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1.
Int J Med Mushrooms ; 26(8): 41-57, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38967210

RESUMO

Bone metastasis in metastatic breast cancer commonly results in osteolytic lesions due to osteoclast activity, promoting bone destruction and tumor progression. The bioactive fungal isolates, 4-acetyl-antroquinonol B (4-AAQB) and erinacine A, have diverse pharmacological and biological activities. However, their effects on breast cancer bone metastasis treatment remain unclear. Our study aimed to examine the impact of 4-AAQB or erinacine A on breast cancer metastases in bone. The effects of 4-AAQB and erinacine A on breast cancer-induced osteoclastogenesis, breast cancer migration, production of prometastatic cytokine (TGF-ß) and marker (MMP-9), as well as potential MAPK signaling transductions were assessed. The results revealed that 4-AAQB and erinacine A effectively suppressed breast cancer-induced osteoclastogenesis and migration, and reduced TGF-ß and MMP-9 production via Erk or JNK signaling transductions, specifically in breast cancer cells or in breast cancer cells-induced osteoclasts. Based on these findings, either 4-AAQB or erinacine A showed promise in preventing breast cancer metastases in bone.


Assuntos
Neoplasias da Mama , Metaloproteinase 9 da Matriz , Osteoclastos , Osteogênese , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Humanos , Feminino , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Animais , Fator de Crescimento Transformador beta/metabolismo , Neoplasias Ósseas/secundário , Neoplasias Ósseas/tratamento farmacológico , Camundongos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Cicloexanonas , 4-Butirolactona/análogos & derivados
2.
PLoS One ; 19(4): e0301096, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38564612

RESUMO

This retrospective study aimed to determine the short-term efficacy and safety of brolucizumab treatment for recalcitrant neovascular age-related macular degeneration (nAMD) in a real-world setting in Taiwan. Recalcitrant nAMD patients who were treated with brolucizumab from November 2021 to August 2022 at Taipei Veterans General Hospital were included. Patients were followed for 3 months after switching to brolucizumab. The primary outcomes were changes in mean best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to the third month. The secondary outcomes included the incidence of intraocular inflammation (IOI), proportion of patients with subretinal and intraretinal fluid (SRF and IRF), and change in pigment epithelial detachment (PED) height from baseline to the third month. The significance level was considered as p < .05 in all tests. A total of 38 patients (40 eyes) with a mean (±SD) age of 76.3 (±10.84) years were included. The baseline BCVA was 0.92±0.64 logMAR, and the CRT and PED height were 329.0±171.18 and 189.8±114.94 um, respectively. The patients had a significant reduction in CRT and resolution of IRF and SRF from baseline to the third month. There were numerical improvements in mean BCVA and PED height, but they were not significant. The percentages of achieving at least 0.1, 0.2, and 0.3 logMAR (equivalent to 5, 10, 15 ETDRS letters) visual gain were 50%, 37.5%, and 30%, respectively, during the first 3 months of follow-up. No IOI occurred in these patients. This study demonstrated that brolucizumab had good short-term structural and functional efficacy in recalcitrant nAMD patients.


Assuntos
Anticorpos Monoclonais Humanizados , Degeneração Macular , Descolamento Retiniano , Degeneração Macular Exsudativa , Humanos , Idoso , Idoso de 80 Anos ou mais , Resultado do Tratamento , Seguimentos , Estudos Retrospectivos , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Tomografia de Coerência Óptica , Acuidade Visual , Injeções Intravítreas , Descolamento Retiniano/etiologia , Transtornos da Visão/complicações , Degeneração Macular/tratamento farmacológico , Degeneração Macular/epidemiologia , Degeneração Macular/complicações , China , Inibidores da Angiogênese/uso terapêutico , Degeneração Macular Exsudativa/tratamento farmacológico , Degeneração Macular Exsudativa/complicações
3.
Toxicology ; 502: 153731, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38253231

RESUMO

Lanthanum (La) and cerium (Ce), rare earth elements with physical properties similar to calcium (Ca), are generally considered non-toxic when used appropriately. However, their ions possess anti-tumor capabilities. This investigation explores the potential applications and mechanisms of LaCl3 or CeCl3 treatment in triple-negative breast cancer (TNBC) cell lines. TNBC, characterized by the absence of estrogen receptor (ERα), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression, is prone to early metastasis and resistant to hormone therapy. Our results demonstrate that La/Ce treatment reduces cell growth, and when combined with cisplatin, it synergistically inhibits cell growth and the PI3K/AKT pathway. La and Ce induce oxidative stress by disrupting mitochondrial function, leading to protein oxidation. Additionally, they interfere with protein homeostasis and induce nucleolar stress. Furthermore, disturbance in F-actin web formation impairs cell migration. This study delves into the mechanism by which calcium-like elements La and Ce inhibit breast cancer cell growth, shedding light on their interference in mitochondrial function, protein homeostasis, and cytoskeleton assembly.


Assuntos
Elementos da Série dos Lantanídeos , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Cálcio , Cisplatino , Lantânio/toxicidade , Linhagem Celular Tumoral
4.
J Neurochem ; 168(1): 39-51, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38055867

RESUMO

Liver function has been suggested as a possible factor in the progression of Alzheimer's disease (AD) development. However, the association between liver function and cerebrospinal fluid (CSF) levels of AD biomarkers remains unclear. In this study, we analyzed the data from 1687 adults without dementia from the Chinese Alzheimer's Biomarker and LifestylE study to investigate differences in liver function between pathological and clinical AD groups, as defined by the 2018 National Institute on Aging-Alzheimer's Association Research Framework. We also examined the linear relationship between liver function, CSF AD biomarkers, and cognition using linear regression models. Furthermore, mediation analyses were applied to explore the potential mediation effects of AD pathological biomarkers on cognition. Our findings indicated that, with AD pathological and clinical progression, the concentrations of total protein (TP), globulin (GLO), and aspartate aminotransferase/alanine transaminase (ALT) increased, while albumin/globulin (A/G), adenosine deaminase, alpha-L-fucosidase, albumin, prealbumin, ALT, and glutamate dehydrogenase (GLDH) concentrations decreased. Furthermore, we also identified significant relationships between TP (ß = -0.115, pFDR < 0.001), GLO (ß = -0.184, pFDR < 0.001), and A/G (ß = 0.182, pFDR < 0.001) and CSF ß-amyloid1-42 (Aß1-42 ) (and its related CSF AD biomarkers). Moreover, after 10 000 bootstrapped iterations, we identified a potential mechanism by which TP and GLDH may affect cognition by mediating CSF AD biomarkers, with mediation effect sizes ranging from 3.91% to 16.44%. Overall, our results suggested that abnormal liver function might be involved in the clinical and pathological progression of AD. Amyloid and tau pathologies also might partially mediate the relationship between liver function and cognition. Future research is needed to fully understand the underlying mechanisms and causality to develop an approach to AD prevention and treatment approach.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Globulinas , Humanos , Doença de Alzheimer/patologia , Proteínas tau/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Albuminas , Fígado , Fragmentos de Peptídeos/líquido cefalorraquidiano
5.
Ophthalmologica ; 246(3-4): 238-244, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37552956

RESUMO

INTRODUCTION: The aim of this study was to evaluate the outcomes and complications associated with the use of same-day bilateral intravitreal dexamethasone (DEX) implants for the treatment of diabetic macular edema (DME). METHODS: This retrospective analysis of an open-label, multicenter, consecutive case series included 130 eyes of 65 patients with bilateral DME who were treated with intravitreal DEX implants. The patients were divided into two groups: a control group (comprising 40 eyes treated with an alternating unilateral regimen) and a study group (comprising 90 eyes treated with concomitant bilateral DEX implants). All patients were followed up monthly after implantation. The changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to sixth month after implantation, and ocular adverse effects such as intraocular pressure, cataract, and tolerability of bilateral implantation were reviewed. The primary endpoint was to assess the safety of the same-day bilateral treatment protocol. The secondary endpoints focused on evaluating the functional and anatomical changes associated with bilateral simultaneous or alternating implantations. RESULTS: At 6 months after implantation, mean BCVA increased and CRT decreased in both groups. Moreover, no serious ocular adverse effects were observed. In addition, no differences were observed between the two groups in the number of patients who required extra follow-up visits or the number of extra visits made in addition to the treatment schedule. CONCLUSIONS: Same-day bilateral intravitreal DEX implants are associated with a low complication rate and are well tolerated by patients. This safe practice may optimize efficiency and reduce the burden on both the health-care system and patients, when used to treat bilateral DME.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Humanos , Dexametasona , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/tratamento farmacológico , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/tratamento farmacológico , Implantes de Medicamento/uso terapêutico , Glucocorticoides , Injeções Intravítreas , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Estudos Retrospectivos , Resultado do Tratamento
6.
Sci Rep ; 13(1): 7428, 2023 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-37156823

RESUMO

To better understand the efficacy of intravitreal dexamethasone implant (Ozurdex) versus antivascular endothelial growth factor (anti-VEGF) treatment in patients with diabetic macular edema (DME). A systematic review and meta-analysis. The study included randomized control trials (RCTs) and non-randomized control trials (Non-RCTs) before December 2021 that compare the efficacy of Ozurdex-related therapyand anti-VEGF therapy. We searched PubMed, Cochrane Library, and EMBASE. The quality of the included studies was assessed carefully. 30 studies were included. Regarding BCVA change, the overall result revealed no significant differences between Ozurdex and anti-VEGF therapies in patients with nonresistant DME, but Ozurdex group had significantly more VA improvement than anti-VEGF therapies in patients with resistant DME (MD 0.12, 95% CI 0.02-0.21). In terms of central retinal thickness (CRT) decrease, there was a significant difference between Ozurdex therapy and anti-VEGF therapy in patients with nonresistant DME (MD 48.10, 95% CI 19.06-77.13) and resistant DME (MD 65.37, 95% CI 3.62-127.13). Overall, Ozurdex therapy resulted in significantly greater VA improvement and CRT decrease than anti-VEGF therapy in resistant DME patients. Ozurdex therapy was not inferior to anti-VEGF therapy in patients with nonresistant DME.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Humanos , Edema Macular/tratamento farmacológico , Ranibizumab , Glucocorticoides/uso terapêutico , Fatores de Crescimento Endotelial , Bevacizumab/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Dexametasona/efeitos adversos , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/induzido quimicamente , Injeções Intravítreas , Diabetes Mellitus/induzido quimicamente
7.
Cell Oncol (Dordr) ; 46(4): 1127-1142, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37067747

RESUMO

PURPOSE: Breast cancer is the most common cancer in women. Triple-negative breast cancer (TNBC) is an aggressive disease with poor outcomes. TNBC lacks effective targeted treatments, and the development of drug resistance limits the effectiveness of chemotherapy. It is crucial to identify new drugs that can enhance the efficacy of traditional chemotherapy to reduce drug resistance and side effects. METHODS: TNBC cell lines, MDA-MB-231 and Hs 578T, and a normal cell line, MCF-10 A, were included in this study. The cells were treated with gallium maltolate (GaM), and their transcriptome was analyzed. Ferroptosis and nucleolar stress markers were detected by qPCR, western blotting, fluorescence microscopy, and flow cytometry. The impairment of ribosome synthesis was evaluated by northern blotting and sucrose gradients. RESULTS: GaM triggered cell death via apoptosis and ferroptosis. In addition, GaM impaired translation and activated nucleolar stress. Cisplatin (DDP) is a chemotherapeutic agent for advanced breast cancer. While single treatment with GaM or DDP at low concentrations did not impact cell growth, co-administration enhanced cell death in TNBC but not in normal breast cells. The enhancement of ferroptosis and nucleolar stress could be observed in TNBC cell lines after co-treatment. CONCLUSIONS: These results suggest that GaM synergizes with cisplatin via activation of nucleolar stress and ferroptosis in human breast carcinoma cells. GaM is marginally toxic to normal cells but impairs the growth of TNBC cell lines. Thus, GaM has the potential to be used as a therapeutic agent against TNBC.


Assuntos
Antineoplásicos , Ferroptose , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias de Mama Triplo Negativas/metabolismo , Linhagem Celular Tumoral , Apoptose , Proliferação de Células
8.
World J Gastrointest Surg ; 14(10): 1131-1140, 2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36386397

RESUMO

BACKGROUND: Thrombectomy and anatomical anastomosis (TAA) has long been considered the optimal approach to portal vein thrombosis (PVT) in liver transplantation (LT). However, TAA and the current approach for non-physiological portal reconstructions are associated with a higher rate of complications and mortality in some cases. AIM: To describe a new choice for reconstructing the portal vein through a posterior pancreatic tunnel (RPVPPT) to address cases of unresectable PVT. METHODS: Between August 2019 and August 2021, 245 adult LTs were performed. Forty-five (18.4%) patients were confirmed to have PVT before surgery, among which seven underwent PV reconstruction via the RPVPPT approach. We retrospectively analyzed the surgical procedure and postoperative complications of these seven recipients that underwent PV reconstruction due to PVT. RESULTS: During the procedure, PVT was found in all the seven cases with significant adhesion to the vascular wall and could not be dissected. The portal vein proximal to the superior mesenteric vein was damaged in one case when attempting thrombolectomy, resulting in massive bleeding. LT was successfully performed in all patients with a mean duration of 585 min (range 491-756 min) and mean intraoperative blood loss of 800 mL (range 500-3000 mL). Postoperative complications consisted of chylous leakage (n = 3), insufficient portal venous flow to the graft (n = 1), intra-abdominal hemorrhage (n = 1), pulmonary infection (n = 1), and perioperative death (n = 1). The remaining six patients survived at 12-17 mo follow-up. CONCLUSION: The RPVPPT technique might be a safe and effective surgical procedure during LT for complex PVT. However, follow-up studies with large samples are still warranted due to the relatively small number of cases.

9.
J Chin Med Assoc ; 85(3): 276-278, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35259130

RESUMO

X-linked juvenile retinoschisis (XLRS) is one of the common early-onset hereditary retinal degenerative diseases in men. The common symptoms of XLRS range from mild to severe central vision loss and radial stripes created by the fovea, the division of the inner layer of the retina in the peripheral retina and the significant decrease in b-wave amplitude (ERG). Retinoschisin, the 224-amino-acid protein product of the retinoschisis 1 (RS1) gene, contains a discoid domain as the primary structural unit, an N-terminal cleavable signal sequence, and an oligomerization-area component. Retinoschisin is a homo-octamer complex with disulfide links that are released by retinal cells. It helps preserve the retina's integrity by binding to the surface of photoreceptors and bipolar cells. As a recessive genetic disease, XLRS was usually treated by prescribing low vision aids in most clinical cases. A gene replacement therapy based on adeno-associated virus vectors was initiated and showed a breakthrough in treating XLRS in 2014. Understanding the revolution of gene therapy for treating XLRS may accelerate its development and make this gene therapy the template for developing therapeutics against other inherited retinal diseases.


Assuntos
Retinosquise , Eletrorretinografia , Proteínas do Olho/genética , Terapia Genética , Humanos , Masculino , Retina , Retinosquise/genética , Retinosquise/metabolismo , Retinosquise/terapia
10.
Eye (Lond) ; 36(8): 1597-1603, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34290439

RESUMO

OBJECTIVES: To determine whether pars plana vitrectomy (PPV) or cataract surgery should be performed first in concurrent epiretinal membrane (ERM) and cataract treatment with respect to visual outcome and pseudophakic cystoid macular oedema (PCMO) incidence. METHODS: Patients who underwent PPV and cataract surgery sequentially at a tertiary medical centre were retrospectively recruited. Best-corrected visual acuity (BCVA) and central macular thickness (CMT) measured from optical coherence tomography (OCT) images collected before and after each surgery were documented. OCT-defined PCMO incidence and its influence on visual outcomes were analysed. RESULTS: In total, 259 and 159 eyes received PPV (ERM-CATA) before and after cataract surgery (CATA-ERM), respectively. The ERM-CATA group had better final BCVA (logMAR: 0.274 vs. 0.558, p < 0.001) and greater BCVA gain (logMAR VA change: -0.379 vs. -0.220, p = 0.001) than did the CATA-ERM group. Baseline BCVA was positively correlated with final BCVA (p < 0.001), whereas baseline CMT, final CMT, and postoperative CMT changes were not. PCMO incidence did not differ significantly between the two groups (15.4% vs. 19.5%, p = 0.287), and final BCVA changes did not significantly differ between eyes with and without PCMO. PCMO incidence was much higher (29.40% vs. 16.30%, p = 0.008) in eyes with baseline CMT ≥ 500 µm. CONCLUSIONS: When managing ERM and cataract, PPV should be performed before cataract surgery to yield better visual outcomes. Both surgical sequences yield similar PCMO rates. Greater baseline CMT is a risk factor for PCMO after cataract surgery.


Assuntos
Catarata , Membrana Epirretiniana , Edema Macular , Catarata/complicações , Membrana Epirretiniana/complicações , Membrana Epirretiniana/epidemiologia , Membrana Epirretiniana/cirurgia , Humanos , Incidência , Edema Macular/epidemiologia , Edema Macular/etiologia , Edema Macular/cirurgia , Estudos Retrospectivos , Tomografia de Coerência Óptica , Acuidade Visual , Vitrectomia/métodos
11.
Acta Diabetol ; 59(4): 501-508, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34786634

RESUMO

AIMS: To report the effect of simultaneous intravitreal dexamethasone (DEX) and aflibercept for the treatment of diabetic macular edema (DME). METHODS: This retrospective analysis of an open-label, multicenter, consecutive case series included 102 eyes of 81 patients with DME. Patients were selected into two groups. The control group consisted of 50 eyes treated with aflibercept alone, and the combination group consisted of 52 eyes treated with simultaneous DEX implant and aflibercept injection. The primary endpoints were changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to month 6. The secondary endpoint was the interval of retreatment. RESULTS: Baseline BCVA increased and CRT decreased at 6 months in both groups. Pseudophakic eyes in the combination group exhibited significantly greater BCVA improvement compared with phakic eyes (p = 0.031). Fewer intravitreal treatments were required for eyes treated with combination therapy than for those treated with aflibercept alone (1.56 ± 0.54 vs. 4.04 ± 1.26, p < .0001), with a mean retreatment interval of 3.66 ± 0.69 months. CONCLUSIONS: Simultaneous intravitreal DEX and aflibercept achieved non-inferior improvement of visual and anatomic outcomes compared with aflibercept alone for DME, but exhibited a significantly longer treatment interval and superior visual outcome in pseudophakic eyes. This therapeutic approach is considered a valid strategy for treating DME in the era of COVID-19.


Assuntos
Tratamento Farmacológico da COVID-19 , Retinopatia Diabética , Edema Macular , Inibidores da Angiogênese , Dexametasona , Retinopatia Diabética/complicações , Retinopatia Diabética/tratamento farmacológico , Implantes de Medicamento , Glucocorticoides , Humanos , Injeções Intravítreas , Edema Macular/complicações , Edema Macular/etiologia , Receptores de Fatores de Crescimento do Endotélio Vascular , Proteínas Recombinantes de Fusão , Estudos Retrospectivos , SARS-CoV-2 , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade Visual
12.
Retina ; 42(4): 712-720, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34908258

RESUMO

PURPOSE: To evaluate the visual outcomes after idiopathic epiretinal membrane surgery in glaucomatous and nonglaucomatous eyes and factors related to unfavorable outcomes in glaucomatous eyes. METHODS: This was a retrospective cohort study including patients undergoing idiopathic epiretinal membrane surgery with ≥12-month follow-up. Final visual acuity at pseudophakic status was compared among groups of glaucoma, glaucoma suspect, and nonglaucoma and correlated with optical coherence tomography and visual field characteristics in patients with glaucoma. RESULTS: Of the 314 patients enrolled, 31 had glaucoma and 22 were glaucoma suspect. Baseline visual acuity and central foveal thickness were similar across the groups. Most patients had improved/stable visual acuity postoperatively, with a lower proportion of 83.9% with glaucoma than 96.9% and 100% without glaucoma and glaucoma suspect, respectively (P = 0.002). The mean visual acuity did not change in the glaucoma group (from 6/29 to 6/23), but it improved from 6/25 to 6/12 (a gain of 16.7 approxETDRS letters) in nonglaucoma and 6/26 to 6/14 in glaucoma suspect (a gain of 14.0 approxETDRS letters) (both P < 0.001). The change of visual acuity was correlated with preoperative visual field defects (P < 0.001, r2 = 0.554). Patients with glaucoma with more advanced, fixation-threatening defects or temporally located inner nuclear layer microcysts were more likely to have worsened visual acuity. CONCLUSION: Visual field testing is imperative for patients with glaucoma before idiopathic epiretinal membrane surgery for outcome assessment.


Assuntos
Membrana Epirretiniana , Glaucoma , Membrana Epirretiniana/complicações , Membrana Epirretiniana/cirurgia , Glaucoma/complicações , Glaucoma/cirurgia , Humanos , Estudos Retrospectivos , Tomografia de Coerência Óptica , Acuidade Visual , Vitrectomia/métodos
13.
Breast ; 61: 35-42, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34894465

RESUMO

Targeted therapies against human epidermal growth factor receptor 2 (HER2) are associated with increased interstitial lung disease (ILD). Trastuzumab, lapatinib, pertuzumab, and trastuzumab emtansine have markedly extended HER2 breast cancer survival but current knowledge on how these HER2-targeted agents induce interstitial lung disease is still poorly defined due to limited cases in the literature. Physicians mostly managed this complication by dose interruption, dose de-escalation, or discontinuation with success. In 2019, the FDA had granted accelerated approval on trastuzumab deruxtecan (T-Dxd) in HER2 breast cancer in the late line setting. Severe ILD incidence rate was over ten percent and led to fatal outcomes in 2.2% of patients in the T-Dxd trial. Searching for biomarkers to detect ILD incidence before it becomes clinically fulminant or for treatment response monitoring is of high clinical value. A Case of life-threatening trastuzumab-induced ILD was encountered in our facility. The ILD was confirmed to be antineutrophil cytoplasmic antibody (ANCA) pulmonary capillaritis. The biomarker of neutrophil extracellular traps (NETs), serum MPO-DNA complex, showed a good correlation with the clinical severity. Soon after B cell depleting agent rituximab usage, the serum MPO-DNA outperformed ANCA autoantibody and maintained its correlation with clinical severity. In addition to the trastuzumab-induced ILD case, a prospective cohort in our facility also confirmed the usefulness of MPO-DNA in monitoring vasculitis activity. We postulated that upfront testing with biomarkers of vasculitis during HER2 targeted treatment with high ILD incidence may be beneficial in the future.


Assuntos
Neoplasias da Mama , Doenças Pulmonares Intersticiais , Vasculite , Anticorpos Anticitoplasma de Neutrófilos , Neoplasias da Mama/tratamento farmacológico , Feminino , Seguimentos , Humanos , Doenças Pulmonares Intersticiais/induzido quimicamente , Neutrófilos , Estudos Prospectivos , Receptor ErbB-2 , Trastuzumab/efeitos adversos
14.
Int J Mol Sci ; 22(11)2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34070492

RESUMO

Inherited retinal dystrophies (IRDs) are rare but highly heterogeneous genetic disorders that affect individuals and families worldwide. However, given its wide variability, its analysis of the driver genes for over 50% of the cases remains unexplored. The present study aims to identify novel driver genes, disease-causing variants, and retinitis pigmentosa (RP)-associated pathways. Using family-based whole-exome sequencing (WES) to identify putative RP-causing rare variants, we identified a total of five potentially pathogenic variants located in genes OR56A5, OR52L1, CTSD, PRF1, KBTBD13, and ATP2B4. Of the variants present in all affected individuals, genes OR56A5, OR52L1, CTSD, KBTBD13, and ATP2B4 present as missense mutations, while PRF1 and CTSD present as frameshift variants. Sanger sequencing confirmed the presence of the novel pathogenic variant PRF1 (c.124_128del) that has not been reported previously. More causal-effect or evidence-based studies will be required to elucidate the precise roles of these SNPs in the RP pathogenesis. Taken together, our findings may allow us to explore the risk variants based on the sequencing data and upgrade the existing variant annotation database in Taiwan. It may help detect specific eye diseases such as retinitis pigmentosa in East Asia.


Assuntos
Catepsina D/genética , Predisposição Genética para Doença , Distrofias Retinianas/genética , Adulto , Idoso , Catepsina D/sangue , Feminino , Mutação da Fase de Leitura , Ontologia Genética , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Musculares/genética , Mutação de Sentido Incorreto , Linhagem , Perforina/genética , ATPases Transportadoras de Cálcio da Membrana Plasmática/genética , Polimorfismo de Nucleotídeo Único , Mapas de Interação de Proteínas , Distrofias Retinianas/congênito , Distrofias Retinianas/patologia , Retinose Pigmentar/congênito , Retinose Pigmentar/diagnóstico por imagem , Retinose Pigmentar/genética , Retinose Pigmentar/patologia , Fatores de Risco , Tomografia de Coerência Óptica , Sequenciamento do Exoma
15.
Sci Rep ; 11(1): 7130, 2021 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-33785808

RESUMO

Polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (nAMD) share some similarity in clinical imaging manifestations. However, their disease entity and treatment strategy as well as visual outcomes are very different. To distinguish these two vision-threatening diseases is somewhat challenging but necessary. In this study, we propose a new artificial intelligence model using an ensemble stacking technique, which combines a color fundus photograph-based deep learning (DL) model and optical coherence tomography-based biomarkers, for differentiation of PCV from nAMD. Furthermore, we introduced multiple correspondence analysis, a method of transforming categorical data into principal components, to handle the dichotomous data for combining with another image DL system. This model achieved a robust performance with an accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve of 83.67%, 80.76%, 84.72%, and 88.57%, respectively, by training nearly 700 active cases with suitable imaging quality and transfer learning architecture. This work could offer an alternative method of developing a multimodal DL model, improve its efficiency for distinguishing different diseases, and facilitate the broad application of medical engineering in a DL model design.


Assuntos
Doenças da Coroide/diagnóstico por imagem , Aprendizado Profundo , Degeneração Macular/diagnóstico por imagem , Diagnóstico Diferencial , Estudos de Viabilidade , Humanos , Estudos Retrospectivos , Tomografia de Coerência Óptica
16.
Sci Rep ; 11(1): 2735, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33531615

RESUMO

Polypoidal choroidal vasculopathy (PCV) is a vision-threatening disease common in Asian populations. However, the optimal treatment for PCV remains under debate. We searched the databases with optimal searching strategy. The study included randomized clinical trials and prospective studies that recruited patients with active PCV who had received interventions, including PDT, anti-VEGF, or a combination of PDT and anti-VEGF. The Grading of Recommendations Assessment, Development, and Evaluation methodology was used for rating the quality of evidence. Our study included 11 studies involving 1277 patients. The network meta-analysis of RCTs revealed the anti-VEGF group, early combination group, and late combination group had significant BCVA changes compared with the PDT group. Early combination therapy led to a significant decrease in CRT compared with PDT, anti-VEGF, and late combination therapy. Additionally, the early combination group had a significantly higher complete polyp regression rate than the anti-VEGF group. No significant differences were detected in the analysis of the number of anti-VEGF injections and safety profile. This network meta-analysis revealed that early combination therapy exhibited better efficacy related to anatomical outcomes than other therapies. Nonetheless, no significant differences related to BCVA change could be detected between anti-VEGF and late combination therapy.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Neovascularização de Coroide/tratamento farmacológico , Fotoquimioterapia/métodos , Pólipos/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Inibidores da Angiogênese/efeitos adversos , Corioide/irrigação sanguínea , Corioide/efeitos dos fármacos , Corioide/patologia , Neovascularização de Coroide/patologia , Humanos , Injeções Intravítreas , Metanálise em Rede , Fotoquimioterapia/efeitos adversos , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/efeitos adversos , Pólipos/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
17.
PLoS One ; 15(10): e0241230, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33095843

RESUMO

Optical coherence tomography angiography (OCTA) is a novel, non-invasive imaging tool used to detect vascular flow. The absence of a flow signal in OCTA in polyps revealed by indocyanine green angiography (ICGA) in patients with polypoidal choroidal vasculopathy (PCV) may indicate slow or compromised filling of blood flow from choroidal vessels. Naïve patients with PCV treated with intravitreal injections of aflibercept (IVI-A) were enrolled in this study to validate the hypothesis that baseline flow may affect the outcome of polyp regression in ICGA. The flow signal of polyps in OCTA was detected by manual segmentation in the corresponding location by ICGA. Polyps were defined as high-flow if both OCTA and ICGA showed positive findings, and low-flow if OCTA showed a negative flow signal in 3 consecutive horizontal scans at the polyp area shown in ICGA. A total of 24 polyps were identified in 13 PCV patients at baseline. Of these 24 polyps, 22 (91.7%) were high-flow and 2 (8.3%) were low-flow. After 3 monthly IVI-A, all low-flow polyps had complete regression in ICGA. Among 17 (77%) high-flow polyps at baseline that had regression after treatment, 10 (58.8%) became low-flow, while 5 (22.7%) persistent polyps remained high-flow. Flow signal of polyps as detected by OCTA could be a predictive factor for treatment response in patients with PCV. Monitoring changes in flow signal after treatment is clinically relevant.


Assuntos
Pólipos/tratamento farmacológico , Fluxo Sanguíneo Regional , Processamento de Sinais Assistido por Computador , Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Idoso , Idoso de 80 Anos ou mais , Neovascularização de Coroide/diagnóstico por imagem , Neovascularização de Coroide/tratamento farmacológico , Feminino , Angiofluoresceinografia , Humanos , Verde de Indocianina , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Pólipos/diagnóstico por imagem , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/farmacologia , Proteínas Recombinantes de Fusão/uso terapêutico , Fluxo Sanguíneo Regional/efeitos dos fármacos , Tomografia de Coerência Óptica , Resultado do Tratamento , Fatores de Crescimento do Endotélio Vascular/metabolismo
18.
Food Sci Technol Int ; 26(8): 715-726, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32423241

RESUMO

The atmospheric-pressure non-thermal dielectric barrier discharge (DBD) plasma has recently emerged as an efficient decontamination method for the food safety enhancement. Thus the objective of this study was to evaluate the effectiveness of a simple DBD plasma treatment, with a relatively low-frequency power supply operating at 60 Hz, for microbial inactivation. A parametric study of operating conditions for bacterial inactivation was conducted using nutrient agar inoculated with Escherichia coli (2.28--6.28 log CFU/ml). The microbial log reduction was enhanced with increasing input power (30, 50, 70 W) and plasma exposure time (0, 1, 3, 5, 7 min). The inactivation effect was increased by decreasing inter-electrode gap (2, 1.5, 1 cm) and by reducing the initial microorganism concentration. Accordingly, a DBD plasma treatment at 50 W for 10 min could lead to complete killing of E. coli and partial inactivation of Listeria innocua on cheese (mean log reduction: 4.75 ± 0.02 and 0.72 ± 0.01, respectively). The decontamination efficacy of DBD plasma was affected by the types of microorganisms. The changes in hardness and color of cheese were unnoticeable after 10 min treatment with a power of 50 W. Overall, the results suggested that the DBD plasma can be potentially exploited to improve the food safety.


Assuntos
Queijo , Descontaminação , Microbiologia de Alimentos , Gases em Plasma , Queijo/microbiologia , Queijo/normas , Contagem de Colônia Microbiana , Descontaminação/métodos , Escherichia coli/efeitos dos fármacos , Contaminação de Alimentos/análise , Contaminação de Alimentos/prevenção & controle , Microbiologia de Alimentos/métodos , Listeria/efeitos dos fármacos , Gases em Plasma/farmacologia
19.
Biomed Res Int ; 2020: 7436274, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32280702

RESUMO

PURPOSE: This study is aimed at investigating the effect of low-intensity electrical stimulation on the voluntary activation level (VA) and the cortical facilitation/inhibition of quadriceps in people with chronic anterior cruciate ligament lesion. METHODS: Twenty former athletes with unilateral ACL deficiencies (ACL group) and 20 healthy subjects (healthy control group) participated in the study. The quadriceps VA level, motor-evoked potential (MEP), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) elicited by transcranial magnetic stimulation were tested before and after 30 minutes of low-intensity electrical stimulation (ES). RESULTS: Before ES, the quadriceps VA in the ACL lesion legs of the ACL group was lower compared to the legs of the healthy control group (P < 0.05). The MEP sizes in the ACL lesion legs and the healthy control were not significantly different. The ACL lesion legs showed lower SICI and higher ICF compared to the healthy control group (P < 0.05). After ES, the quadriceps VA level increased and the SICI-ICF was modulated only in the ACL lesion legs (P < 0.05) but not in the healthy controls. CONCLUSIONS: Low-intensity ES can normalize the modulation of intracortical inhibition and facilitation, thereby ameliorating the activation failure in individuals with ACL lesion.


Assuntos
Lesões do Ligamento Cruzado Anterior/radioterapia , Ligamento Cruzado Anterior/fisiologia , Estimulação Elétrica/métodos , Adulto , Potencial Evocado Motor/fisiologia , Feminino , Humanos , Masculino , Córtex Motor/fisiologia , Córtex Motor/efeitos da radiação , Músculo Quadríceps/efeitos da radiação , Estimulação Magnética Transcraniana/métodos , Adulto Jovem
20.
Sci Rep ; 9(1): 11570, 2019 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399631

RESUMO

Inner nuclear layer(INL) microcysts at central macula are a common finding in patients with epiretinal membrane (ERM) after vitrectomy and membrane peeling. Using en face mode of optical coherence tomography (OCT) angiography, patients with ERM after surgery were retrospectively reviewed to understand the configuration and distribution of microcysts as well as their impact on visual acuity. Forty-six eligible patients were enrolled and their baseline best-corrected visual acuities improved from 20/67 to 20/29 (P < 0.01) after surgery. Twenty-eight (60.9%) patients had microcysts that appeared at a median of 5 months after the surgery and persisted for mean 16 months follow-up. The microcyst appeared as spheroidal shape with length ranged from 20 to 80 µm and widths of 80 µm in average. They tend to group in cluster with a density of 245 microcysts per mm2. The frequency of microcyst distribution was 86%, 54%, 32%, 25% and 18% at the nasal, superior, inferior, temporal quadrants and central 1 mm, respectively. Linear regression analysis showed that INL microcysts at central and temporal quadrants were associated with poorer visual acuity (P = 0.02 and P = 0.01, respectively). The presence of INL microcysts in center subfield and involved wider area is a poor prognostic factor for visual outcomes.


Assuntos
Membrana Epirretiniana/cirurgia , Macula Lutea/cirurgia , Vitrectomia , Idoso , Membrana Epirretiniana/diagnóstico , Membrana Epirretiniana/patologia , Feminino , Humanos , Macula Lutea/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade Visual , Vitrectomia/métodos
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