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1.
J Ethnopharmacol ; 337(Pt 2): 118869, 2024 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-39353479

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria rhynchophylla (UR) is recognized for its therapeutic applications in treating hypertension and inflammation. However, the specific molecular mechanisms how UR and its bioactive constituents modulate inflammatory pathways remain unknown. This study investigates the effects of UR extract and its constituent, hirsuteine (HST), on TRPV1 channel modulation which is related to hypertension and inflammation. MATERIALS AND METHODS: Electrophysiological recordings and calcium imaging experiments were conducted to assess TRPV1 activation by UR extract and HST in HEK293T cells and sensory neurons. RESULTS: UR extract and HST activated TRPV1 in HEK293T cells, with repeated applications causing channel desensitization. HST application on TRPV1-positive sensory neurons significantly reduced electrical activity compared to capsaicin. CONCLUSION: This study demonstrated UR extract and HST are a novel TRPV1 agonists inducing channel desensitization and a potent agent for treatment of TRPV1 dependent pain relief.

2.
Adv Mater ; : e2406316, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39246216

RESUMO

Organic photodetectors (OPDs) have received considerable attention owing to their superior absorption coefficient and tunable bandgap. The introduction of bulk-heterojunction (BHJ) structure aims to maximize charge generation, however, its response speed is constrained by the random distribution of donor and acceptor. Herein, a multiple-active layer design consisting of a single acceptor layer and a bulk-heterojunction layer (A/BHJ structure) is introduced, which combines the benefits of both the planar junction and the BHJ, improving photo-sensing. A transfer process is employed for this structure, which involves calculating the energy release rate at each interface, considering temperature and velocity. Consequently, the OPD with the A/BHJ structure is successfully fabricated through transfer printing, resulting in reduced dark current, superior detectivity (1.06 × 1013 Jones), and rapid response, achieved by creating a high hole injection barrier and suppressing trap sites within the interfaces. By thoroughly investigating charge dynamics in the structure, the A/BHJ structure-based OPD attains large bandwidth detection with high signal-to-noise. An efficient wireless data communication system with digital-to-analog conversion is showcased using the A/BHJ structure-based OPD.

3.
Heliyon ; 10(17): e37497, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39290289

RESUMO

Lignin, an abundant natural resource, has not been effectively utilized. In this study, the functionality of lignin was enhanced through amination to produce amine-crosslinked lignin, and its adsorption behavior toward cationic and anionic dyes was investigated. Chemical structure analysis confirmed the successful introduction of amine groups, thereby improving the molecular weight and thermal stability of the optimized amine-crosslinked lignin. Additionally, the amine-crosslinked lignin exhibited a larger specific surface area than kraft lignin, as well as excellent adsorption capacity for both anionic and cationic dyes. Furthermore, it selectively adsorbed anionic and cationic dyes depending on pH conditions. The adsorption kinetics were described using a pseudo-second-order model, and the adsorption isotherms for congo red and methyl green were determined using the Langmuir and Freundlich equations, respectively. Additionally, the reusability and adsorption efficiency of the optimized amine-crosslinked lignin were evaluated, confirming its stable and repeatable adsorption efficiency for congo red and methyl green even after five repeated cycles. The assumed adsorption mechanism was attributed to electrostatic interactions. Therefore, the successful synthesis and excellent adsorption properties of amine-crosslinked lignin suggest its promising potential for environmentally friendly and efficient removal of both cationic and anionic dyes, thereby offering a sustainable solution for wastewater treatment and remediation.

4.
ACS Appl Mater Interfaces ; 16(29): 38310-38323, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38988312

RESUMO

In this study, a conductive patch for a flexible organic optoelectronic device is proposed and implemented using a poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) polymer electrode based on a transfer process to achieve its high conductivity with an efficient conductive pathway. This PEDOT-dominant surface is induced by phase inversion during the transfer process owing to the solvent affinity of the PSS phase. The PEDOT:PSS patch formed by the transfer process minimizes the power loss in a flexible optoelectronic device due to the improved charge collection and suppressed leakage current responses. In addition, the bending stability of the flexible photoelectronic device is also enhanced by maintaining performance for 1000 bending cycles. Therefore, in the fabrication of a transparent flexible conductive PEDOT:PSS patch, the transfer process of a conducting polymer constitutes an effective strategy that can improve conductivity and embellished morphology.

5.
AAPS J ; 26(4): 81, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38992298

RESUMO

Lack of Factor VIII (FVIII) concentrates is one of limiting factors for Hemophilia A prophylaxis in resource-limited countries. Rondaptivon pegol (BT200) is a pegylated aptamer and has been shown to elevate the level of von Willebrand Factor (VWF) and FVIII in previous studies. A population pharmacokinetic model for BT200 was built and linked to the kinetic models of VWF and FVIII based on reasonable assumptions. The developed PK/PD model for BT200 described the observed kinetic of BT200, VWF, and FVIII in healthy volunteers and patients with mild-to-moderate hemophilia A from two clinical trials. The developed model was evaluated using an external dataset in patients with severe hemophilia A taking recombinant FVIII products. The developed and evaluated PK/PD model was able to describe and predict concentration-time profiles of BT200, VWF, and FVIII in healthy volunteers and patients with hemophilia A. Concentration-time profiles of FVIII were then predicted following coadministration of plasma-derived FVIII concentrate and BT200 under various dosing scenarios in virtual patients with severe hemophilia A. Plasma-derived products, that contain VWF, are more accessible in low-resource countries as compared to their recombinant counterparts. The predicted time above 1 and 3 IU/dL FVIII in one week was compared between scenarios in the absence and presence of BT200. A combination dose of 6 mg BT200 once weekly plus 10 IU/kg plasma-derived FVIII twice weekly maintained similar coverage to a 30 IU/kg FVIII thrice weekly dose in absence of BT200, representing only 22% of the FVIII dose per week.


Assuntos
Fator VIII , Hemofilia A , Fator de von Willebrand , Humanos , Fator VIII/farmacocinética , Fator VIII/administração & dosagem , Hemofilia A/tratamento farmacológico , Hemofilia A/sangue , Fator de von Willebrand/farmacocinética , Fator de von Willebrand/administração & dosagem , Modelos Biológicos , Adulto , Masculino , Adulto Jovem , Cinética , Polietilenoglicóis/farmacocinética , Polietilenoglicóis/administração & dosagem , Adolescente
6.
Healthcare (Basel) ; 12(13)2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38998849

RESUMO

Objectives: This study aimed to analyze the association between alcohol use disorder (AUD) and suicidal ideation (SI) in the general Korean population. Methods: The 2022 Mental Health Awareness Survey was collected from the Chungcheongnam-do Mental Health Welfare Center (CHMHC). Before Propensity Score Matching (PSM), 823 participants were included in this study. After 1:4 PSM, the 255 participants were analyzed using the chi-square test and matched conditional logistic regression. Results: The AUD group had higher odds of experiencing SI than the non-AUD (adjusted odds ratio [AOR]: 2.40, 95% confidence intervals [CI]: 1.10-5.22). Stratified matched conditional logistic regression showed that, among the female, <40 years and single group, the AUD group was more likely to experience SI compared with the non-AUD, respectively (AOR:3.53, 95% CI: 1.20-10.44/AOR:3.45, 95% CI: 1.03-11.55/AOR:4.83, 95% CI: 1.18-19.69). However, among the male, ≥40 years and married group, we discovered no association between AUD and SI. Conclusions: Through this study, we found a strong association between the AUD group and SI. This association was particularly strong among female, <40 years, and single groups. This study elucidates the relationship between AUD and SI in the Chungnam region, which had not been previously identified in Korea, and it is expected to serve as foundational data for reducing the high suicide rate in this region. However, due to the limitation of being a cross-sectional study, future longitudinal research is required.

7.
Vascular ; : 17085381241261752, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38905636

RESUMO

OBJECTIVES: Although the medical field has made significant progress, there has been little improvement in the survival rate of patients with ruptured abdominal aortic aneurysms (rAAAs). We implemented a protocol consisting of five strategies in the management of rAAA patients who underwent open repair surgery. METHODS: The protocol comprised the following strategies: intentional hypotension <70 mmHg, lung first and kidney last policy (restricted fluid resuscitation and permissive oligoanuria), immediate postoperative extubation, free-water intake with active ambulation, and open abdomen with the routine second-look operation. The study included 13 patients (11 male) with a mean age of 75.5 ± 7.4 (range: 58-87) years who underwent the procedure from 2016 to 2018, with a mean follow-up of 40.1 ± 9.04 months. Five deteriorating to hemodynamic shock and decreased consciousness requiring intubation and ventilation prior to surgery were observed. Two of these patients required preoperative cardiopulmonary resuscitation (CPR). RESULTS: All patients regained consciousness after surgery, including the two patients who required cardiopulmonary resuscitation. Immediate postoperative extubation was performed in nine patients, but two (22.2%) of them needed re-intubation due to ventilation/perfusion mismatch. Four patients underwent continuous renal replacement therapy, with three of them having anuria for up to 48 h after surgery. Two of these patients made a full recovery. Daily ambulation was carried out for a mean of 4.77 ± 3.5 (range 1-13) days with an open abdomen, during which no significant events were reported. Four cases of colon ischemia/necrosis were identified in the second-look operation, with two patients requiring Hartman's procedure and the other two undergoing left colon partial resection. There were two in-hospital mortalities (15.4%). CONCLUSIONS: A protocol-based approach, through multidisciplinary team consensus and the development of optimal surgical strategies, could improve clinical outcomes for patients undergoing emergency surgery for rAAA. Further studies with larger sample sizes are needed to refine the protocols.

8.
Sci Rep ; 14(1): 14341, 2024 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-38906916

RESUMO

Glioblastoma (GBM) is a highly aggressive and deadly brain cancer. Temozolomide (TMZ) is the standard chemotherapeutic agent for GBM, but the majority of patients experience recurrence and invasion of tumor cells. We investigated whether TMZ treatment of GBM cells regulates matrix metalloproteinases (MMPs), which have the main function to promote tumor cell invasion. TMZ effectively killed GL261, U343, and U87MG cells at a concentration of 500 µM, and surviving cells upregulated MMP9 expression and its activity but not those of MMP2. TMZ also elevated levels of MMP9 mRNA and MMP9 promoter activity. Subcutaneous graft tumors survived from TMZ treatment also exhibited increased expression of MMP9 and enhanced gelatinolytic activity. TMZ-mediated MMP9 upregulation was specifically mediated through the phosphorylation of p38 and JNK. This then stimulates AP-1 activity through the upregulation of c-Fos and c-Jun. Inhibition of the p38, JNK, or both pathways counteracted the TMZ-induced upregulation of MMP9 and AP-1. This study proposes a potential adverse effect of TMZ treatment for GBM: upregulation of MMP9 expression potentially associated with increased invasion and poor prognosis. This study also provides valuable insights into the molecular mechanisms by which TMZ treatment leads to increased MMP9 expression in GBM cells.


Assuntos
Regulação Neoplásica da Expressão Gênica , Glioblastoma , Metaloproteinase 9 da Matriz , Temozolomida , Proteínas Quinases p38 Ativadas por Mitógeno , Temozolomida/farmacologia , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Glioblastoma/genética , Glioblastoma/patologia , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Humanos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Antineoplásicos Alquilantes/farmacologia , Animais , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Fator de Transcrição AP-1/metabolismo , Regulação para Cima/efeitos dos fármacos , Camundongos
9.
Int J Biol Macromol ; 274(Pt 1): 133211, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38909738

RESUMO

Considering the severity of global environmental issues, biomass-derived products have received significant attention as alternatives to foster sustainability and eco-friendliness. The use of metal nanoparticle catalysts for dye decomposition is emerging as a promising approach for environmentally friendly dye removal. In this study, an aminosilane-modified lignin (AML)/silver nanoparticle (AgNP) composite was fabricated and used as a hydrogenation catalyst. The AgNPs were well dispersed on the AML surface and formed strong bonds within the AML/AgNP complex. AML also served as an effective reducing and capping agent for Ag(I) ions. The AML/AgNPs were found to be an efficient catalyst with excellent dye degradation ability and easy reusability. Biomass-derived lignin can be used as a reducing and capping agent for metals and this complex can be used as a high-value bio-catalyst for wastewater remediation.


Assuntos
Corantes , Química Verde , Lignina , Nanopartículas Metálicas , Prata , Prata/química , Lignina/química , Nanopartículas Metálicas/química , Catálise , Corantes/química , Poluentes Químicos da Água/química , Águas Residuárias/química
10.
J Clin Med ; 13(10)2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38792471

RESUMO

Background/Objectives: Extrauterine growth restriction (EUGR) is associated with high mortality and an increased incidence of poor neurodevelopmental outcomes in preterm infants. In this study, we aimed to compare the Intergrowth-21ST (IG-21ST) and Fenton charts in predicting long-term neurodevelopmental and anthropometric outcomes of very low birth weight (VLBW) infants. Methods: Data were collected from 2649 VLBW infants registered in the Korean Neonatal Network born between 240/7 and 316/7 weeks of gestational age from January 2013 to December 2017. Follow-up assessments were conducted at 18-24 months of age, corrected for prematurity. Multiple logistic regression analysis was performed to evaluate the association between EUGR and long-term outcomes. Results: Among the 2649 VLBW infants, 60.0% (1606/2649) and 36.9% (977/2649) were diagnosed as having EUGR defined by the Fenton chart (EUGRF) and by the IG-21ST chart (EUGRIG), respectively. The EUGRIG group exhibited a higher proportion of infants with cerebral palsy, neurodevelopmental impairment (NDI), and growth failure. In multiple logistic regression analysis, adjusted for risk factors for long-term outcome, the EUGRIG group showed higher risk of cerebral palsy (adjusted odds ratio [aOR], 1.66; 95% confidence interval [CI], 1.04-2.65), NDI (aOR, 2.09; 95% CI, 1.71-2.55), and growth failure (aOR, 1.57; 95% CI, 1.16-2.13). Infants with EUGRF tended to develop NDI (aOR, 1.29; 95%CI, 1.03-1.63) and experience growth failure (aOR, 2.44; 95% CI, 1.77-3.40). Conclusions: The IG-21ST chart demonstrated a more effective prediction of long-term neurodevelopmental outcomes, whereas the Fenton chart may be more suitable for predicting growth failure at 18-24 months.

11.
Int J Biol Macromol ; 272(Pt 1): 132734, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38815950

RESUMO

Kraft lignin (KL) holds significant potential as a renewable resource for the development of innovative materials that are currently not fully utilized. In this study, a novel iminated lignin (IL) was synthesized by grafting primary amine lignin (N-KL) onto salicylaldehyde. The effects of the dosage and reaction temperature on the nitrogen content of N-KL were evaluated. The maximum nitrogen content in N-KL reached to 3.32 %. Characterization by spectroscopy techniques (FT-IR, XPS, and NMR), elemental analysis, and gel permeation chromatography confirmed the imination of lignin. Additionally, the antioxidant activity of the lignin samples was investigated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging ability. Moreover, the DPPH radical scavenging capacity of IL-6 (IC50 = 38.6 ± 3.9 µg/mL) was close to that of commercial antioxidant butylated hydroxytoluene (BHT) (IC50 = 37.7 ± 4.5 µg/mL). Furthermore, the adsorption equilibrium results indicated that IL-6 had a maximum uptake of 115.6 mg/g Pb2+, which was 3.2-fold higher than that of KL. Kinetic adsorption experiments suggested that IL-6 adsorption follows a pseudo-second-order model. Therefore, the synthesized iminated lignin is a promising candidate for the development of environmentally friendly materials with applications as an antioxidant and lead-ion adsorbent.


Assuntos
Sequestradores de Radicais Livres , Chumbo , Lignina , Lignina/química , Chumbo/química , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/síntese química , Compostos de Bifenilo/química , Picratos/química , Cinética , Adsorção , Antioxidantes/química , Antioxidantes/síntese química
12.
Biomed Pharmacother ; 175: 116770, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38772154

RESUMO

Patients with inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), often have concomitant mental disorders such as depression and anxiety. Therefore, a bidirectional approach involving the gut and brain axes is necessary for the prevention and treatment thereof. In this study, we explored the potential of Poncirus trifoliata extract (PT), traditionally known for its neuroprotective effects against gastrointestinal diseases, as a natural treatment agent for IBD in a dextran sulfate sodium (DSS)-induced colitis model. Oral administration of PT ameliorated weight loss and inflammatory responses in mice with DSS-induced colitis. Furthermore, PT treatment effectively restored the colon length and ameliorated enterocyte death by inhibiting DSS-induced reactive oxygen species (ROS)-mediated necroptosis. The main bioactive components of PT, poncirin and naringin, confirmed using ultra-performance liquid chromatography-quadrupole time-of-flight (UPLC-qTOF), can be utilized to regulate necroptosis. The antidepressant-like effects of PT were confirmed using open field test (OFT) and tail suspension test (TST). PT treatment also restored vascular endothelial cell integrity in the hippocampus. In the Cornu Ammonis 1 (CA1) and dentate gyrus (DG) regions of the hippocampus, PT controlled the neuroinflammatory responses of proliferated microglia. In conclusion, PT, which contains high levels of poncirin and naringin, has potential as a bidirectional therapeutic agent that can simultaneously improve IBD-associated intestinal and mental disorders.


Assuntos
Colite , Depressão , Sulfato de Dextrana , Flavanonas , Camundongos Endogâmicos C57BL , Extratos Vegetais , Poncirus , Animais , Poncirus/química , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Masculino , Camundongos , Depressão/tratamento farmacológico , Flavanonas/farmacologia , Flavanonas/isolamento & purificação , Colite/tratamento farmacológico , Colite/induzido quimicamente , Colite/patologia , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Antidepressivos/farmacologia , Antidepressivos/isolamento & purificação , Flavonoides/farmacologia , Flavonoides/isolamento & purificação , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Espécies Reativas de Oxigênio/metabolismo
13.
Front Pharmacol ; 15: 1352842, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590637

RESUMO

Introduction: Fusion of the fragment crystallizable (Fc) to protein therapeutics is commonly used to extend the circulation time by enhancing neonatal Fc-receptor (FcRn)-mediated endosomal recycling and slowing renal clearance. This study applied kinetic modeling to gain insights into the cellular processing contributing to the observed pharmacokinetic (PK) differences between the novel recombinant ADAMTS13 fragment (MDTCS) and its Fc-fusion protein (MDTCS-Fc). Methods: For MDTCS and MDTCS-Fc, their plasma PK profiles were obtained at two dose levels following intravenous administration of the respective proteins to mice. The plasma PK profiles of MDTCS were fitted to a kinetic model with three unknown protein-dependent parameters representing the fraction recycled (FR) and the rate constants for endocytosis (kup, for the uptake into the endosomes) and for the transfer from the plasma to the interstitial fluid (kpi). For MDTCS-Fc, the model was modified to include an additional parameter for binding to FcRn. Parameter optimization was done using the Cluster Gauss-Newton Method (CGNM), an algorithm that identifies multiple sets of approximate solutions ("accepted" parameter sets) to nonlinear least-squares problems. Results: As expected, the kinetic modeling results yielded the FR of MDTCS-Fc to be 2.8-fold greater than that of MDTCS (0.8497 and 0.3061, respectively). In addition, MDTCS-Fc was predicted to undergo endocytosis (the uptake into the endosomes) at a slower rate than MDTCS. Sensitivity analyses identified the association rate constant (kon) between MDTCS-Fc and FcRn as a potentially important factor influencing the plasma half-life in vivo. Discussion: Our analyses suggested that Fc fusion to MDTCS leads to changes in not only the FR but also the uptake into the endosomes, impacting the systemic plasma PK profiles. These findings may be used to develop recombinant protein therapeutics with extended circulation time.

14.
Clin Pharmacol Ther ; 116(1): 72-81, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38666606

RESUMO

Fibroblast growth factor (FGF)-21 analogs are potential therapeutic candidates for metabolic dysfunction-associated steatohepatitis (MASH). This systematic review and meta-analysis aimed to assess the efficacy and safety of the FGF-21 analogs, efruxifermin, pegbelfermin, and pegozafermin for MASH treatment. A comprehensive systematic review and meta-analysis of randomized controlled trials from five major databases was conducted. Primary efficacy outcomes focused on liver histological improvement, while secondary efficacy outcomes encompassed reductions in liver fat content and improvements in biochemical parameters. Safety outcomes examined included treatment-emergent adverse events (TEAEs), treatment-related TEAEs, TEAEs leading to discontinuation, and serious TEAEs. Eight eligible studies involving 963 patients were included in this review. Compared with the placebo group, the FGF-21 analog-treated group exhibited significantly improved primary efficacy outcomes, specifically ≥1 stage improvement in fibrosis with no worsening of MASH (risk ratio [RR] = 1.83; 95% confidence interval [CI] = 1.27-2.62) and at least two-point improvement in the non-alcoholic fatty liver disease activity score with no worsening of fibrosis (RR = 2.85; 95% CI = 2.06-3.95). Despite an increased risk of TEAEs (RR = 1.17; 95% CI = 1.08-1.27) and treatment-related adverse events (RR = 1.75; 95% CI = 1.40-2.19), FGF-21 analogs exhibited an acceptable safety profile. FGF-21 analogs were significantly better in achieving liver histological improvements and beneficial biochemical outcomes compared with placebo, with a tolerable safety pattern. These findings shed light on the efficacy and safety of FGF-21 analogs and provide valuable evidence for their application as MASH therapeutics.


Assuntos
Fatores de Crescimento de Fibroblastos , Humanos , Fatores de Crescimento de Fibroblastos/uso terapêutico , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Fígado Gorduroso/tratamento farmacológico , Doenças Metabólicas/tratamento farmacológico
15.
Pharmacol Res Perspect ; 12(2): e1194, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38573021

RESUMO

The SARS-CoV-2 caused COVID-19 pandemic has posed a global health hazard. While some vaccines have been developed, protection against viral infection is not perfect because of the urgent approval process and the emergence of mutant SARS-CoV-2 variants. Here, we employed UDCA as an FXR antagonist to regulate ACE2 expression, which is one of the key pathways activated by SARS-CoV-2 Delta variant infection. UDCA is a well-known reagent of liver health supplements and the only clinically approved bile acid. In this paper, we investigated the protective efficacy of UDCA on Omicron variation, since it has previously been verified for protection against Delta variant. When co-housing with an Omicron variant-infected hamster group resulted in spontaneous airborne transmission, the UDCA pre-supplied group was protected from weight loss relative to the non-treated group at 4 days post-infection by more than 5%-10%. Furthermore, UDCA-treated groups had a 3-fold decrease in ACE2 expression in nasal cavities, as well as reduced viral expressing genes in the respiratory tract. Here, the data show that the UDCA serves an alternative option for preventive drug, providing SARS-CoV-2 protection against not only Delta but also Omicron variant. Our results of this study will help to propose drug-repositioning of UDCA from liver health supplement to preventive drug of SARS-CoV-2 infection.


Assuntos
COVID-19 , SARS-CoV-2 , Animais , Cricetinae , Humanos , Ácido Ursodesoxicólico/farmacologia , Ácido Ursodesoxicólico/uso terapêutico , Enzima de Conversão de Angiotensina 2/genética , Pandemias
17.
Mar Pollut Bull ; 201: 116262, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38513602

RESUMO

This study investigated the carbonate system and air-sea CO2 exchange in the inshore waters along South Korea's western coastline in 2020. Overlooking these waters might introduce significant errors in estimating air-sea CO2 fluxes of the southeastern Yellow Sea, given their interaction with land, offshore regions, and sediments. During periods other than summer, seasonal variations in seawater CO2 partial pressure (pCO2) could be generally explained by thermal effects. Tidal mixing and shallow depths resulted in weaker stratification-induced carbon export compared to offshore regions. However, during summer, inshore waters exhibited high spatial variability in pCO2, ranging from approximately 185 to 1000 µatm. In contrast to offshore waters that modestly absorbed CO2, inshore waters shallower than 20 m emitted ∼100 Gg C yr-1 to the atmosphere. However, considering the high heterogeneity of the study area, additional observations with high spatial and temporal resolution are required to refine estimates of air-sea CO2 exchange.


Assuntos
Dióxido de Carbono , Água do Mar , Carbono , Carbonatos , Atmosfera
18.
Nature ; 626(8000): 859-863, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38326609

RESUMO

Bacteria in the gastrointestinal tract produce amino acid bile acid amidates that can affect host-mediated metabolic processes1-6; however, the bacterial gene(s) responsible for their production remain unknown. Herein, we report that bile salt hydrolase (BSH) possesses dual functions in bile acid metabolism. Specifically, we identified a previously unknown role for BSH as an amine N-acyltransferase that conjugates amines to bile acids, thus forming bacterial bile acid amidates (BBAAs). To characterize this amine N-acyltransferase BSH activity, we used pharmacological inhibition of BSH, heterologous expression of bsh and mutants in Escherichia coli and bsh knockout and complementation in Bacteroides fragilis to demonstrate that BSH generates BBAAs. We further show in a human infant cohort that BBAA production is positively correlated with the colonization of bsh-expressing bacteria. Lastly, we report that in cell culture models, BBAAs activate host ligand-activated transcription factors including the pregnane X receptor and the aryl hydrocarbon receptor. These findings enhance our understanding of how gut bacteria, through the promiscuous actions of BSH, have a significant role in regulating the bile acid metabolic network.


Assuntos
Aciltransferases , Amidoidrolases , Aminas , Ácidos e Sais Biliares , Biocatálise , Microbioma Gastrointestinal , Humanos , Aciltransferases/metabolismo , Amidoidrolases/metabolismo , Aminas/química , Aminas/metabolismo , Bacteroides fragilis/enzimologia , Bacteroides fragilis/genética , Bacteroides fragilis/metabolismo , Ácidos e Sais Biliares/química , Ácidos e Sais Biliares/metabolismo , Estudos de Coortes , Escherichia coli/enzimologia , Escherichia coli/genética , Escherichia coli/metabolismo , Microbioma Gastrointestinal/fisiologia , Ligantes , Receptor de Pregnano X/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Fatores de Transcrição/metabolismo , Lactente , Técnicas de Cultura de Células
19.
Knee Surg Relat Res ; 36(1): 10, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38419060

RESUMO

PURPOSE: The results of medial open-wedge high tibial osteotomy (MOWHTO) according to age is inconclusive. This study aimed to compare the clinical outcomes and failure of MOWHTO in patients < 55 years and > 65 years. METHODS: Consecutive patients who underwent MOWHTO from July 2009 to August 2020 were retrospectively analyzed. 205 patients were considered for analysis. A 1-to-1 propensity score matched analysis to assess clinical outcomes scores including International Knee Documentation Committee (IKDC) subjective score and Lysholm score, radiologic outcomes, complication, and Total Knee Arthroplasty (TKA) conversion between patients > 65 years and patients < 55 years was performed. Radiologic outcomes included Hip-Knee-Ankle (HKA) angle, Weight Bearing Line ratio (WBLR), posterior tibial slope (PTS), and Insall-Salvati (IS) ratio before and after surgery. RESULTS: The follow-up period was 50.4 months in patients > 65 years and 55.3 months in patients < 55 years. There was no significant difference in the preoperative and postoperative HKA angle, WBLR, PTS, IS ratio, IKDC score and Lysholm score between the two groups. The arthroscopic evaluation of cartilage did not show any statistically significant differences between the two groups. Regarding Minimal clinically important differences (MCID), in the 26% of the older group exceeded MCID of IKDC score; 45% of the older group exceeded MCID of Lysholm score. In the younger group, 24% exceeded MCID of IKDC score and 35% exceeded MCID of Lysholm score. In older group, there were 7 (11.3%) cases of TKA conversion while no TKA conversion was recorded in the younger group. (P = 0.007) The average time to TKA conversion was 67 months. (42 months to 90 months) Kaplan-Meier analysis revealed that the survival rate was 95.2% at 4 years in the older group. CONCLUSION: Similar clinical results were obtained in patients over 65 years of age that were eligible for MOWHTO at minimum 2-year follow-up as in patients under 55 years of age. MOWHTO may be a viable option in older patients if proper indications are met. However, the risk of TKA conversion must be considered preoperatively and discussed with patients. STUDY DESIGN: Cohort study; Level of evidence, 3.

20.
Photodermatol Photoimmunol Photomed ; 40(1): e12945, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38288772

RESUMO

BACKGROUND: Photoprotection is crucial in preventing the development and progression of various skin diseases. However, patients with skin disease have limited awareness of photoprotection. We evaluated the knowledge and behavioral patterns of photoprotection among Koreans with skin diseases. METHODS: A cross-sectional study was conducted in 11 general hospitals across South Korea. The study population consisted of patients aged 19 years or older who visited dermatologic clinics for their skin diseases. A self-administered questionnaire was used to collect patient demographics, knowledge of photoprotection, and photoprotective habits. RESULTS: In this study, 1173 patients with skin cancer, hyperpigmentary disorders, hypopigmentary disorders, or other skin diseases participated. Females scored significantly higher in knowledge of photoprotection compared to males (mean score 8.4 vs. 7.8; p < .001), and younger patients (<50 years) scored higher than older patients (mean score 8.7 vs. 7.5; p < .001). Males also reported longer sun exposure times and lower usage of photoprotective measures (both p < .001). Patients with skin cancer had the lowest mean knowledge score (7.1 ± 2.6) and were less likely to use photoprotective measures compared to other groups (p < .001). In contrast, patients with hyperpigmentation actively avoided sun exposure compared with other groups (p < 0.001). CONCLUSIONS: Knowledge of photoprotection among Korean patients with skin diseases varied depending on the gender, age, and type of skin disease. Their photoprotective behaviors were inadequate, especially among males and those with skin cancer. These findings emphasize the importance of educating and tailoring photoprotection strategies for patients with skin diseases.


Assuntos
Hiperpigmentação , Neoplasias Cutâneas , Masculino , Feminino , Humanos , Raios Ultravioleta/efeitos adversos , Protetores Solares/uso terapêutico , Estudos Transversais , Neoplasias Cutâneas/tratamento farmacológico , Hábitos , Hiperpigmentação/tratamento farmacológico
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