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1.
Invest New Drugs ; 2024 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-39154300

RESUMO

Obstacles facing chemotherapeutic drugs for cancers led scientists to load Gemcitabine (GEM) into nanocarriers like liposomes, known for their nontoxicity profile and targeting capacity. The liposomal nanostructures containing GEM were coated with Fucoidan (FU) due to its anti-tumor properties by targeting cancer cells. Thus four different cationic liposomes formulations were prepared by thin-film hydration method in optimal conditions: DOTAP (formulation A); DPPC/DOTAP (4:1 molar ratio, formulation B), DPPC/DMPC/DOTAP (4:1:1 molar ratio, formulation C) and DPPC/DMPC/DOTAP/DSPE-mPEG2000 (4:1:1:0.1 molar ratio, formulation D). They were studied to identify lipid-compositions offering effective GEM-entrapment and successful coating of FU on the liposome surface. Additional qualitative characteristics, such as particle size, polydispersity index, zeta potential, stability and in vitro drug release were then evaluated. Formulation C gave the best GEM-entrapment efficiency (EE) but formed aggregates when coated with FU, giving non-homogenous large size particles then not suitable for effective delivery. It was the same situation with formulation A and B. Only the formulation D showed a good GEM-EE (> 80%) and affinity by successful coating FU from three different algae species. The PEGylated formulation D coated of FU, with regard to storage stability and drug release studies, revealed to be a promising approach on design of optimal drug delivery system.

2.
J Fungi (Basel) ; 10(8)2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39194880

RESUMO

To delve into the growth and physiological adaptations exhibited by the economically vital black wolfberry (Lycium ruthenicum) upon inoculation with arbuscular mycorrhizal fungi (AMF) under varying levels of saline-alkaline stress A series of pot experiments were conducted in a gradient saline-alkaline environment (0, 200, 400 mM NaCl: NaHCO3 = 1:1). One-year-old cuttings of black wolfberry, inoculated with two AMF species-Funneliformis mosseae (Fm) and Rhizophagus intraradices (Ri)-served as the experimental material, enabling a comprehensive analysis of seedling biomass, chlorophyll content, antioxidant enzyme activities, and other crucial physiological parameters. This study demonstrated that both Fm and Ri could form a symbiotic relationship with the root of Lycium ruthenicum. Notably, Fm inoculation significantly bolstered the growth of the underground parts, while exhibiting a remarkable capacity to scavenge reactive oxygen species (ROS), thereby effectively mitigating membrane oxidative damage induced by stress. Additionally, Fm promoted the accumulation of abscisic acid (ABA) in both leaves and roots, facilitating the exclusion of excess sodium ions from cells. Ri Inoculation primarily contributed to an enhancement in the chlorophyll b (Chlb) content, vital for sustaining photosynthesis processes. Furthermore, Ri's ability to enhance phosphorus (P) absorption under stressful conditions ensured a steady influx of essential nutrients. These findings point to different strategies employed for Fm and Ri inoculation. To holistically assess the saline-alkaline tolerance of each treatment group, a membership function analysis was employed, ultimately ranking the salt tolerance as Fm > Ri > non-mycorrhizal (NM) control. This finding holds paramount importance for the screening of highly resilient Lycium ruthenicum strains and offers invaluable theoretical underpinnings and technical guidance for the remediation of saline-alkaline soils, fostering sustainable agricultural practices in challenging environments.

3.
Int J Biol Macromol ; 277(Pt 3): 134517, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39111497

RESUMO

Fucoidan-coated pH sensitive liposomes were designed for targeted delivery of gemcitabine (FU-GEM PSL) to treat pancreatic cancer (PC). FU-GEM PSL had a particle size of 175.3 ± 4.9 nm, zeta potential of -19.0 ± 3.7 mV, encapsulation efficiency (EE) of 74.05 ± 0.17 %, and drug loading (DL) of 21.27 ± 0.05 %. Cell experiments in vitro showed that FU-GEM PSL could increase the release of GEM and drug concentration, and could inhibit tumor cell proliferation by affecting the cell cycle. FU-GEM PSL entered cells through macropinocytosis and caveolin-mediated endocytosis to exert effects. Meanwhile, the expression of P-selectin was detected in human tissues, demonstrating the feasibility of targeting FU. Moreover, combined with animal experiments in vivo, FU-GEM PSL could inhibit the development of PC. Furthermore, anti-tumor experiments in vivo carried on BALB/c mice indicated that FU-GEM PSL had tumor suppression abilities and safety. Therefore, FU-GEM PSL is a promising formulation for PC therapy.


Assuntos
Proliferação de Células , Desoxicitidina , Gencitabina , Lipossomos , Neoplasias Pancreáticas , Polissacarídeos , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Desoxicitidina/química , Desoxicitidina/administração & dosagem , Animais , Polissacarídeos/química , Polissacarídeos/farmacologia , Lipossomos/química , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Liberação Controlada de Fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Sistemas de Liberação de Medicamentos , Endocitose/efeitos dos fármacos
4.
J Cancer Res Ther ; 20(4): 1274-1283, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38958652

RESUMO

BACKGROUND: We found that the occurrence of hepatocellular carcinoma (HCC) has increased significantly in non-cirrhotic individuals, with HCC being frequently overlooked or misdiagnosed. Contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) is known to have a high diagnostic quality in high-risk HCC patients. Therefore, we aimed to compare the detection accuracy of CEUS LI-RADS for HCC between low- and high-risk individuals, to confirm its value in low-risk patients at increased risk of HCC, but not yet included in the high-risk groups of LI-RADS. In addition, since CEUS LR-4 and LR-M categories contain a relatively high proportion of HCC, and serum alpha-fetoprotein (AFP) is the most commonly used biomarker for HCC, and the clinically valid, we attempted to further improve the early diagnostic capability of CEUS LI-RADS for HCC in the low-risk and high-risk patients by combining CEUS LR-4 and LR-M categories with AFP. METHODS: We defined high-risk groups (HR)-included in the high-risk patients of LI-RADS, low-risk groups (LR)-not included in the high-risk patients of LI-RADS and enrolled 189 HCC patients with LR and HR settings in a retrospective study. All lesions were confirmed histopathologically. The CEUS LI-RADS accuracy for detecting HCC in these two patients was compared. In addition, the diagnostic algorithm in our study was proposed (for CEUS LR-4 and LR-M patients with AFP>20 ng/ml). we analyzed the ability of CEUS LI-RADS as a valid method of establishing the early diagnosis of HCC in LR and HR patients by combining LR-4 and LR-M categories with AFP. RESULTS: Through comparative analysis, the specificity of the CEUS LR-5 category for HCC in the HR group was 78.4%, whereas in the LR group, it was 94.2%. Meanwhile, the sensitivity (63.2% vs. 63.0%) and positive predictive value (PPV) (75.0% vs. 88.7%) did not differ between the LR and HR groups ( P = 0.990, P = 0.299). It is noteworthy that there were the high proportion of HCC in CEUS LR-4 and LR-M categories in our cases and when we combined CEUS LR-4 and LR-M categories with AFP significantly improved the sensitivity by 21.0% (84.2%) in the LR group, and by 16.0% (79.0%) in the HR group, with statistically difference in sensitivity after combination in the HR group ( P = 0.014). CONCLUSIONS: The CEUS LR-5 category has real meaningful utility in the diagnosis of HCC in both LR and HR patients. The early detection power of the CEUS LI-RADS category for HCC patients was further increased when the CEUS LR-4 and LR-M categories were combined with elevated AFP.


Assuntos
Carcinoma Hepatocelular , Meios de Contraste , Detecção Precoce de Câncer , Neoplasias Hepáticas , Ultrassonografia , alfa-Fetoproteínas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Masculino , Feminino , Ultrassonografia/métodos , alfa-Fetoproteínas/análise , alfa-Fetoproteínas/metabolismo , Pessoa de Meia-Idade , Detecção Precoce de Câncer/métodos , Idoso , Adulto , Estudos Retrospectivos , Biomarcadores Tumorais/sangue , Fígado/diagnóstico por imagem , Fígado/patologia
5.
Plants (Basel) ; 13(13)2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38999680

RESUMO

Soil salinization has become one of the major problems that threaten the ecological environment. The aim of this study is to explore the mechanism of salt tolerance of hybrid walnuts (Juglans major × Juglans regia) under long-term salt stress through the dynamic changes of growth, physiological and biochemical characteristics, and anatomical structure. Our findings indicate that (1) salt stress inhibited seedling height and ground diameter increase, and (2) with increasing salt concentration, relative water content (RWC) decreased, and proline (Pro) and soluble sugar (SS) content increased. The Pro content reached a maximum of 549.64 µg/g on the 42nd day. The increase in superoxide dismutase (SOD) activity (46.80-117.16%), ascorbate peroxidase (APX) activity, total flavonoid content (TFC), and total phenol content (TPC) under salt stress reduced the accumulation of malondialdehyde (MDA). (3) Increasing salt concentration led to increases and subsequent decreases in the thickness of palisade tissues, spongy tissues, leaves, and leaf vascular bundle diameter. Upper and lower skin thickness, root periderm thickness, root diameter, root cortex thickness, and root vascular bundle diameter showed different patterns of change at varying stress concentrations and durations. Overall, the study concluded that salt stress enhanced the antireactive oxygen system, increased levels of osmotic regulators, and low salt concentrations promoted leaf and root anatomy, but that under long-term exposure to high salt levels, leaf anatomy was severely damaged. For the first time, this study combined the anatomical structure of the vegetative organ of hybrid walnut with physiology and biochemistry, which is of great significance for addressing the challenge of walnut salt stress and expanding the planting area.

6.
Anal Chem ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39012074

RESUMO

Acute myeloid leukemia (AML) is a fatal hematologic disease. Diagnosis and proper treatment are important for prognosis. High myeloperoxidase (MPO) expression AML cells are characterized with high levels of hypochlorite (ClO-). In this study, we report a ClO--activated theranostic agent, FNC, for AML therapy. FNC responds to ClO- specifically in high MPO expression AML cells, resulting in bright fluorescence and chlorambucil release. FNC can be used to quickly distinguish high MPO expression AML cells from other cells, including low MPO expression leukemia and activated inflammatory cells. FNC exhibits selective toxicity to highly MPO expression AML cells and can efficiently inhibit tumor growth. Meanwhile, FNC can be used to indicate differentiation through the detection of ClO-.

7.
Research (Wash D C) ; 7: 0397, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38952997

RESUMO

Hyperthermia therapy is considered an effective anticancer strategy. However, high temperature can trigger an excessive inflammatory response, leading to tumor self-protection, immunosuppression, metastasis, and recurrence. To address this issue, we reported a multifunctional photothermal nanoplatform to achieve mild hyperthermia photothermal therapy (mild PTT) based on cisplatin (DDP) and a ferrocene metal-organic framework (MOF-Fc) nanocomposite, which can specifically enhance ferroptosis-triggered oxidative stress levels and synchronously amplify mild hyperthermia PTT-mediated anticancer responses. Both in vitro and in vivo antineoplastic results verify the superiority of mild PTT with DDP/MOF-Fc@HA. The combination of DDP and MOF-Fc exhibits Fenton catalytic activity and glutathione depletion capacity, magnifying mild hyperthermia effects via the radical oxygen species (ROS)-adenosine triphosphate (ATP)-HSP silencing pathway, with important implications for clinical hyperthermia therapy.

8.
Foods ; 13(11)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38890922

RESUMO

Hydroxytyrosol (HT), a plant-derived phenolic compound, is recognized for its potent antioxidant capabilities alongside a spectrum of pharmacological benefits, including anti-inflammatory, anti-cancer, anti-bacterial, and anti-viral properties. These attributes have propelled HT into the spotlight as a premier nutraceutical and food additive, heralding a new era in health and wellness applications. Traditional methods for HT production, encompassing physico-chemical techniques and plant extraction, are increasingly being supplanted by biotechnological approaches. These modern methodologies offer several advantages, notably environmental sustainability, safety, and cost-effectiveness, which align with current demands for green and efficient production processes. This review delves into the biosynthetic pathways of HT, highlighting the enzymatic steps involved and the pivotal role of genetic and metabolic engineering in enhancing HT yield. It also surveys the latest progress in the biotechnological synthesis of HT, examining innovative strategies that leverage both genetically modified and non-modified organisms. Furthermore, this review explores the burgeoning potential of HT as a nutraceutical, underscoring its diverse applications and the implications for human health. Through a detailed examination of both the biosynthesis and biotechnological advances in HT production, this review contributes valuable insights to the field, charting a course towards the sustainable and scalable production of this multifaceted compound.

9.
Environ Sci Technol ; 58(23): 10398-10408, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38803193

RESUMO

It is a great challenge to remove VOCs and NOx simultaneously from flue gas in nonelectric industries. This study focuses on the construction of Fe-MnO2 catalysts that perform well in the simultaneous removal of toluene and NOx at low temperatures. Utilizing the Fe-induced phase transition of MnO2, Fe-MnO2-F&R catalysts with a composite morphology of nanoflowers and nanorods were successfully prepared that provided an abundant microporous structure to facilitate the diffusion of molecules of different sizes. Through in-depth investigation of the active sites and reaction mechanism, we discovered that Fe-induced phase transition could modulate the surface acidity of Fe-MnO2-F&R. The higher concentration of surface Mn4+ provided numerous Brønsted acid sites, which effectively promoted the activation of toluene to reactive intermediates, such as benzyl alcohol/benzoate/maleic acid. Simultaneously, Fe provided a large number of Lewis acid sites that anchor and activate NH3 species, thereby inhibiting NH3 nonselective oxidation. Furthermore, additional Brønsted acid sites were generated during the simultaneous reaction process, enhancing toluene activation. Consequently, the simultaneous removal of toluene and NOx was achieved through regulation of the physical structure and the concentration of acidic sites. The present work provides new insights into the rational design of bifunctional catalysts for the synergistic control of VOCs and NOx emissions.


Assuntos
Tolueno , Tolueno/química , Compostos de Manganês/química , Catálise , Óxidos/química , Transição de Fase , Óxidos de Nitrogênio/química , Temperatura Baixa
10.
Pharmaceuticals (Basel) ; 17(3)2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38543149

RESUMO

General anesthetics were first used over 170 years ago; however, the mechanisms of how general anesthetics induce loss of consciousness (LOC) remain unclear. Ciprofol, a novel intravenous anesthetic, has been developed by incorporating cyclopropyl into the chemical structure of propofol. This modification offers the benefits of rapid onset and minimal injection pain. Recent studies have revealed that the glutamatergic neurons of the lateral habenula (LHb) play a crucial role in modulating the LOC induced by propofol and sevoflurane. Nevertheless, the specific involvement of LHb in the anesthetic effects of ciprofol remains uncertain. Here, using targeted recombination in active populations (TRAP) combined with electroencephalogram/electromyography recordings and the righting reflex behavioral test, our study revealed that intravenous infusion of ciprofol for 1 h could lead to the induction of c-Fos expression in the LHb in mice. The combination of TRAP and gene ablation, aimed at selectively ablating ciprofol-activated neurons in the LHb, has been shown to facilitate the emergence of ciprofol anesthesia and decrease the proportion of delta waves during the emergence phase. Chemogenetic inhibition of these neurons produced a comparable effect, whereas chemogenetic activation resulted in the opposite outcome. Chemogenetic activation of ciprofol-activated neurons in the LHb delays the emergence of anesthesia and induces a deep hypnotic state during the emergence phase. Taken together, our findings suggest that LHb ciprofol-activated neurons modulate the state of consciousness and could potentially be targeted to manipulate consciousness during ciprofol anesthesia.

11.
Plant Physiol Biochem ; 210: 108548, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38552263

RESUMO

Salt stress is an important abiotic stress that seriously affects plant growth. In order to research the salt tolerance of walnut rootstocks so as to provide scientific basis for screening salt-tolerant walnut rootstocks, two kinds of black walnut seedlings, Juglans microcarpa L. (JM) and Juglans nigra L. (JN), were treated under salt stress with different concentrations of NaCl (0, 50, 100, and 200 mM) and the growth situation of seedlings were observed. The physiological indexes of JM and JN seedlings were also measured in different days after treatment. Our study showed salt stress inhibited seedlings growth and limited biomass accumulation. Walnut mainly increased osmotic adjustment ability by accumulation Pro and SS. Furthermore, with the duration of treatment time increased, SOD and APX activities decreased, TPC and TFC contents increased. Walnut accumulated Na mostly in roots and transported more K and Ca to aboveground parts. The growth and physiological response performance differed between JM and JN, specifically, the differences occurred in the ability to absorb minerals, regulate osmotic stress, and scavenge ROS. Salt tolerance of JM and JN was assessed by principal component analysis (PCA) and resulted in JN > JM. In conclusion, our results indicated that JN has higher salt tolerance than JM, and JN might be used as a potential germplasm resource for the genetic breeding of walnuts.


Assuntos
Juglans , Tolerância ao Sal , Plântula , Juglans/fisiologia , Juglans/metabolismo , Juglans/efeitos dos fármacos , Plântula/efeitos dos fármacos , Plântula/fisiologia , Plântula/metabolismo , Raízes de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/fisiologia , Superóxido Dismutase/metabolismo , Cloreto de Sódio/farmacologia
12.
Foods ; 12(17)2023 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-37685150

RESUMO

Monascus, a key player in fermented food production, is known for generating Monascus pigments (MPs) and monacolin K (MK), possessing bioactive properties. However, the limited stability of MPs and mycotoxin citrinin (CTN) constrain the Monascus industry. Extremolytes like ectoine, derived from bacteria, exhibit cytoprotective potential. Here, we investigated the impact of ectoine on Monascus purpureus ATCC 16365, emphasizing development and secondary metabolism. Exogenous 5 mM ectoine supplementation substantially increased the yields of MPs and MK (105%-150%) and reduced CTN production. Ectoine influenced mycelial growth, spore development, and gene expression in Monascus. Remarkably, ectoine biosynthesis was achieved in Monascus, showing comparable effects to exogenous addition. Notably, endogenous ectoine effectively enhanced the stability of MPs under diverse stress conditions. Our findings propose an innovative strategy for augmenting the production and stability of bioactive compounds while reducing CTN levels, advancing the Monascus industry.

13.
Medicine (Baltimore) ; 102(37): e35122, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37713832

RESUMO

BACKGROUND: Sapiens spondin-2 (SPON2) is a protein found in the extracellular matrix that plays a role in a number of processes, including immune reactions and cell adhesion, and is closely linked to the emergence of a number of tumor types. However, we know very little about Sapiens spondin-2. Therefore, we performed a systematic pan-carcinogenic analysis to explore the relationship between Sapiens spondin-2 and cancers. MATERIALS AND METHODS: By comprehensive use of datasets from TCGA, GEO, GTEx, HPA, CPTAC, GEPIA2, TIMER2, cBioPortal, STRING, we adopted bioinformatics methods to dig up the potential carcinogenesis of SPON2, including dissecting the correlation between SPON2 and gene expression, prognosis, gene mutation, Immunohistochemistry staining, immune cell infiltration, and constructed the interaction network of a total of 54 SPON2-binding proteins as well as explored the enrichment analysis of SPON2-related partners. RESULTS: The expression of Sapiens spondin-2 in most tumor tissues was higher than that of normal tissues. In addition, SPON2 showed the early diagnostic value in 33 kinds of tumors and was positively or negatively associated with the prognosis of different tumors. It also validates that SPON2 is the gene associated with the majority of immune-infiltrating cells in pan-cancer. High SPON2 expression is associated with tumor progression related pathways. CONCLUSION: We found and validated the potential use of SPON2 in cancer detection for the first time through pan-cancer analysis. The expression levels of SPON2 in various tumors were quite different from those in normal tissues. Furthermore, the performance of SPON2 in tumorigenesis and tumor immunity verified our hypothesis. At the same time, it has high specificity and sensitivity in cancer detection. Therefore, SPON2 can be employed as an auxiliary index for the initial diagnosis of tumors and a prognostic marker for various types of tumors.


Assuntos
Neoplasias , Humanos , Neoplasias/genética , Carcinogênese/genética , Adesão Celular , Transformação Celular Neoplásica , Biologia Computacional , Proteínas de Neoplasias , Proteínas da Matriz Extracelular/genética
14.
Mater Horiz ; 10(10): 4501-4509, 2023 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-37551443

RESUMO

Phase separation has been widely exploited for fabricating structured functional materials. Generally, after being fabricated, the phase structure in a hybrid material system has been set at a specific length scale and remains unchanged during the lifespan of the material. Herein, we report a strategy to construct on-demand and reversible phase switches among homogenous, nano- and macro-phase separation states in a composite elastomer during its lifespan. We trigger the nanophase separation by super-saturating an elastomer matrix with a carefully selected small-molecule organic compound (SMOC). The nanoparticles of SMOC that precipitate out upon quenching will stretch the elastomer network, yet remain stably arrested in the elastomer matrix at low temperatures for a long time. However, at elevated temperatures, the nano-phase separation will transform into the macro-one. The elastic recovery will drive the SMOC onto the elastomer surface. The phase-separated structures can be reconfigured through the homogeneous solution state at a further elevated temperature. Taking advantage of the reversible phase switches leads to a novel strategy for designing high-performance dielectric elastomers. The in situ formed nanoparticles can boost the electro-actuation performance by eliminating electro-mechanical instability and lead to a very large actuation strain (∼146%). Once the actuator broke down, SMOC could on-demand be driven to the breakdown holes and heal the actuator.

15.
Cancer Sci ; 114(10): 3900-3913, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37519194

RESUMO

Colorectal cancer (CRC) metastasis plays a crucial role in disease progression, yet the regulatory mechanisms underlying metastasis remain incompletely understood. Isobutyric acid (IBA), a short-chain fatty acid found at high levels in serum of CRC patients, has been shown to be a critical metabolite influencing CRC proliferation. However, its role in tumor metastasis remains unknown. Here, utilizing liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis, we found that levels of IBA were significantly higher in patients with distant organ metastasis of CRC than in those without. Furthermore, IBA promoted CRC metastasis both in vitro and in vivo. Mass spectrometry, immunofluorescence, and cellular thermal shift assay revealed that IBA interacts with RACK1. Mechanistically, IBA binding to and activating RACK1 promotes regulation of downstream Akt and FAK signaling and CRC metastasis. Collectively, our study highlights the critical interplay between IBA and RACK1 and its impact on tumor metastasis. This study suggests that targeting the IBA-RACK1 signaling axis may be an effective therapeutic strategy for controlling CRC metastasis.


Assuntos
Neoplasias Colorretais , Espectrometria de Massas em Tandem , Humanos , Linhagem Celular Tumoral , Cromatografia Líquida , Neoplasias Colorretais/patologia , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Metástase Neoplásica , Movimento Celular , Receptores de Quinase C Ativada/metabolismo , Proteínas de Neoplasias/metabolismo
16.
Int J Mol Sci ; 24(8)2023 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-37108108

RESUMO

Hydroxytyrosol, a valuable plant-derived phenolic compound, is increasingly produced from microbial fermentation. However, the promiscuity of the key enzyme HpaBC, the two-component flavin-dependent monooxygenase from Escherichia coli, often leads to low yields. To address this limitation, we developed a novel strategy utilizing microbial consortia catalysis for hydroxytyrosol production. We designed a biosynthetic pathway using tyrosine as the substrate and selected enzymes and overexpressing glutamate dehydrogenase GdhA to realize the cofactor cycling by coupling reactions catalyzed by the transaminase and the reductase. Additionally, the biosynthetic pathway was divided into two parts and performed by separate E. coli strains. Furthermore, we optimized the inoculation time, strain ratio, and pH to maximize the hydroxytyrosol yield. Glycerol and ascorbic acid were added to the co-culture, resulting in a 92% increase in hydroxytyrosol yield. Using this approach, the production of 9.2 mM hydroxytyrosol was achieved from 10 mM tyrosine. This study presents a practical approach for the microbial production of hydroxytyrosol that can be promoted to produce other value-added compounds.


Assuntos
Escherichia coli , Tirosina , Escherichia coli/metabolismo , Tirosina/metabolismo , Consórcios Microbianos , Catálise , Engenharia Metabólica/métodos
17.
Int J Nanomedicine ; 17: 5391-5411, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36419717

RESUMO

Introduction: Photoimmunotherapy is a breakthrough treatment for malignant tumors. Its uniqueness is that it uses antibody mediated targeted delivery to achieve high tumor specificity and uses laser-activated biophysical mechanism to accurately induce the rapid death of cancer cells and avoid damaging the surrounding normal tissues. Methods: In this paper, an iron-based micelle was designed to encapsulate the photothermal agent indocyanine green (ICG) and a cyclic tripeptide of arginine-glycine-aspartic acid (cRGD) as targeted multifunctional ICG@SANPs-cRGD nanoparticles for combined photothermal/photodynamic/immune therapy of breast cancer. Results: The experimental results show that ICG@SANPs-cRGD nanoparticles have good biocompatibility and photothermal conversion ability. Photothermal therapy (PTT) and photodynamic therapy (PDT) based on ICG@SANPs-cRGD can not only inhibit the proliferation, invasion and migration of tumor cells, but also directly kill tumor cells by inducing apoptosis or necrosis. Dual-mode fluorescence light (FL) and magnetic resonance imaging (MRI) imaging in mice confirmed the selective accumulation at tumor sites and imaging ability of ICG@SANPs-cRGD. PTT/PDT combined with Anti-PD-L1 immunotherapy based on ICG@SANPs-cRGD mediated the immunogenic cell death (ICD) of tumor cells by regulating the expression of immune-related indicators and activated the body's immune response mechanism, which enhanced the immunotherapy effect of immune checkpoint block (ICB). PTT/PDT combined with Anti-PD-L1 therapy not only prevented the progression of the primary tumor but also inhibited the distant metastasis of the tumor. Discussion: This study explores the biomedical application of PTT/PDT combined with Anti-PD-L1 based on ICG@SANPs-cRGD nanomaterials for breast cancer treatment and demonstrates the potential of ICG@SANPs-cRGD as a multifunctional therapeutic platform for future cancer therapy.


Assuntos
Nanopartículas Multifuncionais , Neoplasias , Fotoquimioterapia , Animais , Camundongos , Terapia Fototérmica , Imunoterapia , Fatores Imunológicos , Verde de Indocianina/farmacologia
18.
Front Med (Lausanne) ; 9: 975698, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36213633

RESUMO

Background: Small intestinal lymphangioma is a very rare benign lesion. Thus far, the literature on small intestinal lymphangioma has mainly involved case reports. The present study retrospectively examined the clinical features of patients with a pathological diagnosis of small intestinal lymphangioma. Materials and methods: From January 2010 to January 2021, 15 patients were pathologically diagnosed with small intestinal lymphangioma. The age, gender, clinical manifestation, computed tomography (CT) findings, endoscopic findings, localization of the lesion, treatment method, complications, and follow-up were retrospectively analyzed. Results: Most of the patients had no symptoms, and those with symptoms had melena or abdominal pain. Lymphangioma was located in the duodenum in nine cases (60.0%), jejunum in two (13.3%), jejunal-ileal junction with mesentery involvement in one (6.7%) and ileum in three (20.0%). Three cases (20.0%) had multiple lesions, and the other 12 (80.0%) had single lesions. The median size of the lesions was 0.8 cm. Thirteen cases were found by endoscopy, and nine cases of them had white-colored spots on the surface. Ten cases (66.7%) underwent endoscopic treatment, three (20.0%) underwent surgical treatment, and two (13.3%) were followed up. Postoperative acute pancreatitis developed in one patient after endoscopic resection of duodenal papillary lymphangioma; postoperative abdominal bleeding occurred in one patient with jejunal lymphangioma who underwent partial small bowel resection. Conclusion: Small intestinal lymphangioma is extremely rare, and its clinical manifestations are non-specific. Endoscopy is of great value in the diagnosis of small intestinal lymphangioma. Depending on the clinical manifestations, the size, location and scope of the lesions, follow-up, endoscopic treatment and surgery can be selected.

19.
Expert Opin Ther Targets ; 26(8): 721-738, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-36217308

RESUMO

INTRODUCTION: Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease (ESRD) worldwide. Currently, there is no effective treatment to completely prevent DKD progression to ESRD. Renal fibrosis and inflammation are the major pathological features of DKD, being pursued as potential therapeutic targets for DKD. AREAS COVERED: Inflammation and renal fibrosis are involved in the pathogenesis of DKD. Anti-inflammatory drugs have been developed to combat DKD but without efficacy demonstrated. Thus, we have focused on the mechanisms of TGF-ß-induced renal fibrosis in DKD, as well as discussing the important molecules influencing the TGF-ß signaling pathway and their potential development into new pharmacotherapies, rather than targeting the ligand TGF-ß and/or its receptors, such options include Smads, microRNAs, histone deacetylases, connective tissue growth factor, bone morphogenetic protein 7, hepatocyte growth factor, and cell division autoantigen 1. EXPERT OPINION: TGF-ß is a critical driver of renal fibrosis in DKD. Molecules that modulate TGF-ß signaling rather than TGF-ß itself are potentially superior targets to safely combat DKD. A comprehensive elucidation of the pathogenesis of DKD is important, which requires a better model system and access to clinical samples via collaboration between basic and clinical researchers.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Falência Renal Crônica , MicroRNAs , Humanos , Fator de Crescimento Transformador beta/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/etiologia , Fator de Crescimento do Tecido Conjuntivo , Proteína Morfogenética Óssea 7 , Fator de Crescimento de Hepatócito , Ligantes , Fibrose , Inflamação/patologia , Histona Desacetilases , Autoantígenos , Fatores de Crescimento Transformadores , Rim/metabolismo , Rim/patologia
20.
Plants (Basel) ; 11(18)2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36145780

RESUMO

In this study, to screen for walnut salt-tolerant rootstocks, Juglans microcarpa L. seedlings were treated in different NaCl concentrations (0, 50, 100, 200, and 300 mmol/L), and the growth situation of seedlings was observed. Moreover, we determined the physiological indexes of seedlings on different days (6, 12, 18, and 24 d) after treatment. The results showed that after salt stress, the external morphology of seedlings displayed salt injury, which manifested as yellowing, withering, curling, and falling off of leaves. High concentrations and long-term stress led to more serious damage, with numerous leaves undergoing withering and shedding. Salt stress significantly inhibited the growth of seedlings. With the increase in salt concentration and stress time, the chlorophyll content and photosynthetic parameters of seedlings reduced to varying degrees; the relative electrical conductivity (REC) and malondialdehyde (MDA) increased. Superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities generally increased, followed by a decrease; proline (Pro) accumulated; and soluble sugar (SS) content first increased and then decreased. In addition, it promoted the production of abscisic acid (ABA) and inhibited the synthesis of indole-3-acetic acid (IAA), gibberellic acid 3 (GA3), and zeatin riboside (ZR). It was found that J.microcarpa L. seedlings were more tolerant under 100 mmol/L salt stress, whereas the damage to growth was more severe at 200 mmol/L to 300 mmol/L salt stress.

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