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1.
Nat Commun ; 15(1): 3971, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38729931

RESUMO

The Berry curvature dipole (BCD) serves as a one of the fundamental contributors to emergence of the nonlinear Hall effect (NLHE). Despite intense interest due to its potential for new technologies reaching beyond the quantum efficiency limit, the interplay between BCD and NLHE has been barely understood yet in the absence of a systematic study on the electronic band structure. Here, we report NLHE realized in NbIrTe4 that persists above room temperature coupled with a sign change in the Hall conductivity at 150 K. First-principles calculations combined with angle-resolved photoemission spectroscopy (ARPES) measurements show that BCD tuned by the partial occupancy of spin-orbit split bands via temperature is responsible for the temperature-dependent NLHE. Our findings highlight the correlation between BCD and the electronic band structure, providing a viable route to create and engineer the non-trivial Hall effect by tuning the geometric properties of quasiparticles in transition-metal chalcogen compounds.

2.
Ann Coloproctol ; 40(2): 89-113, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38712437

RESUMO

Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents.. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients' values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.

3.
Front Endocrinol (Lausanne) ; 15: 1352552, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38699383

RESUMO

Congenital adrenal hyperplasia (CAH) and Williams Syndrome (WS; MIM # 194050) are distinct genetic conditions characterized by unique clinical features. 21-Hydroxylase deficiency (21-OHD; MIM #201910), the most common form of CAH, arises from mutations in the CYP21A2 gene, resulting in virilization of the external genitalia in affected females, early puberty in males, and short stature. Williams syndrome, caused by a microdeletion of 7q11.23, presents with distinctive facial features, intellectual disability, unique personality traits, early puberty, and short stature. This case report describe the clinical features of a 4-year-old girl referred due to progressive virilization and developmental delay. Genetic analysis confirmed concurrent CAH and WS, identifying a novel mutation in the CYP21A2 gene (c.1442T>C). Following corticosteroid therapy initiation, the patient developed central precocious puberty. This case report delves into the pubertal change patterns in a patient affected by overlapping genetic conditions, providing valuable insights in to the intricate clinical manifestation and management of these rare complex disorders.


Assuntos
Hiperplasia Suprarrenal Congênita , Puberdade Precoce , Virilismo , Síndrome de Williams , Humanos , Feminino , Hiperplasia Suprarrenal Congênita/complicações , Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/genética , Puberdade Precoce/diagnóstico , Puberdade Precoce/genética , Puberdade Precoce/etiologia , Síndrome de Williams/complicações , Síndrome de Williams/genética , Síndrome de Williams/diagnóstico , Pré-Escolar , Virilismo/genética , Virilismo/diagnóstico , Esteroide 21-Hidroxilase/genética , Mutação
4.
Jpn J Ophthalmol ; 68(3): 216-224, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38598145

RESUMO

PURPOSE: We introduce selective internal limiting membrane (ILM) peeling, a guideline procedure to determine whether to remove the ILM during vitrectomy for rhegmatogenous retinal detachment (RRD). STUDY DESIGN: Retrospective case series METHODS: Patients who underwent pars plana vitrectomy for RRD and were followed up for 12 months or longer were included. When vitreous cortex remnants (VCRs) were detected with triamcinolone acetonide, the ILM was removed; otherwise, the ILM was preserved ("selective ILM peeling"). The factors associated with the presence of VCRs and incidence of secondary epiretinal membrane (ERM) were analyzed. RESULTS: VCRs were detected in 87 of 133 eyes (65.4%) in which the ILM was removed. Younger age, better preoperative visual acuity, and vitreous hemorrhage were negatively correlated with the presence of VCRs. No ERM occurred in the eyes after ILM peeling. Among the eyes with ILM preservation, subclinical ERM was noticed in 4 eyes (8.7%), and 1 eye (2.1%) required additional surgery owing to ERM. ERM occurred more commonly in eyes with the ILM preserved (P = .004). However, no differences in the rate of additional surgeries were found between the 2 groups. CONCLUSION: Selective ILM peeling offers an alternative option to reduce the burden of ILM peeling or additional surgery.


Assuntos
Membrana Basal , Membrana Epirretiniana , Descolamento Retiniano , Tomografia de Coerência Óptica , Acuidade Visual , Vitrectomia , Humanos , Vitrectomia/métodos , Estudos Retrospectivos , Descolamento Retiniano/cirurgia , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/prevenção & controle , Descolamento Retiniano/etiologia , Membrana Epirretiniana/cirurgia , Membrana Epirretiniana/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Membrana Basal/cirurgia , Idoso , Seguimentos , Complicações Pós-Operatórias/prevenção & controle , Adulto , Idoso de 80 Anos ou mais
5.
Sci Rep ; 14(1): 8680, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622321

RESUMO

We evaluated chemokine expression and its correlation with disease activity in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) (MPA/GPA). Serum CCL2, CCL4, CCL19, CXCL1, CXCL2, and CX3CL1 level in 80 patients were analysed using multiple enzyme-linked immunosorbent assays. Correlations between variables were investigated using Pearson's correlation analysis, and receiver operator curve analysis was performed to identify optimal CX3CL1 values in determining active disease. Multivariate logistic regression analysis was done to evaluate predictors of active disease. CCL4 (r = 0.251, p = 0.025), CXCL1 (r = 0.270, p = 0.015), and CX3CL1 (r = 0.295, p = 0.008) significantly correlated with BVAS, while CX3CL1 was associated with five-factor score (r = - 0.290, p = 0.009). Correlations were revealed between CCL2 and CCL4 (r = 0.267, p = 0.017), CCL4 and CXCL1 (r = 0.368, p < 0.001), CCL4 and CXCL2 (r = 0.436, p < 0.001), and CXCL1 and CXCL2 (r = 0.518, p < 0.001). Multivariate analysis revealed serum CX3CL1 levels > 2408.92 pg/mL could predict active disease (odds ratio, 27.401, p < 0.001). Serum chemokine levels of CCL4, CXCL1, and CX3CL1 showed association with disease activity and especially, CX3CL1 > 2408.92 pg/mL showed potential in predicting active MPA/GPA.


Assuntos
Granulomatose com Poliangiite , Poliangiite Microscópica , Humanos , Análise Multivariada , Anticorpos Anticitoplasma de Neutrófilos
6.
Nano Converg ; 11(1): 14, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622355

RESUMO

Tunability of interfacial effects between two-dimensional (2D) crystals is crucial not only for understanding the intrinsic properties of each system, but also for designing electronic devices based on ultra-thin heterostructures. A prerequisite of such heterostructure engineering is the availability of 2D crystals with different degrees of interfacial interactions. In this work, we report a controlled epitaxial growth of monolayer TaSe2 with different structural phases, 1H and 1 T, on a bilayer graphene (BLG) substrate using molecular beam epitaxy, and its impact on the electronic properties of the heterostructures using angle-resolved photoemission spectroscopy. 1H-TaSe2 exhibits significant charge transfer and band hybridization at the interface, whereas 1 T-TaSe2 shows weak interactions with the substrate. The distinct interfacial interactions are attributed to the dual effects from the differences of the work functions as well as the relative interlayer distance between TaSe2 films and BLG substrate. The method demonstrated here provides a viable route towards interface engineering in a variety of transition-metal dichalcogenides that can be applied to future nano-devices with designed electronic properties.

8.
PLoS One ; 19(4): e0298870, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38564629

RESUMO

Physical fitness (PF) includes various factors that significantly impacts athletic performance. Analyzing PF is critical in developing customized training methods for athletes based on the sports in which they compete. Previous approaches to analyzing PF have relied on statistical or machine learning algorithms that focus on predicting athlete injury or performance. In this study, six machine learning algorithms were used to analyze the PF of 1,489 male adolescent athletes across five sports, including track & field, football, baseball, swimming, and badminton. Furthermore, the machine learning models were utilized to analyze the essential elements of PF using feature importance of XGBoost, and SHAP values. As a result, XGBoost represents the highest performance, with an average accuracy of 90.14, an area under the curve of 0.86, and F1-score of 0.87, demonstrating the similarity between the sports. Feature importance of XGBoost, and SHAP value provided a quantitative assessment of the relative importance of PF in sports by comparing two sports within each of the five sports. This analysis is expected to be useful in analyzing the essential PF elements of athletes in various sports and recommending personalized exercise methods accordingly.


Assuntos
Traumatismos em Atletas , Futebol Americano , Humanos , Masculino , Adolescente , Atletas , Futebol Americano/lesões , Natação , Aptidão Física
9.
Structure ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38579707

RESUMO

Human mixed lineage leukemia 4 (MLL4), also known as KMT2D, regulates cell type specific transcriptional programs through enhancer activation. Along with the catalytic methyltransferase domain, MLL4 contains seven less characterized plant homeodomain (PHD) fingers. Here, we report that the sixth PHD finger of MLL4 (MLL4PHD6) binds to the hydrophobic motif of ten-eleven translocation 3 (TET3), a dioxygenase that converts methylated cytosine into oxidized derivatives. The solution NMR structure of the TET3-MLL4PHD6 complex and binding assays show that, like histone H4 tail, TET3 occupies the hydrophobic site of MLL4PHD6, and that this interaction is conserved in the seventh PHD finger of homologous MLL3 (MLL3PHD7). Analysis of genomic localization of endogenous MLL4 and ectopically expressed TET3 in mouse embryonic stem cells reveals a high degree overlap on active enhancers and suggests a potential functional relationship of MLL4 and TET3.

10.
Dis Esophagus ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587429

RESUMO

Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with type 2 diabetes and a developing several cancers including esophageal cancer (EC). However, the association between MASLD and EC in diabetic patients has not been investigated. Therefore, we aimed to investigate the relation between MASLD and developing EC in diabetic patients. This was a population-based retrospective cohort study of data from the Korean National Health Insurance Service (NHIS). A total of 1,904,468 subjects diagnosed with diabetes who underwent NHIS-provided health checkups from 2009 to 2012 were included. We constructed a Cox proportional hazard model for the association of fatty liver index (FLI) and the risk of EC stratified by potential confounders. Over a mean follow-up duration of 6.9 years, the incidence of EC was higher in the high (≥60) FLI group compared to the low (<30) FLI group (14.4 vs. 13.7 event per 100,000 person-years). The risk of EC correlated with the degree of FLI, particularly in older (P = 0.002), female (P = 0.033), non-smoking (P = 0.002), and non-drinking patients (P = 0.025). Among obese patients, the risk of EC was not associated with FLI; however, the risk of EC was higher in the high FLI group in non-obese patients. Lean MASLD patients had the highest risk of EC (adjusted hazard ratio 1.78; 95% confidence interval, 1.5-2.13). MASLD was associated with an increased risk of EC in diabetic patients, and lean MASLD has the highest risk. Further studies are required to determine the causal relationship between MASLD and EC.

11.
J Med Chem ; 67(9): 7647-7662, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38684226

RESUMO

The elevated activity of leucine-rich repeat kinase 2 (LRRK2) is implicated in the pathogenesis of Parkinson's disease (PD). The quest for effective LRRK2 inhibitors has been impeded by the formidable challenge of crossing the blood-brain barrier (BBB). We leveraged structure-based de novo design and developed robust three-dimensional quantitative structure-activity relationship (3D-QSAR) models to predict BBB permeability, enhancing the likelihood of the inhibitor's brain accessibility. Our strategy involved the synthesis of macrocyclic molecules by linking the two terminal nitrogen atoms of HG-10-102-01 with an alkyl chain ranging from 2 to 4 units, laying the groundwork for innovative LRRK2 inhibitor designs. Through meticulous computational and synthetic optimization of both biochemical efficacy and BBB permeability, 9 out of 14 synthesized candidates demonstrated potent low-nanomolar inhibition and significant BBB penetration. Further assessments of in vitro and in vivo effectiveness, coupled with pharmacological profiling, highlighted 8 as the promising new lead compound for PD therapeutics.


Assuntos
Barreira Hematoencefálica , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Doença de Parkinson , Inibidores de Proteínas Quinases , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/antagonistas & inibidores , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo , Barreira Hematoencefálica/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Animais , Humanos , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/farmacocinética , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/uso terapêutico , Camundongos , Relação Quantitativa Estrutura-Atividade , Permeabilidade , Compostos Macrocíclicos/química , Compostos Macrocíclicos/farmacologia , Compostos Macrocíclicos/síntese química , Compostos Macrocíclicos/farmacocinética , Masculino
12.
PLoS One ; 19(4): e0302481, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38683767

RESUMO

PURPOSE: To evaluate the efficacy of inverted internal limiting membrane (ILM) flap technique in full-thickness macular holes (MHs) with a size of ≤400 µm compared to the ILM peeling technique. METHODS: Related literatures that compared inverted ILM flap and ILM peeling in MHs ≤ 400 µm were reviewed by searching electronic databases including Pubmed, EMbase, ClinicalTrials.gov, and Cochrane Library up to April 2023. The primary outcome measure was hole closure rate, and the secondary outcome measures were the mean postoperative best-corrected visual acuity (BCVA), retinal sensitivity, and outer status of the retinal layers, including the external limiting membrane and ellipsoid zone. The quality of the articles was assessed according to the revised version of the Cochrane risk-of-bias tool for randomized trials or the Newcastle-Ottawa scale. In the case of heterogeneity, a sensitivity analysis was conducted, and publication bias was visually evaluated using a funnel plot. RESULTS: This review included six studies with 610 eyes for the primary outcome and 385 eyes for the secondary outcomes, which were two randomized control trials and four retrospective studies. Pooled data revealed that the overall MH closure rate was 99.4% in the inverted ILM flap group and 96.2% in the ILM peeling group, without significant difference between the two groups (odds ratio = 3.91; 95% confidence interval, 0.82~18.69; P = 0.09). The inverted ILM flap technique did not have a favorable effect on the BCVA, retinal sensitivity, or recovery of the outer retinal layers. These results were consistent with those of the subgroup analysis of the different follow-up periods. No significant publication bias was observed. CONCLUSION: In eyes with MHs of ≤400 µm, both techniques demonstrated excellent surgical outcomes without significant differences. Therefore, surgical techniques can be selected according to surgeon preferences.


Assuntos
Perfurações Retinianas , Retalhos Cirúrgicos , Perfurações Retinianas/cirurgia , Humanos , Acuidade Visual , Vitrectomia/métodos , Resultado do Tratamento
13.
Hematology ; 29(1): 2343163, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38655690

RESUMO

BACKGROUND: Congenital dyserythropoietic anemia Ⅱ (CDA Ⅱ) is a rare inherited disorder of defective erythropoiesis caused by SEC23B gene mutation. CDA Ⅱ is often misdiagnosed as a more common type of clinically related anemia, or it remains undiagnosed due to phenotypic variability caused by the coexistence of inherited liver diseases, including Gilbert's syndrome (GS) and hereditary hemochromatosis. METHODS: We describe the case of a boy with genetically undetermined severe hemolytic anemia, hepatosplenomegaly, and gallstones whose diagnosis was achieved by targeted next generation sequencing. RESULTS: Molecular analysis revealed a maternally inherited novel intronic variant and a paternally inherited missense variant, c.[994-3C > T];[1831C > T] in the SEC23B gene, confirming diagnosis of CDA Ⅱ. cDNA analysis verified that the splice acceptor site variant results in two mutant transcripts, one with an exon 9 skip and one in which exons 9 and 10 are deleted. SEC23B mRNA levels in the patient were lower than those in healthy controls. The patient was also homozygous for the UGT1A1*6 allele, consistent with GS. CONCLUSION: Identification of the novel splice variant in this study further expands the spectrum of known SEC23B gene mutations. Molecular genetic approaches can lead to accurate diagnosis and management of CDA Ⅱ patients, particularly for those with GS coexisting.


Assuntos
Anemia Diseritropoética Congênita , Doença de Gilbert , Proteínas de Transporte Vesicular , Humanos , Anemia Diseritropoética Congênita/genética , Anemia Diseritropoética Congênita/diagnóstico , Masculino , Proteínas de Transporte Vesicular/genética , Doença de Gilbert/genética , Doença de Gilbert/complicações , Doença de Gilbert/diagnóstico , Splicing de RNA , Mutação
14.
Updates Surg ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38507173

RESUMO

Laparoscopic liver resection (LLR) remains controversial in the treatment of intrahepatic cholangiocarcinoma (ICC). The aim of the present study is to investigate the outcomes of LLR for ICC compared to open liver resection (OLR). We retrospectively reviewed patients who underwent surgery for ICC between January 2013 and February 2020. OLR and LLR were compared after propensity score matching (PSM). Overall survival (OS) and recurrence-free survival (RFS) were compared between the matched groups. During the study period, 219 patients met the inclusion criteria (OLR = 170 patients, 77.6%; LLR = 49 patients, 22.4%). Two groups of 43 patients each were analyzed after PSM. The 5-year RFS and OS were 44.6% and 47.9% in the OLR group and 50.9% and 39.8% in the LLR group, respectively. Hospital stay and intensive care unit care were significantly shorter and lower in the LLR group than in the OLR group, respectively. Total postoperative complications and complication rates for those Clavien-Dindo grade 3 or higher were similar between the OLR group and the LLR group. Multiple tumors and lymph node metastases were predisposing factors for tumor recurrence and death in multivariate analysis. The present study suggests that LLR should be considered in selective ICC because of short hospitalization and similar oncologic outcome and overall survival.

15.
Viruses ; 16(3)2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38543842

RESUMO

Coxsackievirus A6 (CV-A6) has emerged as the predominant causative agent of hand, foot, and mouth disease (HFMD) in young children. Since the declaration of coronavirus disease 2019 (COVID-19) as a global pandemic, the incidence of infectious diseases, including HFMD, has decreased markedly. When social mitigation was relaxed during the COVID-19 pandemic in 2022, the re-emergence of HFMD was observed in Gwangju, South Korea, and seasonal characteristics of the disease appeared to have changed. To investigate the molecular characteristics of enterovirus (EV) associated with HFMD during 2022, 277 specimens were collected. Children aged younger than 5 years accounted for the majority of affected individuals. EV detection and genotyping were performed using real-time RT-PCR and nested RT-PCR followed by sequence analysis. The EV detection rate was found to be 82.3%, and the main genotype identified was CV-A6. Sixteen CV-A6 samples were selected for whole genome sequencing. According to phylogenetic analysis, all CV-A6 strains from this study belonged to the sub-genotype D3 clade based on VP1 sequences. Analysis of 3D polymerase phylogeny showed that only the recombinant RF-A group was identified. In conclusion, circulating EV types should be continuously monitored to understand pathogen emergence and evolution during the post-pandemic era.


Assuntos
Enterovirus , Doença de Mão, Pé e Boca , Criança , Humanos , Pré-Escolar , Doença de Mão, Pé e Boca/epidemiologia , Filogenia , Pandemias , Enterovirus/genética , Antígenos Virais/genética , Reação em Cadeia da Polimerase em Tempo Real , Genótipo , China/epidemiologia
16.
Sci Rep ; 14(1): 7306, 2024 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-38538849

RESUMO

This retrospective study aimed to compare objective/subjective torsion and other clinical characteristics of patients with acquired trochlear nerve palsy. This study included 82 consecutive patients who were diagnosed with acquired fourth cranial nerve palsy between 2014 and 2021 and who were followed up for ≥ 6 months. The etiologies, ocular deviation, objective and subjective torsions were reviewed. The etiologies were classified as ischemic, traumatic, brain lesion, idiopathic, or other. The patients were classified into two groups according to the recovery state: full recovery and partial/no-recovery. We compared the torsion and clinical features based on the etiology and recovery state. The average age was 59.1 ± 11.1 years, and 58 (71.0%) of the patients were male. The most common cause was ischemic (n = 49, 59.7%) and other common causes included traumatic (n = 16, 19.5%), brain lesion (n = 8, 9.8%), idiopathic (n = 5, 6.1%) and others (n = 4, 4.9%). Of the 82 patients, 56 (68.3%) were assigned to the full recovery group, and 26 (31.7%) were assigned to the partial/no-recovery group. The average age and number of patients with ischemic causes of palsy were greater in the full recovery group (p = 0.026 and p < 0.000, respectively). The vertical deviation angle, tilted angle on the Lancaster red-green test (LRGT), proportion of patients who experienced subjective torsion on the LRGT, and head tilt were smaller in the full recovery group (p = 0.037, 0.042, 0.045, and 0.006, respectively). Ischemic trochlear nerve palsy, advanced age, a small deviation angle at the primary position, and few cases of excyclotorsion on LRGT were characteristic of the full recovery group of acquired unilateral trochlear nerve palsy patients.


Assuntos
Doenças do Nervo Troclear , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Doenças do Nervo Troclear/etiologia , Doenças do Nervo Troclear/diagnóstico , Estudos Retrospectivos , Paralisia , Anormalidade Torcional
17.
Medicina (Kaunas) ; 60(3)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38541178

RESUMO

Background and Objectives: This study addresses the challenge of bone regeneration in calvarial defects, exploring the efficacy of stem cell-based therapies and enamel matrix derivative (EMD) in tissue engineering. It assesses the regenerative potential of two- and three-dimensional cell constructs combined with mesenchymal stem cells (MSCs) and EMD in rabbit calvarial defects. Materials and Methods: This research involved the use of bone-marrow-derived MSCs cultured in silicon elastomer-based concave microwells to form spheroids. White rabbits were grouped for different treatments, with Group 1 as control, Group 2 receiving only EMD, Group 3 getting EMD plus stem cells, and Group 4 being treated with EMD plus stem cell spheroids. Computed tomography (CT) and microcomputed tomography (micro-CT) imaging were used for structural assessment, while histological evaluations were conducted using hematoxylin and eosin, Masson's trichrome, and Picro-sirius red staining. Results: CT and micro-CT analyses revealed varying degrees of bone regeneration among the groups. Group 4, treated with three-dimensional MSC spheroids and EMD, showed the most significant improvement in bone regeneration. Histological analyses corroborated these findings, with Group 4 displaying enhanced bone formation and better collagen fiber organization. Conclusions: The study supported the biocompatibility and potential efficacy of three-dimensional MSC constructs combined with EMD in bone regeneration. Further investigations are needed to confirm these findings and optimize treatment protocols.


Assuntos
Proteínas do Esmalte Dentário , Células-Tronco Mesenquimais , Osteogênese , Animais , Coelhos , Microtomografia por Raio-X , Regeneração Óssea
18.
Parasites Hosts Dis ; 62(1): 30-41, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38443768

RESUMO

The dense granule protein of Toxoplasma gondii, inhibitor of signal transducer and activator of transcription 1 (IST) is an inhibitor of signal transducer and activator of transcription 1 (STAT1) transcriptional activity that binds to STAT1 and regulates the expression of inflammatory molecules in host cells. A sterile inflammatory liver injury in pathological acute liver failures occurs when excessive innate immune function, such as the massive release of IFN-γ and TNF-α, is activated without infection. In relation to inflammatory liver injury, we hypothesized that Toxoplasma gondii inhibitor of STAT1 transcription (TgIST) can inhibit the inflammatory response induced by activating the STAT1/IRF-1 mechanism in liver inflammation. This study used IFN-γ and TNF-α as inflammatory inducers at the cellular level of murine hepatocytes (Hepa-1c1c7) to determine whether TgIST inhibits the STAT1/IRF-1 axis. In stable cells transfected with TgIST, STAT1 expression decreased with a decrease in interferon regulatory factor (IRF)-1 levels. Furthermore, STAT1 inhibition of TgIST resulted in lower levels of NF-κB and COX2, as well as significantly lower levels of class II transactivator (CIITA), iNOS, and chemokines (CLXCL9/10/11). TgIST also significantly reduced the expression of hepatocyte proapoptotic markers (Caspase3/8/9, P53, and BAX), which are linked to sterile inflammatory liver injury. TgIST also reduced the expression of adhesion (ICAM-1 and VCAM-1) and infiltration markers of programmed death-ligand 1 (PD-L1) induced by hepatocyte and tissue damage. TgIST restored the cell apoptosis induced by IFN-γ/TNF-α stimulation. These results suggest that TgIST can inhibit STAT1-mediated inflammatory and apoptotic responses in hepatocytes stimulated with proinflammatory cytokines.


Assuntos
Toxoplasma , Fator de Necrose Tumoral alfa , Animais , Camundongos , Fator de Transcrição STAT1/genética , Hepatócitos , Transdução de Sinais
19.
Eur Radiol ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38536460

RESUMO

OBJECTIVES: To predict tumor recurrence in patients who underwent surgical resection of ampullary adenocarcinoma using preoperative magnetic resonance (MR) imaging findings combined with clinical findings. METHODS: In this multicenter study, a total of 113 patients (mean age, 62.9 ± 9.8 years; 58 men and 55 women) with ampullary adenocarcinoma who underwent preoperative MR imaging and surgery with margin-negative resection between 2006 and 2017 were retrospectively included. The MR imaging findings were evaluated by two radiologists. Preoperative clinical findings were obtained. Cox proportional regression analyses were used to identify the independent prognostic factors for recurrence-free survival (RFS). A nomogram was created based on the multivariable analysis and was internally validated. RESULTS: Multivariable analysis revealed that presence of infiltrative tumor margin (hazard ratio [HR]: 2.18, p = 0.019), adjacent organ invasion (HR: 3.31, p = 0.006), adjacent vessel invasion (HR: 5.42, p = 0.041), peripancreatic lymph node enlargement (HR: 2.1, p = 0.019), and jaundice (HR: 1.93, p = 0.043) were significantly associated with worse RFS of ampullary adenocarcinoma after surgical resection. These MR imaging and clinical findings were used to construct a nomogram. On internal validation, the calibration plots showed excellent agreement between the predicted probabilities and the actual rates of tumor recurrence, with Harrell's c-index of 0.746. CONCLUSIONS: Combination of preoperative MR imaging and clinical findings can be useful for predicting tumor recurrence after surgical resection of ampullary adenocarcinoma. Identifying these features before surgery may aid in better treatment planning and management of these patients. CLINICAL RELEVANCE STATEMENT: A predictive nomogram using preoperative MR imaging and clinical findings can be useful in estimating the recurrence-free survival after surgical resection of ampullary adenocarcinoma. KEY POINTS: • Presently, tumor size on imaging is the only non-invasive factor that correlates with recurrence-free survival from ampullary adenocarcinoma; other factors are obtained postoperatively. • Infiltrative tumor margin, adjacent organ invasion, adjacent vessel invasion, peripancreatic lymph node enlargement on MRI, and jaundice are significant predictors for recurrence. • A nomogram incorporating significant MR imaging and clinical findings showed good performance in predicting recurrence-free survival, which can help in treatment planning.

20.
Electrophoresis ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38488745

RESUMO

Targeted bisulfite sequencing using single-base extension (SBE) can be used to measure DNA methylation via capillary electrophoresis on genetic analyzers in forensic labs. Several accurate age prediction models have been reported using this method. However, using different genetic analyzers with different software settings can generate different methylation values, leading to significant errors in age prediction. To address this issue, the study proposes and compares four methods as follows: (1) adjusting methylation values using numerous actual body fluid DNA samples, (2) adjusting methylation values using control DNAs with varying methylation ratios, (3) constructing new age prediction models for each genetic analyzer type, and (4) constructing new age prediction models that could be applied to all types of genetic analyzers. To test the methods for adjusting values using actual body fluid DNA samples, previously reported adjusting equations were used for blood/saliva DNA age prediction markers (ELOVL2, FHL2, KLF14, MIR29B2CHG/C1orf132, and TRIM59). New equations were generated for semen DNA age prediction markers (TTC7B, LOC401324/cg12837463, and LOC729960/NOX4) by drawing polynomial regression lines between the results of the three types of genetic analyzers (3130, 3500, and SeqStudio). The same method was applied to obtain adjustment equations using 11 control DNA samples. To develop new age prediction models for each genetic analyzer type, linear regression analysis was conducted using DNA methylation data from 150 blood, 150 saliva, and 62 semen samples. For the genetic analyzer-independent models, control DNAs were used to formulate equations for calibrating the bias of the data from each genetic analyzer, and linear regression analysis was performed using calibrated body fluid DNA data. In the comparison results, the genetic analyzer-specific models showed the highest accuracy. However, genetic analyzer-independent models through bias adjustment also provided accurate age prediction results, suggesting its use as an alternative in situations with multiple constraints.

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