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2.
Bioorg Chem ; 147: 107422, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38705106

RESUMO

Two acylhydrazone based zinc(II) complexes [Zn(HL)2Cl2(CH3OH)2] (Zn1) and [ZnL(AC)]2 (Zn2) were synthesized from 3-(1-(salicyloylhydrazono)ethyl) pyridine (HL). Single crystal X-ray structure analyses showed that complexes Zn1 and Zn2 have a zero-dimensional monomer or dimer structure. Antiproliferative activity studies revealed that Zn1 and Zn2 are both more effective against A549 cells than cisplatin. The results of the reactive oxygen species (ROS) generation assay on A549 cells showed that both Zn1 and Zn2 induced apoptosis through ROS accumulation. The apoptosis-inducing and cell cycle arrest effects of Zn1 and Zn2 on A549 cells indicated that the antitumor effect was achieved through apoptosis induction and inhibition of DNA synthesis by blocking the G0/G1 phase of the cell cycle. What's more, the results of wound-healing assay showed that Zn1 and Zn2 could inhibit the migration of A549 cells. Western blot analysis further demonstrated that Zn1 and Zn2 induced cell apoptosis through the mitochondrial pathway, in which process, the expression level of cytochrome C, cleaved-PARP, cleaved-caspase 3 and cleaved-caspase 9 proteins increased while pro-caspase 3 and pro-caspase 9 expression decreased. In vivo anticancer evaluation demonstrated that both Zn1 and Zn2 complexes effectively inhibited tumor growth without causing significant toxicity in systemic organs.


Assuntos
Antineoplásicos , Apoptose , Proliferação de Células , Complexos de Coordenação , Ensaios de Seleção de Medicamentos Antitumorais , Hidrazonas , Neoplasias Pulmonares , Zinco , Animais , Camundongos , Células A549 , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Relação Dose-Resposta a Droga , Hidrazonas/química , Hidrazonas/farmacologia , Hidrazonas/síntese química , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Neoplasias Experimentais/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade , Zinco/química , Zinco/farmacologia
3.
BMC Cardiovasc Disord ; 24(1): 217, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643100

RESUMO

BACKGROUND: During normal sinus rhythm, atrial depolarization is conducted from right atrium to left atrium through Bachmann's bundle, and a normal P wave axis which is measured on the frontal plane is between 0º and + 75º. The change of P wave polarity is helpful for the analysis of origin point. CASE PRESENTATION: We report a patient with negative P wave in lead I. The characteristics of QRS complex in leads V1 to V6 are helpful to preliminarily differential diagnosis. The 12-lead electrocardiogram (ECG) with correct limb leads (right arm-left arm) placement shows sinus rhythm with complete right bundle branch block (RBBB). CONCLUSIONS: The change of P wave polarity as well as characteristics of QRS complex can help identify limb-lead reversals.


Assuntos
Bloqueio de Ramo , Eletrocardiografia , Humanos , Bloqueio de Ramo/diagnóstico , Nó Sinoatrial , Átrios do Coração , Nó Atrioventricular
4.
JAMA Intern Med ; 184(4): 437-438, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38407870

RESUMO

This case report describes a patient in their 50s who presented with squeezing chest pain for 4 hours and an initial electrocardiogram showing acute inferior wall and right ventricular infarction with third-degree atrioventricular block.


Assuntos
Bradicardia , Taquicardia , Humanos , Bradicardia/diagnóstico , Bradicardia/etiologia , Taquicardia/diagnóstico , Taquicardia/etiologia , Eletrocardiografia , Dor no Peito/diagnóstico , Dor no Peito/etiologia
5.
Sci Rep ; 13(1): 19107, 2023 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-37925591

RESUMO

TGFB1, which encodes TGF-ß1, a potent cytokine regulating varies cellular processes including immune responses. TGF-ß1 plays context-dependent roles in cancers and is increasingly recognized as a therapeutic target to enhance immunotherapy responses. We comprehensively evaluated expression of TGFB1 and its clinical and biological effects across hematological malignancies. TGFB1 expression was first explored using data from the GTEx, CCLE, and TCGA databases. The expression and clinical significances of TGFB1 in hematological malignancies were analyzed using Hemap and our In Silico curated datasets. We also analyzed the relationship between TGFB1 with immune scores and immune cell infiltrations in Hemap. We further assessed the value of TGFB1 in predicting immunotherapy response using TIDE and real-world immunotherapy datasets. TGFB1 showed a hematologic-tissue-specific expression pattern both across normal tissues and cancer types. TGFB1 expression were broadly dysregulated in blood cancers and generally associated with adverse prognosis. TGFB1 expression were associated with distinct TME properties among different blood cancer types. In addition, TGFB1 expression was found to be a useful marker in predicting immunotherapy responses. Our results suggest that TGFB1 is broadly dysregulated in hematological malignancies. TGFB1 might regulate the immune microenvironment in a cancer-type-specific manner, which could be applied in the development of new targeted drugs for immunotherapy.


Assuntos
Neoplasias Hematológicas , Fator de Crescimento Transformador beta1 , Humanos , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Citocinas , Prognóstico , Neoplasias Hematológicas/genética , Microambiente Tumoral/genética , Imunoterapia
7.
JAMA Intern Med ; 183(11): 1259-1260, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37669060

RESUMO

This case report describes a patient in their 70s who presented to the emergency department with sudden-onset tachycardia that had been going on for more than 1 day after experiencing recurrent palpitations for the past 20 years.


Assuntos
Arritmias Cardíacas , Taquicardia , Humanos , Taquicardia/diagnóstico
8.
Medicine (Baltimore) ; 102(28): e34333, 2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37443507

RESUMO

RATIONALE: To investigate the clinical efficacy of the axillary approach in the surgical treatment of Ideberg type I and II scapular glenoid fractures. PATIENT CONCERNS AND DIAGNOSIS: Retrospective analysis of 13 cases of scapular glenoid fracture treated in the affiliated Hospital of Jining Medical College, Jiaxiang County People hospital, Zoucheng City people Hospital, Yanzhou District People Hospital, and Juancheng County people Hospital from December 2020 to January 2022. Eight males (including 1 bilateral) and 5 females, with an average age of 57.5 years (range from 33 to 75 years). According to Ideberg classification, there were 10 cases of type I a, 1 case of type I a combined with type I b, and 2 cases of type II. All patients were treated with axillary approach surgery and 7 patients with combined anterior shoulder dislocation were treated by first-stage manipulation and second-stage reoperation. Seven patients were fixed with a wire anchor, 3 patients with type I a were fixed with a "T" plate, and 5 patients were complicated with rotator cuff tear and were repaired with a wire anchor. At the last follow-up, the Constant-Murley shoulder function score, visual analog score, DASH score, and Hawkins grade were used to evaluate shoulder function, pain, and stability after treatment. INTERVENTION: The intervention was to treat patients with Ideberg type I and II scaphoid fractures using an axillary approach. OUTCOMES: All 13 patients in this group were followed up thoroughly, and the follow-up time was 12 to 25 months, with an average of 18.6 months. The operation time was 65 to 135 minutes, with an average of 85.6 minutes. Intraoperative blood loss ranged from 20 to 120 mL, averaging 55.6 mL. The duration of hospitalization ranged from 7 to 22 days, with an average of 9.6 days. The surgical incisions of all patients were grade-A healing. Bone healing of glenoid fractures was observed 3 months after the operation. LESSONS: The axillary approach for Ideberg type I and II scapular glenoid fractures is a feasible surgical approach with complete access through the muscle gap, minimal surgical trauma, mild postoperative pain, and satisfactory clinical results.


Assuntos
Fixação Interna de Fraturas , Fraturas do Ombro , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Fixação Interna de Fraturas/métodos , Escápula/cirurgia , Escápula/lesões , Ombro/cirurgia , Fraturas do Ombro/cirurgia , Resultado do Tratamento
9.
Aging (Albany NY) ; 15(9): 3498-3523, 2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-37179124

RESUMO

Recent research revealed methionine metabolism as a key mediator of tumor initiation and immune evasion. However, the relationship between methionine metabolism and tumor microenvironment (TME) in lung adenocarcinoma (LUAD) remains unknown. Here, we comprehensively analyzed the genomic alterations, expression patterns, and prognostic values of 68 methionine-related regulators (MRGs) in LUAD. We found that most MRGs were highly prognostic based on 30 datasets including 5024 LUAD patients. Three distinct MRG modification patterns were identified, which showed significant differences in clinical outcomes and TME characteristics: The C2 subtype was characterized by higher immune score, while the C3 subtype had more malignant cells and worse survival. We developed a MethScore to measure the level of methionine metabolism in LUAD. MethScore was positively correlated with T-cell dysfunction and tumor-associated macrophages (TAMs), indicating a dysfunctional TME phenotype in the high MethScore group. In addition, two immunotherapy cohorts confirmed that patients with a lower MethScore exhibited significant clinical benefits. Our study highlights the important role of methionine metabolism in modeling the TME. Evaluating methionine modification patterns will enhance our understanding of TME characteristics and can guide more effective immunotherapy strategies.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Prognóstico , Metionina , Racemetionina , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/terapia , Imunoterapia , Microambiente Tumoral/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia
10.
BMJ ; 380: e072333, 2023 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-36863733
11.
JAMA Intern Med ; 183(1): 74-75, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36409478

RESUMO

This case report describes a patient in their 70s who was referred to the emergency department for worsening shortness of breath, chest tightness, and episodes of palpitations. What is your diagnosis?


Assuntos
Dor no Peito , Serviço Hospitalar de Emergência , Feminino , Humanos , Idoso
12.
Materials (Basel) ; 15(22)2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36431625

RESUMO

This paper uses ANSYS Workbench platform to simulate the casting and rolling composite process, taking the horizontal type casting and rolling machine as the research object, and conducts the numerical simulation study of copper-aluminum composite solid-liquid casting and rolling heat-flow coupling, mainly to study different walking speed, aluminum pouring temperature, casting and rolling zone length, heat transfer coefficient on the temperature field, liquid phase rate influence law, and use it as a theoretical guide for copper-aluminum solid-liquid casting. The experiments of copper-aluminum solid-liquid casting-rolling composite were carried out to optimize the process parameters and to verify the experiments, so as to prepare a well-bonded copper-aluminum composite plate. The composite mechanism in the preparation of copper-aluminum composite plate was analyzed, and it was clarified that the interfacial layer was formed through four stages: contact between copper and aluminum surfaces, contact surface activation, mutual diffusion of copper and aluminum atoms, and reaction diffusion.

13.
Dalton Trans ; 51(39): 14993-15004, 2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36111968

RESUMO

Three metal complexes [CuL(NO3)]n (1), [Cd(HL)(NO3)2]n (2) and [EuL(HCOOH)(H2O)(NO3)2] (3) were synthesized with a pyridyl Schiff ligand L (N'-[(1E)-pyridin-2-ylmethylidene]pyridine-4-carbohydrazide). A crystallographic study revealed that complexes 1 and 2 have a chain structure, and complex 3 is a zero-dimensional monomer. In vitro cytotoxicity studies showed that complex 2 had the best antiproliferative activity against SMMC-7721 cells and complex 3 had the best antiproliferative activity against MDA-MB-231 cells with single-digit IC50 values, both exceeding those of the control drug cisplatin by far. The cell invasion and migration ability through the transwell assay and wound-healing assay showed that the selected complexes could inhibit the invasion and migration of cancer cells. The Hoechst staining assay and ROS generation assay with SMMC-7721 cells indicated that the cytotoxic effects of complex 2 involved apoptosis induction through ROS accumulation. The apoptosis-inducing and cell cycle arrest effects of complex 2 on SMMC-7721 cells indicated that the antitumor effect was achieved through apoptosis induction and inhibition of DNA synthesis by blocking the G0/G1 phase of the cell cycle. In addition, complex 2 showed significant inhibition against B. dysentery with an inhibition circle diameter of 24 mm.


Assuntos
Antineoplásicos , Complexos de Coordenação , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose , Cádmio/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , DNA/química , Ligantes , Piridinas/química , Piridinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Bases de Schiff/química , Bases de Schiff/farmacologia , Relação Estrutura-Atividade
14.
JAMA Intern Med ; 182(10): 1093-1094, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-36036919

RESUMO

This case report describes a man in his 50s with hypertension and diabetes who presented to the emergency department with sudden-onset chest pain radiating to his left arm and profuse sweating.


Assuntos
Artérias , Dor no Peito , Humanos
15.
JAMA Intern Med ; 182(8): 889-890, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35727577
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