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1.
Theranostics ; 14(3): 988-1009, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38250049

RESUMO

The hypothalamus plays a fundamental role in controlling lipid metabolism through neuroendocrine signals. However, there are currently no available drug targets in the hypothalamus that can effectively improve human lipid metabolism. In this study, we found that the antimalarial drug artemether (ART) significantly improved lipid metabolism by specifically inhibiting microglial activation in the hypothalamus of high-fat diet-induced mice. Mechanically, ART protects the thyrotropin-releasing hormone (TRH) neurons surrounding microglial cells from inflammatory damage and promotes the release of TRH into the peripheral circulation. As a result, TRH stimulates the synthesis of thyroid hormone (TH), leading to a significant improvement in hepatic lipid disorders. Subsequently, we employed a biotin-labeled ART chemical probe to identify the direct cellular target in microglial cells as protein kinase Cδ (PKCδ). Importantly, ART directly targeted PKCδ to inhibit its palmitoylation modification by blocking the binding of zinc finger DHHC-type palmitoyltransferase 5 (ZDHHC5), which resulted in the inhibition of downstream neuroinflammation signaling. In vivo, hypothalamic microglia-specific PKCδ knockdown markedly impaired ART-dependent neuroendocrine regulation and lipid metabolism improvement in mice. Furthermore, single-cell transcriptomics analysis in human brain tissues revealed that the level of PKCδ in microglia positively correlated with individuals who had hyperlipemia, thereby highlighting a clinical translational value. Collectively, these data suggest that the palmitoylation of microglial PKCδ in the hypothalamus plays a role in modulating peripheral lipid metabolism through hypothalamus-liver communication, and provides a promising therapeutic target for fatty liver diseases.


Assuntos
Lipoilação , Hepatopatia Gordurosa não Alcoólica , Humanos , Animais , Camundongos , Microglia , Hipotálamo , Metabolismo dos Lipídeos , Artemeter
2.
Echocardiography ; 41(1): e15729, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38113302

RESUMO

We described a case of a double aortic arch (DAA) with a subaortic left brachiocephalic vein (LBCV) and right-side ductus arteriosus using high-definition (HD) flow render mode and spatiotemporal image correlation (STIC). We experienced uncertainty regarding this interesting case despite the diagnosis of right-sided ductus arteriosus. The ductus arteriosus originates from the right pulmonary artery (PA) and converges into the descending aorta (DAO), whereas the vessel originated from the PA and converged into the ascending aorta (AAO). Therefore, we assumed that the vessel connecting the PA to AAO may be a type-C persistent fifth aortic arch (PFAA).


Assuntos
Permeabilidade do Canal Arterial , Canal Arterial , Anel Vascular , Gravidez , Feminino , Humanos , Canal Arterial/diagnóstico por imagem , Aorta Torácica/diagnóstico por imagem , Permeabilidade do Canal Arterial/diagnóstico por imagem , Aorta
3.
Reprod Sci ; 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38012523

RESUMO

A single-center retrospective study of G-band karyotyping and chromosomal microarray analysis (CMA) for the invasive prenatal diagnosis of 6159 fetuses with ultrasound abnormalities was conducted. This study aimed to investigate the incidence rates of chromosomal abnormalities and pregnancy outcomes and postpartum clinical manifestations by long-term follow-up and to explore the correlation between different types of prenatal ultrasound abnormalities and pathogenic chromosomal abnormalities. The overall incidence of pathogenic chromosomal aberrations in fetuses with ultrasound abnormalities was 7.58% (467/6159), which comprised 41.7% (195/467) with chromosome number abnormalities, 57.6% (269/467) with pathogenic copy-number variations (pCNVs), and 0.64% (3/467) with uniparental disomy (UPD). In addition, 1.72% (106/6159) with likely pathogenic copy-number variations (lpCNVs) and 3.04% (187/6159) with variants of unknown significance (VOUS) were detected by CMA. Ultrasound abnormalities were categorized into structural anomalies and soft marker anomalies. The incidence rate of pathogenic and likely pathogenic chromosomal abnormalities was significantly higher among fetuses with structural anomalies than soft markers (11.13% vs 7.59%, p < 0.01). We retrospectively analyzed the prenatal genetic outcomes for a large cohort of fetuses with different types of ultrasound abnormalities. The present study showed that the chromosomal abnormality rate and clinical outcomes of fetuses with different types of ultrasound abnormalities varied greatly. Our data have important implications for prenatal genetic counseling for fetuses with different types of ultrasound abnormalities.

4.
Biotechnol Lett ; 45(11-12): 1431-1440, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37736778

RESUMO

OBJECTIVES: Human heart-type fatty acid binding protein (HFABP) is a biomarker for diagnosis, risk assessment, and prognosis of acute myocardial infarction, and we aimed to establish an immunoassay for HFABP quantitation. METHODS: Human HFABP monoclonal antibodies (mAbs) were developed, evaluated by enzyme-linked immunosorbent assay, and a chemiluminescence enzyme immunoassay (CLEIA) generated. Analytical performance of the CLEIA was evaluated by measuring serum HFABP. RESULTS: The prokaryotically expressed rHFABP was purified and four anti-HFABP mAbs with superior detection performance were obtained after immunizing BALB/c mice. MAbs 2B8 and 6B3 were selected as respective capture and detection antibodies for HFABP measurement by CLEIA (detection range, 0.01-128 µg/L). Results using the CLEIA showed excellent correlation (r, 0.9622) and the correlation coefficient was 0.9809 (P < 0.05) by the Tukey test statistical analysis with those of latex-enhanced immunoturbidimetry in hospitals. CONCLUSION: Our mAbs and CLEIA for HFABP detection represent new diagnostic tools for measurement of human serum HFABP.


Assuntos
Anticorpos Monoclonais , Luminescência , Animais , Camundongos , Humanos , Ensaio de Imunoadsorção Enzimática/métodos , Imunoensaio/métodos , Biomarcadores
5.
Breast J ; 2023: 1682084, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37771427

RESUMO

Purpose: To evaluate the prognosis of patients with benign phyllodes tumors (PTs) treated by different surgical methods and to explore the influencing factors of local recurrence. Methods: We retrospectively analyzed 215 benign PTs from 193 patients who underwent surgery at Chinese PLA General Hospital between October 2008 and December 2020. We stratified our analysis according to surgical factors and explored the clinicopathological factors to influence local recurrence. Results: Among 193 patients, a total of 17 (8.8%, 17/193) recurred during follow-up. There were 89 patients in the US-VAE group, of whom 6 (6.7%) recurred; 8 of 57 patients (14%) in the local lumpectomy group recurred, while 3 of 47 patients (6.4%) in the extended lumpectomy group recurred (P=0.252). Multivariate logistic regression analysis showed that tumor diameter, mitosis, and history of breast myoma were independent risk factors for tumor recurrence (P=0.005, P=0.006, and P=0.004, respectively). The intraoperative blood loss, operation time, and scar length of the US-VAE group were shorter than those of the other two groups (P < 0.05). Conclusion: Negative surgical margins of benign PTs can obtain similar prognosis as negative surgical margins >10 mm. Therefore, we recommend that a follow-up observation policy be adopted for patients with unexpected benign PTs, rather than unnecessary open surgical resection. Patients' maximum tumor diameter, mitosis, and fibroadenoma history were independent predictors for recurrence of benign PTs.


Assuntos
Neoplasias da Mama , Tumor Filoide , Humanos , Feminino , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Tumor Filoide/cirurgia , Tumor Filoide/patologia , Margens de Excisão , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Prognóstico
6.
Front Pharmacol ; 14: 1165356, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37324456

RESUMO

Purpose: Intravitreal injection of conbercept (IVC) is a novel anti-vascular endothelial growth factor (anti-VEGF) treatment for retinopathy of prematurity (ROP). This study aimed to assess the intraocular pressure (IOP) effect of IVC. Methods: All IVC surgeries were performed in the Department of Ophthalmology, Guangdong Women and Children Hospital, from January 2021 to May 2021. In this study, 30 eyes of 15 infants who received intravitreal injections of conbercept at a dose of 0.25 mg/0.025 mL were included. The IOP of all participants was measured prior to administering the injection and subsequently at 2 min, 1 h, 1 day, and 1 week thereafter. Results: We included 30 eyes (10 boys and 5 girls) with ROP. For the male group, the mean birth weight, mean gestational age at birth, and the mean time of postmenstrual age (PMA) at IVC treatment were 1,174.0 ± 446.0 g, 28.4 ± 3.0 weeks, and 37.1 ± 1.6 weeks, respectively; for the female group, they were 1,108 ± 285.5 g, 28.2 ± 2.5 weeks, and 36.8 ± 2.1 weeks, respectively. For the male group, the IOP at baseline, 2 min, 1 h, 1 day, and 1 week after IVC were 12.4 ± 1.5 mmHg, 49.0 ± 3.1 mmHg, 26.3 ± 2.5 mmHg, 13.4 ± 2.2 mmHg, and 11.6 ± 1.7 mmHg, respectively; for the female group, they were 10.7 ± 2.0 mmHg, 47.3 ± 3.2 mmHg, 26.4 ± 3.2 mmHg, 10.7 ± 1.8 mmHg, and 10.2 ± 1.8 mmHg, respectively. In both groups, the IOP immediately (2 min) after the operation was significantly higher than that at any other time point (p < 0.01). IOP values returned to the preoperative baseline level on the first day after surgery, with no significant difference compared with that before injection (p > 0.05). IOP continued to be maintained at the preoperative baseline level on the first week after surgery, with no significant difference compared with that before surgery (p > 0.05). Conclusion: Infants with ROP who received IVC experienced a sharp increase in the IOP immediately after injection, which decreased to below 30 mmHg after 1 h and maintain that level for 1 week or longer.

7.
Zhongguo Zhong Yao Za Zhi ; 48(9): 2464-2470, 2023 May.
Artigo em Chinês | MEDLINE | ID: mdl-37282875

RESUMO

This paper explored the chemical constituents of Boswellia carterii by column chromatography on silica gel, Sephadex LH-20, ODS column chromatography, and semi-preparative HPLC. The structures of the compounds were identified by physicochemical properties and spectroscopic data such as infrared radiation(IR), ultra violet(UV), mass spectrometry(MS), and nuclear magnetic resonance(NMR). Seven diterpenoids were isolated and purified from n-hexane of B. carterii. The isolates were identified as(1S,3E,7E,11R,12R)-11-hydroxy-1-isopropyl-4,8,12-trimethyl-15-oxabicyclo[10.2.1]pentadeca-3,7-dien-5-one(1),(1R,3S,4R,7E,11E)-4,8,12,15,15-pentamethyl-14-oxabicyclo[11.2.1]hexadeca-7,11-dien-4-ol(2), incensole(3),(-)-(R)-nephthenol(4), euphraticanoid F(5), dilospirane B(6), and dictyotin C(7). Among them, compounds 1 and 2 were new and their absolute configurations were determined by comparison of the calculated and experimental electronic circular dichroisms(ECDs). Compounds 6 and 7 were obtained from B. carterii for the first time.


Assuntos
Boswellia , Diterpenos , Estrutura Molecular , Boswellia/química , Diterpenos/química , Espectrometria de Massas
8.
Virus Genes ; 59(5): 670-677, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37328638

RESUMO

Epstein-Barr virus (EBV) is the first identified human oncogenic herpesvirus infecting over 90% of the adults worldwide. However, the safe and effective prophylactic vaccine has not been licensed. The major glycoprotein 350 (gp350) on the EBV envelope is the main target for neutralizing antibodies, and gp350 (aa15-320) was used for the development of monoclonal antibodies in present study. The purified recombinant gp35015-320aa with an estimated molecular weight of 50 kDa was used to immunize six-week-old BALB/c mice, and the hybridoma cell lines that stably secreted monoclonal antibodies (mAbs) were obtained. The ability of developed mAbs for capturing and neutralizing EBV was evaluated, and mAb 4E1 presented better performance to block the infection of EBV in cell line Hone-1. The mAb 4E1 recognized the epitope. Its sequence of variable region genes (VH and VL) presented a unique identity which hadn't been reported. The developed mAbs might benefit the antiviral therapy and immunologic diagnosis for EBV infection.


Assuntos
Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Adulto , Animais , Camundongos , Humanos , Herpesvirus Humano 4/genética , Anticorpos Monoclonais , Anticorpos Antivirais , Anticorpos Neutralizantes , Glicoproteínas/genética
9.
J Clin Transl Hepatol ; 11(3): 540-549, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-36969885

RESUMO

Background and Aims: Chronic active Epstein-Barr virus hepatitis (CAEBVH) is a rare and highly lethal disease characterized by hepatitis and hepatomegaly. This study aimed to investigate the clinicopathological features and pathogenic mechanisms of CAEBVH. Methods: Ten patients with confirmed Epstein-Barr virus hepatitis infection were enrolled. The clinicopathological characteristics of these patients were summarized and analyzed. Flow cytometry was utilized to detect peripheral blood immune cell phenotypes and whole exome sequencing was used to explore pathogenic genetic mechanisms. Lastly, immunohistochemical staining was employed to verify pathogenic mechanisms. Results: Clinical features observed in all Epstein-Barr virus hepatitis patients included fever (7/10), splenomegaly (10/10), hepatomegaly (9/10), abnormal liver function (8/10), and CD8+ T cell lymphopenia (6/7). Hematoxylin and eosin staining revealed lymphocytic infiltration in the liver. Positive Epstein-Barr virus-encoded small RNA in-situ hybridization (EBER-ISH) of lymphocytes of liver tissues was noted. Whole exome sequencing indicated that cytotoxic T lymphocytes and the complement system were involved. The expression of CD8, Fas, FasL, and Caspase-8 expression as well as apoptotic markers was enhanced in the Epstein-Barr virus hepatitis group relative to the controls (p<0.05). Lastly, Complement 1q and complement 3d expression, were higher in CAEBVH patients relative to controls (p<0.05). Conclusions: CAEBVH patients developed fever, hepatosplenomegaly, and lymphadenopathy. Histopathological changes were a diffuse lymphocytic sinusoidal infiltrate with EBER-ISH positivity. Fas/FasL and complement activation were involved in CAEBVH patients.

10.
Nature ; 615(7951): 285-291, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36859541

RESUMO

The germline mutation rate determines the pace of genome evolution and is an evolving parameter itself1. However, little is known about what determines its evolution, as most studies of mutation rates have focused on single species with different methodologies2. Here we quantify germline mutation rates across vertebrates by sequencing and comparing the high-coverage genomes of 151 parent-offspring trios from 68 species of mammals, fishes, birds and reptiles. We show that the per-generation mutation rate varies among species by a factor of 40, with mutation rates being higher for males than for females in mammals and birds, but not in reptiles and fishes. The generation time, age at maturity and species-level fecundity are the key life-history traits affecting this variation among species. Furthermore, species with higher long-term effective population sizes tend to have lower mutation rates per generation, providing support for the drift barrier hypothesis3. The exceptionally high yearly mutation rates of domesticated animals, which have been continually selected on fecundity traits including shorter generation times, further support the importance of generation time in the evolution of mutation rates. Overall, our comparative analysis of pedigree-based mutation rates provides ecological insights on the mutation rate evolution in vertebrates.


Assuntos
Evolução Molecular , Mutação em Linhagem Germinativa , Taxa de Mutação , Vertebrados , Animais , Feminino , Masculino , Aves/genética , Peixes/genética , Mutação em Linhagem Germinativa/genética , Mamíferos/genética , Répteis/genética , Vertebrados/genética
11.
Phytochemistry ; 209: 113637, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36893825

RESUMO

Eleven undescribed isoquinoline analogues, namely edulisines A-K, along with sixteen known alkaloids, were isolated from the whole plants of Corydalis edulis. The structures of the isolated alkaloids were established on the basis of extensive spectroscopic data (1D and 2D NMR, UV, IR, and HRESIMS). Their absolute configurations were determined by single-crystal X-ray crystallographic analysis and ECD. Compounds (+)-1 and (-)-1 are a pair of undescribed isoquinoline alkaloids bearing a unique coupled pattern of coptisine and ferulic acid via Diels-Alder [4 + 2] cycloaddition, while compounds (+)-2 and (-)-2 feature benzo [1,2-d:3,4-d]bis [1,3]dioxole moiety. Compounds (+)-2, (-)-2, (-)-5, 10, 13, 15, 20, 22, and 23 significantly triggered the secretion of insulin in the HIT-T15 cells at a concentration of 40 µM.


Assuntos
Alcaloides , Corydalis , Corydalis/química , Alcaloides/química , Espectroscopia de Ressonância Magnética , Insulina , Isoquinolinas/farmacologia , Isoquinolinas/química , Estrutura Molecular
12.
Bioorg Chem ; 133: 106396, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36758274

RESUMO

Six previously unprecedented 2-(2-phenylethyl)chromone-sesquiterpene hybrids, aquisinenins A-F (1 - 6), were isolated from the resinous wood of Aquilaria sinensis by a LC-MS-guided fractionation procedure. Their structures were determined by extensive spectroscopic analysis (1D and 2D NMR, UV, IR, and HRMS) and experimental and computed ECD data. Compounds 1 - 6 were rare dimeric 2-(2-phenylethyl)chromone-sesquiterpene derivatives featuring 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromone hybridized with different sesquiterpene (eudesmane/guaiane type) moieties via ester bond. Furthermore, all the isolated compounds were evaluated for their protective effects on taurocholic acid (TCA)-induced GES-1 cell injury. The most effective aquisinenin F (6) was used to elucidate the involved mechanism on protection against TCA-induced gastric mucosal damage. Our results indicated that 6 protected against gastric mucosal cell insult by downregulation of the ER stress triggered by TCA.


Assuntos
Sesquiterpenos , Thymelaeaceae , Cromonas , Madeira/química , Flavonoides/química , Thymelaeaceae/química , Resinas Vegetais , Estrutura Molecular
14.
Biomed Res Int ; 2023: 3222686, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36817862

RESUMO

Objective: To study the clinical efficacy of nutritional intervention combined with muscle exercise on sarcopenia patients with femoral fracture. Methods: From January 2019 to January 2021, a total of 100 sarcopenia patients with femoral fracture were included in this study and were divided into a control group (routine postoperative care) and a research group (nutritional intervention and muscle exercise), 50 cases in each group. Primary clinical outcomes included sarcopenia-related indicators and functional independence assessed by activities of daily living scale (ADL). Secondary clinical outcomes included time of fracture healing and hospital stay, pain score as assessed by visual analogue scale (VAS), and nursing satisfaction. Results: Before the intervention, there was no significant difference in the indicators of sarcopenia and the indicators of functional independence assessed by ADL between the two groups (P > 0.05). After 3 months of intervention, the BMI, grip strength, calf circumference, pace, and body muscle rate of the patients in the research group were significantly higher than those in the control group (P < 0.05), while body fat rates were significantly lower than those in the control group (P < 0.05), and the capability of eating, walking, bathing, and doing housework in research group were all significantly higher than those in control group (P < 0.05). In addition, the time of fracture healing and hospital stay in research group were all significantly lower than those in control group (P < 0.05), and the VAS scores of the control group at each time point after intervention were significantly higher than those of the research group (P < 0.05). The nursing satisfaction of the patients in the research group was significantly higher than that in the control group (94.00% vs. 76.00%, P < 0.05). Conclusion: Nutritional intervention combined with muscle exercise can help improve sarcopenia symptoms and promote fracture recovery in patients with sarcopenic femoral fractures.


Assuntos
Fraturas do Fêmur , Sarcopenia , Humanos , Atividades Cotidianas , Projetos Piloto , Resultado do Tratamento , Músculos
15.
Nat Prod Res ; 37(6): 928-935, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35822397

RESUMO

Two pairs of flavonoid enantiomers (1a/1b and 2a/2b) together with three known analogues (3-5) were isolated from the heartwood of Dalbergia odorifera T. Chen. Their structures were elucidated by extensive spectroscopic analysis (1 D and 2 D NMR, UV, IR, and HRMS) and experimental and calculated ECD data. Compound 2 features an unusual 2-methyl-3(2H)-furanone moiety forming the C-ring of flavonoid, and its putative biosynthetic pathway is also proposed. Compounds 3‒5 exhibited significant inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells with IC50 values of 14.7 ± 0.3 µM, 40.2 ± 1.1 µM, and 3.2 ± 0.1 µM, respectively.


Assuntos
Dalbergia , Flavonoides , Camundongos , Animais , Flavonoides/farmacologia , Flavonoides/química , Dalbergia/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Extratos Vegetais/química , Células RAW 264.7
16.
J Photochem Photobiol B ; 238: 112583, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36436360

RESUMO

Cervical carcinoma is the fourth most common gynecological cancer. Here we reported the synthesis of oxygen-carried and lipopolysaccharide (LPS)/ indocyanine green (ICG)-loaded nanoparticles (OLI_NPs) for photo-sonodynamic therapy (PSDT) mediated combination therapy to induce systemic antitumor immune responses. We effectively built a new nanoparticle system, a multifunctional nanoagent that integrated the ability of dual-model imaging and therapy for tumors. In this study, we confirmed that OLI_NPs can act as a multifunctional platform that enables not only to diagnose tumors conveniently but also to efficiently provide treatment of in situ tumors, permitting simultaneous dual-mode imaging and localization of the therapy in combination with PSDT-mediated drug release. Furthermore, our combined strategy could effectively depress the tumor development and extend mouse life by the combination of inducing immunogenic cell death (ICD) with encapsulated LPS. In conclusion, combining therapy of OLI_NPs plus PSDT can induce anti-tumor immune responses and tumor antigen-specific immunity in a common TC-1 graft tumor model. Therefore, this combination therapy is a viable technique for cervical cancer treatment.


Assuntos
Nanopartículas , Neoplasias do Colo do Útero , Humanos , Feminino , Animais , Camundongos , Neoplasias do Colo do Útero/terapia , Modelos Animais de Doenças , Lipopolissacarídeos/farmacologia , Linhagem Celular Tumoral , Verde de Indocianina/farmacologia , Imunidade
17.
J Hepatocell Carcinoma ; 10: 2367-2382, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38164511

RESUMO

Background: PVTT is a hallmark of advanced hepatocellular carcinoma (HCC). We aim to explore the influence of non-invasive biomarkers on the occurrence of PVTT and develop and validate models for predicting prognosis in HBV-related HCC patients without PVTT. Methods: A total of 1026 HBV-related HCC patients without PVTT were enrolled, with 515 in the training cohort, 216 in the internal validation cohort, and 295 in the external validation cohort. We conducted Cox regression analyses to discern the independent risk factors associated with PVTT events, PFS, and OS, then constructed and validated predictive models. The predictive and discriminatory capabilities of models were assessed using the calibration, time-dependent ROC, and DCA curves. Results: In our study, 136 patients (13.3%) experienced PVTT events during the follow-up period. The Cox regression analysis unveiled that male gender, AAPR ≤0.49, APRI >0.48, extrahepatic metastasis, and multiple tumors were independent risk factors for PVTT. In the training cohort, non-invasive biomarkers (AAR and APRI), AFP, ascites, and tumor-related characteristics (extrahepatic metastasis, tumor diameter, tumor number, and PVTT event) were independent risk factors for both OS and PFS, whereas age and ALBI grade independently correlated with OS. The C-indexes of OS and PFS nomogram models were 0.795 and 0.733 in the training cohort, 0.765 and 0.716 in the internal validation cohort, and 0.780 and 0.722 in the external validation cohort, respectively. Our models demonstrated strong predictive and discriminative abilities in all cohorts and yielded a greater net benefit compared to three traditional staging systems. Conclusion: Non-invasive biomarkers are expected to be reliable predictors for assessing PVTT risk and predicting prognosis among HBV-related HCC patients without PVTT.

18.
Front Genet ; 14: 1326737, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38343446

RESUMO

Background: Tousled-like kinase 2 (TLK2) is integral to DNA repair, replication, and cell cycle regulation, crucial for maintaining genome stability and integrity. However, the expression and prognostic value of TLK2 in hepatitis B viral (HBV) -related hepatocellular carcinoma (HCC) remains unclear. Methods: We examined TLK2 expression and prognostic implications in pan-cancer by using diverse databases. Subsequently, TLK2 expression in HBV-related HCC tissues and adjacent tissues was assessed using quantitative real-time PCR and immunohistochemistry. The prognostic value of TLK2 was assessed through ROC curves, time-dependent ROC curves, Cox regression, Kaplan-Meier curve, and decision curve analysis. Additionally, analyses of immune infiltration, protein-protein interactions, key molecules of tumor-related signaling pathways, molecular subtypes, and TLK2-associated differentially expressed genes (DEGs) were conducted, along with GO/KEGG and GSEA enrichment analyses. Results: TLK2 expression was significantly higher in HCC tissues compared to adjacent tissues and correlated with gender, AFP levels, albumin-bilirubin (ALBI) grade, microvascular invasion (MVI), maximum tumor diameter, tumor number, and TNM stage. TLK2 overexpression emerged as an independent risk factor for overall survival (OS) and recurrence-free survival (RFS) in HBV-related HCC patients. An integrated OS nomogram model, incorporating TLK2, age, ALBI grade, MVI, and tumor number, displayed enhanced prognostic capability (C-index: 0.765, 95% CI: 0.732-0.798) in predicting OS and has a higher net benefit than the TNM stage. Moreover, TLK2 expression correlated closely with immune cell infiltration and key molecules of signaling pathways. Functional enrichment analyses highlighted significant associations with DNA duplex unwinding, double-strand break repair, DNA replication, cell cycle, E2F targets, G2M checkpoint, and MYC targets V1. Conclusion: TLK2 is notably overexpressed in HBV-related HCC and emerges as a promising prognostic biomarker, necessitating further validation.

19.
Chemistry (Basel) ; 5(3): 1745-1759, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38371491

RESUMO

While fluorescent sensors have been developed for monitoring metal ions in health and diseases, they are limited by the requirement of an excitation light source that can lead to photobleaching and a high autofluorescence background. To address these issues, bioluminescence resonance energy transfer (BRET)-based protein or small molecule sensors have been developed; however, most of them are not highly selective nor generalizable to different metal ions. Taking advantage of the high selectivity and generalizability of DNAzymes, we report herein DNAzyme-based ratiometric sensors for Zn2+ based on BRET. The 8-17 DNAzyme was labeled with luciferase and Cy3. The proximity between luciferase and Cy3 permiQed BRET when coelenterazine, the substrate for luciferase, was introduced. Adding samples containing Zn2+ resulted in a cleavage of the substrate strand, causing dehybridization of the DNAzyme construct, thus increasing the distance between Cy3 and luciferase and changing the BRET signals. Using these sensors, we detected Zn2+ in serum samples and achieved Zn2+ detection with a smartphone camera. Moreover, since the BRET pair is not the component that determines the selectivity of the sensors, this sensing platform has the potential to be adapted for the detection of other metal ions with other metal-dependent DNAzymes.

20.
Ann Med ; 55(2): 2299574, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38170847

RESUMO

BACKGROUND: To investigate the cognition of cancer warning symptoms and cancer risk factors among Chinese college students, analyze the influencing factors, and explain the correlations between cancer cognition and cancer symptom discrimination, cancer fear and psychological distress. METHODS: Chinese college students were recruited in this cross-sectional study funded by a summer social practice activity in Yunnan Province, China. Cognition rates of cancer warning symptoms and cancer risk factors were evaluated using Cancer Warning symptoms Cognition Questionnaire (CWSCQ) and Cancer Risk Factors Cognition Questionnaire (CRFCQ), respectively. Factors associated with cognition of cancer warning symptoms, and factors associated with cognition of cancer risk factors were evaluated using multiple linear regression analysis. Interactions between cancer cognition, cancer symptom discrimination, psychological distress, and cancer fear were evaluated by structural equation modeling. RESULTS: There were 846 effective samples, with an effective rate of 80.9%. The cognition rates of cancer warning symptoms were from 47.9% to 84.4%, which were affected by cancer symptom discrimination, education, attitudes towards cancer screening, living expenses, drinking history, and ways to obtain cancer knowledge (p < 0.05). The cognition rates of cancer risk factors were from 46.3% to 91.3% in participants, which were affected by education, cancer symptom discrimination, psychological distress, attitudes towards cancer screening, life satisfaction, cancer history in relatives and friends, ways to obtain cancer knowledge, smoking history, and nursing history for cancer patients (p < 0.05). Cancer cognition and cancer symptom discrimination showed intermediary effects on psychological distress and cancer fear (p < 0.001). CONCLUSIONS: The overall cancer cognition situation among Chinese college students is not optimistic, which highlights the necessity of improving the cancer health literacy among Chinese college students. With the increasing morbidity and mortality rates of cancer, it is necessary to raise awareness of early detection, and early treatment of cancer among the general public. Health education interventions are helpful to improve cancer health literacy.


Assuntos
Neoplasias , Estudantes , Humanos , Estudos Transversais , China/epidemiologia , Estudantes/psicologia , Neoplasias/epidemiologia , Inquéritos e Questionários , Fatores de Risco , Cognição , Conhecimentos, Atitudes e Prática em Saúde
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