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1.
Biochim Biophys Acta Bioenerg ; 1865(4): 149492, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38960080

RESUMEN

Mitochondrial DNA (mtDNA) mutations, including the m.3243A>G mutation that causes mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), are associated with secondary coenzyme Q10 (CoQ10) deficiency. We previously demonstrated that PPARGC1A knockdown repressed the expression of PDSS2 and several COQ genes. In the present study, we compared the mitochondrial function, CoQ10 status, and levels of PDSS and COQ proteins and genes between mutant cybrids harboring the m.3243A>G mutation and wild-type cybrids. Decreased mitochondrial energy production, defective respiratory function, and reduced CoQ10 levels were observed in the mutant cybrids. The ubiquinol-10:ubiquinone-10 ratio was lower in the mutant cybrids, indicating blockage of the electron transfer upstream of CoQ, as evident from the reduced ratio upon rotenone treatment and increased ratio upon antimycin A treatment in 143B cells. The mutant cybrids exhibited downregulation of PDSS2 and several COQ genes and upregulation of COQ8A. In these cybrids, the levels of PDSS2, COQ3-a isoform, COQ4, and COQ9 were reduced, whereas those of COQ3-b and COQ8A were elevated. The mutant cybrids had repressed PPARGC1A expression, elevated ATP5A levels, and reduced levels of mtDNA-encoded proteins, nuclear DNA-encoded subunits of respiratory enzyme complexes, MNRR1, cytochrome c, and DHODH, but no change in TFAM, TOM20, and VDAC1 levels. Alterations in the CoQ10 level in MELAS may be associated with mitochondrial energy deficiency and abnormal gene regulation. The finding of a reduction in the ubiquinol-10:ubiquinone-10 ratio in the MELAS mutant cybrids differs from our previous discovery that cybrids harboring the m.8344A>G mutation exhibit a high ubiquinol-10:ubiquinone-10 ratio.

2.
J Korean Soc Radiol ; 85(3): 549-565, 2024 May.
Artículo en Coreano | MEDLINE | ID: mdl-38873382

RESUMEN

MRI is a crucial tool for diagnosing adenomyosis and identifying its related pathologies. To accurately diagnose adenomyosis, it is necessary to recognize both the typical MRI findings and atypical features of the condition. Recently, a standardized classification system has been developed to facilitate precise presurgical diagnosis of adenomyosis and to determine the appropriate treatment method. Differentiating between various subtypes based on MRI-based classification and identifying different MRI phenotypes can aid in categorizing patients with adenomyosis into specific treatment groups and monitoring their response to therapy.

3.
Diagnostics (Basel) ; 14(11)2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38893589

RESUMEN

Myeloid sarcoma, a rare extramedullary manifestation of acute myeloid leukemia (AML), can occur in various anatomic sites but seldom involves the gastrointestinal tract. We report the unusual case of a 49-year-old man with a history of AML who initially presented with abdominal pain and imaging findings suggestive of a paracolic abscess. However, the lesion rapidly progressed to a large descending colon mass with peritoneal involvement over five weeks. Surgical resection and histopathological examination confirmed a diagnosis of myeloid sarcoma. This case highlights the potential of myeloid sarcoma to mimic an inflammatory colonic process at initial presentation prior to manifesting as an overt mass lesion. Although exceedingly rare, myeloid sarcoma should be considered in patients with a history of AML presenting with colon lesions, particularly in those with an aggressive clinical course. Early recognition may expedite appropriate treatment and prevent unnecessary procedures. This report also underscores the importance of correlating imaging findings with clinical history and histopathology findings to establish an accurate diagnosis.

4.
World J Mens Health ; 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38863375

RESUMEN

PURPOSE: To compare the perioperative and postoperative outcomes between traditional trans-vesical robot-assisted simple prostatectomy (TV-RASP) and the newly introduced urethral-sparing (US) RASP. MATERIALS AND METHODS: We retrospectively reviewed 42 patients who underwent TV-RASP (n=22) or US-RASP (n=20) performed by two experienced surgeons at two tertiary centers. Perioperative outcomes including operation time, estimated blood loss, length of hospital stay, and catheterization time were assessed. Postoperative outcomes were evaluated using the International Prostate Symptom Score (IPSS), quality of life (QoL), uroflowmetry parameters, Male Sexual Health Questionnaire-Ejaculation Dysfunction-Short Form (MSHQ-EjD-SF) scores, and maintenance of anterograde ejaculation. RESULTS: This study analyzed 22 and 20 patients who underwent TV-RASP and US-RASP, respectively. Except for the TV-RASP group being older (70.0 years) than the US-RASP group (64.5 years) (p=0.028), no differences among other baseline characteristics existed. Perioperative outcomes indicated that hospital stay and catheterization time were significantly shorter in the US-RASP group than in the TV-RASP group (p<0.001). At postoperative month 1, the median IPSS and QoL scores were significantly better in the US-RASP group than in the TV-RASP group (p=0.001 and p=0.002, respectively). However, at months 6 and 12, no significant differences were noted in IPSS, QoL, maximum flow rate, and postvoid residual urine between the two groups. Sexually active patients in the US-RASP group maintained postoperative MSHQ-EjD functional and bother scores, whereas the TV-RASP group experienced a decline. Notably, 75.0% of patients in the US-RASP group preserved antegrade ejaculation, compared to only 20.0% in the TV-RASP group (p<0.001). CONCLUSIONS: US-RASP is not inferior to TV-RASP in terms of functional outcomes. In addition, US-RASP yielded more rapid symptom improvements and preserved antegrade ejaculation than TV-RASP. However, larger prospective studies are required to confirm these findings and to further investigate the long-term efficacy and safety of US-RASP.

5.
Nutrients ; 16(12)2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38931275

RESUMEN

Probiotics are posited to enhance exercise performance by influencing muscle protein synthesis, augmenting glycogen storage, and reducing inflammation. This double-blind study randomized 88 participants to receive a six-week intervention with either a placebo, Lactococcus lactis subsp. lactis LY-66, Lactobacillus plantarum PL-02, or a combination of both strains, combined with a structured exercise training program. We assessed changes in maximal oxygen consumption (VO2max), exercise performance, and gut microbiota composition before and after the intervention. Further analyses were conducted to evaluate the impact of probiotics on exercise-induced muscle damage (EIMD), muscle integrity, and inflammatory markers in the blood, 24 and 48 h post-intervention. The results demonstrated that all probiotic groups exhibited significant enhancements in exercise performance and attenuation of muscle strength decline post-exercise exhaustion (p < 0.05). Notably, PL-02 intake significantly increased muscle mass, whereas LY-66 and the combination therapy significantly reduced body fat percentage (p < 0.05). Analysis of intestinal microbiota revealed an increase in beneficial bacteria, especially a significant rise in Akkermansia muciniphila following supplementation with PL-02 and LY-66 (p < 0.05). Overall, the combination of exercise training and supplementation with PL-02, LY-66, and their combination improved muscle strength, explosiveness, and endurance performance, and had beneficial effects on body composition and gastrointestinal health, as evidenced by data obtained from non-athlete participants.


Asunto(s)
Microbioma Gastrointestinal , Lactobacillus plantarum , Lactococcus lactis , Fuerza Muscular , Resistencia Física , Probióticos , Humanos , Probióticos/administración & dosificación , Método Doble Ciego , Masculino , Resistencia Física/fisiología , Femenino , Adulto , Adulto Joven , Consumo de Oxígeno , Músculo Esquelético/fisiología , Ejercicio Físico/fisiología
6.
Food Funct ; 15(12): 6424-6437, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38771619

RESUMEN

Obesity requires treatment to mitigate the potential development of further metabolic disorders, including diabetes, hyperlipidemia, tumor growth, and non-alcoholic fatty liver disease. We investigated the anti-obesity effect of a 30% ethanol extract of Eisenia bicyclis (Kjellman) Setchell (EEB) on 3T3-L1 preadipocytes and high-fat diet (HFD)-induced obese C57BL/6 mice. Adipogenesis transcription factors including peroxisome proliferator-activated receptor (PPAR)γ, CCAAT/enhancer-binding protein-alpha (C/EBPα), and sterol regulatory element-binding protein-1 (SREBP-1) were ameliorated through the AMP-activated protein kinase (AMPK) pathway by EEB treatment in differentiated 3T3-L1 cells. EEB attenuated mitotic clonal expansion by upregulating cyclin-dependent kinase inhibitors (CDKIs) while downregulating cyclins and CDKs. In HFD-fed mice, EEB significantly decreased the total body weight, fat tissue weight, and fat in the tissue. The protein expression of PPARγ, C/EBPα, and SREBP-1 was increased in the subcutaneous fat and liver tissues, while EEB decreased the expression levels of these transcription factors. EEB also inhibited lipogenesis by downregulating acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) expression in the subcutaneous fat and liver tissues. Moreover, the phosphorylation of AMPK and ACC was downregulated in the HFD-induced mouse group, whereas the administration of EEB improved AMPK and ACC phosphorylation; thus, EEB treatment may be related to the AMPK pathway. Histological analysis showed that EEB reduced the adipocyte size and fat accumulation in subcutaneous fat and liver tissues, respectively. EEB promotes thermogenesis in brown adipose tissue and improves insulin and leptin levels and blood lipid profiles. Our results suggest that EEB could be used as a potential agent to prevent obesity.


Asunto(s)
Células 3T3-L1 , Proteínas Quinasas Activadas por AMP , Fármacos Antiobesidad , Dieta Alta en Grasa , Ratones Endogámicos C57BL , Obesidad , Extractos Vegetales , Transducción de Señal , Animales , Ratones , Dieta Alta en Grasa/efectos adversos , Extractos Vegetales/farmacología , Proteínas Quinasas Activadas por AMP/metabolismo , Proteínas Quinasas Activadas por AMP/genética , Masculino , Fármacos Antiobesidad/farmacología , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Transducción de Señal/efectos de los fármacos , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Adipogénesis/efectos de los fármacos , PPAR gamma/metabolismo , PPAR gamma/genética , Proteína alfa Potenciadora de Unión a CCAAT/metabolismo , Proteína alfa Potenciadora de Unión a CCAAT/genética , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Algas Comestibles , Kelp
7.
Biofactors ; 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38760159

RESUMEN

Angiopoietin-like protein 4 (ANGPTL4) is a secretory glycoprotein involved in regulating glucose homeostasis in non-pregnant subjects. However, its role in glucose metabolism during pregnancy and the pathophysiology of gestational diabetes mellitus (GDM) remains elusive. Thus, this study aimed to clarify the relationship between ANGPTL4 and GDM and investigate the pathophysiology of placental ANGPTL4 in glucose metabolism. We investigated this issue using blood and placenta samples in 957 pregnant women, the human 3A-sub-E trophoblast cell line, and the L6 skeletal muscle cell line. We found that ANGPTL4 expression in the placenta was higher in obese pregnant women than in lean controls. Palmitic acid significantly induced ANGPTL4 expression in trophoblast cells in a dose-response manner. ANGPTL4 overexpression in trophoblast cells resulted in endoplasmic reticulum (ER) stress, which stimulated the expression and secretion of growth hormone-variant (GH2) but not human placental lactogen. In L6 skeletal muscle cells, soluble ANGPTL4 suppressed insulin-mediated glucose uptake through the epidermal growth factor receptor (EGFR)/extracellular signal-regulated kinases 1/2 (ERK 1/2) pathways. In pregnant women, plasma ANGPTL4 concentrations in the first trimester predicted the incidence of GDM and were positively associated with BMI, plasma triglyceride, and plasma GH2 in the first trimester. However, they were negatively associated with insulin sensitivity index ISI0,120 in the second trimester. Overall, placental ANGPTL4 is induced by obesity and is involved in the pathophysiology of GDM via the induction of ER stress and GH2 secretion. Soluble ANGPTL4 can lead to insulin resistance in skeletal muscle cells and is an early biomarker for predicting GDM.

8.
PLoS One ; 19(5): e0299602, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38696439

RESUMEN

PURPOSE: The purposes of this study were to determine whether biomechanical properties of mature oocytes could predict usable blastocyst formation better than morphological information or maternal factors, and to demonstrate the safety of the aspiration measurement procedure used to determine the biomechanical properties of oocytes. METHODS: A prospective split cohort study was conducted with patients from two IVF clinics who underwent in vitro fertilization. Each patient's oocytes were randomly divided into a measurement group and a control group. The aspiration depth into a micropipette was measured, and the biomechanical properties were derived. Oocyte fertilization, day 3 morphology, and blastocyst development were observed and compared between measured and unmeasured cohorts. A predictive classifier was trained to predict usable blastocyst formation and compared to the predictions of four experienced embryologists. RESULTS: 68 patients and their corresponding 1252 oocytes were included in the study. In the safety analyses, there was no significant difference between the cohorts for fertilization, while the day 3 and 5 embryo development were not negatively affected. Four embryologists predicted usable blastocyst development based on oocyte morphology with an average accuracy of 44% while the predictive classifier achieved an accuracy of 71%. Retaining the variables necessary for normal fertilization, only data from successfully fertilized oocytes were used, resulting in a classifier an accuracy of 81%. CONCLUSIONS: To date, there is no standard guideline or technique to aid in the selection of oocytes that have a higher likelihood of developing into usable blastocysts, which are chosen for transfer or vitrification. This study provides a comprehensive workflow of extracting biomechanical properties and building a predictive classifier using these properties to predict mature oocytes' developmental potential. The classifier has greater accuracy in predicting the formation of usable blastocysts than the predictions provided by morphological information or maternal factors. The measurement procedure did not negatively affect embryo culture outcomes. While further analysis is necessary, this study shows the potential of using biomechanical properties of oocytes to predict embryo developmental outcomes.


Asunto(s)
Blastocisto , Desarrollo Embrionario , Fertilización In Vitro , Oocitos , Humanos , Blastocisto/fisiología , Blastocisto/citología , Femenino , Oocitos/fisiología , Oocitos/citología , Adulto , Fenómenos Biomecánicos , Fertilización In Vitro/métodos , Desarrollo Embrionario/fisiología , Estudios Prospectivos
10.
Nutrients ; 16(10)2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38794745

RESUMEN

Obesity is primarily exacerbated by excessive lipid accumulation during adipogenesis, with triacylglycerol (TG) as a major lipid marker. However, as the association between numerous lipid markers and various health conditions has recently been revealed, investigating the lipid metabolism in detail has become necessary. This study investigates the lipid metabolic effects of Hydrangea serrata (Thunb.) Ser. hot water leaf extract (WHS) on adipogenesis using LC-MS-based lipidomics analysis of undifferentiated, differentiated, and WHS-treated differentiated 3T3-L1 cells. WHS treatment effectively suppressed the elevation of glycerolipids, including TG and DG, and prevented a molecular shift in fatty acyl composition towards long-chain unsaturated fatty acids. This shift also impacted glycerophospholipid metabolism. Additionally, WHS stabilized significant lipid markers such as the PC/PE and LPC/PE ratios, SM, and Cer, which are associated with obesity and related comorbidities. This study suggests that WHS could reduce obesity-related risk factors by regulating lipid markers during adipogenesis. This study is the first to assess the underlying lipidomic mechanisms of the adipogenesis-inhibitory effect of WHS, highlighting its potential in developing natural products for treating obesity and related conditions. Our study provides a new strategy for the development of natural products for the treatment of obesity and related diseases.


Asunto(s)
Células 3T3-L1 , Adipogénesis , Hydrangea , Metabolismo de los Lípidos , Lipidómica , Extractos Vegetales , Hojas de la Planta , Adipogénesis/efectos de los fármacos , Extractos Vegetales/farmacología , Hojas de la Planta/química , Animales , Ratones , Hydrangea/química , Metabolismo de los Lípidos/efectos de los fármacos , Agua/química , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Triglicéridos/metabolismo , Obesidad/prevención & control
11.
World J Mens Health ; 42(3): 658-659, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38606858
12.
Dermatitis ; 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38563786

RESUMEN

Background: Mutations in filaggrin (FLG), the gene that codes for the skin barrier protein, have been shown to be associated with atopic dermatitis (AD). Objective: The objectives of this study were to determine the effects of genetic counseling and parental education on infants at a high risk of AD. Methods: We enrolled 7521 newborns in Taiwan from January 1, 2016, to March 30, 2020, and all of them received genetic testing encompassing 20 known FLG mutations. The genetic counseling and AD prevention and care team consisted of pediatricians, dermatologists, social workers, and genetic counselors. The counseling was arranged for at least 30 minutes within 45 days after delivery. Results: A total of 2963 high-risk infants (39.4%) were identified. Homozygous c.1432C>T was the most commonly identified mutation. A total of 418 neonates' parents were stratified into counseling and noncounseling groups, where the effect of parental education was evaluated. The genetically stratified parental education program was effective in preventing AD development by 63.3% in high-risk infants before 12 months of life (P < 0.0001). Conclusion: Genetic stratification and parental education are effective in preventing the development of AD in high-risk infants before 12 months of life.

13.
Dig Dis ; : 1-7, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38599188

RESUMEN

INTRODUCTION: Clarithromycin resistance is a crucial factor in the eradication of Helicobacter pylori. This study aimed to evaluate the performance of MmaxSure™ H. pylori & ClaR Assay (MmaxSure™) in the diagnosis and detection of clarithromycin resistance in H. pylori. METHODS: Subjects who underwent esophagogastroduodenoscopy between April 2020 and October 2022 were enrolled. The diagnostic performances of MmaxSure™ and dual priming oligonucleotide (DPO)-based multiplex polymerase chain reaction (PCR) were compared with the rapid urease test and culture. Secondary gene sequencing analysis was performed in discordant cases of PCR tests. RESULTS: A total of 156 gastric biopsy samples were analyzed. In H. pylori detection, MmaxSure™ showed a 95.9% sensitivity (95% CI: 90.6-98.6), a 42.7% specificity (95% CI: 26.3-60.7), and a kappa value of 0.457. For the detection of A2143G mutation samples, MmaxSure™ showed a 91.2% sensitivity (95% CI: 76.3-98.1), a 93.4% specificity (95% CI: 87.5-97.1), and a kappa value of 0.804. There were a total of 10 discordant cases compared to gene sequencing in A2143G mutation detection for MmaxSure™. CONCLUSION: In this study, MmaxSure™ showed comparable diagnostic performance to DPO-PCR in the detection of the H. pylori and A2143G mutation. Further research is needed to confirm the clinical effectiveness of the MmaxSure™ assay in H. pylori eradication.

14.
Cancers (Basel) ; 16(5)2024 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-38473283

RESUMEN

This study evaluated the magnetic resonance imaging (MRI) findings of endometrial cancer (EC) patients and identified differences based on risk group and molecular classification. The study involved a total of 175 EC patients. The MRI data were retrospectively reviewed and compared based on the risk of recurrence. Additionally, the associations between imaging phenotypes and genomic signatures were assessed. The low-risk and non-low-risk groups (intermediate, high-intermediate, high, metastatic) showed significant differences in tumor diameter (p < 0.001), signal intensity and heterogeneity on diffusion-weighted imaging (DWI) (p = 0.003), deep myometrial invasion (involvement of more than 50% of the myometrium), cervical invasion (p < 0.001), extrauterine extension (p = 0.002), and lymphadenopathy (p = 0.003). Greater diffusion restriction and more heterogeneity on DWI were exhibited in the non-low-risk group than in the low-risk group. Deep myometrial invasion, cervical invasion, extrauterine extension, lymphadenopathy, recurrence, and stage discrepancy were more common in the non-low-risk group (p < 0.001). A significant difference in microsatellite stability status was observed in the heterogeneity of the contrast-enhanced T1-weighted images (p = 0.027). However, no significant differences were found in MRI parameters related to TP53 mutation. MRI features can be valuable predictors for differentiating risk groups in patients with EC. However, further investigations are needed to explore the imaging markers based on molecular classification.

15.
Investig Clin Urol ; 65(2): 115-123, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38454820

RESUMEN

Non-gonococcal sexually transmitted infections (STIs) include chlamydia, syphilis, and chancroids. Chlamydia is the most common STI caused by Chlamydia trachomatis and is mainly transmitted through sexual intercourse or vertical transmission at birth. Although symptoms are mostly absent or mild, untreated chlamydial infections in females can lead to pelvic inflammatory disease, chronic pelvic pain, and infertility due to the narrowing of fallopian tubes. Syphilis is caused by Treponema pallidum and is divided into phase I, phase II, latent syphilis, and phase III. The incidence of syphilis, including congenital syphilis, has significantly increased in the United States in recent years. The chronic status of this disease can significantly increase morbidity and potentially affect almost all body organs, which, in rare cases, can lead to death. Additionally, untreated maternal syphilis can lead to fetal death and fatal congenital infections in newborns. Chancroid is an STI caused by Haemophilus ducreyi, and its prevalence is gradually decreasing in Korea and worldwide. The symptoms include shallow genital ulcers with suppurative granulomatous inflammation and tender inguinal lymphadenopathy. Chancroids can be differentiated from syphilitic chancres based on their appearance. In contrast to painless chancres, chancroids are painful. Ureaplasma urealyticum, Ureaplasma parvum, and Mycoplasma hominis are considered symbiotic bacteria. Infections caused by these bacteria are usually not considered STIs and do not require treatment unless they are suspected of being associated with infertility. This article presents the 2023 Korean STI guidelines for non-gonococcal bacterial infections.


Asunto(s)
Infecciones Bacterianas , Infertilidad , Enfermedades de Transmisión Sexual , Sífilis , Femenino , Humanos , Recién Nacido , Chlamydia trachomatis , Inflamación , República de Corea , Enfermedades de Transmisión Sexual/complicaciones , Enfermedades de Transmisión Sexual/epidemiología , Sífilis/complicaciones
16.
J Nanobiotechnology ; 22(1): 83, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38424578

RESUMEN

BACKGROUND: Immunotherapy with clodronate-encapsulated liposomes, which induce macrophage depletion, has been studied extensively. However, previously reported liposomal formulation-based drugs (Clodrosome® and m-Clodrosome®) are limited by their inconsistent size and therapeutic efficacy. Thus, we aimed to achieve consistent therapeutic effects by effectively depleting macrophages with uniform-sized liposomes. RESULTS: We developed four types of click chemistry-based liposome nanoplatforms that were uniformly sized and encapsulated with clodronate, for effective macrophage depletion, followed by conjugation with Man-N3 and radiolabeling. Functionalization with Man-N3 improves the specific targeting of M2 macrophages, and radioisotope labeling enables in vivo imaging of the liposome nanoplatforms. The functionalized liposome nanoplatforms are stable under physiological conditions. The difference in the biodistribution of the four liposome nanoplatforms in vivo were recorded using positron emission tomography imaging. Among the four platforms, the clodronate-encapsulated mannosylated liposome effectively depleted M2 macrophages in the normal liver and tumor microenvironment ex vivo compared to that by Clodrosome® and m-Clodrosome®. CONCLUSION: The newly-developed liposome nanoplatform, with finely tuned size control, high in vivo stability, and excellent ex vivo M2 macrophage targeting and depletion effects, is a promising macrophage-depleting agent.


Asunto(s)
Ácido Clodrónico , Liposomas , Masculino , Humanos , Liposomas/farmacología , Ácido Clodrónico/farmacología , Distribución Tisular , Macrófagos
17.
Am J Cancer Res ; 14(1): 169-181, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38323273

RESUMEN

One-carbon metabolism plays a crucial role in tumorigenesis as it supplies the one-carbon units necessary for nucleotide synthesis, epigenetic regulation, and redox metabolism, ensuring the rapid proliferation of cancer cells. However, their roles in prostate cancer progression remain poorly understood. In this study, we investigated the association between genetic variants in the one-carbon metabolism pathway and clinical outcomes in patients receiving androgen deprivation therapy for prostate cancer. The associations of 130 single-nucleotide polymorphisms located within 14 genes involved in the one-carbon metabolism pathway with cancer-specific survival (CSS), overall survival, and progression-free survival were assessed using Cox regression in 630 patients with prostate cancer. Subsequently, functional studies were performed using prostate cancer cell lines. After adjusting for covariates and multiple testing, MTHFD1L rs2073190 was found to be significantly associated with CSS (P = 0.000184). Further pooled analysis of multiple datasets demonstrated that MTHFD1L was upregulated in prostate cancer and increased MTHFD1L expression was positively correlated with tumor aggressiveness and poor patient prognosis. Functionally, MTHFD1L knockdown suppressed prostate cancer cell proliferation and colony formation. RNA sequencing and pathway analysis revealed that differentially expressed genes were predominantly enriched in the cell cycle pathway. In conclusion, genetic variants in MTHFD1L of one-carbon metabolism may serve as promising predictors, and our findings offer valuable insights into the underlying genetic mechanisms of prostate cancer progression.

18.
Korean J Radiol ; 25(1): 43-54, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38184768

RESUMEN

OBJECTIVE: To evaluate the added value of diffusion-weighted imaging (DWI)-based quantitative parameters to distinguish uterine sarcomas from atypical leiomyomas on preoperative magnetic resonance imaging (MRI). MATERIALS AND METHODS: A total of 138 patients (age, 43.7 ± 10.3 years) with uterine sarcoma (n = 44) and atypical leiomyoma (n = 94) were retrospectively collected from four institutions. The cohort was randomly divided into training (84/138, 60.0%) and validation (54/138, 40.0%) sets. Two independent readers evaluated six qualitative MRI features and two DWI-based quantitative parameters for each index tumor. Multivariable logistic regression was used to identify the relevant qualitative MRI features. Diagnostic classifiers based on qualitative MRI features alone and in combination with DWI-based quantitative parameters were developed using a logistic regression algorithm. The diagnostic performance of the classifiers was evaluated using a cross-table analysis and calculation of the area under the receiver operating characteristic curve (AUC). RESULTS: Mean apparent diffusion coefficient value of uterine sarcoma was lower than that of atypical leiomyoma (mean ± standard deviation, 0.94 ± 0.30 10-3 mm²/s vs. 1.23 ± 0.25 10-3 mm²/s; P < 0.001), and the relative contrast ratio was higher in the uterine sarcoma (8.16 ± 2.94 vs. 4.19 ± 2.66; P < 0.001). Selected qualitative MRI features included ill-defined margin (adjusted odds ratio [aOR], 17.9; 95% confidence interval [CI], 1.41-503, P = 0.040), intratumoral hemorrhage (aOR, 27.3; 95% CI, 3.74-596, P = 0.006), and absence of T2 dark area (aOR, 83.5; 95% CI, 12.4-1916, P < 0.001). The classifier that combined qualitative MRI features and DWI-based quantitative parameters showed significantly better performance than without DWI-based parameters in the validation set (AUC, 0.92 vs. 0.78; P < 0.001). CONCLUSION: The addition of DWI-based quantitative parameters to qualitative MRI features improved the diagnostic performance of the logistic regression classifier in differentiating uterine sarcomas from atypical leiomyomas on preoperative MRI.


Asunto(s)
Leiomioma , Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Adulto , Persona de Mediana Edad , Modelos Logísticos , Estudios Retrospectivos , Imagen por Resonancia Magnética , Leiomioma/diagnóstico por imagen , Leiomioma/cirugía , Sarcoma/diagnóstico por imagen , Sarcoma/cirugía
19.
J Korean Med Sci ; 39(3): e33, 2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38258365

RESUMEN

BACKGROUND: Over the last decade, extracorporeal membrane oxygenation (ECMO) use in critically ill children has increased and is associated with favorable outcomes. Our study aims to evaluate the current status of pediatric ECMO in Korea, with a specific focus on its volume and changes in survival rates based on diagnostic indications. METHODS: This multicenter study retrospectively analyzed the indications and outcomes of pediatric ECMO over 10 years in patients at 14 hospitals in Korea from January 2012 to December 2021. Four diagnostic categories (neonatal respiratory, pediatric respiratory, post-cardiotomy, and cardiac-medical) and trends were compared between periods 1 (2012-2016) and 2 (2017-2021). RESULTS: Overall, 1065 ECMO runs were performed on 1032 patients, with the annual number of cases remaining unchanged over the 10 years. ECMO was most frequently used for post-cardiotomy (42.4%), cardiac-medical (31.8%), pediatric respiratory (17.5%), and neonatal respiratory (8.2%) cases. A 3.7% increase and 6.1% decrease in pediatric respiratory and post-cardiotomy cases, respectively, were noted between periods 1 and 2. Among the four groups, the cardiac-medical group had the highest survival rate (51.2%), followed by the pediatric respiratory (46.4%), post-cardiotomy (36.5%), and neonatal respiratory (29.4%) groups. A consistent improvement was noted in patient survival over the 10 years, with a significant increase between the two periods from 38.2% to 47.1% (P = 0.004). Improvement in survival was evident in post-cardiotomy cases (30-45%, P = 0.002). Significant associations with mortality were observed in neonates, patients requiring dialysis, and those treated with extracorporeal cardiopulmonary resuscitation (P < 0.001). In pediatric respiratory ECMO, immunocompromised patients also showed a significant correlation with mortality (P < 0.001). CONCLUSION: Pediatric ECMO demonstrated a steady increase in overall survival in Korea; however, further efforts are needed since the outcomes remain suboptimal compared with global outcomes.


Asunto(s)
Reanimación Cardiopulmonar , Oxigenación por Membrana Extracorpórea , Recién Nacido , Humanos , Niño , Estudios Retrospectivos , Corazón , República de Corea/epidemiología
20.
Clin Chim Acta ; 554: 117775, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38220135

RESUMEN

BACKGROUND: Large-for-gestational-age (LGA) neonates have increased risk of adverse pregnancy outcomes and adult metabolic diseases. We aimed to investigate the relationship between plasma angiopoietin-like protein 4 (ANGPTL4), a protein involved in lipid and glucose metabolism during pregnancy, placental function, growth factors, and the risk of LGA. METHODS: We conducted a prospective cohort study and recruited women with singleton pregnancies at the National Taiwan University Hospital between 2013 and 2018. First trimester maternal plasma ANGPTL4 concentrations were measured. RESULTS: Among 353 pregnant women recruited, the LGA group had higher first trimester plasma ANGPTL4 concentrations than the appropriate-for-gestational-age group. Plasma ANGPTL4 was associated with hemoglobin A1c, post-load plasma glucose, plasma triglyceride, plasma free fatty acid concentrations, plasma growth hormone variant (GH-V), and birth weight, but was not associated with cord blood growth factors. After adjusting for age, body mass index, hemoglobin A1c, and plasma triglyceride concentrations, plasma ANGPTL4 concentrations were significantly associated with LGA risk, and its predictive performance, as measured by the area under the receiver operating characteristic curve, outperformed traditional risk factors for LGA. CONCLUSIONS: Plasma ANGPTL4 is associated with glucose and lipid metabolism during pregnancy, plasma GH-V, and birth weight, and is an early biomarker for predicting the risk of LGA.


Asunto(s)
Glucosa , Metabolismo de los Lípidos , Adulto , Recién Nacido , Embarazo , Femenino , Humanos , Peso al Nacer , Proteína 4 Similar a la Angiopoyetina , Hemoglobina Glucada , Estudios Prospectivos , Placenta , Resultado del Embarazo , Edad Gestacional , Triglicéridos
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