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1.
Medicine (Baltimore) ; 103(27): e38779, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38968506

RESUMO

Lymphedema is known to affect as many as 140 to 250 million people worldwide. Approximately 99% of lymphedemas are secondary cases after lymphadenectomy, radiation, or parasite infection. There has been no accurate estimate of the lymphedema population size in South Korea. This study aimed to quantify the epidemiology of lymphedema in South Korea and analyze the clinical characteristics of patients with lymphedema using a nationwide database. This large-scale cross-sectional study included patients who received one of the following three diagnostic codes - Q82.0 (hereditary lymphedema), I97.2 (breast cancer-related lymphedema), and I89.0 (unclassified lymphedema) from the Korean Health Insurance Review and Assessment service between January 2019 and July 2022 at tertiary hospitals, general hospitals, or other hospitals. The demographics of the lymphedema population, medication use, and medical characteristics were identified. Over the last 4 years, the annual incidence of lymphedema has steadily increased and peaked in 2021 with the number 1.85 out of 1000. Of all patients, 81% were located in the upper extremity, and 10.6% had previous cancer. Most patients were diagnosed in general hospitals (53.2%), at orthopedic surgery department (41.9%). On average, lymphedema patients spent 70.17 US dollar for medication and hospitalized for 16.9 days annually after diagnosis. Commonly prescribed medications were Entelon® (Vitis vinifera seed extract) (66.9%), steroids (40.5%), non-steroidal anti-inflammatory drugs (26.5%) and diuretics (21.8%). Only 5.7% of patients received surgery and 19.2% received herbal medicine. This is the first study in South Korea to quantify demographic and medical characteristics of lymphedema patients. These results will contribute to a comprehensive understanding of lymphedema diagnosis and treatment in our nation.


Assuntos
Linfedema , Humanos , República da Coreia/epidemiologia , Estudos Transversais , Feminino , Masculino , Linfedema/epidemiologia , Pessoa de Meia-Idade , Adulto , Idoso , Incidência , Adolescente , Adulto Jovem
2.
Gland Surg ; 13(6): 987-998, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-39015709

RESUMO

Background: Capsular contracture is one of the most common and severe complications after implant-based breast reconstruction. Recently, prepectoral implant-based breast reconstruction using acellular dermal matrix (ADM) has become an alternative to subpectoral implant-based reconstruction. However, risk factors for capsular contracture associated with recent prepectoral reconstruction trends are not well refined yet. Thus, the aim of this study was to determine risk factors for capsular contracture, and share our experience of treating capsular contracture in prepectoral reconstruction. Methods: This retrospective comparative study focused on 110 patients who underwent prepectoral implant-based breast reconstruction with ADM. Risk factors of capsular contracture were analyzed by comparing a capsular contracture group (27 cases) and a non-capsular contracture group (83 cases). Secondary treatment after capsular contracture development was analyzed in capsular contracture group. Results: According to univariate and multivariate analyses of risk factors for capsular contracture, single staged implant-based reconstruction (direct-to-implant), infection, and postoperative radiotherapy were significantly related to the development of capsular contracture. Also, surgical intervention including capsulectomy and capsulotomy with implant change showed a significant higher remission rate than other groups. Conclusions: Our study provides insights into risk factors and treatment choices for capsular contracture after prepectoral implant-based breast reconstruction with ADM. These findings can aid selection of patients, postoperative care and preventative treatment before reconstruction.

3.
Proc Natl Acad Sci U S A ; 121(24): e2322009121, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38843187

RESUMO

Follicular helper T (TFH) cells mediate germinal center reactions to generate high affinity antibodies against specific pathogens, and their excessive production is associated with the pathogenesis of systemic autoimmune diseases such as systemic lupus erythematosus (SLE). ETV5, a member of the ETS transcription factor family, promotes TFH cell differentiation in mice. In this study, we examined the role of ETV5 in the pathogenesis of lupus in mice and humans. T cell-specific deletion of Etv5 alleles ameliorated TFH cell differentiation and autoimmune phenotypes in lupus mouse models. Further, we identified SPP1 as an ETV5 target that promotes TFH cell differentiation in both mice and humans. Notably, extracellular osteopontin (OPN) encoded by SPP1 enhances TFH cell differentiation by activating the CD44-AKT signaling pathway. Furthermore, ETV5 and SPP1 levels were increased in CD4+ T cells from patients with SLE and were positively correlated with disease activity. Taken together, our findings demonstrate that ETV5 is a lupus-promoting transcription factor, and secreted OPN promotes TFH cell differentiation.


Assuntos
Diferenciação Celular , Lúpus Eritematoso Sistêmico , Osteopontina , Fatores de Transcrição , Animais , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/patologia , Osteopontina/metabolismo , Osteopontina/genética , Camundongos , Humanos , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo , Células T Auxiliares Foliculares/imunologia , Células T Auxiliares Foliculares/metabolismo , Feminino , Modelos Animais de Doenças , Camundongos Knockout
4.
Br J Radiol ; 97(1159): 1286-1294, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38733576

RESUMO

OBJECTIVES: This study aimed to assess the impact of super-resolution deep learning reconstruction (SR-DLR) on coronary CT angiography (CCTA) image quality and blooming artifacts from coronary artery stents in comparison to conventional methods, including hybrid iterative reconstruction (HIR) and deep learning-based reconstruction (DLR). METHODS: A retrospective analysis included 66 CCTA patients from July to November 2022. Major coronary arteries were evaluated for image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). Stent sharpness was quantified using 10%-90% edge rise slope (ERS) and 10%-90% edge rise distance (ERD). Qualitative analysis employed a 5-point scoring system to assess overall image quality, image noise, vessel wall, and stent structure. RESULTS: SR-DLR demonstrated significantly lower image noise compared to HIR and DLR. SNR and CNR were notably higher in SR-DLR. Stent ERS was significantly improved in SR-DLR, with mean ERD values of 0.70 ± 0.20 mm for SR-DLR, 1.13 ± 0.28 mm for HIR, and 0.85 ± 0.26 mm for DLR. Qualitatively, SR-DLR scored higher in all categories. CONCLUSIONS: SR-DLR produces images with lower image noise, leading to improved overall image quality, compared with HIR and DLR. SR-DLR is a valuable image reconstruction algorithm for enhancing the spatial resolution and sharpness of coronary artery stents without being constrained by hardware limitations. ADVANCES IN KNOWLEDGE: The overall image quality was significantly higher in SR-DLR, resulting in sharper coronary artery stents compared to HIR and DLR.


Assuntos
Angiografia por Tomografia Computadorizada , Angiografia Coronária , Aprendizado Profundo , Razão Sinal-Ruído , Stents , Humanos , Estudos Retrospectivos , Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Vasos Coronários/diagnóstico por imagem , Artefatos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia
5.
Biomedicines ; 12(3)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38540123

RESUMO

Wound dressings are widely used to protect wounds and promote healing. The water absorption and antifriction properties of dressings are important for regulating the moisture balance and reducing secondary damages during dressing changes. Herein, we developed a hyaluronic acid (HA)-based foam dressing prepared via the lyophilization of photocrosslinked HA hydrogels with high water absorption and antiadhesion properties. To fabricate the HA-based foam dressing (HA foam), the hydroxyl groups of the HA were modified with methacrylate groups, enabling rapid photocuring. The resulting photocured HA solution was freeze-dried to form a porous structure, enhancing its exudate absorption capacity. Compared with conventional biopolymer-based foam dressings, this HA foam exhibited superior water absorption and antifriction properties. To assess the wound-healing potential of HA foam, animal experiments involving SD rats were conducted. Full-thickness defects measuring 2 × 2 cm2 were created on the skin of 36 rats, divided into four groups with 9 individuals each. The groups were treated with gauze, HA foam, CollaDerm®, and CollaHeal® Plus, respectively. The rats were closely monitored for a period of 24 days. In vivo testing demonstrated that the HA foam facilitated wound healing without causing inflammatory reactions and minimized secondary damages during dressing changes. This research presents a promising biocompatible foam wound dressing based on modified HA, which offers enhanced wound-healing capabilities and improved patient comfort and addresses the challenges associated with conventional dressings.

6.
J Craniofac Surg ; 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38411191

RESUMO

Many surgical techniques for managing epicanthal folds have been reported, but their main drawbacks include a noticeable scar in Asians, acute medial canthal angle, and applicability only in mild or moderate epicanthal folds. This study described a novel surgical technique, Y-W epicanthoplasty, and assessed the medial canthal shape and scarring in patients who underwent Y-W epicanthoplasty. Patients with moderate or severe epicanthal folds between January 2004 and February 2017 were included in this study. Pre- and postoperative intercanthal distance (ICD), inner canthal angle (ICA), and interpupillary distance (IPD) were measured. The ICD ratios (ICD/IPD) and extent of postoperative scarring were evaluated. A Y-W epicanthoplasty was performed on 18 patients. The ICD ratio of the total study cohort showed a significant reduction following surgery (preoperative ICD ratio=0.62±0.04, postoperative ICD ratio=0.58±0.03, P<0.001). The ICA was 51.8±7.7° and 49.8±5.6° in the pre- and postoperative periods, respectively (P=0.086) Eleven patients showed no apparent scar, and 6 patients were found to have minimal scarring that was visible only under close inspection. One patient had a hypertrophic scar that was successfully managed with triamcinolone acetonide injections. Y-W epicanthoplasty can provide good aesthetic results without a visible scar in patients with moderate-to-severe epicanthal folds. The Y-W epicanthoplasty avoids a medially extended skin incision and excessive tension on the skin flaps. Moreover, an acutely shaped or webbed medial canthus after epicanthoplasty can be prevented by adding a small triangular flap. The Y-W epicanthoplasty procedure is simple and straightforward, and it is appropriate for moderate-to-severe epicanthal fold correction.

7.
J Korean Soc Radiol ; 85(1): 197-203, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38362399

RESUMO

Tuberculous pericarditis is an extrapulmonary manifestation of tuberculosis that is most commonly associated with pericardial thickening, effusion, and calcification. We present a case of tuberculous pericarditis mimicking a malignant pericardial tumor in a 77-year-old male. CT revealed an irregular and nodular pericardial thickening. MRI revealed high signal intensity on T1-weighted fat-suppressed images and peripheral rim enhancement after gadolinium administration. MRI can be helpful in determining the differential diagnoses in cases of tuberculous pericarditis with nonspecific imaging findings.

8.
PLoS One ; 19(2): e0297390, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38386632

RESUMO

PURPOSE: To prospectively evaluate whether Lung-RADS classification and volumetric nodule assessment were feasible with ultralow-dose (ULD) chest CT scans with deep learning image reconstruction (DLIR). METHODS: The institutional review board approved this prospective study. This study included 40 patients (mean age, 66±12 years; 21 women). Participants sequentially underwent LDCT and ULDCT (CTDIvol, 0.96±0.15 mGy and 0.12±0.01 mGy) scans reconstructed with the adaptive statistical iterative reconstruction-V 50% (ASIR-V50) and DLIR. CT image quality was compared subjectively and objectively. The pulmonary nodules were assessed visually by two readers using the Lung-RADS 1.1 and automatically using a computerized assisted tool. RESULTS: DLIR provided a significantly higher signal-to-noise ratio for LDCT and ULDCT images than ASIR-V50 (all P < .001). In general, DLIR showed superior subjective image quality for ULDCT images (P < .001) and comparable quality for LDCT images compared to ASIR-V50 (P = .01-1). The per-nodule sensitivities of observers for Lung-RADS category 3-4 nodules were 70.6-88.2% and 64.7-82.4% for DLIR-LDCT and DLIR-ULDCT images (P = 1) and categories were mostly concordant within observers. The per-nodule sensitivities of the computer-assisted detection for nodules ≥4 mm were 72.1% and 67.4% on DLIR-LDCT and ULDCT images (P = .50). The 95% limits of agreement for nodule volume differences between DLIR-LDCT and ULDCT images (-85.6 to 78.7 mm3) was similar to the within-scan nodule volume differences between DLIR- and ASIR-V50-LDCT images (-63.9 to 78.5 mm3), with volume differences smaller than 25% in 88.5% and 92.3% of nodules, respectively (P = .65). CONCLUSION: DLIR enabled comparable Lung-RADS and volumetric nodule assessments on ULDCT images to LDCT images.


Assuntos
Aprendizado Profundo , Neoplasias Pulmonares , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Tomografia Computadorizada por Raios X/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Estudos Prospectivos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Doses de Radiação , Pulmão/diagnóstico por imagem , Processamento de Imagem Assistida por Computador
9.
FEBS Open Bio ; 14(4): 613-625, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38409906

RESUMO

Essential oils derived from plants are major ingredients in the medical and cosmetic industry. Here, we evaluated nine types of plant essential oils to identify potential candidates with antioxidant and elasticity-enhancing properties. Seven essential oils showed at least 10% radical scavenging activity at the highest concentration. Essential oils extracted from Aster glehnii, Cinnamomum cassia, Citrus unshiu, Juniperus chinensis L., and Juniperus chinensis var. sargentii significantly enhanced fibroblast viability, and oils from Cit. unshiu, J. chinensis L., and J. chinensis var. sargentii significantly increased cell proliferation and migration. Expression of extracellular matrix proteins, including collagen 1, collagen 3, and elastin, were upregulated by J. chinensis L. and J. chinensis var. sargentii oil, which also significantly enhanced the contractile activity of skin cells in a three-dimensional gel contraction assay. The results suggest that J. chinensis L. and J. chinensis var. sargentii essential oils may be potential anti-wrinkling and anti-oxidative agents for future consideration of use in the medical and cosmetic industry.


Assuntos
Juniperus , Óleos Voláteis , Óleos Voláteis/farmacologia , Antioxidantes/farmacologia , Óleos de Plantas , Colágeno
10.
Zootaxa ; 5397(3): 397-417, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38221196

RESUMO

In the present study, a total of 30 species of Phyllonorycter Hbner, 1822 (Lepidoptera: Gracillariidae: Lithocolletinae) in Korea are recognized and enumerated. Among them, two species (Phyllonorycter phallustenuis sp. nov. and P. daehana sp. nov.) are newly described to science. In addition, nine species are reported for the first time for the country: P. ginnalae (Ermolaev, 1981), P. jezoniella (Matsumura, 1931), P. lonicerae (Kumata, 1963), P. nigristella (Kumata, 1957), P. ostryae (Kumata, 1963), P. reduncata (Ermolaev, 1986), P. sorbicola (Kumata, 1963), P. tritorrhecta (Meyrick, 1935), and P. zelkovae (Kumata, 1963). Detailed descriptions and illustrations of both adults and genitalia of the new species are provided.


Assuntos
Lepidópteros , Mariposas , Animais , Genitália , Distribuição Animal
11.
Cancers (Basel) ; 15(23)2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38067236

RESUMO

Colorectal cancer is the third most common cancer in the world, with an annual incidence of 2 million cases. The success of first-line chemotherapy plays a crucial role in determining the disease outcome. Therefore, there is an increasing demand for precision medicine to predict drug responses and optimize chemotherapy in order to increase patient survival and reduce the related side effects. Patient-derived organoids have become a popular in vitro screening model for drug-response prediction for precision medicine. However, there is no established correlation between oxaliplatin and drug-response prediction. Here, we suggest that organoid culture conditions can increase resistance to oxaliplatin during drug screening, and we developed a modified medium condition to address this issue. Notably, while previous studies have shown that survivin is a mechanism for drug resistance, our study observed consistent survivin expression irrespective of the culture conditions and oxaliplatin treatment. However, clusterin induced apoptosis inhibition and cell survival, demonstrating a significant correlation with drug resistance. This study's findings are expected to contribute to increasing the accuracy of drug-response prediction in patient-derived APC mutant colorectal cancer organoids, thereby providing reliable precision medicine and improving patient survival rates.

12.
Biodivers Data J ; 11: e115509, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38107164

RESUMO

Background: Liocrobyla Meyrick, 1916 is a relatively small genus within the family Gracillariidae, consisting of nine species worldwide, including five species in Korea. New information: In this study, we recognise five species belonging to the genus Liocrobyla Meyrick, 1916 from Korea. Amongst them, one species, L.indigofera Liu, Wang & Wang, 2018, is reported for the first time in Korea. Figures of adults, male and female genitalia, along with a key to the species of Liocrobyla in Korea, are provided.

13.
PLoS One ; 18(11): e0294194, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37922291

RESUMO

[This corrects the article DOI: 10.1371/journal.pone.0281141.].

14.
Arch Craniofac Surg ; 24(6): 284-287, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37866819

RESUMO

The ultimate goal of cleft palate repair is to achieve an intact palate with the separation of the oral and nasal cavities. However, some patients develop an oronasal fistula in the secondary palate after palatoplasty. Postoperatively, a secondary palatal oronasal fistula may develop, leading to functional problems. In this study, we describe a patient with recurrent oronasal fistula and alveolar cleft with multiple failed previous reconstructions at another clinic. The oronasal fistula and alveolar cleft were repaired using a tongue flap and an iliac bone graft, respectively. The patient demonstrated excellent clinical progress with no recurrence of the oronasal fistula at the 1-year follow-up.

15.
Biomark Res ; 11(1): 80, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37705067

RESUMO

BACKGROUND: Small cell lung cancer (SCLC) has an exceptionally poor prognosis; as most of the cases are initially diagnosed as extensive disease with hematogenous metastasis. Therefore, the early diagnosis of SCLC is very important and may improve its prognosis. METHODS: To investigate the feasibility of early diagnosis of SCLC, we examined exosomal microRNAs (miRNAs) present in serum obtained from patients with SCLC. First, exosomes were isolated in serum from patients with SCLC and healthy individuals and were characterized using particle size and protein markers. Additionally, miRNA array was performed to define SCLC-specific exosomal miRNAs. Second, the obtained miRNAs were further validated employing a large cohort. Finally, the ability to diagnose SCLC was estimated by area under the curve (AUC), and intracellular mRNA change patterns were verified through validated miRNAs. RESULTS: From the miRNA array results, we selected 51-miRNAs based on p-values and top 10 differentially expressed genes, and 25-miRNAs were validated using quantitative reverse transcription-polymerase chain reaction. The 25-miRNAs were further validated employing a large cohort. Among them, 7-miRNAs showed significant differences. Furthermore, 6-miRNAs (miR-3565, miR-3124-5p, miR-200b-3p, miR-6515, miR-3126-3p and miR-9-5p) were up-regulated and 1-miRNA (miR-92b-5p) was down-regulated. The AUC value of each miRNA sets between 0.64 and 0.76, however the combined application of 3-miRNAs (miR-200b-3p, miR-3124-5p and miR-92b-5p) remarkably improved the diagnostic value (AUC = 0.93). Gene ontology analysis revealed that the 3-miRNA panel is linked to various oncogene pathways and nervous system development. When the 3-miRNAs were introduced to cells, the resulting changes in total mRNA expression strongly indicated the presence of lung diseases, including lung cancer. In addition, the 3-miRNA panel was significantly associated with a poorer prognosis, although individual miRNAs have not been validated as prognostic markers. CONCLUSION: Our study identified SCLC-specific exosomal miRNAs, and the 3-miRNAs panel (miR-200b-3p, miR-3124-5p and miR-92b-5p) may serve as a diagnostic and prognostic marker for SCLC.

16.
BMC Med Imaging ; 23(1): 121, 2023 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-37697262

RESUMO

OBJECTIVE: Few studies have explored the clinical feasibility of using deep-learning reconstruction to reduce the radiation dose of CT. We aimed to compare the image quality and lung nodule detectability between chest CT using a quarter of the low dose (QLD) reconstructed with vendor-agnostic deep-learning image reconstruction (DLIR) and conventional low-dose (LD) CT reconstructed with iterative reconstruction (IR). MATERIALS AND METHODS: We retrospectively collected 100 patients (median age, 61 years [IQR, 53-70 years]) who received LDCT using a dual-source scanner, where total radiation was split into a 1:3 ratio. QLD CT was generated using a quarter dose and reconstructed with DLIR (QLD-DLIR), while LDCT images were generated using a full dose and reconstructed with IR (LD-IR). Three thoracic radiologists reviewed subjective noise, spatial resolution, and overall image quality, and image noise was measured in five areas. The radiologists were also asked to detect all Lung-RADS category 3 or 4 nodules, and their performance was evaluated using area under the jackknife free-response receiver operating characteristic curve (AUFROC). RESULTS: The median effective dose was 0.16 (IQR, 0.14-0.18) mSv for QLD CT and 0.65 (IQR, 0.57-0.71) mSv for LDCT. The radiologists' evaluations showed no significant differences in subjective noise (QLD-DLIR vs. LD-IR, lung-window setting; 3.23 ± 0.19 vs. 3.27 ± 0.22; P = .11), spatial resolution (3.14 ± 0.28 vs. 3.16 ± 0.27; P = .12), and overall image quality (3.14 ± 0.21 vs. 3.17 ± 0.17; P = .15). QLD-DLIR demonstrated lower measured noise than LD-IR in most areas (P < .001 for all). No significant difference was found between QLD-DLIR and LD-IR for the sensitivity (76.4% vs. 72.2%; P = .35) or the AUFROCs (0.77 vs. 0.78; P = .68) in detecting Lung-RADS category 3 or 4 nodules. Under a noninferiority limit of -0.1, QLD-DLIR showed noninferior detection performance (95% CI for AUFROC difference, -0.04 to 0.06). CONCLUSION: QLD-DLIR images showed comparable image quality and noninferior nodule detectability relative to LD-IR images.


Assuntos
Aprendizado Profundo , Neoplasias Pulmonares , Humanos , Pessoa de Meia-Idade , Redução da Medicação , Neoplasias Pulmonares/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
17.
Biochem Biophys Res Commun ; 680: 7-14, 2023 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-37703603

RESUMO

AXL is a member of TAM receptor family and has been highlighted as a potential target for cancer treatment. Accumulating evidence has uncovered the critical role of the AXL signaling pathway in tumor growth, metastasis, and resistance against anti-cancer drugs, as well as its association with cancer immune escape. However, the function of AXL as a manipulator of the immune system in the tumor microenvironment (TME) remains unclear. Therefore, in this study, we investigated the impact of AXL on immune cells in the TME of a syngeneic tumor model using AXL knockout (AXL-/-) mice. Compared to AXL wild-type (AXL+/+) mice, tumor growth was significantly suppressed in AXL-/- mice, and an induced population of tumor-infiltrated CD8+ T cells and CD103+ dendritic cells (DCs) was observed. The change of CD8+ T cells and CD103+ DCs was also confirmed in tumor-draining lymph nodes (TdLN). In addition, the clonal expansion of OVA-specific CD8+ T cells was dominant in AXL-/- mice. Finally, anti-PD-1 treatment evidenced synergistic anti-cancer effects in AXL-/- mice. Overall, our data indicate that AXL signaling may inhibit the clonal expansion of tumor-specific CD8+ T cells through the regulation of the migration of CD8+ T cells and DCs in TME. Thus, AXL may be a powerful molecular target to improve anti-cancer effects through single or combined therapy with immune checkpoint inhibitors (ICI).


Assuntos
Linfócitos T CD8-Positivos , Neoplasias , Camundongos , Animais , Receptor Tirosina Quinase Axl , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Células Dendríticas , Microambiente Tumoral , Camundongos Endogâmicos C57BL
18.
Biol Reprod ; 109(2): 215-226, 2023 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-37255320

RESUMO

The present study aimed to investigate the regulation of placentas and uterus remodeling and involvement of estradiol in gestational diabetes mellitus. To achieve this, we established in vitro and in vivo models for gestational diabetes mellitus placentas by culturing human placental choriocarcinoma cells (BeWo) under hyperglycemic concentration and treating pregnant rats with streptozotocin. We evaluated the expression of angiogenesis-related proteins. The expression of the anti-angiogenic factor, excess placental soluble fms-like tyrosine kinase 1 was increased in our in vitro gestational diabetes mellitus model compared with the control. Moreover, the expressions of placental soluble fms-like tyrosine kinase 1 and the von Willebrand factor were also significantly elevated in the placenta of streptozotocin-treated rats. These data indicate the disruption of angiogenesis in the gestational diabetes mellitus placentas. The expression levels of connexin 43, a component of the gap junction and collagen type I alpha 2 chain, a component of the extracellular matrix, were decreased in the gestational diabetes mellitus uterus. These results suggest that uterus decidualization and placental angiogenesis are inhibited in gestational diabetes mellitus rats. Our results also showed upregulation of the expression of genes regulating estradiol synthesis as well as estrogen receptors in vivo models. Accordingly, the concentration of estradiol measured in the culture medium under hyperglycemic conditions, as well as in the serum and placenta of the streptozotocin-treated rats, was significantly elevated compared with the control groups. These results suggest that the dysregulated remodeling of the placenta and uterus may result in the elevation of estradiol and its signaling pathway in the gestational diabetes mellitus animal model to maintain pregnancy.


Assuntos
Diabetes Gestacional , Placenta , Gravidez , Feminino , Ratos , Animais , Humanos , Placenta/metabolismo , Diabetes Gestacional/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Estreptozocina/metabolismo , Útero/metabolismo , Estradiol/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
19.
J Am Pharm Assoc (2003) ; 63(3): 976-979, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36966088

RESUMO

BACKGROUND: The purpose of this case report is to describe a case of vitreous hemorrhage in a patient with a history of diabetic retinopathy and receiving dulaglutide for the management of type 2 diabetes mellitus (T2DM). CASE SUMMARY: A 64-year-old African American male with a past medical history of T2DM and severe diabetic retinopathy for 4 years was restarted on dulaglutide 1.5 mg weekly after being off therapy for 3 months. Baseline laboratory test results included hemoglobin A1c (HbA1c) of 8.8% and random blood glucose (BG) of 280 mg/dL. In addition, the patient had an average fasting BG of 150 mg/dL. In absence of intolerance, the dulaglutide dose was gradually maximized to 4.5 mg weekly and HbA1c decreased to 7.3% and random BG to 121 mg/dL at week 12 since reinitiation. At week 17 of therapy, the patient presented to the emergency department with a 1-day history of vision loss in the left eye and was diagnosed as having vitreous hemorrhage. The etiology for vitreous hemorrhage is unclear and may be a spontaneous episode. In discussion with the patient and the ophthalmologist, dulaglutide was restarted at 1.5 mg once weekly. After 4 weeks of reinitiation, the patient denied any recurrent symptoms of vitreous hemorrhage or worsening diabetic retinopathy. The most recent ophthalmology evaluation indicated no change in diabetic retinopathy. PRACTICE IMPLICATIONS: This case report adds to the limited body of evidence available for the incidence of vitreous hemorrhage in the setting of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) therapy and pre-existing diabetic retinopathy. The case report illustrates that a history of diabetic retinopathy should not automatically preclude the use of GLP-1 RAs.


Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Masculino , Humanos , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Hemoglobinas Glicadas , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Glicemia , Hemorragia Vítrea/tratamento farmacológico , Retinopatia Diabética/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Fragmentos Fc das Imunoglobulinas/efeitos adversos , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Proteínas Recombinantes de Fusão/efeitos adversos
20.
PLoS One ; 18(2): e0281141, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36745609

RESUMO

As the number of contact lens users increases, contact lens induced corneal infection is becoming more common. Acanthamoeba keratitis (AK) is a type of those which is caused by Acanthamoeba species, and may cause severe ocular inflammation and visual loss. We evaluated whether Torreya nucifera (T. nucifera) extract has an anti-amoebic effect and studied its mechanism of action on Acanthamoeba lugdunensis (A. lugdunensis). Cell viability was tested using the alamarBlue™ method, and the cell death mechanism was confirmed using the Tali® Apoptosis Kit. The SYTOX® Green assay was performed to check the plasma membrane permeability. The JC-1 dye was used to measure the mitochondrial membrane potential. A CellTiter-Glo® Luminescent Assay was used to measure the adenosine-triphosphate (ATP) level. Morphological changes in the mitochondria were examined by transmission electron microscopy (TEM). Cystic changes and a decrease in cell viability after treatment with T. nucifera were observed. Both apoptotic and necrotic cells were found in the Tali® Apoptosis assay. There was no significant difference in plasma membrane permeability between the control and T. nucifera treated groups. The collapse of the mitochondrial membrane potential and reduced ATP level in A. lugdunensis was confirmed in the groups treated with T. nucifera. Structural damage to the mitochondria was observed on TEM in the groups treated with T. nucifera. T. nucifera showed an anti-amoebic effect on A. lugdunensis, by inducing the loss of mitochondrial membrane potential. Thus, it could be a future therapeutic agent for AK.


Assuntos
Ceratite por Acanthamoeba , Acanthamoeba , Amebicidas , Humanos , Amebicidas/farmacologia , Amebicidas/uso terapêutico , Ceratite por Acanthamoeba/tratamento farmacológico , Trifosfato de Adenosina/metabolismo , Extratos Vegetais/farmacologia
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