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1.
Adv Sci (Weinh) ; : e2402329, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39120980

RESUMEN

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer and its prognosis remains poor. Although growing numbers of studies have verified the involvement of circular RNAs (circRNAs) in various cancer types, their specific functions in ICC remain elusive. Herein, a circRNA, circUGP2 is identified by circRNA sequencing, which is downregulated in ICC tissues and correlated with patients' prognosis. Moreover, circUGP2 overexpression suppresses tumor progression in vitro and in vivo. Mechanistically, circUGP2 functions as a transcriptional co-activator of PURB over the expression of ADGRB1. It can also upregulate ADGRB1 expression by sponging miR-3191-5p. As a result, ADGRB1 prevents MDM2-mediated p53 polyubiquitination and thereby activates p53 signaling to inhibit ICC progression. Based on these findings, circUGP2 plasmid is encapsulated into a lipid nanoparticle (LNP) system, which has successfully targeted tumor site and shows superior anti-tumor effects. In summary, the present study has identified the role of circUGP2 as a tumor suppressor in ICC through regulating ADGRB1/p53 axis, and the application of LNP provides a promising translational strategy for ICC treatment.

2.
Eur J Med Chem ; 277: 116759, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39137454

RESUMEN

In 2022, the U.S. Food and Drug Administration approved a total of 16 marketing applications for small molecule drugs, which not only provided dominant scaffolds but also introduced novel mechanisms of action and clinical indications. The successful cases provide valuable information for optimizing efficacy and enhancing pharmacokinetic properties through strategies like macrocyclization, bioequivalent group utilization, prodrug synthesis, and conformation restriction. Therefore, gaining an in-depth understanding of the design principles and strategies underlying these drugs will greatly facilitate the development of new therapeutic agents. This review focuses on the research and development process of these newly approved small molecule drugs including drug design, structural modification, and improvement of pharmacokinetic properties to inspire future research in this field.

3.
World J Clin Cases ; 12(20): 4146-4153, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39015927

RESUMEN

BACKGROUND: Cervical intraepithelial neoplasia (CIN) is an important precursor of cervical cancer. Early detection and treatment can reduce the incidence of cervical cancer. AIM: To investigate the detection rate of human papillomavirus (HPV) E6/E7 mRNA in cervical tissue of patients with different types of epithelial cell neoplasia (CIN) and its relationship with CIN progression and diagnosis. METHODS: One hundred women with HPV infection detected by cervical exfoliation cytology between January 2022 and January 2023 were retrospectively selected. These patients were graded CIN based on colposcopy and cervical pathology. The positive expression rates of HPV E6/E7 mRNA and HPV [polymerase chain reaction (PCR)-reverse dot crossing] were compared among all groups. Patients with HPV E6/E7 mRNA expression in the grade 1 CIN group were followed up for 1 yr. The relationship between atypical squamous epithelium and high malignant epithelial neoplasia was investigated by univariate and multivariate analysis. RESULTS: The diagnostic sensitivity, specificity, and sensitivity of PCR-reverse point hybridization technology for secondary CIN were 70.41%, 70.66%, and 0.714, respectively. Sensitivity and specificity for secondary CIN were 752% and 7853%, respectively, the area under the curve value was 0.789. Logistic Multifactorial model analysis revealed that the HPV positive rates and the HPV E6/E7 mRNA positive rates were independent risk factors of CIN grade I (P < 0.05). In CIN grade I patients with positive for HPV E6/E7 mRNA, in its orientation to grade CIN patients, in its orientation to grade CIN patients, at 69.2%, compared with patients negative for HPV E6/E7 mRNA (30.8%), significant difference (P < 0.05). CONCLUSION: HPV E6/E7 mRNA and HPV (PCR-reverse dot hybrid) positive expression have a close relationship with CIN-grade disease progression and is an independent risk factor for high-grade CIN lesions.

4.
J Med Case Rep ; 18(1): 333, 2024 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-39033155

RESUMEN

BACKGROUND: Leiomyosarcoma is a tumor that can develop in any organ that contains smooth muscles. Although leiomyosarcoma is common, its epididymal localization is quite rare. CASE PRESENTATION: A 79-year-old male Chinese Han patient presented with mild pain in the right groin and scrotum for 3 years concomitant with right scrotal swelling. Ultrasonography and magnetic resonance imaging of the scrotum showed a irregular and heterogeneous mass that was extratesticular. Right high orchiectomy was performed, and pathological examination of the resected specimen confirmed the diagnosis of leiomyosarcoma of the epididymis with surgical margins clear of tumor. CONCLUSION: Epididymal leiomyosarcoma is rare and difficult to diagnose preoperatively. The final diagnosis of epididymal leiomyosarcoma requires histologic examination. Resection must be extensive and complete. The effect of chemotherapy and radiation on the epididymal leiomyosarcoma remains unclear. Recurrence is common, so follow-up is necessary.


Asunto(s)
Epidídimo , Neoplasias de los Genitales Masculinos , Leiomiosarcoma , Orquiectomía , Humanos , Masculino , Leiomiosarcoma/patología , Leiomiosarcoma/cirugía , Leiomiosarcoma/diagnóstico por imagen , Leiomiosarcoma/diagnóstico , Anciano , Epidídimo/patología , Epidídimo/diagnóstico por imagen , Epidídimo/cirugía , Neoplasias de los Genitales Masculinos/patología , Neoplasias de los Genitales Masculinos/cirugía , Neoplasias de los Genitales Masculinos/diagnóstico por imagen , Neoplasias de los Genitales Masculinos/diagnóstico , Neoplasias de los Genitales Masculinos/terapia , Imagen por Resonancia Magnética , Ultrasonografía
5.
Food Chem ; 460(Pt 1): 140405, 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39053272

RESUMEN

Stimuli-responsive hydrogel possesses a strong loading capacity to embed luminescent indicators for constructing food safety sensors, which are suitable for field application. In this work, a fluorescent hydrogel sensor was fabricated by incorporating Ag+-modified carbon dots (CDs-Ag+) into a sodium alginate (SA) hydrogel for in-situ detection of thiram. The fluorescence of CDs was quenched due to the combined effects of electrostatic adsorption and electron transfer between Ag+ and CDs. The formation of an AgS bond between thiram and Ag+ facilitates the release of CDs, causing subsequently fluorescence recovery. Combined with smartphone and analysis software, the fluorescence color change of the hydrogel sensor was converted into data information for quantitative detection of thiram. Such a sample-to-result step is completed within 10 min. Notably, the in-situ detection experiment of thiram in fruit and vegetable samples confirmed the practical application of the hydrogel sensor. Therefore, the hydrogel sensor provides a new research direction for the in-situ detection of pesticide residues in the monitoring of food safety.

6.
Eur J Med Chem ; 276: 116706, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39053188

RESUMEN

In 2023, the U.S. Food and Drug Administration has approved 55 novel medications, consisting of 17 biologics license applications and 38 new molecular entities. Although the biologics license applications including antibody and enzyme replacement therapy set a historical record, the new molecular entities comprising small molecule drugs, diagnostic agent, RNA interference therapy and biomacromolecular peptide still account for over 50 % of the newly approved medications. The novel and privileged scaffolds derived from drugs, active molecules and natural products are consistently associated with the discovery of new mechanisms, the expansion of clinical indications and the reduction of side effects. Moreover, the structural modifications based on the promising scaffolds can provide the clinical candidates with the improved biological activities, bypass the patent protection and greatly shorten the period of new drug discovery. Therefore, conducting an appraisal of drug approval experience and related information will expedite the identification of more potent drug molecules. In this review, we comprehensively summarized the pertinent information encompassing the clinical application, mechanism, elegant design and development processes of 28 small molecule drugs, and expected to provide the promising structural basis and design inspiration for pharmaceutical chemists.


Asunto(s)
Aprobación de Drogas , United States Food and Drug Administration , Humanos , Estados Unidos , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología , Estructura Molecular
7.
J Org Chem ; 89(12): 8759-8766, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38863082

RESUMEN

It is universally acknowledged that ligands can improve the reaction activity to simplify the reaction operating conditions and enrich the applicability of the reaction. Therefore, we developed N-octylglycine ligand-accelerated Pd-catalyzed ortho-arylation of benzoic acids under mild conditions with just 6 h; moreover, this N-octylglycine ligand was successfully implemented to carboxyl-directed Pd-catalyzed ß-C(sp3)-H arylation and ortho-arylation of phenylacetic acids under mild conditions.

8.
PLoS One ; 19(6): e0305897, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38905258

RESUMEN

In the context of global aging, promoting the health of the elderly has become a critical issue. However, whether the development of smart cities can impact the health of older adults remains to be further validated. In this paper, based on panel data from the China Health and Retirement Longitudinal Study (CHARLS), a difference in difference model is used to empirically investigate whether smart city construction improves the health of older people in the region. The results show that smart city construction enhances the health of the elderly. Specifically, the construction achieved a significant improvement in the physical health of the elderly who did not live with their children. The health promotion effect of the smart city was more significant for the urban elderly than for the rural elderly. The elucidated mechanisms of influence suggest that smart cities bring about their effects through the promotion of urban leisure infrastructure, enhancement of medical service provision, advancement in urban environmental protection and stimulation of urban information and communication technology infrastructure development.


Asunto(s)
Ciudades , Humanos , China , Anciano , Masculino , Femenino , Estudios Longitudinales , Población Urbana , Población Rural , Promoción de la Salud , Persona de Mediana Edad , Anciano de 80 o más Años , Planificación de Ciudades/métodos , Estado de Salud
9.
JAMA Netw Open ; 7(6): e2418454, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38916895

RESUMEN

This diagnostic/prognostic study assesses the ability of a large language model (LLM) to detect guardian authorship of messages originating from adolescent patient portals.


Asunto(s)
Tutores Legales , Portales del Paciente , Humanos , Adolescente , Masculino , Femenino , Lenguaje
10.
Light Sci Appl ; 13(1): 111, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38734686

RESUMEN

Quantum-confined CsPbBr3 perovskites are promising blue emitters for ultra-high-definition displays, but their soft lattice caused by highly ionic nature has a limited stability. Here, we endow CsPbBr3 nanoplatelets (NPLs) with atomic crystal-like structural rigidity through proper surface engineering, by using strongly bound N-dodecylbenzene sulfonic acid (DBSA). A stable, rigid crystal structure, as well as uniform, orderly-arranged surface of these NPLs is achieved by optimizing intermediate reaction stage, by switching from molecular clusters to mono-octahedra, while interaction with DBSA resulted in formation of a CsxO monolayer shell capping the NPL surface. As a result, both structural and optical stability of the CsPbBr3 NPLs is enhanced by strong covalent bonding of DBSA, which inhibits undesired phase transitions and decomposition of the perovskite phase potentially caused by ligand desorption. Moreover, rather small amount of DBSA ligands at the NPL surface results in a short inter-NPL spacing in their closely-packed films, which facilitates efficient charge injection and transport. Blue photoluminescence of the produced CsPbBr3 NPLs is bright (nearly unity emission quantum yield) and peaks at 457 nm with an extremely narrow bandwidth of 3.7 nm at 80 K, while the bandwidth of the electroluminescence (peaked at 460 nm) also reaches a record-narrow value of 15 nm at room temperature. This value corresponds to the CIE coordinates of (0.141, 0.062), which meets Rec. 2020 standards for ultra-high-definition displays.

11.
J Asthma ; : 1-9, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38696283

RESUMEN

OBJECTIVE: Paclitaxel exhibits outstanding biological activities in inhibiting cell proliferation and inducing cell apoptosis. However, the effects of paclitaxel on airway smooth muscle cells (ASMCs) have not been reported yet. The purpose of this study is to determine the effects of paclitaxel on the proliferation and apoptosis of ASMCs. METHODS: Rat primary ASMCs were isolated and used in all the experiments. Cell Counting Kit-8 assay and Edu assay were used to analyze the cell viability and proliferation, respectively. Flow cytometry was used to detect the cell cycle and apoptosis. Quantitative real-time PCR (qRT-PCR), western blotting, and immunostaining were used to detect the expression of cyclin-dependent kinase 1 (Cdk1). RESULTS: Our study showed that paclitaxel inhibits the proliferation of ASMCs in a dose- and time-gradient-dependent manner. Further study displayed that cell cycle is arrested at G2/M phase. And Cdk1 was dramatically down-regulated by paclitaxel treatment. Cell morphological analysis showed that ASMCs are elliptical with a larger surface area after paclitaxel treatment. Nucleus morphological analysis showed that the nuclei are in a diffuse state after paclitaxel treatment. However, paclitaxel did not induce the apoptosis of ASMCs. CONCLUSIONS: Our study demonstrated that paclitaxel inhibits the proliferation of ASMCs at least partly by negatively regulating Cdk1-cell cycle axis.

12.
Transl Neurosci ; 15(1): 20220338, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38623574

RESUMEN

Background: The deposition of Aß42 has been regarded as one of the important pathological features of Alzheimer's disease (AD). However, drug development for Aß42 toxicity has been progressed slowly. Objective: Our aim was to introduce the effect and related mechanism of trehalose on an Aßarc (arctic mutant Aß42) Drosophila AD model. Methods: The human Aßarc was expressed in Drosophila to construct the AD model. Trehalose was added to the culture vial. The movement ability was determined by detecting climbing ability and flight ability. Enzyme-linked immunosorbent assay was used to detect the levels of Aßarc, ATP, and lactate. Electron microscopy assay, mitochondrial membrane potential assay, and mitochondrial respiration assay were used to assess the mitochondrial structure and function. Results: Trehalose strongly improved the movement ability of Aßarc Drosophila in a concentration gradient-dependent manner. Furthermore, trehalose increased the content of ATP and decreased the content of Aßarc and lactate both in the brain and thorax of Aßarc Drosophila. More importantly, the mitochondrial structure and function were greatly improved by trehalose treatment in Aßarc Drosophila. Conclusion: Trehalose improves movement ability at least partly by reducing the Aßarc level and restoring the mitochondrial structure and function in Aßarc Drosophila.

13.
Ear Nose Throat J ; : 1455613241237772, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38439628

RESUMEN

Objective: Nasopharyngeal melanoma is a rare mucosal malignant melanoma with high recurrence rate, metastasis rate and vascular invasion rate. In this paper, we report a case of primary nasopharyngeal mucosal melanoma. Methods: A case of primary nasopharyngeal mucosal melanoma was reported, and its clinical symptoms, pathological characteristics, treatment and follow-up were described in detail. Results: This report describes a 59-year-old male patient with persistent nasal congestion and suspected malignant nasopharyngeal neoplasm. Patients receive surgical resection and adjuvant radiotherapy after complete resection. Imaging studies showed no tissue invasion or lymph node metastases. The results of immunohistochemistry were Melan-A(+), HMB45(+), and S100(+). The final diagnosis was malignant nasopharyngeal melanoma. After 2 years of follow-up, the prognosis was good, and there was no metastasis or recurrence. Discussion: Nasopharyngeal melanoma is a rare malignancy with a poor prognosis, and surgical resection is the mainstay of treatment. Postoperative adjuvant therapy can improve the rate of local control of lesions. Early diagnosis and thorough examination are extremely important for the patient's prognosis.

14.
J Hum Genet ; 69(5): 197-203, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38374166

RESUMEN

CAPZA2 encodes the α2 subunit of CAPZA, which is vital for actin polymerization and depolymerization in humans. However, understanding of diseases associated with CAPZA2 remains limited. To date, only three cases have been documented with neurodevelopmental abnormalities such as delayed motor development, speech delay, intellectual disability, hypotonia, and a history of seizures. In this study, we document a patient who exhibited seizures, mild intellectual disability, and impaired motor development yet did not demonstrate speech delay or hypotonia. The patient also suffered from recurrent instances of respiratory infections, gastrointestinal and allergic diseases. A novel de novo splicing variant c.219+1 G > A was detected in the CAPZA2 gene through whole-exome sequencing. This variant led to exon 4 skipping in mRNA splicing, confirmed by RT-PCR and Sanger sequencing. To our knowledge, this is the third study on human CAPZA2 defects, documenting the fourth unambiguously diagnosed case. Furthermore, this splicing mutation type is reported here for the first time. Our research offers additional support for the existence of a CAPZA2-related non-syndromic neurodevelopmental disorder. Our findings augment our understanding of the phenotypic range associated with CAPZA2 deficiency and enrich the knowledge of the mutational spectrum of the CAPZA2 gene.


Asunto(s)
Proteína CapZ , Discapacidades del Desarrollo , Epilepsia , Heterocigoto , Hipotonía Muscular , Mutación , Preescolar , Femenino , Humanos , Masculino , Discapacidades del Desarrollo/genética , Discapacidades del Desarrollo/patología , Epilepsia/genética , Secuenciación del Exoma , Discapacidad Intelectual/genética , Discapacidad Intelectual/patología , Hipotonía Muscular/genética , Hipotonía Muscular/patología , Fenotipo , Empalme del ARN/genética , Proteína CapZ/genética
15.
J Asthma ; : 1-12, 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38349366

RESUMEN

OBJECTIVES: Airway remodeling, a prominent feature of asthma, involves aberrant proliferation, apoptosis, and migration of airway smooth muscle cells (ASMCs). Toll-like receptors (TLRs) are implicated in the regulation of the autophagy pathway. In this study, we aimed to investigate the influence of Toll-like receptor 4 (TLR4) on autophagy and its underlying mechanism in ASMC proliferation, apoptosis, and migration. METHODS: Histopathological changes in the lungs of asthmatic mice assessed by Hematoxylin-Eosin (HE) and Masson staining. Cell proliferation, apoptosis and migration were evaluated utilizing CCK8, Edu, Flow cytometry and wound heading assays. The effectiveness of siRNA transfection and the expression of TLR4, autophagy, and proliferation-related proteins after siRNA treatment were examined through RT-PCR and Western blot (WB). CONCLUSION: We observed an increase in TLR4 expression and autophagy in a mouse model of OVA-induced asthma. In vitro experiments showed that siRNA-mediated inhibition of TLR4 suppressed autophagy, proliferation, and migration of ASMCs, whereas TLR4 activation by lipopolysaccharide (LPS) had the opposite effect. Furthermore, the autophagy inhibitor 3-Methyladenine (3MA) inhibited ASMCs proliferation and migration while promoting apoptosis. Significantly, our study demonstrated that autophagy inhibition reversed the promotion effect of LPS on ASMC proliferation and migration. These findings suggest that TLR4 may modulate ASMC behavior through the regulation of autophagy.

16.
Aust J Gen Pract ; 53(1-2): 70-77, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38316485

RESUMEN

BACKGROUND AND OBJECTIVES: Colorectal cancer (CRC) survival in Australia differs by health insurance status, but why this occurs is uncertain. There are growing concerns about out-of-pocket healthcare costs. We examined patient experiences of referral pathways to diagnosis and treatment of CRC in Victoria, Australia, and discussions about costs, comparing public, private and mixed healthcare system users. METHOD: Semistructured telephone interviews were conducted with 16 purposively sampled, English-speaking patients aged ≥40 years with CRC. Interviews were recorded, transcribed and analysed thematically. RESULTS: Private patients described greater out-of-pocket expenses balanced by greater choice of provider and access. Public patients perceived limited choice in their diagnostic or treatment provider, although some considered switching systems. Patients trusted their general practitioner or specialist for referrals. Discussions about costs did not meet guideline recommendations. DISCUSSION: There are limited opportunities for informed decision making about public versus private care for cancer diagnosis and treatment, which could contribute to inequalities in outcomes.


Asunto(s)
Neoplasias Colorrectales , Atención a la Salud , Humanos , Victoria , Investigación Cualitativa , Derivación y Consulta , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/terapia
17.
J Asthma ; : 1-10, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38294683

RESUMEN

BACKGROUND: Asthma is a disease characterized by airway hyperresponsiveness and airway inflammation. Icaritin (ICT) is a plant hormone with various pharmacological activities such as anti-inflammatory, immune regulation, and anti-tumor. This study mainly explored the effects of nebulized inhalation of ICT on airway inflammation and airway remodeling in asthmatic mice. METHOD: Different groups of ovalbumin (OVA)-induced asthma mice with acute and chronic airway inflammation received ICT. Asthmatic mice received budesonide (BDND) aerosol inhalation as a positive control, while normal control and asthma model mice received the same volume of saline. Following finishing of the study, analyses were conducted on behavioral tests, biochemical indices, and histological structures of lung tissues. RESULTS: Aerosol inhalation of ICT can notably reduce inflammatory cells infiltration around the airways and pulmonary vessels, and suppressed goblet cell hyperplasia in asthmatic mice. Long-term inhalation of ICT can decrease airway collagen deposition and airway smooth muscle hyperplasia, and alleviate airway hyperresponsiveness, mirroring the effects observed with hormone employed in clinical practice. CONCLUSION: Nebulized inhalation of ICT can effectively inhibit airway inflammation in asthmatic mice, improve airway remodeling, and reduce airway hyperresponsiveness, with effects similar to those of hormones. It may serve as a potential candidate used as a hormone replacement asthma treatment.

18.
Clin Neurol Neurosurg ; 236: 108081, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38091701

RESUMEN

BACKGROUND: The prognostic role of lactate dehydrogenase (LDH) has been confirmed in many malignant tumors, but the role of serum LDH in primary central nervous system germ cell tumor (GCT) remains unknown. This study aimed to assess the prognostic value of LDH in GCT patients and develop a nomogram to predict prognosis in patients undergoing chemoradiotherapy. METHODS: A total of 161 patients with GCT were included in this study. Using a restricted cubic spline (RCS) model, the optimal cutoff point for LDH was determined to be 217 U/L. The survival of GCT patients was evaluated using the Kaplan-Meier method and log-rank test to analyze the effects of LDH levels. Univariate Cox regression, multivariate Cox regression, and LASSO Cox regression were conducted to identify prognostic factors, which were incorporated into a nomogram for predicting overall survival (OS). The predictive accuracy of the nomogram was assessed using the C-index, calibration curve, area under the time-dependent receiver operating characteristic curve (time-dependent AUC), and risk group stratification. The net benefits of the nomogram at different threshold probabilities were quantified using decision curve analysis (DCA). RESULTS: The high-LDH group had significantly shorter OS compared to the low-LDH group (P = 0.016). Based on the SYSUCC cohort, three variables were shown to be significant factors for OS and were incorporated in the nomogram: LDH, histopathology, and dissemination. It showed good discrimination ability, with C-index of 0.789 (95% CI, 0.671-0.907). Additionally, the clinical usefulness of the nomogram was confirmed by calibration curves and time-dependent AUC. DCA further highlighted the potential of the nomogram to guide clinical treatment strategies for patients. Moreover, there was a significant difference in OS among patients categorized into different risk groups (P < 0.001). CONCLUSION: LDH levels may serve as a reliable predictor for assessing the therapeutic effect of chemoradiotherapy in GCT. The developed nomogram exhibits high accuracy in predicting survival outcomes, aiding in the classification of prognostic groups, and supporting informed clinical decision-making.


Asunto(s)
Neoplasias del Sistema Nervioso Central , Neoplasias de Células Germinales y Embrionarias , Humanos , Pronóstico , Nomogramas , Neoplasias del Sistema Nervioso Central/terapia , Quimioradioterapia , L-Lactato Deshidrogenasa , Neoplasias de Células Germinales y Embrionarias/terapia , Factores de Riesgo , Sistema Nervioso Central
19.
Chinese Journal of Pathology ; (12): 46-51, 2024.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1012423

RESUMEN

Objective: To investigate the biological behavior spectrum of platelet-derived growth factor alpha receptor (PDGFRA)-mutant gastrointestinal stromal tumor (GIST), and to compare the clinical values of the Zhongshan method of benign and malignant evaluation with the modified National Institutes of Health (NIH) risk stratification. Methods: A total of 119 cases of GIST with PDGFRA mutation who underwent surgical resection at Zhongshan Hospital, Fudan University from 2009 to 2020 were collected. The clinicopathological data, follow-up records, and subsequent treatment were reviewed and analyzed statistically. Results: There were 79 males and 40 females. The patients ranged in age from 25 to 80 years, with a median age of 60 years. Among them, 115 patients were followed up for 1-154 months, and 13 patients progressed to disease. The 5-year disease-free survival (DFS) and overall survival (OS) were 90.1% and 94.1%, respectively. According to the modified NIH risk stratification, 8 cases, 32 cases, 38 cases, and 35 cases were very-low risk, low risk, intermediate risk, and high risk, and 5-year DFS were 100.0%, 95.6%, 94.3%, and 80.5%, respectively. There was no significant difference in prognosis among the non-high risk groups, only the difference between high risk and non-high risk groups was significant (P=0.029). However, the 5-year OS was 100.0%, 100.0%, 95.0% and 89.0%, and there was no difference (P=0.221). According to the benign and malignant evaluation Zhongshan method, 43 cases were non-malignant (37.4%), 56 cases were low-grade malignant (48.7%), 9 cases were moderately malignant (7.8%), and 7 cases were highly malignant (6.1%). The 5-year DFS were 100.0%, 91.7%, 77.8%, 38.1%, and the difference was significant (P<0.001). The 5-year OS were 100.0%, 97.5%, 77.8%, 66.7%, the difference was significant (P<0.001). Conclusions: GIST with PDGFRA gene mutation shows a broad range of biological behavior, ranging from benign to highly malignant. According to the Zhongshan method, non-malignant and low-grade malignant tumors are common, the prognosis after surgery is good, while the fewer medium-high malignant tumors showed poor prognosis after surgical resection. The overall biological behavior of this type of GIST is relatively inert, which is due to the low proportion of medium-high malignant GIST. The modified NIH risk stratification may not be effective in risk stratification for PDGFRA mutant GIST.


Asunto(s)
Masculino , Femenino , Humanos , Persona de Mediana Edad , Adulto , Anciano , Anciano de 80 o más Años , Tumores del Estroma Gastrointestinal/cirugía , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Estudios Retrospectivos , Mutación , Pronóstico , Proteínas Proto-Oncogénicas c-kit/genética
20.
Cell Mol Gastroenterol Hepatol ; 17(4): 539-551, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38122985

RESUMEN

BACKGROUND & AIMS: Apolipoprotein A-1 (ApoA-1), the main apolipoprotein of high-density lipoprotein, has been well studied in the area of lipid metabolism and cardiovascular diseases. In this project, we clarify the function and mechanism of ApoA-1 in liver regeneration. METHODS: Seventy percent of partial hepatectomy was applied in male ApoA-1 knockout mice and wild-type mice to investigate the effects of ApoA-1 on liver regeneration. D-4F (ApoA-1 mimetic peptide), autophagy activator, and AMPK activator were used to explore the mechanism of ApoA-1 on liver regeneration. RESULTS: We demonstrated that ApoA-1 levels were highly expressed during the early stage of liver regeneration. ApoA-1 deficiency greatly impaired liver regeneration after hepatectomy. Meanwhile, we found that ApoA-1 deficiency inhibited autophagy during liver regeneration. The activation of autophagy protected against ApoA-1 deficiency in inhibiting liver regeneration. Furthermore, ApoA-1 deficiency impaired autophagy through AMPK-ULK1 pathway, and AMPK activation significantly improved liver regeneration. The administration of D-4F could accelerated liver regeneration after hepatectomy. CONCLUSIONS: These findings suggested that ApoA-1 played an essential role in liver regeneration through promoting autophagy in hepatocytes via AMPK-ULK1 pathway. Our findings enrich the understanding of the underlying mechanism of liver regeneration and provide a potential therapeutic strategy for liver injury.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Apolipoproteína A-I , Animales , Masculino , Ratones , Proteínas Quinasas Activadas por AMP/metabolismo , Apolipoproteína A-I/metabolismo , Apolipoproteína A-I/farmacología , Autofagia , Hígado/metabolismo , Regeneración Hepática
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