RESUMEN

Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion: This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

RESUMEN

BACKGROUND: Keloids and hypertrophic scars result from abnormal collagen accumulation and the inhibition of its degradation. Although the pathogenesis remains unclear, excessive accumulation of the extracellular matrix (ECM) is believed to be associated with the TGF-ß/SMAD pathway. Zinc-alpha-2-glycoprotein (ZAG) inhibits TGF-ß-mediated epithelial-to-mesenchymal transdifferentiation and impacts skin barrier functions. In this study, we investigated the potential of a small ZAG-derived peptide against hypertrophic scars and keloids. METHODS: The study examined cell proliferation and mRNA expression of collagen types I and III in human dermal fibroblast (HDF) cell lines and keloid-derived fibroblasts (KF) following ZAG peptide treatment. A rat incisional wound model was used to evaluate the effect of ZAG peptide in scar tissue. RESULTS: Significantly lower mRNA levels of collagen types I and III were observed in ZAG-treated fibroblasts, whereas matrix metalloproteinase (MMP)-1 and MMP-3 mRNA levels were significantly increased in HDFs and KFs. Furthermore, ZAG peptide significantly reduced protein expression of collagen type I and III, TGF-ß1, and p-Smad2/3 complex in KFs. Rat incisional scar models treated with ZAG peptide presented narrower scar areas and reduced immature collagen deposition, along with decreased expression of collagen type I, α-SMA, and p-Smad2/3. CONCLUSION: ZAG peptide effectively suppresses the TGF-ß and p-Smad2/3 pathway and inhibits excessive cell proliferation during scar formation, suggesting its potential therapeutic implications against keloids and hypertrophic scars.

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This study examines the interplay between ambient temperature, brown adipose tissue (BAT) function, and bone metabolism, emphasizing the effects of cold exposure and BAT mitochondrial activity on bone health. Utilizing ovariectomized (OVX) mice to model primary osteoporosis and BAT-specific mitochondrial dysfunction (BKO) mice, we evaluated the impact of housing temperature on bone density, immune modulation in bone marrow, and the protective role of BAT against bone loss. Cold exposure was found to universally reduce bone mass, enhance osteoclastogenesis, and alter bone marrow T-cell populations, implicating the immune system in bone remodeling under cold stress. The thermogenic function of BAT, driven by mitochondrial oxidative phosphorylation, was crucial in protecting against bone loss. Impaired BAT function, through surgical removal or mitochondrial dysfunction, exacerbated bone loss in cold environments, highlighting BAT's metabolic role in maintaining bone health. Furthermore, cold-induced changes in BAT function led to systemic metabolic shifts, including elevated long-chain fatty acids, which influenced osteoclast differentiation and activity. These findings suggest a systemic mechanism connecting environmental temperature and BAT metabolism with bone physiology, providing new insights into the metabolic and environmental determinants of bone health. Future research could lead to novel bone disease therapies targeting these pathways.

Asunto(s)

Tejido Adiposo Pardo , Frío , Mitocondrias , Osteoporosis , Animales , Tejido Adiposo Pardo/metabolismo , Femenino , Ratones , Mitocondrias/metabolismo , Osteoporosis/metabolismo , Osteoporosis/patología , Osteoclastos/metabolismo , Ratones Endogámicos C57BL , Densidad Ósea , Termogénesis , Ovariectomía/efectos adversos , Huesos/metabolismo , Huesos/patología , Osteogénesis

RESUMEN

Angiopoietin-like 4 (ANGPTL4) has been identified as an adipokine involved in several non-metabolic and metabolic diseases, including angiogenesis, glucose homeostasis, and lipid metabolism. To date, the role of ANGPTL4 in cancer growth and progression, and metastasis, has been variable. Accumulating evidence suggests that proteolytic processing and posttranslational modifications of ANGPTL4 can significantly alter its function, and may contribute to the multiple and conflicting roles of ANGPTL4 in a tissue-dependent manner. With the growing interest in ANGPTL4 in cancer diagnosis and therapy, we aim to provide an up-to-date review of the implications of ANGPTL4 as a biomarker/oncogene in cancer metabolism, metastasis, and the tumor microenvironment (TME). In cancer cells, ANGPTL4 plays an important role in regulating metabolism by altering intracellular glucose, lipid, and amino acid metabolism. We also highlight the knowledge gaps and future prospect of ANGPTL4 in lymphatic metastasis and perineural invasion through various signaling pathways, underscoring its importance in cancer progression and prognosis. Through this review, a better understanding of the role of ANGPTL4 in cancer progression within the TME will provide new insights into other aspects of tumorigenesis and the potential therapeutic value of ANGPTL4. [BMB Reports 2024; 57(8): 343-351].

Asunto(s)

Proteína 4 Similar a la Angiopoyetina , Progresión de la Enfermedad , Neoplasias , Microambiente Tumoral , Humanos , Proteína 4 Similar a la Angiopoyetina/metabolismo , Proteína 4 Similar a la Angiopoyetina/genética , Neoplasias/metabolismo , Neoplasias/patología , Microambiente Tumoral/fisiología , Animales , Metabolismo de los Lípidos/fisiología , Metástasis de la Neoplasia , Transducción de Señal

RESUMEN

Importance: Conventional research and guidelines on postgastrectomy follow-up for gastric cancer often restrict their focus to the first 5 years after surgery. Objective: To evaluate the association of extended regular follow-up after 5 years postgastrectomy in patients with gastric cancer with overall and postrecurrence survival rates. Design, Setting, and Participants: This population-based, retrospective cohort study used Korean National Health Insurance claims data extracted between January 1, 2005, and December 31, 2014, with follow-up data examined until December 31, 2021. Patients without recurrence or other cancers at 5 years postgastrectomy were divided into 2 groups: those who had extended regular follow-up visits and those who did not. The data were analyzed between August 15 and November 15, 2023. Exposures: Regular follow-up vs irregular follow-up after 5 years postgastrectomy. Main Outcomes and Measures: The main outcome was whether extended regular follow-up after 5 years postgastrectomy was independently associated with overall and postrecurrence survival rates using Cox proportional hazards regression. Postrecurrence survival rates were also compared across different follow-up methods and intervals. Results: A total of 40 468 patients with gastric cancer were included, with 14 294 in the regular follow-up group (mean [SD] age, 61.3 [11.7] years; 9669 male [67.8%]) and 26 174 in the irregular follow-up group (mean [SD] age, 58.1 [11.1] years; 18 007 male [68.8%]). Late recurrence or gastric remnant cancer (GRC) was identified in 3138 patients (7.8%), including 1610 of 40 468 patients (4.0%) between 5 and 10 years postgastrectomy and 1528 of 16 287 (9.4%) patients after 10 years postgastrectomy. Regular follow-up was associated with a significantly decreased overall mortality rate after 5 years postgastrectomy (from 49.4% to 36.9% in 15-year mortality rate; P < .001), as well as significant improvement of postrecurrence survival rate after occurrence of late recurrence or GRC (from 32.7% to 71.1% in 5-year postrecurrence survival rate; P < .001). Comparison of follow-up methods revealed that the combination of endoscopy and abdominopelvic computed tomography (CT) (only abdominopelvic CT in total gastrectomy subgroup) yielded the highest 5-year postrecurrence survival rate (endoscopy alone vs abdominopelvic CT alone vs a combination of both, 54.5% vs 47.1% vs 74.5%, respectively). A time interval of more than 2 years between previous endoscopy or abdominopelvic CT and late recurrence and GRC diagnosis was associated with a significantly reduced postrecurrence survival rate (hazard ratio, 1.72 [95% CI, 1.45-2.04] and 1.48 [95% CI, 1.25-1.75], respectively). Conclusions and Relevance: These findings suggest that extended regular follow-up after 5 years postgastrectomy should be implemented clinically and that current practice and value of follow-up protocols in postoperative care of patients with gastric cancer be reconsidered.

Asunto(s)

Estudios de Factibilidad , Gastrectomía , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Anciano , Estudios de Seguimiento , República de Corea/epidemiología , Recurrencia Local de Neoplasia , Factores de Tiempo , Adulto

RESUMEN

Magnoliae Flos (MF) is a medicinal herb widely employed in traditional medicine for relieving sinusitis, allergic rhinitis, headaches, and toothaches. Here, we investigated the potential preventive effects of MF extract (MFE) against 4-vinylcyclohexene diepoxide (VCD)-induced ovotoxicity in ovarian cells and a mouse model of premature ovarian insufficiency (POI). The cytoprotective effects of MFE were assessed using CHO-K1 or COV434 cells. In vivo, B6C3F1 female mice were intraperitoneally injected with VCD for two weeks to induce POI, while MFE was orally administered for four weeks, beginning one week before VCD administration. VCD led to a significant decline in the viabilities of CHO-K1 and COV434 cells and triggered excessive reactive oxygen species (ROS) production and apoptosis specifically in CHO-K1 cells. However, pretreatment with MFE effectively prevented VCD-induced cell death and ROS generation, while also activating the Akt signaling pathway. In vivo, MFE increased relative ovary weights, follicle numbers, and serum estradiol and anti-Müllerian hormone levels versus controls under conditions of ovary failure. Collectively, our results demonstrate that MFE has a preventive effect on VCD-induced ovotoxicity through Akt activation. These results suggest that MFE may have the potential to prevent and manage conditions such as POI and diminished ovarian reserve.

Asunto(s)

Cricetulus , Ovario , Extractos Vegetales , Insuficiencia Ovárica Primaria , Especies Reactivas de Oxígeno , Animales , Femenino , Ratones , Células CHO , Insuficiencia Ovárica Primaria/inducido químicamente , Insuficiencia Ovárica Primaria/prevención & control , Ovario/efectos de los fármacos , Ovario/metabolismo , Ovario/patología , Extractos Vegetales/farmacología , Extractos Vegetales/química , Especies Reactivas de Oxígeno/metabolismo , Apoptosis/efectos de los fármacos , Compuestos de Vinilo/farmacología , Ciclohexenos/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Modelos Animales de Enfermedad , Transducción de Señal/efectos de los fármacos

RESUMEN

BACKGROUND: Although peripartum cardiomyopathy (PPCM) is a fatal disease affecting young patients and fetuses, little is known about its recent prognosis and risk factors. This study investigated temporal trends in clinical characteristics and outcomes for PPCM in a nationwide multicenter registry. METHODS AND RESULTS: The study population comprised 340 patients (mean age, 33 years) who were diagnosed with PPCM between January 2000 and September 2022 in 26 tertiary hospitals in South Korea. PPCM was defined as heart failure with left ventricular ejection fraction ≤45% and no previously known cardiac disease. The main study outcomes included time to the first occurrence of all-cause death, heart transplantation, and cardiovascular hospitalization. The diagnosis of PPCM cases increased notably during the study period (P<0.001). However, clinical outcomes showed no significant improvement (all-cause death for 10 years: 0.9% [2000-2010] versus 2.3% [2011-2022], P=0.450; all-cause death and heart transplantation for 10 years: 3.6% [2000-2010] versus 3.0% [2011-2022] P=0.520; all-cause death, heart transplantation, and cardiovascular hospitalization for 10 years: 11.7% [2000-2010] versus 19.8% [2011-2022], P=0.240). High body mass index (hazard ratio [HR], 1.106 [95% CI, 1.024-1.196]; P=0.011), the presence of gestational diabetes (HR, 5.346 [95% CI, 1.778-16.07]; P=0.002), and increased baseline left ventricular end-diastolic dimension (HR, 1.078 [95% CI, 1.002-1.159]; P=0.044) were significant risk factors for poor prognosis. CONCLUSIONS: While the incidence of PPCM has increased over the past 20 years, the prognosis has not improved significantly. Timely management and close follow-up are necessary for high-risk patients with PPCM with high body mass index, gestational diabetes, or large left ventricular end-diastolic dimension.

Asunto(s)

Cardiomiopatías , Periodo Periparto , Complicaciones Cardiovasculares del Embarazo , Sistema de Registros , Humanos , Femenino , Adulto , Embarazo , República de Corea/epidemiología , Cardiomiopatías/epidemiología , Cardiomiopatías/terapia , Cardiomiopatías/fisiopatología , Cardiomiopatías/mortalidad , Complicaciones Cardiovasculares del Embarazo/epidemiología , Complicaciones Cardiovasculares del Embarazo/terapia , Factores de Riesgo , Factores de Tiempo , Trasplante de Corazón/tendencias , Trasplante de Corazón/estadística & datos numéricos , Pronóstico , Función Ventricular Izquierda , Volumen Sistólico , Causas de Muerte/tendencias , Hospitalización/tendencias , Hospitalización/estadística & datos numéricos , Trastornos Puerperales/epidemiología , Trastornos Puerperales/terapia , Trastornos Puerperales/mortalidad , Trastornos Puerperales/fisiopatología , Estudios Retrospectivos , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca/fisiopatología , Incidencia

RESUMEN

BACKGROUND: Androgenetic alopecia (AGA) is a common and chronic problem characterized by hair follicle miniaturization. AIMS: In this study, heat-treated Limosilactobacillus fermentum LM1020 (HT-LM1020) was investigated in human follicle dermal papilla cell (HFDPC), scalp tissue, and clinical trials for patients with AGA. PATIENTS/METHODS: Cell proliferation and the expression of cyclins and cyclin-dependent kinases (CDKs) were measured in HFDPC. The relative gene expression of 5α-reductase and growth factors were investigated in hair scalp. This double-blind, randomized, placebo-controlled clinical trial was conducted over 24 weeks. Primary efficacy was evaluated by measuring hair density, and secondary efficacy was assessed by experts and self-assessment. Changes in the microbiota of the hair scalps were analyzed using 16S metagenome amplicon sequencing. RESULTS: HT-LM1020 promoted cell growth (p < 0.001) and cyclin B1 expression, and it reduced 5α-reductase and induced fibroblast growth factor 7 (FGF7), FGF10, and epithelial growth factor7 (EGF7) (p < 0.001). In the clinical trial, the experimental group demonstrated an increase in hair density from 133.70 to 148.87 n/cm2 at Week 24 (p < 0.001), while also expressing satisfaction with their hair density, reduced hair loss, and hairline. At Week 24, the total ratio of lactic acid bacteria operational taxonomic unit (OTU) in the scalp increased from 6.65% to 26.19%. At the same period, placebo-controlled group decreased Staphylococcus caprae OTU from 77.95% to 14.57% while experimental group decreased from 65.80% to 41.02%. CONCLUSIONS: These present results showed that HT-LM1020 was a co-effector of ingredients for anti-hair loss contributing to cell proliferation and the expression of CDKs.

Asunto(s)

Alopecia , Limosilactobacillus fermentum , Microbiota , Cuero Cabelludo , Humanos , Alopecia/terapia , Alopecia/microbiología , Alopecia/tratamiento farmacológico , Método Doble Ciego , Cuero Cabelludo/microbiología , Microbiota/efectos de los fármacos , Adulto , Limosilactobacillus fermentum/fisiología , Limosilactobacillus fermentum/aislamiento & purificación , Masculino , Femenino , Cabello/microbiología , Cabello/crecimiento & desarrollo , Persona de Mediana Edad , Folículo Piloso/microbiología , Calor , Proliferación Celular/efectos de los fármacos

RESUMEN

Small plaque psoriasis is the typical form of chronic plaque psoriasis affecting adults in South Korea. The effectiveness of calcipotriol/betamethasone dipropionate (Cal/BD) aerosol foam for large and small psoriasis plaques has not previously been examined. We performed a post hoc analysis of a recent, 4-week observational study of Cal/BD aerosol foam use in routine clinical practice in South Korea. Investigator Global Assessment response ([IGA] 0/1 at week 4), Patient Global Assessment response ([PaGA] 0/1 at week 4), change in Psoriasis Area and Severity Index (PASI), changes in psoriasis symptom scores, change in the Dermatology Life Quality Index (DLQI), and the proportion of patients achieving DLQI ≤5 were analyzed for patients with small (≤5 cm; n = 131) or large (>5 cm; n = 35) baseline plaque size. IGA response rates were similar for patients with small and large plaques (59.5% and 51.4% respectively). Similarly, there was no significant difference between the small and large groups in mean change in PASI (-2.20 vs -3.34), the proportions of patients with DLQI ≤5 (62.3% vs 54.3%) or PaGA 0/1 (29.2% vs 40.0%). Mean improvements in DLQI (-4.04 vs -6.20) and in psoriasis symptoms including itching (-1.50 vs -2.83), sleep loss (-0.67 vs -1.89), dryness (-1.57 vs -2.97), scaling (-1.21 vs -3.57), and redness (-1.17 vs -3.11) were greater in patients with large plaques than those with small plaques. Itching and DLQI differences were not statistically significant after adjustment for baseline characteristics. Stratification by body surface area affected eliminated statistically significant differences between the groups for most outcomes. In conclusion, this analysis suggests that Cal/BD aerosol foam is an effective, well-accepted treatment for adult patients with the small plaques typical of chronic plaque psoriasis in South Korea, as well as for those with large plaques.

Asunto(s)

Aerosoles , Betametasona , Calcitriol , Fármacos Dermatológicos , Psoriasis , Calidad de Vida , Índice de Severidad de la Enfermedad , Humanos , Psoriasis/tratamiento farmacológico , Psoriasis/diagnóstico , Psoriasis/patología , Calcitriol/análogos & derivados , Calcitriol/administración & dosificación , Masculino , Betametasona/administración & dosificación , Betametasona/análogos & derivados , Femenino , República de Corea , Persona de Mediana Edad , Adulto , Resultado del Tratamiento , Fármacos Dermatológicos/administración & dosificación , Combinación de Medicamentos , Anciano

RESUMEN

BACKGROUND AND OBJECTIVES: Accumulating evidence shows that sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce adverse cardiovascular outcomes. However, whether SGLT2i, compared with other antidiabetic drugs, reduce the new development of atrial fibrillation (AF) is unclear. In this study, we compared SGLT2i with dipeptidyl peptidase-4 inhibitors (DPP-4is) in terms of reduction in the risk of AF in individuals with type 2 diabetes. METHODS: We included 42,786 propensity score-matched pairs of SGLT2i and DPP-4i users without previous AF diagnosis using the Korean National Health Insurance Service database between May 1, 2016, and December 31, 2018. RESULTS: During a median follow-up of 1.3 years, SGLT2i users had a lower incidence of AF than DPP-4i users (1.95 vs. 2.65 per 1,000 person-years; hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.55-0.97; p=0.028]). In individuals without heart failure, SGLT2i users was associated with a decreased risk of AF incidence (HR, 0.70; 95% CI, 0.52-0.94; p=0.019) compared to DPP-4i users. However, individuals with heart failure, SGLT2i users was not significantly associated with a change in risk (HR, 1.04; 95% CI, 0.44-2.44; p=0.936). CONCLUSIONS: In this nationwide cohort study of individuals with type 2 diabetes, treatment with SGLT2i was associated with a lower risk of AF compared with treatment with DPP-4i.

RESUMEN

The increasing economic losses associated with growth retardation caused by Enterocytozoon hepatopenaei (EHP), a microsporidian parasite infecting penaeid shrimp, require effective monitoring. The internal transcribed spacer (ITS)-1 region, the non-coding region of ribosomal clusters between 18S and 5.8S rRNA genes, is widely used in phylogenetic studies due to its high variability. In this study, the ITS-1 region sequence (~600-bp) of EHP was first identified, and primers for a polymerase chain reaction (PCR) assay targeting that sequence were designed. A newly developed nested-PCR method successfully detected the EHP in various shrimp (Penaeus vannamei and P. monodon) and related samples, including water and feces collected from Indonesia, Thailand, South Korea, India, and Malaysia. The primers did not cross-react with other hosts and pathogens, and this PCR assay is more sensitive than existing PCR detection methods targeting the small subunit ribosomal RNA (SSU rRNA) and spore wall protein (SWP) genes. Phylogenetic analysis based on the ITS-1 sequences indicated that the Indonesian strain was distinct (86.2% nucleotide sequence identity) from other strains collected from Thailand and South Korea, and also showed the internal diversity among Thailand (N = 7, divided into four branches) and South Korean (N = 5, divided into two branches) samples. The results revealed the ability of the ITS-1 region to determine the genetic diversity of EHP from different geographical origins.

Asunto(s)

ADN Espaciador Ribosómico , Enterocytozoon , Microsporidiosis , Penaeidae , Filogenia , Reacción en Cadena de la Polimerasa , Enterocytozoon/genética , Enterocytozoon/aislamiento & purificación , Enterocytozoon/clasificación , Penaeidae/microbiología , Penaeidae/parasitología , Animales , ADN Espaciador Ribosómico/genética , Reacción en Cadena de la Polimerasa/métodos , Microsporidiosis/microbiología , Microsporidiosis/diagnóstico , ADN de Hongos/genética , Cartilla de ADN/genética , Heces/microbiología , Heces/parasitología , Análisis de Secuencia de ADN , Tailandia

RESUMEN

BACKGROUND: The average glycated hemoglobin (HbA1c) may not accurately reflect glycemic control status during the mid-term after acute myocardial infarction (AMI). We aimed to evaluate changes in HbA1c and their effect on mid-term clinical outcomes in patients with diabetes and AMI. METHODS: We enrolled patients with diabetes ( n  = 967) who underwent HbA1c measurement in the Korean nationwide registry. These patients were categorized into three groups based on changes in HbA1c from index admission to the 1-year follow-up visit: a decrease in HbA1c > 1%, changes in HbA1c within 1%, and an increase in HbA1c > 1%. Clinical outcomes at 24 months were examined. RESULTS: The baseline HbA1c levels were 8.55 ±â€…0.85, 7.00 ±â€…0.98 and 7.07 ±â€…1.05 ( P  = 0.001) and HbA1c levels after 1 year were 6.62 ±â€…0.73, 7.05 ±â€…0.98 and 9.26 ±â€…1.59 ( P  = 0.001) for patients with 3 groups, respectively. Patients with a 1% decrease in HbA1c had significantly lower incidence of major adverse cardiovascular events (MACE), cardiac death, and rehospitalization after 24 months than those with a 1% increase in HbA1c. However, in the Cox regression analysis, a >1% decrease in HbA1c change was not an independent factor for MACE, cardiac death, and rehospitalization. CONCLUSIONS: Our analysis indicates that an HbA1c decrease of >1% within the first 12 months was not an independent prognostic factor until the 24-month mark. Therefore, standard diabetic control is recommended for patients with diabetes and AMI for up to 2 years.

Asunto(s)

Biomarcadores , Diabetes Mellitus , Hemoglobina Glucada , Infarto del Miocardio , Sistema de Registros , Humanos , Hemoglobina Glucada/metabolismo , Masculino , Femenino , Infarto del Miocardio/sangre , Persona de Mediana Edad , República de Corea/epidemiología , Anciano , Factores de Tiempo , Diabetes Mellitus/sangre , Diabetes Mellitus/epidemiología , Biomarcadores/sangre , Factores de Riesgo , Readmisión del Paciente/estadística & datos numéricos , Glucemia/metabolismo , Control Glucémico/métodos , Resultado del Tratamiento

RESUMEN

Objectives: Chronic low-grade inflammation is widely recognized as a pathophysiological defect contributing to ß-cell failure in type 2 diabetes mellitus (T2DM). Statin therapy is known to ameliorate CD8+ T cell senescence, a mediator of chronic inflammation. However, the additional immunomodulatory roles of ezetimibe are not fully understood. Therefore, we investigated the effect of statin or statin/ezetimibe combination treatment on T cell senescence markers. Methods: In this two-group parallel and randomized controlled trial, we enrolled 149 patients with T2DM whose low-density lipoprotein cholesterol (LDL-C) was 100 mg/dL or higher. Patients were randomly assigned to either the rosuvastatin group (N=74) or the rosuvastatin/ezetimibe group (N=75). The immunophenotype of peripheral blood mononuclear cells and metabolic profiles were analyzed using samples from baseline and post-12 weeks of medication. Results: The fractions of CD8+CD57+ (senescent CD8+ T cells) and CD4+FoxP3+ (Treg) significantly decreased after intervention in the rosuvastatin/ezetimibe group (-4.5 ± 14.1% and -1.2 ± 2.3%, respectively), while these fractions showed minimal change in the rosuvastatin group (2.8 ± 9.4% and 1.4 ± 1.5%, respectively). The degree of LDL-C reduction was correlated with an improvement in HbA1c (R=0.193, p=0.021). Changes in the CD8+CD57+ fraction positively correlated with patient age (R=0.538, p=0.026). Notably, the fraction change in senescent CD8+ T cells showed no significant relationship with changes in either HbA1c (p=0.314) or LDL-C (p=0.592). Finally, the ratio of naïve to memory CD8+ T cells increased in the rosuvastatin/ezetimibe group (p=0.011), but not in the rosuvastatin group (p=0.339). Conclusions: We observed a reduction in senescent CD8+ T cells and an increase in the ratio of naive to memory CD8+ T cells with rosuvastatin/ezetimibe treatment. Our results demonstrate the immunomodulatory roles of ezetimibe in combination with statins, independent of improvements in lipid or HbA1c levels.

Asunto(s)

Anticolesterolemiantes , Azetidinas , Diabetes Mellitus Tipo 2 , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Hipercolesterolemia , Humanos , Rosuvastatina Cálcica/uso terapéutico , Ezetimiba/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , LDL-Colesterol , Anticolesterolemiantes/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hemoglobina Glucada , Leucocitos Mononucleares , Hipercolesterolemia/tratamiento farmacológico , Azetidinas/uso terapéutico , Fluorobencenos/uso terapéutico , Pirimidinas , Sulfonamidas/uso terapéutico , Quimioterapia Combinada , Resultado del Tratamiento , Inflamación/tratamiento farmacológico , Linfocitos T

RESUMEN

BACKGROUND: Frailty frequently coexists with hypertension in older patients. We aimed to evaluate the association between frailty and positional change in blood pressure, especially orthostatic hypertension. METHODS: Participants were recruited from 12 University hospitals in South Korea. Using a digital device, trained research nurses measured blood pressure in the supine and standing positions. Physical frailty was evaluated using the Korean version of the FRAIL questionnaire, gait speed, and handgrip strength. Orthostatic hypertension was defined as a ≥20-mm Hg increase in systolic blood pressure within 3 minutes of standing and upright systolic blood pressure of ≥140 mm Hg. RESULTS: We analyzed the data of 2065 participants who had been enrolled until December 31, 2022. The mean age was 73.2±5.6 years, and 52.0% were female. The mean blood pressure was 137.1±14.9/75.1±9.7 mm Hg. Among the participants, 1886 (91.3%) showed normal response after standing, but 94 (4.6%) had orthostatic hypertension, and 85 (4.1%) had orthostatic hypotension. Orthostatic hypertension was associated with female sex, obesity, cognitive function, physical frailty, and lower quality of life. In the multivariable analysis, body mass index and frailty status were independently associated with orthostatic hypertension. CONCLUSIONS: Orthostatic hypertension is associated with physical frailty, cognitive impairment, and low quality of life in older patients with hypertension. Therefore, evaluation of orthostatic blood pressure changes to confirm orthostatic hypertension or hypotension in frail older adults will serve as an important diagnostic procedure in vulnerable patients. Further studies are required to identify the underlying mechanisms of this association.

Asunto(s)

Fragilidad , Hipertensión , Humanos , Femenino , Masculino , Anciano , Fragilidad/fisiopatología , Fragilidad/epidemiología , Fragilidad/diagnóstico , República de Corea/epidemiología , Hipertensión/fisiopatología , Hipertensión/epidemiología , Hipertensión/diagnóstico , Hipotensión Ortostática/fisiopatología , Hipotensión Ortostática/epidemiología , Hipotensión Ortostática/diagnóstico , Presión Sanguínea/fisiología , Anciano Frágil/estadística & datos numéricos , Calidad de Vida , Anciano de 80 o más Años , Fuerza de la Mano/fisiología , Determinación de la Presión Sanguínea/métodos

RESUMEN

BACKGROUND: As the prevalence of hypertension increases with age and the proportion of the older population is also on the rise, research on the characteristics of older hypertensive patients and the importance of frailty is necessary. This study aimed to identify clinical characteristics of older hypertension in Korea and to investigate these characteristics based on frailty status. METHODS: The HOW to Optimize eLDerly systolic BP (HOWOLD-BP) is a prospective, multicenter, open-label, randomized clinical trial that aims to compare intensive (target systolic blood pressure [SBP] ≤ 130 mmHg) with standard (target SBP ≤ 140 mmHg) treatment to reduce cardiovascular events in older hypertensive Korean patients aged ≥ 65 years. Data were analyzed through a screening assessment of 2,085 patients recruited from 11 university hospitals. Demographic, functional (physical and cognitive), medical history, laboratory data, quality of life, and medication history of antihypertensive drugs were assessed. RESULTS: The mean age was 73.2 years (standard deviation ± 5.60), and 48.0% (n = 1,001) were male. Prevalent conditions included dyslipidemia (66.5%), obesity (body mass index ≥ 25 kg/m², 53.6%), and diabetes (28.9%). Dizziness and orthostatic hypotension were self-reported by 1.6% (n = 33) and 1.2% (n = 24), respectively. The majority of patients were on two antihypertensive drugs (48.4%), while 27.5% (n = 574) and 20.8% (n = 433) were on 1 and 3 antihypertensive medications, respectively. Frail to pre-frail patients were older and also tended to have dependent instrumental activities of daily living, slower gait speed, weaker grip strength, lower quality of life, and lower cognitive function. The frail to pre-frail group reported more dizziness (2.6% vs. 1.2%, P < 0.001) and had concerning clinical factors, including lower glomerular filtration rate, more comorbidities such as diabetes, stroke, and a history of admission. Frail to pre-frail older hypertensive patients used slightly more antihypertensive medications than robust older hypertensive patients (1.95 vs. 2.06, P = 0.003). Pre-frail to frail patients often chose beta-blockers as a third medication over diuretics. CONCLUSION: This study described the general clinical characteristics of older hypertensive patients in Korea. Frail hypertensive patients face challenges in achieving positive clinical outcomes because of multifactorial causes: they are older, have more morbidities, decreased function, lower quality of life and cognitive function, and take more antihypertensive medications. Therefore, it is essential to comprehensively evaluate and monitor disease-related or drug-related adverse events more frequently during regular check-ups, which is necessary for pre-frail to frail older patients with hypertension. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0003787.

Asunto(s)

Diabetes Mellitus , Fragilidad , Hipertensión , Anciano , Humanos , Masculino , Femenino , Antihipertensivos/efectos adversos , Fragilidad/epidemiología , Fragilidad/diagnóstico , Calidad de Vida , Actividades Cotidianas , Estudios Prospectivos , Mareo , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Presión Sanguínea , Diabetes Mellitus/epidemiología , Diabetes Mellitus/tratamiento farmacológico , República de Corea/epidemiología

RESUMEN

BACKGROUND: Recent in vitro and in vivo studies have suggested that the elastin peptide improves the skin's biophysical properties, enhancing the proliferation of fibroblasts and elastin synthesis, resulting in anti-aging properties. Therefore, we conducted a randomized, double-blinded, placebo-controlled study to clinically evaluate the effect of elastin peptide intake on human skin. MATERIALS AND METHODS: Healthy adult participants (N = 100) were randomly assigned to receive a test product containing 100 mg of Bonito elastin peptide (VGPG Elastin® ) or placebo. In this study, all participants were Asian from Korea. The parameters of skin wrinkles, hydration, and brightening (melanin index) were measured at baseline and 4, 8, and 12 weeks after intervention. RESULTS: The average skin roughness, maximum peak-to-valley values, maximum peak height of the wrinkle, maximum valley depth of the wrinkle, average maximum height of the wrinkle, and eye wrinkle volume improved considerably in the test group compared with the placebo after 12 weeks of intervention. Skin hydration was enhanced, and the melanin index was significantly lower in the test group than in the placebo group. No participant experienced adverse events related to the test product. CONCLUSION: Oral consumption of Bonito elastin peptide (VGPG Elastin®) reduced fine wrinkles, enhanced skin moisture, and decreased melanin index without significant adverse effects and may be a promising anti-wrinkle, anti-dryness, and anti-pigmentation treatment.

Asunto(s)

Envejecimiento de la Piel , Adulto , Animales , Humanos , Melaninas , Piel , Péptidos/efectos adversos , Elastina/farmacología , Método Doble Ciego

RESUMEN

The aging of white adipose tissue (WAT) involves senescence of adipose stem and progenitor cells (ASPCs) and dysregulation of immune cell populations, serving as a major driver of age-associated adipose dysfunction and metabolic diseases. Conversely, the elimination of senescent ASPCs is associated with improvements in overall health. Intermittent fasting (IF), a dietary intervention that incorporates periodic cycles of fasting and refeeding, has been reported to promote weight loss and fat mass reduction and improve glucose and insulin homeostasis in both murine and human studies. While previous studies have assessed the effects of IF on obesity-associated metabolic dysfunction, few studies have examined the aging-specific changes to ASPCs and immune cell populations in WAT. Here, we show that IF in 18-20-month-old mice reduced senescent phenotypes of ASPCs and restored their adipogenic potential. Intriguingly, IF-treated mice exhibited an increase in adipose eosinophils, which has been reported to be associated with improved WAT homeostasis and immunological fitness in aged mice. The observed cellular and metabolic changes suggest that IF may be a feasible lifestyle regimen to reduce cellular senescence which could result in attenuation of downstream aging-induced WAT dysfunction and metabolic diseases.

Asunto(s)

Inmunosenescencia , Enfermedades Metabólicas , Ratones , Humanos , Animales , Anciano , Ayuno Intermitente , Rejuvenecimiento , Tejido Adiposo Blanco/metabolismo , Obesidad/metabolismo , Enfermedades Metabólicas/metabolismo

RESUMEN

BACKGROUND: More than half of acne patients have truncal acne on their chest, back, and shoulders. However, since most studies on acne have focused on the face, data on clinical characteristics and proper management for truncal acne are insufficient. OBJECTIVE: To establish a Korean Acne Rosacea Society (KARS) consensus for experts' perception and treatment patterns of truncal acne. METHODS: We conducted two rounds of the Dephi technique to gather expert opinion and reach a consensus on truncal acne. The first round comprised 48 questionnaires focusing on various aspects such as epidemiology, clinical features, diagnosis, treatment, prognosis and more, while second rounds consisted of 26 questionnaires. RESULTS: A total of 36 dermatologists (36/38 KARS members, 94.7%) completed this survey. In the first-round survey, consensus was reached on 20 out of the 48 questions (41.7%). In the second-round questionnaire, consensus was achieved on 9 of the 26 questions (34.6%). The most unresponsive lesion to truncal acne treatment was scars (atrophic/hypertrophic). The most commonly used treatments for each non-inflammatory and inflammatory truncal acne lesions were selected to use topical retinoids (78.1% of the responders) and oral antibiotics (93.8% of the responders). CONCLUSION: Our study has yielded valuable insights into the epidemiology, clinical manifestations, diagnosis, treatment, and quality of life of patients with truncal acne. We anticipate that this study will inspire further comprehensive research for individuals with truncal acne.

RESUMEN

This study aimed to determine whether amplitude modulation (A-mode) ultrasound (US) provides accurate and reliable measurements comparable to those obtained using brightness modulation (B-mode) US under diverse conditions. Thirty healthy participants (15 women and 15 men) underwent measurements of subcutaneous fat thickness (SFT), muscle thickness (MT), and muscle quality (MQ) in the trapezius and biceps brachii muscles using both US modes before and after exercises designed to stimulate the respective muscles. Among the three key indices, the results demonstrated the high validity of the A-mode, with minimal mean differences (MDs) between the two devices less than 0.91 mm and intra-class correlation coefficients (ICCs) exceeding 0.95 for all measures. In addition, the correlation coefficients between the error scores and average scores for the trapezius and biceps brachii suggested no evidence of systematic error. The trapezius MT and MQ significantly increased, and the biceps brachii MT significantly increased after the exercises (p < 0.05). Notably, both the A- and B-modes exhibited the same trend in these post-exercise changes in the muscle. This study suggests that low-cost and low-resolution A-mode US provides measurements of SFT, MT, and MQ similar to the more expensive, high-resolution B-mode imaging. A-mode US is an affordable and portable alternative for muscle assessment.