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1.
Cell ; 157(4): 785-94, 2014 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-24813606

RESUMO

Polar bears are uniquely adapted to life in the High Arctic and have undergone drastic physiological changes in response to Arctic climates and a hyper-lipid diet of primarily marine mammal prey. We analyzed 89 complete genomes of polar bear and brown bear using population genomic modeling and show that the species diverged only 479-343 thousand years BP. We find that genes on the polar bear lineage have been under stronger positive selection than in brown bears; nine of the top 16 genes under strong positive selection are associated with cardiomyopathy and vascular disease, implying important reorganization of the cardiovascular system. One of the genes showing the strongest evidence of selection, APOB, encodes the primary lipoprotein component of low-density lipoprotein (LDL); functional mutations in APOB may explain how polar bears are able to cope with life-long elevated LDL levels that are associated with high risk of heart disease in humans.


Assuntos
Evolução Biológica , Ursidae/classificação , Ursidae/genética , Adaptação Fisiológica , Tecido Adiposo/metabolismo , Animais , Apolipoproteínas B/química , Apolipoproteínas B/metabolismo , Regiões Árticas , Ácidos Graxos/metabolismo , Fluxo Gênico , Genética Populacional , Genoma , Ursidae/fisiologia
2.
Angew Chem Int Ed Engl ; 63(24): e202403050, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38579168

RESUMO

Unstable Zn interface with serious detrimental parasitic side-reactions and uncontrollable Zn dendrites severely plagues the practical application of aqueous zinc-ion batteries. The interface stability was closely related to the electrolyte configuration and Zn2+ depositional behavior. In this work, a unique Zn-ion anchoring strategy is originally proposed to manipulate the coordination structure of solvated Zn-ions and guide the Zn-ion depositional behavior. Specifically, the amphoteric charged ion additives (denoted as DM), which act as zinc-ion anchors, can tightly absorb on the Zn surface to guide the uniform zinc-ion distribution by using its positively charged -NR4 + groups. While the negatively charged -SO3 - groups of DM on the other hand, reduces the active water molecules within solvation sheaths of Zn-ions. Benefiting from the special synergistic effect, Zn metal exhibits highly ordered and compact (002) Zn deposition and negligible side-reactions. As a result, the advanced Zn||Zn symmetric cell delivers extraordinarily 7000 hours long lifespan (0.25 mA cm-2, 0.25 mAh cm-2). Additionally, based on this strategy, the NH4V4O10||Zn pouch-cell with low negative/positive capacity ratio (N/P ratio=2.98) maintains 80.4 % capacity retention for 180 cycles. A more practical 4 cm*4 cm sized pouch-cell could be steadily cycled in a high output capacity of 37.0 mAh over 50 cycles.

3.
Angew Chem Int Ed Engl ; : e202406906, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38819764

RESUMO

Eutectic electrolytes show potential beyond conventional low-concentration electrolytes (LCEs) in zinc (Zn)-ion capacitors (ZICs) yet suffer from high viscosity and sluggish kinetics. Herein, we originally develop an intrinsically decoupling strategy to address these issues, producing a novel electrolyte termed "quasi-eutectic" electrolyte (quasi-EE). Joint experimental and theoretical analyses confirm its unique solution coordination structure doped with near-LCE domains. This enables the quasi-EE well inherit the advanced properties at deep-eutectic states while provide facilitated kinetics as well as lower energy barriers via a vehicle/hopping-hybridized charge transfer mechanism. Consequently, a homogeneous electroplating pattern with much enhanced Sandꞌs time is achieved on the Zn surface, followed by a twofold prolonged service-life with drastically reduced concentration polarization. More encouragingly, the quasi-EE also delivers increased capacitance output in ZICs, which is elevated by 12.4%-144.6% compared to that before decoupling. Furthermore, the pouch cell with a cathodic mass loading of 36.6 mg cm-2 maintains competitive cycling performances over 600 cycles, far exceeding other Zn-based counterparts. This work offers fresh insights into eutectic decoupling and beyond.

4.
J Cell Mol Med ; 27(4): 538-552, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36729917

RESUMO

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths among cancer patients. Vascular endothelial growth factor A (VEGFA) is involved in regulating biological processes, such as angiogenesis and vascular permeability, and is very closely related to the pathogenesis of various tumours, especially vascular-rich, solid tumours. Clinical data of patients with HCC and other tumours were analysed through public databases, such as the TCGA database, Gene Expression Omnibus database, Human Protein Atlas database, STRING, Tumour Immune Estimation Resource and Kaplan-Meier Plotter. The tumour tissues and adjacent normal tissues of patients with HCC from Hunan Provincial People's Hospital were collected to verify the expression of VEGFA by immunohistochemistry, immunofluorescence, Western blotting and qPCR. VEGFA expression is elevated in multiple tumour types and correlates with the prognosis of tumour patients. VEGFA is involved in regulating the tumour microenvironment and immune cell function in tumour development. Inhibition of VEGFA reduces proliferation, invasion, and migration and promotes apoptosis in HCC cells. VEGFA is a potential predictive biomarker for the diagnosis and prognosis of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Prognóstico , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Biomarcadores Tumorais/genética , Microambiente Tumoral/genética
5.
J Cell Mol Med ; 27(8): 1131-1143, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36965158

RESUMO

During exogenous bone-graft-mediated bone defect repair, macrophage inflammation dictates angiogenesis and bone regeneration. Exosomes from different human cells have shown macrophage immunomodulation-mediated bone regeneration potential. However, the effect of human serum-derived exosomes (serum-Exo) on macrophage immunomodulation-mediated angiogenesis during bone defect repair has not been investigated yet. In this study, we explored the effects of serum-Exo on macrophage inflammation regulation-mediated angiogenesis during bone defect repair and preliminarily elucidated the mechanism. Healthy serum-Exo was isolated by ultracentrifugation. The effect of serum-Exo on LPS-induced M1 macrophage inflammation was analysed in vitro. The conditioned medium of serum-Exo-treated LPS-induced M1 macrophage (serum-Exo-treated M1 macrophage-CM) was used to culture human umbilical vein endothelial cells (HUVEC), and the effect on angiogenesis was analysed by western blot, qRT-PCR, etc. mRNA-sequencing of HUVECs was performed to identify deferentially expressed genes. Finally, the rat mandibular defect model was established and treated with Bio-Oss and Bio-Oss + Exo. The effect of the Bio-Oss + Exo combination on mandibular bone regeneration was observed by micro-computed tomography (micro-CT), haematoxylin and eosin (HE) staining, Masson staining, and immunohistochemical staining. Serum-Exo promoted the proliferation of RAW264.7 macrophages and reduced the expression of M1-related genes such as IL-6, IL-1ß, iNOS, and CD86. Serum-Exo-treated M1 macrophage-CM induced the proliferation, migration, and angiogenic differentiation of HUVEC, as well as the expression of H-type blood vessel markers CD31 and endomucin (EMCN), compared with M1 macrophage-CM. Moreover, higher expression of vascular endothelial adhesion factor 1 (VCAM1) in HUVEC cultured with serum-Exo-treated M1 macrophage-CM compared with M1 macrophages-CM. Inhibition of VCAM1 signalling abrogated the pro-angiogenic effect of serum-Exo-treated M1 macrophage-CM on HUVEC. Local administration of serum-Exo during mandibular bone defect repair reduced the number of M1 macrophages and promoted angiogenesis and osteogenesis. Collectively, our results demonstrate the macrophage inflammation regulation-mediated pro-angiogenic potential of serum-Exo during bone defect repair possibly via upregulation of VCAM1 signalling in HUVEC.


Assuntos
Exossomos , Humanos , Ratos , Animais , Exossomos/metabolismo , Lipopolissacarídeos/metabolismo , Microtomografia por Raio-X , Regeneração Óssea/genética , Células Endoteliais da Veia Umbilical Humana/metabolismo , Inflamação/genética , Inflamação/metabolismo , Macrófagos
6.
Small ; 19(49): e2303457, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37394714

RESUMO

Water-induced parasitic reactions and uncontrolled dendritic Zn growth are long-lasting tricky problems that severely hinder the development of aqueous zinc-metal batteries. Those notorious issues are closely related to electrolyte configuration and zinc-ion transport behavior. Herein, through constructing aligned dipoles induced electric-field on Zn surface, both the solvation structure and transport behavior of zinc-ions are fundamentally changed. The vertically ordered zinc-ion migration trajectory and gradually concentrated zinc-ion achieved inside the polarized electric-field remarkably eliminate water related side-reactions and Zn dendrites. Zn-metal under the polarized electric-field demonstrated significantly improve reversibility and a dendrite-free surface with strong (002) Zn deposition texturing. Zn||Zn symmetric cell delivers greatly prolonged lifespan up to 1400 h (17 times longer than that of the cell based on bare Zn) while the Zn||Cu half-cell demonstrate ultrahigh 99.9% coulombic efficiency. NH4 V4 O10 ||Zn half-cell delivered exceptional-high 132 mAh g-1 capacity after ultralong 2000 cycles (≈100% capacity retention). In addition, MnO2 ||Zn pouch-cell under aligned dipoles induced electric-field maintains 87.9% capacity retention after 150 cycles under practical condition of high MnO2 mass loading (≈10 mg cm-2 ) and limited N/P ratio. It is considered that this new strategy can also be implemented to other metallic batteries and spur the development of batteries with long-lifespan and high-energy-density.

7.
BMC Cancer ; 23(1): 637, 2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37420211

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common human cancers with poor prognosis in the world. HCC has become the second leading cause of cancer-related death in China. It is urgent to identify novel biomarker and valid target to effectively diagnose, treat or predict the prognosis of HCC. It has been reported that S100A family is closely related to cell proliferation and migration of different cancers. However, the values of S100As in HCC remain to be further analyzed. METHODS: We investigated the transcriptional and translational expression of S100As, as well as the value of this family in HCC patients from the various databases. RESULTS: S100A10 was most relevant to HCC. CONCLUSIONS: The results from HCC patients' tissues and different cells also confirmed the role of S100A10 in HCC. Furthermore, we proved that S100A10 could influenced the cell proliferation of HCC cells via ANXA2/Akt/mTOR pathway. However, it would appear that the relationship between S100A10 and HCC is complex and requires more research.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Biomarcadores , Proliferação de Células/genética , Linhagem Celular , Prognóstico
8.
Cell Mol Biol (Noisy-le-grand) ; 69(9): 43-51, 2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37807335

RESUMO

Lactobacillus acidophilus is widely used as a food additive or medication in our daily lives. The objective of this study was to investigate the effects of L. acidophilus and L. reuteri on bone mass in OVX mice and their associated mechanisms. Fifty 6-week-old female C57BL/6J mice were subjected to five different treatments: sham surgery, OVX surgery, OVXandL. reuteri fed, OVXandL. acidophilus fed, OVXandboth L. reuteri and L. acidophilus co-fed, respectively. Serum samples were collected, and IL-1ß,IL-6,TNF-α, and OCN levels were determined. The bone volume fraction and trabecular number, trabecular thickness, trabecular separation, and cortical thickness of the mice were analyzed by micro-CT in both femurs. Mice feces were taken for Illumina high-throughput sequencing to analyze the microbial composition and characteristics. After probiotic feeding, the bone volume fraction, the trabecular number, and the trabecular thickness increased, and the trabecular separation decreased in OVX mice. IL-1ß, IL-6, and TNF-α in the blood significantly decreased. The observed Chao1 and ACE indexes increased significantly. Changes in intestinal microorganisms occurred in all groups of mice. The change of index in the gut microbes, may indicate that the bone mass of OVX mice is changing. L. acidophilus shares the same role as L. reuteri in preventing bone loss in OVX mice. The mechanism of action may be through inhibition of the activation of inflammatory factors in the osteoclast activation pathway in bone metabolism, modulation of gut microbial diversity, and alteration of the richness of specific microorganisms that lead to attenuation of bone loss.


Assuntos
Microbioma Gastrointestinal , Limosilactobacillus reuteri , Probióticos , Camundongos , Feminino , Animais , Humanos , Lactobacillus acidophilus , Fator de Necrose Tumoral alfa , Interleucina-6 , Camundongos Endogâmicos C57BL , Probióticos/farmacologia , Probióticos/uso terapêutico , Ovariectomia
9.
BMC Anesthesiol ; 23(1): 105, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-37005591

RESUMO

BACKGROUND: The benefit of remote ischemia preconditioning (RIPreC) in pediatric cardiac surgery is unclear. The objective of this systematic review and meta-analysis was to examine the effectiveness of RIPreC in reducing the duration of mechanical ventilation and intensive care unit (ICU) length of stay after pediatric cardiac surgery. METHODS: We searched PubMed, EMBASE and the Cochrane Library from inception to December 31, 2022. Randomized controlled trials comparing RIPreC versus control in children undergoing cardiac surgery were included. The risk of bias of included studies was assessed using the Risk of Bias 2 (RoB 2) tool. The outcomes of interest were postoperative duration of mechanical ventilation and ICU length of stay. We conducted random-effects meta-analysis to calculate weighted mean difference (WMD) with 95% confidence interval (CI) for the outcomes of interest. We performed sensitivity analysis to examine the influence of intraoperative propofol use. RESULTS: Thirteen trials enrolling 1,352 children were included. Meta-analyses of all trials showed that RIPreC did not reduce postoperative duration of mechanical ventilation (WMD -5.35 h, 95% CI -12.12-1.42) but reduced postoperative ICU length of stay (WMD -11.48 h, 95% CI -20.96- -2.01). When only trials using propofol-free anesthesia were included, both mechanical ventilation duration (WMD -2.16 h, 95% CI -3.87- -0.45) and ICU length of stay (WMD -7.41 h, 95% CI -14.77- -0.05) were reduced by RIPreC. The overall quality of evidence was moderate to low. CONCLUSIONS: The effects of RIPreC on clinical outcomes after pediatric cardiac surgery were inconsistent, but both postoperative mechanical ventilation duration and ICU length of stay were reduced in the subgroup of children not exposed to propofol. These results suggested a possible interaction effect of propofol. More studies with adequate sample size and without intraoperative propofol use are needed to define the role of RIPreC in pediatric cardiac surgery.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Precondicionamento Isquêmico , Propofol , Criança , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Respiração Artificial
10.
Chem Biodivers ; 20(2): e202200897, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36631429

RESUMO

Quercetin is a kind of polyphenolic flavonoid compounds which has perfect antioxidant properties. However, quercetin is not available in many situations due to its poor bioavailability. In this work, the QAEs with better solubility and even stronger antioxidant properties were synthesized, through the esterification between quercetin and the chlorinated cinnamic acid or its derivatives, whose chlorination were achieved by using SOCl2 . The protective effects of the QAEs were evaluated by the H2 O2 -induced apoptosis experiment in rat adrenal pheochromocytoma cells (PC12 cells) and its ability to remove ROS generated by oxidative stress. Compared with the original quercetin group, the QAEs groups showed much improved cell viability and capability of removing ROS, which means their higher bioavailability than the parent.


Assuntos
Antioxidantes , Quercetina , Ratos , Animais , Quercetina/farmacologia , Antioxidantes/farmacologia , Espécies Reativas de Oxigênio , Células PC12 , Ésteres/farmacologia , Estresse Oxidativo
11.
Sensors (Basel) ; 23(7)2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-37050633

RESUMO

This work presents a framework that allows Unmanned Surface Vehicles (USVs) to avoid dynamic obstacles through initial training on an Unmanned Ground Vehicle (UGV) and cross-domain retraining on a USV. This is achieved by integrating a Deep Reinforcement Learning (DRL) agent that generates high-level control commands and leveraging a neural network based model predictive controller (NN-MPC) to reach target waypoints and reject disturbances. A Deep Q Network (DQN) utilized in this framework is trained in a ground environment using a Turtlebot robot and retrained in a water environment using the BREAM USV in the Gazebo simulator to avoid dynamic obstacles. The network is then validated in both simulation and real-world tests. The cross-domain learning largely decreases the training time (28%) and increases the obstacle avoidance performance (70 more reward points) compared to pure water domain training. This methodology shows that it is possible to leverage the data-rich and accessible ground environments to train DRL agent in data-poor and difficult-to-access marine environments. This will allow rapid and iterative agent development without further training due to the change in environment or vehicle dynamics.

12.
Int J Mol Sci ; 24(15)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37569697

RESUMO

Piwi proteins play a significant role in germ cell development and the silencing of transposons in animals by associating with small non-coding RNAs known as Piwi-interacting RNAs (piRNAs). While the Piwi gene has been well characterized in various insect species, the role of the Piwi (PxPiwi) gene in the diamondback moth (Plutella xylostella), a globally distributed pest of cruciferous crops, remains unclear. Expression analysis demonstrated the upregulation of PxPiwi in pupae and testes. Furthermore, we generated a PxPiwi-knockout mutant using CRISPR/Cas9 technology, which resulted in a significantly prolonged pupal stage and the failure of pupae to develop into adults. Additionally, the knockdown of PxPiwi, through RNA interference (RNAi), led to a substantial decrease in the oviposition and hatchability of P. xylostella. These findings indicate that PxPiwi is specifically expressed and essential for the development and reproduction of P. xylostella. This is the first report indicating the involvement of the Piwi gene in the development of lepidopteran insects, except for reproduction and germ cell development, which provides a foundation for future investigations into the functions of PxPiwi.


Assuntos
Mariposas , Animais , Feminino , Mariposas/fisiologia , Reprodução/genética , Oviposição , Larva/metabolismo
13.
Acta Orthop Belg ; 89(2): 354-361, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37924554

RESUMO

The posterolateral tibial plateau fracture is an uncommon intra-articular injury and mostly needed surgery. However, its surgical approach remains controversial. This manuscript describes an anterolateral approach to treat posterolateral tibial plateau fractures and evaluates the patient's functional outcomes. From June 2018 to July 2021 seventeen patients with posterolateral tibial plateau fractures were surgically treated through an anterolateral approach. The intraoperative and postoperative follow-up indicators were recorded. The reduction quality of fractures was assessed using Rasmussen radiological score, and postsurgical functional recovery was estimated using Rasmussen clinical score and Lysholm score. The mean follow-up interval was 28.71 ± 9.61 months (range 18-44). The surgery time and blood loss were 111.06 ± 15.62 min (range 85-140) and 118.12 ± 38.45 mL (range 80-250) separately. Postoperatively, the Rasmussen radiological score was 16.24 ± 2.33 (range 12-18). The average time of bone union was 14.29 ± 1.53 weeks (range 12-18). At the final follow-up, the average PTS and MPTA were 9.71 ± 2.76° (range 5-14°) and 86.82 ± 2.04° (range 84-90°) separately. A satisfactory articular reduction was achieved in 16 patients (94.1%). The final ROM was 123.29 ± 19.70° (range 60-142°). The Rasmussen clinical score and Lysholm score were 25.71 ± 5.74 (range 10-30) and 91.47 ± 6.50 (range 75-98) separately. Anterolateral approach has minimal risk of intraoperative neurovascular injuries in the popliteal fossa with satisfactory results. The hardware removal was also facilitated. This approach is feasible, safe and efficient.


Assuntos
Fraturas da Tíbia , Fraturas do Planalto Tibial , Humanos , Resultado do Tratamento , Fixação Interna de Fraturas/métodos , Consolidação da Fratura , Fraturas da Tíbia/diagnóstico por imagem , Fraturas da Tíbia/cirurgia , Estudos Retrospectivos , Placas Ósseas
14.
Small ; 18(17): e2200710, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35304816

RESUMO

Therapeutics that can be activated by radiation in situ to enhance the efficacy of radiotherapy are highly desirable. Herein, 7-Dehydrocholesterol (7-DHC), a biosynthetic precursor of cholesterol, as a radiosensitizer, exploiting its ability to propagate the free radical chain reaction is explored. The studies show that 7-DHC can react with radiation-induced reactive oxygen species and in turn promote lipid peroxidation, double-strand breaks, and mitochondrial damage in cancer cells. For efficient delivery, 7-DHC is encapsulated into poly(lactic-co-glycolic acid) nanoparticles, forming 7-DHC@PLGA NPs. When tested in CT26 tumor bearing mice, 7-DHC@PLGA NPs significantly enhanced the efficacy of radiotherapy, causing complete tumor eradication in 30% of the treated animals. After treatment, 7-DHC is converted to cholesterol, causing no detectable side effects or hypercalcemia. 7-DHC@PLGA NPs represent a radiation-responsive sensitizer with great potential in clinical translation.


Assuntos
Nanopartículas , Neoplasias , Radiossensibilizantes , Animais , Linhagem Celular Tumoral , Desidrocolesteróis , Ácido Láctico , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Ácido Poliglicólico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Radiossensibilizantes/farmacologia , Radiossensibilizantes/uso terapêutico
15.
Bioconjug Chem ; 33(4): 654-665, 2022 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-35385661

RESUMO

Radiation therapy (RT) concurrent with chemotherapy improves local lung cancer control but may cause systemic toxicity. There is an unmet clinical need of treatments that can selectively sensitize cancer cells to RT. Herein, we explored a radiosensitizing strategy that combines doxorubicin (DOX)-encapsulated polyaspartamide nanoparticles and 5-aminolevulinic acid (5-ALA). The DOX-polyaspartamide nanoparticles were coupled with NTSmut, a ligand specific to neurotensin receptor type 1 (NTSR1), for lung cancer targeting. DOX was coupled to the polymer backbone through a pH-sensitive hydrazone linker, which allows for controlled release of the drug in an acidic tumor micromovement. Meanwhile, 5-ALA accumulates in the cancer cell's mitochondria, forming protoporphyrin (PpIX) that amplifies RT-induced oxidative stress. When tested in vitro in H1299 cells, DOX-encapsulated nanoparticles in conjugation with 5-ALA enhanced cancer cell killing owing to the complementary radiosensitizing effects of DOX and 5-ALA. In vivo studies confirmed that the combination improved tumor suppression relative to RT alone without causing toxicity to normal tissues. Overall, our study suggests an effective and selective radiosensitizing approach.


Assuntos
Neoplasias Pulmonares , Nanopartículas , Ácido Aminolevulínico , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Humanos , Concentração de Íons de Hidrogênio , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Polímeros
16.
BMC Cancer ; 22(1): 818, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35883111

RESUMO

BACKGROUND: The mTOR signaling pathway plays an important role in cancer. As a master regulator, the status of MTOR affects pathway activity and the efficacy of mTOR inhibitor therapy. However, little research has been performed to explore MTOR in colorectal cancer (CRC). METHODS: In this study, gene expression and clinical data were analyzed using The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Signaling pathways related to MTOR in CRC were identified by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA). Somatic mutation data were downloaded from TCGA and analyzed using the maftools R package. Tumor Immune Estimation Resource (TIMER) and CIBERSORT were used to analyze correlations between MTOR and tumor-infiltrating immune cells (TIICs). Finally, we detected MTOR mutations in a CRC cohort from our database using whole-exome sequencing. RESULTS: We found that MTOR was overexpressed in Asian CRC patients and associated with a poor prognosis. Enrichment analysis showed that MTOR was involved in metabolism, cell adhesion, and translation pathways in CRC. High MTOR expression was correlated with high tumor mutation burden (TMB) and several TIICs. Finally, we found that the mTOR signaling pathway was activated in CRC lines characterized by microsatellite instability (MSI), and the frequency of MTOR mutations was higher in MSI-high (MSI-H) patients than in microsatellite stable (MSS) patients. CONCLUSIONS: MTOR may represent a comprehensive indicator of prognosis and immunological status in CRC. The genomic signatures of MTOR may provide guidance for exploring the role of mTOR inhibitors in CRC.


Assuntos
Neoplasias Colorretais , Biomarcadores Tumorais/genética , Neoplasias Colorretais/patologia , Genômica , Humanos , Instabilidade de Microssatélites , Prognóstico , Serina-Treonina Quinases TOR/genética
17.
J Nanobiotechnology ; 20(1): 330, 2022 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-35842630

RESUMO

BACKGROUND: Radiodynamic therapy (RDT) holds the potential to overcome the shallow tissue penetration issue associated with conventional photodynamic therapy (PDT). To this end, complex and sometimes toxic scintillator-photosensitizer nanoconjugates are often used, posing barriers for large-scale manufacturing and regulatory approval. METHODS: Herein, we report a streamlined RDT strategy based on CsI(Na)@MgO nanoparticles and 5-aminolevulinic acid (5-ALA). 5-ALA is a clinically approved photosensitizer, converted to protoporphyrin IX (PpIX) in cancer cells' mitochondria. CsI(Na)@MgO nanoparticles produce strong ~ 410 nm X-ray luminescence, which matches the Soret band of PpIX. We hypothesize that the CsI(Na)@MgO-and-5-ALA combination can mediate RDT wherein mitochondria-targeted PDT synergizes with DNA-targeted irradiation for efficient cancer cell killing. Because scintillator nanoparticles and photosensitizer are administered separately, the approach forgoes issues such as self-quenching or uncontrolled release of photosensitizers. RESULTS: When tested in vitro with 4T1 cells, the CsI(Na)@MgO and 5-ALA combination elevated radiation-induced reactive oxygen species (ROS), enhancing damages to mitochondria, DNA, and lipids, eventually reducing cell proliferation and clonogenicity. When tested in vivo in 4T1 models, RDT with the CsI(Na)@MgO and 5-ALA combination significantly improved tumor suppression and animal survival relative to radiation therapy (RT) alone. After treatment, the scintillator nanoparticles, made of low-toxic alkali and halide elements, were efficiently excreted, causing no detectable harm to the hosts. CONCLUSIONS: Our studies show that separately administering CsI(Na)@MgO nanoparticles and 5-ALA represents a safe and streamlined RDT approach with potential in clinical translation.


Assuntos
Nanopartículas , Fotoquimioterapia , Ácido Aminolevulínico/farmacologia , Animais , Linhagem Celular Tumoral , Óxido de Magnésio , Nanopartículas/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico
18.
Langenbecks Arch Surg ; 407(6): 2453-2462, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35589848

RESUMO

BACKGROUND: Chylous ascites (CA) after laparoscopic D3 lymphadenectomy for right colon cancer is not rare. However, the risk factors for CA have not been fully explored. Few studies have investigated the effect of CA on long-term prognosis. METHODS: The clinical data of patients with right colon cancer who underwent laparoscopic D3 lymphadenectomy in five centers from January 2013 to December 2018 were retrospectively collected. Univariate and multivariate analyses were performed to determine the clinicopathological factors associated with CA. Then, the long-term prognosis of patients with and without CA was compared by propensity score matching and Kaplan-Meier survival analysis. RESULTS: The incidence of CA was 4.4% (48/1090). Pathological T stage (p = 0.025), dissection along the left side of the superior mesenteric artery (p < 0.001) and the number of retrieved lymph nodes (p < 0.001) were independent risk factors for CA. After propensity score matching, 48 patients in the CA group and 353 patients in the non-CA group were enrolled. Kaplan-Meier survival analysis indicated that CA was not associated with overall survival (p = 0.454) and disease-free survival (p = 0.163). In patients with stage III right colon cancer, there were no significant differences in overall survival (p = 0.501) and disease-free survival (p = 0.254). CONCLUSIONS: Pathological T stage, number of retrieved lymph nodes, and left side dissection along the superior mesenteric artery were independent risk factors for CA after laparoscopic D3 lymphadenectomy. CA does not impair the oncological outcomes of patients.


Assuntos
Ascite Quilosa , Neoplasias do Colo , Laparoscopia , Ascite Quilosa/etiologia , Ascite Quilosa/cirurgia , Colectomia/efeitos adversos , Neoplasias do Colo/patologia , Intervalo Livre de Doença , Humanos , Laparoscopia/efeitos adversos , Excisão de Linfonodo/efeitos adversos , Estudos Retrospectivos , Fatores de Risco
19.
J Integr Neurosci ; 21(4): 109, 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35864761

RESUMO

BACKGROUND: Peripheral nerve regeneration is a coordinated process of Schwann cell (SC) reprogramming and intrinsic neuronal growth program activation. Panaxydol (PND) is a strong biologically active traditional Chinese medicine monomer extracted from Panax notoginseng rhizomes. In vitro, PND protects neurons and SCs from injury and stimulates the expression and secretion of neurotrophic factors (NTFs) by SCs. We hypothesized that PND may also promote peripheral nerve regeneration in adult animals. METHODS: PND (10 mg/kg body weight) was injected intraperitoneally into the Sprague-Dawley (SD) rats for two consecutive weeks after sciatic nerve transection. The morphology of the repaired sciatic nerve was evaluated after 16 weeks, and sensory and motor function recovery was evaluated using functional and behavioral techniques. RESULTS: PND was biologically safe at an injection dose of 10 mg/kg/day. After 14 days, it significantly increased the myelination of regenerated nerve fibers, and promoted sensory and motor function recovery. In the early stage of injury, PND significantly upregulated the mRNA expression of brain-derived neurotrophic factor (BDNF) and its receptors in distal injured nerves, which may represent a possible mechanism by which PND promotes nerve regeneration in vivo. CONCLUSIONS: Our study demonstrated that PND leads to sensory and motor recovery in a sciatic nerve transection model rat. Furthermore, we showed that BDNF mRNA level was significantly increased in the injured distal nerve, potentially contributing to the functional recovery. Further research is warrantied to examine whether direct injection is a more efficient method to increase BDNF expression compared to an exogenous BDNF administration.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Panax notoginseng , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Di-Inos , Álcoois Graxos , Regeneração Nervosa/fisiologia , Panax notoginseng/genética , Panax notoginseng/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Células de Schwann/metabolismo , Nervo Isquiático/lesões
20.
Sensors (Basel) ; 22(13)2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35808174

RESUMO

Obstacle detection for autonomous navigation through semantic image segmentation using neural networks has grown in popularity for use in unmanned ground and surface vehicles because of its ability to rapidly create a highly accurate pixel-wise classification of complex scenes. Due to the lack of available training data, semantic networks are rarely applied to navigation in complex water scenes such as rivers, creeks, canals, and harbors. This work seeks to address the issue by making a one-of-its-kind River Obstacle Segmentation En-Route By USV Dataset (ROSEBUD) publicly available for use in robotic SLAM applications that map water and non-water entities in fluvial images from the water level. ROSEBUD provides a challenging baseline for surface navigation in complex environments using complex fluvial scenes. The dataset contains 549 images encompassing various water qualities, seasons, and obstacle types that were taken on narrow inland rivers and then hand annotated for use in semantic network training. The difference between the ROSEBUD dataset and existing marine datasets was verified. Two state-of-the-art networks were trained on existing water segmentation datasets and tested for generalization to the ROSEBUD dataset. Results from further training show that modern semantic networks custom made for water recognition, and trained on marine images, can properly segment large areas, but they struggle to properly segment small obstacles in fluvial scenes without further training on the ROSEBUD dataset.


Assuntos
Processamento de Imagem Assistida por Computador , Visão Monocular , Processamento de Imagem Assistida por Computador/métodos , Redes Neurais de Computação , Rios , Semântica
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