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1.
J Ginseng Res ; 48(3): 266-275, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38707642

RESUMO

Cancer stem cells (CSCs) are a rare subpopulation of cancer cells that exhibit stem cell-like characteristics, including self-renewal and differentiation in a multi-stage lineage state via symmetric or asymmetric division, causing tumor initiation, heterogeneity, progression, and recurrence and posing a major challenge to current anticancer therapy. Despite the importance of CSCs in carcinogenesis and cancer progression, currently available anticancer therapeutics have limitations for eradicating CSCs. Moreover, the efficacy and therapeutic windows of currently available anti-CSC agents are limited, suggesting the necessity to optimize and develop a novel anticancer agent targeting CSCs. Ginseng has been traditionally used for enhancing immunity and relieving fatigue. As ginseng's long history of use has demonstrated its safety, it has gained attention for its potential pharmacological properties, including anticancer effects. Several studies have identified the bioactive principles of ginseng, such as ginseng saponin (ginsenosides) and non-saponin compounds (e.g., polysaccharides, polyacetylenes, and phenolic compounds), and their pharmacological activities, including antioxidant, anticancer, antidiabetic, antifatigue, and neuroprotective effects. Notably, recent reports have shown the potential of ginseng-derived compounds as anti-CSC agents. This review investigates the biology of CSCs and efforts to utilize ginseng-derived components for cancer treatment targeting CSCs, highlighting their role in overcoming current therapeutic limitations.

2.
RSC Med Chem ; 15(3): 1066-1071, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38516600

RESUMO

We have developed a novel chemical handle (PFI-E3H1) and a chemical probe (PFI-7) as ligands for the Gid4 subunit of the human E3 ligase CTLH degradation complex. Through an efficient initial hit-ID campaign, structure-based drug design (SBDD) and leveraging the sizeable Pfizer compound library, we identified a 500 nM ligand for this E3 ligase through file screening alone. Further exploration identified a vector that is tolerant to addition of a linker for future chimeric molecule design. The chemotype was subsequently optimized to sub-100 nM Gid4 binding affinity for a chemical probe. These novel tools, alongside the suitable negative control also identified, should enable the interrogation of this complex human E3 ligase macromolecular assembly.

3.
World J Clin Cases ; 12(5): 931-941, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38414613

RESUMO

BACKGROUND: There are limited data on the use of glucose transport protein 1 (GLUT-1) expression as a biomarker for predicting lymph node metastasis in patients with colorectal cancer. GLUT-1 and GLUT-3, hexokinase (HK)-II, and hypoxia-induced factor (HIF)-1 expressions may be useful biomarkers for detecting primary tumors and lymph node metastasis when combined with fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT). AIM: To evaluate GLUT-1, GLUT-3, HK-II, and HIF-1 expressions as biomarkers for detecting primary tumors and lymph node metastasis with 18F-FDG-PET/CT. METHODS: This retrospective study included 169 patients with colorectal cancer who underwent colectomy and preoperative 18F-FDG-PET/CT at Chungbuk National University Hospital between January 2009 and May 2012. Two tissue cores from the central and peripheral areas of the tumors were obtained and were examined by a dedicated pathologist, and the expressions of GLUT-1, GLUT-3, HK-II, and HIF-1 were determined using immunohistochemical staining. We analyzed the correlations among their expressions, various clinicopathological factors, and the maximum standardized uptake value (SUVmax) of PET/CT. RESULTS: GLUT-1 was found at the center or periphery of the tumors in 109 (64.5%) of the 169 patients. GLUT-1 positivity was significantly correlated with the SUVmax of the primary tumor and lymph nodes, regardless of the biopsy site (tumor center, P < 0.001 and P = 0.012; tumor periphery, P = 0.030 and P = 0.010, respectively). GLUT-1 positivity and negativity were associated with higher and lower sensitivities of PET/CT, respectively, for the detection of lymph node metastasis, regardless of the biopsy site. GLUT3, HK-II, and HIF-1 expressions were not significantly correlated with the SUVmax of the primary tumor and lymph nodes. CONCLUSION: GLUT-1 expression was significantly correlated with the SUVmax of 18F-FDG-PET/CT for primary tumors and lymph nodes. Clinicians should consider GLUT-1 expression in preoperative endoscopic biopsy in interpreting PET/CT findings.

4.
World J Clin Cases ; 12(2): 374-382, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38313636

RESUMO

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a non-Hodgkin lymphoma that originates in the central nervous system (CNS) and is exclusively limited to the CNS. Although most PCNSLs are diffuse large B-cell lymphomas, primary CNS T-cell lymphomas (PCNSTLs) are rare. PCNSTLs typically demonstrate some degree of enhancement on contrast-enhanced magnetic resonance imaging (MRI). To the best of our knowledge, non-enhancing PCNSTL has not been reported previously. CASE SUMMARY: A 69-year-old male presented to the neurology department with complaints of mild cognitive impairment and gradual onset of left lower leg weakness over a span of two weeks. Initial MRI showed asymmetric T2-hyperintense lesions within the brain. No enhancement was observed on the contrast-enhanced T1 image. The initial diagnosis was neuro-Behçet's disease. Despite high-dose steroid therapy, no alterations in the lesions were identified on initial MRI. The patient's symptoms deteriorated further. An MRI performed one month after the initial scan revealed an increased lesion extent. Subsequently, brain biopsy confirmed the diagnosis of PCNSTL. The patient underwent definitive combined chemo-radiotherapy. However, the patient developed bacteremia and died of septic shock approximately three months after diagnosis. CONCLUSION: The absence of enhancement in the lesion did not rule out PCNSTL. A biopsy approach is advisable for pathological confirmation.

5.
Plants (Basel) ; 13(3)2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38337979

RESUMO

In today's time, agricultural productivity is severely affected by climate change and increasing pollution. Hence, several biotechnological approaches, including genetic and non-genetic strategies, have been developed and adapted to increase agricultural productivity. One of them is nano-priming, i.e., seed priming with nanomaterials. Thus far, nano-priming methods have been successfully used to mount desired physiological responses and productivity attributes in crops. In this review, the literature about the utility of nano-priming methods for increasing seed vigor, germination, photosynthetic output, biomass, early growth, and crop yield has been summarized. Moreover, the available knowledge about the use of nano-priming methods in modulating plant antioxidant defenses and hormonal networks, inducing salinity tolerance and disease resistance, as well as alleviating heavy metal toxicity in plants, is reviewed. The significance of nano-priming methods in the context of phytotoxicity and environmental safety has also been discussed. For future perspectives, knowledge gaps in the present literature are highlighted, and the need for optimization and validation of nano-priming methods and their plant physiological outcomes, from lab to field, is emphasized.

6.
Chem Sci ; 15(5): 1752-1757, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38303957

RESUMO

We present a metal-free strategy to access fluoroalkyl-olefin linkages from fluoroalkane precursors and vinyl-pinacol boronic ester (BPin) reagents. This reaction sequence is templated by the boron reagent, which induces C-C bond formation upon oxidation. We developed this strategy into a one-pot synthetic protocol using RCF2H precursors directly with vinyl-BPin reagents in the presence of a Brønsted base, which tolerated oxygen- and nitrogen-containing heterocycles, and aryl halogens. We also found that HCF3 (HCF-23; a byproduct of the Teflon industry) and CH2F2 (HCF-32; a low-cost refrigerant) are amenable to this protocol, representing distinct strategies to generate RCF2H and RCF3 molecules. Finally, we demonstrate that the vinyldifluoromethylene products can be readily derivatized, representing an avenue for late-stage modification after installing the fluoroalkyl unit.

7.
HERD ; : 19375867241226601, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38305232

RESUMO

OBJECTIVES: We empirically investigated to what extent plants in the emergency department (ED) waiting areas influence patient wait experiences (i.e., anxiety, perceived service quality, and perception of wait time) depending on individual differences in cognitive thinking styles and one's bonds with the natural world. BACKGROUND: Positive effects of nature on patient experiences in healthcare environments are well established by empirical research findings. However, evidence is scarce on the impact of nature on patient wait experiences and the roles of patient traits often related to their backgrounds. METHODS: A within-subjects study was conducted (N = 116) with two virtually built ED waiting rooms: with versus without indoor and outdoor plants. RESULTS: Findings confirmed that plants lower anxiety and improve perceptions of service quality and wait time. Cognitive thinking style significantly moderated how plants affected patient wait experiences. Although participants with higher connectedness to nature showed more positive responses to the nature condition, connectedness to nature did not significantly affect the association between nature and wait experiences. CONCLUSIONS: This study contributes to the existing body of knowledge on nature's effects in healthcare environments by examining the roles of individual differences in patients' and visitors' cognitive styles and connectedness to nature. Results highlighted the impact of these differences in patient experiences for effective implications of nature in waiting areas of healthcare facilities.

8.
Clin Nutr Res ; 13(1): 1-7, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38362128

RESUMO

Nutritional support in critically ill patients is an essential aspect of treatment. In particular, the benefits of enteral nutrition (EN) are well recognized, and various guidelines recommend early EN within 48 hours in critically ill patients. However, there is still controversy regarding EN in critically ill patients with septic shock requiring vasopressors. Therefore, this case report aims to provide basic data for the safe and effective nutritional support in septic shock patients who require vasopressors. A 62-year-old male patient was admitted to the intensive care unit with a deep neck infection and mediastinitis that progressed to a septic condition. Mechanical ventilation was initiated after intubation due to progression of respiratory acidosis and deterioration of mental status, and severe hypotension required the initiation of norepinephrine. Due to hemodynamic instability, the patient was kept nil per os. Subsequently, trophic feeding was initiated at the time of norepinephrine dose tapering and was gradually increased to achieve 75% of the energy requirement through EN by the 7th day of enteral feeding initiation. Although there were signs of feeding intolerance during the increasing phase of EN, adjusting the rate of EN resolved the issue. This case report demonstrates the gradual progression and adherence to EN in septic shock patient requiring vasopressors, and the progression observed was relatively consistent with existing studies and guidelines. In the future, further case reports and continuous research will be deemed necessary for safe and effective nutritional support in critically ill patients with septic shock requiring vasopressors.

9.
NPJ Vaccines ; 9(1): 34, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360752

RESUMO

The implications of administration of mRNA vaccines to individuals with chronic inflammatory diseases, including myocarditis, rheumatoid arthritis (RA), and inflammatory bowel disease (IBD), are unclear. We investigated mRNA vaccine effects in a chronic inflammation mouse model implanted with an LPS pump, focusing on toxicity and immunogenicity. Under chronic inflammation, mRNA vaccines exacerbated cardiac damage and myocarditis, inducing mild heart inflammation with heightened pro-inflammatory cytokine production and inflammatory cell infiltration in the heart. Concurrently, significant muscle damage occurred, with disturbances in mitochondrial fusion and fission factors signaling impaired muscle repair. However, chronic inflammation did not adversely affect muscles at the vaccination site or humoral immune responses; nevertheless, it partially reduced the cell-mediated immune response, particularly T-cell activation. These findings underscore the importance of addressing mRNA vaccine toxicity and immunogenicity in the context of chronic inflammation, ensuring their safe and effective utilization, particularly among vulnerable populations with immune-mediated inflammatory diseases.

10.
Diagn Pathol ; 19(1): 16, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38243242

RESUMO

BACKGROUND: Epithelioid angiomyolipoma (EAML) is a rare variant of angiomyolipoma that predominantly consists of epithelioid cells and belongs to the perivascular epithelioid cell neoplasm (PEComa) family. The majority of EAMLs arise in the kidneys, and primary hepatic EAML appears to be much less common than renal EAML. Most PEComas arise sporadically, but may be associated with tuberous sclerosis complex (TSC), an autosomal dominant genetic disorder characterized by germline mutations in the TSC1 or TSC2 genes. However, PEComas have previously been reported in five patients with Li-Fraumeni syndrome (LFS), which is an inherited cancer susceptibility disorder resulting from germline mutations in the TP53 tumor suppressor gene. CASE PRESENTATION: We report a 49-year-old female patient with hepatic EAML and pancreatic cancer. Because she had previously been diagnosed with bilateral breast cancer at the age of 30, we performed a comprehensive genetic analysis to identify genetic alterations associated with any cancer predisposition syndrome. Whole-exome sequencing of a blood sample identified a heterozygous germline variant of TP53 (NM_000546.5):c.708C>A, and targeted next-generation sequencing of liver EAML and pancreatic cancer tissue samples demonstrated the same TP53 (NM_000546.5):c.708C>A variant in both. This, plus the patient's history of early-onset breast cancer, met the 2015 version of the Chompret criteria for diagnosis of LFS. CONCLUSIONS: There have been very few case reports regarding the presence of PEComa in LFS, and to the best of our knowledge, this is the first report of EAML of the liver in a patient with LFS.


Assuntos
Angiomiolipoma , Neoplasias da Mama , Neoplasias Renais , Síndrome de Li-Fraumeni , Neoplasias Hepáticas , Neoplasias Pancreáticas , Feminino , Humanos , Pessoa de Meia-Idade , Síndrome de Li-Fraumeni/complicações , Síndrome de Li-Fraumeni/diagnóstico , Síndrome de Li-Fraumeni/genética , Angiomiolipoma/diagnóstico , Angiomiolipoma/genética , Angiomiolipoma/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Renais/patologia , Predisposição Genética para Doença
11.
Medicine (Baltimore) ; 103(2): e36945, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38215099

RESUMO

RATIONALE: Myofibromas are rare benign spindle cell tumors of the soft tissue, bone, or internal organs that occur at any age. Here, we report a post-surgical thyroid bed myofibroma that mimicked a papillary thyroid carcinoma. PATIENT CONCERNS: A 56-year-old male presented with a mass in the thyroid surgical bed, detected 3 years post thyroidectomy following papillary carcinoma. DIAGNOSIS: Thyroid ultrasonography revealed a well-defined, lobulated, hypoechoic, solid nodule, with large rod-like echogenic foci in the thyroid surgical bed. The development of a postoperative suture granuloma was considered. However, ultrasonography performed 12 months later showed a marked increase in the lesion size. Two fine needle aspiration cytology yielded nondiagnostic results. INTERVENTION: Considering the possibility of local tumor recurrence, surgical resection was performed. OUTCOME: The diagnosis of a myofibroma was confirmed, and no additional treatment was administered. LESSONS: It is challenging to differentiate lesions occurring on the thyroid surgical bed after surgery, from recurrent thyroid cancer. A lesion measuring 6 mm, with a degree of punctate echogenicity, suggests tumor recurrence. Moreover, myofibromas are extremely rare. This case highlights that it is advisable to perform a core needle biopsy in cases of nondiagnostic fine needle aspiration results.


Assuntos
Leiomioma , Miofibroma , Neoplasias da Glândula Tireoide , Masculino , Humanos , Pessoa de Meia-Idade , Câncer Papilífero da Tireoide/diagnóstico , Câncer Papilífero da Tireoide/cirurgia , Miofibroma/cirurgia , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/patologia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia/métodos , Leiomioma/cirurgia
12.
Cancer Imaging ; 24(1): 6, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191489

RESUMO

OBJECTIVES: To use clinical, radiographic, and CT radiomics features to develop and validate a preoperative prediction model for the early recurrence of pancreatic cancer. METHODS: We retrospectively analyzed 190 patients (150 and 40 in the development and test cohort from different centers) with pancreatic cancer who underwent pancreatectomy between January 2018 and June 2021. Radiomics, clinical-radiologic (CR), and clinical-radiologic-radiomics (CRR) models were developed for the prediction of recurrence within 12 months after surgery. Performance was evaluated using the area under the curve (AUC), Brier score, sensitivity, and specificity. RESULTS: Early recurrence occurred in 36.7% and 42.5% of the development and test cohorts, respectively (P = 0.62). The features for the CR model included carbohydrate antigen 19-9 > 500 U/mL (odds ratio [OR], 3.60; P = 0.01), abutment to the portal and/or superior mesenteric vein (OR, 2.54; P = 0.054), and adjacent organ invasion (OR, 2.91; P = 0.03). The CRR model demonstrated significantly higher AUCs than the radiomics model in the internal (0.77 vs. 0.73; P = 0.048) and external (0.83 vs. 0.69; P = 0.038) validations. Although we found no significant difference between AUCs of the CR and CRR models (0.83 vs. 0.76; P = 0.17), CRR models showed more balanced sensitivity and specificity (0.65 and 0.87) than CR model (0.41 and 0.91) in the test cohort. CONCLUSIONS: The CRR model outperformed the radiomics and CR models in predicting the early recurrence of pancreatic cancer, providing valuable information for risk stratification and treatment guidance.


Assuntos
Neoplasias Pancreáticas , Radiômica , Humanos , Estudos Retrospectivos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Área Sob a Curva , Tomografia Computadorizada por Raios X
13.
Ecotoxicol Environ Saf ; 269: 115798, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38086261

RESUMO

Di(2-ethylhexy) phthalate (DEHP) is a widely used plasticizer that is ubiquitously found in the environment. Using a mouse model, we investigated the impact of early life DEHP exposure ranging from the prenatal to peripubertal developmental period of the female reproductive system. Pregnant female mice were allocated to three groups as follows: control, 100 mg/kg/day, and 500 mg/kg/day DEHP treatment. DEHP exposure was introduced through feeding during pregnancy (3 weeks) and lactation (3 weeks). After weaning, the offspring were also exposed to DEHP through feeding for another 2 weeks. Observations were conducted on female offspring at 10 and 24 weeks. The number of live offspring per dam was significantly lower in the high-DEHP-exposed group (500 mg/kg/day) compared to the control group (7.67 ± 1.24 vs. 14.17 ± 0.31; p < 0.05) despite no difference in pregnancy rates across the groups. Low-DEHP exposure (100 mg/kg/day) resulted to a decreased body weight (36.07 ± 3.78 vs. 50.11 ± 2.11 g; p < 0.05) and decreased left uterine length (10.60 ± 1.34 vs. 14.77 ± 0.82 mm; p < 0.05) in 24-week- old female mice. As early as 10 weeks, endometrial atrophy and fibrosis were observed, and endometrial cystic hyperplasia was noted in female mice at 24 weeks. Our study is the first to demonstrate that female mice exposed to DEHP in the early life developed endometrial fibrosis in the female offspring. Further studies on the consequences of these observations in fecundity and other reproductive functions are warranted.


Assuntos
Dietilexilftalato , Ácidos Ftálicos , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Humanos , Feminino , Dietilexilftalato/toxicidade , Fibrose
14.
J Med Virol ; 95(12): e29309, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38100632

RESUMO

The E6 and E7 proteins of specific subtypes of human papillomavirus (HPV), including HPV 16 and 18, are highly associated with cervical cancer as they modulate cell cycle regulation. The aim of this study was to investigate the potential antitumor effects of a messenger RNA-HPV therapeutic vaccine (mHTV) containing nononcogenic E6 and E7 proteins. To achieve this, C57BL/6j mice were injected with the vaccine via both intramuscular and subcutaneous routes, and the resulting effects were evaluated. mHTV immunization markedly induced robust T cell-mediated immune responses and significantly suppressed tumor growth in both subcutaneous and orthotopic tumor-implanted mouse model, with a significant infiltration of immune cells into tumor tissues. Tumor retransplantation at day 62 postprimary vaccination completely halted progression in all mHTV-treated mice. Furthermore, tumor expansion was significantly reduced upon TC-1 transplantation 160 days after the last immunization. Immunization of rhesus monkeys with mHTV elicited promising immune responses. The immunogenicity of mHTV in nonhuman primates provides strong evidence for clinical application against HPV-related cancers in humans. All data suggest that mHTV can be used as both a therapeutic and prophylactic vaccine.


Assuntos
Proteínas Oncogênicas Virais , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Animais , Camundongos , Papillomavirus Humano , Proteínas Oncogênicas Virais/genética , Infecções por Papillomavirus/prevenção & controle , RNA Mensageiro/genética , Proteínas E7 de Papillomavirus/genética , Camundongos Endogâmicos C57BL , Vacinação/métodos , Imunização , Neoplasias do Colo do Útero/prevenção & controle
15.
Carbohydr Res ; 534: 108980, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37952447

RESUMO

The polysaccharide fraction PNE-P1 was isolated from hot water extract (PNE) of the defatted meal of pine nuts (Pinus koraiensis) using DEAE-cellulose column chromatography. This fraction had three components of molecular masses 1251, 616, and 303 g/mol consisting mainly of arabinose, xylose, and galacturonic acid at a molar ratio of 2:1.6:1. Structural analysis with FTIR/Raman, methylation and GC-MS, and NMR revealed that PNE-P1 is a cell wall polysaccharide complex including arabinan, heteroxylan, homogalacturonan (HM) and rhamnogalacturonan I (RG-I) parts. Being nontoxic to RAW 264.7 macrophages in the concentration range of 10-200 µg/mL, PNE-P1 promoted proliferation of these cells, significantly induced the secretion of proinflammatory cytokines (TNF-α and IL-6) and chemokines (RANTES and MIP-1α) and enhanced the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and nitric oxide (NO). PNE-P1 also markedly induced macrophage-mediated phagocytosis of apoptotic Jurkat T cells. These results demonstrate that pine nuts Pinus koraiensis contain a complex of water-soluble plant cell wall polysaccharides, which can stimulate innate immunity by potentiating macrophage function.


Assuntos
Nozes , Pinus , Nozes/química , Pinus/química , Polissacarídeos/química , Cromatografia Gasosa-Espectrometria de Massas , Xilose
17.
J Phys Chem Lett ; 14(39): 8837-8845, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37751387

RESUMO

CsPbBr3 perovskite nanocrystals (CNCs) were densely anchored on multiwalled carbon nanotubes (MWNTs) via a nanoseeding intermediate stage, in which lead-based nuclei are formed on the nanotube surface. After the formation of the intermediate, a cesium precursor was added to promote the growth of CNCs from the surface nuclei and to thereby obtain CNC-decorated MWNT nanohybrids (CMNHs). The morphology and properties of the CMNHs were determined by the reaction temperature employed during their synthesis. Importantly, the use of MWNTs promoted the formation of larger CNCs that emitted intense green light and modified the electronic structure and bandgap energy of the CNCs. Consequently, the CMNHs could function as optoelectronic transducers and exhibit a "turn-on" photocurrent response when exposed to UV light of narrow specific-range wavelengths. In a novel approach for preventing counterfeit products, the CMNHs were used as a light-emitting black ink to create quick-response codes with fake pixels.

18.
Free Radic Biol Med ; 208: 820-832, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37776917

RESUMO

SQSTM1/p62 (sequestosome 1) is a multifunctional protein that serves as a receptor for selective autophagy and scaffold. In selective autophagy, p62 functions as a bridge between polyubiquitinated proteins and autophagosomes. Further, p62 acts as a signaling hub for many cellular pathways including mTORC1, NF-κB, and Keap1-Nrf2. Post-translational modifications of p62, such as ubiquitination and phosphorylation, are known to determine its binding partners and regulate their intracellular functions. However, the mechanism of p62 deubiquitination remains unclear. In this study, we found that ubiquitin-specific protease 13 (USP13), a member of the USP family, directly binds p62 and removes ubiquitin at Lys7 (K7) of the PB1 domain. USP13-mediated p62 deubiquitination enhances p62 protein stability and facilitates p62 oligomerization, resulting in increased autophagy and degradation of Keap1, which is a negative regulator of the antioxidant response that promotes Nrf2 activation. Thus, USP13 can be considered a therapeutic target as a deubiquitination enzyme of p62 in autophagy-related diseases.


Assuntos
Antioxidantes , Autofagia , Fator 2 Relacionado a NF-E2 , Proteína Sequestossoma-1 , Proteases Específicas de Ubiquitina , Humanos , Antioxidantes/farmacologia , Autofagia/genética , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Proteína Sequestossoma-1/genética , Proteína Sequestossoma-1/metabolismo , Proteases Específicas de Ubiquitina/metabolismo
19.
J Int Med Res ; 51(8): 3000605231194902, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37632411

RESUMO

Malignant transformation of a heterotopic pancreas in the duodenum is very rare. To our knowledge, only 15 cases have been reported worldwide, including the present case. We herein report a rare case of malignant transformation of a heterotopic pancreas in the duodenum along with a review of the literature.A 65-year-old man was admitted to our hospital for evaluation of dyspepsia and vomiting. Esophagogastroduodenoscopy showed a stricture of the duodenal bulb. Laparoscopic distal gastrectomy was performed. Although a duodenal tumor had not been suspected, histopathological examination of the surgical specimen showed adenocarcinoma arising from a heterotopic pancreas (Heinrich type III) in the duodenum. Four months postoperatively, the patient received adjuvant chemotherapy. He was still alive without recurrence at 24 months of follow-up.Adenocarcinoma arising in a heterotopic pancreas is rare; therefore, preoperative diagnosis is difficult to obtain. Effective management of a heterotopic pancreas depends on the presence or absence of symptoms. Awareness of the possibility of malignant change in a heterotopic pancreas of the duodenum prior to surgery is helpful for the diagnosis and appropriate management of such patients.


Assuntos
Adenocarcinoma , Duodeno , Masculino , Humanos , Idoso , Duodeno/cirurgia , Adenocarcinoma/cirurgia , Quimioterapia Adjuvante , Constrição Patológica , Pâncreas/diagnóstico por imagem , Pâncreas/cirurgia
20.
J Microbiol Biotechnol ; 33(12): 1576-1586, 2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-37644733

RESUMO

Vaccination is the most effective method for preventing the spread of the influenza virus. Cell-based influenza vaccines have been developed to overcome the disadvantages of egg-based vaccines and their production efficiency has been previously discussed. In this study, we investigated whether treatment with forskolin (FSK), an adenylyl cyclase activator, affected the output of a cell-based influenza vaccine. We found that FSK increased the propagation of three influenza virus subtypes (A/H1N1/California/4/09, A/H3N2/Mississippi/1/85, and B/Shandong/7/97) in Madin-Darby canine kidney (MDCK) cells. Interestingly, FSK suppressed the growth of MDCK cells. This effect could be a result of protein kinase A (PKA)-Src axis activation, which downregulates extracellular signal-regulated kinase (ERK)1/2 activity and delays cell cycle progression from G1 to S. This delay in cell growth might benefit the binding and entry of the influenza virus in the early stages of viral replication. In contrast, FSK dramatically upregulated ERK1/2 activity via the cAMP-PKA-Raf-1 axis at a late stage of viral replication. Thus, increased ERK1/2 activity might contribute to increased viral ribonucleoprotein export and influenza virus propagation. The increase in viral titer induced by FSK could be explained by the action of cAMP in assisting the entry and binding of the influenza virus. Therefore, FSK addition to cell culture systems could help increase the production efficiency of cell-based vaccines against the influenza virus.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Animais , Cães , Humanos , Células Madin Darby de Rim Canino , Adenilil Ciclases , Colforsina/farmacologia , Vírus da Influenza A Subtipo H3N2 , Sistema de Sinalização das MAP Quinases , Influenza Humana/prevenção & controle
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