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1.
J Nanobiotechnology ; 22(1): 461, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39090622

RESUMO

BACKGROUND: The combination of programmed cell death ligand-1 (PD-L1) immune checkpoint blockade (ICB) and immunogenic cell death (ICD)-inducing chemotherapy has shown promise in cancer immunotherapy. However, triple-negative breast cancer (TNBC) patients undergoing this treatment often face obstacles such as systemic toxicity and low response rates, primarily attributed to the immunosuppressive tumor microenvironment (TME). METHODS AND RESULTS: In this study, PD-L1-targeted theranostic systems were developed utilizing anti-PD-L1 peptide (APP) conjugated with a bio-orthogonal click chemistry group. Initially, TNBC was treated with azide-modified sugar to introduce azide groups onto tumor cell surfaces through metabolic glycoengineering. A PD-L1-targeted probe was developed to evaluate the PD-L1 status of TNBC using magnetic resonance/near-infrared fluorescence imaging. Subsequently, an acidic pH-responsive prodrug was employed to enhance tumor accumulation via bio-orthogonal click chemistry, which enhances PD-L1-targeted ICB, the pH-responsive DOX release and induction of pyroptosis-mediated ICD of TNBC. Combined PD-L1-targeted chemo-immunotherapy effectively reversed the immune-tolerant TME and elicited robust tumor-specific immune responses, resulting in significant inhibition of tumor progression. CONCLUSIONS: Our study has successfully engineered a bio-orthogonal multifunctional theranostic system, which employs bio-orthogonal click chemistry in conjunction with a PD-L1 targeting strategy. This innovative approach has been demonstrated to exhibit significant promise for both the targeted imaging and therapeutic intervention of TNBC.


Assuntos
Antígeno B7-H1 , Química Click , Imunoterapia , Piroptose , Neoplasias de Mama Triplo Negativas , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Antígeno B7-H1/metabolismo , Animais , Feminino , Imunoterapia/métodos , Camundongos , Piroptose/efeitos dos fármacos , Humanos , Linhagem Celular Tumoral , Microambiente Tumoral/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Doxorrubicina/farmacologia , Doxorrubicina/química , Doxorrubicina/uso terapêutico , Imagem Óptica/métodos , Pró-Fármacos/química , Pró-Fármacos/farmacologia
2.
J Craniofac Surg ; 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39072648

RESUMO

OBJECTIVE: To study the clinical effect of conjoint fascial sheath (CFS) suspension and levator palpebrae superioris muscle shortening in the treatment of severe blepharoptosis. METHODS: Forty-five patients with severe blepharoptosis (75 eyes) from May 2020 to February 2022 in the authors' hospital were divided into 2 groups: group A (n = 33, 43 eyes) and group B (n = 24, 32 eyes). Group A was operated on by CFS + levator muscle shortening, and group B was operated on by frontal muscle flap suspension + levator muscle shortening. Both groups were followed up for 12 months (until February 2023). The clinical effect was counted in 6 months after operation, the early complications were counted in 1 month after operation, and the late complications were counted in 1 month to 12 months after operation. Margin to corneal reflex distance 1 (MRD1) and palpebral fissure height (PFH) were recorded before, 1 week, 3 months, and 12 months postoperatively, and the amount of eyelid retrogression was counted again. RESULTS: The good correction rate was 90.70% in group A, higher than in group B (71.88%), and the difference was statistically significant (P< 0.05); the early postoperative complication rate was 9.30%, lower than in group B (24.38%), and the difference was statistically significant (P< 0.05); the late postoperative complication rate was 2.33%, lower than group B (18.75%), and the difference was statistically significant (P< 0.05). The MRD1 and PFH of group A were higher than those of group B (P< 0.05) at 3 months postoperatively and 12 months postoperatively; the MRD1 and PFH of group A were lower than those of group B (P< 0.05) at 3 months postoperatively and 12 months postoperatively. Repeated measurement analysis of variance showed that there were significant differences in the main effects of MRD1, PFH, eyelid retrogression, and time in group A and group B (P< 0.05), and there was interaction between intervention and time (P< 0.05). CONCLUSION: Conjoint fascial sheath suspension combined with levator palpebrae superioris muscle shortening can effectively improve MRD1 and PFH, and the amount of upper eyelid retraction is controllable 1 year after operation.

3.
Phytother Res ; 38(7): 3782-3800, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38839050

RESUMO

Pediatric intestinal development is immature, vulnerable to external influences and produce a variety of intestinal diseases. At present, breakthroughs have been made in the treatment of pediatric intestinal diseases, but there are still many challenges, such as toxic side effects, drug resistance, and the lack of more effective treatments and specific drugs. In recent years, dietary polyphenols derived from plants have become a research hotspot in the treatment of pediatric intestinal diseases due to their outstanding pharmacological activities such, as anti-inflammatory, antibacterial, antioxidant and regulation of intestinal flora. This article reviewed the mechanism of action and clinical evidence of dietary polyphenols in the treatment of pediatric intestinal diseases, and discussed the influence of physiological characteristics of children on the efficacy of polyphenols, and finally prospected the new dosage forms of polyphenols in pediatrics.


Assuntos
Enteropatias , Polifenóis , Humanos , Polifenóis/farmacologia , Criança , Enteropatias/tratamento farmacológico , Enteropatias/dietoterapia , Enteropatias/prevenção & controle , Antioxidantes/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Dieta
4.
Pharmaceutics ; 16(6)2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38931924

RESUMO

Breast cancer (BC) poses a significant threat to women's health, with triple-negative breast cancer (TNBC) representing one of the most challenging and aggressive subtypes due to the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. Traditional TNBC treatments often encounter issues such as low drug efficiency, limited tumor enrichment, and substantial side effects. Therefore, it is crucial to explore novel diagnostic and treatment systems for TNBC. Multifunctional molecular probes (MMPs), which integrate target recognition as well as diagnostic and therapeutic functions, introduce advanced molecular tools for TNBC theranostics. Using an MMP system, molecular drugs can be precisely delivered to the tumor site through a targeted ligand. Real-time dynamic monitoring of drug release achieved using imaging technology allows for the evaluation of drug enrichment at the tumor site. This approach enables accurate drug release, thereby improving the therapeutic effect. Therefore, this review summarizes the recent advancements in MMPs for TNBC theranostics, encompassing the design and synthesis of MMPs as well as their applications in the field of TNBC theranostics.

5.
J Hazard Mater ; 473: 134690, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38781857

RESUMO

N-Nitroso compounds (NOCs) are recognized as important factors that promote gastric cancer development, but the specific effects and potential mechanisms by which NOC exposure promotes gastric cancer are still poorly understood. In this study, we explored the effects and potential molecular mechanisms of NOCs on the promotion of gastric cancer using methylnitronitrosoguanidine (MNNG), a classical direct carcinogen of NOC. The results of in vivo and in vitro experiments showed that chronic and low-concentration MNNG exposure significantly promoted the malignant progression of tumors, including cell migration, cell invasion, vasculogenic mimicry (VM) formation, cell spheroid formation, stem cell-like marker expression, and gastric cancer growth and metastasis. Mechanistically, we revealed that demethylase ALKBH5 regulated the level of the N6­methyladenosine (m6A) modification in the 3'UTR and CDS region of the ZKSCAN3 mRNA to promote ZKSCAN3 expression, mediated the binding of ZKSCAN3 to the VEGFA promoter region to regulate VEGFA transcription, and participated in MNNG-induced gastric cancer cell migration, invasion, VM formation, cell spheroid formation, stem cell-like marker expression and ultimately gastric cancer progression. In addition, our study revealed that ALKBH5-ZKSCAN3-VEGFA signaling was significantly activated during MNNG-induced gastric carcinogenesis, and further studies in gastric cancer patients showed that ALKBH5, ZKSCAN3, and VEGFA expression were upregulated in cancers compared with paired gastric mucosal tissues, that ALKBH5, ZKSCAN3, and VEGFA could serve as important biomarkers for determining patient prognosis, and that the molecular combination showed greater prognostic value. These findings provide a theoretical basis for developing gastric cancer interventions for NOCs and for determining gastric cancer progression.


Assuntos
Adenosina , Homólogo AlkB 5 da RNA Desmetilase , Movimento Celular , Progressão da Doença , Metilnitronitrosoguanidina , Neoplasias Gástricas , Fator A de Crescimento do Endotélio Vascular , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/induzido quimicamente , Homólogo AlkB 5 da RNA Desmetilase/metabolismo , Homólogo AlkB 5 da RNA Desmetilase/genética , Humanos , Animais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Linhagem Celular Tumoral , Metilnitronitrosoguanidina/toxicidade , Movimento Celular/efeitos dos fármacos , Camundongos Nus , Masculino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Carcinógenos/toxicidade , Camundongos Endogâmicos BALB C , Camundongos
6.
Mol Med Rep ; 30(2)2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38818834

RESUMO

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the Transwell migration assay data shown in Fig. 4D on p. 4876 were strikingly similar to data that had already been published in different form in another article written by different authors at a different research institute. In addition, a pair of the data panels in Fig. 4D were overlapping, indicating that data derived from the same original source had been used to represent what were intended to be the results obtained from differently performed experiments.  Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 13: 4872­4878, 2016; DOI: 10.3892/mmr.2016.5127].

7.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2699-2709, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38812170

RESUMO

A systematic evaluation of the differences in the chemical composition and efficacy of the different forms of Galli Gigerii Endothelium Corneum(GGEC) was conducted based on modern analytical techniques and a functional dyspepsia(FD) rat model, which clarifies the material basis of the digestive efficacy of GGEC. Proteins, enzymes, polysaccharides, amino acids, and flavonoids in GGEC powder and decoction were determined respectively. The total protein of the powder and decoction was 0.06% and 0.65%, respectively, and the pepsin and amylase potency of the powder was 27.03 and 44.05 U·mg~(-1) respectively. The polysaccharide of the decoction was 0.03%, and there was no polysaccharide detected in the powder. The total L-type amino acids in the powder and decoction were 279.81 and 8.27 mg·g~(-1) respectively, and the total flavonoid content was 59.51 µg·g~(-1). Enzymes and flavonoids were not detected in the decoction. The powder significantly reduced nutrient paste viscosity, while the decoction and control group showed no significant reduction in nutrient paste viscosity. FD rat models were prepared by iodoacetamide gavage and irregular diet. The results showed that both powder and decoction significantly increased the gastric emptying effect, small intestinal propulsion rate, digestive enzymes activity, gastrin(GAS), motilin(MTL), ghrelin(GHRL) and reduced vasoactive intestinal peptide(VIP), 3-(2-ammo-nioethyl)-5-hydroxy-1H-indolium maleate(5-HT), and somatostatin(SST) content in rats(P<0.05, P<0.01). Comparison of GGEC decoction and powder administration between groups of the same dosage level showed that gastrointestinal propulsion and serum levels of GAS, GHRL, VIP, and SST in the powder group were significantly superior to those in the decoction and that the gastrointestinal propulsion, as well as serum levels of MTL, GAS, and GHRL were slightly higher than those of the decoction with two times its raw dose, and the serum levels of SST, 5-HT, and VIP in the powder group were slightly lower than those of the decoction with two times its raw dose. In conclusion, both decoction and powder have therapeutic effects on FD, but there is a significant difference between the two effects. Under the same dosage, the digestive efficacy of the powder is significantly better than that of the decoction, and the decoction needs to increase the dosage to compensate for the efficacy. It is hypothesized that the digestive efficacy of the GGEC has a duality, and the digestive active ingredients of the powder may include enzymes and L-type amino acids, while the decoction mainly relies on L-type amino acids to exert its efficacy. This study provides new evidence to investigate the digestive active substances of the GGEC and to improve the effectiveness of the drug in the clinic.


Assuntos
Dispepsia , Ratos Sprague-Dawley , Animais , Ratos , Masculino , Dispepsia/tratamento farmacológico , Dispepsia/fisiopatologia , Dispepsia/metabolismo , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Humanos , Flavonoides/química , Flavonoides/farmacologia , Motilina , Peptídeo Intestinal Vasoativo/metabolismo , Grelina , Somatostatina
8.
ACS Nano ; 18(18): 11560-11572, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38682810

RESUMO

Second near-infrared (NIR-II) carbon dots, with absorption or emission between 1000 and 1700 nm, are gaining increasing attention in the biomaterial field due to their distinctive properties, which include straightforward preparation processes, stable photophysical characteristics, excellent biocompatibility, and low cost. As a result, there is a growing focus on the controlled synthesis and modulation of the photochemical and photophysical properties of NIR-II carbon dots, with the aim to further expand their biomedical applications, a current research hotspot. This account aims to provide a comprehensive overview of the recent advancements in NIR-II carbon dots within the biomedical field. The review will cover the following topics: (i) the design, synthesis, and purification of NIR-II carbon dots, (ii) the surface modification strategies, and (iii) the biomedical applications, particularly in the domain of cancer theranostics. Additionally, this account addresses the challenges encountered by NIR-II carbon dots and will outline future directions in the realm of cancer theranostics. By exploring carbon-based NIR-II biomaterials, we can anticipate that this contribution will garner increased attention and contribute to the development of next-generation advanced functional carbon dots, thereby offering enhanced tools and strategies in the biomedical field.


Assuntos
Carbono , Raios Infravermelhos , Pontos Quânticos , Carbono/química , Pontos Quânticos/química , Humanos , Neoplasias/tratamento farmacológico , Materiais Biocompatíveis/química , Materiais Biocompatíveis/síntese química , Animais , Nanomedicina Teranóstica
9.
Zhongguo Zhong Yao Za Zhi ; 48(20): 5410-5418, 2023 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-38114135

RESUMO

Aconiti Lateralis Radix Praeparata polysaccharides(AP) are a class of bioactive macromolecules extracted from the herbs of Aconiti Lateralis Radix Praeparata and its various processed products. Since the AP was first separated in 1986, its pharmacological effects include immune regulation, anti-tumor, anti-depression, organ protection, hypoglycemia, and anti-inflammatory had been found. In recent years, with the development of polysaccharide extraction, separation, and structure identification technologies, more than 20 kinds of AP have been separated from Aconiti Lateralis Radix Praeparata and its processed products, and they have ob-vious differences in relative molecular weight, monosaccharide composition, glycosidic bond, structural characteristics, and biological activities. In particular, AP may be dissolved, degraded, or allosteric under the complex processing environment of fermentation, soaking, cooking, etc., leading to the diversified structure of AP, which provides a possibility for further understanding of the structure-activity relationship of AP. Therefore, this study systematically reviewed the research progress on the structure and structure-activity relationship of AP, summarized the biological activity and potential action mechanism of AP, and discussed the technical challenges in the development and application of AP, so as to promote the quality control and further development and utilization of AP.


Assuntos
Aconitum , Medicamentos de Ervas Chinesas , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Aconitum/química , Polissacarídeos/farmacologia , Relação Estrutura-Atividade , Tecnologia
10.
Talanta ; 265: 124806, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37364382

RESUMO

A modified miniaturized hydrogen flame ionization detector (m-FID) was developed and evaluated. An integrated nozzle assembly was constructed to solve the gas leakage caused by adhesive crack during repeated high-low temperature processes or vibration. An embedded sealing structure was designed to realize the face sealing, thus improving the sealing stability and reliability of the m-FID. Polyimide was employed as seal and insulation material to ensure the detector can be used at 300 °C for a long term. The hydrogen and air consumption of the m-FID was 12 mL/min and 110 mL/min, which is about 1/3 of the FID gas consumption of commercial laboratory instruments. The limit of detection (LOD) for n-hexadecane was 3.2 × 10-12 g/s, with a linear response range of nearly 5 orders of magnitude. Finally, it was installed onto an on-site gas chromatograph to detect drug samples with wide boiling point range from room temperature up to 535 °C.

11.
Zhongguo Zhong Yao Za Zhi ; 48(8): 2138-2145, 2023 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-37282902

RESUMO

The powder modification technology was used to improve the powder properties and microstructure of Dioscoreae Rhizoma extract powder, thereby solving the problem of poor solubility of Dioscoreae Rhizoma formula granules. The influence of modifier dosage and grinding time on the solubility of Dioscoreae Rhizoma extract powder was investigated with the solubility as the evaluation index, and the optimal modification process was selected. The particle size, fluidity, specific surface area, and other powder properties of Dioscoreae Rhizoma extract powder before and after modification were compared. At the same time, the changes in the microstructure before and after modification was observed by scanning electron microscope, and the modification principle was explored by combining with multi-light scatterer. The results showed that after adding lactose for powder modification, the solubility of Dioscoreae Rhizoma extract powder was significantly improved. The volume of insoluble substance in the liquid of modified Dioscoreae Rhizoma extract powder obtained by the optimal modification process was reduced from 3.8 mL to 0 mL, and the particles obtained by dry granulation of the modified powder could be completely dissolved within 2 min after being exposed to water, without affecting the content of its indicator components adenosine and allantoin. After modification, the particle size of Dioscoreae Rhizoma extract powder decreased significantly, d_(0.9) decreased from(77.55±4.57) µm to(37.91±0.42) µm, the specific surface area and porosity increased, and the hydrophilicity improved. The main mechanism of improving the solubility of Dioscoreae Rhizoma formula granules was the destruction of the "coating membrane" structure on the surface of starch granules and the dispersion of water-soluble excipients. This study introduced powder modification technology to solve the solubility problem of Dioscoreae Rhizoma formula granules, which provided data support for the improvement of product quality and technical references for the improvement of solubility of other similar varieties.


Assuntos
Tecnologia Farmacêutica , Tecnologia , Pós , Solubilidade , Extratos Vegetais , Tamanho da Partícula
12.
Zhongguo Zhong Yao Za Zhi ; 48(10): 2757-2766, 2023 May.
Artigo em Chinês | MEDLINE | ID: mdl-37282936

RESUMO

In this study, the crude polysaccharides was extracted from Shengfupian and purified by Sevag deproteinization. Then, the purified neutral polysaccharide fragment was obtained by the DEAE-52 cellulose chromatography column and Sephadex G-100 co-lumn. The structure of polysaccharides was characterized by ultraviolet spectroscopy, infrared spectroscopy, ion chromatography, and gel permeation chromatography. To investigate the anti-inflammatory activity of Shengfupian polysaccharides, LPS was used to induce inflammation in RAW264.7 cells. The expression of the CD86 antibody on surface of M1 cells, the function of macrophages, and the content of NO and IL-6 in the supernatant were examined. An immunodepression model of H22 tumor-bearing mice was established, and the immunomodulatory activity of Shengfupian polysaccharides was evaluated based on the tumor inhibition rate, immune organ index and function, and serum cytokine levels. Research indicated that Shengfupian polysaccharides(80 251 Da) was composed of arabinose, galactose, glucose, and fructose with molar ratio of 0.004∶0.018∶0.913∶0.065. It was smooth and lumpy under the scanning electron microscope. In the concentration range of 25-200 µg·mL~(-1), Shengfupian polysaccharides exhibited little or no toxicity to RAW264.7 cells and could inhibit the polarization of cells to the M1 type and reduce the content of NO and IL-6 in the cell supernatant. It could suppress the phagocytosis of cells at the concentration of 25 µg·mL~(-1), while enhancing the phagocytosis of RAW264.7 cells within the concentration range of 100-200 µg·mL~(-1). The 200 mg·kg~(-1) Shengfupian polysaccharides could alleviate the spleen injury caused by cyclophosphamide, increase the levels of IL-1ß and IL-6, and decrease the level of TNF-α in the serum of mice. In conclusion, Shengfupian polysaccharides has anti-inflammatory effect and weak immunomodulatory effect, which may the material basis of Aconm Lateralis Radix Praeparaia for dispelling cold and relieving pain.


Assuntos
Citocinas , Interleucina-6 , Animais , Camundongos , Interleucina-6/genética , Citocinas/metabolismo , Polissacarídeos/farmacologia , Polissacarídeos/química , Células RAW 264.7 , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Espectrofotometria Infravermelho
13.
Ecotoxicol Environ Saf ; 259: 115043, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37224781

RESUMO

Cigarette smoking is an independent risk factor for lung cancer. Nicotine, as an addictive substance in tobacco and e-cigarettes, is known to promote tumor progression and metastasis despite being a non-carcinogen. As a tumor suppressor gene, JWA is widely involved in the inhibition of tumor growth and metastasis and the maintenance of cellular homeostasis, including in non-small cell lung cancer (NSCLC). However, the role of JWA in nicotine-induced tumor progression remains unclear. Here, we reported for the first time that JWA was significantly downregulated in smoking-related lung cancer and associated with overall survival. Nicotine exposure reduced JWA expression in a dose-dependent manner. Gene Set Enrichment Analysis (GSEA) analysis showed the tumor stemness pathway was enriched in smoking-related lung cancer, and JWA was negatively associated with stemness molecules CD44, SOX2, and CD133. JWA also inhibited nicotine-enhanced colony formation, spheroid formation, and EDU incorporation in lung cancer cells. Mechanically, nicotine downregulated JWA expression via the CHRNA5-mediated AKT pathway. Lower JWA expression enhanced CD44 expression through inhibition of ubiquitination-mediated degradation of Specificity Protein 1 (SP1). The in vivo data indicated that JAC4 through the JWA/SP1/CD44 axis inhibited nicotine-triggered lung cancer progression and stemness. In conclusion, JWA via down-regulating CD44 inhibited nicotine-triggered lung cancer cell stemness and progression. Our study may provide new insights to develop JAC4 for the therapy of nicotine-related cancers.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Sistemas Eletrônicos de Liberação de Nicotina , Neoplasias Pulmonares , Receptores Nicotínicos , Humanos , Neoplasias Pulmonares/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Nicotina/toxicidade , Proteínas Proto-Oncogênicas c-akt/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Receptores de Hialuronatos/genética , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Receptores Nicotínicos/metabolismo , Fator de Transcrição Sp1/genética , Fator de Transcrição Sp1/metabolismo
14.
Int J Mol Sci ; 24(10)2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37240137

RESUMO

Lung adenocarcinoma (LUAD) is the most common lung cancer, with high mortality. As a tumor-suppressor gene, JWA plays an important role in blocking pan-tumor progression. JAC4, a small molecular-compound agonist, transcriptionally activates JWA expression both in vivo and in vitro. However, the direct target and the anticancer mechanism of JAC4 in LUAD have not been elucidated. Public transcriptome and proteome data sets were used to analyze the relationship between JWA expression and patient survival in LUAD. The anticancer activities of JAC4 were determined through in vitro and in vivo assays. The molecular mechanism of JAC4 was assessed by Western blot, quantitative real-time PCR (qRT-PCR), immunofluorescence (IF), ubiquitination assay, co-immunoprecipitation, and mass spectrometry (MS). Cellular thermal shift and molecule-docking assays were used for confirmation of the interactions between JAC4/CTBP1 and AMPK/NEDD4L. JWA was downregulated in LUAD tissues. Higher expression of JWA was associated with a better prognosis of LUAD. JAC4 inhibited LUAD cell proliferation and migration in both in-vitro and in-vivo models. Mechanistically, JAC4 increased the stability of NEDD4L through AMPK-mediated phosphorylation at Thr367. The WW domain of NEDD4L, an E3 ubiquitin ligase, interacted with EGFR, thus promoting ubiquitination at K716 and the subsequent degradation of EGFR. Importantly, the combination of JAC4 and AZD9191 synergistically inhibited the growth and metastasis of EGFR-mutant lung cancer in both subcutaneous and orthotopic NSCLC xenografts. Furthermore, direct binding of JAC4 to CTBP1 blocked nuclear translocation of CTBP1 and then removed its transcriptional suppression on the JWA gene. The small-molecule JWA agonist JAC4 plays a therapeutic role in EGFR-driven LUAD growth and metastasis through the CTBP1-mediated JWA/AMPK/NEDD4L/EGFR axis.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Proteínas Quinases Ativadas por AMP/metabolismo , Linhagem Celular Tumoral , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Proliferação de Células , Receptores ErbB/genética , Receptores ErbB/metabolismo , Regulação Neoplásica da Expressão Gênica
15.
JCI Insight ; 8(12)2023 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-37192004

RESUMO

Tumor vascular normalization prevents tumor cells from breaking through the basement membrane and entering the vasculature, thereby inhibiting metastasis initiation. In this study, we report that the antitumor peptide JP1 regulated mitochondrial metabolic reprogramming through AMPK/FOXO3a/UQCRC2 signaling, which improved the tumor microenvironment hypoxia. The oxygen-rich tumor microenvironment inhibited the secretion of IL-8 by tumor cells, thereby promoting tumor vascular normalization. The normalized vasculature resulted in mature and regular blood vessels, which made the tumor microenvironment form a benign feedback loop consisting of vascular normalization, sufficient perfusion, and an oxygen-rich microenvironment, prevented tumor cells from entering the vasculature, and inhibited metastasis initiation. Moreover, the combined therapy of JP1 and paclitaxel maintained a certain vascular density in the tumor and promoted tumor vascular normalization, increasing the delivery of oxygen and drugs and enhancing the antitumor effect. Collectively, our work highlights the antitumor peptide JP1 as an inhibitor of metastasis initiation and its mechanism of action.


Assuntos
Interleucina-8 , Neoplasias , Humanos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/prevenção & controle , Neovascularização Patológica/patologia , Neoplasias/tratamento farmacológico , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Oxigênio , Microambiente Tumoral
16.
Pharmaceutics ; 15(3)2023 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-36986621

RESUMO

Photodynamic therapy (PDT) is a treatment that employs exogenously produced reactive oxygen species (ROS) to kill cancer cells. ROS are generated from the interaction of excited-state photosensitizers (PSs) or photosensitizing agents with molecular oxygen. Novel PSs with high ROS generation efficiency is essential and highly required for cancer photodynamic therapy. Carbon dots (CDs), the rising star of carbon-based nanomaterial family, have shown great potential in cancer PDT benefiting from their excellent photoactivity, luminescence properties, low price, and biocompatibility. In recent years, photoactive near-infrared CDs (PNCDs) have attracted increasing interest in this field due to their deep therapeutic tissue penetration, superior imaging performance, excellent photoactivity, and photostability. In this review, we review recent progress in the designs, fabrication, and applications of PNCDs in cancer PDT. We also provide insights of future directions in accelerating the clinical progress of PNCDs.

17.
Adipocyte ; 12(1): 2173513, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36775902

RESUMO

The healing of skin wounds is a highly coordinated multi-step process that occurs after trauma including surgical incisions, thermal burns, and chronic ulcers. In this study, the authors investigated lncRNA FOXD2-AS1 function in adipose mesenchymal exosomes from ADMSCs that were successfully extracted. Highly expressed lncRNA FOXD2-AS1 in ADMSCs-exosomes accelerated HaCaT cell migration and proliferation. LncRNA FOXD2-AS1 negatively targeted miR-185-5p, and miR-185-5p negatively targeted ROCK2. Highly expressed lncRNA FOXD2-AS1 in ADMSCs-exosomes promoted HaCaT cell migration and proliferation via down-regulating miR-185-5p and further up-regulating ROCK2. In conclusion, LncRNA FOXD2-AS1 overexpression in ADMSCs derived exosomes might accelerate HaCaT cell migration and proliferation via modulating the miR-185-5p/ROCK2 axis.


Assuntos
Exossomos , Células-Tronco Mesenquimais , MicroRNAs , RNA Longo não Codificante , Quinases Associadas a rho , Humanos , Células HaCaT , MicroRNAs/genética , RNA Longo não Codificante/genética
18.
J Craniofac Surg ; 34(2): e164-e167, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36227780

RESUMO

BACKGROUND: Eye bags especially give an impression of aging and mental exhaustion. At present, the surgical methods of bags mainly include conjunctival approach and lower eyelid skin approach. With the continuous upgrading of the concept of facial esthetics, the lower eyelid pouch surgery for middle-aged and elderly patients pays more attention to reducing surgical trauma, improving tear trough deformity along with the effacement of lid­cheek junction. OBJECTIVE: This paper discusses the clinical effect of the lower lid blepharoplasty involved orbital septum fat repositioning based on oral fixation via conjunctival approach combined with relaxation skin resection in the treatment of eye bags in elderly patient. METHODS: Fifty elderly patients underwent blepharoplasty between January of 2021 and June of 2021 at our hospital. The lower eyelid orbital septum fat was released along with the prezygomatic space and the premaxillary space were stripped through the conjunctival approach. The released cellulite was redistributed in the prezygomatic space/premaxillary space and fixed in the oral vestibular with 5-0 Polysorb through the middle facial tunnel. Finally, the appropriate skin was finally removed. RESULTS: After operation, 48 patients were satisfied with the operation results, with tight lower eyelid skin and natural lid­cheek junction. One patient with conjunctival infection was cured after 7 days of antibiotic eye drops. One patient felt foreign body when chewing, and the symptoms disappeared naturally after 5 days without treatment. CONCLUSION: For middle-aged and elderly patients with bags, the surgical method in this study not only has good postoperative effect, but also has small damage to the lower eyelid orbicularis muscle. The appearance is natural and the lower eyelid skin is tight. The effacement of lid­cheek junction and recreating a smooth transition of lower lid cheek interface, which can correct lacrimal groove deformity. The patients have high acceptance and satisfaction, which can be widely used in clinical practice.


Assuntos
Blefaroplastia , Pálpebras , Pessoa de Meia-Idade , Idoso , Humanos , Pálpebras/cirurgia , Blefaroplastia/métodos , Túnica Conjuntiva/cirurgia , Músculos Oculomotores/cirurgia , Órbita/cirurgia , Tecido Adiposo/transplante
19.
Food Chem ; 405(Pt B): 134946, 2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-36410216

RESUMO

Astringency is a feeling of dryness in the mouth. Microscopically, it is manifested in the diversity of ingredients and mechanisms that can cause astringency, astringent components are mainly flavonoids, phenolic acids, tannin and other polyphenols components. Macroscopically, it is manifested in the rich variety of foods with astringent taste, because polyphenols are common secondary metabolites of plants. With the improvement of people's living standards, the demand for reducing or removing astringency in food and medicine is also increasing, and polysaccharides, as commonly used flavoring agents and food additives, have become the ideal choice for decreasing astringency. In this paper, the material basis, molecular mechanism, possible pathways and related cases of polysaccharides moderating of astringency are mainly reviewed, so as to illustrate the feasibility of polysaccharides decreasing of astringency and provide a reference for reducing the astringency of food and drugs.


Assuntos
Adstringentes , Polifenóis , Humanos , Polissacarídeos , Taninos , Alimentos
20.
Genes (Basel) ; 15(1)2023 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-38254910

RESUMO

Luisia, a genus of the subtribe Aeridinae of Orchidaceae, comprises ca. 40 species. Members of Luisia exhibit unique morphological characteristics and represent a valuable ornamental orchid genus. However, due to the scarcity of distinct morphological characters, species identification within this genus is ambiguous and controversial. In the present study, next-generation sequencing (NGS) methods were used to assemble the plastomes of five Luisia species and compare them with one publicly available Luisia plastid genome data. The plastomes of Luisia possessed a quadripartite structure, with sizes ranging from 146,243 bp to 147,430 bp. The plastomes of six Luisia species contained a total of 120 genes, comprising 74 protein-coding genes, 38 tRNA genes and eight rRNA genes. Notably, all ndh genes were pseudogenized or lost. An analysis of codon usage bias showed that leucine (Leu) exhibited the highest frequency, while cysteine (Cys) exhibited the lowest frequency. A total of 57 to 64 SSRs and 42 to 49 long repeats were identified. Five regions and five coding sequences were identified for DNA barcodes, based on the nucleotide diversity (Pi) analysis. The species of Luisia constituted a monophyletic group and were sister to Paraphalaenopsis with strong support. Our study deepens the understanding of species identification, plastome evolution and the phylogenetic positions of Luisia.


Assuntos
Orchidaceae , Orchidaceae/genética , Filogenia , Uso do Códon , Cisteína , Éxons
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