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1.
Wiley Interdiscip Rev RNA ; 15(3): e1851, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38702938

RESUMO

Long noncoding RNAs (lncRNA) are a class of non-coding RNAs greater than 200 bp in length with limited peptide-coding function. The transcription of LINC00152 is derived from chromosome 2p11.2. Many studies prove that LINC00152 influences the progression of various tumors via promoting the tumor cells malignant phenotype, chemoresistance, and immune escape. LINC00152 is regulated by multiple transcription factors and DNA hypomethylation. In addition, LINC00152 participates in the regulation of complex molecular signaling networks through epigenetic regulation, protein interactions, and competitive endogenous RNA (ceRNA). Here, we provide a systematic review of the upstream regulatory factors of LINC00152 expression level in different types of tumors. In addition, we revisit the main functions and mechanisms of LINC00152 as driver oncogene and biomarker in pan-cancer. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Methods > RNA Analyses in Cells RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.


Assuntos
Neoplasias , Oncogenes , RNA Longo não Codificante , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Oncogenes/genética , Regulação Neoplásica da Expressão Gênica
2.
Heliyon ; 10(10): e30528, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38765046

RESUMO

Diagnosing liver disease presents a significant medical challenge in impoverished countries, with over 30 billion individuals succumbing to it each year. Existing models for detecting liver abnormalities suffer from lower accuracy and higher constraint metrics. As a result, there is a pressing need for improved, efficient, and effective liver disease detection methods. To address the limitations of current models, this method introduces a deep liver segmentation and classification system based on a Customized Mask-Region Convolutional Neural Network (cm-RCNN). The process begins with preprocessing the input liver image, which includes Adaptive Histogram Equalization (AHE). AHE helps dehaze the input image, remove color distortion, and apply linear transformations to obtain the preprocessed image. Next, a precise region of interest is segmented from the preprocessed image using a novel deep strategy called cm-RCNN. To enhance segmentation accuracy, the architecture incorporates the ReLU activation function and the modified sigmoid activation function. Subsequently, a variety of features are extracted from the segmented image, including ResNet features, shape features (area, perimeter, approximation, and convex hull), and enhanced median binary pattern. These extracted features are then used to train a hybrid classification model, which incorporates classifiers like SqueezeNet and DeepMaxout models. The final classification outcome is determined by averaging the scores obtained from both classifiers.

3.
J Cancer Res Clin Oncol ; 150(5): 221, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38687357

RESUMO

Vascular endothelial growth factor A (VEGF-A), a highly conserved dimeric glycoprotein, is a key regulatory gene and a marker molecule of angiogenesis. The upregulation of VEGF-A facilitates the process of tumor vascularization, thereby fostering the initiation and progression of malignant neoplasms. Many genes can adjust the angiogenesis of tumors by changing the expression of VEGF-A. In addition, VEGF-A also exhibits immune regulatory properties, which directly or indirectly suppresses the antitumor activity of immune cells. The emergence of VEGF-A-targeted therapy alone or in rational combinations has revolutionized the treatment of various cancers. This review discusses how diverse mechanisms in various tumors regulate VEGF-A expression to promote tumor angiogenesis and the role of VEGF-A in tumor immune microenvironment. The application of drugs targeting VEGF-A in tumor therapy is also summarized including antibody molecule drugs and traditional Chinese medicine.


Assuntos
Terapia de Alvo Molecular , Neoplasias , Neovascularização Patológica , Microambiente Tumoral , Fator A de Crescimento do Endotélio Vascular , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Terapia de Alvo Molecular/métodos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Animais , Regulação Neoplásica da Expressão Gênica , Inibidores da Angiogênese/uso terapêutico
4.
Adv Mater ; 36(21): e2309655, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38517062

RESUMO

Surgery is the standard treatment regimen for resectable colorectal cancer (CRC). However, it is very hard to completely remove all cancer cells in clinical practice, leading to the high recurrence rates of the disease. Moreover, the post-surgery tissue adhesion greatly prevents the possibility of reoperation, significantly limiting the long-term surviving of CRC patients. To overcome CRC recurrence and avoid the post-surgery tissue adhesion, this work develops a novel stimulator of interferon genes "STING" membrane based on the coaxial electrospinning technology and hyaluronic acid modification. A reactive oxygen species responsive prodrug of gambogic acid (GB) and a potent STING agonist (CDN) are coloaded in the core-shell structure of the membrane, which endows the loaded drug with sustained and sequential release patterns. The localized delivery of GB and CDN can selectively induce efficient immunogenic cell death of cancer cells and then evoke the systemic anticancer immunity by activating the Cyclic GMP-AMP (cGAMP) synthase/STING pathway. As-designed "STING" membrane not only safely prevents tumor recurrence through the synergistic chemoimmunotherapy but also efficiently avoids the post-surgery tissue adhesion, facilitating the clinical intervention of CRC.


Assuntos
Neoplasias Colorretais , Proteínas de Membrana , Recidiva Local de Neoplasia , Xantonas , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Animais , Humanos , Proteínas de Membrana/metabolismo , Camundongos , Recidiva Local de Neoplasia/prevenção & controle , Xantonas/química , Xantonas/farmacologia , Linhagem Celular Tumoral , Aderências Teciduais/prevenção & controle , Membranas Artificiais , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Ácido Hialurônico/química
5.
Biosens Bioelectron ; 254: 116233, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38518563

RESUMO

Intracellular microenvironment (viscosity and polarity) and peroxynitrite ions (ONOO-) are involved in maintaining cell morphology, cell function, and signaling so that it is crucial to explore their level changes in vitro and vivo. In this work, we designed and synthesized a mitochondria-targeted fluorescence probe XBL for monitoring the dynamic changes of viscosity, polarity, and ONOO- based on TICT and ICT mechanism. The fluorescence spectra showed obvious changes for polarity at 500 nm as well as ONOO- and viscosity at 660 nm, respectively. The XBL can image simultaneously viscosity, polarity, and ONOO- in cells, and the results showed excess ONOO- leaded to the increase of viscosity in mitochondrial. The ferroptosis process was accompanied by increase of intracellular viscosity and ONOO- levels (or decrease of polarity), which allowed us to better understand the relevant physiological and pathological processes. The XBL can distinguish normal cells and cancerous cells by the fluorescence intensity changes in green and red channels, and image viscosity in inflamed mice. Thus, XBL can provided the chemical tool to understand the physiological and pathological mechanisms of disease by simultaneous detection of viscosity, polarity and ONOO-.


Assuntos
Técnicas Biossensoriais , Corantes Fluorescentes , Camundongos , Animais , Viscosidade , Células RAW 264.7 , Mitocôndrias , Ácido Peroxinitroso
6.
Chem Commun (Camb) ; 60(26): 3469-3483, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38444260

RESUMO

The unique high surface area and tunable cavity size endow metal-organic cages (MOCs) with superior performance and broad application in gas adsorption and separation. Over the past three decades, for instance, numerous MOCs have been widely explored in adsorbing diverse types of gas including energy gases, greenhouse gases, toxic gases, noble gases, etc. To gain a better understanding of the structure-performance relationships, great endeavors have been devoted to ligand design, metal node regulation, active metal site construction, cavity size adjustment, and function-oriented ligand modification, thus opening up routes toward rationally designed MOCs with enhanced capabilities. Focusing on the unveiled structure-performance relationships of MOCs towards target gas molecules, this review consists of two parts, gas adsorption and gas separation, which are discussed separately. Each part discusses the cage assembly process, gas adsorption strategies, host-guest chemistry, and adsorption properties. Finally, we briefly overviewed the challenges and future directions in the rational development of MOC-based sorbents for application in challenging gas adsorption and separation, including the development of high adsorption capacity MOCs oriented by adsorbability and the development of highly selective adsorption MOCs oriented by separation performance.

8.
J Inorg Biochem ; 255: 112523, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38489864

RESUMO

The prevalence of antibiotic-resistant pathogenic bacteria poses a significant threat to public health and ranks among the principal causes of morbidity and mortality worldwide. Antimicrobial photodynamic therapy is an emerging therapeutic technique that has excellent potential to embark upon antibiotic resistance problems. The efficacy of this therapy hinges on the careful selection of suitable photosensitizers (PSs). Transition metal complexes, such as Ruthenium (Ru) and Iridium (Ir), are highly suitable for use as PSs because of their surface plasmonic resonance, crystal structure, optical characteristics, and photonics. These metals belong to the platinum family and exhibit similar chemical behavior due to their partially filled d-shells. Ruthenium and Iridium-based complexes generate reactive oxygen species (ROS), which interact with proteins and DNA to induce cell death. As photodynamic therapeutic agents, these complexes have been widely studied for their efficacy against cancer cells, but their potential for antibacterial activity remains largely unexplored. Our study focuses on exploring the antibacterial photodynamic effect of Ruthenium and Iridium-based complexes against both Gram-positive and Gram-negative bacteria. We aim to provide a comprehensive overview of various types of research in this area, including the structures, synthesis methods, and antibacterial photodynamic applications of these complexes. Our findings will provide valuable insights into the design, development, and modification of PSs to enhance their photodynamic therapeutic effect on bacteria, along with a clear understanding of their mechanism of action.


Assuntos
Complexos de Coordenação , Fotoquimioterapia , Rutênio , Rutênio/farmacologia , Rutênio/química , Irídio/farmacologia , Irídio/química , Antibacterianos/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química
9.
Med Biol Eng Comput ; 62(6): 1733-1749, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38363487

RESUMO

Chronic obstructive pulmonary disease (COPD) is a common lung disease that can lead to restricted airflow and respiratory problems, causing a significant health, economic, and social burden. Detecting the COPD stage can provide a timely warning for prompt intervention in COPD patients. However, existing methods based on inspiratory (IN) and expiratory (EX) chest CT images are not sufficiently accurate and efficient in COPD stage detection. The lung region images are autonomously segmented from IN and EX chest CT images to extract the 1 , 781 × 2 lung radiomics and 13 , 824 × 2 3D CNN features. Furthermore, a strategy for concatenating and selecting features was employed in COPD stage detection based on radiomics and 3D CNN features. Finally, we combine all the radiomics, 3D CNN features, and factor risks (age, gender, and smoking history) to detect the COPD stage based on the Auto-Metric Graph Neural Network (AMGNN). The AMGNN with radiomics and 3D CNN features achieves the best performance at 89.7 % of accuracy, 90.9 % of precision, 89.5 % of F1-score, and 95.8 % of AUC compared to six classic machine learning (ML) classifiers. Our proposed approach demonstrates high accuracy in detecting the stage of COPD using both IN and EX chest CT images. This method can potentially establish an efficient diagnostic tool for patients with COPD. Additionally, we have identified radiomics and 3D CNN as more appropriate biomarkers than Parametric Response Mapping (PRM). Moreover, our findings indicate that expiration yields better results than inspiration in detecting the stage of COPD.


Assuntos
Redes Neurais de Computação , Doença Pulmonar Obstrutiva Crônica , Tomografia Computadorizada por Raios X , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Tomografia Computadorizada por Raios X/métodos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Inalação/fisiologia , Expiração/fisiologia , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Aprendizado de Máquina
10.
Cell Commun Signal ; 22(1): 66, 2024 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-38273373

RESUMO

Tumor immunotherapy, which targets immune checkpoints, presents a promising strategy for the treatment of various cancer types. However, current clinical data indicate challenges in its application to solid tumors. Recent studies have revealed a significant correlation between the degree of immune response in immunotherapy and the tumor microenvironment, particularly with regard to tumor-infiltrating immune cells. Among these immune cells, macrophages, a critical component, are playing an increasingly vital role in tumor immunotherapy. This review focuses on elucidating the role of macrophages within solid tumors and provides an overview of the progress in immunotherapy approaches centered around modulating macrophage responses through various immune factors. Video Abstract.


Assuntos
Neoplasias , Humanos , Neoplasias/patologia , Macrófagos , Imunoterapia , Microambiente Tumoral
11.
Sci Total Environ ; 917: 170526, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38286296

RESUMO

The use of iron-manganese oxide (FMO) as a promising amendment for remediating arsenic (As) contamination in soils has gained attention, but its application is limited owing to agglomeration issues. This study aims to address agglomeration using surfactant-modified FMO and investigate their stabilization behavior towards As and resulting environmental changes upon amendments. The results confirmed the efficacy of surfactants and demonstrated that cetyltrimethylammonium-bromide-modified FMO significantly reduced the leaching concentration of As by 92.5 % and effectively suppressed the uptake of As by 85.8 % compared with the control groups. The ratio of the residual fraction increased from 30.5-41.6 % in unamended soil to 67.9-69.2 %. The number of active sites was through the introduction of surfactants and immobilized As via complexation, ion exchange, and redox reactions. The study also revealed that amendments and the concentration of As influenced the soil physicochemical properties and enriched bacteria associated with As and Fe reduction and changed the distribution of C, N, Fe, and As metabolism genes, which promoted the stabilization of As. The interactions among cetyltrimethylammonium bromide, FMO, and microorganisms were found to have the greatest effect on As immobilization.

12.
J Mater Chem B ; 12(3): 800-813, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38186029

RESUMO

A multifunctional nanoplatform is obtained by modifying copper hexacyanoferrate (Cu-HCF) nanozyme with hyaluronic acid (HA) and further loading platinum (Pt) nanoparticles. This Cu-HCF-HA@Pt platform shows peroxidase-like and glutathione oxidase-like dual-enzyme catalytic activities and photothermal properties, enabling synergistic chemodynamic and photothermal tumor therapy. HA binds to the CD44 receptor, which is highly expressed on the exterior surface of tumor cells, endowing the nanoplatform with tumor specificity. Cu-HCF-HA@Pt catalyzes the decomposition of H2O2 to produce abundant hydroxyl radicals within tumor cells, increasing intracellular oxidative stress levels and inducing tumor cell apoptosis. Meanwhile, Cu-HCF-HA@Pt catalyzes the conversion of intracellular reduced glutathione (GSH) to oxidized glutathione, resulting in GSH exhaustion. The conversion of CuII to CuI in Cu-HCF via a Fenton-like reaction can improve the peroxidase-like property of Cu-HCF-HA@Pt. After the probe is targeted to the tumor site, irradiation by an 808 nm near-infrared laser causes local heating and brings about photothermal tumor apoptosis when reaching 45 °C. The prepared Cu-HCF-HA@Pt combines nanozyme-catalyzed therapy with photothermal therapy to induce apoptosis in tumor cells.


Assuntos
Cobre , Ferrocianetos , Platina , Cobre/farmacologia , Platina/farmacologia , Espécies Reativas de Oxigênio , Peróxido de Hidrogênio , Peroxidase , Peroxidases , Corantes
13.
Mol Ther Oncolytics ; 31: 100747, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38046893

RESUMO

CD47 and its receptor signal regulatory protein α (SIRPα) act as a dominant antiphagocytic, "don't eat me" signal. Recent studies reveal CD24 as a novel target for cancer immunotherapy by macrophages in ovarian cancer and breast cancer. However, whether simultaneous blockade of CD47 and CD24 by a bispecific antibody may result in a potential synergy is still unclear. In the present study, we for the first time designed and developed a bispecific antibody fusion protein, PPAB001 for cotargeting CD47 and CD24. Data demonstrate that simultaneous blockade of CD47/SIRPα and CD24/Siglec-10 signaling by PPAB001 potently promoted macrophage phagocytosis of tumor cells. Compared to single CD47 or CD24 targeting agents, PPAB001 was more effective in inhibiting tumor growth in both mouse 4T-1 syngeneic and human SK-OV-3 xenogeneic tumor models. Mechanistically, we found that PPAB001 therapy markedly increased the proportion of tumor-infiltrating macrophages and upregulated interleukin-6 and tumor necrosis factor-α levels that were representative macrophage inflammatory cytokines. Notably, an increased ratio of M1/M2 in tumor-infiltrating macrophages in the mice treated with PPAB001 suggested that the dual blockade may promote the transition of macrophages from M2 to M1. Taken together, our data supported the development of PPAB001 as a novel immunotherapeutic in the treatment of CD47 and CD24 double-positive cancers.

14.
ACS Omega ; 8(50): 48104-48112, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38144079

RESUMO

Iron (Fe)-loaded biochar has garnered attention for its potential applications in recent years. However, the pyrolysis process of Fe-loaded biochar generates polycyclic aromatic hydrocarbons (PAHs), which can have adverse effects on both human health and the environment. This study explored the correlation between Fe loading and PAH production in Fe-loaded biochar. The results indicate that increasing Fe loading in biochar reduces the PAH concentration, with the most significant decrease observed in naphthalene (0.02-0.08 mg/kg). This reduction can be attributed to the decrease in precursor compounds (e.g., C2H2), substitution of the C=O bond by Fe-O, and a decrease in the dissolved organic matter concentration (3.19-10.76 mg/L) with Fe loading. When Fe loading increased from 0 to 10%, the ecological toxicity of biochar increased by 33.48% due to an elevated production of dibenzo[a,h]anthracene, which poses a significant risk to human health. Therefore, it is imperative to take into consideration the ecological risk of PAHs prior to the application of Fe-loaded biochar. This study presents a comprehensive risk assessment of Fe-loaded biochar and provides valuable insights into the optimization of its production and safe application.

15.
World J Gastrointest Surg ; 15(11): 2513-2524, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38111775

RESUMO

BACKGROUND: Accurate preoperative staging of gastric cancer (GC), a common malignant tumor worldwide, is critical for appropriate treatment plans and prognosis. Dynamic three-phase enhanced computed tomography (CT) scanning for preoperative staging of GC has limitations in evaluating tumor angiogenesis. CD34, a marker on vascular endothelial cell surfaces, is promising in evaluating tumor angiogenesis. We explored the value of their combination for preoperative staging of GC to improve the efficacy and prognosis of patients with GC. AIM: To explore the evaluation value of CD34 expression + dynamic three-phase enhanced CT scanning in preoperative staging of GC. METHODS: Medical records of 106 patients with GC treated at the First People's Hospital of Lianyungang between February 2021 and January 2023 were retrospectively studied. All patients underwent three-phase dynamic contrast-enhanced CT scanning before surgery, and CD34 was detected in gastroscopic biopsy specimens. Using surgical and pathological results as the gold standard, the diagnostic results of three-phase dynamic contrast-enhanced CT scanning at different T and N stages were analyzed, and the expression of CD34-marked microvessel density (MVD) at different T and N stages was determined. The specificity and sensitivity of three-phase dynamic contrast-enhanced CT and CD34 in T and N staging were calculated; those of the combined diagnosis of the two were evaluated in parallel. Independent factors affecting lymph node metastasis were analyzed using multiple logistic regression. RESULTS: The accuracy of three-phase dynamic contrast-enhanced CT scanning in diagnosing stages T1, T2, T3 and T4 were 68.00%, 75.00%, 79.41%, and 73.68%, respectively, and for diagnosing stages N0, N1, N2, and N3 were 75.68%, 74.07%, 85.00%, and 77.27%, respectively. CD34-marked MVD expression increased with increasing T and N stages. Specificity and sensitivity of three-phase dynamic contrast-enhanced CT in T staging were 86.79% and 88.68%; for N staging, 89.06% and 92.86%; for CD34 in T staging, 64.15% and 88.68%; and for CD34 in N staging, 84.38% and 78.57%, respectively. Specificity and sensitivity of joint diagnosis in T staging were 55.68% and 98.72%, and N staging were 75.15% and 98.47%, respectively, with the area under the curve for diagnosis improving accordingly. According to multivariate analysis, a longer tumor diameter, higher pathological T stage, lower differentiation degree, and higher expression of CD34-marked MVD were independent risk factors for lymph node metastasis in patients with GC. CONCLUSION: With high accuracy in preoperatively determining the invasion depth and lymph node metastasis of GC, CD34 expression and three-phase dynamic contrast-enhanced CT can provide a reliable basis for surgical resection.

16.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(5): 1024-1029, 2023 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-37866963

RESUMO

Objective: To investigate the relationship between thrombin-antithrombin complex (TAT), plasmin-α 2-plasmininhibitor complex (PIC), soluble thrombomodulin (sTM), and tissue plasminogen activator-inhibitor complex (tPAIC) and postoperative complications in the early stage after liver transplantation (LT). Methods: We analyzed the perioperative clinical data, including plasma TAT, PIC, sTM, and tPAIC, of 130 post-LT patients admitted to the intensive care unit (ICU), West China Hospital, Sichuan University between December 2021 and November 2022. Patients were divided into two groups, a complication group and a non-complication group, according to whether they experienced complications of Clavien-Dindo (CD) grade Ⅲb and above within 30 days after the surgery. Univariate analysis and binary multivariate logistic regression models were used to determine the risk factors for complications within 30 days post-LT. Results: The incidence of complications of CD grade Ⅲb and above within 30 days post-LT was 33.1% (43/130). Patients in the complication group had significantly higher scores for the Model for End-Stage Liver Disease (MELD), operative time, intraoperative red blood cell transfusion volume, intraoperative plasma transfusion volume, and plasma TAT, PIC, sTM and tPAIC measured at the time of admission to ICU after the operation than those in the non-complication group did (all P<0.05). Logistic regression showed that for every single U of red blood cells transfused during the transplant surgery, the probabilities of complications within 30 days post-LT increased by 15.1% (95% confidence interval [ C I]: 1.070-1.239, P<0.001) and for the increase of every single TU/mL of plasma sTM measured upon post-LT admission to ICU, the probabilities of complications increased by 13.7% (95% CI: 1.060-1.220, P<0.001). Conclusion: Plasma sTM measured upon admission to ICU after LT is an independent risk factor for complications within 30 days post-LT, and additional assessment of sTM may help predict complications in the early stage post-LT.


Assuntos
Doença Hepática Terminal , Transplante de Fígado , Humanos , Ativador de Plasminogênio Tecidual , Transplante de Fígado/efeitos adversos , Transfusão de Componentes Sanguíneos , Doença Hepática Terminal/etiologia , Índice de Gravidade de Doença , Plasma , Fatores de Risco , Estudos Retrospectivos
17.
J Cancer Res Clin Oncol ; 149(17): 16239-16246, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37676267

RESUMO

Hypopharyngeal cancer (HPC) has one of the most unfavorable prognoses among head and neck squamous cell carcinomas. Immunotherapy in combination with chemotherapy, the same as conventional induction chemotherapy, has emerged as a vital part of the induction therapy protocol for HPC. Meanwhile, the incidence of immune-related adverse events is increasing. In this light, we present the first reported case of immune-associated encephalitis in a patient with hypopharyngeal cancer treated with Camrelizumab (a PD-1 inhibitor). After receiving immunotherapy combined with chemotherapy as induction therapy, along with concurrent chemoradiotherapy, the patient presented with symptoms of fatigue, tremors, drowsiness, and an abnormal signal in the right temporal lobe as shown on a brain magnetic resonance imaging (MRI). Despite the minor elevation in protein and IgG index observed in the lumbar puncture, there is no evidence of abnormal autoantibodies or evidence of pathogenic infection. Following a thorough multidisciplinary consultation, the patient is suspected to be afflicted with immune-related autoimmune encephalitis. Intravenous methylprednisolone was prescribed as an empirical treatment at an initial dosage of 120 mg/day for 3 days, followed by steroid tapering. Finally, the patient experienced complete neurologic and radiographic (brain MRI) recovery. This case serves as a critical reminder that encephalitis is a potential diagnosis that should never be overlooked in patients undergoing immunotherapy who present with abnormal signs of the brain. The timely diagnosis and initiation of immunosuppressive therapy are key components of treating ICI-associated encephalitis.


Assuntos
Encefalite , Neoplasias Hipofaríngeas , Humanos , Nivolumabe , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Hipofaríngeas/tratamento farmacológico , Hipofaringe/patologia , Encefalite/induzido quimicamente , Encefalite/patologia
18.
Dalton Trans ; 52(35): 12478-12489, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37602756

RESUMO

Ruthenium(II) polypyridyl complexes have drawn growing attention due to their photophysical properties and anticancer activity. Herein we report four ruthenium(II) polypyridyl complexes [(N^N)2RuII(L)]2+ (1-4, L = 4-anilinoquinazoline derivatives, N^N = bidentate ligands with bis-nitrogen donors) as multi-functional anticancer agents. The epidermal growth factor receptor (EGFR) is overexpressed in a broad range of cancer cells and related to many kinds of malignance. EGFR inhibitors, such as gefitinib and erlotinib, have been approved as clinical anticancer drugs. The EGFR-inhibiting 4-anilinoquinazoline ligands greatly enhanced the in vitro anticancer activity of these ruthenium(II) polypyridyl complexes against a series of human cancer cell lines compared to [Ru(bpy)2(phen)], but interestingly, these complexes were actually not potent EGFR inhibitors. Further mechanism studies revealed that upon irradiation with visible light, complexes 3 and 4 generated a high level of singlet oxygen (1O2), and their in vitro anticancer activities against human non-small-cell lung (A549), cervical (HeLa) and squamous (A431) cancer cells were significantly improved. Specifically, complex 3 displayed potent phototoxicity upon irradiation with blue light, of which the photo-toxicity indexes (PIs) against HeLa and A431 cells were 11 and 8.3, respectively. These complexes exhibited strong fluorescence emission at ca. 600 nm upon excitation at about 450 nm. A subcellular distribution study by fluorescence microscopy imaging and secondary ion mass spectrometry imaging (ToF-SIMS) demonstrated that complex 3 mainly localized at the cytoplasm and complex 4 mainly localized in the nuclei of cells. Competitive binding with ctDNA showed that complex 4 was more favorable to bind to the DNA minor groove than complex 3. These differences support that complex 3 possibly exerts its anticancer activities majorly by photo-induced 1O2 generation and complex 4 by binding to DNA.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Rutênio , Humanos , Ligantes , Luz , Receptores ErbB
19.
Anal Methods ; 15(35): 4524-4532, 2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37622388

RESUMO

A novel magnetic agitating heater powered by a USB port has been developed and applied to synthesize silver colloid substrate for surface-enhanced Raman scattering (SERS) detection of sodium saccharin content on the tipping paper of cigarettes. The heater device allows the convenient synthesis of the Ag colloid, and the reaction can be completed on-site in 15 min under mild conditions. The on-site synthesis of SERS substrate effectively avoided the need for storage and concerns regarding the poor stability and short lifespan of colloid substrates. The results demonstrated that the substrate obtained with the device could achieve SERS detection of Rhodamine 6G (R6G) at as low as 10-9 mol L-1 while maintaining a stable intensity with a relative standard deviation (RSD) of 5.52% (n = 5). Using the prepared substrate at the optimal conditions, the limit of detection of sodium saccharin (SS) was 1 mg L-1. By introducing an internal standard KSCN, a linear relationship was observed between the relative intensity at 708 cm-1 and the concentration of the SS in a range of 20-100 mg L-1 (R2 = 0.98). With the developed method, SS was directly extracted from the cigarette paper by immersing it in water, and the extracted solution was subsequently detected. The quantitative spike-recoveries were in the range of 95.5-116.7%, with RSD between 2.3-12.6%. The whole detection procedure including the on-site substrate preparation, took only about 30 min. This work opens new avenues for colloidal synthesis, and the detection method of SS on the cigarette paper also holds great promise in food safety applications.

20.
J Intensive Care ; 11(1): 29, 2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37408020

RESUMO

BACKGROUND: A unified clinical definition of feeding intolerance (FI) is urged for better management of enteral nutrition (EN) in critically ill patients. We aimed to identify optimum clinical FI definitions based on reported evidence. METHODS: We searched clinical studies comparing FI with non-FI with a clear definition, summarized the evidence by random-effect meta-analyses, and rated the certainty of evidence by the Grading of Recommendations Assessment, Development and Evaluation frameworks. RESULTS: Five thousand five hundred twenty-five records were identified, of which 26 eligible studies enrolled 25,189 adult patients. Most patient-centered outcomes were associated with FI overall. Low to very low certainty evidence established FI defined as large gastric residual volume (GRV) ≥ 250 ± 50 mL combined with any other gastrointestinal symptoms (GIS) had a significant association with high mortalities in particular all-cause hospital mortality (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.40-2.57), the incidence of pneumonia (OR 1.54, 95% CI 1.13-2.09) and prolonged length of hospital stay (mean difference 4.20, 95% CI 2.08-6.32), with a moderate hospital prevalence (41.49%, 95% CI 31.61-51.38%). 3-day enteral feeding (EF) delivered percentage < 80% had a moderate hospital prevalence (38.23%, 95% CI 24.88-51.58) but a marginally significant association with all-cause hospital mortality (OR 1.90, 95% CI 1.03-3.50). CONCLUSIONS: In critically ill adult patients receiving EN, the large-GRV-centered GIS to define FI seemed to be superior to 3-day EF-insufficiency in terms of both close associations with all-cause hospital mortality and acceptable hospital prevalence (Registered PROSPERO: CRD42022326273). TRIAL REGISTRATION: The protocol for this review and meta-analysis was registered with PROSPERO: CRD42022326273. Registered 10 May 2022.

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