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1.
Drug Des Devel Ther ; 18: 2641-2652, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974125

RESUMO

Background: Management of hypertension and hyperlipidemia, which are common comorbid risk factors for cardiovascular diseases, require multiple medications. The development of a fixed-dose combination (FDC) containing ezetimibe, rosuvastatin, telmisartan, and amlodipine aims to enhance patient adherence and persistence, but the potential interactions among the four medications have not been studied. This study aimed to evaluate the pharmacokinetic (PK) interactions between the FDC of ezetimibe/rosuvastatin 10/20 mg (ER) and the FDC of telmisartan/amlodipine 80/5 mg (TA). Methods: An open-label, single-sequence, three-period, three-treatment crossover study was conducted in healthy male subjects. All subjects received ER for 7 days, TA for 9 days and ER combined with TA for 7 days during each treatment period. For PK analysis of total/free ezetimibe, rosuvastatin, telmisartan, and amlodipine, serial blood samples were collected for 24 hours at steady state. Safety profiles were assessed throughout the study. Results: Thirty-eight subjects were enrolled, and 34 subjects completed the study. The systemic exposure to each active ingredient after coadministration of the two FDCs was similar to that after each FDC alone. The geometric mean ratios and 90% confidence intervals for the maximum plasma concentration (µg/L) and the area under the plasma concentration-time curve (h·µg/L) of the combination therapy to monotherapy, assessed at steady state, were as follows: total ezetimibe, 1.0264 (0.8765-1.2017) and 0.9359 (0.7847-1.1163); free ezetimibe, 1.5713 (1.2821-1.9257) and 0.9941 (0.8384-1.1788); rosuvastatin, 2.1673 (1.7807-2.6379) and 1.1714 (0.9992-1.3733); telmisartan, 1.0745 (0.8139-1.4186) and 1.1057 (0.8379-1.4591); and amlodipine, 0.9421 (0.8764-1.0126) and 0.9603 (0.8862-1.0405). Both combination therapy and monotherapy were well tolerated by the subjects. Conclusion: The coadministration of ezetimibe/rosuvastatin 10/20 mg and ezetimibe/rosuvastatin 10/20 mg was well tolerated in healthy subjects, and the PK interaction between those two FDCs was not clinically significant.


Assuntos
Anlodipino , Estudos Cross-Over , Combinação de Medicamentos , Ezetimiba , Voluntários Saudáveis , Rosuvastatina Cálcica , Telmisartan , Humanos , Telmisartan/administração & dosagem , Telmisartan/farmacocinética , Rosuvastatina Cálcica/farmacocinética , Rosuvastatina Cálcica/administração & dosagem , Anlodipino/farmacocinética , Anlodipino/administração & dosagem , Masculino , Ezetimiba/administração & dosagem , Ezetimiba/farmacocinética , Adulto , Adulto Jovem , Benzoatos/farmacocinética , Benzoatos/administração & dosagem , Benzimidazóis/farmacocinética , Benzimidazóis/administração & dosagem , Relação Dose-Resposta a Droga , Interações Medicamentosas
2.
Sci Rep ; 14(1): 16057, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992103

RESUMO

To investigate alteration of outer nuclear layer (ONL) and choroidal vascularity index (CVI) in different status of central serous chorioretinopathy (CSC). A retrospective review of 65 CSC eyes with subretinal fluid (manifest CSC) and 40 control eyes was conducted in a single tertiary university hospital. Differences in best-corrected visual acuity (BCVA), ONL, and CVI were compared. CVI was assessed both in the entire choroid (CVI-EC) and around the 1500 µm leakage area (CVI-1500). Measurements were repeated after the subretinal fluid resorption (quiescent CSC), and compared. CSC eyes showed worse BCVA, thinner ONL and greater CVI than controls. Quiescent CSC showed a recovery of ONL compared to the manifest CSC, along with the BCVA improvement. The resolution of the CSC revealed a decrease across all three choroidal areas (total, stromal and luminal), with a more pronounced reduction in the stromal than in the luminal choroidal area, leading to an increase in the CVI. This phenomenon was shown in both CVI-EC and CVI-1500. Conclusively, ONL thickness can be used as a quantitative biomarker for photoreceptor function in CSC. Increased CVI may reflect a disease activity. The stromal choroidal area is particularly sensitive in illustrating leakage from the choroidal vasculature.


Assuntos
Coriorretinopatia Serosa Central , Corioide , Tomografia de Coerência Óptica , Acuidade Visual , Coriorretinopatia Serosa Central/patologia , Coriorretinopatia Serosa Central/diagnóstico por imagem , Humanos , Corioide/irrigação sanguínea , Corioide/patologia , Corioide/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Doença Aguda , Angiofluoresceinografia
3.
PLoS One ; 19(7): e0305694, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38985701

RESUMO

OBJECTIVES: Intraoperative ultrasonography (IOUS) offers the advantage of providing real-time imaging features, yet it is not generally used. This study aims to discuss the benefits of utilizing IOUS in spinal cord surgery and review related literature. MATERIALS AND METHODS: Patients who underwent spinal cord surgery utilizing IOUS at a single institution were retrospectively collected and analyzed to evaluate the benefits derived from the use of IOUS. RESULTS: A total of 43 consecutive patients were analyzed. Schwannoma was the most common tumor (35%), followed by cavernous angioma (23%) and ependymoma (16%). IOUS confirmed tumor extent and location before dura opening in 42 patients (97.7%). It was particularly helpful for myelotomy in deep-seated intramedullary lesions to minimize neural injury in 13 patients (31.0% of 42 patients). IOUS also detected residual or hidden lesions in 3 patients (7.0%) and verified the absence of hematoma post-tumor removal in 23 patients (53.5%). In 3 patients (7.0%), confirming no intradural lesions after removing extradural tumors avoided additional dural incisions. IOUS identified surrounding blood vessels and detected dural defects in one patient (2.3%) respectively. CONCLUSIONS: The IOUS can be a valuable tool for spinal cord surgery in identifying the exact location of the pathologic lesions, confirming the completeness of surgery, and minimizing the risk of neural and vascular injury in a real-time fashion.


Assuntos
Neoplasias da Medula Espinal , Medula Espinal , Ultrassonografia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Neoplasias da Medula Espinal/cirurgia , Neoplasias da Medula Espinal/diagnóstico por imagem , Estudos Retrospectivos , Ultrassonografia/métodos , Medula Espinal/diagnóstico por imagem , Medula Espinal/cirurgia , Adolescente , Adulto Jovem , Neurilemoma/cirurgia , Neurilemoma/diagnóstico por imagem , Criança , Ependimoma/cirurgia , Ependimoma/diagnóstico por imagem , Procedimentos Neurocirúrgicos/métodos , Procedimentos Neurocirúrgicos/efeitos adversos
4.
Skin Res Technol ; 30(6): e13799, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38853243
5.
Artigo em Inglês | MEDLINE | ID: mdl-38943223

RESUMO

Se-free n-type (Bi,Sb)2Te3 thermoelectric materials, outperforming traditional n-type Bi2(Te,Se)3, emerge as a compelling candidate for practical applications of recovering low-grade waste heat. A 100% improvement in the maximum ZT of n-type Bi1.7Sb0.3Te3 is demonstrated by using melt-spinning and excess Te-assisted transient liquid phase sintering (LPS). Te-rich sintering promotes the formation of intrinsic defects (TeBi), elevating the carrier concentration and enhancing the electrical conductivity. Melt-spinning with excess Te fine-tunes the electronic band, resulting in a high power-factor of 0.35 × 10-3 W·m-1 K-2 at 300 K. Rapid volume change during sintering induces the formation of dislocation networks, significantly suppressing the lattice thermal conductivity (0.4 W·m-1 K-1). The developed n-type legs achieve a high maximum ZT of 1.0 at 450 K resulting in a 70% improvement in the output power of the thermoelectric device (7.7 W at a temperature difference of 250 K). This work highlights the synergy between melt-spinning and transient LPS, advancing the tailored control of both electronic and thermal properties in thermoelectric technology.

6.
Environ Sci Technol ; 58(26): 11331-11341, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38907708

RESUMO

Carbonate minerals are ubiquitous in nature, and their dissolution impacts many environmentally relevant processes including preferential flow during geological carbon sequestration, pH buffering with climate-change induced ocean acidification, and organic carbon bioavailability in melting permafrost. In this study, we advance the atomic level understanding of calcite dissolution mechanisms to improve our ability to predict this complex process. We performed high pressure and temperature (1300 psi and 50 °C) batch experiments to measure transient dissolution of freshly cleaved calcite under H2O, H+, and H2CO3-dominated conditions, without and with an inhibitory anionic surfactant present. Before and after dissolution experiments, we measured dissolution etch-pit geometries using laser profilometry, and we used density functional theory to investigate relative adsorption energies of competing species that affect dissolution. Our results support the hypothesis that calcite dissolution is controlled by the ability of H2O to preferentially adsorb to surface Ca atoms over competing species, even when dissolution is dominated by H+ or H2CO3. More importantly, we identify for the first time that adsorbed H+ enhances the role of water by weakening surface Ca-O bonds. We also identify that H2CO3 undergoes dissociative adsorption resulting in adsorbed HCO3- and H+. Adsorbed HCO3- that competes with H2O for Ca acute edge sites inhibits dissolution, while adsorbed H+ at the neighboring surface of CO3 enhances dissolution. The net effect of the dissociative adsorption of H2CO3 is enhanced dissolution. These results will impact future efforts to more accurately model the impact of solutes in complex water matrices on carbonate mineral dissolution.


Assuntos
Carbonato de Cálcio , Ácido Carbônico , Prótons , Água , Carbonato de Cálcio/química , Ácido Carbônico/química , Água/química , Solubilidade , Adsorção
7.
Adv Sci (Weinh) ; : e2402934, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38859618

RESUMO

Thermoelectric devices have received significant attention because of their potential for sustainable energy recovery. In these devices, a thermal design that optimizes heat transfer and dissipation is crucial for maximizing the power output. Heat dissipation generally requires external active or passive cooling devices, which often suffer from inevitable heat loss and heavy systems. Herein, the design of heat-sink integrated thermoelectric legs is proposed to enhance heat dissipation without external cooling devices, realized by finite element model simulation and 3D printing of ternary silver chalcogenide-based thermoelectric materials. Owing to the self-induced surface charges of the synthesized AgBiSe2 (n-type) and AgSbTe2 (p-type) particles, these particle-based colloidal inks exhibited high viscoelasticity, which enables the creation of complex heat-dissipation architectures via 3D printing. Power generators made from 3D-printed heat-dissipating legs exhibit higher temperature differences and output power than traditional cuboids, offering a new strategy for enhancing thermoelectric power generation.

8.
Mycology ; 15(2): 238-254, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38813476

RESUMO

Asexual spores, called conidia, are key reproductive fungal particles that enable survival in harsh environmental conditions or host systems. The conidia can infect humans, animals, and plants to cause various fungal diseases. Transcription factors, including VosA, WetA, and SscA, have key roles in conidia formation and long-term survival in Aspergillus nidulans. Herein, we report the pleiotropic functions of SscA in the conidia of the human pathogen A. fumigatus. The deletion of sscA increased conidia formation despite decreased fungal growth. Absence of sscA impaired long-term survival and reduced spore resistance to various stresses, including heat, UV, and oxidation. Transcriptomic analyses showed that SscA involved the mRNA expression of cell wall organisation-related genes. Importantly, the sscA deletion mutant conidia contained an increased amount of ß-glucan and chitin compared to wild type conidia. In addition, conidial gliotoxin production was decreased in the sscA deletion strain. Overall, SscA has pleiotropic roles in conidia formation, maturation and dormancy and mycotoxin production in A. fumigatus.

9.
Front Cell Infect Microbiol ; 14: 1369301, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774630

RESUMO

Dual-specificity LAMMER kinases are highly evolutionarily conserved in eukaryotes and play pivotal roles in diverse physiological processes, such as growth, differentiation, and stress responses. Although the functions of LAMMER kinase in fungal pathogens in pathogenicity and stress responses have been characterized, its role in Cryptococcus neoformans, a human fungal pathogen and a model yeast of basidiomycetes, remains elusive. In this study, we identified a LKH1 homologous gene and constructed a strain with a deleted LKH1 and a complemented strain. Similar to other fungi, the lkh1Δ mutant showed intrinsic growth defects. We observed that C. neoformans Lkh1 was involved in diverse stress responses, including oxidative stress and cell wall stress. Particularly, Lkh1 regulates DNA damage responses in Rad53-dependent and -independent manners. Furthermore, the absence of LKH1 reduced basidiospore formation. Our observations indicate that Lkh1 becomes hyperphosphorylated upon treatment with rapamycin, a TOR protein inhibitor. Notably, LKH1 deletion led to defects in melanin synthesis and capsule formation. Furthermore, we found that the deletion of LKH1 led to the avirulence of C. neoformans in a systemic cryptococcosis murine model. Taken together, Lkh1 is required for the stress response, sexual differentiation, and virulence of C. neoformans.


Assuntos
Criptococose , Cryptococcus neoformans , Proteínas Fúngicas , Virulência , Animais , Feminino , Humanos , Camundongos , Parede Celular/metabolismo , Criptococose/microbiologia , Cryptococcus neoformans/patogenicidade , Cryptococcus neoformans/genética , Cryptococcus neoformans/enzimologia , Modelos Animais de Doenças , Dano ao DNA , Cápsulas Fúngicas/metabolismo , Cápsulas Fúngicas/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Deleção de Genes , Regulação Fúngica da Expressão Gênica , Melaninas/metabolismo , Camundongos Endogâmicos BALB C , Estresse Oxidativo , Fosforilação , Sirolimo/farmacologia , Esporos Fúngicos/crescimento & desenvolvimento , Estresse Fisiológico
10.
Food Funct ; 15(12): 6424-6437, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38771619

RESUMO

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


Assuntos
Células 3T3-L1 , Proteínas Quinases Ativadas por AMP , Fármacos Antiobesidade , Dieta Hiperlipídica , Camundongos Endogâmicos C57BL , Obesidade , Extratos Vegetais , Transdução de Sinais , Animais , Camundongos , Dieta Hiperlipídica/efeitos adversos , Extratos Vegetais/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Masculino , Fármacos Antiobesidade/farmacologia , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Adipogenia/efeitos dos fármacos , PPAR gama/metabolismo , PPAR gama/genética , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Algas Comestíveis , Kelp
11.
Polymers (Basel) ; 16(9)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38732748

RESUMO

A polysaccharide fraction from Diospyros kaki (PLE0) leaves was previously reported to possess immunostimulatory, anti-osteoporotic, and TGF-ß1-induced epithelial-mesenchymal transition inhibitory activities. Although a few beneficial effects against colon cancer metastasis have been reported, we aimed to investigate the anti-metastatic activity of PLE0 and its underlying molecular mechanisms in HT-29 and HCT-116 human colon cancer cells. We conducted a wound-healing assay, invasion assay, qRT-PCR analysis, western blot analysis, gelatin zymography, luciferase assay, and small interfering RNA gene silencing in colon cancer cells. PLE0 concentration-dependently inhibited metastasis by suppressing cell migration and invasion. The suppression of N-cadherin and vimentin expression as well as upregulation of E-cadherin through the reduction of p-GSK3ß and ß-catenin levels resulted in the outcome of this effect. PLE0 also suppressed the expression and enzymatic activity of matrix metalloproteinases (MMP)-2 and MMP-9, while simultaneously increasing the protein and mRNA levels of the tissue inhibitor of metalloproteinases (TIMP-1). Furthermore, signaling data disclosed that PLE0 suppressed the transcriptional activity and phosphorylation of p65 (a subunit of NF-κB), as well as the phosphorylation of c-Jun and c-Fos (subunits of AP-1) pathway. PLE0 markedly suppressed JNK phosphorylation, and JNK knockdown significantly restored PLE0-regulated MMP-2/-9 and TIMP-1 expression. Collectively, our data indicate that PLE0 exerts an anti-metastatic effect in human colon cancer cells by inhibiting epithelial-mesenchymal transition and MMP-2/9 via downregulation of GSK3ß/ß-catenin and JNK signaling.

12.
Korean J Ophthalmol ; 38(3): 203-211, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38622066

RESUMO

PURPOSE: To evaluate the ocular adverse event (OAE) and the incidence rate that can occur after the COVID-19 vaccination. METHODS: Patients who visited with an ophthalmologic diagnosis within a month of COVID-19 vaccination were retrospectively analyzed. OAEs were categorized as ischemia and inflammation by their presumed pathogenesis and were compared by types of vaccine: messenger RNA (mRNA) and viral vector vaccine. The crude incidence rate was calculated using data from the Korea Disease Control and Prevention Agency. RESULTS: Twenty-four patients with OAEs after COVID-19 vaccination were reviewed: 10 patients after mRNA and 14 after viral vector vaccine. Retinal vein occlusion (nine patients) and paralytic strabismus (four patients) were the leading diagnoses. Ischemic OAE was likely to occur after viral vector vaccines, while inflammatory OAE was closely related to mRNA vaccine (p = 0.017). The overall incidence rate of OAE was 5.8 cases per million doses: 11.5 per million doses in viral vector vaccine and 3.4 per million doses in mRNA vaccine. CONCLUSIONS: OAEs can be observed shortly after the COVID-19 vaccination, and their category was different based on the types of vaccine. The information and incidence of OAE based on the type of vaccine can help monitor patients who were administered the COVID-19 vaccine.


Assuntos
Vacinas contra COVID-19 , Inflamação , Isquemia , Oclusão da Veia Retiniana , Vacinação , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Incidência , Inflamação/induzido quimicamente , Inflamação/epidemiologia , Isquemia/induzido quimicamente , Isquemia/epidemiologia , República da Coreia/epidemiologia , Oclusão da Veia Retiniana/induzido quimicamente , Oclusão da Veia Retiniana/epidemiologia , Estudos Retrospectivos , Vacinação/efeitos adversos
13.
Bioorg Med Chem ; 102: 117658, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38460487

RESUMO

Aurora kinases (AurkA/B/C) regulate the assembly of bipolar mitotic spindles and the fidelity of chromosome segregation during mitosis, and are attractive therapeutic targets for cancers. Numerous ATP-competitive AurkA inhibitors have been developed as potential anti-cancer agents. Recently, a few allosteric inhibitors have been reported that bind to the allosteric Y-pocket within AurkA kinase domain and disrupt the interaction between AurkA and its activator TPX2. Herein we report a novel allosteric AurkA inhibitor (6h) of N-benzylbenzamide backbone. Compound 6h suppressed the both catalytic activity and non-catalytic functions of AurkA. The inhibitory activity of 6h against AurkA (IC50 = 6.50 µM) was comparable to that of the most potent allosteric AurkA inhibitor AurkinA. Docking analysis against the Y-pocket revealed important pharmacophores and interactions that were coherent with structure-activity relationship. In addition, 6h suppressed DNA replication in G1-S phase, which is a feature of allosteric inhibition of AurA. Our current study may provide a useful insight in designing potent allosteric AurkA inhibitors.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Proteínas de Ciclo Celular , Aurora Quinase A , Neoplasias/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Replicação do DNA , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico
14.
ACS Appl Mater Interfaces ; 16(14): 18040-18051, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38530805

RESUMO

Inkjet printing is a powerful direct material writing process. It can be used to deposit microfluidic droplets in designated patterns at submicrometer resolution, which reduces materials usage. Nonetheless, predicting jetting characterizations is not easy because of the intrinsic complexity of the ink-nozzle-air interactions. Thus, inkjet processes are monitored by skilled engineers to ensure process reliability. This is a bottleneck in industry, resulting in high labor costs for multiple nozzles. To address this, we present a deep learning-based method for jetting characterizations. Inkjet printing is recorded by an in situ CCD camera and each droplet is detected by YOLOv5, a 1-stage detector using a convolutional neural network (CNN). The precision, recall, and mean average precision (mAP) at a 0.5 intersection over the union (IoU) threshold of the trained model were 0.86, 0.89, and 0.90, respectively. Each regression result for a detected droplet is accumulated in chronological order for each class of droplet and nozzle. The quantified information includes velocity, diameter, length, and translation, which can be used to synchronize multinozzle jetting and, eventually, the printed patterns. This demonstrates the feasibility of autonomous real-time process testing for large-scale electronics manufacturing, such as the high-resolution patterning of biosensor electrodes and QD display pixels while exploiting big data obtained from jetting characterizations.

15.
J Clin Med ; 13(3)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38337561

RESUMO

BACKGROUND: regular intravitreal anti-vascular endothelial growth factor (VEGF) treatment is crucial for patients with neovascular age-related macular degeneration (nAMD), and delayed treatment can exacerbate disease progression. METHODS: we compared the outcomes of on-time versus delayed intravitreal anti-VEGF treatment for patients with nAMD. This study was conducted during the coronavirus disease 2019 (COVID-19) pandemic with a 2-year follow-up period. The best-corrected visual acuity (BCVA) and anatomical findings were evaluated before the pandemic, during the pandemic, and at 6-, 12-, 18-, and 24-months post-pandemic. RESULTS: The delayed and on-time groups comprised 54 and 72 patients, respectively. After the pandemic, the injection interval increased by 0.65 ± 1.51 months (p = 0.003), with 22.2% of the patients in the delayed group switching to the treat-and-extended regimen (p < 0.001). The delayed group showed greater mean BCVA deterioration (p = 0.027) and central subfield thickness (p = 0.037) at 6 months and worse maximum subretinal fluid height (p = 0.022) at 18 months than the on-time group. No difference was observed between the groups in the second year. CONCLUSION: the negative effects of delaying anti-VEGF treatment because of the COVID-19 pandemic can be ameliorated by changing the treatment regimen and shortening treatment intervals.

16.
Elife ; 122024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38270169

RESUMO

The α-arrestins form a large family of evolutionally conserved modulators that control diverse signaling pathways, including both G-protein-coupled receptor (GPCR)-mediated and non-GPCR-mediated pathways, across eukaryotes. However, unlike ß-arrestins, only a few α-arrestin targets and functions have been characterized. Here, using affinity purification and mass spectrometry, we constructed interactomes for 6 human and 12 Drosophila α-arrestins. The resulting high-confidence interactomes comprised 307 and 467 prey proteins in human and Drosophila, respectively. A comparative analysis of these interactomes predicted not only conserved binding partners, such as motor proteins, proteases, ubiquitin ligases, RNA splicing factors, and GTPase-activating proteins, but also those specific to mammals, such as histone modifiers and the subunits of V-type ATPase. Given the manifestation of the interaction between the human α-arrestin, TXNIP, and the histone-modifying enzymes, including HDAC2, we undertook a global analysis of transcription signals and chromatin structures that were affected by TXNIP knockdown. We found that TXNIP activated targets by blocking HDAC2 recruitment to targets, a result that was validated by chromatin immunoprecipitation assays. Additionally, the interactome for an uncharacterized human α-arrestin ARRDC5 uncovered multiple components in the V-type ATPase, which plays a key role in bone resorption by osteoclasts. Our study presents conserved and species-specific protein-protein interaction maps for α-arrestins, which provide a valuable resource for interrogating their cellular functions for both basic and clinical research.


Assuntos
Arrestina , ATPases Vacuolares Próton-Translocadoras , Animais , Humanos , Histonas , Drosophila , Arrestinas , Mamíferos
17.
Int J Mol Sci ; 25(2)2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38256022

RESUMO

Our study investigated the embryo-ototoxic effects of deodorant2 (DA2) on zebrafish embryos, which serve as valuable model organisms due to genetic and physiological similarities to humans. We focused on understanding DA2's impact on zebrafish hair cells, which are vital for sensory perception and balance regulation. DA2, provided by the Ministry of Environment, Republic of Korea, was used at 460 µg/mL in dimethyl sulfoxide (DMSO), with a 0.43% DMSO solvent control group. Three experiments, each using 10 zebrafish specimens from each group, showed an initial 13% hair cell count reduction in the DA2-exposed group. Subsequent experiments demonstrated reductions of 37% and 22%, each with one mortality case. Statistical analysis revealed a significant 24% hair cell count reduction in the DA2-exposed group. We also assessed DA2's impact on zebrafish behavior. Although not statistically significant, differences in distances traveled (0.33-0.39, 95% confidence interval: -0.46-1.1, p = 0.2033) and latencies (-0.016-0.018, 95% confidence interval: -0.052-0.021, p = 0.1917) hinted at negative effects. These results highlight DA2's ototoxic properties affecting zebrafish auditory systems and behavior. Further investigation into DA2's effects on aquatic organisms and potential mitigation strategies are essential. These findings contribute to understanding DA2's safety profile, benefiting aquatic ecosystems and human health assessments.


Assuntos
Desodorantes , Ototoxicidade , Perciformes , Humanos , Animais , Dimetil Sulfóxido , Ecossistema , Peixe-Zebra , Embrião de Mamíferos
18.
Sci Rep ; 14(1): 1977, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263203

RESUMO

The increase in telecommuting during COVID-19 and advances in digital technology have necessitated the establishment of guidelines for maximizing productivity through indoor space design for telecommuters. Additionally, understanding the physiological response of individuals working in indoor spaces has attracted attention. This study applied mixed-reality environment to alter the design of the indoor space in real-time, while monitoring the task performance and representative psycho-physiological indicators (electroencephalogram and heart rate variability) of 30 individuals with telecommuting experience. To this end, four tasks, including spatial memory, attention, execution, and working memory, were conducted, and the psycho-physiological data from these tests were statistically analyzed. The results revealed that the design of the indoor space did not affect the spatial memory; however, the parasympathetic nerves were stimulated in visually non-preferred spaces, thus reducing mental stress and leading to high efficiency in short-term work. According to the Yerkes-Dodson law, the working memory of an individual is generally efficient and physically stable over time if they adjust to a preferred or decision-making space. Thus, the future design of telecommuting spaces must consider the type of work being done, and guidelines for spatial design should be developed by recognizing the psycho-physiological status of users, while increasing efficiency.


Assuntos
Realidade Aumentada , COVID-19 , Humanos , Análise e Desempenho de Tarefas , Teletrabalho , Vias Autônomas
19.
Retina ; 44(2): 261-268, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37782951

RESUMO

PURPOSE: To investigate the association between visual outcomes and choroidal changes in patients with macula-off rhegmatogenous retinal detachment. METHODS: This study retrospectively reviewed 63 eyes of patients with macula-off rhegmatogenous retinal detachment who underwent vitrectomy. Their fellow eyes were analyzed as a control group. The choroidal vascularity index (CVI), ellipsoid zone/external limiting membrane integrity, central foveal thickness, and subfoveal choroidal thickness were documented and analyzed. Linear regression analyses were performed to identify factors affecting the final best-corrected visual acuity. RESULTS: Eyes with rhegmatogenous retinal detachment showed increased CVI (68.8 ± 4.1) compared with the control group (66.1 ± 8.8, P = 0.028). Multivariate linear regression analysis revealed that patients with a poor final best-corrected visual acuity had a longer detachment duration ( P = 0.002), worse baseline best-corrected visual acuity ( P = 0.034), thinner central foveal thickness ( P = 0.005), and greater CVI ( P = 0.001) and were more likely to be tamponated with silicone oil ( P = 0.001). Choroidal vascularity index was particularly increased in eyes with poor ellipsoid zone/external limiting membrane integrity, prolonged detachment duration, thin central foveal thickness, and worse best-corrected visual acuity. CONCLUSION: Increased CVI could indicate poor visual outcomes in patients with macula-off rhegmatogenous retinal detachment. Choroidal remodeling could be associated with the disruption of the ellipsoid zone/external limiting membrane integrity.


Assuntos
Macula Lutea , Descolamento Retiniano , Humanos , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/cirurgia , Estudos Retrospectivos , Tomografia de Coerência Óptica , Acuidade Visual , Macula Lutea/cirurgia , Vitrectomia
20.
Nutrients ; 15(21)2023 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-37960252

RESUMO

Air pollution causes various airway diseases. However, many commonly used treatments can have high risks of side effects or are costly. To examine the anti-inflammatory properties of Inula japonica Thunb. and Potentilla chinensis Ser., a mouse model was generated via inhalation of both particulate matter 10 and diesel particulate matter, and 30% ethanol extracts of either I. japonica (IJ) or P. chinensis (PC) and a mixture of both ethanol extracts (IP) were orally administered to BALB/c mice for 12 days. IJ, PC, and IP inhibited immune cell numbers and their regulation in both the bronchoalveolar lavage fluid (BALF) and lungs. These agents suppressed the levels of interleukin (IL)-1α, IL-17, tumor necrosis factor (TNF)-α, C-X-C motif chemokine ligand (CXCL)-1, and CXCL-2 in BALF, and also inhibited F4/80 and IL-1 receptor-associated kinase (IRAK)-1 in lungs. They reduced the gene expression of TNF-α, CXCL-1, inducible NOS, COX-2, Mucin 5AC, and transient receptor potential cation channel subfamily V member 1 in lungs. These extracts also reduced histopathological changes and inflammatory progression, manifested as decreased cell infiltration, collagen deposition, and respiratory epithelial cell thickness. I. japonica and P. chinensis show potential for development as pharmaceuticals that suppress inflammatory progression and alleviate airway inflammation diseases caused by air pollutants.


Assuntos
Inula , Potentilla , Camundongos , Animais , Material Particulado/toxicidade , Inula/metabolismo , Pulmão/patologia , Inflamação/patologia , Líquido da Lavagem Broncoalveolar , Fator de Necrose Tumoral alfa/farmacologia , Componentes Aéreos da Planta , Citocinas/metabolismo
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