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1.
Adv Sci (Weinh) ; : e2403107, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38704679

RESUMO

Uveal melanoma (UM) is a leading intraocular malignancy with a high 5-year mortality rate, and radiotherapy is the primary approach for UM treatment. However, the elevated lactic acid, deficiency in ROS, and hypoxic tumor microenvironment have severely reduced the radiotherapy outcomes. Hence, this study devised a novel CoMnFe-layered double oxides (LDO) nanosheet with multienzyme activities for UM radiotherapy enhancement. On one hand, LDO nanozyme can catalyze hydrogen peroxide (H2O2) in the tumor microenvironment into oxygen and reactive oxygen species (ROS), significantly boosting ROS production during radiotherapy. Simultaneously, LDO efficiently scavenged lactic acid, thereby impeding the DNA and protein repair in tumor cells to synergistically enhance the effect of radiotherapy. Moreover, density functional theory (DFT) calculations decoded the transformation pathway from lactic to pyruvic acid, elucidating a previously unexplored facet of nanozyme activity. The introduction of this innovative nanomaterial paves the way for a novel, targeted, and highly effective therapeutic approach, offering new avenues for the management of UM and other cancer types.

2.
J Agric Food Chem ; 72(11): 5526-5541, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38457666

RESUMO

Peptide self-assembly, due to its diverse supramolecular nanostructures, excellent biocompatibility, and bright application prospects, has received wide interest from researchers in the fields of biomedicine and green life technology and the food industry. Driven by thermodynamics and regulated by dynamics, peptides spontaneously assemble into supramolecular structures with different functional properties. According to the functional properties derived from peptide self-assembly, applications and development directions in foods can be found and explored. Therefore, in this review, the regulatory mechanism is elucidated from the perspective of self-assembly thermodynamics and dynamics, and the functional properties and application progress of peptide self-assembly in foods are summarized, with a view to more adaptive application scenarios of peptide self-assembly in the food industry.


Assuntos
Nanoestruturas , Peptídeos , Peptídeos/química , Nanoestruturas/química , Termodinâmica
3.
Int J Biol Macromol ; 263(Pt 2): 130439, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38423420

RESUMO

Conductive hydrogels become increasing attractive for flexible electronic devices and biosensors. However, challenges still remain in fabrication of flexible hydrogels with high electrical conductivity, self-healing capability and adhesion property. Herein, a conductive hydrogel (PSDM) was prepared by solution-gel method using MXene and dopamine modified polypyrrole as conductive enhanced materials, polyvinyl alcohol and silk fibroin as gel networks, and borax as cross-linking agent. Notably, the PSDM hydrogels not only showed high permeability (13.82 mg∙cm-2∙h-1), excellent stretch ability (1235 %), high electrical conductivity (11.3 S/m) and long-term stability, but also exhibited high adhesion performance and self-healing properties. PSDM hydrogels displayed outstanding sensing performance and durability for monitoring human activities including writing, finger bending and wrist bending. The PSDM hydrogel was made into wearable flexible electrodes and realized accurate, sensitive and reliable detection of human electromyographic and electrocardiographic signals. The sensor was also applied in human-computer interaction by collecting electromyography signals of different gestures for machine learning and gesture recognition. According to 480 groups of data collected, the recognition accuracy of gestures by the electrodes was close to 100 %, indicating that the PSDM hydrogel electrodes possessed excellent sensing performance for high precision data acquisition and human-computer interaction interface.


Assuntos
Fibroínas , Nitritos , Prunella , Elementos de Transição , Dispositivos Eletrônicos Vestíveis , Humanos , Polímeros , Álcool de Polivinil , Pirróis , Condutividade Elétrica , Hidrogéis
4.
J Texture Stud ; 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37968073

RESUMO

The effect of soybean oil (SO) on freeze-thaw (F-T)-treated surimi was investigated and its related mechanism was revealed by molecular dynamics (MD) simulations. The results displayed that SO has a disrupting effect on the structure of fresh samples. However, in the F-T-treated samples, surimi gels supplemented with SO had a more uniform microstructure. Simultaneously, when SO was added from 0% to 7% in the F-T-treated samples, the gel strength increased from 46.66 to 51.86 N · mm $$ 46.66\ \mathrm{to}\ 51.86\;\mathrm{N}\cdotp \mathrm{mm} $$ (p < .05), the physically bound water was increased from 92.90% to 94.15% (p < .05), and storage modulus was increased from 5939 to 6523 Pa. Triglycerides of SO generated hydrophobic interactions with myosin mainly in carbon chains. Computational results from MD simulations illustrated that the structure of myosin combined with triglycerides was more stable than that of myosin alone during temperature fluctuations (-20 to 4°C). During ice crystal growth, triglycerides absorbed on the myosin surface inhibited the growth of surrounding ice crystals and mitigated the ice crystal growth rate (from 7.54 to 5.99 cm/s). The addition of SO during the F-T treatments allowed myosin to be less negatively affected by ice crystal formation and temperature fluctuations and ultimately contributed to the formation of a more uniform network gel structure.

5.
Cancer Commun (Lond) ; 43(11): 1185-1206, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37466203

RESUMO

BACKGROUND: Diversified histone deacetylation inhibitors (HDACis) have demonstrated encouraging outcomes in multiple malignancies. N6-methyladenine (m6 A) is the most prevalent messenger RNA modification that plays an essential role in the regulation of tumorigenesis. Howbeit, an in-depth understanding of the crosstalk between histone acetylation and m6 A RNA modifications remains enigmatic. This study aimed to explore the role of histone acetylation and m6 A modifications in the regulation of tumorigenesis of ocular melanoma. METHODS: Histone modification inhibitor screening was used to explore the effects of HDACis on ocular melanoma cells. Dot blot assay was used to detect the global m6 A RNA modification level. Multi-omics assays, including RNA-sequencing, cleavage under targets and tagmentation, single-cell sequencing, methylated RNA immunoprecipitation-sequencing (meRIP-seq), and m6 A individual nucleotide resolution cross-linking and immunoprecipitation-sequencing (miCLIP-seq), were performed to reveal the mechanisms of HDACis on methyltransferase-like 14 (METTL14) and FAT tumor suppressor homolog 4 (FAT4) in ocular melanoma. Quantitative real-time polymerase chain reaction (qPCR), western blotting, and immunofluorescent staining were applied to detect the expression of METTL14 and FAT4 in ocular melanoma cells and tissues. Cell models and orthotopic xenograft models were established to determine the roles of METTL14 and FAT4 in the growth of ocular melanoma. RNA-binding protein immunoprecipitation-qPCR, meRIP-seq, miCLIP-seq, and RNA stability assay were adopted to investigate the mechanism by which m6 A levels of FAT4 were affected. RESULTS: First, we found that ocular melanoma cells presented vulnerability towards HDACis. HDACis triggered the elevation of m6 A RNA modification in ocular melanoma. Further studies revealed that METTL14 served as a downstream candidate for HDACis. METTL14 was silenced by the hypo-histone acetylation status, whereas HDACi restored the normal histone acetylation level of METTL14, thereby inducing its expression. Subsequently, METTL14 served as a tumor suppressor by promoting the expression of FAT4, a tumor suppressor, in a m6 A-YTH N6-methyladenosine RNA-binding protein 1-dependent manner. Taken together, we found that HDACi restored the histone acetylation level of METTL14 and subsequently elicited METTL14-mediated m6 A modification in tumorigenesis. CONCLUSIONS: These results demonstrate that HDACis exert anti-cancer effects by orchestrating m6 A modification, which unveiling a "histone-RNA crosstalk" of the HDAC/METTL14/FAT4 epigenetic cascade in ocular melanoma.


Assuntos
Histonas , Melanoma , Humanos , Metilação , Histonas/metabolismo , Histona Desacetilases/metabolismo , Linhagem Celular Tumoral , Melanoma/genética , Carcinogênese , RNA/metabolismo , Proteínas de Ligação a RNA/genética , Metiltransferases/genética , Metiltransferases/metabolismo
6.
Food Chem ; 418: 135871, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36958184

RESUMO

For food preservation, the packaging film needs to have higher antibacterial activity in initial phase and keep longer activity. In this study, cinnamaldehyde (CA) and its sulfobutyl ether-ß-cyclodextrin inclusion complex (CA/S) were used to fabricate fish gelatin antibacterial composite films. The addition enhanced the elongation at break and light barrier property of the films. Film forming solution incorporated with CA and CA/S presented the most excellent inhibition ratio against Pseudomonas aeruginosa, which was 98.43 ± 1.11% in initial period and still 82.97 ± 4.55% at 72 h. Further, the packaging solution of gelatin combined CA and CA/S effectively inhibited the growth of microorganisms during preservation of grass carp slices. Especially, the total volatile salt-based nitrogen (TVB-N) did not exceed 10 mg/100 g at the end of storage, indicating that the active coating could obviously extend the shelf life of fish muscle. This work provided a promising food packaging system with antimicrobial and environmentally friendly.


Assuntos
Gelatina , beta-Ciclodextrinas , Animais , Antibacterianos/farmacologia , Embalagem de Alimentos , Peixes , Éteres
7.
Food Chem ; 414: 135695, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-36809728

RESUMO

The membrane-separated silver carp hydrolysates (>10 kD, 3-10 kD and < 3 kD) displayed abilities to mitigate oxidation and denaturation of myofibrillar protein and cryoprotective activities for frozen surimi. However, the mechanism of the membrane-separated fractions on ice crystal growth in the system is still unknown. Therefore, the cryoprotective activities (recrystallization inhibition, RI and thermal hysteresis activity, THA) of the fractions were investigated and the mechanism was explored by molecular dynamics (MD) simulation to predict the probable binding sites and model the possible interactions between the peptides and water/ice. The fractions < 3 kD displayed remarkable RI activity, with significantly higher THA (0.60 ± 0.13 °C) and lower amount of ice nuclei (4.74 ± 0.53%) than that of fractions > 10 kD and 3-10 kD. The results of MD simulation certified that the main peptides in the fractions < 3 kD interacted firmly with water molecules and inhibited growth of ice crystals with mechanism compatible with Kelvin effect. Hydrophilic and hydrophobic amino acid residues in the membrane-separated fractions offered synergistic effects on the inhibition of ice crystals.


Assuntos
Carpas , Gelo , Animais , Simulação de Dinâmica Molecular , Cristalização , Congelamento , Água/química , Peptídeos/química , Proteínas Anticongelantes , Crioprotetores/farmacologia
8.
J Sci Food Agric ; 103(8): 4211-4220, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36647322

RESUMO

BACKGROUND: Apple polyphenols (APs) with multiple biological effects have attracted extensive attention due to their broad opportunities for application. However, the use of APs is hampered by their instability in the face of environmental changes. Designing efficient carriers to improve the bioavailability of APs is the key to solving these problems. In this study, gelatin-chitooligosaccharide nanoparticles produced by the Maillard reaction (GCM) were fabricated to encapsulate AP, and the structure, antioxidant activity, and stability of the GMM-AP nanoparticle system were evaluated. RESULTS: The results of endogenous fluorescence spectrum, Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction, and simultaneous thermal analysis confirmed structural changes and interactions between GCM and AP. Combination with GCM did not adversely affect the antioxidant properties of AP, and the GCM-AP nanoparticles possessed superior temperature and storage stability. In comparison with fish gelatin-apple polyphenol nanoparticles, the GCM-AP nanoparticles were more stable at a wider pH range, and were more resistant to the electrostatic shielding effect of NaCl. After simulating gastric digestion, the particle size and polydispersity index (PDI) of GCM-AP nanoparticles were almost unchanged. CONCLUSION: The findings suggest that GCM nanoparticles loaded with AP could be used as good carriers with good antioxidant activity and stability. This study therefore provides a theoretical foundation for the development and industrial application of food functional factors. © 2023 Society of Chemical Industry.


Assuntos
Nanopartículas , Polifenóis , Animais , Polifenóis/química , Antioxidantes , Gelatina/química , Quitina , Nanopartículas/química , Tamanho da Partícula
9.
Food Res Int ; 163: 112299, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36596202

RESUMO

Freeze denaturation of protein caused by ice crystals is the main motivation for the quality deterioration of surimi during circulation and storage. This investigation aimed to cryoprotect surimi by adding antifreeze peptides from Takifugu obscurus skin (TsAFP) which can inhibit ice recrystallization, and to elucidate regulating mechanism. The comprehensive results showed that 4% TsAFP, half dosage of commercial cryoprotectant, had good cryoprotection on surimi by reducing the moisture variation and maintaining protein solubility of surimi at macro level, as well as inhibiting the degeneration and structure changes of myofibrillar proteins at micro level. Meanwhile, TsAFP could directly bind to the structural cavity of myosin, inhibit protein freezing-induced oxidation, maintain the spatial structure of myosin and water retention ability to preserve the surimi quality. This study helped better comprehend the protective mechanisms of antifreeze peptides in frozen surimi and was expected to provide a promising cryoprotectant for low-sweetness and low-calorie surimi.


Assuntos
Crioprotetores , Gelo , Congelamento , Crioprotetores/farmacologia , Crioprotetores/química , Miosinas , Proteínas Anticongelantes
10.
J Plast Reconstr Aesthet Surg ; 77: 104-110, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36563635

RESUMO

The application of navigation and endoscope is an area of intense interest in the surgical repair of orbital fractures. This study explored the advantages of a combined endoscopy navigation technique (ENT) for repairing large orbital floor and medial wall fractures (OFMWFs) with destruction of the inferomedial strut (IMS). Fifty-two consecutive patients with large OFMWFs with the destruction of the IMS underwent ENT-assisted surgical repair from January 2013 to February 2016. Patient demographics, causes of injury, clinical features, imaging data, and follow-up information (diplopia, ocular dysmotility, enophthalmos, infraorbital hypoesthesia, and other conditions) were collected and analyzed. Orbital volumes and implant positions were also evaluated. The median follow-up duration was 21 (range, 16-29) months. At the end of the follow-up visits, orbital reconstruction was demonstrated by orbital computed tomography. Of the 30 patients with diplopia within the 30-degree visual field of gaze, 27 (90%) reached diplopia remission. Of 40 patients, 34 (85%) achieved complete elimination of ocular dysmotility. Of 47 patients with enophthalmos of >2 mm, 43 (91%) acquired good symmetry with a mean improvement of 3.00 ± 1.00 mm. Of 33 patients, 27 (82%) recovered from infraorbital hypoesthesia. The postoperative orbital volumes of the two sides showed no significant differences (p = 0.087, paired t-test). Early surgical repair showed better outcomes of diplopia, ocular motility, and enophthalmos than late repair (p = 0.001, p = 0.007, and p = 0.000, generalized estimated equations). No patient developed surgery-related complications of visual acuity compromise, strabismus, ectropion, entropion, or lacrimal canaliculus injuries. ENT-assisted surgery appears to be safe, precise, and effective for the repair of large OFMWFs with destruction of the IMS.


Assuntos
Enoftalmia , Fraturas Orbitárias , Humanos , Fraturas Orbitárias/diagnóstico por imagem , Fraturas Orbitárias/cirurgia , Fraturas Orbitárias/complicações , Enoftalmia/etiologia , Enoftalmia/cirurgia , Diplopia/etiologia , Hipestesia/complicações , Endoscopia/métodos , Estudos Retrospectivos , Resultado do Tratamento
11.
Food Chem ; 403: 134335, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36156396

RESUMO

Finding functional preparations that could improve the bioavailability of calcium is one of the keys to solving calcium deficiency. In this study, glycosylated peptides-calcium chelate with calcium absorption promoting activity, named XOS-CSPHs-Ca-MR, was prepared from Crimson Sapper scales protein hydrolysates (CSPHs) and xylooligosaccharides (XOS) via Maillard reaction. Results showed that amino nitrogen, carboxyl oxygen, and carbonyl oxygen atom were the primary calcium chelating sites. Remarkably, XOS-CSPHs-Ca-MR exhibited good calcium phosphate crystallization inhibitory activity, gastrointestinal stability, and could promote calcium transport efficiency in the Caco-2 cell monolayer. In vitro fermentation results showed that XOS-CSPHs-Ca-MR improved the gut microbiota structure of calcium-deficient mice. Its prebiotic effect was achieved by increasing the number of beneficial bacteria, boosting the production of short-chain fatty acids, and improving the colonization ability of microbiota. Therefore, this study could lay a foundation for the study of glycosylated peptide-calcium chelate as a novel calcium supplement with prebiotic effect.


Assuntos
Cálcio , Prebióticos , Humanos , Camundongos , Animais , Cálcio/química , Células CACO-2 , Cálcio da Dieta , Hidrolisados de Proteína/química , Peptídeos/química , Oxigênio
12.
J Agric Food Chem ; 70(44): 14148-14156, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36314886

RESUMO

Foodborne hydrolyzed antifreeze peptides have been widely used in the food industry and the biomedical field. However, the components of hydrolyzed peptides are complex and the molecular mechanism remains unclear. This study focused on identification and mechanism analysis of novel antifreeze peptides from Takifugu obscurus skin by traditional methods and computer-assisted techniques. Results showed that three peptides (EGPRAGGAPG, GDAGPSGPAGPTG, and GEAGPAGPAG) possessed cryoprotection via reducing the freezing point and inhibiting ice crystal growth. Molecular docking confirmed that the cryoprotective property was related to peptide structure, especially α-helix, and hydrogen bond sites. Moreover, the antifreeze peptides were double-faces, which controlled ice crystals while affecting the arrangement of surrounding water molecules, thus exhibiting a strong antifreeze activity. This investigation deepens the comprehension of the mechanism of antifreeze peptides at molecular scale, and the novel efficient antifreeze peptides can be developed in antifreeze materials design and applied in food industry.


Assuntos
Gelo , Takifugu , Animais , Cristalização , Simulação de Acoplamento Molecular , Congelamento , Proteínas Anticongelantes/química , Peptídeos/química
13.
Contrast Media Mol Imaging ; 2022: 6291497, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35845734

RESUMO

Diabetic foot ulcers (DFU) are among the serious complications which are closely linked to diabetes mellitus. However, there is still a lack of accurate and effective standard prevention and treatment programs for DFU. In this manuscript, we have investigated the function of lncRNA cancer susceptibility candidate 2 (CASC2)/miR-155/hypoxia-inducible factor 1-alpha (HIF-1α) in the wound healing of DFU. We have analyzed lncRNA CASC2`s expression in the marginal tissues of ulcers in patients and mice with DFU. Additionally, the interaction relationship and mechanism between lncRNA CASC2, miR-155, and HIF-1α were determined, which proved the effects of lncRNA CASC2/miR-155/HIF-1α on fibroblasts apoptosis, proliferation, and migration. According to our study, the lncRNA CASC2's expression was low in the tissues of ulcers of DFU mice and patients. lncRNA CASC2's overexpression promoted fibroblasts migration, proliferation, and inhibited apoptosis and was beneficial for the healing of wounds, preferably in the DFU mice. In addition, lncRNA CASC2 directly targets miR-155 and HIF-1α functions as miR-155's target gene. Overexpression of miR-155 abrogated the function of lncRNA CASC2. Similarly, HIF-1α's inhibition has reversed the effect of miR-155 downregulation on fibroblasts. In general, overexpression of lncRNA CASC2 facilitated wound healing through miR-155/HIF-1α in DFU.


Assuntos
Diabetes Mellitus , Pé Diabético , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante , Proteínas Supressoras de Tumor/metabolismo , Cicatrização , Animais , Movimento Celular , Proliferação de Células , Pé Diabético/genética , Pé Diabético/metabolismo , Camundongos , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
14.
J Colloid Interface Sci ; 625: 197-209, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35716615

RESUMO

Conductive hydrogel-based flexible electronics have attracted immense interest in wearable sensor, soft robot and human-machine interface. However, the application of hydrogels in flexible electronics is limited by the deterioration of mechanical and electrical properties due to freezing at low temperature and desiccation after long-term use. Meanwhile, flexible electronics based on hydrogel are usually not breathable, which has a great impact on wearing comfort and signal stability in long-term sensing. In this work, an adjustable porous gelatin/polypyrrole/reduction graphene oxide (Gel/PPy/rGO) organohydrogel with high breathability (14 g∙cm-2∙h-1), conductivity (5.25 S/m), mechanical flexibility, anti-freezing and long-term stability is prepared via the combination method of biological fermentation and salt-out toughening crosslinking. The sensor fabricated from the prepared porous organohydrogel exhibits excellent sensing sensitivity, fast response ability, and good endurance, which monitors both weak and intense human activities effectively like finger bending, elbow bending, walking and running, and tiny pulse beating. A pressure sensor array prepared from the porous organohydrogel detects pressure variation in 2D sensitively. Furthermore, the porous organohydrogel is utilized as flexible electrodes for the accurate collection and recognition of human physiological signals (EMG, ECG) and as an interface between human and machine.


Assuntos
Polímeros , Dispositivos Eletrônicos Vestíveis , Condutividade Elétrica , Eletrônica , Gelatina , Grafite , Humanos , Hidrogéis , Porosidade , Pirróis
15.
J Food Sci ; 87(6): 2692-2706, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35590483

RESUMO

Myofibrillar proteins (MPs) are important to the gel formation that occurs in frozen surimi. Importantly, their unique gel-forming ability indicates that surimi may be a promising material for use in 3D printing. The objective of the present study was to investigate the effects of collagen peptides on the cryoprotection of MPs during freeze-thaw (FT) cycles and the subsequent printability of surimi. The results showed that the collagen peptide had both protective and destructive actions during the tested FT cycles. The addition of 1.0% collagen peptide provided significant cryoprotection to the MPs. This addition effectively maintained the structural stability of MPs while also weakening FT effects on bound water and its mobility. We also assessed the rheological and 3D-printing characteristics of surimi with 1.0% collagen peptide. The rheological results indicated that the surimi with collagen peptides had better characteristics, including shear-thinning behavior, better recovery, and improved mechanical properties. Combined with the actual printing effect, materials with good shear-thinning behavior, high apparent viscosity, and high recovery might be more suitable for 3D printing. Moreover, the high G' contributed to good structural maintenance after printing. Collectively, these results indicated that collagen peptide may serve as a new, low-sugar cryoprotectant for use in surimi. Moreover, that its use would result in a healthier system that has increased stability, precision, and formability with applications in extrusion-based 3D printing. The results of this study provide theoretical reference for the development of new surimi materials with freezing stability and good 3D printing performance. PRACTICAL APPLICATION: This study confirmed the protective action of 1.0% collagen peptides for surimi and the contribution of it to well printing precision and structure maintenance for 3D printing, providing a firm foundation for the use of collagen peptide as a low-sugar cryoprotectant and developed a new type of surimi as a food material for 3D printing.


Assuntos
Crioprotetores , Impressão Tridimensional , Colágeno , Crioprotetores/química , Congelamento , Peptídeos , Açúcares
16.
Bioengineered ; 13(5): 12772-12782, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35609321

RESUMO

Cardiovascular risk factors have attracted increasing attention in recent years with the acceleration of population aging, amongst which cardiac hypertrophy is the initiating link to heart failure. Pirfenidone is a promising agent for the treatment of idiopathic pulmonary fibrosis and has recently proven to exert inhibitory effects on the inflammatory response. This study proposes to explore the potential pharmacological action of Pirfenidone in treating cardiac hypertrophy in a rodent model. Four groups of mice were used in the present study: the control, ISO (5 mg/kg/day) for 7 days, Pirfenidone (200 mg/kg/day) for 14 days, and Spironolactone (SPI) (200 mg/kg/day) for 14 days groups. Increased heart weight index, left ventricle (LV) weight index, LV wall thickness, declined LV volume, and elevated serum levels of CK-MB, AST, and LDH were observed in ISO-challenged mice, all of which were dramatically reversed by the administration of Pirfenidone or SPI. Furthermore, an elevated cross-sectional area of cardiomyocytes in the wheat germ agglutinin (WGA) staining of heart cross-sections, upregulated atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), ß Myosin Heavy Chain (ß-MHC), and excessively released tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) in cardiac tissues were observed in the ISO group but greatly alleviated by Pirfenidone or SPI. Lastly, the promoted expression levels of p-JAK-2/JAK-2 and p-STAT3/STAT-3 in the cardiac tissues of ISO-challenged mice were significantly repressed by Pirfenidone or SPI. Collectively, our data reveals a therapeutic property of Pirfenidone on ISO-induced cardiac hypertrophy in mice.


Assuntos
Fator de Transcrição STAT3 , TYK2 Quinase , Animais , Cardiomegalia/tratamento farmacológico , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Isoproterenol/metabolismo , Isoproterenol/farmacologia , Isoproterenol/uso terapêutico , Camundongos , Miócitos Cardíacos/metabolismo , Piridonas , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , TYK2 Quinase/metabolismo , TYK2 Quinase/farmacologia , TYK2 Quinase/uso terapêutico , Tirosina/metabolismo
17.
Clin Transl Med ; 12(1): e660, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35075807

RESUMO

OBJECTIVE: To explore the therapeutic potential and the underlying mechanism of metformin, an adenosine monophosphate-activated kinase (AMPK) activator, in ocular melanoma. METHODS: CCK8, transwell, and colony formation assays were performed to detect the proliferation and migration ability of ocular melanoma cells. A mouse orthotopic xenograft model was built to detect ocular tumor growth in vivo. Western blot, immunofluorescence, and electron microscopy were adopted to evaluate the autophagy levels of ocular melanoma cells, and high-throughput proteomics and CUT & Tag assays were performed to analyze the candidate for autophagy alteration. RESULTS: Here, we revealed for the first time that a relatively low dose of metformin induced significant tumorspecific inhibition of the proliferation and migration of ocular melanoma cells both in vitro and in vivo. Intriguingly, we found that metformin significantly attenuated autophagic influx in ocular melanoma cells. Through high-throughput proteomics analysis, we revealed that optineurin (OPTN), which is a key candidate for autophagosome formation and maturation, was significantly downregulated after metformin treatment. Moreover, excessive OPTN expression was associated with an unfavorable prognosis of patients. Most importantly, we found that a histone deacetylase, SIRT1, was significantly upregulated after AMPK activation, resulting in histone deacetylation in the OPTN promoter. CONCLUSIONS: Overall, we revealed for the first time that metformin significantly inhibited the progression of ocular melanoma, and verified that metformin acted as an autophagy inhibitor through histone deacetylation of OPTN. This study provides novel insights into metformin - guided suppression of ocular melanoma and the potential mechanism underlying the dual role of metformin in autophagy regulation.


Assuntos
Autofagia/efeitos dos fármacos , Proteínas de Ciclo Celular/efeitos dos fármacos , Histona Desmetilases/efeitos dos fármacos , Melanoma/tratamento farmacológico , Proteínas de Membrana Transportadoras/efeitos dos fármacos , Metformina/agonistas , Animais , Proteínas de Ciclo Celular/metabolismo , Modelos Animais de Doenças , Olho/efeitos dos fármacos , Olho/metabolismo , Melanoma/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Metformina/uso terapêutico , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo
18.
Crit Rev Food Sci Nutr ; 62(19): 5113-5129, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33567903

RESUMO

Traditionally, walnuts have occupied an imperative position in the functional food market with consistently recognized nutritious and functional properties. In the past years, the lipid profile of walnuts has brought much scientific attention via linking a cascade of biological attributes and health-promoting effects. Over time, researchers have focused on diversified composition (polyphenols and vitamins) of different parts of walnut (flower, pellicle, and kernel) and emphasized their physiological significance. Consequently, a plethora of reports has emerged on the potential role of walnut consumption against a series of diseases including cancer, gut dysbiosis, cardiovascular, and neurodegenerative diseases. Therefore, we accumulated the updated data on composition and classification, extraction methods, and utilization of different parts of walnuts as well as associated beneficial effects under in vivo and clinical studies. Altogether, this review summarized the ameliorative effects of a walnut-enriched diet in chronic diseases which can be designated to the synergistic or individual effects of walnut components mainly through anti-oxidative and anti-inflammatory role.


Assuntos
Juglans , Anti-Inflamatórios , Dieta , Nozes/química , Polifenóis/análise
19.
J Craniofac Surg ; 33(3): e238-e240, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34374675

RESUMO

ABSTRACT: The aim of the study was to report a novel forkhead box L2 (FOXL2) missense mutation in a Chinese blepharophimosis/ ptosis/epicanthus inversus syndrome family. Three generations of the Chinese family with blepharophimosis/ptosis/epicanthus inversus syndrome were enrolled in this study. Blood samples from patients of this family were collected and then analyzed by whole-exome sequencing. Confocal microscopy was performed to detect the subcellular location of FOXL2. Transactivation studies were performed and verified with real time polymerase chain reaction. A novel mutation (c.1068G>C) located in the downstream of deoxyribonucleic acid-binding forkhead domain was identified. Confocal photos showed the novel mutation did not disturb FOXL2 function, and the mutant protein could still transactivate steroidogenic acute regulatory protein, a key regulator of primary ovarian failure (POF). Our study revealed a novel missense mutation (c.1068G>C) and expanded the spectrum of FOXL2 gene mutations.


Assuntos
Blefarofimose , Proteína Forkhead Box L2 , Anormalidades da Pele , Anormalidades Urogenitais , Blefarofimose/diagnóstico , Blefarofimose/genética , China , Proteína Forkhead Box L2/genética , Humanos , Mutação de Sentido Incorreto , Linhagem , Anormalidades da Pele/diagnóstico , Anormalidades da Pele/genética , Anormalidades Urogenitais/diagnóstico , Anormalidades Urogenitais/genética
20.
Food Sci Nutr ; 9(9): 5279-5292, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34532034

RESUMO

Microalgae is one of the most important components in the aquatic ecosystem, and they are increasingly used in food and medicine production for human consumption due to their rapid growth cycle and survival ability in the harsh environment. Now, the exploration of microalgae has been gradually deepening, mainly focused on the field of nutrition, medicine, and cosmetics. A great deal of studies has shown that microalgae have a variety of functions in regulating the body health and preventing disease, such as nitrogen fixation, antitumor, antivirus, antioxidation, anti-inflammatory, and antithrombotic. Furthermore, microalgae can synthesize various high-valued bioactive substances, such as proteins, lipids, polysaccharides, and pigments. In this paper, we have briefly reviewed the research progress of main bioactive components in microalgae, proteins, lipids, polysaccharides, pigments, and other nutrients included, as well as their present application situation. This paper can provide the guidance for research and development of industrial production of microalgae.

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