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1.
Sci Total Environ ; 857(Pt 1): 159276, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36216057

RESUMO

Improving volatile fatty acid (VFA) production, rather than producing methane from the anaerobic digestion (AD) of waste, has become a new strategy of resource utilization. In regard to animal wastewater, the effectiveness of persulfate/biochar (potassium peroxodisulfate, PDS/BC) on the hydrolysis and acidogenesis stages and the reaction mechanisms are still unclear. In this study, the AD process on cow wastewater was controlled at the hydrolysis and acidification stages by setting the hydraulic retention time (HRT) at 25 days. The results showed that the contents of total solids (TS) and volatile solids (VS) were further reduced by PDS/BC treatment with 0.15 gPDS/gTS of PDS added. The VFAs production increased by 12.4 % from day 0 to 25 compared to the blank set. Based on our molecular analysis, the rate of increase for the dissolved organic matter with low molecular weight (0-10 kDa) was 699.5 mg/(L·d) in the first 10 days. The change rate increased nearly 2.1 times, leading to higher VFAs yield. Moreover, the activities of fermentative bacteria were enhanced and Anaerocella was determined to be the specific and critical genus. However, excessive PDS (0.3 gPDS/gTS) prolonged the acidification period and caused the inactivation of fermentative bacteria. Structural equation modeling demonstrated that PDS can directly affect VFAs yield and also had an indirect effect by influencing the decomposition of particulate matter and microbial activities. Therefore, the enhancement of VFAs production using the PDS/BC method could be due to synergistic chemical and microbial effects. Findings from this study can provide a practical strategy to enhance the VFAs production of AD technology for livestock wastewater and help reveal the reaction mechanism of PDS/BC treatment.


Assuntos
Reatores Biológicos , Águas Residuárias , Bovinos , Animais , Feminino , Anaerobiose , Reatores Biológicos/microbiologia , Ácidos Graxos Voláteis , Metano , Esgotos/química , Bactérias
2.
Food Chem ; 404(Pt A): 134602, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36444020

RESUMO

Although mannoprotein (MP) is known to increase the stability of anthocyanins, the MP-anthocyanin interactions and structural changes induced by the same remain underexplored. To bridge this gap, this work examined the complexation of cyanidin-3-glucoside (C3G) by MP and probed its effect on C3G properties. As a result, this complexation was shown to induce the static fluorescence quenching of MP and increase the thermal stability and antioxidant activity of C3G while decreasing its susceptibility to ascorbic acid, sucrose, and Fe3+-induced degradation and increasing its bioavailability during simulated in vitro digestion. Hydrogen bonding and van der Waals interactions were identified as the main complexation drivers and were demonstrated to change the self-aggregation behavior of both compounds and favor the formation of a cross-linked structure. Thus, our results show that MP addition is an efficient anthocyanin protection method and provide a theoretical basis for the utilization of MP and C3G.


Assuntos
Antocianinas , Ácido Ascórbico , Digestão
3.
Front Surg ; 9: 1021098, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338649

RESUMO

Background: Three-dimensional (3D) exoscope systems have been developed and are reported to be adequate alternatives to the conventional microscope. This study aimed to evaluate the feasibility and effectivity of microvascular anastomosis using a 4 K 3D exoscope in an in vivo animal study. Methods: The abdominal aortas of mice were selected as the target vessels for comparing the outcomes of microvascular anastomosis for both the conventional microscope and 3D exoscope. We recorded the vessel separation, temporary occlusion, and total procedure durations. Local conditions at the sutures were also recorded. Typical histopathological images were presented, and the patency of anastomotic vessels within 5 and 30 min were evaluated. All procedures included both superficial and deep anastomosis. Results: Sixty mice were included in the analysis; the weight and vascular diameter were 38.5 ± 5.8 g and 0.77 ± 0.06 mm, respectively, and around 8 stiches were required. Regarding feasibility, vessel separation duration, temporary occlusion duration, total procedure duration, blood leak, and number of vascular folds between stiches, the results were comparable between the two types of microscopes. The feasibility of anastomosis was also confirmed by pathology. Regarding effectiveness, anastomotic vascular patency at 5 and 30 min were similar for both microscopes. Even in the more difficult scenario of deep anastomosis, the results were comparable. Conclusions: In a challenging experimental setting, comparable outcomes of microvascular anastomosis were observed for the conventional microscope and 3D exoscope in these animal experiments. Therefore, in vivo microvascular anastomosis is feasible and effective using a 3D exoscope.

4.
Exp Ther Med ; 24(6): 725, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36340602

RESUMO

Regulator of chromosome condensation 2 (RCC2) is highly involved in the development of tumor malignancies. The underlying mechanisms remain to be elucidated. The present study aimed to explore the role of RCC2 in the development of tumor malignancies and explore the underlying mechanisms in colorectal cancer (CRC). RCC2 expression and survival analysis were performed in human pan-cancer. The results of searching its mRNA expression in The Cancer Genome Atlas (TCGA) database showed that RCC2 was highly expressed in different types of cancer. High RCC2 expression levels were significantly correlated with poor survival outcomes by the Kaplan-Meier analysis in the TCGA database. Immunohistochemistry revealed that RCC2 was higher expressed in 36 CRC tissues than in adjacent normal tissues. Co-immunoprecipitation revealed that RCC2 bound to high mobility group A2 (HMGA2). Ectopic expression of RCC2 promoted cell proliferation, migration and invasion, whereas knockdown of HMGA2 exerted the opposite effects. Collectively, the data provided a novel biomarker of RCC2 in various types of cancer. High RCC2 expression levels were correlated with poor prognosis in different types of cancer. In addition, RCC2 may combine with HMGA2 to promote CRC malignancy.

5.
BMC Cancer ; 22(1): 1200, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36419008

RESUMO

BACKGROUND: In our previous study, N end of the Circumsporozoite protein (CSP I-plus) modified recombinant human Endostatin (rEndostatin, endostar) (rES-CSP) was constructed, which had antiangiogenic capability and bound to hepatocellular carcinoma in vivo and in vitro. In this study, the inhibition of rES-CSP on hepatocellular carcinoma metastasis was verified in vivo and in vitro, and its possible mechanism was explored. METHODS: Firstly, the impact of rES-CSP on the migration, adhesion of hepatoma cell HCCLM3 was identified by wound healing, transwell, and on metastasis of orthotopic xenograft model was identified in nude mouse. Then the expression of metastasis-associated molecules (MMP2, E-cadherin, integrinß1) and angiogenesis-related factors (VEGFA) in vitro and in vivo were detected by real-time PCR, western blotting, immunohistochemistry. RESULTS: Finally, we found that rES-CSP could inhibit the migration and invasion of HCCLM3, and decrease tumor metastasis and growth in nude mouse orthotopic xenograft models. The tumor inhibiting rates of rES-CSP and Endostar were 42.46 ± 5.39% and 11.1 ± 1.88%. The lung metastasis rates of the control, Endostar and rES-CSP were 71, 50, and 42.8%, respectively. Compared with Endostar, rES-CSP significantly down-regulated the expression of VEGFA and integrinß1. Heparin, a competitive inhibitor of CSP I-plus, which can be bind to the highly-sulfated heparan sulfate proteoglycans (HSPGs) over-expressed in liver and hepatocellular carcinoma, alleviated the down-regulation of VEGFA and integrinß1. CONCLUSIONS: These indicate that rES-CSP may play a role in inhibiting tumor growth and metastasis by down-regulating the angiogenic factor VEGF and the metastasis-related molecules or by interfering with HSPGs-mediated tumor metastasis.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Camundongos , Animais , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Regulação para Baixo , Neoplasias Hepáticas/patologia , Camundongos Nus , Células Hep G2 , Processos Neoplásicos , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
6.
Front Immunol ; 13: 1005695, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36420274

RESUMO

Long noncoding RNAs (lncRNAs) play a critical role in the immune regulation and tumor microenvironment of pancreatic cancer (PaCa). To construct a novel immune-related prognostic risk model for PaCa and evaluate the prognostic prediction of lncRNAs, essential immune-related lncRNAs (IRlncRNAs) were identified by Pearson correlation analysis of differentially expressed immune-related genes (IRGs) and IRlncRNAs in PaCa from The Cancer Genome Atlas (TCGA) and GTEx databases. Least absolute shrinkage and selection operator (LASSO) regression was also applied to construct a prognostic risk model of IRlncRNAs, and gene set enrichment analysis (GSEA) was further applied for functional annotation for these IRlncRNAs. A total of 148 IRlncRNAs were identified in PaCa to construct a prognostic risk model. Among them, lncRNA LINC02325, FNDC1-AS1, and ZEB2-AS1 were significantly upregulated in 69 pairs of PaCa tissues by qRT-PCR. ROC analyses showed that LINC02325 (AUC = 0.80), FNDC1-AS1 (AUC = 0.76), and ZEB2-AS1 (AUC = 0.75) had a good predictive effect on 5-year survival prognosis. We demonstrated that high expression levels of ZEB2-AS1 and LINC02325 were not only positively associated with tumor size and CA199, but elevated levels of ZEB2-AS1 and FNDC1-AS1 were also positively correlated with tumor stage. GSEA further revealed that immune-related pathways were mainly enriched in the high-risk groups. Several immune-related algorithms demonstrated that four IRlncRNAs were related to immune infiltration, immune checkpoints, and immune-related functions. Thus, the prognostic risk model based on IRlncRNAs in Paca indicates that the four IRlncRNA signatures may serve as predictors of survival and potential predictive biomarkers of the pancreatic tumor immune response.


Assuntos
Neoplasias Pancreáticas , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Prognóstico , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Neoplasias Pancreáticas/genética , Microambiente Tumoral/genética , Proteínas de Neoplasias/genética
7.
Small ; : e2205248, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36417577

RESUMO

Helicobacter pylori (H. pylori) infection has been the leading cause of gastric cancer development. In recent years, the resistance of H. pylori against antibiotic treatment has been a great challenge for most countries worldwide. Since biofilm formation is one of the reasons for the antibiotic resistance of H. pylori, and phototherapy has emerged as a promisingly alternative antibacterial treatment, herein the bacteria-targeted near-infrared (NIR) photosensitizer (T780T-Gu) by combining positively-charged guanidinium (Gu) with an efficient phototherapeutic agent T780T is developed. The proposed molecule T780T-Gu exhibits synergistic photothermal therapy/photodynamic therapy effect against both H. pylori biofilms and multidrug-resistant (MDR) clinical strains. More importantly, the phototherapy mechanism of T780T-Gu acquired by the RNA-seq analysis indicates that structural deficiency as well as a decrease in metabolism and defense activity are the possible reasons for the efficient H. pylori phototherapy.

8.
Front Pediatr ; 10: 990724, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405836

RESUMO

We investigated the effects of high- vs. standard-dose vitamin D supplementation on kidney function and bone metabolism in children with chronic kidney disease (CKD). Children were randomized to receive one of two formulations: 75 participants received 2,000 IU/D of oral supplementation of vitamin D, while 75 participants received 400 IU/d for a minimum of 4 months. We investigated the effects of vitamin D supplementation on kidney-related indicators and bone metabolism-related indicators at different doses. A total of 158 participants were screened, among whom 150 met the inclusion criteria. The indicators of chronic kidney disease such as eGFR and serum uric acid were negatively correlated with the 25(OH)D level and BMD. Serum 25(OH)D and osteocalcin levels were positively correlated with spine BMD. The standard dose of vitamin D can improve the serum uric acid level, but high doses of vitamin D supplementation had no significant effect on the serum uric acid level. High doses of vitamin D supplementation can also improve the alkaline phosphatase level. When comparing the results of different doses of vitamin D supplementation, it was found that high-dose vitamin D supplementation did not improve bone density in the spine and femur neck relative to the standard dose of vitamin D but improved hypocalcemia and N-terminal propeptide of the human procollagen type I (PINP) level. Among the children with clinical kidney disease, high-dose vitamin D treatment for 4 months resulted in statistically significant improvement in kidney function but no significant difference in bone metabolism compared with the standard-dose vitamin D treatment.

9.
Neurol India ; 70(5): 1787-1792, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36352566

RESUMO

Background: Carotid endarterectomy (CEA) has been the standard therapy for carotid artery stenosis (CAS). Modified eversion carotid endarterectomy (mECEA) was recently introduced to treat CAS. However, the short-term safety and long-term efficacy of mECEA are still controversial among studies. This systematic review aims to summarize the current literatures about safety and efficacy of mECEA in treating CAS. Methods: A systematic review of mECEA was conducted in the main bibliographic databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Clinical studies on the safety and efficacy of mECEA in treating CAS with clinical results of transient ischemic attack (TIA), stroke, death, and restenosis were included. Results: The initial search and screening found 15 references from the main databases, and 7 studies were finally included after full-text article assessment, which consisted of 3 single-arm studies and 4 comparative studies. The risks of postoperative complications including TIA, stroke, myocardial infarction (MI), and death ranged from 1.1% to 2%, 0% to 2.5%, 0% to 4.4%, and 0% to 2.32%, respectively. The mECEA was significantly related to lower risk of carotid artery occlusion, incision numbness, and shorter lengths of stay in hospital and average scar when separately compared with conventional CEA (cCEA), CEA with patch closure (pCEA), and eversion CEA (eCEA). Conclusions: The mECEA is a promising surgical option for CAS with acceptable clinical outcomes. In order to prove its safety and efficacy, future practices need to be conducted by more medical workers in more large-scale trials.


Assuntos
Doenças das Artérias Carótidas , Estenose das Carótidas , Endarterectomia das Carótidas , Ataque Isquêmico Transitório , Acidente Vascular Cerebral , Humanos , Endarterectomia das Carótidas/efeitos adversos , Estenose das Carótidas/cirurgia , Estenose das Carótidas/complicações , Ataque Isquêmico Transitório/etiologia , Ataque Isquêmico Transitório/cirurgia , Acidente Vascular Cerebral/complicações , Doenças das Artérias Carótidas/complicações , Resultado do Tratamento , Stents/efeitos adversos , Fatores de Risco
10.
11.
Molecules ; 27(21)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36364107

RESUMO

Hepatocellular carcinoma (HCC) is the most common primary liver malignant tumor, and the targeted therapy for HCC is very limited. Our previous study demonstrated that prodigiosin(PG), a secondary metabolite from Serratia marcescens found in the intestinal flora of cockroaches, inhibits the proliferation of HCC and increases the expression of CHOP, a marker protein for endoplasmic reticulum stress (ERS)-mediated apoptosis, in a dose-dependent manner. However, the mechanisms underlying the activity of PG in vivo and in vitro are unclear. This study explored the molecular mechanisms of PG-induced ERS against liver cancer in vitro and in vivo. The apoptosis of hepatocellular carcinoma cells induced by PG through endoplasmic reticulum stress was observed by flow cytometry, colony formation assay, cell viability assay, immunoblot analysis, and TUNEL assay. The localization of PG in cells was observed using laser confocal fluorescence microscopy. Flow cytometry was used to detect the intracellular Ca2+ concentration after PG treatment. We found that PG could promote apoptosis and inhibit the proliferation of HCC. It was localized in the endoplasmic reticulum of HepG2 cells, where it induces the release of Ca2+. PG also upregulated the expression of key unfolded response proteins, including PERK, IRE1α, Bip, and CHOP, and related apoptotic proteins, including caspase3, caspase9, and Bax, but down-regulated the expression of anti-apoptotic protein Bcl-2 in liver cancer. Alleviating ERS reversed the above phenomenon. PG had no obvious negative effects on the functioning of the liver, kidney, and other main organs in nude mice, but the growth of liver cancer cells was inhibited by inducing ERS in vivo. The findings of this study showed that PG promotes apoptosis of HCC by inducing ERS.


Assuntos
Carcinoma Hepatocelular , Baratas , Neoplasias Hepáticas , Camundongos , Animais , Carcinoma Hepatocelular/metabolismo , Estresse do Retículo Endoplasmático , Neoplasias Hepáticas/patologia , Prodigiosina/farmacologia , Endorribonucleases/metabolismo , Serratia marcescens/metabolismo , Camundongos Nus , Baratas/metabolismo , Proteínas Serina-Treonina Quinases , Apoptose , Proliferação de Células
12.
Front Pharmacol ; 13: 967787, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386133

RESUMO

Background: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory arthropathy. Recommendations for RA, specifically on pharmacotherapy, are essential in clinical practice. However, the direction and strength of recommendations are controversial across current clinical practice guidelines (CPGs) of RA. Objective: To systematically analyze the consistency of recommendations regarding pharmacotherapy of RA across CPGs. Methods: 11 electronic databases and websites were comprehensively searched from inception to 14 March 2022, to identify CPGs for diagnosis, therapy, and management of RA. Unambiguous and discrete specifications of the population-intervention-comparison (PIC) framework were used to classify the recommendations. Based on the PIC framework, consistency analyses across CPGs on pharmacotherapy of RA were performed. Two researchers reached a consensus on coding the direction and strength of each recommendation. Results: Finally, 26 CPGs were included in this study, and 14 of them, which included pharmacotherapy, were performed consistency analysis. 1) 64 recommendations from 14 CPGs were classified into 18 PICs. 2) Seven PICs (38%) were consistent in direction and strength, 10 PICs (56%) were consistent in direction but inconsistent in strength, and one PIC (6%) was inconsistent in direction (hydroxychloroquine, HCQ). 3) Sensitivity analysis tested the robustness, and the inconsistency remained high. Conclusion: The direction was highly consistent among the recommendations of pharmacotherapy for RA, but the strength was highly inconsistent. Reasons for the inconsistency need to be further investigated, and consistent recommendations could guide the pharmacotherapy of RA in clinical practice.

13.
Chemosphere ; 312(Pt 1): 137064, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36334734

RESUMO

Human hair has increasingly been used as a noninvasive biomonitoring matrix for assessment of human exposure to various organic contaminants (OCs). However, the accumulation processes of OCs in hair remains unclear thus far, which raised concerns on the reliability of hair analysis results for OCs. Herein, Chinese population was selected as the study subject, the effects of changes in hair biological characteristics, including length and color, on the accumulation of OCs in hair was investigated. With the growing of hair shaft and the increased distance from the scalp, a significant increasing trend was found for levels of polychlorinated biphenyls (PCBs) and organophosphate flame retardants (PFRs) along the hair shafts (p < 0.05). Source identification using Chemical Mass Balance model indicated that PCBs in hair were mainly from exogenous sources (air and dust). The accumulation rates of PCB and PFR individuals in the hair shaft decreased with increasing of log Kow values. Additionally, the levels of OCs in hair decreased with the change in color from black to white, probably because of the loss of melanin in white hair. The ratios (R) of Cblack/Cwhite were significantly correlated with the log Kow values for individual chemicals (p < 0.05), implying that OCs with high log Kow values tend to accumulate more readily in black hair. The results of this study demonstrated the growth and change in colors of hair, as well as the physicochemical properties of chemicals, play vital roles in the accumulation of OCs in hair. The present study provides fundamental basis for the precise assessment of human exposure to OCs using hair as a biomonitoring matrix in future studies.

14.
Nanomaterials (Basel) ; 12(22)2022 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-36432281

RESUMO

Magnetosomes (MAGs) extracted from magnetotactic bacteria are well-defined membrane-enveloped single-domain magnetic nanoparticles. Due to their superior magnetic and structural properties, MAGs constitute potential materials that can be manipulated via genetic and chemical engineering for use in biomedical and biotechnological applications. However, the long-term effects exerted by MAGs on cells are of concern in the context of in vivo applications. Meanwhile, it remains relatively unclear which mechanisms are employed by cells to process and degrade MAGs. Hence, a better understanding of MAGs' degradation and fundamental signal modulations occurring throughout this process is essential. In the current study, we investigated the potential actions of MAGs on endothelial cells over a 10-day period. MAGs were retained in cells and found to gradually gather in the lysosome-like vesicles. Meanwhile, iron-ion release was observed. Proteomics further revealed a potential cellular mechanism underlying MAGs degradation, in which a group of proteins associated with vesicle biogenesis, and lysosomal enzymes, which participate in protein hydrolysis and lipid degradation, were rapidly upregulated. Moreover, the released iron triggered the regulation of the iron metabolic profiles. However, given that the levels of cell oxidative damage were relatively stable, the released iron ions were handled by iron metabolic profiles and incorporated into normal metabolic routes. These results provide insights into the cell response to MAGs degradation that may improve their in vivo applications.

15.
Biomimetics (Basel) ; 7(4)2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36412725

RESUMO

Uncertainty of target motion, limited perception ability of onboard cameras, and constrained control have brought new challenges to unmanned aerial vehicle (UAV) dynamic target tracking control. In virtue of the powerful fitting ability and learning ability of the neural network, this paper proposes a new deep reinforcement learning (DRL)-based end-to-end control method for UAV dynamic target tracking. Firstly, a DRL-based framework using onboard camera image is established, which simplifies the traditional modularization paradigm. Secondly, neural network architecture, reward functions, and soft actor-critic (SAC)-based speed command perception algorithm are designed to train the policy network. The output of the policy network is denormalized and directly used as speed control command, which realizes the UAV dynamic target tracking. Finally, the feasibility of the proposed end-to-end control method is demonstrated by numerical simulation. The results show that the proposed DRL-based framework is feasible to simplify the traditional modularization paradigm. The UAV can track the dynamic target with rapidly changing of speed and direction.

16.
J Sci Food Agric ; 2022 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-36335532

RESUMO

BACKGROUND: Rice is an important food crop plant in the world and is also a model plant for genetics and breeding research. The germination rate is an important indicator that measures the performance of rice seeds. Currently, solutions involving image processing techniques have substantial challenges in the identification of seed germination. The detection of rice seed germination without human intervention involves challenges because the rice seeds are small and densely distributed. RESULTS: In this article, we develop a convolutional neural network (YOLO-r) that can detect the germination status of rice seeds and automatically evaluate the total number of germinations. Image partition, the Transformer encoder, a small target detection layer, and CDIoU loss are exploited in YOLO-r to improve the detection accuracy. A total of 21 429 seeds were collected, which have different phenotypic characteristics in length, shape, and color. The results show that the mean average precision of YOLO-r is 0.9539, which is higher than the compared models. Moreover, the average detection time per image of YOLO-r was 0.011 s, which meets the real-time requirements. The experimental results demonstrate that YOLO-r is robust to complex situations such as water stains, impurities, awns, adhesion, and so on. The results also show that the mean absolute error of the predicted germination rate mainly exists within 0.1. CONCLUSIONS: Numerous experimental studies have demonstrated that YOLO-r can predict rice germination rate in a fast, easy, and accurate manner. © 2022 Society of Chemical Industry.

17.
Nature ; 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36356599

RESUMO

The T cell receptor (TCR) provides the fine specificity of T cells to recognize mutations in cancer cells 1-3. We developed a clinical-grade approach based on CRISPR/Cas9 non-viral precision genome editing to simultaneously knock-out the two endogenous TCR genes, TCRα (TRAC) and TCRß (TRBC), and insert in the TRAC locus the two chains of a neoantigen-specific TCR (neoTCR), isolated from the patient's own circulating T cells using a personalized library of soluble predicted neoantigen-HLA capture reagents. Sixteen patients with refractory solid cancers received up to three distinct neoTCR-transgenic cell products, each expressing a patient-specific neoTCR, in a cell dose-escalation, first-in-human phase 1 clinical trial (NCT03970382). One patient had grade 1 cytokine release syndrome, and one grade 3 encephalitis. All had the expected side effects from the lymphodepleting chemotherapy. Five patients had stable disease, and the other 11 had disease progression as best response on therapy. NeoTCR-transgenic T cells were detected in tumour biopsies post-infusion at frequencies higher than the native TCRs pre-infusion. This study demonstrates the feasibility of isolating and cloning multiple TCRs recognizing mutational neoantigens, the simultaneous knock-out of the endogenous TCR and knock-in of the neoTCRs using single-step, non-viral precision genome editing, the manufacturing of neoTCR engineered T cells at clinical grade, the safety of infusing up to three gene edited neoTCR T cell products, and the ability of the transgenic T cells to traffic to the patients' tumours.

19.
World J Gastrointest Oncol ; 14(11): 2238-2252, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36438702

RESUMO

BACKGROUND: The features of gastric cancer based on the anatomic site remain unknown in northern China patients. AIM: To analyze gastric cancer features and associated trends based on the anatomical site in northern China patients. METHODS: This cross-sectional study used incident gastric cancer case data from 10 Peking University-affiliated hospitals (2014 to 2018). The clinical and prevailing local features were analyzed. RESULTS: A total of 10709 patients were enrolled, including antral (42.97%), cardia (34.30%), and stomach body (18.41%) gastric cancer cases. Cancer in the cardia had the highest male:female ratio, proportion of elderly patients, and patients with complications, including hypertension, diabetes, cerebrovascular, and coronary diseases (P < 0.001). gastric cancer involving the antrum showed the lowest proportion of patients from rural areas and accounted for the highest hospitalization rate and cost (each P < 0.001). The proportion of patients with cancer involving the cardia increased with an increase in the number of gastroesophageal reflux disease cases during the same period (P < 0.001). Multivariate analysis revealed that tumor location in the cardia increased the risk of in-hospital mortality (P = 0.046). Anatomical subsite was not linked to postoperative complications. CONCLUSION: The features of gastric cancer based on the anatomical site differ between northern China and other regions, both globally and within the country. Social factors may account for these differences and should affect policy-making and clinical practice.

20.
Anal Chem ; 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36445943

RESUMO

Recently, nanoformulations have been widely applied in the delivery of organic photothermal agents (OPTAs) for cancer therapy to prolong blood circulation or improve tumor-targeting capacity. However, the systematic evaluations of their effects on the photothermal behavior of OPTAs are limited, especially for different types of nanoparticle systems. Herein, we prepared two kinds of nanoparticles (BSA and PEG nanoparticles (NPs)) to load an OPTA, a cyanine photosensitizer (IR780-O-TPE), and investigated their photothermal response, organelle targeting, and in vivo therapeutic efficacy. Due to different assembly forms, the two NPs showed distinct morphological changes after exposure to laser or hyperthermia. Under laser irradiation at 808 nm, BSA NPs could release IR780-O-TPE more efficiently than PEG NPs. We speculate that this phenomenon is probably caused by dual-responsive release of IR780-O-TPE from BSA NPs against light and hyperthermia. Moreover, IR780-O-TPE/BSA NPs were highly mitochondria-targeting and therefore displayed significant inhibition of cell viability. In contrast, IR780-O-TPE/PEG NPs were "shell-core" nanostructures and more stable under laser stimulation. As a consequence, the mitochondria-targeting and anticancer photothermal therapy by IR780-O-TPE/PEG NPs was less obvious. This study revealed the significance of nanocarrier design for OPTA delivery and demonstrated that BSA NPs could release IR780-O-TPE more effectively for efficient photothermal therapy. We also believe that the dual-responsive release of OPTAs from NPs can provide an effective strategy to promote anticancer photothermal treatment.

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