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1.
ACS Nano ; 2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38764224

RESUMO

Traditional monoclonal antibodies such as Trastuzumab encounter limitations when treating Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer, particularly in cases that develop resistance. This study introduces plant-derived anti-HER2 variable fragments of camelid heavy chain domain (VHH) fragment crystallizable region (Fc) KEDL(K) antibody as a potent alternative for overcoming these limitations. A variety of biophysical techniques, in vitro assays, and in vivo experiments uncover the antibody's nanoscale binding dynamics with transmembrane HER2 on living cells. Single-molecule force spectroscopy reveals the rapid formation of two robust bonds, exhibiting approximately 50 pN force resistance and bond lifetimes in the second range. The antibody demonstrates a specific affinity for HER2-positive breast cancer cells, including those that are Trastuzumab-resistant. Moreover, in immune-deficient mice, the plant-derived anti-HER2 VHH-FcK antibody exhibits superior antitumor activity, especially against tumors that are resistant to Trastuzumab. These findings underscore the plant-derived antibody's potential as an impactful immunotherapeutic strategy for treating Trastuzumab-resistant HER2-positive breast cancer.

2.
Cell Death Dis ; 15(4): 287, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654003

RESUMO

This study aimed to elucidate the role of O-GlcNAc cycling in 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD)-like neurodegeneration and the underlying mechanisms. We observed dose-dependent downregulation of O-GlcNAcylation, accompanied by an increase in O-GlcNAcase following 6-OHDA treatment in both mouse brain and Neuro2a cells. Interestingly, elevating O-GlcNAcylation through glucosamine (GlcN) injection provided protection against PD pathogenesis induced by 6-OHDA. At the behavioral level, GlcN mitigated motor deficits induced by 6-OHDA, as determined using the pole, cylinder, and apomorphine rotation tests. Furthermore, GlcN attenuated 6-OHDA-induced neuroinflammation and mitochondrial dysfunction. Notably, augmented O-GlcNAcylation, achieved through O-GlcNAc transferase (OGT) overexpression in mouse brain, conferred protection against 6-OHDA-induced PD pathology, encompassing neuronal cell death, motor deficits, neuroinflammation, and mitochondrial dysfunction. These collective findings suggest that O-GlcNAcylation plays a crucial role in the normal functioning of dopamine neurons. Moreover, enhancing O-GlcNAcylation through genetic and pharmacological means could effectively ameliorate neurodegeneration and motor impairment in an animal model of PD. These results propose a potential strategy for safeguarding against the deterioration of dopamine neurons implicated in PD pathogenesis.


Assuntos
Camundongos Endogâmicos C57BL , N-Acetilglucosaminiltransferases , Oxidopamina , Doença de Parkinson , Animais , Oxidopamina/farmacologia , Camundongos , N-Acetilglucosaminiltransferases/metabolismo , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Masculino , Glucosamina/farmacologia , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/patologia , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Acetilglucosamina/metabolismo , Acetilglucosamina/farmacologia , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/efeitos dos fármacos , beta-N-Acetil-Hexosaminidases/metabolismo , Modelos Animais de Doenças
3.
J Pers Med ; 14(4)2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38672971

RESUMO

BACKGROUND: This study aimed to evaluate the association between initial fibrinogen levels and massive transfusion (MT) in emergency department (ED) patients with primary postpartum hemorrhage (PPH). METHODS: This retrospective study was conducted in the ED of a university-affiliated, tertiary referral center from January 2004 to August 2023. Patients were divided into two groups: the MT group, which included those who received a transfusion of 10 or more units of packed red blood cells within the first 24 h, and the Non-MT group. RESULTS: Out of the 364 patients included in the study, 97 (26.6%) required MT. Fibrinogen, shock index, and lactate were independently associated with MT (odds ratio [OR] 0.987; 95% confidence interval [CI] 0.983-0.991; p < 0.001, OR 7.277; 95% CI 1.856-28.535; p = 0.004, and OR 1.261; 95% CI 1.021-1.557; p = 0.031, respectively). The area under the receiver operating characteristic curve for fibrinogen, shock index, and lactate in predicting MT was 0.871 (95% CI 0.832-0.904; p < 0.001), 0.821 (95% CI 0.778-0.859; p < 0.001), and 0.784 (95% CI 0.738-0.825; p < 0.001), respectively. When the cutoff value of fibrinogen was 400 mg/dL, both the sensitivity and negative predictive values for predicting MT were 100.0%. When the cutoff value of fibrinogen was 100 mg/dL, the specificity and positive predictive values were 91.8% and 70.7%, respectively. CONCLUSION: The initial fibrinogen levels were independently associated with the need for MT in ED patients with primary PPH.

4.
Coron Artery Dis ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38682470

RESUMO

BACKGROUND: The average glycated hemoglobin (HbA1c) may not accurately reflect glycemic control status during the mid-term after acute myocardial infarction (AMI). We aimed to evaluate changes in HbA1c and their effect on mid-term clinical outcomes in patients with diabetes and AMI. METHODS: We enrolled patients with diabetes (n = 967) who underwent HbA1c measurement in the Korean nationwide registry. These patients were categorized into three groups based on changes in HbA1c from index admission to the 1-year follow-up visit: a decrease in HbA1c > 1%, changes in HbA1c within 1%, and an increase in HbA1c > 1%. Clinical outcomes at 24 months were examined. RESULTS: The baseline HbA1c levels were 8.55 ±â€…0.85, 7.00 ±â€…0.98 and 7.07 ±â€…1.05 (P = 0.001) and HbA1c levels after 1 year were 6.62 ±â€…0.73, 7.05 ±â€…0.98 and 9.26 ±â€…1.59 (P = 0.001) for patients with 3 groups, respectively. Patients with a 1% decrease in HbA1c had significantly lower incidence of major adverse cardiovascular events (MACE), cardiac death, and rehospitalization after 24 months than those with a 1% increase in HbA1c. However, in the Cox regression analysis, a >1% decrease in HbA1c change was not an independent factor for MACE, cardiac death, and rehospitalization. CONCLUSIONS: Our analysis indicates that an HbA1c decrease of >1% within the first 12 months was not an independent prognostic factor until the 24-month mark. Therefore, standard diabetic control is recommended for patients with diabetes and AMI for up to 2 years.

5.
Med Sci Monit ; 30: e943286, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38437191

RESUMO

BACKGROUND The modified shock index (MSI) is calculated as the ratio of heart rate (HR) to mean arterial pressure (MAP) and has been used to predict the need for massive transfusion (MT) in trauma patients. This retrospective study from a single center aimed to compare the MSI with the traditional shock index (SI) to predict the need for MT in 612 women diagnosed with primary postpartum hemorrhage (PPH) at the Emergency Department (ED) between January 2004 and August 2023. MATERIAL AND METHODS The patients were divided into the MT group and the non-MT group. The predictive power of MSI and SI was compared using the areas under the receiver operating characteristic curve (AUC). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated. RESULTS Out of 612 patients, 105 (17.2%) required MT. The MT group had higher median values than the non-MT group for MSI (1.58 vs 1.07, P<0.001) and SI (1.22 vs 0.80, P<0.001). The AUC for MSI, with a value of 0.811 (95% confidence interval [CI], 0.778-0.841), did not demonstrate a significant difference compared to the AUC for SI, which was 0.829 (95% CI, 0.797-0.858) (P=0.066). The optimal cutoff values for MSI and SI were 1.34 and 1.07, respectively. The specificity and PPV for MT were 77.1% and 40.2% for MSI, and 83.2% and 45.9% for SI. CONCLUSIONS Both MSI and SI were effective in predicting MT in patients with primary PPH. However, MSI did not demonstrate superior performance to SI.


Assuntos
Hemorragia Pós-Parto , Gravidez , Humanos , Feminino , Estudos Retrospectivos , Hemorragia Pós-Parto/terapia , Transfusão de Sangue , Serviço Hospitalar de Emergência , Frequência Cardíaca
6.
Elife ; 122024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38536720

RESUMO

Chemoresistance is a major cause of treatment failure in many cancers. However, the life cycle of cancer cells as they respond to and survive environmental and therapeutic stress is understudied. In this study, we utilized a microfluidic device to induce the development of doxorubicin-resistant (DOXR) cells from triple negative breast cancer (TNBC) cells within 11 days by generating gradients of DOX and medium. In vivo chemoresistant xenograft models, an unbiased genome-wide transcriptome analysis, and a patient data/tissue analysis all showed that chemoresistance arose from failed epigenetic control of the nuclear protein-1 (NUPR1)/histone deacetylase 11 (HDAC11) axis, and high NUPR1 expression correlated with poor clinical outcomes. These results suggest that the chip can rapidly induce resistant cells that increase tumor heterogeneity and chemoresistance, highlighting the need for further studies on the epigenetic control of the NUPR1/HDAC11 axis in TNBC.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/genética , Resistencia a Medicamentos Antineoplásicos , Doxorrubicina/farmacologia , Proteínas Nucleares/metabolismo , Dispositivos Lab-On-A-Chip , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica
7.
Eur J Cardiothorac Surg ; 65(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38407382

RESUMO

OBJECTIVES: The timing of preoperative imaging in patients with lung cancer is a debated topic, as there are limited data on cancer progression during the interval between clinical staging by imaging and pathological staging after resection. We quantified disease progression during this interval in patients with early stage non-small-cell lung cancer (NSCLC) to better understand if its length impacts upstaging. METHODS: We retrospectively reviewed our institutional database to identify patients who underwent surgery for clinically staged T1N0M0 NSCLC from January 2015 through September 2022. Tumour upstaging between chest computed tomography (CT) and surgery were analysed as a function of time (<30, 30-59, ≥60 days) for different nodule subtypes. We analysed data across 3 timeframes using Pearson's chi-squared and analysis of variance tests. RESULTS: During the study period, 622 patients underwent surgery for clinically staged T1N0M0 NSCLC. CT-to-surgery interval was <30 days in 228 (36.7%), 30-59 days in 242 (38.9%) and ≥60 days in 152 (24.4%) with no differences in patient or nodule characteristics observed between these groups. T-stage increased in 346 patients (55.6%) between CT imaging and surgery. Among these patients, 126 (36.4%) had ground-glass nodules, 147 (42.5%) had part-solid nodules and 73 (21.1%) had solid nodules. CT-to-surgery interval length was not associated with upstaging of any nodule subtype (full-cohort, P = 0.903; ground-glass, P = 0.880; part-solid, P = 0.858; solid, P = 0.959). CONCLUSIONS: This single-centre experience suggests no significant association between tumour upstaging and time from imaging to lung resection in patients with clinical stage IA NSCLC. Further studies are needed to better understand the risk factors for upstaging.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Fatores de Risco , Estadiamento de Neoplasias
8.
JTCVS Open ; 17: 306-319, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38420534

RESUMO

Objective: The impact of conduit dimensions and location of esophagogastric anastomosis on long-term quality of life after esophagectomy remains unexplored. We investigated the association of these parameters with surgical outcomes and patient-reported quality of life at least 18 months after esophagectomy. Methods: We identified all patients who underwent esophagectomy for cancer from 2018 to 2020 in our institution. We reviewed each patient's initial postoperative computed tomography scan measuring the gastric conduit's greatest width (centimeters), linear staple line length (centimeters), and relative location of esophagogastric anastomosis (vertebra). Quality of life was ascertained using patient-reported outcome measures. Perioperative complications, length of stay, and mortality were collected. Multivariate regressions were performed. Results: Our study revealed that a more proximal anastomosis was linked to an increased risk of pulmonary complications, a lower recurrence rate, and greater long-term insomnia. Increased maximum intrathoracic conduit width was significantly associated with trouble enjoying meals and reflux long term after esophagectomy. A longer conduit stapled line correlated with fewer issues related to insomnia, improved appetite, less dysphagia, and significantly enhanced "social," "role," and "physical'" aspects of the patient's long-term quality of life. Conclusions: The dimensions of the gastric conduit and the height of the anastomosis may be independently associated with outcomes and long-term quality of life after esophagectomy for cancer.

9.
Plant Dis ; 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38173269

RESUMO

Peanut (Arachis hypogaea L.) has long been cultivated worldwide as an important crop for oil and protein production. Among the various diseases in peanut plants, wilt diseases caused by soil-borne pathogens such as Ralstonia solanacearum and Verticillium dahliae are especially destructive and substantially diminish both quantity and quality in peanut production (Kokalis-Burelle et al., 1997; Thiessen et al., 2012). In July 2022, wilt symptoms were observed in 1 to 3% of the area of peanut fields in Yeoju-si, Korea (37°23´04.0˝N; 127°33´43.0˝E). The xylem in the stems of the wilted plants was dark brown at the soil-surface, which is a representative symptom of vascular wilt pathogens (Yadeta et al. 2013). To isolate the causative pathogens, the stems exhibiting dark lesions were disinfected with 1% NaOCl for 1 min, rinsed with sterile distilled water, and placed on potato dextrose agar medium. The plates were incubated at 25℃ for 2 days, and white hyphae that grew out from the tissues were subcultured twice on V8 juice agar (V8A) medium. Among the 3 isolates, morphological characteristics of the representative strain YJ1-2 were observed under a microscope. The sporangia were terminal intercalary, filamentous, inflated lobulate, and ranging from 37.4 to 73.6 µm in diameter. The antheridia were diclinous, with clavate, elongate, and crook-necked shapes. The oogonia were mostly globose, with an average of 27.1 µm (range from 20.2 to 35.2 µm, n = 50) in diameter, and mated with one to several antheridia. Both plerotic or aplerotic oospores were observed. Overall, the morphological characteristics of the sporangia, antheridia, oogonia, and oospores indicated that YJ1-2 belongs to the genus Pythium. To genetically characterize YJ1-2, genomic DNA was extracted using cetyltrimethylammonium bromide buffer, and the internal transcribed spacer (ITS) region and cytochrome c oxidase subunit I (cox1) gene were amplified by PCR using primer sets ITS4/ITS5 and OomCoxI-Levlo/ OomCoxI-Levup, respectively (White et al., 1990; Robideau et al. 2011), sequenced, and identified using BLASTN (NCBI, National Center for Biotechnology Information). The ITS sequence (NCBI Acc. No. OR125595) of YJ1-2 has 99% similarity with that of P. myriotylum isolate PY39 (NCBI Acc. No. KX671096). A neighbor-joining phylogenetic tree was constructed from aligned cox1 sequence (NCBI Acc. No. OR224334) of the 10 Pythium species strains including YJ1-2 by CLUSTALW method was used as an outgroup. The YJ1-2 was most closely related to P. myriotylum isolate PM30 (NCBI Acc. No. MT823167). To substantiate the pathogenicity of YJ1-2, the crown roots of peanut plants grown in pots for 4 weeks were wounded using a sterile tweezer, and the mycelial plugs of YJ1-2 cultured for 5 days on V8A were inoculated on the wounds. The inoculated plants were cultivated in a growth chamber at 30℃ and 70% relative humidity with a 12-h photoperiod. The infected peanut plants exhibited wilt symptoms 11 days after inoculation, consistent with the initial observation, while uninoculated plants remained healthy. To satisfy Koch's postulates, white mycelia were re-isolated from the stems of inoculated plants and axenically cultured in V8A. The morphologies and ITS sequences of the re-isolates were consistent with those of YJ1-2. P. myriotylum has been reported as a causal pathogen of peanut pod rot in the United States and China. However, to the best of our knowledge, this is the first report of wilt disease in peanut plants caused by P. myriotylum in Korea. To prevent the incidence of wilt disease, we will continue our investigations to develop control strategies, including the selection of appropriate agrochemicals.

10.
Osteoporos Int ; 35(5): 775-783, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38240755

RESUMO

With the analysis of nationwide health claim data, treatment with the composite agent of SERMs and vitamin D reduces the risk of osteoporotic fracture and hip fracture better compared to SERMs treatment in women with osteoporosis aged ≥ 50 years. PURPOSE: This study compared the potential of the composite agent of selective estrogen receptor modulators (SERMs) and vitamin D (SERM + VitD) with that of SERMs-only for fracture prevention and mortality reduction in women aged ≥ 50 years. METHODS: The incidence of osteoporotic fracture (fractures of the vertebrae, hip, wrist, or humerus) and all-cause death after treatment with SERM + VitD and SERMs were characterized using the Korean National Health Insurance Service database 2017-2019. The participants were divided into two groups (SERM + VitD vs SERMs). After exclusion and propensity score matching, 2,885 patients from each group were included in the analysis. Fracture incidence was compared between groups. Kaplan-Meier curves were used to compare mortality. Cox proportional hazards regression analysis was used to compare the risks of fracture occurrence and mortality between the groups. RESULTS: The incidence rate (138.6/10,000 vs. 192.4/10,000 person-years), and risk of osteoporotic fractures (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61-0.97; p = 0.024) were lower in the SERM + VitD group than in the SERMs group. Analysis for specific fractures showed a lower hazard of hip fracture in the SERM + VitD group (HR, 0.25; 95% CI, 0.09-0.71; p = 0.009). No difference was observed between the groups regarding mortality. CONCLUSION: The risk of osteoporotic fractures, especially hip fractures, was lower in the SERM + VitD group than in the SERMs group. Therefore, the composite agent of SERMs and vitamin D can be considered as a viable option for postmenopausal women with a relatively low fracture risk.


Assuntos
Fraturas do Quadril , Osteoporose Pós-Menopausa , Osteoporose , Fraturas por Osteoporose , Humanos , Feminino , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/prevenção & controle , Vitamina D/uso terapêutico , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/epidemiologia , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/prevenção & controle , Vitaminas
11.
BMB Rep ; 57(2): 92-97, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37964636

RESUMO

Elevated blood glucose is associated with an increased risk of atherosclerosis. Data from the current study showed that glucosamine (GlcN), a normal glucose metabolite of the hexosamine biosynthetic pathway (HBP), promoted lipid accumulation in RAW264.7 macrophage cells. Oleic acid- and lipopolysaccharide (LPS)-induced lipid accumulation was further enhanced by GlcN in RAW264.7 cells, although there was no a significant change in the rate of fatty acid uptake. GlcN increased acetyl CoA carboxylase (ACC), fatty acid synthase (FAS), scavenger receptor class A, liver X receptor, and sterol regulatory elementbinding protein-1c (SREBP-1c) mRNA expression, and; conversely, suppressed ATP-binding cassette transporter A1 (ABCA-1) and ABCG-1 expression. Additionally, GlcN promoted O-GlcNAcylation of nuclear SREBP-1 but did not affect its DNA binding activity. GlcN stimulated phosphorylation of mammalian target of rapamycin (mTOR) and S6 kinase. Rapamycin, a mTOR-specific inhibitor, suppressed GlcN-induced lipid accumulation in RAW264.7 cells. The GlcN-mediated increase in ACC and FAS mRNA was suppressed, while the decrease in ABCA-1 and ABCG-1 by GlcN was not significantly altered by rapamycin. Together, our results highlight the importance of the mTOR signaling pathway in GlcN-induced macrophage lipid accumulation and further support a potential link between mTOR and HBP signaling in lipogenesis. [BMB Reports 2024; 57(2): 92-97].


Assuntos
Glucosamina , Transdução de Sinais , Animais , Camundongos , Glucosamina/farmacologia , Lipopolissacarídeos , Macrófagos , Células RAW 264.7 , RNA Mensageiro , Sirolimo , Serina-Treonina Quinases TOR , Fatores de Transcrição
12.
Am J Emerg Med ; 75: 53-58, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37913715

RESUMO

BACKGROUND: The predictive value of the respiratory rate­oxygenation (ROX) index for a high-flow nasal cannula (HFNC) in patients with COVID-19 with acute hypoxemic respiratory failure (AHRF) may differ from patients without COVID-19 with AHRF, but these patients have not yet been compared. We compared the diagnostic accuracy of the ROX index for HFNC failure in patients with AHRF with and without COVID-19 during acute emergency department (ED) visits. METHODS: We performed a retrospective analysis of patients with AHRF treated with an HFNC in an ED between October 2020 and April 2022. The ROX index was calculated at 1, 2, 4, 6, 12, and 24 h after HFNC placement. The primary outcome was the failure of the HFNC, which was defined as the need for subsequent intubation or death within 72 h. A receiver operating characteristic (ROC) curve was used to evaluate discriminative power of the ROX index for HFNC failure. RESULTS: Among 448 patients with AHRF treated with an HFNC in an ED, 78 (17.4%) patients were confirmed to have COVID-19. There was no significant difference in the HFNC failure rates between the non-COVID-19 and COVID-19 groups (29.5% vs. 33.3%, p = 0.498). The median ROX index was higher in the non-COVID-19 group than in the COVID-19 group at all time points. The prognostic power of the ROX index for HFNC failure as evaluated by the area under the ROC curve was generally higher in the COVID-19 group (0.73-0.83) than the non-COVID-19 group (0.62-0.75). The timing of the highest prognostic value of the ROX index for HFNC failure was at 4 h for the non-COVID-19 group, whereas in the COVID-19 group, its performance remained consistent from 1 h to 6 h. The optimal cutoff values were 6.48 and 5.79 for the non-COVID-19 and COVID-19 groups, respectively. CONCLUSIONS: The ROX index had an acceptable discriminative power for predicting HFNC failure in patients with AHRF with and without COVID-19 in the ED. However, the higher ROX index thresholds than those in previous publications involving intensive care unit (ICU) patients suggest the need for careful monitoring and establishment of a new threshold for patients admitted outside the ICU.


Assuntos
COVID-19 , Ventilação não Invasiva , Insuficiência Respiratória , Humanos , Cânula , COVID-19/terapia , Taxa Respiratória , Estudos Retrospectivos , Insuficiência Respiratória/terapia , Oxigenoterapia
13.
Int J Mol Sci ; 24(21)2023 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-37958960

RESUMO

In present study, icariin (ICA)/tannic acid (TA)-nanodiamonds (NDs) were prepared as follows. ICA was anchored to ND surfaces with absorbed TA (ICA/TA-NDs) and we evaluated their in vitro anti-inflammatory effects on lipopolysaccharide (LPS)-activated macrophages and in vivo cartilage protective effects on a rat model of monosodium iodoacetate (MIA)-induced osteoarthritis (OA). The ICA/TA-NDs showed prolonged release of ICA from the NDs for up to 28 days in a sustained manner. ICA/TA-NDs inhibited the mRNA levels of pro-inflammatory elements, including matrix metalloproteinases-3 (MMP-3), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and increased the mRNA levels of anti-inflammatory factors (i.e., IL-4 and IL-10) in LPS-activated RAW 264.7 macrophages. Animal studies exhibited that intra-articular injection of ICA/TA-NDs notably suppressed levels of IL-6, MMP-3, and TNF-α and induced level of IL-10 in serum of MIA-induced OA rat models in a dose-dependent manner. Furthermore, these noticeable anti-inflammatory effects of ICA/TA-NDs remarkably contributed to the protection of the progression of MIA-induced OA and cartilage degradation, as exhibited by micro-computed tomography (micro-CT), gross findings, and histological investigations. Accordingly, in vitro and in vivo findings suggest that the prolonged ICA delivery of ICA/TA-NDs possesses an excellent latent to improve inflammation as well as defend against cartilage disorder in OA.


Assuntos
Cartilagem Articular , Nanodiamantes , Osteoartrite , Ratos , Animais , Interleucina-10/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 3 da Matriz/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Microtomografia por Raio-X , Cartilagem Articular/metabolismo , Osteoartrite/metabolismo , Anti-Inflamatórios/farmacologia , Ácido Iodoacético/efeitos adversos , RNA Mensageiro/metabolismo , Modelos Animais de Doenças
14.
Viruses ; 15(11)2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-38005817

RESUMO

This study delves into the complex landscape of viral infections in tomatoes (Solanum lycopersicum) using available transcriptome data. We conducted a virome analysis, revealing 219 viral contigs linked to four distinct viruses: tomato chlorosis virus (ToCV), southern tomato virus (STV), tomato yellow leaf curl virus (TYLCV), and cucumber mosaic virus (CMV). Among these, ToCV predominated in contig count, followed by STV, TYLCV, and CMV. A notable finding was the prevalence of coinfections, emphasizing the concurrent presence of multiple viruses in tomato plants. Despite generally low viral levels in fruit transcriptomes, STV emerged as the primary virus based on viral read count. We delved deeper into viral abundance and the contributions of RNA segments to replication. While initially focused on studying the impact of sound treatment on tomato fruit transcriptomes, the unexpected viral presence underscores the importance of considering viruses in plant research. Geographical variations in virome communities hint at potential forensic applications. Phylogenetic analysis provided insights into viral origins and genetic diversity, enhancing our understanding of the Korean tomato virome. In conclusion, this study advances our knowledge of the tomato virome, stressing the need for robust pest control in greenhouse-grown tomatoes and offering insights into virus management and crop protection.


Assuntos
Infecções por Citomegalovirus , Vírus de Plantas , Solanum lycopersicum , Transcriptoma , Frutas , Filogenia , Viroma , Vírus de Plantas/genética , Doenças das Plantas
15.
Plants (Basel) ; 12(18)2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37765420

RESUMO

Plant transcriptomes offer a valuable resource for studying viral communities (viromes). In this study, we explore how plant transcriptome data can be applied to virome research. We analyzed 40 soybean transcriptomes across different growth stages and identified six viruses: broad bean wilt virus 2 (BBWV2), brassica yellow virus (BrYV), beet western yellow virus (BWYV), cucumber mosaic virus (CMV), milk vetch dwarf virus (MDV), and soybean mosaic virus (SMV). SMV was the predominant virus in both Glycine max (GM) and Glycine soja (GS) cultivars. Our analysis confirmed its abundance in both, while BBWV2 and CMV were more prevalent in GS than GM. The viral proportions varied across developmental stages, peaking in open flowers. Comparing viral abundance measured by viral reads and fragments per kilobase of transcript per million (FPKM) values revealed insights. SMV showed similar FPKM values in GM and GS, but BBWV2 and CMV displayed higher FPKM proportions in GS. Notably, the differences in viral abundance between GM and GS were generally insignificant based on the FPKM values across developmental stages, except for the apical bud stage in four GM cultivars. We also detected MDV, a multi-segmented virus, in two GM samples, with variable proportions of its segments. In conclusion, our study demonstrates the potential of plant transcriptomes for virome research, highlighting their strengths and limitations.

16.
Hip Pelvis ; 35(3): 193-199, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37727293

RESUMO

Purpose: Cephalomedullary (CM) nailing is widely performed in treatment of elderly patients with femoral intertrochanteric fractures. However, in cases of fixation failure, re-operation is usually necessary, thus determining factors that may contribute to fixation failure is important. In this study, we examined factors affecting the occurrence of fixation failure, such as age or fracture stability, after CM nailing in elderly patients. Materials and Methods: This study was conducted retrospectively using registered data. From April 2011 to December 2018, CM nailing was performed in 378 cases diagnosed with femoral intertrochanteric fractures, and 201 cases were finally registered. Cases involving patients who were bed-ridden before injury, who died from causes unrelated to surgery, and those with a follow-up period less than six months were excluded. Results: Fixation failure occurred in eight cases. Comparison of the surgical success and fixation failure group showed that the mean age was significantly higher in the fixation failure group compared with the control group (81.3±6.4 vs. 86.4±6.8; P=0.034). A significantly high proportion of unstable fractures was also observed (139/54 vs. 3/5; P=0.040), with a significantly high ratio of intramedullary reduction (176/17 vs. 5/3; P=0.034). A significantly higher ratio of unstable fractures compared with that of stable fractures was observed in the intramedullary reduction group (132/49 vs. 10/10; P=0.033). Conclusion: Fixation failure of CM nailing is likely to occur in patients who are elderly or have unstable fracture patterns. Thus, care should be taken in order to avoid intramedullary reduction.

17.
Inorg Chem ; 62(37): 15084-15093, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37667823

RESUMO

We report the synthesis and characterization of various compounds containing the 1,7,9-hydroxylated closo-dodecahydrododecaborate (B12H9(OH)32-) cluster motif. Specifically, we show how the parent compound can be synthesized on the multigram scale and further perhalogenated, leading to a new class of vertex-differentiated weakly coordinating anions. We show that a postmodification of the hydroxyl groups by alkylation affords further opportunities for tailoring these anions' stability, steric bulk, and solubility properties. The resulting dodecaborate-based salts were subjected to a full thermal and electrochemical stability evaluation, showing that many of these anions maintain thermal stability up to 500 °C and feature no redox activity below ∼1 V vs Fc/Fc+. Mixed hydroxylated/halogenated clusters show enhanced solubility compared to their purely halogenated analogs and retain weakly coordinating properties in the solid state, as demonstrated by ionic conductivity measurements of their Li+ salts.

18.
Front Cardiovasc Med ; 10: 1215389, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37492160

RESUMO

Background: Primary cardiac tumors are rare, and malignant primary cardiac tumors are even rarer. Cardiac osteosarcoma is a very rare type of malignant primary cardiac tumor with limited reported cases. We present a case report of cardiac osteosarcoma and review its characteristics and the related literature. Case summary: A 44-year-old female patient without a specific medical history presented with intermittent dyspnea that started 1 month prior to presentation. A heterogeneous mass was observed in the left atrium on echocardiography and a large mass was observed in the left atrium on computed tomography. Surgery was performed under the suspicion of atypical cardiac myxoma, and the tumor was successfully removed. However, postoperative histopathological examination revealed cardiac osteosarcoma. The patient underwent chemotherapy and has been well maintained without recurrence for 10 years. Conclusion: We present a case report of the echocardiographic features and treatment strategies for cardiac osteosarcoma, an extremely rare cardiac tumor. Multimodal imaging can be helpful; however, a histological diagnosis through surgical resection is essential. Appropriate treatment and follow-up based on histological findings are necessary.

19.
Sensors (Basel) ; 23(10)2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37430819

RESUMO

Pedestrian tracking is a challenging task in the area of visual object tracking research and it is a vital component of various vision-based applications such as surveillance systems, human-following robots, and autonomous vehicles. In this paper, we proposed a single pedestrian tracking (SPT) framework for identifying each instance of a person across all video frames through a tracking-by-detection paradigm that combines deep learning and metric learning-based approaches. The SPT framework comprises three main modules: detection, re-identification, and tracking. Our contribution is a significant improvement in the results by designing two compact metric learning-based models using Siamese architecture in the pedestrian re-identification module and combining one of the most robust re-identification models for data associated with the pedestrian detector in the tracking module. We carried out several analyses to evaluate the performance of our SPT framework for single pedestrian tracking in the videos. The results of the re-identification module validate that our two proposed re-identification models surpass existing state-of-the-art models with increased accuracies of 79.2% and 83.9% on the large dataset and 92% and 96% on the small dataset. Moreover, the proposed SPT tracker, along with six state-of-the-art (SOTA) tracking models, has been tested on various indoor and outdoor video sequences. A qualitative analysis considering six major environmental factors verifies the effectiveness of our SPT tracker under illumination changes, appearance variations due to pose changes, changes in target position, and partial occlusions. In addition, quantitative analysis based on experimental results also demonstrates that our proposed SPT tracker outperforms the GOTURN, CSRT, KCF, and SiamFC trackers with a success rate of 79.7% while beating the DiamSiamRPN, SiamFC, CSRT, GOTURN, and SiamMask trackers with an average of 18 tracking frames per second.

20.
Plants (Basel) ; 12(12)2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37375999

RESUMO

Wheat (Triticum aestivum L.) is one of the most important staple crops in the world, along with maize and rice. More than 50 plant viruses are known to infect wheat worldwide. To date, there are no studies on the identification of viruses infecting wheat in Korea. Therefore, we investigated virome in wheat from three different geographical regions where wheat is mainly cultivated in Korea using Oxford Nanopore Technology (ONT) sequencing and Illumina sequencing. Five viral species, including those known to infect wheat, were identified using high-throughput sequencing strategies. Of these, barley virus G (BVG) and Hordeum vulgare endornavirus (HvEV) were consistently present in all libraries. Sugarcane yellow leaf virus (SCYLV) and wheat leaf yellowing-associated virus (WLYaV) were first identified in Korean wheat samples. The viruses identified by ONT and Illumina sequencing were compared using a heatmap. Though the ONT sequencing approach is less sensitive, the analysis results were similar to those of Illumina sequencing in our study. Both platforms served as reliable and powerful tools for detecting and identifying wheat viruses, achieving a balance between practicality and performance. The findings of this study will provide deeper insights into the wheat virosphere and further help improve disease management strategies.

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