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Inhibition of LSD1 was proposed as promising and attractive therapies for treating osteoporosis. Here, we synthesized a series of novel TCP-(MP)-Caffeic acid analogs as potential LSD1 inhibitors to assess their inhibitory effects on osteoclastogenesis by using TRAP-staining assay and try to explore the preliminary SAR. Among them, TCP-MP-CA (11a) demonstrated osteoclastic bone loss both in vitro and in vivo, showing a significant improvement in the in vivo effects compared to the LSD1 inhibitor GSK-LSD1. Additionally, we elucidated a mechanism that 11a and its precursor that 11e directly bind to LSD1/CoREST complex through FAD to inhibit LSD1 demethylation activity and influence its downstream IκB/NF-κB signaling pathway, and thus regulate osteoclastic bone loss. These findings suggested 11a or 11e as potential novel candidates for treating osteoclastic bone loss, and a concept for further development of TCP-(MP)-Caffeic acid analogs for therapeutic use in osteoporosis clinics.
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Ácidos Cafeicos , Osteoclastos , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Ácidos Cafeicos/farmacología , Ácidos Cafeicos/química , Ácidos Cafeicos/síntesis química , Animales , Relación Estructura-Actividad , Ratones , Estructura Molecular , Relación Dosis-Respuesta a Droga , Descubrimiento de Drogas , Humanos , Osteoporosis/tratamiento farmacológico , Resorción Ósea/tratamiento farmacológico , Células RAW 264.7 , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/síntesis químicaRESUMEN
PURPOSE: To investigate the correlation between the autonomic nervous system and choroidal vascularity in patients with central serous chorioretinopathy (CSC), using heart rate variability (HRV) analysis, optical coherence tomography (OCT) and OCT angiography (OCTA). METHODS: We retrospectively analyzed data of 25 patients with unilateral CSC (50 eyes, including the unaffected fellow eyes) and 25 healthy controls. The assessment involved a 5-minute HRV analysis encompassing both frequency and time domains, especially low frequency (LF), high frequency (HF), and LF/HF ratio. In OCT (12 × 9 mm) and en-face OCTA (3 × 3 mm) scans, we measured parameters including choroidal vascularity index (CVI), choroidal vessel density in the middle and deep layers, and choriocapillaris flow void. Regression analysis was conducted to elucidate the associations between HRV parameters and OCT/OCTA measurements. RESULTS: Normalized LF(LFnorm) and LF/HF ratios were higher in patients with CSC than in healthy controls. LFnorm and the log-transformed ratio of LF to HF [log(LF/HF)] demonstrated a significant and borderline correlation with CVI in the linear regression analysis (P = 0.040, R2 = 0.171, and P = 0.059, R2 = 0.147, respectively). Both CVI and deep choroid vessel density showed a more significant association with LFnorm and log (LF/HF) in the non-linear quadratic regression analysis than in the linear analysis (all, P < 0.04, R2 > 0.25). CONCLUSION: The frequency-domain parameters of HRV, including LFnorm and log (LF/HF), demonstrated a significant association with indicators reflective of large choroidal vessel luminal area on macular OCT/OCTA scans. This observation implies complicated modulation of choroidal blood flow by the autonomic nervous system in CSC.
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PURPOSE: This single center retrospective study aimed to investigate the factors associated with central nervous system (CNS) involvement of primary vitreoretinal lymphoma (PVRL). METHODS: Clinical features of patients with PVRL (Group 1), those diagnosed with vitreoretinal lymphoma (VRL) after primary CNS lymphoma diagnosis (Group 2), and those concurrently diagnosed with CNS lymphoma and VRL (Group 3), were compared. The main outcomes included sex, age, types of treatment, survival, visual acuity, diagnostic methods, VRL recurrence, ocular manifestations, and interleukin levels in the aqueous humor. RESULTS: Groups 1, 2, and 3 included 66 eyes in 38 patients, 29 eyes in 18 patients, and 14 eyes in 8 patients, respectively. Group 3 had shorter overall survival (OS) than Groups 1 and 2 (P = 0.042 and P = 0.009, respectively). The three groups did not differ in progression-free survival (P = 0.060). The 5-year survival rates of Groups 1, 2, and 3 were 56.5%, 44.0%, and 25.0%, respectively (P = 0.001). Patients with CNS involvement in Group 1 exhibited VRL recurrence (P < 0.001), high interleukin-10 (P = 0.024), and sub-retinal pigment epithelium (RPE) infiltration (P = 0.009). Patients experiencing VRL recurrence in Group 1 tended to show CNS involvement (P < 0.001). CONCLUSION: Patients concurrently diagnosed with CNS lymphoma and VRL had a shorter OS and a lower 5-year survival rate. In patients with PVRL, the recurrence of VRL, high interleukin-10, and sub-RPE infiltration were associated with CNS involvement.
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Linfoma Intraocular , Neoplasias de la Retina , Agudeza Visual , Cuerpo Vítreo , Humanos , Masculino , Femenino , Neoplasias de la Retina/diagnóstico , Neoplasias de la Retina/patología , Estudios Retrospectivos , Persona de Mediana Edad , Cuerpo Vítreo/patología , Cuerpo Vítreo/metabolismo , Anciano , Adulto , Linfoma Intraocular/diagnóstico , Linfoma Intraocular/metabolismo , Anciano de 80 o más Años , Estudios de Seguimiento , Tasa de Supervivencia/tendencias , Neoplasias del Sistema Nervioso Central/diagnóstico , Humor Acuoso/metabolismoRESUMEN
PURPOSE: Although leukemic retinopathy accounts for 80% of ocular complications in acute leukemia, its pathogenesis remains unclear. To evaluate changes in retinal and choroicapillaris and structural parameters in patients with acute leukemia, we analyzed the correlation between vascular perfusion metrics and laboratory parameters and assessed the changes after hematopoietic stem cell transplantation (HSCT). METHODS: Herein, 104 eyes of 52 patients aged 18 and above with acute leukemia were enrolled. 80 eyes of 40 healthy patients were recruited as control participants. All participants underwent optical coherence tomography (OCT) and OCT angiography (OCTA) at baseline. RESULTS: Patients with acute leukemia had a significantly thicker ganglion cell-inner plexiform layer (GCIPL) and lower circularity index than the control participants. Post-HSCT perfusion metrics did not differ significantly, but parafoveal thickness decreased significantly. During the active phase of acute leukemia, lower platelet levels were associated with significant GCIPL thickening and increased foveal avascular zone and perimeter. D-dimer levels positively correlated with GCIPL thickness. CONCLUSION: Patients with acute leukemia had subclinical retinal microvascular deficits on OCTA and GCIPL thickening on OCT, possibly associated with bone marrow function. GCIPL thickness may indicate acute ischemia in such patients. Further studies must elucidate their clinical and prognostic significance.
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PURPOSE: To assess the longitudinal surgical outcomes of macular telangiectasia type 2 macular hole (MacTel-MH) and compare them with those of idiopathic MH. METHODS: This retrospective, single-tertiary center study included patients who underwent MH surgery between January 2015 and September 2023. Patients with characteristic optical coherence tomography (OCT) findings of MacTel in both eyes or those who underwent fluorescence angiography were classified as having MacTel MH. Baseline and postoperative best-corrected visual acuity and OCT parameters were reviewed. RESULTS: Totally, 27 and 243 eyes with MacTel and idiopathic MH, respectively, were included. MH closure rate was better achieved in idiopathic than in MacTel MH group at 2 years postoperatively. Temporal recovery of ellipsoid zone and external limiting membrane was more prominent in MacTel than in idiopathic MH group. Statistically significant visual acuity improvement was seen between 3 months and 2 years postoperatively in MacTel MH group. CONCLUSION: To the best of our knowledge, this is the first study to analyze the surgical outcomes of MacTel MH in both anatomical and functional aspects and compare them with patients with idiopathic MH. Postoperative microglia change would have affected the restoration of outer retinal layer of patients; however, further studies are needed for clarification.
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PURPOSE: To investigate the preoperative choriocapillaris perfusion (CCP) as a biomarker in patients with idiopathic epiretinal membrane (iERM). MATERIALS AND METHODS: 28 patients (28 eyes) with unilateral iERM who received pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling were included for retrospective observational study. Optical coherence tomography (OCT) and angiography (OCTA) was performed before and after PPV. Area, perimeter, and circularity of superficial foveal avascular zone (FAZ) were analyzed preoperatively in both eyes using OCTA. Preoperative CCP was also analyzed with binarized en-face OCTA images. Measurements of best-corrected visual acuity (BCVA) and central foveal thickness (CFT) by OCT were conducted at the baseline and 6 months following the surgery. The correlations of preoperative OCT parameters with postoperative BCVA and CFT reduction were analyzed. RESULTS: CCP was significantly lower (p < 0.001) and FAZ had shrunk (p < 0.001) in eyes with iERM compared to unaffected fellow eyes before surgery. BCVA and CFT became significantly improved after surgery (p = 0.001, p < 0.001). Multiple regression analysis revealed that preoperative CCP was significantly related with BCVA improvement (ß = 0.185, p = 0.005), postoperative BCVA (ß = 0.108, p = 0.023) and ratio of post- to preoperative CFT (ß = 0.106, p = 0.044). CONCLUSIONS: Preoperative CCP is a biomarker for poor functional and anatomical prognosis after surgery in iERM.
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Biomarcadores , Coroides , Membrana Epirretinal , Tomografía de Coherencia Óptica , Vitrectomía , Humanos , Membrana Epirretinal/cirugía , Membrana Epirretinal/diagnóstico por imagen , Membrana Epirretinal/patología , Masculino , Femenino , Coroides/irrigación sanguínea , Coroides/diagnóstico por imagen , Coroides/patología , Anciano , Tomografía de Coherencia Óptica/métodos , Persona de Mediana Edad , Estudios Retrospectivos , Agudeza Visual , Fóvea Central/irrigación sanguínea , Fóvea Central/diagnóstico por imagen , Fóvea Central/patología , Angiografía con Fluoresceína/métodosRESUMEN
Exposure to blue light can lead to retinal degeneration, causing adverse effects on eye health. Although the loss of retinal cells due to blue light exposure has been observed, the precise molecular mechanisms underlying this process remain poorly understood. In this study, we investigate the role of alpha-crystallin A (CRYAA) in neuro-retinal degeneration and their regulation by blue light. We observed significant apoptotic cell death in both the retina of rats and the cultured neuro-retinal cells. The expressions of Cryaa mRNA and protein were significantly downregulated in the retina exposed to blue light. We identified that miR-325-3p reduces Cryaa mRNA and protein by binding to its 3'-untranslated region. Upregulation of miR-325-3p destabilized Cryaa mRNA and suppresses CRYAA, whereas downregulation of miR-325-3p increased both expressions. Blue light-induced neuro-retinal cell death was alleviated by CRYAA overexpression. These results highlight the critical role of Cryaa mRNA and miR-325-3p molecular axis in blue light-induced retinal degeneration. Consequently, targeting CRYAA and miR-325-3p presents a potential strategy for protecting against blue light-induced retinal degeneration.
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Luz , MicroARNs , Retina , Animales , MicroARNs/genética , MicroARNs/metabolismo , Luz/efectos adversos , Ratas , Retina/metabolismo , Retina/efectos de la radiación , Cadena A de alfa-Cristalina/metabolismo , Cadena A de alfa-Cristalina/genética , Degeneración Retiniana/metabolismo , Degeneración Retiniana/genética , Degeneración Retiniana/patología , Degeneración Retiniana/etiología , Apoptosis/efectos de la radiación , Ratas Sprague-Dawley , Masculino , Regulación hacia Abajo , Regiones no Traducidas 3' , Luz AzulRESUMEN
Neuromodulation technique using electric stimulation is widely applied in neural prosthesis, therapy, and neuroscience research. Various stimulation techniques have been developed to enhance stimulation efficiency and to precisely target the specific area of the brain which involves optimizing the geometry and the configuration of the electrode, stimulation pulse type and shapes, and electrode materials. Although the effects of electrode shape, size, and configuration on the performance of neural stimulation have individually been characterized, to date, there is no integrative investigation of how this factor affects neural stimulation. In this study, we computationally modeled the various types of electrodes with varying shapes, sizes, and configurations and simulated the electric field to calculate the activation function. The electrode geometry is then integratively assessed in terms of stimulation efficiency and stimulation focality. We found that stimulation efficiency is enhanced by making the electrode sharper and smaller. A center-to-vertex distance exceeding 100 µm shows enhanced stimulation efficiency in the bipolar configuration. Additionally, the separation distance of less than 1 mm between the reference and stimulation electrodes exhibits higher stimulation efficiency compared to the monopolar configuration. The region of neurons to be stimulated can also be modified. We found that sharper electrodes can locally activate the neuron. In most cases, except for the rectangular electrode shape with a center-to-vertex distance smaller than 100 µm, the bipolar electrode configuration can locally stimulate neurons as opposed to the monopolar configuration. These findings shed light on the optimal selection of neural electrodes depending on the target applications.
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Background and Objectives: Essential thrombocythemia (ET) is a myeloproliferative neoplasm that overproduces platelets and is associated with life-threatening thrombosis. Medical cytoreduction either with hydroxyurea (HU) or anagrelide (AG) is widely used, but drug intolerance or resistance are major concerns. Low-dose combination of HU and AG as an alternative strategy has been explored in various studies. It showed comparable response with acceptable toxicity in second-line settings for patients who experienced side effects from prior monotherapy. In this study, we evaluated the efficacy and safety of upfront combination for ET patients. Materials and Methods: From January 2018 to June 2022, a total of 241 ET patients with intermediate to high risk were enrolled. We identified 21 patients with initial drug combinations and compared treatment outcomes and adverse events (AEs) between combination and monotherapy groups. Results: The median age was 62 years old (range, 26-87) and median platelet count was 912 × 109/L (range, 520-1720). Overall treatment response did not exhibit significant differences between the groups, although there was a trend towards a lower response rate in patients treated with AG alone at 3 months post-treatment (AG + HU, 85.7% vs. AG alone, 75.4%, p = 0.068). AEs of any grade occurred in 52.3% of the combination group, 44.3% of the HU monotherapy group, and 43.4% of the AG single group, respectively. Of note was that the HU plus AG combination group suffered a lower incidence of grade 3-4 AEs compared to the other two groups, with statistical significance (p = 0.008 for HU monotherapy vs. combination therapy and p < 0.01 for AG monotherapy vs. combination therapy). Conclusions: Our findings demonstrated that the upfront low-dose combination approach showed feasible clinical outcomes with significantly lower severe AEs compared to conventional monotherapy. These results may offer valuable insights to clinicians for future prospective investigations.
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PURPOSE: To determine the cut-off points of minimum linear diameter (MLD) and base diameter (BD) at which the progression rate of idiopathic full-thickness macular holes (MHs) decreases before vitrectomy. STUDY DESIGN: A retrospective study. METHODS: We investigated the differences in MLD and BD between baseline and operation days in patients with stages 2, 3, and 4 MHs using optical coherence tomography (OCT). Each difference in OCT parameters was divided by the time interval to calculate the MH progression rates and the cut-off points of MLD and BD. RESULTS: Overall, 269 patients (282 eyes) were included. It took an average of 36.02 ± 24.69 (7-197) days from baseline to operation. MLD and BD progressed faster in stages 2 and 3 without posterior vitreous detachment (PVD) than in stage 4 with PVD (MLD: p < 0.001 and p = 0.007; BD: p < 0.001 and p = 0.019, respectively). Simple linear regression showed the relationship between baseline MLD and BD, and the progression rate; the progression rate decreased as baseline MLD (p = 0.004) and BD increased ( p < 0.001). For baseline MLD and BD, the cut-off points where the progression rate decreased were 306.0 and 470.0 µm, respectively. CONCLUSION: The group without PVD progressed faster than the group with PVD. Moreover, the progression rates were faster in MHs with MLD < 306.0 µm and BD < 470.0 µm. In these patients, vitrectomy without delay is expected to improve the visual prognosis.
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Perforaciones de la Retina , Desprendimiento del Vítreo , Humanos , Perforaciones de la Retina/diagnóstico , Perforaciones de la Retina/cirugía , Estudios Retrospectivos , Agudeza Visual , Retina , Vitrectomía/métodos , Tomografía de Coherencia Óptica/métodosRESUMEN
Objective: Acute leukemia (AL) is a life-threatening malignant disease that occurs in the bone marrow and blood, and is classified as either acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). Diagnosing AL warrants testing methods, such as flow cytometry, which require trained professionals, time, and money. We aimed to develop a model that can classify peripheral blood images of 12 cell types, including pathological cells associated with AL, using artificial intelligence. Methods: We acquired 42,386 single-cell images of peripheral blood slides from 282 patients (82 with AML, 40 with ALL, and 160 with immature granulocytes). Results: The performance of EfficientNet-V2 (B2) using the original image size exhibited the greatest accuracy (accuracy, 0.8779; precision, 0.7221; recall, 0.7225; and F1 score, 0.7210). The next-best accuracy was achieved by EfficientNet-V1 (B1), with a 256 × 256 pixels image. F1 score was the greatest for EfficientNet-V1 (B1) with the original image size. EfficientNet-V1 (B1) and EfficientNet-V2 (B2) were used to develop an ensemble model, and the accuracy (0.8858) and F1 score (0.7361) were improved. The classification performance of the developed ensemble model for the 12 cell types was good, with an area under the receiver operating characteristic curve above 0.9, and F1 scores for myeloblasts and lymphoblasts of 0.8873 and 0.8006, respectively. Conclusions: The performance of the developed ensemble model for the 12 cell classifications was satisfactory, particularly for myeloblasts and lymphoblasts. We believe that the application of our model will benefit healthcare settings where the rapid and accurate diagnosis of AL is difficult.
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Objective: Modern healthcare systems face challenges related to the stable and sufficient blood supply of blood due to shortages. This study aimed to predict the monthly blood transfusion requirements in medical institutions using an artificial intelligence model based on national open big data related to transfusion. Methods: Data regarding blood types and components in Korea from January 2010 to December 2021 were obtained from the Health Insurance Review and Assessment Service and Statistics Korea. The data were collected from a single medical institution. Using the obtained information, predictive models were developed, including eXtreme Gradient Boosting (XGBoost), Light Gradient Boosting Machine (LGBM), and category boosting (CatBoost). An ensemble model was created using these three models. Results: The prediction performance of XGBoost, LGBM, and CatBoost demonstrated a mean absolute error ranging from 14.6657 for AB+ red blood cells (RBCs) to 84.0433 for A+ platelet concentrate (PC) and a root mean squared error ranging from 18.5374 for AB+ RBCs to 118.6245 for B+ PC. The error range was further improved by creating ensemble models, wherein the department requesting blood was the most influential parameter affecting transfusion prediction performance for different blood products and types. Except for the department, the features that affected the prediction performance varied for each product and blood type, including the number of RBC antibody screens, crossmatch, nationwide blood donations, and surgeries. Conclusion: Based on blood-related open big data, the developed blood-demand prediction algorithm can efficiently provide medical facilities with an appropriate volume of blood ahead of time.
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PURPOSE: To quantitatively analyze choroidal and retinal vascular changes in HLA-B27-associated anterior uveitis. STUDY DESIGN: A retrospective study. METHODS: Medical records of 51 eyes with unilateral HLA-B27-associated anterior uveitis, their fellow eyes and 47 sex and age-matched healthy eyes were retrospectively reviewed. Their choroidal and retinal vasculature were analyzed using swept-source (SS) optical coherence tomography (OCT) and OCT angiography (OCTA) scans. RESULTS: Deep capillary plexus (DCP) vessel density (VD) (p < 0.001), choroidal vascularity index (CVI) (p = 0.012), and choriocapillary flow deficit (CCFD) (p < 0.001) of uveitic and fellow eye group were significantly higher than those of control group. On the contrary, superficial capillary plexus (SCP) VD (p < 0.001) of uveitic and fellow eye group were significantly lower than of control group. The vascular parameters of uveitis and fellow eye group showed no significant difference between uveitic and resolution period. CONCLUSION: Certain choroidal and retinal vascular parameters were significantly changed in both HLA-B27-associated anterior uveitis without posterior segment involvement and the quiet fellow eyes, suggesting their possible effects as a systemic inflammatory disorder.
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To assess the diagnostic utility of bone turnover markers (BTMs) and demographic variables for identifying individuals with osteoporosis. A cross-sectional study involving 280 participants was conducted. Serum BTM values were obtained from 88 patients with osteoporosis and 192 controls without osteoporosis. Six machine learning models, including extreme gradient boosting (XGBoost), light gradient boosting machine (LGBM), CatBoost, random forest, support vector machine, and k-nearest neighbors, were employed to evaluate osteoporosis diagnosis. The performance measures included the area under the receiver operating characteristic curve (AUROC), F1-score, and accuracy. After AUROC optimization, LGBM exhibited the highest AUROC of 0.706. Post F1-score optimization, LGBM's F1-score was improved from 0.50 to 0.65. Combining the top three optimized models (LGBM, XGBoost, and CatBoost) resulted in an AUROC of 0.706, an F1-score of 0.65, and an accuracy of 0.73. BTMs, along with age and sex, were found to contribute significantly to osteoporosis diagnosis. This study demonstrates the potential of machine learning models utilizing BTMs and demographic variables for diagnosing preexisting osteoporosis. The findings highlight the clinical relevance of accessible clinical data in osteoporosis assessment, providing a promising tool for early diagnosis and management.
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Biomarcadores , Aprendizaje Automático , Osteoporosis , Humanos , Osteoporosis/diagnóstico , Femenino , Masculino , Estudios Transversales , Biomarcadores/sangre , Persona de Mediana Edad , Anciano , Remodelación Ósea/fisiología , Curva ROCRESUMEN
Esculentin-2CHa(1-30) (?ESC") has been reported as a potent anti-diabetic peptide with little toxicity. However, its very short plasma residence time severely limits the therapeutic efficacy. To address this issue, we genetically engineered a fusion protein of tandem trimeric ESC with an albumin binding domain (ABD) and a fusion partner, SUMO (named ?SUMO-3×ESC-ABD"). The SUMO-3×ESC-ABD, successfully produced from E. coli, showed low cellular and hemolytic toxicity while displaying potent activities for the amelioration of hyperglycemia as well as non-alcoholic fatty liver disease (NAFLD) in vitro. In animal studies, the estimated plasma half-life of SUMO-3×ESC-ABD was markedly longer (427-fold) than that of the ESC peptide. In virtue of the extended plasma residence, the SUMO-3×ESC-ABD could produce significant anti-hyperglycemic effects that lasted for >2 days, while both the ESC or ESC-ABD peptides elicited little effects. Further, twice-weekly treatment for 10 weeks, the SUMO-3×ESC-ABD displayed significant improvement in blood glucose control with a reduction in body weight. Most importantly, a significant improvement in the conditions of NAFLD was observed in the SUMO-3×ESC-ABD-treated mice. Along the systemic effects (by improved glucose tolerance and body weight reduction), direct inhibition of the hepatocyte lipid uptake was suggested as the major mechanism of the anti-NAFLD effects. Overall, this study demonstrated the utility of the long-acting SUMO-3×ESC-ABD as a potent drug candidate for the treatment of NAFLD.
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Hipoglucemiantes , Enfermedad del Hígado Graso no Alcohólico , Proteínas Recombinantes de Fusión , Animales , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/farmacología , Humanos , Masculino , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Ratones Endogámicos C57BL , Ratones , Glucemia/efectos de los fármacos , Glucemia/análisis , Células Hep G2 , Ingeniería de ProteínasRESUMEN
BACKGROUND: The emergence of immune checkpoint inhibitors, a novel class of immunotherapy drugs, represents a major breakthrough in cancer immunotherapy, substantially improving patient survival post-treatment. Blocking programmed death-ligand 1 (PD-L1) and programmed death protein-1 (PD-1) has demonstrated promising clinical results in various human cancer types. The US FDA has recently permitted only monoclonal antibody (mAb)-based PD-L1 or PD-1 blockers. Although these antibodies exhibit high antitumor efficacy, their size- and affinity-induced side effects limit their applicability. PURPOSE: As small-molecule-based PD-1/PD-L1 blockers capable of reducing the side effects of antibody therapies are needed, this study focuses on exploring natural ingredient-based small molecules that can target hPD-L1/PD-1 using herbal medicines and their components. METHODS: The antitumor potential of evening primrose (Oenothera biennis) root extract (EPRE), a globally utilized traditional herbal medicine, folk remedy, and functional food, was explored. A coculture system was established using human PD-L1-expressed murine MC38 cells (hPD-L1-MC38s) and CD8+ tumor-infiltrating T lymphocytes (CD8+ TILs) expressing humanized PD-1. The in vivo experiments utilized a colorectal cancer (CRC) C57BL/6 J mouse model bearing MC38 cells expressing humanized PD-L1 and PD-1 proteins. RESULTS: EPRE and its active compound oenothein B effectively hindered the molecular interaction between hPD-L1 and hPD-1. EPRE stimulated tumor-specific T lymphocytes of a hPD-L1/PD-1 CRC mice. This action resulted in the elevated infiltration of cytotoxic CD8+T lymphocytes and subsequent tumor growth reduction. Moreover, the combined therapy of oenothein B, a PD-1/PD-L1 blocker, and FOLFOX (5-fluorouracil plus oxaliplatin) cooperatively suppressed hPD-L1-MC38s growth in the ex vivo model through activated CD8+ TIL antitumor immune response. Oenothein B exhibited a high binding affinity for hPD-L1 and hPD-1. We believe that this study is the first to uncover the inhibitory effects of EPRE and its component, oenothein B, on PD-1/PD-L1 interactions. CONCLUSION: This study identified a promising small-molecule candidate from natural products that blocks the hPD-L1/PD-1 signaling pathway. These findings emphasize the potential of EPRE and oenothein B as effective anticancer drugs.