The tumors were located in the colon in 46(71.88%) patients and in the rectum in 18(28.12%) patients.Sixty(93.75%) patients presented adenocarcinoma,and 4(6.25%) patients presented other types of tumors.The patients in T1/T2 and T3/T4 phases accounted for 17.19%(n=11) and 82.81%(n=53),respectively.Lymph node metastasis occurred in 24(37.50%) patients.The immunohistochemical staining results showed partially down-regulated or absent expression of SMARCA4 in 1(1.56%) patient,positive BRAF expression in 4(6.25%) patients,and mutant expression of P53 in 35(54.69%) patients.The PD-1-expressing tumor associated immune cell was proportion score<10% in 45(70.31%) patients and≥10% in 19(29.69%) patients.The PD-L1 combined positive score was<10 in 52(81.25%) patients and≥10 in 12(18.75%) patients.The gene fusion of NTRK1,NTRK2,and NTRK3 was negative in all the patients,and BRAF V600E gene mutation was positive in 4(6.25%) patients.The SMARCA4 gene alteration was not detected in the patient with partial expression missing of SMARCA4.The PD-L1 combine positive score was correlated with the deficient mismatch repair(dMMR)/microsatellite instability-high (MSI-H) and the PD-1 expression (χ2=10.223,P=0.001;χ2=11.979,P=0.001). Conclusions The down-regulated or absent SMARCA4 expression and NTRK gene fusion are rare in the patients with colorectal cancer in Tibet.A few patients present BRAF V600E gene mutations,and Pan-TRK and BRAF expression can be used for the primary screening of NTRK gene fusion and BRAF gene mutation.The patients with dMMR/MSI-H are prone to high expression of PD-L1 and expected to benefit from immunotherapy.No significant correlation exists between P53 mutation and PD-L1 expression.The high expression of PD-1 is positively correlated with the high expression of PD-L1.
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Antígeno B7-H1 , Biomarcadores Tumorais , Neoplasias Colorretais , Imunoterapia , Proteínas Proto-Oncogênicas B-raf , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Tibet , Proteínas Proto-Oncogênicas B-raf/genética , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Fatores de Transcrição/genética , DNA Helicases/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/metabolismo , Idoso , Terapia de Alvo Molecular , Mutação , AdultoRESUMO
The histone methyltransferase enhancer of zeste homolog 2 (EZH2) is overexpressed in a variety of malignancies including prostate cancer (PCa) and may play important roles in tumor progression. Gene copy number gains, enhanced transcription, and a few circRNAs have been reported to upregulate EZH2. It was not known whether EZH2 itself generates circRNAs that promote its own expression. We here report the identification of circEZH2E2/E3 that is derived from exons 2 and 3 of the EZH2 gene and overexpressed in PCa. We show that circEZH2E2/E3 functions as a dual inhibitor for both miR363 and miR708 that target the EZH2 3'UTR and CDS, respectively, resulting in the upregulation of EZH2 expression and hence the downregulation of EZH2-repressed genes (e.g., CDH1 and DAB2IP), and enhancement of PCa cell proliferation, migration, invasion, and xenograft PCa growth. Overexpression of circEZH2E2/E3 is significantly correlated with higher tumor grade, tumor progression, and unfavorable progression-free and disease-specific survival in PCa patients. These findings show a novel autoenhancing EZH2-circEZH2E2/E3 -miR363/miR708-EZH2 regulatory loop, by which circEZH2E2/E3 plays important roles in PCa tumorigenesis and progression by upregulating EZH2, and may have potential diagnostic, prognostic, and therapeutic uses in PCa management.
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MicroRNAs , Neoplasias da Próstata , Masculino , Humanos , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Complexo Repressor Polycomb 2/genética , Complexo Repressor Polycomb 2/metabolismo , RNA Circular , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Neoplasias da Próstata/patologia , Proliferação de Células/genética , Proteínas Ativadoras de ras GTPase/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
The type VI secretion system (T6SS) is a spear-like nanomachine found in gram-negative pathogens for delivery of toxic effectors to neighboring bacterial and host cells. Its assembly requires a tip spike complex consisting of a VgrG-trimer, a PAAR protein, and the interacting effectors. However, how the spike controls T6SS assembly remains elusive. Here we investigated the role of three VgrG-effector pairs in Aeromonas dhakensis strain SSU, a clinical isolate with a constitutively active T6SS. By swapping VgrG tail sequences, we demonstrate that the C-terminal ~30 amino-acid tail dictates effector specificity. Double deletion of vgrG1&2 genes (VgrG3+) abolished T6SS secretion, which can be rescued by ectopically expressing chimeric VgrG3 with a VgrG1/2-tail but not the wild type VgrG3. In addition, deletion of effector-specific chaperones also severely impaired T6SS secretion, despite the presence of intact VgrG and effector proteins, in both SSU and Vibrio cholerae V52. We further show that SSU could deliver a V. cholerae effector VasX when expressing a plasmid-borne chimeric VgrG with VasX-specific VgrG tail and chaperone sequences. Pull-down analyses show that two SSU effectors, TseP and TseC, could interact with their cognate VgrGs, the baseplate protein TssK, and the key assembly chaperone TssA. Effectors TseL and VasX could interact with TssF, TssK and TssA in V. cholerae. Collectively, we demonstrate that chimeric VgrG-effector pairs could bypass the requirement of heterologous VgrG complex and propose that effector-stuffing inside the baseplate complex, facilitated by chaperones and the interaction with structural proteins, serves as a crucial structural determinant for T6SS assembly.
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Aeromonas/metabolismo , Proteínas de Bactérias/metabolismo , Interações Hospedeiro-Patógeno/fisiologia , Sistemas de Secreção Tipo VI/metabolismo , Vibrio cholerae/metabolismo , Aeromonas/patogenicidade , Vibrio cholerae/patogenicidadeRESUMO
Objective To study the pathological types,expression of mismatch repair protein,human epidermal growth factor receptor 2(HER2),and Pan-TRK,and Epstein-Barr virus(EBV)infection in patients with colorectal cancer resected in Tibet. Methods A total of 79 patients with colorectal cancer resected in Tibet Autonomous Region People's Hospital from December 2013 to July 2021 were enrolled in this study.The clinical and pathological data of the patients were collected.The expression of mismatch repair protein,HER2,and Pan-TRK was detected by immunohistochemical(IHC)staining,and detection of HER2 gene by fluorescence in situ hybridization(FISH)in the patients with HER2 IHC results of 2+ or above.EBV was detected by in situ hybridization with EBV-encoded small RNA. Results A total of 79 colorectal cancer patients were included in this study,with the male-to-female ratio of 1.26:1 and the mean age of(57.06±12.74)years(24-83 years).Among them,4 patients received preoperative neoadjuvant therapy.Colonic cancer and rectal cancer occurred in 57(57/79,72.15%,including 31 and 26 in the right colon and left colon,respectively)and 22(22/79,27.85%)patients,respectively.The maximum diameter of tumor varied within the range of 1-20 cm,with the mean of(6.61±3.33)cm.Among the 79 colorectal cancer patients,75(75/79,94.94%)patients showed adenocarcinoma.Lymph node metastasis occurred in 12(12/21,57.14%)out of the 21 patients with severe tumor budding,13(13/23,56.52%)out of the 23 patients with moderate tumor budding,and 2(2/31,6.45%)out of the 31 patients with mild tumor budding,respectively.The lymph node metastasis rate showed differences between the patients with severe/moderate tumor budding and the patients with mild tumor budding(all P<0.001).The IHC staining showed that mismatch repair protein was negative in 10(10/65,15.38%)patients,including 5 patients with both MSH2 and MSH6 negative,4 patients with both MLH1 and PMS2 negative,and 1 patient with MSH6 negative.Pan-TRK was negative in 65 patients.The IHC results of HER2 showed 0 or 1+ in 60 patients and 2+ in 5 patients.FISH showed no positive signal in the 5 patients with HER2 IHC results of 2+.The detection with EBV-encoded small RNA showed positive result in 1(1/65,1.54%)patient. Conclusions Non-specific adenocarcinoma of the right colon is the most common in the patients with colorectal cancer resected in Tibet,and 15% of the patients showed mismatch repair protein defects.EBV-associated colorectal carcer is rare,Pan-TRK expression and HER2 gene amplification are seldom.The colorectal cancer patients with moderate and severe tumor budding are more likely to have lymph node metastasis.
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Adenocarcinoma , Neoplasias Colorretais , Infecções por Vírus Epstein-Barr , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Neoplasias Colorretais/patologia , Reparo de Erro de Pareamento de DNA , Proteínas de Ligação a DNA/genética , Infecções por Vírus Epstein-Barr/diagnóstico , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/metabolismo , Hibridização in Situ Fluorescente , Metástase Linfática , Tibet , Adulto Jovem , Idoso de 80 Anos ou maisRESUMO
OBJECTIVE: The systemic spread of colorectal cancer (CRC) is dominated by the portal system and exhibits diverse patterns of metastasis without systematical genomic investigation. Here, we evaluated the genomic evolution of CRC with multiorgan metastases using multiregion sequencing. DESIGN: Whole-exome sequencing was performed on multiple regions (n=74) of matched primary tumour, adjacent non-cancerous mucosa, liver metastasis and lung metastasis from six patients with CRC. Phylogenetic reconstruction and evolutionary analyses were used to investigate the metastatic seeding pattern and clonal origin. Recurrent driver gene mutations were analysed across patients and validated in two independent cohorts. Metastatic assays were performed to examine the effect of the novel driver gene on the malignant behaviour of CRC cells. RESULTS: Based on the migration patterns and clonal origins, three models were revealed (sequential, branch-off and diaspora), which not only supported the anatomic assumption that CRC cells spread to lung after clonally expanding in the liver, but also illustrated the direct seeding of extrahepatic metastases from primary tumours independently. Unlike other cancer types, polyphyletic seeding occurs in CRC, which may result in late metastases with intermetastatic driver gene heterogeneity. In cases with rapid dissemination, we found recurrent trunk loss-of-function mutations in ZFP36L2, which is enriched in metastatic CRC and associated with poor overall survival. CRISPR/Cas9-mediated knockout of ZFP36L2 enhances the metastatic potential of CRC cells. CONCLUSION: Our results provide genomic evidence for metastatic evolution and indicate that biopsy/sequencing of metastases may be considered for patients with CRC with multiorgan or late postoperative metastasis.
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Neoplasias Colorretais/genética , Neoplasias Colorretais/secundário , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Mutação/genética , Fatores de Transcrição/genética , China , Estudos de Coortes , Evolução Molecular , Humanos , Neoplasias Hepáticas/genética , Neoplasias Pulmonares/genética , Modelos Genéticos , Sequenciamento do ExomaRESUMO
As the most seriously controlled mycotoxin produced by Aspergillus spp. and Penicillium spp., ochratoxin A (OTA) results in various toxicological effects and widely contaminates agro-products. Biological detoxification is the highest priority regarding OTA in food and feed industry, but currently available detoxification enzymes have relatively low effectiveness in terms of time and cost. Here we show a superefficient enzyme, ADH3, identified from Stenotrophomonas acidaminiphila that has a strong ability to transform OTA into nontoxic ochratoxin-α by acting as an amidohydrolase. Recombinant ADH3 (1.2 µg/mL) completely degrades 50 µg/L OTA within 90 s, while the other most efficient OTA hydrolases available take several hours. The kinetic constant showed that rADH3 (Kcat/Km) catalytic efficiency was 56.7 to 35,000 times higher than those of previous hydrolases rAfOTase, rOTase, and commercial carboxypeptidase A (CPA). Protein structure-based assay suggested that ADH3 has a preference for hydrophobic residues to form a larger hydrophobic area than other detoxifying enzymes at the cavity of the catalytic sites, and this structure allows OTA easier access to the catalytic sites. In addition, ADH3 shows considerable temperature adaptability to exert hydrolytic function at the temperature down to 0°C or up to 70°C. Collectively, we report a superefficient OTA detoxifying enzyme with promising potential for industrial applications. IMPORTANCE Ochratoxin A (OTA) can result in various toxicological effects and widely contaminates agro-products and feedstuffs. OTA detoxifications by microbial strains and bio-enzymes are significant to food safety. Although previous studies showed OTA could be transformed through several pathways, the ochratoxin-α pathway is recognized as the most effective one. However, the most currently available enzymes are not efficient enough. Here, a superefficient hydrolase, ADH3, which can completely transform 50 µg/L OTA into ochratoxin-α within 90 s was screened and characterized. The hydrolase ADH3 shows considerable temperature adaptability (0 to 70°C) to exert the hydrolytic function. Findings of this study supplied an efficient OTA detoxifying enzyme and predicted the superefficient degradation mechanism, laying a foundation for future industrial applications.
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Micotoxinas , Ocratoxinas , Aspergillus/metabolismo , Contaminação de Alimentos , Hidrolases , Ocratoxinas/metabolismoRESUMO
OBJECTIVE: Gastric-type cervical adenocarcinoma (GCA) is a rare and aggressive type of endocervical adenocarcinoma (ECA) with distinct histopathologic features and unfavorable treatment outcomes, but no genomic prognostic factor has been revealed. We aimed to systematically investigate the somatic alterations of GCA at genome-wide level and evaluate their prognostic value. METHODS: We performed whole-exome sequencing (WES) on 25 pairs of tumor and matched normal samples to characterize the genomic features of Chinese patients with GCA and investigated their relations to histopathological characterizations and prognosis. The prognostic value of the genomic alterations was evaluated in a total of 58 GCA patients. RESULTS: Mutations were commonly observed in reported GCA-related driver genes, including TP53 (32%), CDKN2A (20%), SKT11 (20%), BRCA2 (12%), SMAD4 (12%), and ERBB2 (12%). Recurrent novel trunk mutations were also observed in PBRM1 (12%), FRMPD4 (12%), and NOP2 (8%) with high variant allele frequency. Moreover, enrichment of the APOBEC signature was attributed to frequent gain of somatic copy number alteration (SCNA) of APOBEC3B (20%), which perfectly matched the nuclear-positive staining of APOBEC3B through immunohistochemistry. In contrast, APOBEC3B alteration was absent in patients with conventional type of ECA (N = 52). Notably, positive APOBEC3B was consistently enriched in patients with favorable prognosis in both the discovery cohort and an additional 33 GCA patients, thus indicating a significant association with lower relapse risk of GCA independent of cancer stage (P = 0.02). CONCLUSION: Our results can aid understanding of the molecular basis of GCA in the Chinese population by providing genomic profiles and highlighting the potential prognostic value of APOBEC3B for GCA through routine clinical IHC.
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Adenocarcinoma , Neoplasias Gástricas , Neoplasias do Colo do Útero , Adenocarcinoma/genética , Adenocarcinoma/patologia , Citidina Desaminase/genética , Feminino , Humanos , Antígenos de Histocompatibilidade Menor/genética , Mutação , Recidiva Local de Neoplasia , Prognóstico , Neoplasias Gástricas/genética , Neoplasias do Colo do Útero/genéticaRESUMO
Nucleophilic aromatic substitution (SNAr) reaction in classic textbook is a stepwise mechanism, and few examples of concerted reactions have been reported. Herein, we developed a concerted SNAr reaction of 5-bromo-1,2,3-triazines with phenols in which the nonclassic mechanism of this reaction could be revealed by calculation. Furthermore, the resulting 5-aryloxy-1,2,3-triazines could be used as convenient precursors to access biologically important 3-aryloxy-pyridines in one-pot manner.
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Fenóis , TriazinasRESUMO
BACKGROUND: LINC00152 (long intergenic non-protein coding RNA 152) was identified as an oncogenic lncRNA in multiple cancers. In the current study, we aimed to explore the transcriptional profile of LINC00152 in oral squamous cell carcinoma (OSCC) and its regulations at the transcriptional level. METHODS: Bioinformatic analysis was performed by extracting the OSCC subset from The Cancer Genome Atlas (TCGA)-Head and Neck Squamous Cell Carcinoma (HNSC). LINC00152 subcellular localization and its interacting transcriptional factors (TFs) were explored. Dual-luciferase assay and ChIP-qPCR were applied to study transcriptional regulation. In vitro and in vivo tumor cell growth models were used for functional assays. RESULTS: NR_024206.2 was the dominant isoform that accounts for 80% of all transcripts of LINC00152. LINC00152 upregulation was associated with unfavorable survival of patients with OSCC. LINC00152 knockdown significantly impaired OSCC cell growth in vitro and in vivo. RNA FISH assay confirmed nuclear and cytoplasmic distribution of LINC00152. It physically interacted with Upstream Transcription Factor 1 (USF1), a common transcription factor in mammalian cells. USF1 could bind to the promoter region of MRPL52 (Mitochondrial Ribosomal Protein L52) and activate its transcription. LINC00152 could enhance the binding, thereby indirectly elevating MRPL52 expression. USF1 or MRPL52 knockdown slowed the proliferation of OSCC cells and partly canceled LINC00152-mediated growth-promoting effects. CONCLUSION: This study revealed a novel LINC00152-USF1/MRPL52 axis promoting OSCC tumor growth.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Fator 1-alfa Nuclear de Hepatócito/metabolismo , MicroRNAs , Neoplasias Bucais , RNA Longo não Codificante/genética , Animais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias de Cabeça e Pescoço/genética , Humanos , Mamíferos/genética , Mamíferos/metabolismo , MicroRNAs/genética , Neoplasias Bucais/genética , RNA Longo não Codificante/metabolismo , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcrição GênicaRESUMO
Radiation-induced skin injury (RISI) is an important challenge for clinical treatments. The main causes of RISI include hypoxia in the wound microenvironment, reactive oxygen species (ROS) activation, and downregulation of DNA repair proteins. Here, a multiple radioresistance strategy was designed for microRNA therapy and attenuating hypoxia. A novel mesoporous silica (MS) firmly anchored and dispersed cerium (IV) oxide (CeO2) nanoparticles to form MS-CeO2 nanocomposites, which exhibit superior activity in inhibiting radiation-induced ROS and HIF-1α activation and ultimately promote RISI wound healing. The miR129 serum concentrations in patients can promote radioresistance by directly targeting RAD17 and regulating the Chk2 pathway. Subsequently, MS-CeO2 nanocomposites with miR129 were conjugated with iRGD-grafted polyoxyethylene glycol (short for nano-miR129), which increased the stability and antibacterial character, efficiently delivered miR129 to wound blood capillaries, and exhibited low toxicity. Notably, nano-miR129 promoted radioresistance and enhanced anti-ROS therapeutic efficacy in a subcutaneous RISI mouse model. Overall, this MS-CeO2 nanozyme and miR129-based multiresistance radiotherapy protection strategy provided a promising therapeutic approach for RISI.
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Cério , Dióxido de Silício , Animais , Cério/farmacologia , Hipóxia , Camundongos , CicatrizaçãoRESUMO
The present study aimed to identify the composition of the aerial parts of Rubia cordifolia L. A chemical investigation on the EtOAc extracts from the aerial parts of Rubia cordifolia resulted in the isolation of four new anthraquinones, namely Cordifoquinone A-D (1-4), along with 16 known anthraquinones. Their structures were elucidated on the basis of NMR and HR-ESIMS data. All isolates were assessed for their inhibitory effects on NO production in LPS-stimulated RAW 264.7 macrophage cells. Compounds 1, 3 and 10 exhibited significant inhibitory activities with IC50 values of 14.05, 23.48 and 29.23 µmol·L-1, respectively. Their antibacterial activities of four bacteria, Escherichia coli (ATCC 25922), Staphylococcus aureus subsp. aureus (ATCC 29213), Salmonella enterica subsp. enterica (ATCC 14028) and Pseudomonas aeruginosa (ATCC 27853), were also evaluated. Our results indicated that the antibacterial activity of these compounds is inactive.
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RubiaRESUMO
Objective To analyze the disease spectrum and clinicopathological characteristics of central nervous system(CNS)diseases diagnosed based on pathological findings in Tibet. Methods We collected the data of all the cases with CNS lesions in Tibet Autonomous Region People's Hospital from January 2013 to December 2020.The clinicopathological features were analyzed via light microscopy,immunohistochemical staining,and special staining. Results A total of 383 CNS cases confirmed by pathological diagnosis were enrolled in this study,with a male-to-female ratio of 188â¶195 and an average age of(40.03±17.39)years(0-74 years).Among them,127(33.2%)cases had non-neoplastic diseases,with a male-to-female ratio of 82â¶45 and an average age of(31.99±19.29)years;256(66.8%)cases had neoplastic diseases,with a male-to-female ratio of 106â¶150 and an average age of(44.01±14.87)years.The main non-neoplastic diseases were nervous system infectious diseases,cerebral vascular diseases,meningocele,cerebral cyst,and brain trauma.Among the infectious diseases,brain abscess,granulomatous inflammation,cysticercosis,and hydatidosis were common.The main neoplastic diseases included meningioma,pituitary adenoma,neuroepithelial tumor,schwannoma,metastatic tumor,and hemangioblastoma.The meningioma cases consisted of 95.4%(103/108)cases of grade â ,3.7%(4/108)cases of grade â ¡,and only 1(1/108,0.9%)case of grade â ¢.Among the neuroepithelial tumor cases,the top three were glioblastoma,grade â ¢ diffuse glioma,and ependymoma. Conclusions There are diverse CNS diseases confirmed by pathological diagnosis in Tibet,among which non-neoplastic diseases account for 1/3 of all the cases.Infectious and vascular diseases are the most common non-neoplastic diseases in Tibet,and tuberculosis and parasitic infections are relatively common.The types and proportion of brain tumors in Tibet are different from those in other regions of China,and meningioma is the most common in Tibet,with higher proportion than neuroepithelial tumor.
Assuntos
Neoplasias Encefálicas , Doenças do Sistema Nervoso Central , Ependimoma , Neoplasias Meníngeas , Adolescente , Adulto , Idoso , Neoplasias Encefálicas/diagnóstico , Doenças do Sistema Nervoso Central/epidemiologia , Doenças do Sistema Nervoso Central/patologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tibet/epidemiologia , Adulto JovemRESUMO
Primary cutaneous anaplastic large cell lymphoma is a rare non-Hodgkin's lymphoma.The tumor cells have the characteristics of anaplastic cells,expressing CD30 but not anaplastic lymphoma kinase.In this study,we reported a case of primary cutaneous anaplastic large cell lymphoma in a Tibetan child and summarized the clinicopathological features,aiming to strengthen the understanding of this disease.
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Linfoma Anaplásico Cutâneo Primário de Células Grandes , Neoplasias Cutâneas , Criança , Humanos , Antígeno Ki-1 , Neoplasias Cutâneas/patologiaRESUMO
Objective To investigate the expression of androgen receptor(AR)and its correlations with different molecular subtypes and clinicopathological features of breast invasive carcinoma of no special type(IBC-NST)in females of Tibetan ethnic minority in Tibet.Methods This study enrolled 54 female patients of Tibetan ethnic minority with IBC-NST surgically removed in the Tibet Autonomous Region People's Hospital from December 2015 to March 2021 for retrospective analysis.The clinical and pathological data of all the enrolled patients were collected.The immunohistochemical method was employed to determine the expression of AR,cell proliferation marker antigen (Ki-67),estrogen receptor(ER),human epidermal growth factor receptor 2(HER-2),and progesterone receptor(PR).For those with unclear HER-2 results,fluorescence in situ hybridization was employed for the determination.The relationship of AR expression with molecular subtypes and clinicopathological features was then analyzed.Results The expression of AR in Tibetan female patients with IBC-NST was correlated with ER(χ2=8.200,P=0.004),PR(χ2=9.900,P=0.003),and molecular subtype(χ2=11.690,P=0.009)and not correlated with tumor location,age,size,histological grade,lymph node metastasis,vascular invasion,clinical stage,or expression of HER-2 and Ki-67(all P>0.05).Molecular subtype was correlated with histological grade(χ2=24.970, P=0.001),clinical stage(χ2=9.035, P=0.029),and lymph node metastasis(χ2=9.691,P=0.021).Conclusions The positive expression rate of AR in the triple-negative IBC-NST patients of Tibetan ethnic minority was significantly lower than that in ER-or PR-positive patients in Tibet.Molecular subtype was correlated with histological grade,clinical stage,and lymph node metastasis.