Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 94
Filtrar
1.
J Environ Sci (China) ; 146: 226-236, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38969450

RESUMO

Defluoridation of coal mining water is of great significance for sustainable development of coal industry in western China. A novel one-step mechanochemical method was developed to prepare polymeric aluminum modified powder activated carbon (PAC) for effective fluoride removal from coal mining water. Aluminum was stably loaded on the PAC through facile solid-phase reaction between polymeric aluminum (polyaluminum chloride (PACl) or polyaluminum ferric chloride (PAFC)) and PAC (1:15 W/W). Fluoride adsorption on PACl and PAFC modified PAC (C-PACl and C-PAFC) all reached equilibrium within 5 min, at rate of 2.56 g mg-1 sec-1 and 1.31 g mg-1 sec-1 respectively. Larger increase of binding energy of Al on C-PACl (AlF bond: 76.64 eV and AlFOH bond: 77.70 eV) relative to that of Al on C-PAFC (AlF bond: 76.52 eV) explained higher fluoride uptake capacity of C-PACl. Less chloride was released from C-PACl than that from C-PAFC due to its higher proportion of covalent chlorine and lower proportion of ionic chlorine. The elements mapping and atomic composition proved the stability of Al loaded on the PAC as well as the enrichment of fluoride on both C-PACl and C-PAFC. The Bader charge, formation energy and bond length obtained from DFT computational results explained the fluoride adsorption mechanism further. The carbon emission was 7.73 kg CO2-eq/kg adsorbent prepared through mechanochemical process, which was as low as 1:82.3 to 1:8.07 × 104 compared with the ones prepared by conventional hydrothermal methods.


Assuntos
Carvão Vegetal , Minas de Carvão , Fluoretos , Poluentes Químicos da Água , Fluoretos/química , Poluentes Químicos da Água/química , Carvão Vegetal/química , Adsorção , Alumínio/química , Polímeros/química , Purificação da Água/métodos , Eliminação de Resíduos Líquidos/métodos
2.
Transl Oncol ; 46: 102020, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38843659

RESUMO

This study investigated the synergistic potential of an oncolytic herpes simplex virus armed with interleukin 12 (VT1092M) in combination with immune checkpoint inhibitors for enhancing antitumor responses. The potential of this combination treatment to induce systemic antitumor immunity was assessed using bilateral subcutaneous tumor and tumor re-challenge mouse models. The antitumor efficacy of various OV and ICI treatment combinations and the underlying mechanisms were explored through diverse analytical techniques, including flow cytometry and RNA sequencing. Using VT1092M, either alone or in combination with an anti-PD-L1 antibody, significantly reduced the sizes of both the injected and untreated abscopal tumors in a bilateral tumor mouse model. The combination therapy demonstrated superior antitumor efficacy to the other treatment conditions tested, which was accompanied by an increase in T cell numbers and CD8+T cell activation. Results from the survival and tumor re-challenge experiments showed that the combination therapy elicited long-term, tumor-specific immune responses, which were associated with tumor clearance and prolonged survival. Immune cell depletion assays identified CD8+T cells as the crucial mediators of systemic antitumor immunity during combination therapy. In conclusion, the combination of VT1092M and PD-L1 blockade emerged as a potent inducer of antitumor immune responses, surpassing the efficacy of each monotherapy. This synergistic approach holds promise for achieving robust and sustained antitumor immunity, with potential implications for preventing tumor metastasis in patients with cancer.

3.
J Exp Clin Cancer Res ; 43(1): 125, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664705

RESUMO

BACKGROUND: Immunotherapy has emerged as a potent clinical approach for cancer treatment, but only subsets of cancer patients can benefit from it. Targeting lactate metabolism (LM) in tumor cells as a method to potentiate anti-tumor immune responses represents a promising therapeutic strategy. METHODS: Public single-cell RNA-Seq (scRNA-seq) cohorts collected from patients who received immunotherapy were systematically gathered and scrutinized to delineate the association between LM and the immunotherapy response. A novel LM-related signature (LM.SIG) was formulated through an extensive examination of 40 pan-cancer scRNA-seq cohorts. Then, multiple machine learning (ML) algorithms were employed to validate the capacity of LM.SIG for immunotherapy response prediction and survival prognostication based on 8 immunotherapy transcriptomic cohorts and 30 The Cancer Genome Atlas (TCGA) pan-cancer datasets. Moreover, potential targets for immunotherapy were identified based on 17 CRISPR datasets and validated via in vivo and in vitro experiments. RESULTS: The assessment of LM was confirmed to possess a substantial relationship with immunotherapy resistance in 2 immunotherapy scRNA-seq cohorts. Based on large-scale pan-cancer data, there exists a notably adverse correlation between LM.SIG and anti-tumor immunity as well as imbalance infiltration of immune cells, whereas a positive association was observed between LM.SIG and pro-tumorigenic signaling. Utilizing this signature, the ML model predicted immunotherapy response and prognosis with an AUC of 0.73/0.80 in validation sets and 0.70/0.87 in testing sets respectively. Notably, LM.SIG exhibited superior predictive performance across various cancers compared to published signatures. Subsequently, CRISPR screening identified LDHA as a pan-cancer biomarker for estimating immunotherapy response and survival probability which was further validated using immunohistochemistry (IHC) and spatial transcriptomics (ST) datasets. Furthermore, experiments demonstrated that LDHA deficiency in pancreatic cancer elevated the CD8+ T cell antitumor immunity and improved macrophage antitumoral polarization, which in turn enhanced the efficacy of immunotherapy. CONCLUSIONS: We unveiled the tight correlation between LM and resistance to immunotherapy and further established the pan-cancer LM.SIG, holds the potential to emerge as a competitive instrument for the selection of patients suitable for immunotherapy.


Assuntos
Imunoterapia , Neoplasias , Humanos , Imunoterapia/métodos , Prognóstico , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/mortalidade , Neoplasias/metabolismo , Neoplasias/genética , Ácido Láctico/metabolismo , Camundongos , Animais , Feminino
4.
Zhongguo Yi Liao Qi Xie Za Zhi ; 48(2): 179-183, 2024 Mar 30.
Artigo em Chinês | MEDLINE | ID: mdl-38605618

RESUMO

Objective: To introduce a locating device for the entry point of intramedullary nail based on the inertial navigation technology, which utilizes multi-dimensional angle information to assist in rapid and accurate positioning of the ideal direction of femoral anterograde intramedullary nails' entry point, and to verify its clinical value through clinical tests. Methods: After matching the locating module with the developing board, which are the two components of the locating device, they were placed on the skin surface of the proximal femur of the affected side. Anteroposterior fluoroscopy was performed. The developing angle corresponding to the ideal direction of entry point was selected based on the X-ray image, and then the yaw angle of the locating module was reset to zero. After resetting, the locating module was combined with the surgical instrument to guide the insertion angle of the guide wire. The ideal direction of entry point was accurately located based on the angle guidance. By setting up an experimental group and a control group for clinical surgical operations, the number of guide wire insertion times, surgical time, fluoroscopy frequency, and intraoperative blood loss with or without the locating device was recorded. Results: Compared to the control group, the experimental group showed significant improvement in the number of guide wire insertion times, surgical time, fluoroscopy frequency, and intraoperative blood loss, with a statistically significant difference (P<0.01). Conclusion: The locating device can assist doctors in quickly locating the entry point of intramedullary nail, effectively reducing the fluoroscopy frequency and surgical time by improving the success rate of the guide wire insertion with one shot, improving surgical efficiency, and possessing certain clinical value.


Assuntos
Fixação Intramedular de Fraturas , Cirurgia Assistida por Computador , Humanos , Pinos Ortopédicos , Perda Sanguínea Cirúrgica , Fluoroscopia/métodos , Fixação Intramedular de Fraturas/métodos , Cirurgia Assistida por Computador/métodos
5.
J Virol Methods ; 327: 114933, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38582377

RESUMO

Baculovirus has been widely used for foreign protein expression in biomedical studies, and budded virus (BV) surface display has developed into an important research tool for heterogenous membrane protein studies. The basic strategy of surface display is to construct a recombinant virus where the target gene is fused with a complete or partial gp64 gene. In this study, we further investigate and develop this BV surface displaying strategy. We constructed stable insect cell lines to express the target protein flanking with different regions of signal peptide (SP) and GP64 transmembrane domain (TMD). Subsequently, recombinant BmNPV was used to infect the cell, and the integration of heterogeneous protein into BV was detected. The results indicated that deletion of the n-region of SP (SPΔn) decreased the incorporation rate more than that of the full-length SP. However, the incorporation rate of the protein fused with h and c-region deletion of SP (SPΔh-c) was significantly enhanced by 35-40 times compare to full-length SP. Moreover, the foreign protein without SP and TMD failed to display on the BV, while the integration of foreign proteins with GP64 TMD fusion at the c-terminal was significantly enhanced by 12-26 times compared to the control. Thus, these new strategies developed the BV surface display system further.


Assuntos
Nucleopoliedrovírus , Vírion , Animais , Nucleopoliedrovírus/genética , Nucleopoliedrovírus/metabolismo , Linhagem Celular , Vírion/genética , Vírion/metabolismo , Bombyx/virologia , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismo , Sinais Direcionadores de Proteínas/genética , Domínios Proteicos , Células Sf9 , Montagem de Vírus
6.
World J Surg Oncol ; 22(1): 83, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38523264

RESUMO

BACKGROUND: Aimed to assess clinical effect of three-port inflatable robot-assisted thoracoscopic surgery in mediastinal tumor resection by comparing results of the robot group with the video group. METHODS: Retrospectively analyze 179 patients diagnosed with anterior mediastinal tumor from May 2017 to August 2021. Two groups were divided according to the surgical approach, including 92 cases in the RATS group and 87 cases in the VATS group. The results were analyzed between two groups with variables of age, sex, BMI, tumor size, and diagnosis. Perioperative clinical data was gathered to compare. RESULT: There were no significant differences between the 2 groups with regards to demographic data and clinical features. There were no significant differences inoperative time and duration of chest tube via RATS vs. VATS. The intraoperative blood loss was statistically significantly different among the RATS and VATS groups (75.9 ± 39.6 vs. 97.4 ± 35.8 ml p = 0.042). The postoperative stay of patients in RATS group were significantly shorter than that in VATS group (2.3 ± 1.0 vs. 3.4 ± 1.4 day p = 0.035), CONCLUSION: Three-port inflatable robot-assisted thoracoscopic surgery for mediastinal tumor is feasible and reliable it is more advantageous, and it provides the surgeon with advice on treatment choice.


Assuntos
Neoplasias do Mediastino , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Neoplasias do Mediastino/cirurgia , Estudos Retrospectivos , Cirurgia Torácica Vídeoassistida/métodos
7.
Sci Rep ; 14(1): 4254, 2024 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383716

RESUMO

This study aimed to assess the feasibility and safety of robot-assisted thoracic surgery (RATS) for resecting benign tumors of the cervicothoracic junction. Between 2017 and 2021, a total of 54 patients with benign cervicothoracic junction tumors were included. Among them, 46 underwent RATS while 8 underwent open surgery. Using a propensity score based on four variables (age, sex, comorbidity, and tumor size). The outcomes compared included short-term outcomes such as blood loss, as well as long-term outcomes including respiratory function and patients' postoperative health-related quality of life. No operative deaths occurred in this study. RATS was associated with less intraoperative blood loss (102 < 380 ml, P = 0.001) and a shorter length of hospital stay (1.8 < 4.8, P < 0.001). After a median follow-up of 37 months, no recurrences were reported, and no statistically significant differences were found in the 3-year survival between the two groups. The postoperative respiratory function of patients with open surgery showed a significant decrease compared to preoperative levels and were lower than those of RATS patients. In terms of health-related quality of life, RATS was associated with a better mean EQ-5D-5L index than open surgery (0.808 > 0.650, P < 0.05). In RATS, tumor sizes > 5 cm (mean ± SD = 0.768 ± 0.111, P = 0.028) and neurogenic tumors (mean ± SD = 0.702 ± 0.082, P < 0.001) remained significantly and independently associated with a lower EQ-5D-5L index. This study demonstrated that robot-assisted thoracic surgery for benign tumors of the cervicothoracic junction is a safe and technically feasible procedure, particularly for tumors < 5 cm and non-neurogenic tumors.


Assuntos
Neoplasias , Robótica , Cirurgia Torácica , Humanos , Qualidade de Vida , Resultado do Tratamento , Estudos Retrospectivos
8.
J Thorac Dis ; 15(10): 5585-5592, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37969296

RESUMO

Background: Rib tumors are typically curable through rib resection, associated with an excellent prognosis. Although transthoracic robotic first rib resection for thoracic outlet syndrome (TOS) has been previously documented, this paper presents our experience and technique in conducting robotic-assisted wire saw resections for high-position rib tumors. Methods: From January 2019 to May 2022, five patients diagnosed with high-position rib tumors underwent robotic-assisted wire saw resections. For our entire portal approach, we employed two 8-mm working ports, a 12-mm camera port, and a 12-mm assistant port. Data regarding the short-term and clinical long-term treatment effects were collected. Results: The median operation time was 124.2 minutes (range, 87-185 minutes), with no observed complications. The average intraoperative blood loss was 185 mL (range, 85-410 mL). Chest tubes were typically removed between 1 and 3 days post-operation. The average hospital stay post-surgery was 2.8 days, with a range of 2-5 days. We observed no relevant intraoperative or postoperative complications. No recurrence was reported during routine follow-ups 12 months post-surgery. Conclusions: Our findings indicate that the technique of robotic-assisted wire saw resection for high-position rib tumors is both feasible and reliable. This provides valuable insights for surgeons to consider robotic-assisted resection for high-position rib tumors.

9.
Cancer Med ; 12(23): 21199-21208, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37933476

RESUMO

BACKGROUND: The pancreatic index (PI) is a useful preoperative imaging predictor for pancreatic ductal adenocarcinoma (PDAC). In this retrospective study, we determined the predictive effect of PI to distinguish patients of pancreatic body/tail cancer (PBTC) with vascular involvement who can benefit from upfront surgery. METHOD: All patients who received distal pancreatectomy for PDAC from 2016 to 2020 at the Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine were considered for the study. A total of 429 patients with PBTC were assessed in relation to the value of PI. Fifty-five patients were eventually included and divided into low PI group and 29 patients in the normal PI group. RESULTS: The median overall survival (mOS) was significantly shorter in the low PI group (13.1 vs. 30.0 months, p = 0.002) in this study, and PI ≥ 0.78 (OR = 0.552, 95% CI: 0.301-0.904, p = 0.020) was an independent influencing factor confirmed by multivariate analysis. Subgroup analysis showed that PI was an independent prognostic factor for LA-PBTC (OR = 0.272, 95% CI: 0.077-0.969, p = 0.045). As for BR PBTC, PI (OR = 0.519, 95% CI: 0.285-0.947, p = 0.033) combined with carbohydrate antigen 125 (CA125) (OR = 2.806, 95% CI: 1.206-6.526, p = 0.017) and chemotherapy (OR = 0.327, 95% CI: 0.140-0.763, p = 0.010) were independent factors. CONCLUSION: This study suggests that the PI can be used as a predictive factor to optimize the surgical indication for PBTC with vascular involvement. Preoperative patients with normal PI and CA125 can achieve a long-term prognosis comparable to that of resectable PBTC patients.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Estudos Retrospectivos , Prognóstico , China , Neoplasias Pancreáticas/patologia , Pancreatectomia/métodos
10.
Adv Healthc Mater ; 12(29): e2301604, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37584445

RESUMO

Previous parathyroid hormone (PTH)-related peptides (PTHrPs) cannot be used to prevent implant loosening in osteoporosis patients due to the catabolic effect of local sustained release. A novel PTHrP (PTHrP-2) that can be used locally to promote osseointegration of macroporous titanium alloy scaffold (mTAS) and counteract implant slippage in osteoporosis patients is designed. In vitro, PTHrP-2 enhances the proliferation, adhesion, and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) within the mTAS. Further, it promotes proliferation, migration, angiogenesis-related protein expression, and angiogenesis in human umbilical vein endothelial cells (HUVECs). Compared to PTH(1-34), PTHrP-2 can partially weaken the osteoclast differentiation of RAW 264.7 cells. Even in an oxidative stress microenvironment, PTHrP-2 safeguards the proliferation and migration of BMSCs and HUVECs, reduces reactive oxygen species generation and mitochondrial damage, and partially preserves the angiogenesis of HUVECs. In the Sprague-Dawley (SD) rat osteoporosis model, the therapeutic benefits of PTHrP-2-releasing mTAS (mTASP2 ) and ordinary mTAS implanted for 12 weeks via micro-CT, sequential fluorescent labeling, and histology are compared. The results demonstrate that mTASP2 exhibits high bone growth rate, without osteophyte formation. Consequently, PTHrP-2 exhibits unique local synthesis properties and holds the potential for assisting the osseointegration of alloy implants in osteoporosis patients.


Assuntos
Osseointegração , Osteoporose , Ratos , Animais , Humanos , Proteína Relacionada ao Hormônio Paratireóideo/farmacologia , Proteína Relacionada ao Hormônio Paratireóideo/uso terapêutico , Titânio/química , Ratos Sprague-Dawley , Osteogênese , Ligas/farmacologia , Células Endoteliais , Osteoporose/tratamento farmacológico , Impressão Tridimensional
11.
STAR Protoc ; 4(2): 102298, 2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-37329508

RESUMO

Defects of glycosylphosphatidylinositol (GPI)-anchor synthesis lead to the production of pro-proteins with altered functions. However, pro-protein-specific antibodies for functional analysis are lacking. Here, we present a protocol to differentiate GPI-anchored prion protein (PrP) from pro-PrP in cancer cells using a complementary approach applicable to other GPI-anchored proteins. We first describe steps for phosphatidylinositol-specific phospholipase C treatment and flow-cytometry-based detection. We then detail the carboxypeptidase Y (CPDY) assay including antibody immobilization, affinity purification, CPDY treatment, and western-blot-based detection. For complete details on the use and execution of this protocol, please refer to Li et al. (2022).1.

12.
J Biol Chem ; 299(8): 104982, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37390992

RESUMO

Endoplasmic reticulum (ER) stress and unfolded protein response are cells' survival strategies to thwart disruption of proteostasis. Tumor cells are continuously being challenged by ER stress. The prion protein, PrP, normally a glycosylphosphatidylinositol (GPI)-anchored protein exists as a pro-PrP retaining its GPI-peptide signal sequence in human pancreatic ductal cell adenocarcinoma (PDAC). Higher abundance of pro-PrP indicates poorer prognosis in PDAC patients. The reason why PDAC cells express pro-PrP is unknown. Here, we report that persistent ER stress causes conversion of GPI-anchored PrP to pro-PrP via a conserved ATF6-miRNA449c-5p-PIGV axis. Mouse neurons and AsPC-1, a PDAC cell line, express GPI-anchored PrP. However, continuous culture of these cells with the ER stress inducers thapsigargin or brefeldin A results in the conversion of a GPI-anchored PrP to pro-PrP. Such a conversion is reversible; removal of the inducers allows the cells to re-express a GPI-anchored PrP. Mechanistically, persistent ER stress increases the abundance of an active ATF6, which increases the level of miRNA449c-5p (miR449c-5p). By binding the mRNA of PIGV at its 3'-UTRs, miR449c-5p suppresses the level of PIGV, a mannosyltransferase pivotal in the synthesis of the GPI anchor. Reduction of PIGV leads to disruption of the GPI anchor assembly, causing pro-PrP accumulation and enhancing cancer cell migration and invasion. The importance of ATF6-miR449c-5p-PIGV axis is recapitulated in PDAC biopsies as the higher levels of ATF6 and miR449c-5p and lower levels of PIGV are markers of poorer outcome for patients with PDAC. Drugs targeting this axis may prevent PDAC progression.


Assuntos
Adenocarcinoma , Carcinoma Ductal Pancreático , Estresse do Retículo Endoplasmático , Glicosilfosfatidilinositóis , Neoplasias Pancreáticas , Proteínas Priônicas , Animais , Humanos , Camundongos , Fator 6 Ativador da Transcrição/genética , Adenocarcinoma/patologia , Glicosilfosfatidilinositóis/metabolismo , Neoplasias Pancreáticas/metabolismo , Proteínas Priônicas/genética , Proteínas Priônicas/metabolismo , Neoplasias Pancreáticas
13.
Adv Sci (Weinh) ; 10(22): e2300516, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37229774

RESUMO

The local application of drug-loaded bioactive scaffold materials is one of the important directions to solve the clinical problem of osteoporotic (OP) bone defects. This study retains the advantages of drug loading and mechanical properties of natural 3D bioactive scaffolds. The scaffolds are functionally modified through chemical and self-assembly approaches with application of polydopamine (PDA) nanoparticles and parathyroid hormone-related peptide-1 (PTHrP-1) for efficient local drug loading. This study investigates the effects of the novel bioactive scaffolds on ossification, osteoclastogenesis, and macrophage polarization. This work elucidates the effects of the scaffolds in regulating osteoclastic activity and new bone formation in vitro. Further studies on the establishment and repair of OP bone defects in small animals are conducted, and the potential of natural bioactive porous scaffold materials to promote the repair of OP bone defects is initially verified. The preparation of safe and economical anti-OP bone repair material provides a theoretical basis for clinical translational applications.


Assuntos
Osteoporose , Alicerces Teciduais , Animais , Alicerces Teciduais/química , Regeneração Óssea , Proteína Relacionada ao Hormônio Paratireóideo/farmacologia , Proteína Relacionada ao Hormônio Paratireóideo/uso terapêutico , Osteogênese , Osteoporose/tratamento farmacológico
14.
Cancer Med ; 12(14): 15141-15148, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37255405

RESUMO

BACKGROUND: High body mass index was considered as a risk factor for minimally invasive surgery. The short-term outcomes of robot-assisted pancreaticoduodenectomy (RPD) remain controversial. This study aims to investigate the feasibility and advantage of RPD in patients with high body mass index compared to open pancreaticoduodenectomy (OPD). METHODS: Clinical data of 304 patients who underwent pancreaticoduodenectomy from January 2016 to December 2019 in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine was collected. Patients with BMI >25 kg/m2 were included and divided into RPD and OPD group. After PSM at a 1:1 ratio, 75 patients of OPD and 75 patients of RPD were recorded and analyzed. RESULTS: The RPD group showed advantages in the estimated blood loss (EBL) (323.3 mL vs. 480.7 mL, p = 0.010), the postoperative abdominal infection rate (24% vs. 44%, p = 0.010), the incidence of Clavien-Dindo III-V complications (14.7% vs. 28.0%, p = 0.042) over OPD group. CONCLUSION: RPD shows advantages in less EBL, lower incidence rate of Clavien-Dindo III-V complications over OPD in overweight and obese patients. RPD was confirmed as a safe and feasible surgical approach for overweight or obsess patients.


Assuntos
Laparoscopia , Neoplasias Pancreáticas , Robótica , Humanos , Pancreaticoduodenectomia/efeitos adversos , Índice de Massa Corporal , Pontuação de Propensão , Sobrepeso , Estudos Retrospectivos , Tempo de Internação , Resultado do Tratamento , China/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Neoplasias Pancreáticas/cirurgia
15.
Biomater Sci ; 11(10): 3486-3501, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-36974898

RESUMO

Bone defects are one of the toughest challenges faced by orthopedic surgeons worldwide, especially at critical sizes, which are caused by severe trauma, malignancy, or congenital disease. The ideal bone tissue-engineered scaffold for bone regeneration is the one that has good osteoconductivity, osteoinductivity, pore structure, and antibacterial properties. Metal ions have been recognized in recent years to be essential regulators of bone metabolism, and they are widely used for bone tissue engineering. In particular, zinc ions are of interest because of their ideal biocompatibility, osteogenesis-promoting properties, and antibacterial properties. Moreover, the dual role of strontium (Sr) in promoting osteogenesis and inhibiting osteolysis provides academic support for Zn-Sr co-doped scaffolds. Based on true bone ceramics (TBC), Zn-Sr-sintered scaffolds with good pore structures were prepared using immersion-calcination. The biocompatibility, cell adhesion, osteogenic properties, and antibacterial activity of Zn-Sr-sintered TBC scaffolds in bone marrow mesenchymal stem cells (BMSCs) are superior to those of control TBC scaffolds. The Zn-Sr-sintered TBC scaffold was used to repair rat cranial defects. Its good in vivo repair performance was confirmed by osseointegration and inward bone growth compared with that of the control TBC scaffold. Zn0.25Sr0.20-TBC is an ideal material for bone repair because of its good biocompatibility and favorable in vitro osteogenic properties.


Assuntos
Estrôncio , Alicerces Teciduais , Ratos , Animais , Estrôncio/farmacologia , Estrôncio/química , Alicerces Teciduais/química , Osteogênese , Engenharia Tecidual , Regeneração Óssea , Cerâmica/farmacologia , Cerâmica/química , Zinco/química
16.
Cell Rep ; 41(12): 111834, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36543142

RESUMO

Aberrant activation of receptor tyrosine kinase (RTK) is usually a result of mutation and plays important roles in tumorigenesis. How RTK without mutation affects tumorigenesis remains incompletely understood. Here we show that in human melanomas pro-prion (pro-PrP) is an adaptor protein for an E3 ligase c-Cbl, enabling it to polyubiquitinate activated insulin-like growth factor-1 receptor (IGF-1R), leading to enhanced melanoma metastasis. All human melanoma cell lines studied here express pro-PrP, retaining its glycosylphosphatidylinositol-peptide signal sequence (GPI-PSS). The sequence, PVILLISFLI in the GPI-PSS of pro-PrP, binds c-Cbl, docking c-Cbl to the inner cell membrane, forming a pro-PrP/c-Cbl/IGF-1R trimeric complex. Subsequently, IGF-1R polyubiquitination and degradation are augmented, which increases autophagy and tumor metastasis. Importantly, the synthetic peptide PVILLISFLI disrupts the pro-PrP/c-Cbl/IGF-1R complex, reducing cancer cell autophagy and mitigating tumor aggressiveness in vitro and in vivo. Targeting cancer-associated GPI-PSS may provide a therapeutic approach for treating human cancers expressing pro-PrP.


Assuntos
Melanoma , Príons , Humanos , Ubiquitina-Proteína Ligases/metabolismo , Proteínas de Membrana/metabolismo , Príons/metabolismo , Linhagem Celular Tumoral , Melanoma/patologia , Ubiquitinação , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Carcinogênese , Proteínas Proto-Oncogênicas c-cbl/genética , Proteínas Proto-Oncogênicas c-cbl/metabolismo
17.
J Control Release ; 352: 338-370, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36206948

RESUMO

Glioma is often referred to as one of the most dreadful central nervous system (CNS)-specific tumors with rapidly-proliferating cancerous glial cells, accounting for nearly half of the brain tumors at an annual incidence rate of 30-80 per a million population. Although glioma treatment remains a significant challenge for researchers and clinicians, the rapid development of nanomedicine provides tremendous opportunities for long-term glioma therapy. However, several obstacles impede the development of novel therapeutics, such as the very tight blood-brain barrier (BBB), undesirable hypoxia, and complex tumor microenvironment (TME). Several efforts have been dedicated to exploring various nanoformulations for improving BBB permeation and precise tumor ablation to address these challenges. Initially, this article briefly introduces glioma classification and various pathogenic factors. Further, currently available therapeutic approaches are illustrated in detail, including traditional chemotherapy, radiotherapy, and surgical practices. Then, different innovative treatment strategies, such as tumor-treating fields, gene therapy, immunotherapy, and phototherapy, are emphasized. In conclusion, we summarize the article with interesting perspectives, providing suggestions for future glioma diagnosis and therapy improvement.


Assuntos
Neoplasias Encefálicas , Glioma , Nanoestruturas , Humanos , Glioma/terapia , Glioma/tratamento farmacológico , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/tratamento farmacológico , Nanomedicina , Nanoestruturas/uso terapêutico , Barreira Hematoencefálica , Microambiente Tumoral
18.
Cancer Med ; 11(18): 3397-3406, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35434972

RESUMO

BACKGROUND: The pre-adjuvant chemotherapy (PAC) status of postoperative pancreatic ductal adenocarcinoma (PDAC) patients has not been studied and elaborated well previously. METHOD: The association of PAC variables and prognoses was explored using a multivariable Cox model, restricted cubic spline analysis, and correlation analysis. The main outcomes were overall survival (OS) and progression-free survival (PFS). The secondary outcome was chemotherapy completeness (CHC). RESULTS: A total of 401 eligible patients were enrolled in sequential surgery and chemotherapy. The chemotherapy regimen, PAC fasting blood glucose (FBG), and elevated fasting blood glucose (eFBG) status were associated with CHC (regimen types: p = 0.005, continuous FBG: p = 0.014, eFBG status: p = 0.012). Early administration of adjuvant chemotherapy (<34 days) was a risk factor for the limited OS and PFS (OS: aHR: 1.61 [1.09-2.38], p = 0.016; PFS: aHR: 1.91 [1.29-2.82], p = 0.001). Patients with higher PAC body mass index (BMI), receiving Gemcap regimen, and with lower PAC tumor marker value were observed with better survival prognoses (PAC BMI: OS: 0.927 [0.875-0.983], p = 0.011; Gemcap: OS: 0.533 [0.312-0.913], p = 0.022; Gemcap: PFS: 0.560 [0.341-0.922], p = 0.023; PAC CA125: OS: 1.004 [1.002-1.006], p < 0.001; PAC CA125: PFS: 1.003 [1.000-1.005], p = 0.031; PAC CEA: OS: 1.050 [1.026-1.074], p < 0.001). The BMI decrease was mainly concentrated in the first 3 months of chemotherapy courses (first 3 months: p < 0.001; latter 3 months: p = 0.097). And CEA, compared to CA125 and CA199, was a better prognostic indicator (CEA: first 3 months: PFS p = 0.011, OS p < 0.001; latter 3 months: PFS p = 0.024, OS p = 0.041). CONCLUSION: PDAC patients should be treated with adjuvant chemotherapy over 34 postoperative days. PAC sarcopenia was a risk factor for OS, but not PFS and limited CHC. Those with higher PAC FBG levels were more likely to finish chemotherapy. CEA, compared to CA125 and CA199, was a better prognostic indicator.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Biomarcadores Tumorais , Glicemia , Antígeno Ca-125 , Antígeno Carcinoembrionário , Carcinoma Ductal Pancreático/patologia , Quimioterapia Adjuvante , Humanos , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos , Neoplasias Pancreáticas
19.
Adv Sci (Weinh) ; 9(11): e2103820, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35128831

RESUMO

Bone tissue engineering is becoming an ideal strategy to replace autologous bone grafts for surgical bone repair, but the multihierarchical complexity of natural bone is still difficult to emulate due to the lack of suitable biomaterials. Supramolecular peptide nanofiber hydrogels (SPNHs) are emerging biomaterials because of their inherent biocompatibility, satisfied biodegradability, high purity, facile functionalization, and tunable mechanical properties. This review initially focuses on the multihierarchical fabrications by SPNHs to emulate natural bony extracellular matrix. Structurally, supramolecular peptides based on distinctive building blocks can assemble into nanofiber hydrogels, which can be used as nanomorphology-mimetic scaffolds for tissue engineering. Biochemically, bioactive motifs and bioactive factors can be covalently tethered or physically absorbed to SPNHs to endow various functions depending on physiological and pharmacological requirements. Mechanically, four strategies are summarized to optimize the biophysical microenvironment of SPNHs for bone regeneration. Furthermore, comprehensive applications about SPNHs for bone tissue engineering are reviewed. The biomaterials can be directly used in the form of injectable hydrogels or composite nanoscaffolds, or they can be used to construct engineered bone grafts by bioprinting or bioreactors. Finally, continuing challenges and outlook are discussed.


Assuntos
Nanofibras , Engenharia Tecidual , Materiais Biocompatíveis/química , Hidrogéis/química , Nanofibras/química , Peptídeos
20.
J Med Virol ; 94(4): 1535-1539, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34850404

RESUMO

The novel coronavirus disease 2019 (COVID-19) has become a global health emergency. Early detection and intervention are key factors for improving outcomes in patients with COVID-19. Real-time reverse transcriptase polymerase chain reaction-based molecular assays and antibody for detecting SARS-CoV-2 in respiratory specimens are the current reference standard for COVID-19 diagnosis. Clinical implications of different specimen types for nucleic acid and antibody testing of COVID-19 in Zhongnan hospital of Wuhan University were analyzed. Compared with health groups, tumor patients had higher rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (+/-) immunoglobulin M (IgM) (+) immunoglobulin G (IgG) (+). The rate of SARS-CoV-2 (-) IgM (+) IgG (-) or SARS-CoV-2 (-) IgM (-) IgG (+) in female was significantly higher than that in male. These results can help governments to take screening measures to prevent the COVID-19 pandemic again.


Assuntos
Anticorpos Antivirais/sangue , COVID-19/epidemiologia , Neoplasias/epidemiologia , SARS-CoV-2/isolamento & purificação , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/imunologia , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/imunologia , Teste para COVID-19 , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lactente , Recém-Nascido , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , SARS-CoV-2/imunologia , Sensibilidade e Especificidade , Distribuição por Sexo , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA