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1.
Transl Lung Cancer Res ; 13(8): 1768-1779, 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39263025

RESUMO

Background: Molecular and transcription factor subtyping were recently introduced to identify patients with unique clinical features in small cell lung cancer (SCLC). However, its prognostic relevance is yet to be established. This study aims to investigate the clinical implications and prognostic significance of transcription factor subtyping in SCLC using immunohistochemistry. Methods: One hundred and ninety consecutive SCLC patients treated with platinum-based chemotherapy at a single institution were retrospectively reviewed. Expression of ASCL1, NeuroD1, POU2F3, and YAP1 was assessed by immunohistochemical staining and applied to determine the transcription factor subtype of each case. Results: The association among transcription factors was not entirely mutually exclusive. YAP1 expression was the most significant prognostic indicator compared with other transcription factors or their related subtypes. Among patients with limited-stage disease (LD), complete response (CR) rates were 46.2% and 22.4% in the YAP1-positive and YAP1-negative groups, respectively. The median duration of response among patients who achieved CR was 64.8 and 36.4 months in the YAP1-positive and YAP1-negative groups, respectively (P=0.06). Median overall survival (OS) in LD was 35.6 and 16.9 months in the YAP1-positive and YAP1-negative groups, respectively (P=0.03). In extensive-stage disease (ED), the median OS was 11.3 months for the YAP1-positive group and 11 months for the YAP1-negative group (P=0.03). Conclusions: Positive expression of YAP1 can be associated with durable CR and favorable survival outcomes in patients with SCLC, especially in LD.

2.
Gene ; 931: 148895, 2024 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-39187137

RESUMO

Root-knot nematode (Meloidogyne incognita) causes severe crop damage and large economic losses worldwide. Several cultivars of sweetpotato [Ipomoea batatas (L.) Lam)] have been developed with root-knot nematode-resistant traits; however, many of these cultivars do not have favorable agronomic characteristics. To understand the genetic traits underlying M. incognita resistance in sweetpotato, whole genome resequencing was conducted on three RKN-susceptible (Dahomi, Shinhwangmi, and Yulmi) and three RKN-resistant (Danjami, Pungwonmi, and Juhwangmi) sweetpotato cultivars. Three SNPs (single nucleotide polymorphisms) in promotor sequences were shared in RKN-resistant cultivars and were correlated with disease resistance. One of these SNPs was located in G6617|TU10904, which encoded a homolog of RIBOSOMAL PROTEIN EL15Z, and was associated with reduced expression in RKN-resistant cultivars only. Alongside SNP analysis, mRNA-seq data were analyzed for the same cultivars with and without nematode infection, and 18 nematode-sensitive genes were identified that responded in a cultivar-specific manner. Of these genes, expression of G8735|TU14367 was lower in sensitive cultivars than in RKN-resistant cultivars. Overall, this study identified two genes that potentially have key roles in the regulation of nematode resistance and will be useful targets for nematode resistance breeding programs.


Assuntos
Resistência à Doença , Ipomoea batatas , Doenças das Plantas , Polimorfismo de Nucleotídeo Único , Tylenchoidea , Ipomoea batatas/genética , Ipomoea batatas/parasitologia , Animais , Resistência à Doença/genética , Tylenchoidea/genética , Tylenchoidea/fisiologia , Doenças das Plantas/parasitologia , Doenças das Plantas/genética , Raízes de Plantas/genética , Raízes de Plantas/parasitologia , Variação Genética
3.
Trends Biotechnol ; 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39174388

RESUMO

We report the development of a metabolically engineered bacterium for the fermentative production of polyesters containing aromatic side chains, serving as sustainable alternatives to petroleum-based plastics. A metabolic pathway was constructed in an Escherichia coli strain to produce poly[d-phenyllactate(PhLA)], followed by three strategies to enhance polymer production. First, polyhydroxyalkanoate (PHA) granule-associated proteins (phasins) were introduced to increase the polymer accumulation. Next, metabolic engineering was performed to redirect the metabolic flux toward PhLA. Furthermore, PHA synthase was engineered based on in silico simulation results to enhance the polymerization of PhLA. The final strain was capable of producing 12.3 g/l of poly(PhLA), marking it the first bio-based process for producing an aromatic homopolyester. Additional heterologous gene introductions led to the high level production of poly(3-hydroxybutyrate-co-11.7 mol% PhLA) copolymer (61.4 g/l). The strategies described here will be useful for the bio-based production of aromatic polyesters from renewable resources.

4.
Korean Circ J ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39175343

RESUMO

BACKGROUND AND OBJECTIVES: Familial hypercholesterolemia (FH) increases the risk of premature cardiovascular disease through disrupted low-density lipoprotein cholesterol (LDL-C) metabolism. Although FH is a severe condition, it remains widely underdiagnosed, which can be attributed to barriers in genetic testing and a lack of awareness. This study aims to propose and evaluate a targeted screening program for FH in South Korea by integrating the General Health Screening Program (GHSP) with cascade genetic screening. METHODS: The study included individuals with LDL-C levels ≥190 mg/dL identified during the 2021 GHSP (primary participants). Data on demographics, lifestyle, medical history, and family history were collected through questionnaires. Targeted next-generation sequencing was used to identify pathogenic mutations in the PCSK9, APOB, LDLRAP1, and LDLR genes associated with FH. Pathogenic mutations found in primary participants were confirmed in their relatives (secondary participants) using Sanger sequencing. Participant characteristics were analyzed based on the presence of pathogenic mutations. RESULTS: Among 83 individuals with severe hypercholesterolemia identified through the GHSP, 7 primary participants (8.4%) carried pathogenic mutations in the LDLR and PCSK9 genes. In secondary participants, pathogenic mutations were identified in 61.1% of the relatives of 4 patients with pathogenic mutations. The prevalence of pathogenic mutations was significantly higher in primary participants compared to secondary participants. CONCLUSIONS: Integrating community resources with FH screening can enhance the early detection and treatment of FH. By utilizing GHSP data and adding genetic screening, the proposed model provides a strategy to reduce the cardiovascular risks associated with FH, supporting its wider adoption at the national level.

5.
Artigo em Inglês | MEDLINE | ID: mdl-39115991

RESUMO

Output stabilizing control of biological systems is of utmost importance in systems biology since key phenotypes of biological networks are often encoded by a small subset of their phenotypic marker nodes. This study addresses the challenge of output stabilizing control for complex biological systems modeled by Boolean networks (BNs). The objective is to identify a set of constant control inputs capable of driving the BN toward a desirable long-term behavior with respect to specified output nodes. Leveraging the algebraic properties of Boolean logic, we develop a novel control algorithm that reformulates the output stabilizing control problem into a simple graph theoretic problem involving auxiliary BNs, the scale of which significantly decreases compared to the original BN. The proposed method ensures superiority over previous results in terms of both the number of control inputs and computational loads, since it searches for the solution within the reduced BNs while retaining essential structures needed for output stabilization. The efficacy of the proposed control scheme is demonstrated through extensive numerical experiments with complex random BNs and real biological networks. To support the reproducible research initiative, detailed results of numerical experiments are provided in the supplementary material, and all the implementation codes are made accessible at https://github.com/choonlog/OutputStabilization.

6.
Korean J Radiol ; 25(8): 715-725, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39109500

RESUMO

OBJECTIVE: To evaluate the outcomes of drug-eluting bead transarterial chemoembolization (DEB-TACE) according to the size of the beads for the treatment of small hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This retrospective study included 212 patients with a single HCC ≤5 cm from five tertiary institutions. One hundred and nine patients were treated with 70-150-µm doxorubicin DEBs (group A), and 103 patients received 100-300-µm doxorubicin DEBs (group B). The initial tumor response (assessed between 3 weeks and 2 months after DEB-TACE), time to local tumor progression (TTLTP), restricted mean duration of complete response (RMDCR), rate of complications, incidence of post-embolization syndrome, and length of hospital stay were compared between the two groups. Logistic regression was used to analyze prognostic factors for initial tumor response. RESULTS: The initial objective response rates were 91.7% (100/109) and 84.5% (87/103) for groups A and B, respectively (P = 0.101). In the subgroup analysis of tumors ≤3 cm, the initial objective response rates were 94.6% (53/56) and 78.0% (39/50) for groups A and B, respectively (P = 0.012). There was no significant difference in the TTLTP (median, 23.7 months for group A vs. 19.0 months for group B; P = 0.278 [log-rank], 0.190 [multivariable Cox regression]) or RMDCR at 24 months (11.4 months vs. 8.5 months, respectively; P = 0.088). In the subgroup analysis of tumors >3-cm, the RMDCR at 24 months was significantly longer in group A than in group B (11.8 months vs. 5.7 months, P = 0.024). The incidence of mild bile duct dilatation after DEB-TACE was significantly higher in group B than in group A (5.5% [6/109] vs. 18.4% [19/103], P = 0.003). CONCLUSION: DEB-TACE using 70-150-µm microspheres demonstrated a higher initial objective response rate in ≤3-cm HCCs and a longer RMDCR at 24 months in 3.1-5-cm HCCs compared to larger DEBs (100-300-µm).


Assuntos
Antibióticos Antineoplásicos , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Doxorrubicina , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/diagnóstico por imagem , Quimioembolização Terapêutica/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doxorrubicina/administração & dosagem , Resultado do Tratamento , República da Coreia , Idoso , Antibióticos Antineoplásicos/administração & dosagem , Microesferas , Adulto
7.
Biomed Eng Online ; 23(1): 75, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39075456

RESUMO

The effects of the novel synthetic peptide, A7-1, on wound healing and skin grafts were evaluated in a C57BL/6 mouse model. Two 15-mm wide circular skin excisions were made on the backs of mice and to each excision, 100 µM A7-1 or normal saline was applied daily. The treatments were applied and sutured for skin graft analysis. Digital photos were acquired on days 4, 7, 11, and 14 and fluorescein angiography was conducted. Wound sizes were verified using stereoscopic microscopy. Histological analysis was performed via hematoxylin and eosin staining and Masson's trichrome staining. Western blotting was performed using vascular endothelial growth factor. Using a stereoscopic microscope, significantly faster wound healing (17.3%) and skin graft healing (16.5%) were observed in the A7-1 treatment group in comparison to that of the control. The angiogenesis was significantly faster in fluorescein angiography examination in wound healing (11%) and skin grafts (15%). However, the average completion of epithelization (overall time for wound healing), did not show any significant differences. In comparison to the control, the new protein, A7-1, led to significantly faster wound healing in the initial angiogenesis.


Assuntos
Camundongos Endogâmicos C57BL , Peptídeos , Cicatrização , Animais , Cicatrização/efeitos dos fármacos , Camundongos , Peptídeos/farmacologia , Peptídeos/química , Pele/efeitos dos fármacos , Masculino , Modelos Animais de Doenças , Transplante de Pele , Neovascularização Fisiológica/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo
8.
Eur J Pharmacol ; 979: 176854, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39059568

RESUMO

Obesity-induced muscle atrophy leads to physical impairment and metabolic dysfunction, which are risky for older adults. The activity of pyruvate dehydrogenase (PDH), a critical regulator of glucose metabolism, is reduced in obesity. Additionally, PDH activator dichloroacetate (DCA) improves metabolic dysfunction. However, the effects of PDH activation on skeletal muscles in obesity remain unclear. Thus, this study aimed to evaluate the effects of PDH activation by DCA treatment on obesity-induced muscle atrophy in vitro and in vivo and elucidate the possible underlying mechanisms. Results showed that PDH activation by DCA treatment ameliorated muscle loss, decreased the cross-sectional area, and reduced grip strength in C57BL/6 mice fed a high-fat diet (HFD). Elevation of muscle atrophic factors atrogin-1 and muscle RING-finger protein-1 (MuRF-1) and autophagy factors LC3BII and p62 were abrogated by DCA treatment in palmitate-treated C2C12 myotubes and in the skeletal muscles of HFD-fed mice. Moreover, p-Akt, p-FoxO1, and p-FoxO3 protein levels were reduced and p-NF-κB p65 and p-p38 MAPK protein levels were elevated in palmitate-treated C2C12 myotubes, which were restored by DCA treatment. However, the protective effects of DCA treatment against myotube atrophy were reversed by treatment with Akt inhibitor MK2206. Taken together, our study demonstrated that PDH activation by DCA treatment can alleviate obesity-induced muscle atrophy. It may serve as a basis for developing novel strategies to prevent obesity-associated muscle loss.


Assuntos
Ácido Dicloroacético , Dieta Hiperlipídica , Camundongos Endogâmicos C57BL , Atrofia Muscular , Obesidade , Animais , Ácido Dicloroacético/farmacologia , Ácido Dicloroacético/uso terapêutico , Atrofia Muscular/prevenção & controle , Atrofia Muscular/etiologia , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Obesidade/complicações , Obesidade/tratamento farmacológico , Camundongos , Masculino , Dieta Hiperlipídica/efeitos adversos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Músculo Esquelético/metabolismo , Complexo Piruvato Desidrogenase/metabolismo , Linhagem Celular , Ativação Enzimática/efeitos dos fármacos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/patologia , Fibras Musculares Esqueléticas/metabolismo , Autofagia/efeitos dos fármacos
9.
Pharmaceuticals (Basel) ; 17(7)2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-39065776

RESUMO

The incidence of cardiovascular diseases, such as high blood pressure, is increasing worldwide, owing to population aging and irregular lifestyle habits. Previous studies have reported the vasorelaxant effects of Prunus yedoensis bark methanol extract. However, various solvent extracts of P. yedoensis bark and their vascular relaxation mechanisms have not been sufficiently studied. We prepared extracts of P. yedoensis bark using various solvents (water, 30% ethanol, and 70% ethanol). P. yedoensis bark 30% ethanol extract (PYB-30E) decreased the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin in human umbilical vein endothelial cells (HUVECs) activated with 200 ng/mL TNF-α. Additionally, PYB-30E showed vasodilatory effects on isolated rat aortic rings. This was confirmed to be the result of the activation of the NO/cGMP pathway, regulation of non-selective calcium-activated K+ channels, and calcium channel blockade. Additionally, PYB-30E significantly reduced systolic and diastolic blood pressure in spontaneously hypertensive rats (SHR). Taken together, our results indicated that PYB-30E is a candidate functional material with preventive and therapeutic effects against hypertension.

10.
Bioresour Technol ; 407: 131116, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39019197

RESUMO

Methane, a potent greenhouse gas, requires sustainable mitigation strategies. Here, the microbial upcycling of methane to phytoene, a valuable colorless carotenoid with applications in the cosmeceutical industry was demonstrated. To achieve this goal, a stepwise metabolic engineering approach was employed in Methylocystis sp. MJC1, a methane-oxidizing bacterium. The incorporation of crtE and crtB genes from Deinococcus radiodurans R1 established the phytoene biosynthetic pathway. This pathway was fine-tuned through promoter optimization, resulting in a phytoene production of 450 µg/L from 37 mmol/L methane. Disrupting the ackA gene reduced a by-product, acetate, by 50 % and increased phytoene production by 56 %. Furthermore, overexpressing the dxs gene boosted phytoene titer 3-fold. The optimized strain produced 15 mg/L phytoene from 2 mol/L methane in fed-batch fermentation, a 4-fold increase in phytoene titer and 4-fold in yield. This demonstrates Methylocystis sp. MJC1's potential for efficient phytoene production and presents a novel approach for greenhouse gas reduction.


Assuntos
Engenharia Metabólica , Metano , Methylocystaceae , Metano/metabolismo , Engenharia Metabólica/métodos , Methylocystaceae/metabolismo , Methylocystaceae/genética , Carotenoides/metabolismo , Fermentação , Deinococcus/metabolismo , Deinococcus/genética , Regiões Promotoras Genéticas
11.
Thorac Cancer ; 15(21): 1646-1655, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38886905

RESUMO

BACKGROUND: Systemic inflammation is believed to contribute to small cell lung cancer (SCLC) progression, but the underlying relationship remains unclear. Lipocalin-2, a potential biomarker of inflammation, has been implicated in various cancers but its prognostic value in SCLC is underexplored. METHODS: We retrospectively analyzed 191 patients with SCLC (72 with limited-stage [LD] and 119 with extensive-stage) treated using platinum-based chemotherapy. Lipocalin-2 expression was evaluated using immunohistochemistry. Optimal cutoff values for lipocalin-2 and neutrophil-to-lymphocyte ratio (NLR) were determined using time-dependent receiver operating characteristic curve analysis. The pectoralis muscle index was used to assess sarcopenia. RESULTS: In LD-SCLC, high lipocalin-2 expression was associated with worse progression-free survival (PFS; median: 7.0 vs. 15.9 months, p = 0.015) and overall survival (OS; median: 12.9 vs. 30.3 months, p = 0.035) compared with low lipocalin-2 expression. Patients were stratified into three prognostic groups by combining lipocalin-2 with NLR: low lipocalin-2/low NLR, high lipocalin-2/low NLR or low lipocalin-2/high NLR, and high lipocalin-2/high NLR (median PFS: 17.3 vs. 11.0 vs. 6.3 months, p = 0.004; median OS: 30.5 vs. 17.3 vs. 8.6 months, p = 0.002). Similar trends were observed when combining lipocalin-2 with the pectoralis muscle index. High lipocalin-2 expression was also associated with lower complete response rates (18.9% vs. 34.3%, p = 0.035). No significant prognostic implications were found for lipocalin-2 in extensive-stage SCLC. CONCLUSIONS: High lipocalin-2 expression is potentially associated with poorer survival in LD-SCLC. Combining lipocalin-2 with other inflammation-related markers could improve prognostic stratification.


Assuntos
Biomarcadores Tumorais , Inflamação , Lipocalina-2 , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Lipocalina-2/metabolismo , Masculino , Feminino , Prognóstico , Carcinoma de Pequenas Células do Pulmão/metabolismo , Carcinoma de Pequenas Células do Pulmão/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Idoso , Pessoa de Meia-Idade , Biomarcadores Tumorais/metabolismo , Estudos Retrospectivos , Inflamação/metabolismo , Adulto , Idoso de 80 Anos ou mais
12.
Chemosphere ; 362: 142589, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38866334

RESUMO

The enrichment of phosphorus (P) and nitrogen (N) in aquatic systems can cause eutrophication. Moreover, P rocks may become exhausted in the next 100 years. A slow-release fertilizer called struvite (MgNH4PO4.6H2O) can reduce surface runoff. However, the high cost of raw material or chemicals is a bottleneck in their economical production. Therefore, incinerated sewage sludge ash, food wastewater, and bittern were combined as the sources of P, N, and Mg, respectively. Sawdust biochar was used to enhance the adsorptive recovery of nutrients. First, recovery kinetics was studied by comparing bittern-impregnated biochar (BtB) with the Mg-impregnated biochar (MgB). Subsequently, the synergistic physical and chemical interactions were observed for P and N recovery. Almost complete PO43-P recoveries were achieved within 10 min for both biochars. However, NH4+-N recovery was stable after 2 h, with 26% recovery by MgB and 20% recovery by BtB. Biochars activated with steam (steam-activated biochar) and KOH (KOH-activated biochar) gave superior activities to those of unactivated biochars and activated carbon (AC) nutrient recovery and struvite purity. Moreover, the activated biochars showed a lower risk of surface runoff, similar to that of AC. Therefore, activated biochars can be used as an alternative to AC for economical struvite production from a combination of wastewater sources.


Assuntos
Carvão Vegetal , Fertilizantes , Nitrogênio , Fósforo , Estruvita , Eliminação de Resíduos Líquidos , Águas Residuárias , Estruvita/química , Carvão Vegetal/química , Águas Residuárias/química , Fósforo/química , Fósforo/análise , Nitrogênio/química , Nitrogênio/análise , Fertilizantes/análise , Eliminação de Resíduos Líquidos/métodos , Nutrientes/análise , Esgotos/química , Adsorção , Poluentes Químicos da Água/química , Poluentes Químicos da Água/análise , Compostos de Magnésio/química , Fosfatos/química
13.
Cancers (Basel) ; 16(12)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38927986

RESUMO

This study investigates the role of SMARCD3 in gastric cancer by comparing its expression in signet ring cell (SRC) and well-differentiated (WD) groups within gastric cancer cell lines and tissues. We observed elevated SMARCD3 levels in the SRC group compared to the WD group. Functional analysis was conducted through both SMARCD3 knock-in and knock-out methods. Kaplan-Meier survival analysis indicated that higher SMARCD3 expression correlates with poorer overall survival in gastric cancer patients (HR 2.16, p < 0.001). SMARCD3 knock-out cells showed decreased proliferation, migration, invasion, and expression of epithelial-mesenchymal transition (EMT) markers, contrasting with results from temporary and stable SMARCD3 overexpression experiments, which demonstrated increased cell area and irregularity (p < 0.001). Further analysis revealed that SMARCD3 overexpression in MKN-74 cells significantly enhanced p-AKT-S473 and p-ERK levels (p < 0.05), and in KATO III cells, it increased ß-catenin and PI3Kp85 activities (p < 0.05). Conversely, these activities decreased in SNU 601 cells following SMARCD3 depletion. The study concludes that SMARCD3 overexpression may serve as a negative prognostic marker and a potential therapeutic target in gastric cancer treatment due to its role in promoting EMT.

14.
J Korean Med Sci ; 39(20): e169, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38804013

RESUMO

BACKGROUND: This research article investigates the age, period, and birth cohort effects on prevalence of obesity in the Korean population, with the goal of identifying key factors to inform effective public health strategies. METHODS: We analyzed data from the Korea National Health and Nutrition Examination Survey, spanning 2007-2021, including 35,736 men and 46,756 women. Using the hierarchical age-period-cohort (APC) analysis with cross-classified random effects modeling, we applied multivariable mixed logistic regression to estimate the marginal prevalence of obesity across age, period, and birth cohort, while assessing the interaction between APC and lifestyle and socioeconomic factors. RESULTS: Our findings reveal an inverted U-shaped age effect on obesity, influenced by smoking history (P for interaction = 0.020) and physical activity (I for interaction < 0.001). The period effect was positive in 2020 and 2021, while negative in 2014 (P for period effect < 0.001). A declining trend in obesity prevalence was observed in birth cohorts from 1980s onward. Notably, disparities in obesity rates among recent birth cohorts have increased in relation to smoking history (P for interaction = 0.020), physical activity (P for interaction < 0.001), and residence (P for interaction = 0.005). Particularly, those born after 1960 were more likely to be obese if they were ex-smokers, physical inactive, or lived in rural areas. CONCLUSION: These findings highlight growing disparities in obesity within birth cohorts, underscoring the need for targeted health policies that promote smoking cessation and physical activity, especially in rural areas.


Assuntos
Inquéritos Nutricionais , Obesidade , Humanos , República da Coreia/epidemiologia , Masculino , Obesidade/epidemiologia , Feminino , Pessoa de Meia-Idade , Adulto , Prevalência , Idoso , Estudos de Coortes , Fatores Socioeconômicos , Fumar/epidemiologia , Exercício Físico , Modelos Logísticos , Fatores Etários , Estilo de Vida , Adulto Jovem
15.
Pharmaceutics ; 16(5)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38794236

RESUMO

The blood-brain-barrier (BBB) is made up of blood vessels whose permeability enables the passage of some compounds. A predictive model of BBB permeability is important in the early stages of drug development. The predicted BBB permeabilities of drugs have been confirmed using a variety of in vitro methods to reduce the quantities of drug candidates needed in preclinical and clinical trials. Most prior studies have relied on animal or cell-culture models, which do not fully recapitulate the human BBB. The development of microfluidic models of human-derived BBB cells could address this issue. We analyzed a model for predicting BBB permeability using the Emulate BBB-on-a-chip machine. Ten compounds were evaluated, and their permeabilities were estimated. Our study demonstrated that the permeability trends of ten compounds in our microfluidic-based system resembled those observed in previous animal and cell-based experiments. Furthermore, we established a general correlation between the partition coefficient (Kp) and the apparent permeability (Papp). In conclusion, we introduced a new paradigm for predicting BBB permeability using microfluidic-based systems.

16.
Front Plant Sci ; 15: 1365298, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38736441

RESUMO

Cannabis sativa L. is an industrially valuable plant known for its cannabinoids, such as cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), renowned for its therapeutic and psychoactive properties. Despite its significance, the cannabis industry has encountered difficulties in guaranteeing consistent product quality throughout the drying process. Hyperspectral imaging (HSI), combined with advanced machine learning technology, has been used to predict phytochemicals that presents a promising solution for maintaining cannabis quality control. We examined the dynamic changes in cannabinoid compositions under diverse drying conditions and developed a non-destructive method to appraise the quality of cannabis flowers using HSI and machine learning. Even when the relative weight and water content remained constant throughout the drying process, drying conditions significantly influenced the levels of CBD, THC, and their precursors. These results emphasize the importance of determining the exact drying endpoint. To develop HSI-based models for predicting cannabis quality indicators, including dryness, precursor conversion of CBD and THC, and CBD : THC ratio, we employed various spectral preprocessing methods and machine learning algorithms, including logistic regression (LR), support vector machine (SVM), k-nearest neighbor (KNN), random forest (RF), and Gaussian naïve Bayes (GNB). The LR model demonstrated the highest accuracy at 94.7-99.7% when used in conjunction with spectral pre-processing techniques such as multiplicative scatter correction (MSC) or Savitzky-Golay filter. We propose that the HSI-based model holds the potential to serve as a valuable tool for monitoring cannabinoid composition and determining optimal drying endpoint. This tool offers the means to achieve uniform cannabis quality and optimize the drying process in the industry.

17.
Brain Tumor Res Treat ; 12(2): 132-140, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38742263

RESUMO

Giant cell tumors (GCTs) are locally aggressive primary bone tumors of osteoclast-like cells. Most GCTs occur within the long bones, and primary GCTs involving the clivus are extremely rare. We present the case of an 18-year-old boy with binocular horizontal diplopia with an insidious onset who was found to have a hypointense enhancing mass involving the clivus and left side dorsum sellae on magnetic resonance images. The tumor was completely resected via an endoscopic endonasal transclival approach, and histopathologic examination via immunohistochemistry indicated a GCT. The patient's left abducens nerve palsy improved slightly after surgery. Because of the rarity of GCTs, there is no consensus about the definitive treatment protocol. However, we suggest that gross total resection is the treatment of choice, and denosumab plays a critical role in patients with subtotal resection.

18.
Cancer Cell Int ; 24(1): 153, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38685086

RESUMO

BACKGROUND: The exosome-mediated extracellular secretion of miRNAs occurs in many cancers, and RAB27A is a potent regulator of exosome secretion. For metastatic renal cell carcinoma (RCC), this study examines the mechanisms of cancer metastasis via the RAB27A-regulated secretion of specific miRNAs. METHODS: RAB27A knockdown (KD) and overexpressing (OE) RCC cells were used to examine cell migration and adhesion. The particle counts and sizes of exosomes in RAB27A OE cells were analyzed using Exoview, and those of intraluminal vesicles (ILV) and multivesicular bodies (MVB) were measured using an electron microscope. Analysis of RNA sequences, protein-protein interaction networks, and the competing endogenous RNA (ceRNA) network were used to identify representative downregulated miRNAs that are likely to undergo cargo-sorting into exosomes and subsequent secretion. A molecular beacon of miR-137-3p, one of the most representatively downregulated genes with a fold change of 339, was produced, and its secretion was analyzed using Exoview. RAB27A OE and control cells were incubated in an exosome-containing media to determine the uptake of tumor suppressor miRNAs that affect cancer cell metastasis. RESULTS: Migration and cell adhesion were higher in RAB27A OE cells than in RAB27A KD cells. Electron microscopy revealed that the numbers of multivesicular bodies and intraluminal vesicles per cell were higher in RAB27A OE cells than in control cells, suggesting their secretion. The finding revealed that miR-127-3p was sorted into exosomes and disposed of extracellularly. Protein-protein interaction analysis revealed MYCN to be the most significant hub for RAB27A-OE RCC cells. ceRNA network analysis revealed that MAPK4 interacted strongly with miR-127-3p. CONCLUSION: The disposal of miR-127-3p through exosome secretion in RAB27A overexpressing cells may not inhibit the MAPK pathway to gain metastatic potential by activating MYCN. The exosomes containing miRNAs are valuable therapeutic targets for cancer treatment.

19.
J Pers Med ; 14(4)2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38673066

RESUMO

BACKGROUND: This study aimed to compare surgical outcomes between two new robotic single-site myomectomy (RSSM)-complementary techniques: coaxial robotic single-site myomectomy (Coaxial-RSSM) and hybrid robotic single-site myomectomy (Hybrid-RSSM). METHODS: Medical records for 132 women undergoing Coaxial-RSSM and 150 undergoing Hybrid-RSSM, consecutively, were retrospectively reviewed. Patient characteristics and surgical outcomes were assessed and compared after propensity score matching (PSM). RESULTS: In the outcomes of PSM, the Coaxial-RSSM group showed significantly reduced blood loss (79.71 vs. 163.75 mL, p < 0.001) and reduced hospital duration (4.18 ± 0.62 vs. 4.63 ± 0.90) relative to the Hybrid-RSSM group. Conversely, Hybrid-RSSM allowed for a shorter operative time compared with Coaxial-RSSM (119.19 vs. 156.01 min, p = 0.007). No conversions to conventional laparoscopy or laparotomy or any need for the multi-site robotic approach occurred in either group. Postoperative complications, including ileus, fever, and wound dehiscence, showed no statistically significant differences between the two groups. CONCLUSIONS: Blood loss was lower with Coaxial-RSSM, and operative time was shorter for Hybrid-RSSM. A follow-up prospective study is warranted for more comprehensive comparison of surgical outcomes between the two techniques.

20.
Plant Pathol J ; 40(2): 106-114, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38606441

RESUMO

Fusarium head blight (FHB), predominantly caused by Fusarium graminearum and F. asiaticum, is a significant fungal disease impacting small-grain cereals. The absence of highly resistant cultivars underscores the need for vigilant FHB surveillance to mitigate its detrimental effects. In 2023, a notable FHB outbreak occurred in the southern region of Korea. We assessed FHB disease severity by quantifying infected spikelets and grains. Isolating fungal pathogens from infected samples often encounters interference from various microorganisms. We developed a cost-effective, selective medium, named BGT (Burkholderia glumae Toxoflavin) medium, utilizing B. glumae, which is primarily known for causing bacterial panicle blight in rice. This medium exhibited selective growth properties, predominantly supporting Fusarium spp., while substantially inhibiting the growth of other fungi. Using the BGT medium, we isolated F. graminearum and F. asiaticum from infected wheat and barley samples across Korea. To further streamline the process, we used a direct PCR approach to amplify the translation elongation factor 1-α (TEF-1α) region without a separate genomic DNA extraction step. Phylogenetic analysis of the TEF-1α region revealed that the majority of the isolates were identified as F. asiaticum. Our results demonstrate that BGT medium is an effective tool for FHB diagnosis and Fusarium strain isolation.

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