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1.
J Clin Med ; 13(10)2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38792530

RESUMO

Background: DaVinci® single-port (SP) robotic surgery offers several benefits compared to traditional multiport laparoscopic or robotic surgeries. One of the main advantages is that it allows for a minimally invasive approach, resulting in a single, smaller incision and reduced trauma to the patient's body, leading to less postoperative pain, faster recovery, and reduced risk of complications. The cosmesis of a single port with minimal visible scarring is also an attractive aspect to the patients; however, many surgeons use an additional port for energy device, stapler use, and drain insertion. Pure single-port surgery with one incision is still rare. Here, we share our experience of our first 10 cases using the SP robotic platform in colorectal surgery. Methods: From May 2023 to December 2023, colorectal patients who underwent SP robotic surgery were analyzed. Placement of the incision was the umbilicus for eight patients, and right lower quadrant for two patients, through which ileostomy maturation was performed. Data on perioperative parameters and postoperative outcomes were analyzed, with a median follow-up of 4.6 months (range 0.6-7.4 months). Results: A total of 10 colorectal patients underwent DaVinci® single-port robotic colorectal surgery at our institution during this period. The patient demographic was four males (40%) and six females (60%) with a median age of 63.5 years (range 50-75 years). Median body mass index (BMI) was 22.89 kg/m2 (range 19.92-26.84 kg/m2). Nine patients were diagnosed with colorectal cancer, and one patient was diagnosed with a rectal gastrointestinal tumor. One patient underwent anterior resection and cholecystectomy simultaneously. Mean operation time was 222 min (range 142-316 min), and mean wound size was 3.25 cm (range 2.5-4.5 cm). Nine patients underwent surgery with single incision through which a single-port trocar was inserted, and one patient had one additional port for drain insertion. Mean hospital stay was 6 days (range 4-8 days) with one postoperative complication of bleeding requiring transfusion, but there was no readmission within 30 days. Conclusions: Overall, our experience with single-port robotic colorectal surgery has been promising. With only one patient with additional port for drain insertion, all nine patients underwent SP-robotic surgery with single incision for colon as well as rectal surgeries. Compared to an average postoperative length of stay of 6.5-8 days in laparoscopic colorectal surgeries reported in literature, SP-robotic surgery 33showed faster recovery of 6 days highlighting its benefits in patient recovery and satisfaction.

2.
Antioxidants (Basel) ; 13(5)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38790646

RESUMO

In this study, we investigated the hepatoprotective effects of an ethanol extract of Sophora flavescens Aiton (ESF) on an alcohol-induced liver disease mouse model. Alcoholic liver disease (ALD) was caused by the administration of ethanol to male C57/BL6 mice who were given a Lieber-DeCarli liquid diet, including ethanol. The alcoholic fatty liver disease mice were orally administered ESF (100 and 200 mg/kg bw/day) or silymarin (50 mg/kg bw/day), which served as a positive control every day for 16 days. The findings suggest that ESF enhances hepatoprotective benefits by significantly decreasing serum levels of aspartate transaminase (AST) and alanine transaminase (ALT), markers for liver injury. Furthermore, ESF alleviated the accumulation of triglyceride (TG) and total cholesterol (TC), increased serum levels of superoxide dismutase (SOD) and glutathione (GSH), and improved serum alcohol dehydrogenase (ADH) activity in the alcoholic fatty liver disease mice model. Cells and organisms rely on the Kelch-like ECH-associated protein 1- Nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2) system as a critical defensive mechanism in response to oxidative stress. Therefore, Nrf2 plays an important role in ALD antioxidant responses, and its level is decreased by increased reactive oxidation stress (ROS) in the liver. ESF increased Nrf2, which was decreased in ethanol-damaged livers. Additionally, four polyphenol compounds were identified through a qualitative analysis of the ESF using LC-MS/MS. This study confirmed ESF's antioxidative and hangover-elimination effects and suggested the possibility of using Sophora flavescens Aiton (SF) to treat ALD.

3.
Antioxidants (Basel) ; 13(5)2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38790680

RESUMO

Inflammatory bowel disease (IBD) is a chronic inflammatory condition caused by the disruption of the intestinal barrier. The intestinal barrier is maintained by tight junctions (TJs), which sustain intestinal homeostasis and prevent pathogens from entering the microbiome and mucosal tissues. Ziziphus jujuba Miller (Z. jujuba) is a natural substance that has been used in traditional medicine as a therapy for a variety of diseases. However, in IBD, the efficacy of Z. jujuba is unknown. Therefore, we evaluated ZJB in Caco2 cells and a dextran sodium sulfate (DSS)-induced mouse model to demonstrate its efficacy in IBD. Z. jujuba extracts were prepared using 70% ethanol and were named ZJB. ZJB was found to be non-cytotoxic and to have excellent antioxidant effects. We confirmed its anti-inflammatory properties via the down-regulation of inflammatory factors, including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). To evaluate the effects of ZJB on intestinal barrier function and TJ improvement, the trans-epithelial electrical resistance (TEER) and fluorescein isothiocyanate-dextran 4 kDa (FITC-Dextran 4) permeability were assessed. The TEER value increased by 61.389% and permeability decreased by 27.348% in the 200 µg/mL ZJB group compared with the 50 ng/mL IL-6 group after 24 h. Additionally, ZJB alleviated body weight loss, reduced the disease activity index (DAI) score, and induced colon shortening in 5% DSS-induced mice; inflammatory cytokines, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were down-regulated in the serum. TJ proteins, such as Zonula occludens (ZO)-1 and occludin, were up-regulated by ZJB in an impaired Caco2 mouse model. Additionally, according to the liquid chromatography results, in tandem with mass spectrometry (LC-MS/MS) analysis, seven active ingredients were detected in ZJB. In conclusion, ZJB down-regulated inflammatory factors, protected intestinal barrier function, and increased TJ proteins. It is thus a safe, natural substance with the potential to be used as a therapeutic agent in IBD treatment.

4.
Int J Pharm ; 657: 124177, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38697582

RESUMO

We present a promising method for producing amorphous drug particles using a nozzle-free ultrasonic nebulizer with polymers, specifically polyvinylpyrrolidone (PVP), poly(acrylic acid) (PAA), and Eudragit® S 100 (EUD). Model crystalline phase drugs-Empagliflozin, Furosemide, and Ilaprazole-are selected. This technique efficiently produces spherical polymer-drug composite particles and demonstrates enhanced stability against humidity and thermal conditions, compared to the drug-only amorphous particles. The composite particles exhibit improved water dissolution compared to the original crystalline drugs, indicating potential bioavailability enhancements. While there are challenges, including the need for continuous water supply for ultrasonic component cooling, dependency on the solubility of polymers and drugs in volatile organic solvents, and mildly elevated temperatures for solvent evaporation, our method offers significant advantages over traditional approaches. It provides a straightforward, flexible process adaptable to various drug-polymer combinations and consistently yields spherical amorphous solid dispersion (ASD) particles with a narrow size distribution. These attributes make our method a valuable advancement in pharmaceutical drug formulation and delivery.


Assuntos
Nebulizadores e Vaporizadores , Tamanho da Partícula , Polímeros , Polímeros/química , Estabilidade de Medicamentos , Solubilidade , Composição de Medicamentos/métodos , Resinas Acrílicas/química , Povidona/química , Ultrassom , Ácidos Polimetacrílicos/química , Furosemida/química , Química Farmacêutica/métodos
5.
Respir Med ; 230: 107679, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38797345

RESUMO

The Lancet Commissions on COPD recommended a new classification based on five main risk factors. Patients with COPD were prospectively enrolled in a Korean COPD subgroup study cohort between April 2012 and June 2022. Patients were classified according to the etiologies (Type 1: Genetically determined (COPD-G), Type 2: Abnormal lung development (COPD-D), Type 3: Infections (COPD-I), Type 4: Cigarette smoking (COPD-C), Type 5: Biomass and pollution (COPD-P)). The database enrolled 3476 patients. Among 3392 patients, 52 (2 %), 1339 (39 %), 2930 (86 %), and 2221 (65 %) were compatible with type 2 (COPD-D), 3 (COPD-I), 4 (COPD-C), and 5 (COPD-P), respectively. Most patients (71 %, 2405) had multiple risk factors contributing to their COPD. However, 93, 712, and 182 patients had only type 3 (COPD-I), 4 (COPD-C), and 5 (COPD-P), respectively. Type 3 (COPD-I) only patients were significantly younger, more often female, and had lower lung function. Both the rate and frequency of severe exacerbations were significantly higher in type 3 (COPD-I) only patients (p = 0.038 and p = 0.048, respectively). Compared with type 5 (COPD-P) only, type 3 (COPD-I) only was significantly associated with the risk of severe exacerbation (Odds ratio, 5.7 [95 % CI, 1.0-32.4]; P = 0.049, incident rate ratio, 8.7 [95 % CI, 1.7-44.0]; P = 0.009). Many patients were affected by multiple factors. Therefore, it is important to consider not only smoking history, but also other potential risk factors when evaluating patients with COPD. Further research is needed to explore the implications of this new COPD classification system for clinical practice and treatment strategies.

6.
Animals (Basel) ; 14(7)2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38612332

RESUMO

Sinus venosus atrial septal defects (SVASDs), concurrent with partial anomalous pulmonary venous connections (PAPVCs), are a rare congenital heart disease in dogs. Surgical correction is essential when clinical signs or significant hemodynamic changes are present. We aimed to report on the successful surgical correction of an SVASD with PAPVCs, using a computed tomography (CT)-based customized 3D cardiac model. A 10-month-old male poodle was referred for corrective surgery for an ASD. Echocardiography confirmed a hemodynamically significant left-to-right shunting flow through an interatrial septal defect and severe right-sided heart volume overload. For a comprehensive diagnosis, a CT scan was performed, which confirmed an SVASD with PAPVCs. A customized 3D cardiac model was used for preoperative decision-making and surgical rehearsal. The defect was repaired using an autologous pericardial patch under a cardiopulmonary bypass (CPB). Temporary pacing was applied for sinus bradycardia and third-degree atrioventricular block. The patient recovered from the anesthesia without further complications. The pacemaker was removed during hospitalization and the patient was discharged without complications 2 weeks post-surgery. At the three-month follow-up, there was no shunting flow in the interatrial septum and the right-sided volume overload had been resolved. The cardiac medications were discontinued, and there were no complications. This report indicates the validity of surgical correction under CPB for an SVASD with PAPVCs, and the advantages of utilizing a CT-based 3D cardiac model for preoperative planning to increase the surgical success rate.

7.
Arch Plast Surg ; 51(2): 208-211, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38596157

RESUMO

Intraneural hematoma is a rare disease that results in an impaired nerve function because of bleeding around the peripheral nerve, with only 20 cases reported. Trauma, neoplasm, and bleeding disorders are known factors for intraneural hematoma. However, here we report atypical features of asymptomatic and spontaneous intraneural hematoma which are difficult to diagnose. A 60-year-old woman visited our clinic with the complaint of a palpable mass on the right calf. She reported no medical history or trauma to the right calf and laboratory findings showed normal coagulopathy. Ultrasonography was performed, which indicated hematoma near saphenous vein and sural nerve or neurogenic tumor. We performed surgical exploration and intraneural hematoma was confirmed on sural nerve. Meticulous paraneuriotomy and evacuation was performed without nerve injury. Histological examination revealed intraneural hematoma with a vascular wall. No neurologic symptoms were observed. In literature review, we acknowledge that understanding anatomy of nerve, using ultrasonography as a diagnostic tool and surgical decompression is key for intraneural hematoma. Our case report may help establish the implications of diagnosis and treatment. Also, we suggested surgical treatment is necessary even in cases that do not present symptoms because neurological symptoms and associated symptoms may occur later.

8.
Ann Surg Treat Res ; 106(4): 189-194, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38586552

RESUMO

Purpose: Recent advances in the treatment of breast cancer have led to the improvement of breast cancer patient's survival. With the prolonged survival of these patients, pregnancy became an important issue, especially in young cancer patient aged 35 years or under. Increased hormone levels during pregnancy, however, raise concerns about elevating the risk of cancer recurrence. The aim of this study was to validate the notion of increased risk associated with pregnancy after breast cancer treatment in young patients. Methods: From January 2009 to December 2020, newly diagnosed breast cancer patients 35 years old or under who underwent optimal surgery in Korea University Guro Hospital were enrolled in this study. Patients were categorized into 3 groups: nulliparous, pregnancy prior to treatment of breast cancer, and patients with pregnancy after breast cancer treatment. Their overall survival and disease-free survival were evaluated. Results: A total of 107 patients were enrolled in this study. Thirteen patients (12.1%) conceived and successfully delivered. The mean follow-up period after surgery was 58.9 (± 33.5) months. There was no significant difference in overall survival (P = 0.608) and disease-free survival (P = 0.591) among different groups. Conclusion: In young patients, pregnancy after treatment for breast cancer did not affect their overall survival or diseasefree survival as compared to nullipara or previously delivered groups. Therefore, pregnancy counseling should not be prevented in young breast cancer patients 35 years old or under.

9.
Korean J Neurotrauma ; 20(1): 17-26, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38576499

RESUMO

Objective: This study aims to explore the epidemiology and outcomes of severe traumatic brain injury (TBI) in Incheon, focusing on regional characteristics using data from a local trauma center. Methods: From January 2018 to December 2022, 559 patients with severe TBI were studied. We analyzed factors related to demography, prehospitalization, surgery, complications, and clinical outcomes, including intensive care unit stay, ventilator use, hospital stay, mortality, and Glasgow outcome scale (GOS) scores at discharge and after 6 months. Results: In this study, most severe TBI patients were in the 60-79 age range, constituting 37.4% of cases. Most patients (74.1%) used public emergency medical services for transportation, and 75.3% arrived directly at the hospital, a significantly higher proportion compared to transferred patients. Timewise, 40.0% reached the hospital within an hour of injury. Complication rates stood at 16.1%, with pneumonia being the most common. The mortality rate was 44.0%, and at discharge, 81.2% of patients had unfavorable outcomes (GOS 1-3), reducing to 70.1% at 6 months. Conclusion: As a pioneering study at Incheon's trauma center, this research provides insights into severe TBI outcomes, enhancing understanding by contrasting local and national data.

10.
Int J Mol Sci ; 25(8)2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38674135

RESUMO

Colorectal cancer (CRC) is the third most prevalent cancer to be diagnosed, and it has a substantial mortality rate. Despite numerous studies being conducted on CRC, it remains a significant health concern. The disease-free survival rates notably decrease as CRC progresses, emphasizing the urgency for effective diagnostic and therapeutic approaches. CRC development is caused by environmental factors, which mostly lead to the disruption of signaling pathways. Among these pathways, the Wingless/Integrated (Wnt) signaling pathway, Phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway, Mitogen-Activated Protein Kinase (MAPK) signaling pathway, Transforming Growth Factor-ß (TGF-ß) signaling pathway, and p53 signaling pathway are considered to be important. These signaling pathways are also regulated by non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). They have emerged as crucial regulators of gene expression in CRC by changing their expression levels. The altered expression patterns of these ncRNAs have been implicated in CRC progression and development, suggesting their potential as diagnostic and therapeutic targets. This review provides an overview of the five key signaling pathways and regulation of ncRNAs involved in CRC pathogenesis that are studied to identify promising avenues for diagnosis and treatment strategies.


Assuntos
Neoplasias Colorretais , Regulação Neoplásica da Expressão Gênica , RNA não Traduzido , Transdução de Sinais , Humanos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Animais
11.
Sci Rep ; 14(1): 8504, 2024 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-38605094

RESUMO

This work aims to investigate the clinical feasibility of deep learning-based synthetic CT images for cervix cancer, comparing them to MR for calculating attenuation (MRCAT). Patient cohort with 50 pairs of T2-weighted MR and CT images from cervical cancer patients was split into 40 for training and 10 for testing phases. We conducted deformable image registration and Nyul intensity normalization for MR images to maximize the similarity between MR and CT images as a preprocessing step. The processed images were plugged into a deep learning model, generative adversarial network. To prove clinical feasibility, we assessed the accuracy of synthetic CT images in image similarity using structural similarity (SSIM) and mean-absolute-error (MAE) and dosimetry similarity using gamma passing rate (GPR). Dose calculation was performed on the true and synthetic CT images with a commercial Monte Carlo algorithm. Synthetic CT images generated by deep learning outperformed MRCAT images in image similarity by 1.5% in SSIM, and 18.5 HU in MAE. In dosimetry, the DL-based synthetic CT images achieved 98.71% and 96.39% in the GPR at 1% and 1 mm criterion with 10% and 60% cut-off values of the prescription dose, which were 0.9% and 5.1% greater GPRs over MRCAT images.


Assuntos
Aprendizado Profundo , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/diagnóstico por imagem , Estudos de Viabilidade , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Planejamento da Radioterapia Assistida por Computador/métodos
12.
Br J Cancer ; 130(9): 1571-1584, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38467827

RESUMO

BACKGROUND: Molecular analysis of advanced tumors can increase tumor heterogeneity and selection bias. We developed a robust prognostic signature for gastric cancer by comparing RNA expression between very rare early gastric cancers invading only mucosal layer (mEGCs) with lymph node metastasis (Npos) and those without metastasis (Nneg). METHODS: Out of 1003 mEGCs, all Npos were matched to Nneg using propensity scores. Machine learning approach comparing Npos and Nneg was used to develop prognostic signature. The function and robustness of prognostic signature was validated using cell lines and external datasets. RESULTS: Extensive machine learning with cross-validation identified the prognostic classifier consisting of four overexpressed genes (HDAC5, NPM1, DTX3, and PPP3R1) and two downregulated genes (MED12 and TP53), and enabled us to develop the risk score predicting poor prognosis. Cell lines engineered to high-risk score showed increased invasion, migration, and resistance to 5-FU and Oxaliplatin but maintained sensitivity to an HDAC inhibitor. Mouse models after tail vein injection of cell lines with high-risk score revealed increased metastasis. In three external cohorts, our risk score was identified as the independent prognostic factor for overall and recurrence-free survival. CONCLUSION: The risk score from the 6-gene classifier can successfully predict the prognosis of gastric cancer.


Assuntos
Biomarcadores Tumorais , Mucosa Gástrica , Neoplasias Gástricas , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Humanos , Prognóstico , Animais , Camundongos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Mucosa Gástrica/patologia , Mucosa Gástrica/metabolismo , Metástase Linfática/genética , Feminino , Masculino , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Aprendizado de Máquina , Pessoa de Meia-Idade
13.
Poult Sci ; 103(5): 103580, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38428354

RESUMO

Despite the acknowledged significance of nutrition in bone development, effects of methionine (Met) and cysteine (Cys) on bone quality remain under-researched, particularly during Eimeria challenge. We investigated the effects of different supplemental Met to Cys ratios (MCR) on bone quality of broilers under Eimeria challenge. A total of 720 fourteen-day old Cobb500 broilers were allocated into a 5 × 2 factorial arrangement. Five diets with Met and Cys supplemented at MCR of 100:0, 75:25, 50:50, 25:75, and 0:100 were fed to the birds with or without Eimeria challenge. Body composition was measured by dual energy x-ray absorptiometry, and the femur bone characteristics were assessed by microtomography. Data were analyzed by two-way ANOVA and orthogonal polynomial contrast. The results reaffirmed the detrimental effects of Eimeria challenge on bone quality. On 9 d post inoculation (DPI), significant interaction effects were found for whole body bone mineral content (BMC), lean tissue weight, and body weight (P < 0.05); in the nonchallenged group (NCG), these parameters linearly decreased as MCR decreased (P < 0.05). In the challenged group (CG), body weight and lean tissue weight were unaffected by MCR, and BMC linearly increased as MCR decreased (P < 0.05). For the cortical bone of femoral metaphysis on 6 DPI, bone mineral density (BMD) linearly increased as MCR decreased (P < 0.05). Bone volume to tissue volume ratio (BV/TV) in the CG linearly increased as MCR decreased (P < 0.05). On 9 DPI, BMC and TV linearly increased as MCR decreased (P < 0.05) in the NCG. BMD and BV/TV changed quadratically as MCR decreased (P < 0.05). For the trabecular bone of femoral metaphysis on 9 DPI, BV/TV, and trabecular number linearly increased as MCR decreased (P < 0.05) in the NCG. For the femoral diaphysis, BV, TV, BMC on 6 DPI, and BMD on 9 DPI linearly increased as MCR decreased (P < 0.05). In conclusion, this study showed that both Eimeria challenge and varying supplemental MCR could influence bone quality of broilers.


Assuntos
Absorciometria de Fóton , Ração Animal , Densidade Óssea , Galinhas , Coccidiose , Cisteína , Dieta , Suplementos Nutricionais , Eimeria , Metionina , Doenças das Aves Domésticas , Animais , Galinhas/fisiologia , Eimeria/fisiologia , Ração Animal/análise , Metionina/administração & dosagem , Metionina/farmacologia , Metionina/análogos & derivados , Coccidiose/veterinária , Coccidiose/parasitologia , Absorciometria de Fóton/veterinária , Suplementos Nutricionais/análise , Dieta/veterinária , Densidade Óssea/efeitos dos fármacos , Doenças das Aves Domésticas/parasitologia , Cisteína/farmacologia , Cisteína/administração & dosagem , Cisteína/análogos & derivados , Microtomografia por Raio-X/veterinária , Masculino , Relação Dose-Resposta a Droga , Fêmur/efeitos dos fármacos , Distribuição Aleatória
14.
Nutrients ; 16(5)2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38474770

RESUMO

Sepsis, a leading cause of death worldwide, is a harmful inflammatory condition that is primarily caused by an endotoxin released by Gram-negative bacteria. Effective targeted therapeutic strategies for sepsis are lacking. In this study, using an in vitro and in vivo mouse model, we demonstrated that CM1, a derivative of the natural polyphenol chrysin, exerts an anti-inflammatory effect by inducing the expression of the ubiquitin-editing protein TNFAIP3 and the NAD-dependent deacetylase sirtuin 1 (SIRT1). Interestingly, CM1 attenuated the Toll-like receptor 4 (TLR4)-induced production of inflammatory cytokines by inhibiting the extracellular-signal-regulated kinase (ERK)/MAPK and nuclear factor kappa B (NF-κB) signalling pathways. In addition, CM1 induced the expression of TNFAIP3 and SIRT1 on TLR4-stimulated primary macrophages; however, the anti-inflammatory effect of CM1 was abolished by the siRNA-mediated silencing of TNFAPI3 or by the genetic or pharmacologic inhibition of SIRT1. Importantly, intravenous administration of CM1 resulted in decreased susceptibility to endotoxin-induced sepsis, thereby attenuating the production of pro-inflammatory cytokines and neutrophil infiltration into the lung compared to control mice. Collectively, these findings demonstrate that CM1 has therapeutic potential for diverse inflammatory diseases, including sepsis.


Assuntos
Flavonoides , Sepse , Choque Séptico , Camundongos , Animais , Sirtuína 1/metabolismo , Receptor 4 Toll-Like/metabolismo , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Choque Séptico/tratamento farmacológico , Endotoxinas , Citocinas/metabolismo , Sepse/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico
15.
ACS Appl Mater Interfaces ; 16(11): 13662-13673, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38441999

RESUMO

In this study, we present our successful fabrication of commercial-grade pure aluminum anode foil (99.5%, 2NAl) with an ultrafine-grained (UFG) microstructure and high hardness, achieved through cold rolling. Under identical rolling conditions, a coarse-grained microstructure with a low hardness was attained from the high-purity Al foil (99.99%, 4NAl). The UFG 2NAl foil exhibited enhanced lithium-ion diffusivity and reduced nucleation and activation overpotentials for forming the ß-LiAl phase compared to the 4NAl foil. The high-density grain boundaries in the UFG 2NAl foil facilitated the rapid formation of a uniform ß-LiAl phase layer on its surface, thereby mitigating mechanical damage within the ß-LiAl phase layer caused by volume changes during the lithiation and delithiation processes. The high hardness of the UFG 2NAl sample effectively prevented macroscopic plastic deformation during cycling, thus preserving the integrity of the ß-LiAl phase layer and inhibiting the formation of cracks within the unreacted Al matrix. The collective advantages of reduced overpotential, enhanced Li-ion diffusivity, and high resistance to mechanical damage and plastic deformation in UFG 2NAl contribute to its superior durability and capacity retention compared to the high-purity Al in electrochemical cycling.

16.
Int J Mol Sci ; 25(5)2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38474212

RESUMO

Calcium-activated potassium (KCa) channels are ubiquitously expressed throughout the body and are able to regulate membrane potential and intracellular calcium concentrations, thereby playing key roles in cellular physiology and signal transmission. Consequently, it is unsurprising that KCa channels have been implicated in various diseases, making them potential targets for pharmaceutical interventions. Over the past two decades, numerous studies have been conducted to develop KCa channel-targeting drugs, including those for disorders of the central and peripheral nervous, cardiovascular, and urinary systems and for cancer. In this review, we synthesize recent findings regarding the structure and activating mechanisms of KCa channels. We also discuss the role of KCa channel modulators in therapeutic medicine. Finally, we identify the major reasons behind the delay in bringing these modulators to the pharmaceutical market and propose new strategies to promote their application.


Assuntos
Sistema Cardiovascular , Canais de Potássio Cálcio-Ativados , Cálcio/metabolismo , Sistema Cardiovascular/metabolismo , Potenciais da Membrana , Preparações Farmacêuticas , Humanos
17.
Transplant Proc ; 56(3): 701-704, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38548510

RESUMO

BACKGROUND: Liver fibrosis is a chronic inflammatory disease that progresses and has a high mortality rate. This study was performed to investigate the protective effect of rapamycin on experimentally induced chronic liver injury in mice models using both biochemical parameters of liver function enzymes. METHODS: Twenty-four mice were divided randomly into 4 equal groups: [1] the normal group, n = 6; [2] the liver fibrosis (LF) group, n = 6; [3] the LF with the treatment of rapamycin group, n = 6; [4] the LF with the treatment of silimaryn, n = 6. RESULTS: In the group receiving oral administration of rapamycin, aspartate aminotransferase, alanine aminotransferase, urea, and creatinine were found to significantly decrease compared to the liver fibrosis group. Rapamycin, in the orally administered group, demonstrated a statistically significant decrease in the expression of interleukin (IL) 10, IL-1B, inducible nitric oxide synthase, and tumor necrosis factor alpha compared to the liver fibrosis group. CONCLUSIONS: In this study, we explored the potential therapeutic effects of rapamycin on liver fibrosis in an animal model.


Assuntos
Modelos Animais de Doenças , Cirrose Hepática , Camundongos Endogâmicos C57BL , Sirolimo , Animais , Sirolimo/farmacologia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Camundongos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Aspartato Aminotransferases/sangue , Alanina Transaminase/sangue , Óxido Nítrico Sintase Tipo II/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Creatinina/sangue
18.
Poult Sci ; 103(6): 103660, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38552568

RESUMO

Coccidiosis caused by Eimeria spp. results in substantial economic losses in the poultry industry. The objective of this study was to investigate the effects of dietary supplementation with n-3 polyunsaturated fatty acids-enriched fish oil on growth performance, intestinal barrier integrity, and intestinal immune response of broilers challenged with Eimeria spp. A total of 576 fourteen-day-old broilers were randomly assigned in a completely randomized design with a 3 × 2 factorial arrangement, comprising 2 diets supplemented with either 5% fish oil or 5% soybean oil, and 3 Eimeria spp. infection levels: a nonchallenge control, a low dose of Eimeria challenge, and a high challenge dose. The results of the study revealed significant interactions between diet and Eimeria challenge to parameters of gut barrier integrity and feed intake. A significant interaction was observed in feed intake between 5 and 8 d postinfection (DPI), where the fish oil groups exhibited a higher amount of feed intake compared to the soybean oil diet groups after coccidiosis infection. The effects of the fish oil diet resulted in enhanced gut barrier integrity, as evidenced by a trend of decreased gastrointestinal leakage and a lower mean of small intestine lesion scores after Eimeria challenge. Additionally, significant interactions were noted between Eimeria spp. challenge and diet regarding jejunal crypt depth. The positive impact of the fish oil diet was particularly noticeable with the high Eimeria challenge dose. Overall, these findings underscore the relationship between the fish oil diet and Eimeria challenge on broiler chicken intestinal health. Dietary supplementation of fish oil has the potential to maintain small intestine barrier integrity with severe Eimeria infection conditions.


Assuntos
Ração Animal , Galinhas , Coccidiose , Dieta , Suplementos Nutricionais , Eimeria , Ácidos Graxos Ômega-3 , Óleos de Peixe , Doenças das Aves Domésticas , Animais , Galinhas/fisiologia , Coccidiose/veterinária , Coccidiose/parasitologia , Coccidiose/imunologia , Óleos de Peixe/administração & dosagem , Óleos de Peixe/farmacologia , Doenças das Aves Domésticas/parasitologia , Ração Animal/análise , Eimeria/fisiologia , Dieta/veterinária , Suplementos Nutricionais/análise , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/farmacologia , Intestinos/parasitologia , Intestinos/efeitos dos fármacos , Distribuição Aleatória , Masculino
19.
J Clin Med ; 13(6)2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38541832

RESUMO

Background: Wagstaffe fracture constitutes an indirect injury to the AITFL and can precipitate syndesmotic instability. The prevailing fixation methods often involve the use of mini-screws or K-wires, with absorbable suture repair reserved for cases with small or comminuted fragments exhibiting instability. In this study, we devised a mini-plate fixation method capable of securing the fracture fragment irrespective of its size or condition. Methods: A retrospective chart review was conducted on patients who underwent surgery for ankle fractures between May 2022 and October 2023. The surgical technique involved direct fixation of the Wagstaffe fracture using mini-plate fixation. Radiologic evaluation was performed using postoperative CT images, and clinical outcomes were assessed using the OMAS and VAS. Results: Fourteen patients with an average age of 62.5 years were included. Most fractures were associated with the supination-external rotation type. The average preoperative OMAS significantly improved from 5.95 to 83.57 postoperatively. The average VAS score decreased from 7.95 preoperatively to 0.19 postoperatively. Conclusions: The mini-plate technique for Wagstaffe fractures exhibited dependable fixation strength, effective fracture reduction, a minimal complication rate, and judicious surgical procedure duration.

20.
Stem Cell Res Ther ; 15(1): 69, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38454492

RESUMO

BACKGROUND: A significant unmet need in inflammatory bowel disease is the lack of anti-fibrotic agents targeting intestinal fibrosis. This study aimed to investigate the anti-fibrogenic properties and mechanisms of the conditioned medium (CM) from human umbilical cord/placenta-derived mesenchymal stem cells (UC/PL-MSC-CM) in a murine intestinal fibrosis model and human primary intestinal myofibroblasts (HIMFs). METHODS: UC/PL-MSC-CM was concentrated 15-fold using a 3 kDa cut-off filter. C57BL/6 mice aged 7 weeks old were randomly assigned to one of four groups: (1) control, (2) dextran sulfate sodium (DSS), (3) DSS + CM (late-phase treatment), and (4) DSS + CM (early-phase treatment). Chronic DSS colitis and intestinal fibrosis was induced by three cycles of DSS administration. One DSS cycle consisted of 7 days of oral DSS administration (1.75%, 2%, and 2.5% DSS), followed by 14 days of drinking water. UC/PL-MSC-CM was intraperitoneally administered in the late phase (from day 50, 10 times) or early phase (from day 29, 10 times) of DSS cycles. HIMFs were treated with TGF-ß1 and co-treated with UC/PL-MSC-CM (10% of culture media) in the cellular model. RESULTS: In the animal study, UC/PL-MSC-CM reduced submucosa/muscularis propria thickness and collagen deposition, which improved intestinal fibrosis in chronic DSS colitis. The UC/PL-MSC-CM significantly reduced the expressions of procollagen1A1 and α-smooth muscle actin, which DSS significantly elevated. The anti-fibrogenic effect was more apparent in the UC-MSC-CM or early-phase treatment model. The UC/PL-MSC-CM reduced procollagen1A1, fibronectin, and α-smooth muscle actin expression in HIMFs in the cellular model. The UC/PL-MSC-CM downregulated fibrogenesis by suppressing RhoA, MRTF-A, and SRF expression. CONCLUSIONS: Human UC/PL-MSC-CM inhibits TGF-ß1-induced fibrogenic activation in HIMFs by blocking the Rho/MRTF/SRF pathway and chronic DSS colitis-induced intestinal fibrosis. Thus, it may be regarded as a novel candidate for stem cell-based therapy of intestinal fibrosis.


Assuntos
Colite , Células-Tronco Mesenquimais , Humanos , Camundongos , Animais , Fator de Crescimento Transformador beta1/metabolismo , Meios de Cultivo Condicionados/farmacologia , Meios de Cultivo Condicionados/metabolismo , Actinas/metabolismo , Camundongos Endogâmicos C57BL , Colite/induzido quimicamente , Colite/terapia , Colite/metabolismo , Fatores Imunológicos , Fibrose , Células-Tronco Mesenquimais/metabolismo , Cordão Umbilical , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças
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