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1.
Clin Transplant Res ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38725178

RESUMO

Organ transplantation from donors with immune thrombocytopenia (ITP), a condition involving the autoantibody-mediated destruction of platelets, is a topic of debate due to the potential for transplantation-mediated autoimmune thrombocytopenia (TMAT), a rare but potentially fatal complication. Previous reports have described transplants from deceased liver donors with ITP who had very low platelet counts and disease largely refractory to treatment. Here, we present the first case of living kidney transplantation from a donor with ITP who underwent preoperative treatment, with concurrent splenectomy performed to reduce the long-term risk of spontaneous hemorrhage. To ensure the safety of the procedure, we monitored perioperative rotational thromboelastometry parameters and platelet counts, leading to the normalization of the donor's platelet levels. The recipient experienced an uneventful recovery of renal function without perioperative bleeding or the development of TMAT. Our report suggests that kidney transplantation from a donor with well-managed ITP is safe, and such a condition should not be considered a contraindication for donation.

2.
Plant J ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38743909

RESUMO

Low temperature (LT) greatly restricts grain filling in maize (Zea mays L.), but the relevant molecular mechanisms are not fully understood. To better understand the effect of LT on grain development, 17 hybrids were subjected to LT stress in field trials over 3 years, and two hybrids of them with contrasting LT responses were exposed to 30/20°C and 20/10°C for 7 days during grain filling in a greenhouse. At LT, thousand-kernel weight declined, especially in LT-sensitive hybrid FM985, while grain-filling rate was on average about 48% higher in LT-tolerant hybrid DK159 than FM985. LT reduced starch synthesis in kernel mainly by suppression of transcript levels and enzyme activities for sucrose synthase and hexokinase. Brassinolide (BR) was abundant in DK159 kernel, and genes involved in BR and cytokinin signals were inducible by stress. LT downregulated the genes in light-harvesting complex and photosystem I/II subunits, accompanied by reduced photosynthetic rate and Fv/Fm in ear leaf. The LT-tolerant hybrid could maintain a high soluble sugar content and fast interconversion between sucrose and hexose in the stem internode and cob, improving assimilate allocation to kernel at LT stress and paving the way for simultaneous growth and LT stress responses.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38747496

RESUMO

For practical industrial applications, enhancing the longevity and the reliability of thermoelectric modules (TEMs) is equally as crucial as improving their conversion efficiency. This study proposes a strategy for extending the lifespan and introduces the quality evaluation criteria for the most extensively used commercial bismuth telluride TEM. By varying the soldering pressure during module assembly, its impact on the quality of the module's internal interfacial connections was investigated, via analyzing its contact resistivity, shear modulus, and antifatigue ability through thermal cycling tests. The findings reveal that increasing the soldering pressure leads to a slight reduction in interfacial contact resistivity and has no significant effect on the shear modulus but notably enhances the module's antifatigue ability during thermal cycling tests. According to the SEM results, it can be evidently deduced that the aforementioned phenomena are directly correlated with the size and quantity of voids distributed in the solder layer, which is regarded as the origin of antifatigue ability. Thus, it can be inferred that augmenting the soldering pressure represents an effective approach to prolonging the lifespan of TEMs assembled by using the soldering method. Furthermore, the existence of voids within the solder layer can serve as a criterion for an initial assessment of module longevity. This study provides a reference for both the industrial assembly and lifespan evaluation of commercial bismuth telluride TEMs.

4.
Oncol Lett ; 28(1): 293, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38737976

RESUMO

Transfer (t)RNA-derived small RNAs (tsRNAs) are a class of novel non-coding small RNAs that are created via precise cleavage of tRNAs or tRNA precursors by different enzymes. tsRNAs are specific biological molecules that serve essential roles in cell proliferation, apoptosis, transcriptional regulation, post-transcriptional modification and translational regulation. Additionally, tsRNAs participate in the pathogenesis of several diseases, particularly in the development of malignant tumors. At present, the process of discovering and understanding the functions of tsRNAs is still in its early stages. The present review introduces the known biological functions and mechanisms of tsRNAs, and discusses the tsRNAs progression in several types of cancers as well as the possibility of tsRNAs becoming novel tumor biomarkers. Furthermore, tsRNAs may promote and hinder tumor formation according to different mechanisms and act as oncogenic or oncostatic molecules. Therefore, tsRNAs may be future potential tumor biomarkers or therapeutic targets.

5.
Front Pharmacol ; 15: 1379338, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38738180

RESUMO

Background: Chinese patent medicine is commonly used in China as an important treatment mechanism to thwart the progression of chronic kidney disease (CKD) stages 3-5, among which Niaoduqing granules are a representative Chinese patent medicine; however, its long-term efficacy on CKD prognosis remains unclear. Methods: Patients were grouped according to Niaoduqing granule prescription duration (non-Niaoduqing granule (non-NDQ) group vs Niaoduqing granule (NDQ) group). Serum creatinine (SCr) variation was compared using a generalized linear mixed model (GLMM). Multivariate Cox regression models were constructed, adjusting for confounding factors, to explore the risk of composite outcomes (receiving renal replacement therapy (RRT) or having an estimated glomerular filtration rate (eGFR)<5 mL/min/1.73 m2, ≥50% decline in the eGFR from the baseline, and doubling of SCr) in individuals consuming Niaoduqing granules. Results: A total of 1,271 patients were included, with a median follow-up duration of 29.71 (12.10, 56.07) months. The mean SCr Z-scores for the non-NDQ group and NDQ group were -0.175 and 0.153, respectively, at baseline (p = 0.015). The coefficients of the NDQ group from visit 1 to visit 5 were -0.207 (95% CI: -0.346, -0.068, p = 0.004), -0.214 (95% CI: 0.389, -0.039, p = 0.017), -0.324 (95% CI: 0.538, -0.109, p = 0.003), -0.502 (95% CI: 0.761, -0.243, p = 0.000), and -0.252 (95% CI: 0.569, 0.065, p = 0.119), respectively. The survival probability was significantly higher in the NDQ group (p = 0.0039). Taking Niaoduqing granules was a significant protective factor for thwarting disease progression (model 1: HR 0.654 (95% CI 0.489-0.875, p = 0.004); model 2: HR 0.646 (95% CI 0.476, 0.877, p = 0.005); and model 3: HR 0.602 (95% CI 0.442, 0.820, p = 0.001)). Conclusion: The long-term use of Niaoduqing granules improved SCr variation and lowered the risk of CKD progression by 39.8%.

6.
Can J Cardiol ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38734205

RESUMO

BACKGROUND: Single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is widely used to identify ischemia. There is limited research to evaluate if there is a risk threshold below which SPECT-MPI may not add significant prognostic value. METHODS: Between January 1, 2012, and December 31, 2018, individuals who underwent SPECT-MPI were stratified into four risk groups. The primary outcome was acute myocardial infarction (MI) or death. Multivariable Cox proportional hazards regression analysis was used to calculated HRs with 95% CIs. RESULTS: Among 48,845 patients (52.3% male, median age 67 years), 8.5% were low risk, 4.8% borderline risk, 18.1% intermediate risk, and 68.6% high risk based on the American College of Cardiology pooled cohort equation. Ischemia was more commonly detected in the high-risk cohort (19.4% in high-risk vs. 6.5% in low-risk). SPECT-MPI testing was associated with a significantly increased use of preventive medications such as statin therapy, regardless of stress test results. At a median follow-up of 4.2 years, there was no significant association between ischemia and death or MI in the low-risk cohort (adjusted HR 1.91, 95% CI 0.94-3.92) or the borderline-risk cohort (adjusted HR 1.58, 95% CI 0.79-3.15). Ischemia was associated with a higher risk of death or MI in the intermediate-risk (adjusted HR 1.57, 95% CI 1.24-1.99) and high-risk groups (adjusted HR 1.54, 95% CI 1.44-1.64). CONCLUSION: SPECT-MPI was less useful for risk stratification among low-risk patients due to their low event rates regardless of test result.

8.
PLoS One ; 19(5): e0302753, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38739634

RESUMO

Leprosy has a high rate of cripplehood and lacks available early effective diagnosis methods for prevention and treatment, thus novel effective molecule markers are urgently required. In this study, we conducted bioinformatics analysis with leprosy and normal samples acquired from the GEO database(GSE84893, GSE74481, GSE17763, GSE16844 and GSE443). Through WGCNA analysis, 85 hub genes were screened(GS > 0.7 and MM > 0.8). Through DEG analysis, 82 up-regulated and 3 down-regulated genes were screened(|Log2FC| > 3 and FDR < 0.05). Then 49 intersection genes were considered as crucial and subjected to GO annotation, KEGG pathway and PPI analysis to determine the biological significance in the pathogenesis of leprosy. Finally, we identified a gene-pathway network, suggesting ITK, CD48, IL2RG, CCR5, FGR, JAK3, STAT1, LCK, PTPRC, CXCR4 can be used as biomarkers and these genes are active in 6 immune system pathways, including Chemokine signaling pathway, Th1 and Th2 cell differentiation, Th17 cell differentiation, T cell receptor signaling pathway, Natural killer cell mediated cytotoxicity and Leukocyte transendothelial migration. We identified 10 crucial gene markers and related important pathways that acted as essential components in the etiology of leprosy. Our study provides potential targets for diagnostic biomarkers and therapy of leprosy.


Assuntos
Biomarcadores , Redes Reguladoras de Genes , Hanseníase , Hanseníase/genética , Hanseníase/microbiologia , Humanos , Biomarcadores/metabolismo , Biologia Computacional/métodos , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Mapas de Interação de Proteínas/genética , Transdução de Sinais
9.
Cancer Cell ; 42(5): 727-731, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38701791

RESUMO

As immunotherapy makes its way into the perioperative setting, a growing number of clinical trials are expanding the evidence base for resectable non-small cell lung cancer (NSCLC) management. Identifying the optimal treatment pattern-whether it's neoadjuvant, adjuvant, or a combination of both-is a crucial next step, particularly in pinpointing which patients benefit the most. This decision-making process requires a multi-disciplinary treatment team capable of utilizing tissue and plasma genomic testing to inform therapeutic choices. Leveraging the perioperative treatment platform, it remains pivotal to integrate circulating tumor DNA (ctDNA) monitoring into clinical trial design efficiently and provide clear guidance on treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Imunoterapia , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Imunoterapia/métodos , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Biomarcadores Tumorais/genética , Terapia Neoadjuvante/métodos , Ensaios Clínicos como Assunto
10.
bioRxiv ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38765966

RESUMO

Microenvironment niches determine cellular fates of metastatic cancer cells. However, robust and unbiased approaches to identify niche components and their molecular profiles are lacking. We established Sortase A-Based Microenvironment Niche Tagging (SAMENT), which selectively labels cells encountered by cancer cells during metastatic colonization. SAMENT was applied to multiple cancer models colonizing the same organ and the same cancer to different organs. Common metastatic niche features include macrophage enrichment and T cell depletion. Macrophage niches are phenotypically diverse between different organs. In bone, macrophages express the estrogen receptor alpha (ERα) and exhibit active ERα signaling in male and female hosts. Conditional knockout of Esr1 in macrophages significantly retarded bone colonization by allowing T cell infiltration. ERα expression was also discovered in human bone metastases of both genders. Collectively, we identified a unique population of ERα+ macrophages in the metastatic niche and functionally tied ERα signaling in macrophages to T cell exclusion during metastatic colonization. HIGHLIGHTS: SAMENT is a robust metastatic niche-labeling approach amenable to single-cell omics.Metastatic niches are typically enriched with macrophages and depleted of T cells.Direct interaction with cancer cells induces ERα expression in niche macrophages. Knockout of Esr1 in macrophages allows T cell infiltration and retards bone colonization.

11.
J Cancer Res Clin Oncol ; 150(5): 263, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38767702

RESUMO

BACKGROUND: Gastric cancer (GC) is one of the most prevalent malignant tumors worldwide. The low effectiveness of common biomarkers for the detection of early GC makes it essential to seek new biomarkers to improve diagnostic efficacy. tsRNAs (transfer RNA-derived small RNAs) are related to the growth of malignant tumors. In this article, we focused on whether tsRNAs may be employed as biomarkers for GC. METHODS: tRF-17-18VBY9M was screened in the tsRFun database as a research object. The methodological efficacy of tRF-17-18VBY9M was evaluated using Sanger sequencing, agarose gel electrophoresis assays, and gradient dilution. The χ2 test was applied to assess the interaction between tRF-17-18VBY9M expression and clinicopathologic characteristics. The receiver operating characteristic (ROC) curve was utilized to investigate the clinical efficiency of tRF-17-18VBY9M in GC. RESULTS: The Chi-square test demonstrated that high-expressed tRF-17-18VBY9M was closely associated with the T stage, tumor node metastasis stage (TNM), lymph node metastasis, and neurological/vascular invasion. ROC curve analysis revealed that the diagnostic value of tRF-17-18VBY9M in GC was superior to carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), and carbohydrate antigen 724 (CA724). CONCLUSION: tRF-17-18VBY9M is up-regulated in both GC sera and tissues. Differential tRF-17-18VBY9M expression distinguishes GC patients from healthy donors and gastritis patients, which suggests tRF-17-18VBY9M could act as a diagnostic biomarker in GC.


Assuntos
Biomarcadores Tumorais , Neoplasias Gástricas , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Humanos , Biomarcadores Tumorais/genética , Masculino , Feminino , Pessoa de Meia-Idade , RNA de Transferência/genética , Idoso , Prognóstico
12.
Clin Transl Allergy ; 14(5): e12357, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38730525

RESUMO

BACKGROUND: Asthma is the most common chronic disease among children and poses a significant threat to their health. This study aims to assess the relationship between various plasma proteins and childhood asthma, thereby identifying potential therapeutic targets. METHODS: Based on publicly available genome-wide association study summary statistics, we employed a two-sample Mendelian randomization (MR) approach to elucidate the causal relationship between plasma proteins and asthma. Mediation analysis was then conducted to evaluate the indirect influence of plasma proteins on childhood asthma mediated through risk factors. Comprehensive analysis was also conducted to explore the association between plasma proteins and various phenotypes using the UK Biobank dataset. RESULTS: MR analysis uncovered a causal relationship between 10 plasma proteins and childhood asthma. Elevated levels of seven proteins (TLR4, UBP25, CBR1, Rac GTPase-activating protein 1 [RGAP1], IL-21, MICB, and PDE4D) and decreased levels of three proteins (GSTO1, LIRB4 and PIGF) were associated with an increased risk of childhood asthma. Our findings further validated the connections between reported risk factors (body mass index, mood swings, hay fever or allergic rhinitis, and eczema or dermatitis) and childhood asthma. Mediation analysis revealed the influence of proteins on childhood asthma outcomes through risk factors. Furthermore, the MR analysis identified 73 plasma proteins that exhibited causal associations with at least one risk factor for childhood asthma. Among them, RGAP1 mediates a significant proportion (25.10%) of the risk of childhood asthma through eczema or dermatitis. Finally, a phenotype-wide association study based on these 10 proteins and 1403 diseases provided novel associations between these biomarkers and multiple phenotypes. CONCLUSION: Our study comprehensively investigated the causal relationship between plasma proteins and childhood asthma, providing novel insights into potential therapeutic targets.

13.
Adv Healthc Mater ; : e2304209, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691391

RESUMO

Photodynamic therapy (PDT) is a minimally invasive cancer treatment that, despite its significant attention, faces limitations in penetration depth, which restrict its effectiveness. Herein, it is found that gold nanobipyramid (AuNBs) coated with TiO2 can form a core-shell heterogeneous structure (AuNBs@TiO2) with strong absorption at second near infrared (NIR-II) region. A substantial quantity of reactive oxygen species (ROS), including singlet oxygen (1O2), superoxide anion radicals, and hydroxyl radicals, can be rapidly generated when subjecting the AuNBs@TiO2 aqueous suspension to 1064 nm laser irradiation. The quantum yield for sensitization of 1O2 by AuNBs@TiO2 is 0.36 at 1064 nm light excitation. In addition, the Au element as high-Z atoms in the nanosystem can improve the ability of computed tomographic (CT) imaging. As compared to commercial iohexol, the AuNBs@TiO2 nanoparticle exhibits significantly better CT imaging effect, which can be used to guide PDT. In addition, the nano-photosensitizer shows a remarkable therapeutic effect against established solid tumors and prevents tumor metastasis and potentiates immune checkpoint blockade therapy. More importantly, here the great potentials of AuNBs@TiO2 are highlighted as a theranostic platform for CT-guided cancer photodynamic immunotherapy.

14.
Protein Sci ; 33(6): e5007, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38723187

RESUMO

The identification of an effective inhibitor is an important starting step in drug development. Unfortunately, many issues such as the characterization of protein binding sites, the screening library, materials for assays, etc., make drug screening a difficult proposition. As the size of screening libraries increases, more resources will be inefficiently consumed. Thus, new strategies are needed to preprocess and focus a screening library towards a targeted protein. Herein, we report an ensemble machine learning (ML) model to generate a CDK8-focused screening library. The ensemble model consists of six different algorithms optimized for CDK8 inhibitor classification. The models were trained using a CDK8-specific fragment library along with molecules containing CDK8 activity. The optimized ensemble model processed a commercial library containing 1.6 million molecules. This resulted in a CDK8-focused screening library containing 1,672 molecules, a reduction of more than 99.90%. The CDK8-focused library was then subjected to molecular docking, and 25 candidate compounds were selected. Enzymatic assays confirmed six CDK8 inhibitors, with one compound producing an IC50 value of ≤100 nM. Analysis of the ensemble ML model reveals the role of the CDK8 fragment library during training. Structural analysis of molecules reveals the hit compounds to be structurally novel CDK8 inhibitors. Together, the results highlight a pipeline for curating a focused library for a specific protein target, such as CDK8.


Assuntos
Quinase 8 Dependente de Ciclina , Aprendizado de Máquina , Simulação de Acoplamento Molecular , Inibidores de Proteínas Quinases , Quinase 8 Dependente de Ciclina/antagonistas & inibidores , Quinase 8 Dependente de Ciclina/química , Quinase 8 Dependente de Ciclina/metabolismo , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Humanos , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos
15.
Chem Res Toxicol ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38771128

RESUMO

Lung cancer is the main cause of cancer deaths around the world. Nitrosamine 4-(methyl nitrosamine)-1-(3-pyridyl)-1-butanone (NNK) is a tobacco-specific carcinogen of lung cancer. Abundant evidence implicates long noncoding RNAs (lncRNAs) in tumorigenesis. Yet, the effects and mechanisms of lncRNAs in NNK-induced carcinogenesis are still unclear. In this study, we discovered that NNK-induced transformed Beas-2B cells (Beas-2B-NNK) showed increased cell migration and proliferation while decreasing rates of apoptosis. RNA sequencing and differentially expressed lncRNAs analyses showed that lncRNA PSMB8-AS1 was obviously upregulated. Interestingly, silencing the lncRNA PSMB8-AS1 in Beas-2B-NNK cells reduced cell proliferation and migration and produced cell cycle arrest in the G2/M phase along with a decrease in CDK1 expression. Conclusively, our results demonstrate that lncRNA PSMB8-AS1 could promote the malignant characteristics of Beas-2B-NNK cells by regulating CDK1 and affecting the cell cycle, suggesting that it may supply a new prospective epigenetic mechanism for lung cancer.

16.
Chin J Cancer Res ; 36(2): 103-113, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38751442

RESUMO

Objective: IMpower210 (NCT02813785) explored the efficacy and safety of single-agent atezolizumab vs. docetaxel as second-line treatment for advanced non-small cell lung cancer (NSCLC) in East Asian patients. Methods: Key eligibility criteria for this phase III, open-label, randomized study included age ≥18 years; histologically documented advanced NSCLC per the Union for International Cancer Control/American Joint Committee on Cancer staging system (7th edition); Eastern Cooperative Oncology Group performance status of 0 or 1; and disease progression following platinum-based chemotherapy for advanced or metastatic NSCLC. Patients were randomized 2:1 to receive either atezolizumab (1,200 mg) or docetaxel (75 mg/m2). The primary study endpoint was overall survival (OS) in the intention-to-treat (ITT) population with wild-type epidermal growth factor receptor expression (ITT EGFR-WT) and in the overall ITT population. Results: Median OS in the ITT EGFR-WT population (n=467) was 12.3 [95% confidence interval (95% CI), 10.3-13.8] months in the atezolizumab arm (n=312) and 9.9 (95% CI, 7.8-13.9) months in the docetaxel arm [n=155; stratified hazard ratio (HR), 0.82; 95% CI, 0.66-1.03]. Median OS in the overall ITT population was 12.5 (95% CI, 10.8-13.8) months with atezolizumab treatment and 11.1 (95% CI, 8.4-14.2) months (n=377) with docetaxel treatment (n=188; stratified HR, 0.87; 95% CI, 0.71-1.08). Grade 3/4 treatment-related adverse events (TRAEs) occurred in 18.4% of patients in the atezolizumab arm and 50.0% of patients in the docetaxel arm. Conclusions: IMpower210 did not meet its primary efficacy endpoint of OS in the ITT EGFR-WT or overall ITT populations. Atezolizumab was comparatively more tolerable than docetaxel, with a lower incidence of grade 3/4 TRAEs.

17.
J Hazard Mater ; 472: 134504, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38704910

RESUMO

The relationship of ozone (O3), particularly the long-term exposure, with impacting metabolic homeostasis in population was understudied and under-recognised. Here, we used data from ChinaHEART, a nationwide, population-based cohort study, combined with O3 and PM2.5 concentration data with high spatiotemporal resolution, to explore the independent association of exposure to O3 with the prevalence of insulin resistance (IR). Among the 271 540 participants included, the crude prevalence of IR was 39.1%, while the age and sex standardized prevalence stood at 33.0%. Higher IR prevalence was observed with each increase of 10.0 µg/m3 in long-term O3 exposure, yielding adjusted odds ratios (OR) of 1.084 (95% CI: 1.079-1.089) in the one-pollutant model and 1.073 (95% CI: 1.067-1.079) in the two-pollutant model. Notably, a significant additive interaction between O3 and PM2.5 on the prevalence of IR was observed (P for additive interaction < 0.001). Our main findings remained consistent and robust in the sensitivity analyses. Our study suggests long-term exposure to O3 was independently and positively associated with prevalence of IR. It emphasized the benefits of policy interventions to reduce O3 and PM2.5 exposure jointly, which could ultimately alleviate the health and economic burden related to DM.

18.
J Vasc Access ; : 11297298241250246, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38708823

RESUMO

AIM: Arteriovenous fistula (AVF) dysfunction resulting from stenosis or occlusion, is a prevalent issue in end-stage renal failure patients reliant on autogenous AVFs for dialysis. Recently, a distal transradial approach (dTRA) has emerged, offering advantages such as diminished access site complications, better patient comfort and reduced risk of radial artery occlusion. Our study seeks to assess the effectiveness, outcomes and complication rates of employing dTRA for arteriovenous fistuloplasty in Singaporean patients. METHODS: A retrospective review of all dTRA fistuloplasties performed on dysfunctional or slow to mature AVFs from 2017 to 2023 in our institution was performed. Patients with a distal radial artery measuring 2 mm or more with no evidence of occlusion or thrombosis were included. Patients who required central venoplasty or cutting balloon angioplasty were excluded. Outcome measures included technical success, mean procedure duration, complications and post-intervention primary patency at 1, 3 and 6 months. Patients were followed up for 12 months post-intervention. RESULTS: A total of 37 patients were included. 97.3% of patients undergoing dTRA fistuloplasty had radiocephalic fistulas while 2.7% had brachiobasilic fistulas. There was 100% technical success (defined as success in radial artery cannulation, sheath insertion and crossing of stenotic lesions) in our study as all patients successfully underwent fistuloplasty via dTRA approach. One-month patency rate was 97.4%, 3-month patency rate was 92.1% and 6-month patency rate was 86.8%. There were no immediate complications (haematoma, infection, bleeding, pseudoaneurysm, occlusion) of the radial artery post-intervention. CONCLUSION: Our paper illustrates the safety and efficacy of utilising dTRA for arteriovenous fistuloplasty. This approach offers distinct benefits in addressing non-mature or dysfunctional distal forearm arteriovenous fistulas and should be taken into account in anatomically suitable cases.

19.
Cell Metab ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38703762

RESUMO

The mitochondrial genome transcribes 13 mRNAs coding for well-known proteins essential for oxidative phosphorylation. We demonstrate here that cytochrome b (CYTB), the only mitochondrial-DNA-encoded transcript among complex III, also encodes an unrecognized 187-amino-acid-long protein, CYTB-187AA, using the standard genetic code of cytosolic ribosomes rather than the mitochondrial genetic code. After validating the existence of this mtDNA-encoded protein arising from cytosolic translation (mPACT) using mass spectrometry and antibodies, we show that CYTB-187AA is mainly localized in the mitochondrial matrix and promotes the pluripotent state in primed-to-naive transition by interacting with solute carrier family 25 member 3 (SLC25A3) to modulate ATP production. We further generated a transgenic knockin mouse model of CYTB-187AA silencing and found that reduction of CYTB-187AA impairs females' fertility by decreasing the number of ovarian follicles. For the first time, we uncovered the novel mPACT pattern of a mitochondrial mRNA and demonstrated the physiological function of this 14th protein encoded by mtDNA.

20.
Pediatr Pulmonol ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38695627

RESUMO

BACKGROUND: Tracheal agenesis, or tracheal atresia, is a rare congenital anomaly. The presence of a tracheoesophageal fistula (TEF) can help with breathing for newborns with tracheal agenesis. In this article, we presented three unique cases and outcomes of neonates with tracheal agenesis along with a review of the literature. METHODS: This study consisted of a single center case series followed by a review of literature. Case reports were generated using both written and electronic medical records from a single hospital. We summarized three unique cases and outcomes of neonates with tracheal agenesis and performed a review of the literature. RESULTS: We identified three cases of tracheal agenesis presented with severe cyanosis without spontaneous crying upon birth. Experienced pediatricians attempted to intubate the babies but were unsuccessful. Endotracheal tubes were subsequently either accidentally or purposely placed into the esophagus, and oxygen saturation levels improved. This suggested tracheal agenesis with TEF. Two cases underwent surgical intervention after resuscitation with esophageal intubation. CONCLUSION: Esophageal intubation may be a life-sustaining ventilation support for patients with tracheal agenesis and TEF at initial resuscitation. Clinicians should suspect tracheal agenesis when a newborn presents with severe cyanosis and voiceless crying upon birth, and esophageal intubation should be immediately attempted.

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