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1.
Int J Mol Sci ; 25(7)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38612554

RESUMO

Root extracts of Ancistrocladus tectorius (AT), a shrub native to China, have been shown to have antiviral and antitumor activities, but the anti-obesity effects of AT aerial parts, mainly the leaves and stems, have not been investigated. This study is the first to investigate the anti-obesity effects and molecular mechanism of AT 70% ethanol extract in 3T3-L1 adipocytes and high-fat diet (HFD)-fed C57BL/6J mice. Treatment with AT extract inhibited lipid accumulation in 3T3-L1 cells and decreased the expression of adipogenesis-related genes. AT extract also upregulated the mRNA expression of genes related to mitochondrial dynamics in 3T3-L1 adipocytes. AT administration for 12 weeks reduced body weight and organ weights, including liver, pancreas, and white and brown adipose tissue, and improved plasma profiles such as glucose, insulin, homeostasis model assessment of insulin resistance, triglyceride (TG), and total cholesterol in HFD-fed mice. AT extract reduced HFD-induced hepatic steatosis with levels of liver TG and lipogenesis-related genes. AT extract upregulated thermogenesis-related genes such as Cidea, Pgc1α, Ucp1, Prdm16, Adrb1, and Adrb3 and mitochondrial dynamics-related genes such as Mff, Opa1, and Mfn2 in brown adipose tissue (BAT). Therefore, AT extract effectively reduced obesity by promoting thermogenesis and the mitochondrial dynamics of BAT in HFD-fed mice.


Assuntos
Caryophyllales , Dieta Hiperlipídica , Animais , Camundongos , Camundongos Endogâmicos C57BL , Dieta Hiperlipídica/efeitos adversos , Dinâmica Mitocondrial , Insulina , Extratos Vegetais/farmacologia
2.
Breast Cancer Res ; 26(1): 65, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609935

RESUMO

BACKGROUND: Sentinel lymph node biopsy (SLNB) is recommended for patients with ductal carcinoma in situ (DCIS) undergoing mastectomy, given the concerns regarding upstaging and technical difficulties of post-mastectomy SLNB. However, this may lead to potential overtreatment, considering favorable prognosis and de-escalation trends in DCIS. Data regarding upstaging and axillary lymph node metastasis among these patients remain limited. METHODS: We retrospectively reviewed patients with DCIS who underwent mastectomy with SLNB or axillary lymph node dissection at Gangnam Severance Hospital between January 2010 and December 2021. To explore the feasibility of omitting SLNB, we assessed the rates of DCIS upgraded to invasive carcinoma and axillary lymph node metastasis. Binary Cox regression analysis was performed to identify clinicopathologic factors associated with upstaging and axillary lymph node metastasis. RESULTS: Among 385 patients, 164 (42.6%) experienced an invasive carcinoma upgrade: microinvasion, pT1, and pT2 were confirmed in 53 (13.8%), 97 (25.2%), and 14 (3.6%) patients, respectively. Seventeen (4.4%) patients had axillary lymph node metastasis. Multivariable analysis identified age ≤ 50 years (adjusted odds ratio [OR], 12.73; 95% confidence interval [CI], 1.18-137.51; p = 0.036) and suspicious axillary lymph nodes on radiologic evaluation (adjusted OR, 9.31; 95% CI, 2.06-41.99; p = 0.004) as independent factors associated with axillary lymph node metastasis. Among patients aged > 50 years and/or no suspicious axillary lymph nodes, only 1.7-2.3%) experienced axillary lymph node metastasis. CONCLUSIONS: Although underestimation of the invasive component was relatively high among patients with DCIS undergoing mastectomy, axillary lymph node metastasis was rare. Our findings suggest that omitting SLNB may be feasible for patients over 50 and/or without suspicious axillary lymph nodes on radiologic evaluation.


Assuntos
Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Humanos , Feminino , Biópsia de Linfonodo Sentinela , Carcinoma Intraductal não Infiltrante/cirurgia , Metástase Linfática , Neoplasias da Mama/cirurgia , Estudos Retrospectivos , Mastectomia
3.
Imaging Sci Dent ; 54(1): 93-104, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38571777

RESUMO

Chronic nonbacterial osteomyelitis (CNO) is histologically characterized by nonspecific osteitis. This inflammatory disorder, which lacks an infectious origin, typically presents with chronic pain and swelling at the affected site that can persist for months or even years. However, it is rare for CNO to affect the mandible. A 10-year-old girl presented with a primary complaint of pain in her left mandible. She had no significant medical or dental history. On examination, swelling was visible on the left buccal side, and imaging revealed radiolucent bone deterioration within the left mandible. This case report presents the radiological changes observed over a 12-year follow-up period. Variations in radiopacity, radiolucency, and periosteal reactions were noted periodically. This case highlights the radiological characteristics and findings that are crucial for the diagnosis of CNO, a condition for which no clear diagnostic criteria are currently available.

5.
PLoS One ; 19(4): e0300054, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38635747

RESUMO

This study aimed to identify underlying demographic and clinical characteristics among individuals who had previously attempted suicide, utilizing the comprehensive Health Insurance Review and Assessment Service (HIRA) database. Data of patients aged 18 and above who had attempted suicide between January 1 and December 31, 2014, recorded in HIRA, were extracted. The index date was identified when a suicide attempt was made within the year 2014. The medical history of the three years before the index date and seven years of follow-up data after the index date were analyzed. Kaplan-Meier estimate was used to infer reattempt of the suicide attempters, and Cox-proportional hazard analysis was used to investigate risk factors associated with suicide reattempts. A total of 17,026 suicide attempters were identified, of which 1,853 (10.9%) reattempted suicide; 4,925 (28.9%) patients had been diagnosed with depressive disorder. Of the reattempters, 391 (21.1%) demonstrated a history of suicide attempts in the three years before the index date, and the mean number of prior attempts was higher compared to that of the non-reattempters (1.7 vs.1.3, p-value < 0.01). Prior psychiatric medication, polypharmacy, and an increase in the number of psychotropics were associated with suicide reattempt in overall suicide attempters. (Hazard ratio (HR) = 3.20, 95% confidence interval [CI] = 2.56-4.00; HR = 2.42, 95% CI = 1.87-3.14; HR = 19.66, 95% CI = 15.22-25.39 respectively). The risk of reattempt decreased in individuals receiving antidepressant prescriptions compared to those unmedicated, showing a reduction of 78% when prescribed by non-psychiatrists and 89% when prescribed by psychiatrists. Similar risk factors for suicide reattempts were observed in the depressive disorder subgroup, but the median time to reattempt was shorter (556.5 days) for this group compared to that for the overall attempters (578 days). Various risk factors including demographics, clinical characteristics, and medications should be considered to prevent suicide reattempts among suicide attempters, and patients with depressive disorder should be monitored more closely.


Assuntos
Tentativa de Suicídio , Humanos , Tentativa de Suicídio/psicologia , Estudos Retrospectivos , Fatores de Risco , Modelos de Riscos Proporcionais , República da Coreia/epidemiologia
6.
Acta Otolaryngol ; : 1-5, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38491920

RESUMO

BACKGROUND: Cervical lymph node metastasis (CLNM) from remote primary sites is rare in head and neck cancer. The efficacy of neck dissection is still being investigated for therapeutic benefits of local management in oligometastasis from non-head and neck cancer. OBJECTIVES: To evaluate the clinical efficacy of neck dissection (ND) in CLNM from distant primary cancers and identify factors contributing to improved survival. MATERIALS AND METHODS: This retrospective case-control study enrolled patients who underwent ND for CLNM from distant primary cancer at Asan Medical Centre between January 2010 and December 2020. We analysed overall survival and association between clinical covariate and survival. RESULTS: The study included 31 (14 males, 17 females) among 114 patients. Ovarian cancer was the most common primary malignancy (32.3%). Patients with fewer than three metastatic lymph nodes, without extranodal extension and with adjuvant therapy after surgery had better survival rates. CONCLUSION AND SIGNIFICANCE: In patients with CLNM from a distant primary cancer, ND is beneficial as local treatment. And adequate selection of patients for ND is pivotal to improve prognosis.

7.
Viruses ; 16(3)2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38543842

RESUMO

Coxsackievirus A6 (CV-A6) has emerged as the predominant causative agent of hand, foot, and mouth disease (HFMD) in young children. Since the declaration of coronavirus disease 2019 (COVID-19) as a global pandemic, the incidence of infectious diseases, including HFMD, has decreased markedly. When social mitigation was relaxed during the COVID-19 pandemic in 2022, the re-emergence of HFMD was observed in Gwangju, South Korea, and seasonal characteristics of the disease appeared to have changed. To investigate the molecular characteristics of enterovirus (EV) associated with HFMD during 2022, 277 specimens were collected. Children aged younger than 5 years accounted for the majority of affected individuals. EV detection and genotyping were performed using real-time RT-PCR and nested RT-PCR followed by sequence analysis. The EV detection rate was found to be 82.3%, and the main genotype identified was CV-A6. Sixteen CV-A6 samples were selected for whole genome sequencing. According to phylogenetic analysis, all CV-A6 strains from this study belonged to the sub-genotype D3 clade based on VP1 sequences. Analysis of 3D polymerase phylogeny showed that only the recombinant RF-A group was identified. In conclusion, circulating EV types should be continuously monitored to understand pathogen emergence and evolution during the post-pandemic era.


Assuntos
Enterovirus , Doença de Mão, Pé e Boca , Criança , Humanos , Pré-Escolar , Doença de Mão, Pé e Boca/epidemiologia , Filogenia , Pandemias , Enterovirus/genética , Antígenos Virais/genética , Reação em Cadeia da Polimerase em Tempo Real , Genótipo , China/epidemiologia
8.
Biochem Biophys Res Commun ; 709: 149828, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38537596

RESUMO

Long intergenic non-coding RNA 346 (LINC00346) has been reported to be involved in the development of atherosclerosis and specific cancers by affecting signaling pathways. However, its function in inflammation has not been thoroughly studied. Therefore, its expression pattern and function were determined in the human macrophage-like cell line THP-1. Lipopolysaccharide (LPS) treatment induced the expression of LINC00346. LPS-induced NF-κB activation and proinflammatory cytokine expression were suppressed or enhanced by the overexpression or knockdown of LINC00346, respectively. Analyses using dual luciferase assay and decoy RNAs that could block RNA-RNA interactions indicated that LINC00346 improves phosphatase and tensin homolog (PTEN) expression by sponging miR-25-3p. Subsequently, PTEN suppresses phosphoinositide-3 kinase (PI3K)-mediated conversion of phosphatidylinositol-4,5-bisphosphate (PIP2) into phosphatidylinositol-3,4,5-trisphosphate (PIP3) as well as consequent activation of protein kinase B (AKT) and NF-κB. Interestingly, database analysis revealed that the expression levels of LINC00346 and PTEN were simultaneously decreased in breast cancer tissues. Further analyses conducted using a breast cancer cell line, MDA-MB-231, confirmed the functional relationship among LINC00346, miR-25-3p, and PTEN in LPS-induced activation of NF-κB. These results indicate that miR-25-3p-sponging activity of LINC00346 affects the balance between PTEN and PI3K as well as the downstream activation of AKT/NF-κB pathway in inflammatory conditions.


Assuntos
Neoplasias da Mama , MicroRNAs , Humanos , Feminino , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinase , Fosfatidilinositol 3-Quinases/metabolismo , Lipopolissacarídeos/farmacologia , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Células MCF-7 , MicroRNAs/genética , MicroRNAs/metabolismo , Fosfatidilinositóis
9.
Front Toxicol ; 6: 1285768, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38523647

RESUMO

Introduction: The Adverse Outcome Pathway (AOP) concept facilitates rapid hazard assessment for human health risks. AOPs are constantly evolving, their number is growing, and they are referenced in the AOP-Wiki database, which is supported by the OECD. Here, we present a study that aims at identifying well-defined biological areas, as well as gaps within the AOP-Wiki for future research needs. It does not intend to provide a systematic and comprehensive summary of the available literature on AOPs but summarizes and maps biological knowledge and diseases represented by the already developed AOPs (with OECD endorsed status or under validation). Methods: Knowledge from the AOP-Wiki database were extracted and prepared for analysis using a multi-step procedure. An automatic mapping of the existing information on AOPs (i.e., genes/proteins and diseases) was performed using bioinformatics tools (i.e., overrepresentation analysis using Gene Ontology and DisGeNET), allowing both the classification of AOPs and the development of AOP networks (AOPN). Results: AOPs related to diseases of the genitourinary system, neoplasms and developmental anomalies are the most frequently investigated on the AOP-Wiki. An evaluation of the three priority cases (i.e., immunotoxicity and non-genotoxic carcinogenesis, endocrine and metabolic disruption, and developmental and adult neurotoxicity) of the EU-funded PARC project (Partnership for the Risk Assessment of Chemicals) are presented. These were used to highlight under- and over-represented adverse outcomes and to identify and prioritize gaps for further research. Discussion: These results contribute to a more comprehensive understanding of the adverse effects associated with the molecular events in AOPs, and aid in refining risk assessment for stressors and mitigation strategies. Moreover, the FAIRness (i.e., data which meets principles of findability, accessibility, interoperability, and reusability (FAIR)) of the AOPs appears to be an important consideration for further development.

10.
ACS Appl Mater Interfaces ; 16(12): 14583-14594, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38478505

RESUMO

Healing chronic diabetic wounds is challenging because of excessive reactive oxygen species (ROS) and hypoxia in the wound microenvironment. To address this issue, we propose a hydrogel wound dressing composed of polyethylene glycol (PEG) cross-linked with a biomimetic catalase, Fe-containing porphyrin (FeP) (i.e., FeP hydrogel). The immobilized FeP can serve as a catalyst for both ROS scavenging and O2 generation. The properties of the hydrogels were optimized by varying the composition ratios of the two constituent materials based on their mechanical properties and catalytic activity. Our in vitro cell experiments revealed that the FeP-80 hydrogel enhanced the proliferation and migration of keratinocytes and dermal fibroblasts and promoted the expression of angiogenic growth factors in keratinocytes. When tested with an in vivo diabetic chronic wound model, the FeP-80 hydrogel promoted wound healing by facilitating re-epithelialization, promoting angiogenesis, and suppressing inflammation, compared with other control groups.


Assuntos
Diabetes Mellitus , Hidrogéis , Humanos , Hidrogéis/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Oxigênio , Cicatrização , Antibacterianos
11.
Biomed Pharmacother ; 174: 116436, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38508081

RESUMO

In cancer immunotherapy, chimeric antigen receptors (CARs) targeting specific antigens have become a powerful tool for cell-based therapy. CAR-natural killer (NK) cells offer selective anticancer lysis with reduced off-tumor toxicity compared to CAR-T cells, which is beneficial in the heterogeneous milieu of solid tumors. In the tumor microenvironment (TME) of glioblastoma (GBM), pericytes not only support tumor growth but also contribute to immune evasion, underscoring their potential as therapeutic targets in GBM treatment. Given this context, our study aimed to target the GBM TME, with a special focus on pericytes expressing CD19, to evaluate the potential effectiveness of CD19 CAR-iNK cells against GBM. We performed CD19 CAR transduction in induced pluripotent stem cell-derived NK (iNK) cells. To determine whether CD19 CAR targets the TME pericytes in GBM, we developed GBM-blood vessel assembloids (GBVA) by fusing GBM spheroids with blood vessel organoids. When co-cultured with GBVA, CD19 CAR-iNK cells migrated towards the pericytes surrounding the GBM. Using a microfluidic chip, we demonstrated CD19 CAR-iNK cells' targeted action and cytotoxic effects in a perfusion-like environment. GBVA xenografts recapitulated the TME including human CD19-positive pericytes, thereby enabling the application of an in vivo model for validating the efficacy of CD19 CAR-iNK cells against GBM. Compared to GBM spheroids, the presence of pericytes significantly enhanced CD19 CAR-iNK cell migration towards GBM and reduced proliferation. These results underline the efficacy of CD19 CAR-iNK cells in targeting pericytes within the GBM TME, suggesting their potential therapeutic value for GBM treatment.

12.
Cancer Med ; 13(3): e7023, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38396380

RESUMO

BACKGROUND: This study aimed to compare the outcomes of proton beam therapy (PBT) and carbon ion radiotherapy (CIRT) by a systematic review and meta-analysis of the existing clinical evidence. METHODS: A systematic literature search was performed to identify studies comparing the clinical outcomes of PBT and CIRT. The included studies were required to report oncological outcomes (local control [LC], progression-free survival [PFS], or overall survival [OS]) or adverse events. RESULTS: Eighteen articles comprising 1857 patients (947 treated with PBT and 910 treated with CIRT) were included in the analysis. The pooled analysis conducted for the overall population yielded average hazard ratios of 0.690 (95% confidence interval (CI), 0.493-0.967, p = 0.031) for LC, 0.952 (95% CI, 0.604-1.500, p = 0.590) for PFS, and 1.183 (0.872-1.607, p = 0.281) for OS with reference to CIRT. The subgroup analyses included patients treated in the head and neck, areas other than the head and neck, and patients with chordomas and chondrosarcomas. These analyses revealed no significant differences in most outcomes, except for LC in the subgroup of patients treated in areas other than the head and neck. Adverse event rates were comparable in both groups, with an odds ratio (OR) of 1.097 (95% CI, 0.744-1.616, p = 0.641). Meta-regression analysis for possible heterogeneity did not demonstrate a significant association between treatment outcomes and the ratio of biologically effective doses between modalities. CONCLUSION: This study highlighted the comparability of PBT and CIRT in terms of oncological outcomes and adverse events.


Assuntos
Radioterapia com Íons Pesados , Terapia com Prótons , Humanos , Terapia com Prótons/efeitos adversos , Radioterapia com Íons Pesados/efeitos adversos , Resultado do Tratamento , Intervalo Livre de Progressão
13.
Biofabrication ; 16(2)2024 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-38306679

RESUMO

Although three-dimensional (3D) printing techniques are used to mimic macro- and micro-structures as well as multi-structural human tissues in tissue engineering, efficient target tissue regeneration requires bioactive 3D printing scaffolds. In this study, we developed a bone morphogenetic protein-2 (BMP-2)-immobilized polycaprolactone (PCL) 3D printing scaffold with leaf-stacked structure (LSS) (3D-PLSS-BMP) as a bioactive patient-tailored bone graft. The unique LSS was introduced on the strand surface of the scaffold via heating/cooling in tetraglycol without significant deterioration in physical properties. The BMP-2 adsorbed on3D-PLSS-BMPwas continuously released from LSS over a period of 32 d. The LSS can be a microtopographical cue for improved focal cell adhesion, proliferation, and osteogenic differentiation.In vitrocell culture andin vivoanimal studies demonstrated the biological (bioactive BMP-2) and physical (microrough structure) mechanisms of3D-PLSS-BMPfor accelerated bone regeneration. Thus, bioactive molecule-immobilized 3D printing scaffold with LSS represents a promising physically and biologically activated bone graft as well as an advanced tool for widespread application in clinical and research fields.


Assuntos
Osteogênese , Tecidos Suporte , Humanos , Tecidos Suporte/química , Engenharia Tecidual/métodos , Regeneração Óssea , Poliésteres/química , Impressão Tridimensional
14.
Transl Psychiatry ; 14(1): 80, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38320993

RESUMO

Although depression is an emerging disorder affecting many people worldwide, most genetic studies have been performed in European descent populations. Herein, a genome-wide association study (GWAS) was conducted in Korean population to elucidate the genomic loci associated with depressive symptoms. Two independent cohorts were used as discovery datasets, which consisted of 6474 (1484 cases and 4990 controls) and 1654 (557 cases and 1097 controls) Korean participants, respectively. The participants were divided into case and control groups based on the Beck Depression Inventory (BDI). Meta-analysis using the two cohorts revealed that rs6945590 was significantly associated with the risk of depressive symptoms [P = 2.83 × 10-8; odds ratio (OR) = 1.23; 95% confidence interval (CI): 1.15-1.33]. This association was validated in other independent cohorts which were another Korean cohort (258 cases and 1757 controls) and the East Asian study of the Psychiatric Genomics Consortium (PGC) (12,455 cases and 85,548 controls). The predicted expression levels of thromboxane A synthase 1 gene (TBXAS1), which encodes the enzyme thromboxane A synthase 1 and participates in the arachidonic acid (AA) cascade, was significantly decreased in the whole blood tissues of the participants with depressive symptoms. Furthermore, Mendelian randomization (MR) analysis showed a causal association between TBXAS1 expression and the risk of depressive symptoms. In conclusion, as the number of risk alleles (A) of rs6945590 increased, TBXAS1 expression decreased, which subsequently caused an increase in the risk of depressive symptoms.


Assuntos
Depressão , Estudo de Associação Genômica Ampla , Humanos , Depressão/genética , Predisposição Genética para Doença , Tromboxano-A Sintase/genética , República da Coreia , Polimorfismo de Nucleotídeo Único
15.
Heliyon ; 10(2): e24919, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38312694

RESUMO

Garlic (Allium sativum) is a key ingredient in Korean cuisine, particularly in the preparation of kimchi, contributing to its flavor and taste. Garlic has been a potential resource for lactic acid bacteria (LAB) in kimchi. However, the mechanism by which it influences microbial diversity and metabolite production is unclear. This study investigated the effect of garlic on the bacterial composition of and metabolite changes in kimchi. To achieve this, four separate batches of kimchi were prepared with varying garlic concentrations (w/w): 0 %, 1 %, 2 %, and 4 %, and the bacterial communities and metabolite production were monitored. In the early stages of fermentation, the count of LAB, operational taxonomic units (OTUs), and Shannon index increased linearly with the increase in garlic content. This indicated that garlic is a rich resource and contributes to the diversity of LAB during kimchi fermentation. Compared with the kimchi samples with a lower garlic content, those with a high garlic content (≥2 %) exhibited increased abundance of Lactobacillus and Leuconostoc as well as noticeable differences in functional diversity, including carbohydrate, amino acid, and energy metabolisms. Correlation analysis between sugars, organic acids, and predominant LAB in the garlic-containing kimchi samples suggested that in kimchi samples with high garlic content, LAB played a significant role in the fermentation process by metabolizing sugars and producing organic acids. Overall, this study demonstrated that the addition of garlic has a positive impact on the bacterial diversity and metabolite production during kimchi fermentation, potentially affecting the fermentation process and flavor profile of kimchi.

16.
Diabetes Metab J ; 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38311057

RESUMO

Background: Reactive oxygen species (ROS) and inflammation are reported to have a fundamental role in the pathogenesis of ischemia-reperfusion (IR) injury, a leading cause of acute kidney injury. The present study investigated the role of pyruvate dehydrogenase kinase 4 (PDK4) in ROS production and inflammation following IR injury. Methods: We used a streptozotocin-induced diabetic C57BL6/J mouse model, which was subjected to IR by clamping both renal pedicles. Cellular apoptosis and inflammatory markers were evaluated in NRK-52E cells and mouse primary tubular cells after hypoxia and reoxygenation using a hypoxia work station. Results: Following IR injury in diabetic mice, the expression of PDK4, rather than the other PDK isoforms, was induced with a marked increase in pyruvate dehydrogenase E1α (PDHE1α) phosphorylation. This was accompanied by a pronounced ROS activation, as well as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and monocyte chemoattractant protein-1 (MCP-1) production. Notably, sodium dichloroacetate (DCA) attenuated renal IR injury-induced apoptosis which can be attributed to reducing PDK4 expression and PDHE1α phosphorylation levels. DCA or shPdk4 treatment reduced oxidative stress and decreased TNF-α, IL-6, IL-1ß, and MCP-1 production after IR or hypoxia-reoxygenation injury. Conclusion: PDK4 inhibition alleviated renal injury with decreased ROS production and inflammation, supporting a critical role for PDK4 in IR mediated damage. This result indicates another potential target for reno-protection during IR injury; accordingly, the role of PDK4 inhibition needs to be comprehensively elucidated in terms of mitochondrial function during renal IR injury.

17.
J Yeungnam Med Sci ; 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38351610

RESUMO

Acute kidney ischemia-reperfusion (IR) injury is a life-threatening condition that predisposes individuals to chronic kidney disease. Since the kidney is one of the most energy-demanding organs in the human body and mitochondria are the powerhouse of cells, mitochondrial dysfunction plays a central role in the pathogenesis of IR-induced acute kidney injury. Mitochondrial dysfunction causes a reduction in adenosine triphosphate production, loss of mitochondrial dynamics (represented by persistent fragmentation), and impaired mitophagy. Furthermore, the pathological accumulation of succinate resulting from fumarate reduction under oxygen deprivation (ischemia) in the reverse flux of the Krebs cycle can eventually lead to a burst of reactive oxygen species driven by reverse electron transfer during the reperfusion phase. Accumulating evidence indicates that improving mitochondrial function, biogenesis, and dynamics, and normalizing metabolic reprogramming within the mitochondria have the potential to preserve kidney function during IR injury and prevent progression to chronic kidney disease. In this review, we summarize recent advances in understanding the detrimental role of metabolic reprogramming and mitochondrial dysfunction in IR injury and explore potential therapeutic strategies for treating kidney IR injury.

18.
Angew Chem Int Ed Engl ; 63(16): e202314904, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38329158

RESUMO

Oxidative alkene functionalization reactions are a fundamental class of complexity-building organic transformations. However, the majority of established approaches rely on electrophilic reagents that limit the diversity of groups that can be installed. Recent advances have established a new approach that instead relies on the transformation of alkenes into thianthrene-derived cationic electrophiles. These linchpin intermediates can be generated selectively and undergo a diverse array of mechanistically distinct reactions with abundant nucleophiles. Taken together, this unlocks a suite of net oxidative alkene transformations that have been elusive using conventional strategies. This Minireview describes these advances and is organized around the three distinct synthons formally accessible from alkenes via thianthrenation: 1) alkenyl cations; 2) vicinal dications; 3) allyl cations. Throughout the Minireview, we illustrate how thianthrenium salts address key limitations endemic to classic alkene-derived electrophiles and highlight the mechanistic origins of these distinctions wherever possible.

19.
Cancers (Basel) ; 16(2)2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38254866

RESUMO

Shear-wave elastography (SWE) is an effective tool in discriminating malignant lesions of breast and axillary lymph node metastasis in patients with breast cancer. However, the association between the baseline elasticity value of breast cancer and the treatment response of neoadjuvant chemotherapy is yet to be elucidated. Baseline SWE measured mean stiffness (E-mean) and maximum stiffness (E-max) in 830 patients who underwent neoadjuvant chemotherapy and surgery from January 2012 to December 2022. Association of elasticity values with breast pCR (defined as ypTis/T0), pCR (defined as ypTis/T0, N0), and tumor-infiltrating lymphocytes (TILs) was analyzed. Of 830 patients, 356 (42.9%) achieved breast pCR, and 324 (39.0%) achieved pCR. The patients with low elasticity values had higher breast pCR and pCR rates than those with high elasticity values. A low E-mean (adjusted odds ratio (OR): 0.620; 95% confidence interval (CI): 0.437 to 0.878; p = 0.007) and low E-max (adjusted OR: 0.701; 95% CI: 0.494 to 0.996; p = 0.047) were independent predictive factors for breast pCR. Low elasticity values were significantly correlated with high TILs. Pretreatment elasticity values measured using SWE were significantly associated with treatment response and inversely correlated with TILs, particularly in HR+HER2- breast cancer and TNBC.

20.
Korean J Transplant ; 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38282513

RESUMO

To address a donor kidney shortage, marginal grafts have been applied in deceased donor kidney transplantation (DDKT). These grafts exhibit comparatively unfavorable outcomes, particularly when cold ischemia time (CIT) is prolonged. Hypothermic machine perfusion (HMP) has been investigated to mitigate the effects of prolonged CIT during graft transport. The present case involved successful management of the longest CIT recorded in Korea by employing HMP in DDKT. The donor was a 54-year-old man (Korean Kidney Donor Profile Index, 82%) with diabetes. The recipient, a 51-year-old man on peritoneal dialysis, had end-stage renal disease secondary to diabetic nephropathy. Following procurement, the left kidney was preserved using HMP. Inclement weather delayed graft transportation; consequently, the total CIT was 28 hours and 6 minutes, with the kidney preserved by HMP for 22 hours and 35 minutes. Postoperative graft function gradually recovered, and urine output was satisfactory. Delayed graft function was not observed, and the patient was discharged on postoperative day 13 without significant complications. Five months after surgery, his serum creatinine level was 1.7 mg/dL. Successful DDKT with a marginal donor graft via HMP, despite the longest CIT yet observed in Korea, underscores the usefulness of HMP in enhancing graft quality and preserving function.

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