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1.
Sci Rep ; 14(1): 8837, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632294

RESUMO

In this study, we investigate the communication networks of urban, suburban, and rural communities from three US Midwest counties through a stochastic model that simulates the diffusion of information over time in disaster and in normal situations. To understand information diffusion in communities, we investigate the interplay of information that individuals get from online social networks, local news, government sources, mainstream media, and print media. We utilize survey data collected from target communities and create graphs of each community to quantify node-to-node and source-to-node interactions, as well as trust patterns. Monte Carlo simulation results show the average time it takes for information to propagate to 90% of the population for each community. We conclude that rural, suburban, and urban communities have different inherent properties promoting the varied flow of information. Also, information sources affect information spread differently, causing degradation of information speed if any source becomes unavailable. Finally, we provide insights on the optimal investments to improve disaster communication based on community features and contexts.

2.
JAMA Surg ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38656413

RESUMO

Importance: Surgical site infections (SSIs) are prevalent hospital-acquired infections with significant patient impacts and global health care burdens. The World Health Organization recommends using wound protector devices in abdominal surgery as a preventive measure to lower the risk of SSIs despite limited evidence. Objective: To examine the efficacy of a dual-ring, plastic wound protector in lowering the SSI rate in open gastrointestinal (GI) surgery irrespective of intra-abdominal contamination levels. Design, Setting, and Participants: This multicenter, patient-blinded, parallel-arm randomized clinical trial was conducted from August 2017 to October 2022 at 13 hospitals in an academic setting. Patients undergoing open abdominal bowel surgery (eg, for bowel perforation) were eligible for inclusion. Intervention: Patients were randomized 1:1 to a dual-ring, plastic wound protector to protect the incision site of the abdominal wall (experimental group) or a conventional surgical gauze (control group). Main Outcomes and Measures: The primary end point was the rate of SSI within 30 days of open GI surgery. Results: A total of 458 patients were randomized; after 1 was excluded from the control group, 457 were included in the intention-to-treat analysis (mean [SD] age, 58.4 [12.1] years; 256 [56.0%] male; 341 [74.6%] with a clean-contaminated wound): 229 in the wound protector group and 228 in the surgical gauze group. The overall SSI rate in the intention-to-treat analysis was 15.7% (72 of 458 patients). The SSI rate for the wound protector was 10.9% (25 of 229 patients) compared with 20.5% (47 of 229 patients) with surgical gauze. The wound protector significantly reduced the risk of SSI, with a relative risk reduction (RRR) of 46.81% (95% CI, 16.64%-66.06%). The wound protector significantly decreased the SSI rate for clean-contaminated wounds (RRR, 43.75%; 95% CI, 3.75%-67.13%), particularly for superficial SSIs (RRR, 42.50%; 95% CI, 7.16%-64.39%). Length of hospital stay was similar in both groups (mean [SD], 15.2 [10.5] vs 15.3 [10.2] days), as were the overall postoperative complication rates (20.1% vs 18.8%). Conclusions and Relevance: This randomized clinical trial found a significant reduction in SSI rates when a plastic wound protector was used during open GI surgery compared with surgical gaze, supporting the World Health Organization recommendation for use of wound protector devices in abdominal surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT03170843.

3.
Nat Commun ; 15(1): 46, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167804

RESUMO

Addressing age-related immunological defects through therapeutic interventions is essential for healthy aging, as the immune system plays a crucial role in controlling infections, malignancies, and in supporting tissue homeostasis and repair. In our study, we show that stimulating toll-like receptor 5 (TLR5) via mucosal delivery of a flagellin-containing fusion protein effectively extends the lifespan and enhances the healthspan of mice of both sexes. This enhancement in healthspan is evidenced by diminished hair loss and ocular lens opacity, increased bone mineral density, improved stem cell activity, delayed thymic involution, heightened cognitive capacity, and the prevention of pulmonary lung fibrosis. Additionally, this fusion protein boosts intestinal mucosal integrity by augmenting the surface expression of TLR5 in a certain subset of dendritic cells and increasing interleukin-22 (IL-22) secretion. In this work, we present observations that underscore the benefits of TLR5-dependent stimulation in the mucosal compartment, suggesting a viable strategy for enhancing longevity and healthspan.


Assuntos
Longevidade , Receptor 5 Toll-Like , Animais , Camundongos , Flagelina/metabolismo , Mucosa Intestinal/metabolismo , Longevidade/genética , Pulmão/metabolismo
5.
Adv Healthc Mater ; 13(2): e2301124, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37820720

RESUMO

A nanopatterned interdigitated electrode array (nanoIEA)-based impedance assay is developed for quantitative real-time measurement of aligned endothelial cell (EC) barrier functions in vitro. A bioinspired poly(3,4-dihydroxy-L-phenylalanine) (poly (l-DOPA)) coating is applied to improve the human brain EC adhesion onto the Nafion nanopatterned surfaces. It is found that a poly (l-DOPA)-coated Nafion grooved nanopattern makes the human brain ECs orient along the nanopattern direction. Aligned human brain ECs on Nafion nanopatterns exhibit increased expression of genes encoding tight and adherens junction proteins. Aligned human brain ECs also have enhanced impedance and resistance versus unaligned ones. Treatment with a glycogen synthase kinase-3 inhibitor (GSK3i) further increases impedance and resistance, suggesting synergistic effects occur on the cell-cell tightness of in vitro human brain ECs via a combination of anisotropic matrix nanotopography and GSK3i treatment. It is found that this enhanced cell-cell tightness of the combined approach is accompanied by increased expression of claudin protein. These data demonstrate that the proposed nanoIEA assay integrated with poly (l-DOPA)-coated Nafion nanopatterns and interdigitated electrode arrays can make not only biomimetic aligned ECs, but also enable real-time measurement of the enhanced barrier functions of aligned ECs via tighter cell-cell junctions.


Assuntos
Células Endoteliais , Polímeros de Fluorcarboneto , Levodopa , Humanos , Impedância Elétrica , Levodopa/metabolismo , Levodopa/farmacologia , Endotélio
6.
Small ; : e2308672, 2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38155506

RESUMO

Layered 2D transition metal dichalcogenides (TMDs) have been suggested as efficient substitutes for Pt-group metal electrocatalysts in the hydrogen evolution reaction (HER). However, poor catalytic activities in neutral and alkaline electrolytes considerably hinder their practical applications. Furthermore, the weak adhesion between TMDs and electrodes often impedes long-term durability and thus requires a binder. Here, a universal platform is reported for robust dual-atom doped 2D electrocatalysts with superior HER performance over a wide pH range media. V:Co-ReS2 on a wafer scale is directly grown on oxidized Ti foil by a liquid-phase precursor-assisted approach and subsequently used as highly efficient electrocatalysts. The catalytic performance surpasses that of Pt group metals in a high current regime (≥ 100 mA cm-2 ) at pH ≥ 7, with a high durability of more than 70 h in all media at 200 mA cm-2 . First-principles calculations reveal that V:Co dual doping in ReS2 significantly reduces the water dissociation barrier and simultaneously enables the material to achieve the thermoneutral Gibbs free energy for hydrogen adsorption.

7.
PLoS One ; 18(10): e0287595, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37903104

RESUMO

BACKGROUND: Small circular staplers possess the advantage of being relatively easy to use when compared to larger circular staplers. However, there is some contention as to whether the use of small circular staples in colorectal surgery increases the incidence of anastomotic strictures. This study aimed to determine whether the frequency of anastomosis site stricture formation differs depending on stapler size when performing anastomosis in colorectal surgery. METHODS: Patients who underwent surgery for colon or rectal disease between June 1, 2009, and December 31, 2021, and who had circular staplers used for the formation of intestinal anastomoses post colectomy were included in our study. Propensity score matching with a 1:1 ratio using logistic regression was performed. The primary outcome was the anastomotic stricture rate, and the secondary outcome was total anastomotic complications. RESULTS: A total of 875 patients who were operated on by surgeons using 28/29-mm and 25-mm circular staplers were included. After propensity score matching, 106 patients were assigned to each group. Anastomotic strictures occurred in two cases (1.9%) from the 25-mm group and in four cases (3.8%) from the 28/29-mm group. There were no statistically significant differences between the two groups (p = 0.683). Anastomotic complications were observed in two cases (1.9%) from the 25-mm group and in six cases (5.7%) from the 28/29-mm group; no statistically significant differences were found (p = 0.280). CONCLUSION: Circular stapler size does not influence anastomotic stricture formation in colorectal surgery.


Assuntos
Cirurgia Colorretal , Humanos , Constrição Patológica/etiologia , Constrição Patológica/epidemiologia , Pontuação de Propensão , Grampeadores Cirúrgicos/efeitos adversos , Anastomose Cirúrgica/efeitos adversos , Fístula Anastomótica/etiologia , Estudos Retrospectivos
8.
Medicine (Baltimore) ; 102(40): e35387, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37800766

RESUMO

PURPOSE: To evaluate the correlation between contrast-enhanced (CE) MRI and cerebrospinal fluid (CSF) cytology for the evaluation of leptomeningeal metastasis (LM) on MRI after targeted therapy with tyrosine kinase inhibitors. METHODS: We retrospectively reviewed the data of nonsmall cell lung cancer patients registered with NCT03257124 from May 2017 to December 2018, with progressive disease despite targeted therapy. Twenty-nine patients whose MRI scans exhibited LM at the time of registration were enrolled. During the targeted therapy with osimertinib, MRI scans, and subsequent CSF examinations were performed in every 2 months. In total, 113 MRI scans and CSF cytology data after treatment were collected. For each CE MRI scan, LM positivity was evaluated on 3D T1-weighted image (T1WI) and 2D FLAIR. The correlation between MRI and CSF cytology results and the diagnostic performance of MRI with CSF cytology as a reference standard were evaluated. RESULTS: After treatment, MRI revealed positivity for LM in 81 and negativity in 32. CSF results were positive in 69 examinations and negative in 44. The diagnostic accuracy of CE 3D T1WI and 2D FLAIR was 0.52 and 0.46, respectively. After targeted therapy, discrepancy in the CSF and MRI results tended to increase over time. The proportions of concordant MRI and CSF cytology results after targeted therapy were 66%, 58%, 62%, and 47% at the first, second, third, and fourth follow-up, respectively. CONCLUSION: The discrepancy of MRI in evaluation of LM and CSF cytology increases over time after targeted therapy with osimertinib. LM positivity on MRI could be a surrogate imaging marker in the pre- and immediate posttargeted-treatment with Osimertinib but not after sessions of osimertinib.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinomatose Meníngea , Humanos , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/patologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Carcinomatose Meníngea/tratamento farmacológico , Carcinomatose Meníngea/secundário , Estudos Retrospectivos , Ensaios Clínicos como Assunto
9.
Korean J Radiol ; 24(9): 860-870, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37634641

RESUMO

OBJECTIVE: The intra-parotid facial nerve (FN) can be visualized using three-dimensional double-echo steady-state water-excitation sequence magnetic resonance imaging (3D-DESS-WE-MRI). However, the clinical impact of FN imaging using 3D-DESS-WE-MRI before parotidectomy has not yet been explored. We compared the clinical outcomes of parotidectomy in patients with and without preoperative 3D-DESS-WE-MRI. MATERIALS AND METHODS: This prospective, non-randomized, single-institution study included 296 adult patients who underwent parotidectomy for parotid tumors, excluding superficial and mobile tumors. Preoperative evaluation with 3D-DESS-WE-MRI was performed in 122 patients, and not performed in 174 patients. FN visibility and tumor location relative to FN on 3D-DESS-WE-MRI were evaluated in 120 patients. Rates of FN palsy (FNP) and operation times were compared between patients with and without 3D-DESS-WE-MRI; propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to adjust for surgical and tumor factors. RESULTS: The main trunk, temporofacial branch, and cervicofacial branch of the intra-parotid FN were identified using 3D-DESS-WE-MRI in approximately 97.5% (117/120), 44.2% (53/120), and 25.0% (30/120) of cases, respectively. The tumor location relative to FN, as assessed on magnetic resonance imaging, concurred with surgical findings in 90.8% (109/120) of cases. Rates of temporary and permanent FNP did not vary between patients with and without 3D-DESS-WE-MRI according to PSM (odds ratio, 2.29 [95% confidence interval {CI} 0.64-8.25] and 2.02 [95% CI: 0.32-12.90], respectively) and IPTW (odds ratio, 1.76 [95% CI: 0.19-16.75] and 1.94 [95% CI: 0.20-18.49], respectively). Conversely, operation time for surgical identification of FN was significantly shorter with 3D-DESS-WE-MRI (median, 25 vs. 35 min for PSM and 25 vs. 30 min for IPTW, P < 0.001). CONCLUSION: Preoperative FN imaging with 3D-DESS-WE-MRI facilitated anatomical identification of FN and its relationship to the tumor during parotidectomy. This modality reduced operation time for FN identification, but did not significantly affect postoperative FNP rates.


Assuntos
Nervo Facial , Imageamento por Ressonância Magnética , Adulto , Humanos , Nervo Facial/diagnóstico por imagem , Estudos Prospectivos , Glândula Parótida/diagnóstico por imagem , Glândula Parótida/cirurgia , Resultado do Tratamento
10.
Clin Exp Otorhinolaryngol ; 16(4): 334-341, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37641856

RESUMO

OBJECTIVES: Acute low-tone sensorineural hearing loss (ALHL) is thought to have a different etiology from that of idiopathic sudden sensorineural hearing loss. We hypothesized that endolymphatic hydrops (EH) in the inner ear organ contributes to ALHL, even in patients without vertigo. This study investigated the presence of EH in ALHL and compared the clinical characteristics of patients with or without EH. METHODS: We retrospectively reviewed 38 patients diagnosed with ALHL without vertigo from January 2017 to March 2022. EH was measured in all patients using inner ear magnetic resonance imaging (MRI). In addition, we selected patients who showed only mid- or high-frequency hearing loss and had available MRI data as a control group and compared the ALHL and control groups. RESULTS: After treatment, the pure-tone average at low frequencies significantly improved compared to the initial hearing (P<0.001). Hearing recovery was observed in 63.1% of patients; however, the recovery rate did not differ based on the treatment method. During the follow-up period, six patients (15.8%) progressed to Meniere's disease, and 18 (47.4%) experienced recurrence. In the ALHL group, the cochlear hydrops ratio on the affected side (0.34±0.09) was significantly higher than on the contralateral side (0.29±0.12) (P=0.005), and most patients showed hydrops in the apex area of the cochlea. Compared with the control group (0.25±0.15), the ALHL group showed a significantly higher cochlear hydrops ratio (P=0.043). The correlation analysis showed a tendency for hearing thresholds at low frequencies to increase as the hydrops ratio increased, albeit without statistical significance. CONCLUSION: The cochlear hydrops ratio, especially in the apex area on the affected side, was significantly higher in patients with ALHL, suggesting that EH in the cochlea contributes to the pathogenesis of ALHL.

11.
Lab Chip ; 23(16): 3628-3638, 2023 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-37448298

RESUMO

Surgery, radiation, hormonal therapy, chemotherapy, and immunotherapy are standard treatment strategies for metastatic breast cancer. However, the heterogeneous nature of the disease poses challenges and continues to make it life-threatening. It is crucial to elucidate further the underlying signaling pathways to improve treatment efficacy. Our study established two triple-negative breast cancer cell lines (TW-1 and TW-2) that were physically deformed using 3 µm pores to investigate the relationship between cancer cell deformation and metastasis within a heterogeneous population. The physical transformation of TW-1 and TW-2 cells significantly affected their growth and migration speed, as evidenced by wound healing assays for collective cell migration and microchannel assays for single-cell migration. We conducted bulk RNA sequencing to gain insights into the genes influenced by physical deformation. Additionally, we evaluated the effects of trametinib resistance on breast cancer cell metastasis by assessing cell viability and migration rates. Interestingly, TW-1 and TW-2 cells exhibited resistance to trametinib treatment. We observed a significant upregulation of GABRA-3, a protein commonly expressed in malignant breast cancer, and the critical transcription factor Myc in TW-1 and TW-2 cells compared to the control group (Ori). However, we did not observe a significant difference in Myc expression between TW-1 and TW-2 cells. In contrast, in the trametinib-resistant cell lines (TW-1-Tra and TW-2-Tra), we found increased expression of OCT4 and SOX2 rather than GABRA-3 or Myc. These findings highlight the differential expression patterns of these genes in our study, suggesting their potential role in cancer cell deformation and drug resistance. Our study presents a potential in vitro model for metastatic and drug-resistant breast cancer cells. By investigating the correlation between cancer cell deformation and metastasis, we contribute to understanding breast cancer heterogeneity and lay the groundwork for developing improved treatment strategies.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Linhagem Celular Tumoral , Neoplasias da Mama/genética , Neoplasias da Mama/tratamento farmacológico , Transdução de Sinais , Resultado do Tratamento , Sobrevivência Celular , Proliferação de Células
12.
Ann Surg Treat Res ; 105(1): 1-9, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37441319

RESUMO

Purpose: Although the overall survival (OS) of breast cancer patients is increasing with improved detection and therapies, so is the risk of breast cancer patients developing subsequent malignancies. We investigated the OS of breast cancer survivors according to sites of second primary malignancies (SPM). The OS of the second primary hematologic malignancy (SPHM) was then compared with that of metastatic breast cancer (MBC). Methods: We retrospectively analyzed patients diagnosed with primary breast cancer between 1998 and 2019. Only those with SPM were eligible for analysis. First, the OS of patients with SPM diagnosed as the first event after the diagnosis of breast cancer was analyzed. Next, the OS of patients with SPHM, with or without breast cancer relapse, was compared with that of patients with MBC, matched using the propensity score. Results: Patients diagnosed with SPM without breast cancer relapse as the first event had a significantly better OS than did patients with MBC, but the OS of those with SPHM as the first event did not differ significantly from that of patients with MBC (hazard ratio [HR], 1.558; 95% confidence interval [CI], 0.856-2.839; P = 0.147). The OS of patients with SPHM with or without breast cancer relapse was worse than that of the MBC group after propensity score matching (HR, 1.954; 95% CI, 1.045-3.654; P = 0.036). Conclusion: Prognosis of SPM diagnosed as the first event was statistically better than that of MBC, except in case of SPHM. Patients with SPHM, with or without MBC, showed poor OS before and after propensity score matching.

13.
J Minim Invasive Surg ; 26(2): 55-63, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37347098

RESUMO

Purpose: This study aimed to compare the postoperative outcomes and patient-surveyed scar assessments of single-port laparoscopic appendectomy (SPLA) with the outcomes of multiport laparoscopic appendectomy (MPLA). Methods: Between August 2014 and November 2017, the prospective randomized study comprised 98 patients diagnosed with acute appendicitis and indicated for surgery. Fifty-one patients had MPLA and 47 patients received SPLA. The primary endpoint was the total score of Patient Scar Assessment Questionnaire (PSAQ) administered to patients 6 weeks after surgery. Results: SPLA involved a shorter median operative time than MPLA (47.5 minutes vs. 60.0 minutes, p = 0.02). There were no apparent differences in the time before diet tolerance, length of hospital stay, and postoperative complication. SPLA patients had shorter total incision length (2.0 cm vs. 2.5 cm, p < 0.01) and required fewer analgesics on the day of surgery than MPLA patients (p = 0.011). The PSAQ favored the SPLA approach, revealing significant differences in total score (48 vs. 55, p = 0.026), appearance (15 vs. 18, p = 0.002), and consciousness (8 vs. 10, p = 0.005), while satisfaction with appearance and symptoms scale did not (p = 0.162 and p = 0.690, respectively). Conclusion: The postoperative scar evaluated by the patient was better with SPLA than with MPLA, and patient satisfaction with the scar was comparable between the two techniques.

14.
Biomedicines ; 11(4)2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37189780

RESUMO

The use of intraoperative colonoscopy (IOC) to evaluate the integrity of newly created anastomosis has been advocated by some surgeons. However, whether direct visualization of fresh anastomosis can help reduce anastomotic problems is still unclear. This study investigates the impact of immediate endoscopic assessment of colorectal anastomosis on anastomotic problems. This is a retrospective study conducted at a single center. Among six hundred forty-nine patients who underwent stapled anastomosis for left-sided colorectal cancer, the anastomotic complications were compared between patients who underwent IOC and those who did not. Additionally, patients with subsequent intervention after the IOC were compared to those without the intervention. Twenty-seven patients (5.0%) developed anastomotic leakage, and six (1.1%) experienced anastomotic bleeding postoperatively. Of the patients with IOC, 70 patients received reinforcement sutures to secure anastomotic stability. Of 70 patients, 39 patients showed abnormal findings in IOC. Thirty-seven patients (94.9%) who underwent reinforcement sutures did not develop postoperative anastomotic problems. This study demonstrates that IOC assessment with reinforcement sutures does not imminently reduce the rate of anastomotic complications. However, its use may play a role in detecting early technical failure and preventing postoperative anastomotic complications.

15.
Biochem Biophys Res Commun ; 654: 94-101, 2023 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-36898229

RESUMO

The human cytomegalovirus (HCMV)-encoded US12 gene family is a group of ten predicted seven-transmembrane domain proteins that are structurally similar to G-protein-coupled receptors or transmembrane Bax inhibitor-1 motif-containing proteins; however, the roles of US12 family proteins in virus-host interactions remain to be discovered. Here, we suggest a new function of the US12 protein in regulating cellular autophagy. US12 is predominantly located to the lysosome and interacts with the lysosomal membrane protein 2 (LAMP2). A liquid chromatography-mass spectrometry (MS)/MS-based targeted proteomics analysis shows that US12 is tightly correlated with autophagy. US12 induces autophagy via upregulating ULK1 phosphorylation and subsequent LC3-II conversion, thereby accelerating autophagic flux. Moreover, HeLa cells overexpressing US12 displays intense LC3-specific staining and autolysosome formation even under nutrient-sufficient conditions. Furthermore, the physical interaction of p62/SQSTM1 with US12 is involved in the resistance to the degradation of p62/SQSTM1 by autophagy, despite the induction of both autolysosome formation and autophagic flux. Although the effect of US12 expression in HCMV infection on autophagy remains undetermined, these findings provide new insights into the viral drivers of host autophagy during HCMV evolution and pathogenesis.


Assuntos
Citomegalovirus , Proteínas Virais , Humanos , Citomegalovirus/genética , Proteínas Virais/metabolismo , Células HeLa , Proteína Sequestossoma-1/metabolismo , Proteínas de Membrana/metabolismo , Autofagia/genética
16.
Nat Commun ; 14(1): 700, 2023 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-36755029

RESUMO

The cortical actin cytoskeleton plays a critical role in maintaining intestinal epithelial integrity, and the loss of this architecture leads to chronic inflammation, as seen in inflammatory bowel disease (IBD). However, the exact mechanisms underlying aberrant actin remodeling in pathological states remain largely unknown. Here, we show that a subset of patients with IBD exhibits substantially higher levels of tripartite motif-containing protein 40 (TRIM40), a gene that is hardly detectable in healthy individuals. TRIM40 is an E3 ligase that directly targets Rho-associated coiled-coil-containing protein kinase 1 (ROCK1), an essential kinase involved in promoting cell-cell junctions, markedly decreasing the phosphorylation of key signaling factors critical for cortical actin formation and stabilization. This causes failure of the epithelial barrier function, thereby promoting a long-lived inflammatory response. A mutant TRIM40 lacking the RING, B-box, or C-terminal domains has impaired ability to accelerate ROCK1 degradation-driven cortical actin disruption. Accordingly, Trim40-deficient male mice are highly resistant to dextran sulfate sodium (DSS)-induced colitis. Our findings highlight that aberrant upregulation of TRIM40, which is epigenetically silenced under healthy conditions, drives IBD by subverting cortical actin formation and exacerbating epithelial barrier dysfunction.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Proteínas com Motivo Tripartido , Animais , Masculino , Camundongos , Actinas/metabolismo , Colite/induzido quimicamente , Colite/genética , Colite/metabolismo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/metabolismo , Intestinos , Camundongos Endogâmicos C57BL , Humanos , Proteínas com Motivo Tripartido/genética , Proteínas com Motivo Tripartido/metabolismo
17.
ACS Omega ; 8(1): 1389-1400, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36643538

RESUMO

Gold is of considerable interest for electrochemical active surfaces because thiol-modified chemicals and biomolecules can be easily immobilized with a simple procedure. However, most gold surfaces are damaged with repetitive measurements, so they are difficult to reuse. Here we demonstrate a novel electrochemical cleaning method of gold surfaces to reuse electrodes with a simple protocol that is easy and nontoxic. This electrochemical cleaning consists of two steps by using different solutions. The 1st step is a cyclic voltammetry sweep using a very low concentration of sulfuric acid, and the 2nd step is a cyclic voltammetry sweep using potassium ferricyanide. Different cleaning methods were also considered for comparison. Consequently, after assembling and desorption of the cell and antigen, the changes in gold electrode performance, as immunosensor and cytosensor, were investigated by electrochemical impedance and cyclic voltammetry. It was found that repetitive measurement is possible until five times while maintaining the reproducibility. It is believed that this method is capable of enabling reuse of gold electrodes and can be used for long-term and accurate monitoring of biological effects, especially at a low cost.

18.
Ann Coloproctol ; 39(2): 175-177, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34311544

RESUMO

Metachronous carcinoma at the colostomy site is very rare after abdominoperineal resection. A 53-year-old male patient underwent an abdominoperineal resection 6 years earlier for rectal cancer developed metachronous carcinoma at the site of stoma. A portion of the colon, including the stoma and the surrounding skin, was resected and a new stoma was created in the transverse colon. Although the occurrence of carcinoma at the stoma site is a rare condition, careful observation for the stoma and colonoscopy for surveillance are necessary.

19.
World J Mens Health ; 41(3): 612-622, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36102102

RESUMO

PURPOSE: To evaluate the efficacy and safety of udenafil 75 mg once daily in patients with erectile dysfunction following bilateral nerve-sparing robot-assisted laparoscopic radical prostatectomy (BNS-RALP). MATERIALS AND METHODS: A multi-center, prospective, randomized, controlled, double-blind study was conducted. Among patients with localized prostate cancer with international index of erectile function-erectile function domain (IIEF-EF) score of 18 or higher before BNS-RALP, those who developed postoperative erectile dysfunction (IIEF-EF score 14 or less at 4 weeks after BNS-RALP) were enrolled. Enrolled patients were randomly assigned to the udenafil 75 mg daily group or the placebo group in a 2:1 ratio. Each subject was followed up at 8 weeks (V2), 20 weeks (V3), and 32 weeks (V4) to evaluate the efficacy and safety of udenafil. RESULTS: In all, 101 patients were screened, of whom 99 were enrolled. Of the 99 patients, 67 were assigned to the experimental group and 32 to the control group. Ten (14.93%) patients in the experimental group and 10 (31.25%) in the control group dropped out of the study. After 32 weeks of treatment, IIEF-EF score of 22 or higher was seen in 36.51% (23/63) of patients in the experimental group and 13.04% (3/23) patients in the control group (p=0.021). The proportion of patients with IIEF-EF improvement of 25% or more compared to the baseline was 82.54% (52/63) in the experimental group and 62.96% (17/27) in the control group (p=0.058). CONCLUSIONS: Udenafil 75 mg once daily after BNS-RALP improved the erectile function without any severe adverse effects.

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