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1.
J Cell Mol Med ; 28(8): e18265, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38534098

RESUMO

Mitochondria and their related genes (MTRGs) are pivotal in the tumour microenvironment (TME) of cervical cancer, influencing prognosis and treatment response. This study developed a prognostic model using MTRGs to predict overall survival (OS) in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), aiming for personalized therapy. Analysing 14 MTRGs like ISCU and NDUFA11 through techniques such as univariate Cox regression, we found that a low mitochondrial (MT) score is associated with better survival, while a high MT score predicts poorer outcomes. The TME score, particularly influenced by CD8 T cells, also correlates with prognosis, with a high score indicating favourable outcomes. The interplay between MT and TME subtypes revealed that the best prognosis is seen in patients with a low MT and high TME score. Our findings highlight the role of MTRGs as potential biomarkers and therapeutic targets in cervical cancer, offering a novel approach to improving patient outcomes through a more nuanced understanding of mitochondrial function and immune interactions within the TME. This model presents a promising avenue for enhancing the precision of prognostic assessments in CESC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias do Colo do Útero , Humanos , Feminino , Microambiente Tumoral , Mitocôndrias , DNA Mitocondrial
2.
Cancer Immunol Immunother ; 73(9): 179, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38960949

RESUMO

Adoptive cellular therapy (ACT) using memory-like (ML) natural killer (NK) cells, generated through overnight ex vivo activation with IL-12, IL-15, and IL-18, has shown promise for treating hematologic malignancies. We recently reported that a multifunctional fusion molecule, HCW9201, comprising IL-12, IL-15, and IL-18 domains could replace individual cytokines for priming human ML NK cell programming ("Prime" step). However, this approach does not include ex vivo expansion, thereby limiting the ability to test different doses and schedules. Here, we report the design and generation of a multifunctional fusion molecule, HCW9206, consisting of human IL-7, IL-15, and IL-21 cytokines. We observed > 300-fold expansion for HCW9201-primed human NK cells cultured for 14 days with HCW9206 and HCW9101, an IgG1 antibody, recognizing the scaffold domain of HCW9206 ("Expand" step). This expansion was dependent on both HCW9206 cytokines and interactions of the IgG1 mAb with CD16 receptors on NK cells. The resulting "Prime and Expand" ML NK cells exhibited elevated metabolic capacity, stable epigenetic IFNG promoter demethylation, enhanced antitumor activity in vitro and in vivo, and superior persistence in NSG mice. Thus, the "Prime and Expand" strategy represents a simple feeder cell-free approach to streamline manufacturing of clinical-grade ML NK cells to support multidose and off-the-shelf ACT.


Assuntos
Memória Imunológica , Células Matadoras Naturais , Proteínas Recombinantes de Fusão , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Humanos , Animais , Proteínas Recombinantes de Fusão/genética , Camundongos , Terapia Baseada em Transplante de Células e Tecidos/métodos , Imunoterapia Adotiva/métodos , Interleucina-15/metabolismo
3.
Heart Fail Rev ; 29(4): 751-768, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38498262

RESUMO

Heart failure (HF) can be caused by a variety of causes characterized by abnormal myocardial systole and diastole. Ca2+ current through the L-type calcium channel (LTCC) on the membrane is the initial trigger signal for a cardiac cycle. Declined systole and diastole in HF are associated with dysfunction of myocardial Ca2+ function. This disorder can be correlated with unbalanced levels of phosphorylation / dephosphorylation of LTCC, endoplasmic reticulum (ER), and myofilament. Kinase and phosphatase activity changes along with HF progress, resulting in phased changes in the degree of phosphorylation / dephosphorylation. It is important to realize the phosphorylation / dephosphorylation differences between a normal and a failing heart. This review focuses on phosphorylation / dephosphorylation changes in the progression of HF and summarizes the effects of phosphorylation / dephosphorylation of LTCC, ER function, and myofilament function in normal conditions and HF based on previous experiments and clinical research. Also, we summarize current therapeutic methods based on abnormal phosphorylation / dephosphorylation and clarify potential therapeutic directions.


Assuntos
Cálcio , Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Fosforilação , Cálcio/metabolismo , Canais de Cálcio Tipo L/metabolismo , Retículo Endoplasmático/metabolismo , Miocárdio/metabolismo , Miofibrilas/metabolismo
4.
BMC Cancer ; 24(1): 742, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890585

RESUMO

BACKGROUND: Nasopharyngeal adenoid cystic carcinoma (NACC) is a relatively rare salivary gland tumor that is generally associated with poor outcomes. High-dose radiotherapy is a key treatment for patients with NACC. This study reported the long-term efficacy and safety of particle beam radiation therapy (PBRT) for NACC. METHODS AND MATERIALS: Twenty-six patients with nonmetastatic NACC who received definitive PBRT alone were included in this retrospective study. The majority of patients (92.3%) had locally advanced disease. Twenty-five (96.15%) patients received intensity-modulated proton radiotherapy (IMPT) followed by a carbon ion radiotherapy (CIRT) boost, and one patient received CIRT alone. Overall survival (OS), local control (LC), regional control (RC), and distant metastasis control (DMC) rates were calculated via the Kaplan-Meier method. RESULTS: The median follow-up time was 46.95 months for the entire cohort. Seven patients experienced local recurrence, and one patient experience neck lymph node recurrence. The 3- and 4-year OS, LC, RC, and DMC rates were 100% and 91.7%, 92.3% and 84.6%, 95.8% and 87.8%, and 90.2% and 71.3%, respectively. A total of 91.3% of the patients achieved complete remission of gross tumors at 1 year after PBRT. Severe acute toxicity was observed in only two patients. A grade 4 decrease in visual acuity was observed in one patient with orbital apex invasion. No late grade 3 or 5 toxicity was observed. CONCLUSION: Definitive PBRT provided a satisfactory 4-year OS for patients with locally advanced NACC. The toxicity was acceptable and mild. Further follow-up is necessary to confirm the efficacy and safety of definitive PBRT for patients with NACC.


Assuntos
Carcinoma Adenoide Cístico , Neoplasias Nasofaríngeas , Terapia com Prótons , Humanos , Carcinoma Adenoide Cístico/radioterapia , Carcinoma Adenoide Cístico/mortalidade , Carcinoma Adenoide Cístico/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Adulto , Estudos Retrospectivos , Resultado do Tratamento , Idoso , Terapia com Prótons/efeitos adversos , Terapia com Prótons/métodos , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Adulto Jovem , Seguimentos , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Recidiva Local de Neoplasia/radioterapia , Radioterapia com Íons Pesados/efeitos adversos , Radioterapia com Íons Pesados/métodos
5.
Molecules ; 29(5)2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38474689

RESUMO

Hollow silica spheres have been widely studied for drug delivery because of their excellent biosecurity and high porosity. However, difficulties with degradation in the tumor microenvironment (TME) and premature leaking during drug delivery limit their clinical applications. To alleviate these problems, herein, hollow organosilica spheres (HOS) were initially prepared using a "selective etching strategy" and loaded with a photothermal drug: new indocyanine green (IR820). Then, the Cu2+-tannic acid complex (Cu-TA) was deposited on the surface of the HOS, and a new nanoplatform named HOS@IR820@Cu-TA (HICT) was finally obtained. The deposition of Cu-TA can gate the pores of HOS completely to prevent the leakage of IR820 and significantly enhance the loading capacity of HOS. Once in the mildly acidic TME, the HOS and outer Cu-TA decompose quickly in response, resulting in the release of Cu2+ and IR820. The released Cu2+ can react with the endogenous glutathione (GSH) to consume it and produce Cu+, leading to the enhanced production of highly toxic ·OH through a Fenton-like reaction due to the overexpressed H2O2 in the TME. Meanwhile, the ·OH generation was remarkably enhanced by the NIR light-responsive photothermal effect of IR820. These collective properties of HICT enable it to be a smart nanomedicine for dually enhanced chemodynamic therapy through GSH depletions and NIR light-triggered photothermal effects.


Assuntos
Complexos de Coordenação , Nanopartículas , Neoplasias , Polifenóis , Humanos , Peróxido de Hidrogênio , Sistemas de Liberação de Medicamentos , Glutationa , Microambiente Tumoral , Linhagem Celular Tumoral
6.
J Cell Mol Med ; 27(9): 1239-1249, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36977201

RESUMO

Although similar to trunk and limb skeletal muscles, masticatory muscles are believed as unique in both developmental origins and myogenesis. Gαi2 has been demonstrated to promote muscle hypertrophy and muscle satellite cell differentiation in limb muscles. However, the effect of Gαi2 on masticatory muscles is still unexplored. This study aimed to identify the role of Gαi2 in the proliferation and differentiation of masticatory muscle satellite cells, further exploring the metabolic mechanism of masticatory muscles. The proliferation rate, myotube size, fusion index of masticatory muscle satellite cells and Pax7, Myf5, MyoD, Tcf21 and Musculin expressions were significantly decreased by Gαi2 knockdown, while in cells infected with AdV4-Gαi2, the proliferation rate, myotube size, fusion index and Tbx1 expression were significantly increased. Masticatory muscle satellite cells also displayed phenotype transformation as Gαi2 changed. In addition, Gαi2 altered myosin heavy chain (MyHC) isoforms of myotubes with less MyHC-2A expression in siGαi2 group and more MyHC-slow expression in AdV4-Gαi2 group. In conclusion, Gαi2 could positively affect the adult myogenesis of masticatory muscle satellite cells and maintain the superiority of MyHC-slow. Masticatory muscle satellite cells may have their unique Gαi2-regulated myogenic transcriptional networks, although they may share some common characteristics with trunk and limb muscles.


Assuntos
Células Satélites de Músculo Esquelético , Células Satélites de Músculo Esquelético/metabolismo , Células Cultivadas , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Cadeias Pesadas de Miosina/genética , Diferenciação Celular/genética , Desenvolvimento Muscular/genética
7.
Cancer Sci ; 114(1): 105-114, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36114749

RESUMO

Lung cancer is one of the leading causes of death among cancer patients worldwide. Carbon-ion radiotherapy is a radical nonsurgical treatment with high local control rates and no serious adverse events. N6-methyladenosine (m6A) modification is one of the most common chemical modifications in eukaryotic messenger RNA (mRNA) and has important effects on the stability, splicing, and translation of mRNAs. Recently, the regulatory role of m6A in tumorigenesis has been recognized more and more. However, the dysregulation of m6A and its role in carbon-ion radiotherapy of non-small-cell lung cancer (NSCLC) remains unclear. In this study, we found that the level of methyltransferase-like 3 (METTL3) and its mediated m6A modification were elevated in NSCLC cells with carbon-ion radiotherapy. Knockdown of METTL3 in NSCLC cells impaired proliferation, migration, and invasion in vitro and in vivo. Moreover, we found that METTL3-mediated m6A modification of mRNA inhibited the decay of H2A histone family member X (H2AX) mRNA and enhanced its expression, which led to enhanced DNA damage repair and cell survival.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Metiltransferases/genética , Metiltransferases/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , Carbono
8.
Cancer Immunol Immunother ; 72(12): 4077-4088, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37777634

RESUMO

Carbon ion radiotherapy (CIRT) may yield satisfactory clinical outcomes for patients who are resistant to radiotherapy. However, the therapeutic impact of carbon ions is still limited in certain recurring or refractory tumors. Therefore, we aimed to evaluate the synergistic anti-tumor effects of immune checkpoint inhibitors (ICIs) in combination with CIRT. We then explored the involvement of ferroptosis in a preliminary investigation. A tumor-bearing mouse model was established, and mice were inoculated subcutaneously with B16-OVA cells into the flanks of both hind legs. Mice were assigned to four groups to receive CIRT, ICIs, or combined treatment. Thereafter, we conducted transcriptome sequencing (RNA-seq), bioinformatics analysis, and various immune-related experiments on the available tumor tissues to investigate differences in the synergistic anticancer effects and potential mechanisms across the groups. The combination therapies significantly improved the survival of mice and inhibited tumor growth, both at local and distant sites. Based on bioinformatics and RNA-seq data, immune-related pathways and genes, immune cell infiltration, and the production of cytokines and chemokines were the most enhanced in the combined treatment group compared to other groups. Finally, we identified a potential role for ferroptosis in the development of local anti-tumor synergy during CIRT combination treatment. In conclusion, this study showed that CIRT and ICIs can enhance the anti-tumor immune effects. We also proposed that ferroptosis may induce anti-tumor effects in CIRT combination therapy, offering a unique perspective on its ability to enhance immunotherapy responses.


Assuntos
Ferroptose , Radioterapia com Íons Pesados , Humanos , Recidiva Local de Neoplasia/patologia , Terapia Combinada , Imunoterapia
9.
J Neurooncol ; 162(3): 503-514, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36583815

RESUMO

PURPOSE: According to the presence or absence of isocitrate dehydrogenase (IDH) mutation, the 2021 WHO classification system bisected diffuse gliomas into IDH-mutant tumors and IDH-wildtype tumors. This study was aimed to evaluate the outcomes of proton radiotherapy treating IDH-mutant diffuse gliomas. PATIENTS AND METHODS: Between May 2015 and May 2022, a total of 52 consecutive patients with IDH-mutant diffuse gliomas were treated at Shanghai Proton and Heavy Ion Center. Tumor histologies were 33 cases of astrocytoma and 19 cases of oligodendroglioma. Tumor classified by WHO grade 2, 3 and 4 were 22, 25, and 5 cases, respectively. All 22 patients with WHO grade 2 tumors and one patient with brain stem WHO grade 4 tumor were irradiated with 54GyE. The other 29 patients with WHO grade 3 and 4 tumors were irradiated with 60GyE. Temozolomide was recommended to all patients, and was eventually conducted in 50 patients. RESULTS: The median follow-up time was 21.7 months. The 12/24-month progression-free survival (PFS) and overall survival (OS) rates for the entire cohort were 97.6%/78.4% and 100%/91.0% group. Examined by both univariate and multivariate analysis, WHO grade of tumor were of the most significant impact for both PFS and OS. No severe acute toxicity (grade 3 or above) was found. In terms of late toxicity, grade 3 radio-necrosis was developed in one case of oligodendroglioma, WHO grade 3. CONCLUSION: Proton radiotherapy produced a favorable outcome with acceptable adverse-effects in patients with IDH-mutant diffuse gliomas.


Assuntos
Neoplasias do Tronco Encefálico , Glioma , Íons Pesados , Oligodendroglioma , Humanos , Isocitrato Desidrogenase/genética , Prótons , China , Glioma/genética , Glioma/radioterapia , Glioma/patologia
10.
J Neurooncol ; 165(2): 241-250, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37976030

RESUMO

PURPOSE: To investigate the efficacy and safety of particle beam radiotherapy (PBRT) in the management of patients with WHO grade 2 and 3 meningiomas. METHODS: Thirty-six consecutive and non-selected patients with WHO grade 2 (n = 28) and grade 3 (n = 8) meningiomas were treated at the Shanghai Proton and Heavy Ion Center, from May 2015 to March 2022. The median age of the cohort at PBRT was 48 years. There were 25 and 11 patients treated with PBRT in the setting of newly diagnosed diseases and progressive/recurrent diseases, respectively. PBRT was utilized as re-irradiation in 5 patients. Proton radiotherapy (PRT) and carbon-ion radiotherapy (CIRT), with a median dose of 60 Gy-Equivalent (GyE), were provided to 30 and 6 patients, respectively. RESULTS: With a median follow-up of 23.3 months, the local control rates were 92.0%, 82.0%, and 82.0% at 1, 2, and 3 years for the entire cohort, respectively. Patients with WHO grade 2 meningiomas (100%, 94.1%, 94,1% at 1,2,3 years) had a much better local control than those with WHO grade 3 meningiomas (50%, 25%, 25% at 1,2,3 years; P < 0.001). Three patients, all with WHO grade 3 meningiomas, had deceased at the time of this analysis. Multivariate analyses revealed that WHO grade (grade 2 vs. 3) (p = 0.016) was a significant prognosticator for local control. No severe toxicities (G3 or above) were observed. CONCLUSIONS: Treatment-induced efficacy and toxicities to PBRT in WHO grade 2 and 3 meningiomas were both highly acceptable. Longer follow-up is needed to evaluate the long-term outcome in terms of disease control, survival, as well as potential late effects.


Assuntos
Íons Pesados , Neoplasias Meníngeas , Meningioma , Terapia com Prótons , Humanos , Pessoa de Meia-Idade , Prótons , Terapia com Prótons/efeitos adversos , China/epidemiologia , Organização Mundial da Saúde , Recidiva Local de Neoplasia/radioterapia
11.
Mol Ther ; 30(3): 1171-1187, 2022 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-35051615

RESUMO

Therapy induced senescence (TIS) in tumors and TIS cancer cells secrete proinflammatory senescence-associated secretory phenotype (SASP) factors. SASP factors promote TIS cancer cells to re-enter the growth cycle with stemness characteristics, resulting in chemo-resistance and disease relapse. Herein, we show that the immunotherapeutic HCW9218, comprising transforming growth factor-ß (TGF-ß) receptor II and interleukin (IL)-15/IL-15 receptor α domains, enhances metabolic and cytotoxic activities of immune cells and reduces TIS tumor cells in vivo to improve the efficacy of docetaxel and gemcitabine plus nab-paclitaxel against B16F10 melanoma and SW1990 pancreatic tumors, respectively. Mechanistically, HCW9218 treatment reduces the immunosuppressive tumor microenvironment and enhances immune cell infiltration and cytotoxicity in the tumors to eliminate TIS cancer cells. Immuno-depletion analysis suggests that HCW9218-activated natural killer cells play a pivotal role in TIS cancer cell removal. HCW9218 treatment following docetaxel chemotherapy further enhances efficacy of tumor antigen-specific and anti-programmed death-ligand 1 (PD-L1) antibodies in B16F10 tumor-bearing mice. We also show that HCW9218 treatment decreases TIS cells and lowers SASP factors in off-target tissues caused by chemotherapy of tumor-bearing mice. Collectively, HCW9218 has the potential to significantly enhance anti-tumor efficacy of chemotherapy, therapeutic antibodies, and checkpoint blockade by eliminating TIS cancer cells while reducing TIS-mediated proinflammatory side effects in normal tissues.


Assuntos
Antígeno B7-H1 , Células Matadoras Naturais , Animais , Antígeno B7-H1/metabolismo , Linhagem Celular Tumoral , Senescência Celular , Docetaxel/metabolismo , Docetaxel/farmacologia , Imunoterapia/métodos , Células Matadoras Naturais/metabolismo , Camundongos , Microambiente Tumoral
12.
Plant Dis ; 107(4): 1027-1034, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36096101

RESUMO

On a global basis, potato cyst nematodes (Globodera spp. Skarbilovich 1959 [Behrens 1975]) are one of the most serious soilborne pathogens in potato (Solanum tuberosum L.) production. In 2019 to 2020, 188 soil samples were taken from rhizosphere soil associated with the roots of stunted and chlorotic potato plants in the main potato-growing areas of Yunnan and Sichuan Provinces of China. Globodera rostochiensis Wollenweber 1923 (Skarbilovich 1959) was recovered from 112 of the samples. Nematode identification was as confirmed by morphometric, light microscopy, electron microscopy, and molecular methodologies. Population densities of G. rostochiensis ranged from 47.0 to 69.0 eggs/g of soil. A BLASTn homology search program was used to compare the sequences of populations of G. rostrochienses from Yunnan and Sichuan Provinces with populations of other Heteroderinae spp. and populations of G. rostochiensis from other nations. Although potato has been grown in China for at least 400 years and the nation produces more potato than any other country, potato cyst nematodes were not reported in China until 2022.


Assuntos
Nematoides , Solanum tuberosum , Animais , China , Solo
13.
Plant J ; 105(3): 800-815, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33179343

RESUMO

Caleosins constitute a small protein family with one calcium-binding EF-hand motif. They are involved in the regulation of development and response to abiotic stress in plants. Nevertheless, how they impact salt stress tolerance in rice is largely unknown. Thereby, biochemical and molecular genetic experiments were carried out, and the results revealed that OsClo5 was able to bind calcium and phospholipids in vitro and localized in the nucleus and endoplasmic reticulum in rice protoplasts. At the germination and early seedlings stages, overexpression transgenic lines and T-DNA mutant lines exhibited reduced and increased tolerance to salt stress, respectively, compared with the wild-type. Yeast two-hybrid, bimolecular fluorescence complementation and in vitro pull-down assays demonstrated that the EF-hand motif of OsClo5 was essential for the interactions with itself and OsDi19-5. Yeast one-hybrid, electrophoretic migration shift and dual-luciferase reporter assays identified OsDi19-5 as a transcriptional repressor via the TACART cis-element in the promoters of two salt stress-related target genes, OsUSP and OsMST. In addition, OsClo5 enhanced the inhibitory effect of OsDi19-5 in the tobacco transient system, which was confirmed by qRT-PCR analysis in rice seedlings under salt stress. The collective results deepen the understanding of the molecular mechanism underlying the roles of caleosin in the salt stress response. These findings will also inform efforts to improve salt tolerance of rice.


Assuntos
Oryza/fisiologia , Proteínas de Plantas/genética , Tolerância ao Sal/fisiologia , Ácido Abscísico/farmacologia , Motivos de Aminoácidos , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Regulação da Expressão Gênica de Plantas , Germinação , Oryza/efeitos dos fármacos , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Plântula/fisiologia , Estresse Fisiológico/fisiologia , Nicotiana/genética
14.
Mol Ther ; 29(10): 2949-2962, 2021 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-34091051

RESUMO

Advances in immunostimulatory and anti-immunosuppressive therapeutics have revolutionized cancer treatment. However, novel immunotherapeutics with these dual functions are not frequently reported. Here we describe the creation of a heterodimeric bifunctional fusion molecule, HCW9218, constructed using our soluble tissue factor (TF)-based scaffold technology. This complex comprises extracellular domains of the human transforming growth factor-ß (TGF-ß) receptor II and a human interleukin-15 (IL-15)/IL-15 receptor α complex. HCW9218 can be readily expressed in CHO cells and purified using antibody-based affinity chromatography in a large-scale manufacturing setting. HCW9218 potently activates mouse natural killer (NK) cells and CD8+ T cells in vitro and in vivo to enhance cell proliferation, metabolism, and antitumor cytotoxic activities. Similarly, human immune cells become activated with increased cytotoxicity following incubation with HCW9218. This fusion complex also exhibits TGF-ß neutralizing activity in vitro and sequesters plasma TGF-ß in vivo. In a syngeneic B16F10 melanoma model, HCW9218 displayed strong antitumor activity mediated by NK cells and CD8+ T cells and increased their infiltration into tumors. Repeat-dose subcutaneous administration of HCW9218 was well tolerated by mice, with a half-life sufficient to provide long-lasting biological activity. Thus, HCW9218 may serve as a novel therapeutic to simultaneously provide immunostimulation and lessen immunosuppression associated with tumors.


Assuntos
Linfócitos T CD8-Positivos/metabolismo , Interleucina-15/genética , Células Matadoras Naturais/metabolismo , Melanoma Experimental/tratamento farmacológico , Receptor do Fator de Crescimento Transformador beta Tipo II/química , Receptores de Interleucina-15/genética , Proteínas Recombinantes de Fusão/administração & dosagem , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Injeções Subcutâneas , Interleucina-15/metabolismo , Melanoma Experimental/imunologia , Camundongos , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Receptor do Fator de Crescimento Transformador beta Tipo II/metabolismo , Receptores de Interleucina-15/metabolismo , Proteínas Recombinantes de Fusão/farmacologia , Fator de Crescimento Transformador beta/sangue , Fator de Crescimento Transformador beta/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
15.
J Assist Reprod Genet ; 39(2): 493-504, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35094183

RESUMO

PURPOSE: This study aimed to explore the perceived changes in sexual behaviour during COVID-19 lockdown, anxiety symptoms, and couple relationship of patients with infertility. METHODS: We performed an observational cross-sectional study between 20 November 2020 and 15 January 2021. We used stratified analysis of different stress levels and Quality of Marriage Index (QMI) scores to compare the perceived changes in sexual behaviour, anxiety symptoms, and couple relationship. The logistic regression model was performed to assess factors correlated with couples' relationship quality during the lockdown. Furthermore, we performed pathway analyses to assess whether the changes in sexual behaviour, stress level, or psychological anxiety during the lockdown could predict the quality of couple relationship. RESULTS: A total of 940 patients with infertility were included in this study. When we conducted a stratified analysis of the participants, significant differences were found between the changes in their sexual behaviour, stress levels, and couple relationship quality. The logistic regression model showed that sex, anxiety symptoms, decreased sexual satisfaction, sexual activity frequency, and income levels were closely related to couple relationship quality. Pathway analyses indicated that changes in their sexual behaviour, anxiety symptoms, and stress levels could all predict the quality of couple relationship. CONCLUSIONS: The perceived changes in sexual behaviour with different stress levels and couple relationship quality showed significant differences. Analysing the related factors that affect the quality of couple relationship, especially in times of crisis, is of great significance as this information can contribute to the improvement of treatment for patients with infertility.


Assuntos
COVID-19 , Infertilidade , Ansiedade/epidemiologia , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Estudos Transversais , Humanos , Infertilidade/terapia , Comportamento Sexual/psicologia
16.
Clin Oral Investig ; 26(9): 5625-5642, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35786783

RESUMO

OBJECTIVES: The purpose of this systematic review was to compare the accuracy of digital and conventional full-arch impressions in vivo. MATERIALS AND METHODS: This systematic review was conducted according to the PRISMA and registered at the PROSPERO (CRD42021232736). Electronic and hand searches were performed to identify in vivo studies comparing the linear or 3D accuracy of digital and conventional impressions. The risk of bias (ROB) of included studies was assessed by QUADAS-2, and the overall quality of evidence was assessed by GRADE. RESULTS: Twenty-two studies met the inclusion criteria, and 13 studies were included in the meta-analysis. There was no significant difference between digital and conventional impressions in the linear measurements of tooth width, anterior Bolton ratio, overall Bolton ratio, intercanine distance (ICD), and intermolar distance (IMD). The repeated measurement mean errors (RMEs) were less than 0.1 mm, the intra-examiner intraclass correlation coefficient (ICC) values were more than 0.9, and the inter-examiner ICC values were more than 0.87 for both impression techniques. The 3D deviation between digital and alginate impressions was 0.09 mm. The 3D precision of both impression techniques was less than 0.1 mm. CONCLUSIONS: The trueness of digital and alginate full-arch impressions was similar, and both impression techniques showed high precision. More research was needed to compare digital impressions and other conventional impression materials. CLINICAL RELEVANCE: For patients with completely natural dentition, the digital impressions obtained directly from intraoral scanning can be considered a viable alternative to alginate impressions.


Assuntos
Técnica de Moldagem Odontológica , Modelos Dentários , Alginatos , Desenho Assistido por Computador , Arco Dental , Materiais para Moldagem Odontológica , Humanos , Imageamento Tridimensional/métodos
17.
J Neuroinflammation ; 18(1): 165, 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34311746

RESUMO

BACKGROUND: Malignant glioma, especially glioblastoma, is a highly aggressive disease with a dismal prognosis. Vacuole membrane protein 1 (VMP1) is a critical autophagy-associated protein with roles in oncogenesis and tumor progression. However, the contribution of VMP1 to glioma development as well as its prognostic value has not been established. METHODS: The expression of VMP1 and clinicopathologic data for 1996 glioma samples were collected from authoritative public databases to explore its prognostic value. Lentiviral CRISPR-Cas9 gene editing system was performed to deplete VMP1 expression. Apoptosis assays, cell cycle assays, colony formation assays, and EdU incorporation analysis were conducted to validate the biological function of VMP1. Transmission electron microscopy was used to determine the role of VMP1 in regulating autophagy. RESULTS: VMP1 overexpression was associated with advanced disease and had a poor prognosis in patients with glioma. The depletion of VMP1 by CRISPR-Cas9 gene editing significantly inhibited cell proliferation, increased cell death, and induced cell cycle arrest. Mechanistically, VMP1 knockout blocked autophagic flux and thus sensitized glioma cells to radiotherapy and chemotherapy. Moreover, a nomogram model showed that VMP1 expression has high prognostic value for determining survival in glioma. CONCLUSIONS: Our results provide insights into the pathological and biological functions of VMP1, including its roles in promoting tumor growth and progression, and support its value as a new diagnostic and prognostic biomarker for glioma.


Assuntos
Autofagia , Glioma/metabolismo , Glioma/patologia , Proteínas de Membrana/metabolismo , Apoptose , Autofagia/genética , Biomarcadores , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Edição de Genes/métodos , Humanos , Proteínas de Membrana/genética , Microscopia Eletrônica de Transmissão , Estadiamento de Neoplasias , Prognóstico
18.
Nanotechnology ; 32(25)2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33721849

RESUMO

In this work, one-dimensional nitrogen doped porous carbon nano-arrays arranged by carbon nanotube (1D CNTs@NPC) were first constructed, using a coating technology at room temperature and followed by high temperature carbonization. It was expected that the resulting glassy carbon electrodes modified by 1D CNTs@NPC (CNTs@NPC/GCE) could express different electrochemical responses to ascorbic acid (AA), dopamine (DA), uric acid (UA), by virtue of the synergistic-improved effect between CNTs and NPC. Under the optimized conditions, there were excellent analytical parameters for CNTs@NPC/GCE to detect AA, DA and UA, i.e. a wide linear range of 40-2100µM for AA, 0.5-49µM for DA and 3-50µM for AA with low detection limits of 0.36µM, 0.02µmol l-1and 0.57µM respectively. Importantly, the proposed CNTs@NPC/GCE was efficiently applied to determine AA, DA and UA in some real samples with high stability, reproducibility and selectivity. This work will offer an efficient potential for diagnosing ascorbic acid, dopamine or uric acid-related diseases on clinical testing in future.


Assuntos
Ácido Ascórbico/análise , Dopamina/análise , Técnicas Eletroquímicas/métodos , Nanotubos de Carbono/química , Ácido Úrico/análise , Limite de Detecção , Nitrogênio/química , Porosidade
19.
Bioorg Chem ; 110: 104789, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33714760

RESUMO

TD-DFT quantum calculation was performed to predict and/or illustrate the electronic transition, the related absorption and emission maxima of some pyrrole-difluoroboron derivatives with different electron donor-acceptor unit or π-conjugated degree. Upon the calculated results, a new near infrared (NIR) fluorophore (abbreviated as TPBD-BP) was designed and fabricated through linking triphenylamine and pyrrole-difluoroboron units to benzothiadiazole (BTD) backbone. The fluorescence of TPBD-BP in solid state centered at 932 nm, which was 985 nm for TPBD-BP nanoparticles (TPBD-BP dots) encapsulated in PEG-6000. The fluorescence of TPBD-BP in both solid state and dots exhibited off-peak tail emission to NIR-II region (extended to 1300 nm). The TPBD-BP dots showed excellent water solubility, biocompatibility and aggregation induced emission (AIE), which was suitable to be applied in vivo imaging. NIR-II emission signal of TPBD-BP dots can be observed in the reproductive organ of normal nude mice after tail vein injection. This attractive combination of computational and experimental investigation would help to develop new-typed small-molecular NIR fluorophores.


Assuntos
Compostos de Boro/química , Teoria da Densidade Funcional , Corantes Fluorescentes/química , Imagem Óptica , Tiadiazóis/química , Animais , Compostos de Boro/administração & dosagem , Corantes Fluorescentes/administração & dosagem , Corantes Fluorescentes/síntese química , Raios Infravermelhos , Camundongos , Camundongos Nus , Estrutura Molecular , Tiadiazóis/administração & dosagem
20.
Asia Pac J Clin Nutr ; 30(1): 113-121, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33787047

RESUMO

BACKGROUND AND OBJECTIVES: This study evaluated the impact of 12 months of ketogenic dietary treatment (KDT) on growth in Chinese infants with refractory epilepsy. METHODS AND STUDY DESIGN: The KDT group included patients who were divided into groups A (age 6-12 months), B (12-24 months) and C (24-36 months). The normal group included infants aged approximately 6-12 months, 12-24 months and 24-36 months who were classified into groups A1, B1 and C1, respectively. Data on height, weight, aspartate transaminase (AST), alanine transaminase (ALT), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), zinc, iron, calcium, magnesium, and haemoglobin (Hb) were extracted from the medical records. Then, we compared the impacts of 12 months of KDT on growth. RESULTS: Forty-one patients were included in the KDT group, and 90 infants were included in the normal group. The overall prevalence of underweight (WAZ <-2 SD), stunting (HAZ <-2 SD), wasting (BAZ <-2 SD), and overweight/obesity (BAZ ≥2 SD) were relatively lower in the A and B groups. The prevalence of anaemia in group A was significantly higher than that in group A1. No significant differences were observed in the KDT groups with regard to HDL, LDL, AST, ALT, iron, calcium, magnesium, or zinc. A greater than 50% reduction in weekly seizure frequency was evident in 100% of group A, 78.6% of group B and 77.8% of group C. CONCLUSIONS: The results revealed that patients less than 2 years old who received KDT maintained appropriate growth at the 12-month follow-up.


Assuntos
Dieta Cetogênica , Epilepsia Resistente a Medicamentos , Alanina Transaminase , Aspartato Aminotransferases , Pré-Escolar , China/epidemiologia , Humanos , Lactente , Triglicerídeos
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