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1.
Medicine (Baltimore) ; 103(19): e37981, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38728508

RESUMO

The incidence of chronic atrophic gastritis (CAG) is on the rise due to the growing pressure in modern social life, increasing bad living habits and emotional disorders (such as anxiety and depression), and the aging of the population. Of note, digestive system diseases are the dominant diseases in the field of traditional Chinese medicine (TCM). Therefore, this study evaluated the efficacy and safety of Piwei Peiyuan Prescription, a TCM prescription, in the treatment of CAG through a multicenter, double-blind, randomized, controlled design. This research was organized by the Second Affiliated Hospital of Anhui University of TCM and simultaneously performed in 6 centers. A total of 120 CAG patients were included and randomized into 2 groups: group A (treatment with Piwei Peiyuan granules plus Weifuchun Simulant) and Group B (treatment with Weifuchun Tablets plus Piwei Peiyuan Simulant). These 2 groups were compared in terms of gastroscopy scores, TCM syndrome scores, and serological indicators at baseline and within 12 weeks after treatment. According to endoscopic biopsy for pathological observation, atrophy (2.56 ±â€…1.08 vs 3.00 ±â€…1.00, P = .028) and intestinal epithelial hyperplasia (1.00 ±â€…1.43 vs 1.69 ±â€…1.80, P = .043) scores were lower in group A than in group B. For the more, group A had higher effective rates for inflammation, atrophy, and intestinal metaplasia (IM) in various regions of the stomach, especially for atrophy/IM of the gastric angle (64%, P = .034) and atrophy/IM of the lesser curvature of gastric antrum (63%, P = .042) than group B. According to TCM syndrome scores, Piwei Peiyuan Prescription improved the scores of gastric distension (2.30 ±â€…1.13 vs 2.80 ±â€…0.99, P = .022), preference for warmth and pressure (1.44 ±â€…1.06 vs 1.36 ±â€…1.10, P = .041), and poor appetite and indigestion (0.78 ±â€…0.66 vs 1.32 ±â€…0.72, P = .018). GAS, MTL, and PGE2 expression was significantly elevated after treatment with Piwei Peiyuan Prescription (P < .001). Piwei Peiyuan Prescription is effective for CAG treatment with high safety.


Assuntos
Medicamentos de Ervas Chinesas , Gastrite Atrófica , Humanos , Gastrite Atrófica/tratamento farmacológico , Feminino , Masculino , Método Duplo-Cego , Pessoa de Meia-Idade , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/efeitos adversos , Adulto , Resultado do Tratamento , Doença Crônica , Medicina Tradicional Chinesa/métodos , Idoso , Gastroscopia
2.
Environ Toxicol Pharmacol ; : 104463, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38734395

RESUMO

Phthalates can induce hepatotoxicity in animal studies. We aimed to assess the associations of individual and mixture of urinary phthalate metabolites with serum liver function indicators among 764 women undergoing assisted reproductive technology (ART). In linear models, we observed inverse correlations between urinary mono-benzyl phthalate and serum total protein (TP) as well as globulin (ß=-0.27 and -0.23, respectively, P<0.05). Additionally, negative associations were identified between mono-isobutyl phthalate and mono-butyl phthalate (MBP) and aspartate aminotransferase-to-alanine transaminase ratio (AST/ALT) (P<0.05). MBP and the sum of all phthalate metabolites (∑all.phth.m) were positively associated with bilirubin, with ß ranging from 0.14 to 0.47. Most phthalate metabolites were also positively related to gamma-glutamyl transferase (GGT) (all P<0.05). In Bayesian kernel machine regression models, phthalate mixture was positively associated with bilirubin and GGT, whereas inversely associated with AST/ALT and TP. Our results suggest that phthalate exposure may impair liver function among women undergoing ART.

3.
Small Methods ; : e2301778, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38741551

RESUMO

With the rapid development and maturity of electrochemical CO2 conversion involving cathodic CO2 reduction reaction (CO2RR) and anodic oxygen evolution reaction (OER), conventional ex situ characterizations gradually fall behind in detecting real-time products distribution, tracking intermediates, and monitoring structural evolution, etc. Nevertheless, advanced in situ techniques, with intriguing merits like good reproducibility, facile operability, high sensitivity, and short response time, can realize in situ detection and recording of dynamic data, and observe materials structural evolution in real time. As an emerging visual technique, scanning electrochemical microscope (SECM) presents local electrochemical signals on various materials surface through capturing micro-current caused by reactants oxidation and reduction. Importantly, SECM holds particular potentials in visualizing reactive intermediates at active sites and obtaining instantaneous morphology evolution images to reveal the intrinsic reactivity of active sites. Therefore, this review focuses on SECM fundamentals and its specific applications toward CO2RR and OER, mainly including electrochemical behavior observation on local regions of various materials, target products and onset potentials identification in real-time, reaction pathways clarification, reaction kinetics exploration under steady-state conditions, electroactive materials screening and multi-techniques coupling for a joint utilization. This review undoubtedly provides a leading guidance to extend various SECM applications to other energy-related fields.

4.
Chem Commun (Camb) ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38742267

RESUMO

Over the past decade, significant progress has been made in the direct C-H acylation of naphthalenes, occurring at the α or ß-positions to yield valuable ketones through Friedel-Crafts acylation or transition-metal-catalysed carbonylative coupling reactions. Nevertheless, highly regioselective acylation of naphthalenes remains a formidable challenge. Herein, we developed a nickel-catalysed reductive ring-opening reaction of 7-oxabenzonorbornadienes with acyl chlorides as the electrophilic coupling partner, providing a new method for the exclusive preparation of ß-acyl naphthalenes.

5.
Inorg Chem ; 63(19): 8919-8924, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38698558

RESUMO

The introduction of transition metal (TM) ions into polyoxometalates (POMs) cannot only bring about interesting structural diversities but also enable changes in properties. However, TM-containing Silverton-type polyoxomolybdates are still lacking in terms of structural diversity and application development. Herein, two Zn(II)-containing Silverton-type {UMo12O42}-based polyoxomolybdates, H1.89Na4.11(H2O)9Zn[UMo12O42]·4.5H2O (Zn-1) and H1.8Na4.2(H2O)12Zn[UMo12O42] (Zn-2) were hydrothermally synthesized, demonstrating a practical strategy to assembly of TM-containing Silverton-type POMs. Zn-1 is proven to be an excellent and recyclable heterogeneous catalyst in cross-dehydrogenation coupling of 1,4-naphthoquinones with amines reactions, and a series of 2-amino-1,4-naphthoquinones with potential medicinal value have been constructed.

6.
World J Gastrointest Oncol ; 16(5): 2200-2218, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38764808

RESUMO

BACKGROUND: The lack of specific symptoms of gastric cancer (GC) causes great challenges in its early diagnosis. Thus it is essential to identify the risk factors for early diagnosis and treatment of GC and to improve the survival rates. AIM: To assist physicians in identifying changes in the output of publications and research hotspots related to risk factors for GC, constructing a list of key risk factors, and providing a reference for early identification of patients at high risk for GC. METHODS: Research articles on risk factors for GC were searched in the Web of Science core collection, and relevant information was extracted after screening. The literature was analyzed using Microsoft Excel 2019, CiteSpace V, and VOSviewer 1.6.18. RESULTS: A total of 2514 papers from 72 countries and 2507 research institutions were retrieved. China (n = 1061), National Cancer Center (n = 138), and Shoichiro Tsugane (n = 36) were the most productive country, institution, or author, respectively. The research hotspots in the study of risk factors for GC are summarized in four areas, namely: Helicobacter pylori (H. pylori) infection, single nucleotide polymorphism, bio-diagnostic markers, and GC risk prediction models. CONCLUSION: In this study, we found that H. pylori infection is the most significant risk factor for GC; single-nucleotide polymorphism (SNP) is the most dominant genetic factor for GC; bio-diagnostic markers are the most promising diagnostic modality for GC. GC risk prediction models are the latest current research hotspot. We conclude that the most important risk factors for the development of GC are H. pylori infection, SNP, smoking, diet, and alcohol.

7.
Int J Ophthalmol ; 17(5): 963-968, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38766345

RESUMO

Although selective laser trabeculoplasty (SLT) is a recognized method for the treatment of glaucoma, the exact changes in the target tissue and mechanism for its intraocular pressure lowing effect are still unclear. The purpose of this review is to summarize the potential mechanisms of SLT on trabecular meshwork both in vivo and in vitro, so as to reveal the potential mechanism of SLT. SLT may induce immune or inflammatory response in trabecular meshwork (TM) induced by possible oxidative damage etc, and remodel extracellular matrix. It may also induce monocytes to aggregate in TM tissue, increase Schlemm's canal (SC) cell conductivity, disintegrate cell junction and promote permeability through autocrine and paracrine forms. This provides a theoretical basis for SLT treatment in glaucoma.

8.
J Robot Surg ; 18(1): 201, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38713337

RESUMO

To compare the clinical efficacy and safety of robot-assisted resection and open surgery for cholangiocarcinoma (CCA). We conducted a comprehensive search of PubMed, the Cochrane Library, and Embase databases for studies comparing treatment for CCA, covering the period from database inception to January 30, 2024. Two researchers will independently screen literature and extract data, followed by meta-analysis using Review Manager 5.3 software. A total of 5 articles with 513 patients were finally included. Among them, 231 in the robotic group, and 282 in the open group. The Meta-analysis revealed that the robotic group had a significant advantage in terms of intraoperative blood loss (MD = - 101.44, 95% CI - 135.73 to - 67.15, P < 0.05), lymph node harvest(MD = 1.03, 95% CI 0.30- 1.76, P < 0.05) and length of hospital stay(MD = - 1.92, 95% CI - 2.87 to- 0.97, P < 0.05). However, there were no statistically significant differences between the two groups in terms of transfusion rate (OR = 0.62, 95% CI 0.31-1.23, P > 0.05), R0 resection (OR = 1.49, 95% CI 0.89- 2.50, P > 0.05), 30-day mortality (OR = 1.68, 95% CI 0.43-6.65, P > 0.05) and complications (OR = 0.76, 95% CI 0.30- 1.95, P > 0.05). Robotic-assisted radical resection for CCA is feasible and safe, and its long-term efficacy and oncological outcomes need to be confirmed by further studies.


Assuntos
Neoplasias dos Ductos Biliares , Perda Sanguínea Cirúrgica , Colangiocarcinoma , Tempo de Internação , Procedimentos Cirúrgicos Robóticos , Humanos , Neoplasias dos Ductos Biliares/cirurgia , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Transfusão de Sangue/estatística & dados numéricos , Colangiocarcinoma/cirurgia , Tempo de Internação/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento
9.
Cell Biol Toxicol ; 40(1): 35, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38771546

RESUMO

Neural tube defects (NTDs) represent a prevalent and severe category of congenital anomalies in humans. Cadmium (Cd) is an environmental teratogen known to cause fetal NTDs. However, its underlying mechanisms remain elusive. This study aims to investigate the therapeutic potential of lipophagy in the treatment of NTDs, providing valuable insights for future strategies targeting lipophagy activation as a means to mitigate NTDs.We successfully modeled NTDs by Cd exposure during pregnancy. RNA sequencing was employed to investigate the transcriptomic alterations and functional enrichment of differentially expressed genes in NTD placental tissues. Subsequently, pharmacological/genetic (Atg5-/- placentas) experiments confirmed that inducing placental lipophagy can alleviate Cd induced-NTDs. We found that Cd exposure caused NTDs. Further analyzed transcriptomic data from the placentas with NTDs which revealed significant downregulation of low-density lipoprotein receptor associated protein 1(Lrp1) gene expression responsible for positive regulation of low-density lipoprotein cholesterol (LDL-C) transport. Correspondingly, there was an increase in maternal serum/placenta/amniotic fluid LDL-C content. Subsequently, we have discovered that Cd exposure activated placental lipophagy. Pharmacological/genetic (Atg5-/- placentas) experiments confirmed that inducing placental lipophagy can alleviate Cd induced-NTDs. Furthermore, our findings demonstrate that activation of placental lipophagy effectively counteracts the Cd-induced elevation in LDL-C levels. Lipophagy serves to mitigate Cd-induced NTDs by reducing LDL-C levels within mouse placentas.


Assuntos
Cádmio , LDL-Colesterol , Defeitos do Tubo Neural , Placenta , Feminino , Animais , Gravidez , Placenta/metabolismo , Placenta/efeitos dos fármacos , Defeitos do Tubo Neural/genética , Defeitos do Tubo Neural/induzido quimicamente , Defeitos do Tubo Neural/metabolismo , Camundongos , Cádmio/toxicidade , LDL-Colesterol/sangue , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout
10.
Eur J Med Res ; 29(1): 286, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745338

RESUMO

BACKGROUND: Our study aimed to confirm a simplified radiological scoring system, derived from a modified Reiff score, to evaluate its relationship with clinical symptoms and predictive outcomes in Taiwanese patients with noncystic fibrosis bronchiectasis (NCFB). METHODS: This extensive multicenter retrospective study, performed in Taiwan, concentrated on patients diagnosed with NCFB verified through high-resolution computed tomography (HRCT) scans. We not only compared the clinical features of various types of bronchiectasis (cylindrical, varicose, and cystic). Furthermore, we established relationships between the severity of clinical factors, including symptom scores, pulmonary function, pseudomonas aeruginosa colonization, exacerbation and admission rates, and HRCT parameters using modified Reiff scores. RESULTS: Data from 2,753 patients were classified based on HRCT patterns (cylindrical, varicose, and cystic) and severity, assessed by modified Reiff scores (mild, moderate, and severe). With increasing HRCT severity, a significant correlation was found with decreased forced expiratory volume in the first second (FEV1) (p < 0.001), heightened clinical symptoms (p < 0.001), elevated pathogen colonization (pseudomonas aeruginosa) (p < 0.001), and an increased annual hospitalization rate (p < 0.001). In the following multivariate analysis, elderly age, pseudomonas aeruginosa pneumonia, and hospitalizations per year emerged as the only independent predictors of mortality. CONCLUSION: Based on our large cohort study, the simplified CT scoring system (Reiff score) can serve as a useful adjunct to clinical factors in predicting disease severity and prognosis among Taiwanese patients with NCFB.


Assuntos
Bronquiectasia , Índice de Gravidade de Doença , Humanos , Masculino , Feminino , Bronquiectasia/fisiopatologia , Bronquiectasia/diagnóstico por imagem , Taiwan/epidemiologia , Pessoa de Meia-Idade , Prognóstico , Idoso , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Volume Expiratório Forçado , Adulto , Pseudomonas aeruginosa/isolamento & purificação
11.
Aging (Albany NY) ; 16(9): 7889-7901, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38709264

RESUMO

Despite neoadjuvant chemoradiotherapy (CRT) being the established standard for treating advanced rectal cancer, clinical outcomes remain suboptimal, necessitating the identification of predictive biomarkers for improved treatment decisions. Previous studies have hinted at the oncogenic properties of the Fc fragment of IgG binding protein (FCGBP) in various cancers; however, its clinical significance in rectal cancer remains unclear. In this study, we first conducted an analysis of a public transcriptome comprising 46 rectal cancer patients. Focusing on cell adhesion during data mining, we identified FCGBP as the most upregulated gene associated with CRT resistance. Subsequently, we assessed FCGBP immunointensity using immunohistochemical staining on 343 rectal cancer tissue blocks. Elevated FCGBP immunointensity correlated with lymph node involvement before treatment (p = 0.001), tumor invasion, and lymph node involvement after treatment (both p < 0.001), vascular invasion (p = 0.001), perineural invasion (p = 0.041), and reduced tumor regression (p < 0.001). Univariate analysis revealed a significant association between high FCGBP immunoexpression and inferior disease-specific survival, local recurrence-free survival, and metastasis-free survival (all p ≤ 0.0002). Furthermore, high FCGBP immunoexpression independently emerged as an unfavorable prognostic factor for all three survival outcomes in the multivariate analysis (all p ≤ 0.025). Enriched pathway analysis substantiated the role of FCGBP in conferring resistance to radiation. In summary, our findings suggest that elevated FCGBP immunoexpression in rectal cancer significantly correlates with a poor response to CRT and diminished patient survival. FCGBP holds promise as a valuable prognostic biomarker for rectal cancer patients undergoing CRT.


Assuntos
Quimiorradioterapia , Neoplasias Retais , Humanos , Neoplasias Retais/terapia , Neoplasias Retais/metabolismo , Neoplasias Retais/patologia , Neoplasias Retais/genética , Neoplasias Retais/mortalidade , Feminino , Masculino , Pessoa de Meia-Idade , Quimiorradioterapia/métodos , Idoso , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Prognóstico , Resultado do Tratamento , Terapia Neoadjuvante/métodos , Adulto
13.
World J Pediatr ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38713366

RESUMO

BACKGROUND: SARS-CoV-2 continues to mutate over time, and reports on children infected with Omicron BA.5 are limited. We aimed to analyze the specific symptoms of Omicron-infected children and to improve patient care. METHODS: We selected 315 consecutively hospitalized children with Omicron BA.5 and 16,744 non-Omicron-infected febrile children visiting the fever clinic at our hospital between December 8 and 30, 2022. Specific convulsions and body temperatures were compared between the two cohorts. We analyzed potential associations between convulsions and vaccination, and additionally evaluated the brain damage among severe Omicron-infected children. RESULTS: Convulsion rates (97.5% vs. 4.3%, P < 0.001) and frequencies (median: 2.0 vs. 1.6, P < 0.001) significantly differed between Omicron-infected and non-Omicron-infected febrile children. The body temperatures of Omicron-infected children were significantly higher during convulsions than when they were not convulsing and those of non-Omicron-infected febrile children during convulsions (median: 39.5 vs. 38.2 and 38.6 °C, both P < 0.001). In the three Omicron-subgroups, the temperature during convulsions was proportional to the percentage of patients and significantly differed ( P < 0.001), while not in the three non-Omicron-subgroups ( P = 0.244). The convulsion frequency was lower in the 55 vaccinated children compared to the 260 non-vaccinated children (average: 1.8 vs. 2.1, P < 0.001). The vaccination dose and convulsion frequency in Omicron-infected children were significantly correlated ( P < 0.001). Fifteen of the 112 severe Omicron cases had brain damage. CONCLUSIONS: Omicron-infected children experience higher body temperatures and frequencies during convulsions than those of non-Omicron-infected febrile children. We additionally found evidence of brain damage caused by infection with omicron BA.5. Vaccination and prompt fever reduction may relieve symptoms.

14.
J Biol Chem ; : 107379, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38762184

RESUMO

Bacterial RecJ exhibits 5'→3' exonuclease activity that is specific to single-stranded DNA (ssDNA); however, archaeal RecJs show 5' or 3' exonuclease activity. The hyperthermophilic archaea Methanocaldococcus jannaschii encodes the 5'-exonuclease MjRecJ1 and the 3'-exonuclease MjRecJ2. In addition to nuclease activity, archaeal RecJ interacts with GINS, a structural subcomplex of the replicative DNA helicase complex. However, MjRecJ1 and MjRecJ2 do not interact with MjGINS. Here, we report the structural basis for the inability of the MjRecJ2 homologous dimer to interact with MjGINS and its efficient 3' hydrolysis polarity for short dinucleotides. Based on the crystal structure of MjRecJ2, we propose that the interaction surface of the MjRecJ2 dimer overlaps the potential interaction surface for MjGINS and blocks the formation of the MjRecJ2-GINS complex. Exposing the interaction surface of the MjRecJ2 dimer restores its interaction with MjGINS. The cocrystal structures of MjRecJ2 with substrate dideoxynucleotides or product dCMP/CMP show that MjRecJ2 has a short substrate binding patch, which is perpendicular to the longer patch of bacterial RecJ. Our results provide new insights into the function and diversification of archaeal RecJ/Cdc45 proteins.

15.
Dev Biol ; 512: 13-25, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38703942

RESUMO

Drosophila melanogaster is an ideal model organism for investigating spermatogenesis due to its powerful genetics, conserved genes and visible morphology of germ cells during sperm production. Our previous work revealed that ocnus (ocn) knockdown resulted in male sterility, and CG9920 was identified as a significantly downregulated protein in fly abdomen after ocn knockdown, suggesting a role of CG9920 in male reproduction. In this study, we found that CG9920 was highly expressed in fly testes. CG9920 knockdown in fly testes caused male infertility with no mature sperms in seminal vesicles. Immunofluorescence staining showed that depletion of CG9920 resulted in scattered spermatid nuclear bundles, fewer elongation cones that did not migrate to the anterior region of the testis, and almost no individualization complexes. Transmission electron microscopy revealed that CG9920 knockdown severely disrupted mitochondrial morphogenesis during spermatogenesis. Notably, we found that CG9920 might not directly interact with Ocn, but rather was inhibited by STAT92E, which itself was indirectly affected by Ocn. We propose a possible novel pathway essential for spermatogenesis in D. melanogaster, whereby Ocn indirectly induces CG9920 expression, potentially counteracting its inhibition by the JAK-STAT signaling pathway.

16.
Front Cardiovasc Med ; 11: 1306055, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38689859

RESUMO

Introduction: Signal-averaged electrocardiography (SAECG) provides diagnostic and prognostic information regarding cardiac diseases. However, its value in other nonischemic cardiomyopathies (NICMs) remains unclear. This study aimed to investigate the role of SAECG in patients with NICM. Methods and results: This retrospective study included consecutive patients with NICM who underwent SAECG, biventricular substrate mapping, and ablation for ventricular arrhythmia (VA). Patients with baseline ventricular conduction disturbances were excluded. Patients who fulfilled at least one SAECG criterion were categorized into Group 1, and the other patients were categorized into Group 2. Baseline and ventricular substrate characteristics were compared between the two groups. The study included 58 patients (39 men, mean age 50.4 ± 15.5 years), with 34 and 24 patients in Groups 1 and 2, respectively. Epicardial mapping was performed in eight (23.5%) and six patients (25.0%) in Groups 1 and 2 (p = 0.897), respectively. Patients in Group 1 had a more extensive right ventricular (RV) low-voltage zone (LVZ) and scar area than those in Group 2. Group 1 had a larger epicardial LVZ than Group 2. Epicardial late potentials were more frequent in Group 1 than in Group 2. There were more arrhythmogenic foci within the RV outflow tract in Group 1 than in Group 2. There was no significant difference in long-term VA recurrence. Conclusion: In our NICM population, a positive SAECG was associated with a larger RV endocardial scar, epicardial scar/late potentials, and a higher incidence of arrhythmogenic foci in the RV outflow tract.

17.
Hum Cell ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691335

RESUMO

Chimeric antigen receptor T (CART) cell therapy has demonstrated promising potential in the treatment of hematologic malignancies. However, its application to solid tumors is limited due to the restrictive nature of the tumor microenvironment, resulting in functional failure and poor persistence of CART cells. Overexpression of Bcl-2 in human CART cells (hCART) has been found to significantly enhance their anti-apoptotic effects both in vitro and in vivo. Nevertheless, the evaluation of hCART cells in preclinical studies has predominantly relied on immunodeficient mice xenograft tumor models, making it challenging to assess the impact of hCART cells on normal tissues and the immune system. We established a murine CART (mCART) that overexpresses Bcl-2 and targets the epidermal growth factor receptor variant III (EGFRvIII), named EGFRvIII·mCART-Bcl2. It demonstrated superior proliferation, cytotoxicity, and anti-apoptotic capabilities in vitro. In an immunocompetent mouse model of abdominal metastasis of colorectal cancer, EGFRvIII·mCART-Bcl2 exhibited improved survival of CART in the abdomen, increased tumor clearance, and significantly prolonged overall mouse survival. In summary, our study provides evidence that the introduction of Bcl-2 into mCART cells can enhance their therapeutic efficacy against solid tumors while ensuring safety.

18.
Sci Total Environ ; 931: 172938, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38703850

RESUMO

Cadmium (Cd) is a widely distributed typical environmental pollutant and one of the most toxic heavy metals. It is well-known that environmental Cd causes testicular damage by inducing classic types of cell death such as cell apoptosis and necrosis. However, as a new type of cell death, the role and mechanism of pyroptosis in Cd-induced testicular injury remain unclear. In the current study, we used environmental Cd to generate a murine model with testicular injury and AIM2-dependent pyroptosis. Based on the model, we found that increased cytoplasmic mitochondrial DNA (mtDNA), activated mitochondrial proteostasis stress occurred in Cd-exposed testes. We used ethidium bromide to generate mtDNA-deficient testicular germ cells and further confirmed that increased cytoplasmic mtDNA promoted AIM2-dependent pyroptosis in Cd-exposed cells. Uracil-DNA glycosylase UNG1 overexpression indicated that environmental Cd blocked UNG-dependent repairment of damaged mtDNA to drive the process in which mtDNA releases to cytoplasm in the cells. Interestingly, we found that environmental Cd activated mitochondrial proteostasis stress by up-regulating protein expression of LONP1 in testes. Testicular specific LONP1-knockdown significantly reversed Cd-induced UNG1 protein degradation and AIM2-dependent pyroptosis in mouse testes. In addition, environmental Cd significantly enhanced the m6A modification of Lonp1 mRNA and its stability in testicular germ cells. Knockdown of IGF2BP1, a reader of m6A modification, reversed Cd-induced upregulation of LONP1 protein expression and pyroptosis activation in testicular germ cells. Collectively, environmental Cd induces m6A modification of Lonp1 mRNA to activate mitochondrial proteostasis stress, increase cytoplasmic mtDNA content, and trigger AIM2-dependent pyroptosis in mouse testes. These findings suggest that mitochondrial proteostasis stress is a potential target for the prevention of testicular injury.


Assuntos
Cádmio , Mitocôndrias , Piroptose , Testículo , Animais , Cádmio/toxicidade , Masculino , Camundongos , Testículo/efeitos dos fármacos , Testículo/metabolismo , Piroptose/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Proteostase , Proteínas Mitocondriais/metabolismo , Exposição Ambiental/efeitos adversos , DNA Mitocondrial , Proteases Dependentes de ATP/metabolismo , Estresse Proteotóxico
19.
Mil Med Res ; 11(1): 29, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741175

RESUMO

Peri-implantitis is a bacterial infection that causes soft tissue inflammatory lesions and alveolar bone resorption, ultimately resulting in implant failure. Dental implants for clinical use barely have antibacterial properties, and bacterial colonization and biofilm formation on the dental implants are major causes of peri-implantitis. Treatment strategies such as mechanical debridement and antibiotic therapy have been used to remove dental plaque. However, it is particularly important to prevent the occurrence of peri-implantitis rather than treatment. Therefore, the current research spot has focused on improving the antibacterial properties of dental implants, such as the construction of specific micro-nano surface texture, the introduction of diverse functional coatings, or the application of materials with intrinsic antibacterial properties. The aforementioned antibacterial surfaces can be incorporated with bioactive molecules, metallic nanoparticles, or other functional components to further enhance the osteogenic properties and accelerate the healing process. In this review, we summarize the recent developments in biomaterial science and the modification strategies applied to dental implants to inhibit biofilm formation and facilitate bone-implant integration. Furthermore, we summarized the obstacles existing in the process of laboratory research to reach the clinic products, and propose corresponding directions for future developments and research perspectives, so that to provide insights into the rational design and construction of dental implants with the aim to balance antibacterial efficacy, biological safety, and osteogenic property.


Assuntos
Materiais Biocompatíveis , Implantes Dentários , Peri-Implantite , Peri-Implantite/terapia , Peri-Implantite/prevenção & controle , Peri-Implantite/tratamento farmacológico , Humanos , Implantes Dentários/normas , Materiais Biocompatíveis/uso terapêutico , Materiais Biocompatíveis/farmacologia , Biofilmes/efeitos dos fármacos , Propriedades de Superfície , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia
20.
Trials ; 25(1): 231, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570855

RESUMO

BACKGROUND: Breast cancer is the most prevalent cancer among women globally, and surgical procedures continue to be the primary treatment. However, over 50% of patients experience preoperative anxiety due to the unknown and fear associated with surgery. Although drug therapy is commonly used to address this anxiety, its side effects have led to a heated debate regarding its effectiveness. Consequently, non-pharmacological therapies, such as preoperative education, have emerged as an alternative approach to alleviate anxiety. WeChat, a widely popular social media platform, offers a public platform that can potentially be utilized for effective preoperative education. This study aims to evaluate the use of WeChat public platform as a tool for preoperative education in patients undergoing breast surgery. METHODS: This is a prospective, randomized, and controlled trial will involve 392 adult women scheduled for breast cancer resection. Participants will be randomly assigned to either the WeChat education group or the regular group. In addition to regular preoperative visits, the WeChat education group will also watch science videos through the WeChat public platform. The regular group will only receive education from ward nurses during preoperative visits. The primary outcome measure will be the incidence of preoperative anxiety, defined by scores of the State Anxiety Inventory (SAI) exceeding 40 points. Secondary outcome measures include the incidence of severe anxiety (SAI > 44) on the day before surgery, incidence of anxiety 72 h after surgery, incidence of severe anxiety 72 h after surgery, NRS scores for pain at rest and during activity 24, 48, and 72 h after surgery, incidence of nausea and vomiting within 24 h after surgery, subjective sleep score at 1 week postoperatively, quality of life QoR-15 scores at 1 and 3 months postoperatively, incidence of chronic pain at 3 months postoperatively, bowel function recovery, length of hospital stay, and hospitalization expenses. DISCUSSION: This is the first clinical trial to investigate the use of WeChat public platform for delivering preoperative education on perioperative anxiety in breast cancer patients. By utilizing the renowned WeChat public platform, our study aims to improve patient outcomes by providing video education that explains the disease, surgery, and anesthesia in a more accessible manner, thereby reducing the incidence of perioperative anxiety. If our hypothesis is confirmed, this non-pharmacological approach can be universally acknowledged as a cost-effective and practical method in clinical care. Its application can also be extended to other medical fields beyond breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05291494. Registered on 29 December 2021.


Assuntos
Neoplasias da Mama , Qualidade de Vida , Adulto , Humanos , Feminino , Neoplasias da Mama/cirurgia , Estudos Prospectivos , Ansiedade/diagnóstico , Ansiedade/etiologia , Ansiedade/prevenção & controle , Cuidados Pré-Operatórios/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto
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