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2.
Cell Death Dis ; 15(6): 464, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38942749

RESUMO

The role of mitochondria peptides in the spreading of glioblastoma remains poorly understood. In this study, we investigated the mechanism underlying intracranial glioblastoma progression. Our findings demonstrate that the mitochondria-derived peptide, humanin, plays a significant role in enhancing glioblastoma progression through the intratumoral activation of the integrin alpha V (ITGAV)-TGF beta (TGFß) signaling axis. In glioblastoma tissues, humanin showed a significant upregulation in the tumor area compared to the corresponding normal region. Utilizing multiple in vitro pharmacological and genetic approaches, we observed that humanin activates the ITGAV pathway, leading to cellular attachment and filopodia formation. This process aids the subsequent migration and invasion of attached glioblastoma cells through intracellular TGFßR signaling activation. In addition, our in vivo orthotopic glioblastoma model provides further support for the pro-tumoral function of humanin. We observed a correlation between poor survival and aggressive invasiveness in the humanin-treated group, with noticeable tumor protrusions and induced angiogenesis compared to the control. Intriguingly, the in vivo effect of humanin on glioblastoma was significantly reduced by the treatment of TGFBR1 inhibitor. To strengthen these findings, public database analysis revealed a significant association between genes in the ITGAV-TGFßR axis and poor prognosis in glioblastoma patients. These results collectively highlight humanin as a pro-tumoral factor, making it a promising biological target for treating glioblastoma.


Assuntos
Progressão da Doença , Glioblastoma , Integrina alfaV , Transdução de Sinais , Fator de Crescimento Transformador beta , Glioblastoma/metabolismo , Glioblastoma/patologia , Glioblastoma/genética , Humanos , Fator de Crescimento Transformador beta/metabolismo , Animais , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Tumoral , Integrina alfaV/metabolismo , Integrina alfaV/genética , Camundongos , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Movimento Celular/efeitos dos fármacos , Camundongos Nus , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I/genética , Receptor do Fator de Crescimento Transformador beta Tipo I/antagonistas & inibidores , Invasividade Neoplásica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
3.
Cells ; 13(11)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38891110

RESUMO

Precise control of neuronal activity is crucial for the proper functioning of neurons. How lipid homeostasis contributes to neuronal activity and how much of it is regulated by cells autonomously is unclear. In this study, we discovered that absence of the lipid regulator nhr-49, a functional ortholog of the peroxisome proliferator-activated receptor (PPAR) in Caenorhabditis elegans, resulted in defective pathogen avoidance behavior against Pseudomonas aeruginosa (PA14). Functional NHR-49 was required in the neurons, and more specifically, in a set of oxygen-sensing body cavity neurons, URX, AQR, and PQR. We found that lowering the neuronal activity of the body cavity neurons improved avoidance in nhr-49 mutants. Calcium imaging in URX neurons showed that nhr-49 mutants displayed longer-lasting calcium transients in response to an O2 upshift, suggesting that excess neuronal activity leads to avoidance defects. Cell-specific rescue of NHR-49 in the body cavity neurons was sufficient to improve pathogen avoidance, as well as URX neuron calcium kinetics. Supplementation with oleic acid also improved avoidance behavior and URX calcium kinetics, suggesting that the defective calcium response in the neuron is due to lipid dysfunction. These findings highlight the role of cell-autonomous lipid regulation in neuronal physiology and immune behavior.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Metabolismo dos Lipídeos , Neurônios , Pseudomonas aeruginosa , Animais , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/microbiologia , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Neurônios/metabolismo , Cálcio/metabolismo , Mutação/genética , Aprendizagem da Esquiva , Receptores Citoplasmáticos e Nucleares
4.
Colorectal Dis ; 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38881232

RESUMO

AIM: The aim of this study was to compare the clinicopathological and oncological characteristics of sporadic colorectal cancer (CRC) between young and elderly patients without any genetic mutations that cause hereditary CRC. METHOD: In this cross-sectional, retrospective study conducted at three tertiary referral hospitals, we enrolled 1599 patients with CRC who underwent surgery between January 2010 and December 2017, including 157 young patients (age ≤ 40 years; yCRC) and 1442 elderly patients (age ≥ 70 years; eCRC). The clinicopathological and oncological outcomes were compared between the two groups. RESULTS: The median age at diagnosis was 37 years in the yCRC group (range 33.0-39.2 years) and 76 years in the eCRC group (range 72.0-79.0 years). The yCRC group did not present with advanced stages at diagnosis compared with the eCRC group, and the distribution of tumour stages was similar between the two groups. Microsatellite instability (MSI) testing revealed no difference in the frequency of tumours with high MSI (7.8% in yCRC, 5.8% in eCRC), and the frequency of mutations in the KRAS, NRAS and BRAF genes was also similar. The 3-year overall survival was better in the yCRC group than in the eCRC group (97.4% vs. 83.5%, p < 0.001); however, no such difference was observed in cancer-specific survival. CONCLUSION: Genetically proven sporadic CRCs did not differ significantly between young and elderly patients in terms of tumour stage, tumour location and various molecular features. CLINICAL TRIAL REGISTRATION NUMBER: The study was retrospectively registered with Clinical Trials.gov (no. NCT05601609).

5.
PLoS Biol ; 22(5): e3002592, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38691548

RESUMO

Stomata are pores on plant aerial surfaces, each bordered by a pair of guard cells. They control gas exchange vital for plant survival. Understanding how guard cells respond to environmental signals such as atmospheric carbon dioxide (CO2) levels is not only insightful to fundamental biology but also relevant to real-world issues of crop productivity under global climate change. In the past decade, multiple important signaling elements for stomatal closure induced by elevated CO2 have been identified. Yet, there is no comprehensive understanding of high CO2-induced stomatal closure. In this work, we assemble a cellular signaling network underlying high CO2-induced stomatal closure by integrating evidence from a comprehensive literature analysis. We further construct a Boolean dynamic model of the network, which allows in silico simulation of the stomatal closure response to high CO2 in wild-type Arabidopsis thaliana plants and in cases of pharmacological or genetic manipulation of network nodes. Our model has a 91% accuracy in capturing known experimental observations. We perform network-based logical analysis and reveal a feedback core of the network, which dictates cellular decisions in closure response to high CO2. Based on these analyses, we predict and experimentally confirm that applying nitric oxide (NO) induces stomatal closure in ambient CO2 and causes hypersensitivity to elevated CO2. Moreover, we predict a negative regulatory relationship between NO and the protein phosphatase ABI2 and find experimentally that NO inhibits ABI2 phosphatase activity. The experimental validation of these model predictions demonstrates the effectiveness of network-based modeling and highlights the decision-making role of the feedback core of the network in signal transduction. We further explore the model's potential in predicting targets of signaling elements not yet connected to the CO2 network. Our combination of network science, in silico model simulation, and experimental assays demonstrates an effective interdisciplinary approach to understanding system-level biology.


Assuntos
Arabidopsis , Dióxido de Carbono , Modelos Biológicos , Estômatos de Plantas , Transdução de Sinais , Estômatos de Plantas/efeitos dos fármacos , Estômatos de Plantas/metabolismo , Estômatos de Plantas/fisiologia , Dióxido de Carbono/metabolismo , Dióxido de Carbono/farmacologia , Arabidopsis/metabolismo , Arabidopsis/genética , Arabidopsis/fisiologia , Simulação por Computador , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética
6.
Ann Pediatr Endocrinol Metab ; 29(2): 90-94, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38712492

RESUMO

PURPOSE: The gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard for diagnosing central precocious puberty (CPP). Gonadorelin (Relefact) is used for the test but is not always readily available; triptorelin is used as an alternative. The purpose of this study was to evaluate the diagnostic validity of the triptorelin test compared with the GnRH test in the diagnosis of CPP in girls. METHODS: This retrospective study included 100 girls with premature thelarche (PT) who underwent a hypothalamic-pituitary-gonadal axis evaluation. In the overall group, 50 girls were tested with intravenous gonadorelin (Relefact) and 50 girls were tested with subcutaneous triptorelin acetate (Decapeptyl). Luteinizing hormone (LH) and follicle-stimulating hormone levels were measured at baseline and 30, 45, 60, and 90 minutes after gonadorelin injection or 30, 60, 90, and 120 minutes after triptorelin injection. RESULTS: Clinical characteristics of age, height, weight, body mass index, and bone age were similar between the 2 groups. The highest LH level was reached 60 minutes after stimulation in both groups. Approximately 20% of the gonadorelin group and 24% of the triptorelin group were diagnosed with CPP (P=0.52). Among those diagnosed with CPP, the mean peak LH concentrations were 8.15 mIU/mL and 9.73 mIU/mL in the gonadorelin and triptorelin groups, respectively. CONCLUSION: The triptorelin test showed similar trends of LH elevation and diagnostic rate compared with the traditional GnRH test for diagnosing CPP. This suggests that the triptorelin test may be a valid alternative to the GnRH test for differentiating CPP from self-limiting PT. Our study also demonstrated that a triptorelin stimulation test for up to 120 minutes was sufficient to diagnose CPP.

7.
Acta Ophthalmol ; 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38706195

RESUMO

PURPOSE: To investigate the long-term efficacy and safety of intravitreal brolucizumab (BRZ) injections in patients with typical neovascular age-related macular degeneration (typical nAMD) and polypoidal choroidal vasculopathy (PCV). METHODS: This multicentre retrospective study included 401 eyes of 398 patients with nAMD who received BRZ injection(s), with a follow-up duration of ≥12 months. Changes in best-corrected visual acuity (BCVA), retinal fluid evaluation and central subfield thickness (CST) on optical coherence tomography were assessed. The efficacy of BRZ was compared between typical nAMD and PCV groups. RESULTS: Analyses were conducted with 280 eyes of 278 patients with typical nAMD and 121 eyes of 120 patients with PCV (mean age, 71.1 ± 8.6 years). 29 eyes (7.2%) were treatment naïve. The mean follow-up period was 15.3 ± 2.8 months; the mean number of BRZ injections within 1 year was 4.5 ± 1.7. BCVA was maintained during the follow-up period, and CST significantly improved from the first injection month and was maintained for 12 months in both the typical nAMD and PCV groups. The dry macula proportion increased from 2.7% at baseline to 56.1% at 1 month and 42.9% at 12 months. Among the 18 eyes that underwent indocyanine green angiography both before and after treatment, 10 (55.6%) showed polyp regression. Overall, the incidence of intraocular inflammation (IOI), retinal vasculitis and occlusive retinal vasculitis was 9.4% (38 eyes), 1.2% (5 eyes) and 0.5% (2 eyes), respectively. IOI occurred from the first to the sixth injections, with an average IOI onset of 28.5 ± 1.4 days. All eyes achieved IOI resolution, although the two eyes with occlusive retinal vasculitis showed a severe visual decline after IOI resolution. CONCLUSION: Brolucizumab was effective in maintaining BCVA and managing fluid in eyes with nAMD for up to 1 year, exhibiting a high polyp regression rate. However, the not uncommon incidence of IOI and the severe visual decline caused by the rare occlusive retinal vasculitis following BRZ treatment underscore the importance of careful monitoring and timely management.

8.
FASEB J ; 38(9): e23638, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38713098

RESUMO

Diabetic retinopathy (DR) is associated with ocular inflammation leading to retinal barrier breakdown, vascular leakage, macular edema, and vision loss. DR is not only a microvascular disease but also involves retinal neurodegeneration, demonstrating that pathological changes associated with neuroinflammation precede microvascular injury in early DR. Macrophage activation plays a central role in neuroinflammation. During DR, the inflammatory response depends on the polarization of retinal macrophages, triggering pro-inflammatory (M1) or anti-inflammatory (M2) activity. This study aimed to determine the role of macrophages in vascular leakage through the tight junction complexes of retinal pigment epithelium, which is the outer blood-retinal barrier (BRB). Furthermore, we aimed to assess whether interleukin-10 (IL-10), a representative M2-inducer, can decrease inflammatory macrophages and alleviate outer-BRB disruption. We found that modulation of macrophage polarization affects the structural and functional integrity of ARPE-19 cells in a co-culture system under high-glucose conditions. Furthermore, we demonstrated that intravitreal IL-10 injection induces an increase in the ratio of anti-inflammatory macrophages and effectively suppresses outer-BRB disruption and vascular leakage in a mouse model of early-stage streptozotocin-induced diabetes. Our results suggest that modulation of macrophage polarization by IL-10 administration during early-stage DR has a promising protective effect against outer-BRB disruption and vascular leakage. This finding provides valuable insights for early intervention in DR.


Assuntos
Barreira Hematorretiniana , Diabetes Mellitus Experimental , Retinopatia Diabética , Interleucina-10 , Macrófagos , Animais , Humanos , Masculino , Camundongos , Barreira Hematorretiniana/metabolismo , Barreira Hematorretiniana/patologia , Polaridade Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/metabolismo , Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , Modelos Animais de Doenças , Interleucina-10/metabolismo , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Estreptozocina
9.
Sci Rep ; 14(1): 8242, 2024 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589440

RESUMO

The aim of this study was to introduce novel vector field analysis for the quantitative measurement of retinal displacement after epiretinal membrane (ERM) removal. We developed a novel framework to measure retinal displacement from retinal fundus images as follows: (1) rigid registration of preoperative retinal fundus images in reference to postoperative retinal fundus images, (2) extraction of retinal vessel segmentation masks from these retinal fundus images, (3) non-rigid registration of preoperative vessel masks in reference to postoperative vessel masks, and (4) calculation of the transformation matrix required for non-rigid registration for each pixel. These pixel-wise vector field results were summarized according to predefined 24 sectors after standardization. We applied this framework to 20 patients who underwent ERM removal to obtain their retinal displacement vector fields between retinal fundus images taken preoperatively and at postoperative 1, 4, 10, and 22 months. The mean direction of displacement vectors was in the nasal direction. The mean standardized magnitudes of retinal displacement between preoperative and postoperative 1 month, postoperative 1 and 4, 4 and 10, and 10 and 22 months were 38.6, 14.9, 7.6, and 5.4, respectively. In conclusion, the proposed method provides a computerized, reproducible, and scalable way to analyze structural changes in the retina with a powerful visualization tool. Retinal structural changes were mostly concentrated in the early postoperative period and tended to move nasally.


Assuntos
Membrana Epirretiniana , Humanos , Membrana Epirretiniana/cirurgia , Acuidade Visual , Retina/diagnóstico por imagem , Retina/cirurgia , Vasos Retinianos , Fundo de Olho , Vitrectomia , Tomografia de Coerência Óptica/métodos , Estudos Retrospectivos
10.
J Nat Prod ; 87(4): 1230-1234, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38626456

RESUMO

Three new cyclic heptapeptides, talaromides A-C (1-3), were isolated from cultures produced by the fungus Talaromyces siglerae (Ascomycota), isolated from an unidentified sponge. The structures, featuring an unusual proline-anthranilic moiety, were elucidated by analysis of spectroscopic data and chemical transformations, including the advanced Marfey's method and GITC derivatization. Talaromides A and B inhibited migration activity against PANC-1 human pancreatic cancer cells without significant cytotoxicity.


Assuntos
Peptídeos Cíclicos , Poríferos , Talaromyces , Talaromyces/química , Animais , Poríferos/microbiologia , Humanos , Estrutura Molecular , Peptídeos Cíclicos/farmacologia , Peptídeos Cíclicos/química , Peptídeos Cíclicos/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais , Biologia Marinha , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação
11.
Urolithiasis ; 52(1): 66, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630256

RESUMO

The purpose of this study was to measure and compare renal pelvic pressure (RPP) between prone and supine percutaneous nephrolithotomy (PCNL) in a benchtop model. Six identical silicone kidney models were placed into anatomically correct prone or supine torsos constructed from patient CT scans in the corresponding positions. A 30-Fr renal access sheath was placed in either the upper, middle, or lower pole calyx for both prone and supine positions. Two 9-mm BegoStones were placed in the respective calyx and RPPs were measured at baseline, irrigating with a rigid nephroscope, and irrigating with a flexible nephroscope. Five trials were conducted for each access in both prone and supine positions. The average baseline RPP in the prone position was significantly higher than the supine position (9.1 vs 2.7 mmHg; p < 0.001). Similarly, the average RPP in prone was significantly higher than supine when using both the rigid and flexible nephroscopes. When comparing RPPs for upper, middle, and lower pole access sites, there was no significant difference in pressures in either prone or supine positions (p > 0.05 for all). Overall, when combining all pressures at baseline and with irrigation, with all access sites and types of scopes, the mean RPP was significantly higher in the prone position compared to the supine position (14.0 vs 3.2 mmHg; p < 0.001). RPPs were significantly higher in the prone position compared to the supine position in all conditions tested. These differences in RPPs between prone and supine PCNL could in part explain the different clinical outcomes, including postoperative fever and stone-free rates.


Assuntos
Nefrolitotomia Percutânea , Humanos , Nefrolitotomia Percutânea/efeitos adversos , Pelve Renal , Rim/diagnóstico por imagem , Rim/cirurgia , Cálices Renais , Posicionamento do Paciente
12.
Artigo em Inglês | MEDLINE | ID: mdl-38684017

RESUMO

High-Ni layered oxide cathodes are promising candidates for lithium-ion batteries due to their high energy density. However, their cycle stability is compromised by the poor mechanical durability of the particle microstructure. In this study, we investigate the impact of the calcination temperature on microstructural changes, including primary particle growth and pore evolution, using LiNi0.88Mn0.08Co0.04O2 (N884), with an emphasis on the critical calcination temperature for polycrystalline and single-crystal designs in high-Ni cathodes. As the calcination temperature increases, the primary particles undergo a rectangular growth pattern while the pore population decreases. Beyond a certain critical temperature (in this case, 850 °C), a sudden increase in primary particle size and a simultaneous rapid reduction in the pore population are observed. This sudden microstructure evolution leads to poor cycle retention in N884. In contrast, single-crystal particles, free of grain boundaries, synthesized at this critical temperature exhibit superior cycle retention, underscoring the significance of microstructural design over crystalline quality for achieving long-term cyclability. Our study sheds light on the interplay between calcination temperature and microstructural evolution, proposing the critical temperature as a key criterion for single-crystal synthesis.

13.
Molecules ; 29(8)2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38675653

RESUMO

Leishmaniasis, an infectious disease caused by pathogenic Leishmania parasites, affects millions of people in developing countries, and its re-emergence in developed countries, particularly in Europe, poses a growing public health concern. The limitations of current treatments and the absence of effective vaccines necessitate the development of novel therapeutics. In this study, we focused on identifying small molecule inhibitors which prevents the interaction between peroxin 5 (PEX5) and peroxisomal targeting signal 1 (PTS1), pivotal for kinetoplastid parasite survival. The Leishmania donovani PEX5, containing a C-terminal tetratricopeptide repeat (TPR) domain, was expressed and purified, followed by the quantification of kinetic parameters of PEX5-PTS1 interactions. A fluorescence polarization-based high-throughput screening assay was developed and small molecules inhibiting the LdPEX5-PTS1 interaction were discovered through the screening of a library of 51,406 compounds. Based on the confirmatory assay, nine compounds showed half maximal inhibitory concentration (IC50) values ranging from 3.89 to 24.50 µM. In silico docking using a homology model of LdPEX5 elucidated that the molecular interactions between LdPEX5 and the inhibitors share amino acids critical for PTS1 binding. Notably, compound P20 showed potent activity against the growth of L. donovani promastigotes, L. major promastigotes, and Trypanosoma brucei blood stream form, with IC50 values of 12.16, 19.21, and 3.06 µM, respectively. The findings underscore the potential of targeting LdPEX5-PTS1 interactions with small molecule inhibitors as a promising strategy for the discovery of new anti-parasitic compounds.


Assuntos
Ensaios de Triagem em Larga Escala , Leishmania donovani , Simulação de Acoplamento Molecular , Receptor 1 de Sinal de Orientação para Peroxissomos , Proteínas de Protozoários , Leishmania donovani/efeitos dos fármacos , Leishmania donovani/metabolismo , Ensaios de Triagem em Larga Escala/métodos , Receptor 1 de Sinal de Orientação para Peroxissomos/metabolismo , Receptor 1 de Sinal de Orientação para Peroxissomos/química , Proteínas de Protozoários/antagonistas & inibidores , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/química , Polarização de Fluorescência/métodos , Ligação Proteica , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/química , Antiprotozoários/farmacologia , Antiprotozoários/química , Humanos
14.
Int J Mol Sci ; 25(8)2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38673975

RESUMO

Previously, we reported that epidermal growth factor-like module-containing mucin-like hormone receptor-like 1 (EMR1/ADGRE1) is abnormally expressed in colon cancer (CC) and is a risk factor for lymph node metastasis (LNM) and poor recurrence-free survival in patients with abundant tumor-associated macrophages (TAMs). However, the signaling pathways associated with EMR1 expression in CC progression remain unclear. In this study, we aimed to explore the role of EMR1 and its signaling interactions with macrophages in CC progression. Spatial transcriptomics of pT3 microsatellite unstable CC tissues revealed heightened Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling in EMR1-HL CC with LNM compared to EMR1-N CC without LNM. Through in vitro coculture of CC cells with macrophages, EMR1 expression by CC cells was found to be induced by TAMs, ultimately interacting with upregulated JAK/STAT signaling, increasing cell proliferation, migration, and motility, and reducing apoptosis. JAK2/STAT3 inhibition decreased the levels of EMR1, JAK2, STAT1, and STAT3, significantly impeded the proliferation, migration, and mobility of cells, and increased the apoptosis of EMR1+ CC cells compared to their EMR1KO counterparts. Overall, TAMs-induced EMR1 upregulation in CC cells may promote LNM and CC progression via JAK2/STAT1,3 signaling upregulation. This study provides further insights into the molecular mechanisms involving macrophages and intracellular EMR1 expression in CC progression, suggesting its clinical significance and offering potential interventions to enhance patient outcomes.


Assuntos
Neoplasias do Colo , Janus Quinase 2 , Transdução de Sinais , Macrófagos Associados a Tumor , Humanos , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/patologia , Janus Quinase 2/metabolismo , Janus Quinase 2/genética , Neoplasias do Colo/patologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica , Progressão da Doença , Regulação para Cima , Proliferação de Células , Linhagem Celular Tumoral , Movimento Celular/genética , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Apoptose/genética
15.
Resuscitation ; 199: 110207, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38582440

RESUMO

AIM: To assess the ability of clinical examination, biomarkers, electrophysiology and brain imaging, individually or in combination to predict good neurological outcomes at 6 months after CA. METHODS: This was a retrospective analysis of the Korean Hypothermia Network Prospective Registry 1.0, which included adult out-of-hospital cardiac arrest (OHCA) patients (≥18 years). Good outcome predictors were defined as both pupillary light reflex (PLR) and corneal reflex (CR) at admission, Glasgow Coma Scale Motor score (GCS-M) >3 at admission, neuron-specific enolase (NSE) <17 µg/L at 24-72 h, a median nerve somatosensory evoked potential (SSEP) N20/P25 amplitude >4 µV, continuous background without discharges on electroencephalogram (EEG), and absence of anoxic injury on brain CT and diffusion-weighted imaging (DWI). RESULTS: A total of 1327 subjects were included in the final analysis, and their median age was 59 years; among them, 412 subjects had a good neurological outcome at 6 months. GCS-M >3 at admission had the highest specificity of 96.7% (95% CI 95.3-97.8), and normal brain DWI had the highest sensitivity of 96.3% (95% CI 92.9-98.4). When the two predictors were combined, the sensitivities tended to decrease (ranging from 2.7-81.1%), and the specificities tended to increase, ranging from81.3-100%. Through the explorative variation of the 2021 European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) prognostication strategy algorithms, good outcomes were predicted, with a specificity of 83.2% and a sensitivity of 83.5% in patients by the algorithm. CONCLUSIONS: Clinical examination, biomarker, electrophysiology, and brain imaging predicted good outcomes at 6 months after CA. When the two predictors were combined, the specificity further improved. With the 2021 ERC/ESICM guidelines, the number of indeterminate patients and the uncertainty of prognostication can be reduced by using a good outcome prediction algorithm.


Assuntos
Parada Cardíaca Extra-Hospitalar , Sistema de Registros , Humanos , Parada Cardíaca Extra-Hospitalar/terapia , Masculino , Feminino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Estudos Prospectivos , Idoso , Prognóstico , Estudos Retrospectivos , Reanimação Cardiopulmonar/métodos , Biomarcadores/sangue , Reflexo Pupilar/fisiologia , Escala de Coma de Glasgow , Potenciais Somatossensoriais Evocados/fisiologia , Eletroencefalografia/métodos , Adulto , Fosfopiruvato Hidratase/sangue
16.
Angew Chem Int Ed Engl ; 63(24): e202317177, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38606608

RESUMO

Co-intercalation reactions make graphite a feasible anode in Ca ion batteries, yet the correlation between Ca ion intercalation behaviors and electrolyte structure remains unclear. This study, for the first time, elucidates the pivotal role of anions in modulating the Ca ion solvation structures and their subsequent intercalation into graphite. Specifically, the electrostatic interactions between Ca ion and anions govern the configurations of solvated-Ca-ion in dimethylacetamide-based electrolytes and graphite intercalation compounds. Among the anions considered (BH4 -, ClO4 -, TFSI- and [B(hfip)4]-), the coordination of four solvent molecules per Ca ion (CN=4) leads to the highest reversible capacities and the fastest reaction kinetics in graphite. Our study illuminates the origins of the distinct Ca ion intercalation behaviors across various anion-modulated electrolytes, employing a blend of experimental and theoretical approaches. Importantly, the practical viability of graphite anodes in Ca-ion full cells is confirmed, showing significant promise for advanced energy storage systems.

17.
J Am Soc Mass Spectrom ; 35(6): 1301-1309, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38657000

RESUMO

Small interfering RNA (siRNA) is known for its ability to silence the expression of specific genes, demonstrating its promising potential as a therapeutic approach. Self-assembled micelle inhibitory RNA (SAMiRNA) is an oligonucleotide duplex developed to overcome the in vivo delivery limitations of siRNA. SAMiRNA has hydrophilic and hydrophobic groups at both ends of a sense strand, forming a spherical nanostructure that enhances the in vivo delivery efficiency. Ion-pairing reversed-phase liquid chromatography (IP-RPLC) is the most commonly used method for the analysis of oligonucleotides. Since SAMiRNA is heavily chemically modified, the behavior of SAMiRNA in IP-RPLC combined with mass spectrometry (MS) is anticipated to differ from that of the conventional siRNA drug. The current investigation using IP-RPLC-MS revealed that a distinct duplex peak along with two minor separate strands of antisense and sense was observed at column temperatures below 35 °C in the IP-RPLC system with a 100 mM ammonium bicarbonate buffer system. At column temperatures higher than 35 °C, however, two fully denatured single strands were observed. The mass spectrum from the chromatographic peak of the SAMiRNA duplex contained signals from the duplex, the antisense, and the sense, probably due to duplex denaturation during the MS ionization process. The current comprehensive analysis results will make a substantial contribution to the future application of IP-RPLC-MS in the analysis of SAMiRNA.


Assuntos
Cromatografia de Fase Reversa , Micelas , RNA Interferente Pequeno , Cromatografia de Fase Reversa/métodos , RNA Interferente Pequeno/química , RNA Interferente Pequeno/análise , RNA Interferente Pequeno/genética , Espectrometria de Massas/métodos
18.
Sci Rep ; 14(1): 5251, 2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438402

RESUMO

Congenital and infantile (CI) cataract is one of the most important and preventable cause of blindness in children, but the incidence has not been studied in Korea. We collected data from the national claims database of the National Health Insurance Service of Korea from 2002 through 2019. We identified children who underwent cataract surgery within the age of 5 years, and cumulative incidence rates were calculated for each of the three age criteria. 989 patients out of 4,221,459 births underwent surgery with CI cataract during the period. The cumulative incidence rates per 10,000 births were 1.60 (0-1 years), 2.38 (0-3 years), and 2.95 (0-5 years), respectively. The incidence peaked in the 2007 birth cohort, which coincides with the start of the national screening program for infants/children. Primary intraocular lens implantation was performed in 439 patients (44%). Strabismus and glaucoma requiring surgery occurred in 291 patients (29.4%) and 32 patients (3.2%), respectively, within 8 years after cataract surgery. The incidence rates of CI cataract in Korea appear to be comparable to previous studies in other regions. The early screening program for infants may reduce delayed diagnosis and increase the proportion of patients undergoing surgery at a critical time for visual development.


Assuntos
Extração de Catarata , Catarata , Oftalmologia , Criança , Lactente , Humanos , Pré-Escolar , Incidência , Catarata/epidemiologia , República da Coreia/epidemiologia
19.
Sci Rep ; 14(1): 5249, 2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438557

RESUMO

To compare the efficacy of scleral buckling with adjuvant pneumatic retinopexy (SB with PR) and scleral buckling (SB) alone for primary rhegmatogenous retinal detachment (RRD). This retrospective and comparative study included patients who underwent SB with PR (n = 88) or SB alone (n = 161) for primary RRD. The primary anatomical success rate for SB with PR was 81.8%, whereas that for SB alone was 80.7% (P = 0.836). Among patients who achieved primary anatomical success, those in the SB with PR group showed postoperative epiretinal membrane (ERM) formation more frequently than those in the SB alone group (11 of 72 [15.3%] vs. 6 of 130 [4.6%]) (P = 0.009). The mean time to subretinal fluid absorption was not significantly different between the SB with PR and SB alone groups (11.2 ± 6.2 vs. 11.4 ± 5.8 months, P = 0.881). In the SB with PR group, retinal detachment involving ≥ three quadrants was a significant risk factor for surgical failure (hazard ratio, 3.04; P = 0.041). Adjuvant pneumatic retinopexy does not provide additional benefit in improving the surgical outcomes of SB for primary RRD repair.


Assuntos
Descolamento Retiniano , Recurvamento da Esclera , Humanos , Descolamento Retiniano/cirurgia , Estudos Retrospectivos , Adjuvantes Imunológicos , Adjuvantes Farmacêuticos
20.
J Nat Prod ; 87(4): 976-983, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38438310

RESUMO

Three unique linear oligomeric depsipeptides, designated as cavomycins A-C (1-3), were identified from Streptomyces cavourensis, a gut bacterium associated with the annelid Paraleonnates uschakovi. The structures of these depsipeptides were determined through a combination of spectroscopic methods and chemical derivatization techniques, including methanolysis, the modified Mosher's method, advanced Marfey's methods, and phenylglycine methyl ester derivatization. The unique dipeptidyl residue arrangements in compounds 1-3 indicate that they are not degradation products of valinomycin. Compound 2 and its methylation derivative 2a exhibited antiproliferative activity against PANC-1 pancreatic cancer cells with IC50 values of 1.2 and 1.7 µM, respectively.


Assuntos
Depsipeptídeos , Streptomyces , Streptomyces/química , Depsipeptídeos/farmacologia , Depsipeptídeos/química , Depsipeptídeos/isolamento & purificação , Humanos , Estrutura Molecular , Animais , Ensaios de Seleção de Medicamentos Antitumorais , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação
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