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1.
Photoacoustics ; 38: 100610, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38726025

RESUMO

Expansion microscopy (ExM) is a promising technology that enables nanoscale imaging on conventional optical microscopes by physically magnifying the specimens. Here, we report the development of a strategy that enables i) on-demand labeling of subcellular organelles in live cells for ExM through transfection of fluorescent proteins that are well-retained during the expansion procedure; and ii) non-fluorescent chromogenic color-development towards efficient bright-field and photoacoustic imaging in both planar and volumetric formats, which is applicable to both cultured cells and biological tissues. Compared to the conventional ExM methods, our strategy provides an expanded toolkit, which we term as expansion fluorescence and photoacoustic microscopy (ExFLPAM), by allowing on-demand fluorescent protein labeling of cultured cells, as well as non-fluorescent absorption contrast-imaging of biological samples.

2.
Phytochemistry ; 219: 113987, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38218306

RESUMO

Cyano tends to have better biological activity, but it is rarely reported in natural products, especially in the C20-diterpene alkaloids. Herein, three unprecedented C20-diterpenoid alkaloids, brunonianines A-C (1-3), possessing rare cyano functional group as well as an atisine backbone constructed from a phenethyl substituent and a tetrahydropyran ring, along with four C19-alkaloids (4-7) and one amide alkaloids (8), were isolated from the whole plant of Delphinium brunonianum Royle. Compounds 1-3 are also the first atisine type diterpenoid alkaloids with cyano group obtained from nature. The structures of the previously undescribed compounds were elucidated by HR-ESI-MS, 1D/2D NMR spectroscopic data and electronic circular dichroism calculations and single-crystal X-ray diffraction. Reasonable speculations have also been made regarding the biogenic synthetic pathways of compounds 1-3. In addition, the inhibitory activity of all compounds was also tested against four tumor lines: A549, Caco-2, H460 and Skov-3, where compound 2 (IC50 2.20 ± 0.21 µM) showed better inhibitory activity against Skov-3 cells than the hydroxycamptothecin. Using flow cytometry, cell staining, migration and invasion analysis, and Western blot, compound 2 was found to arrest cells in the G2/M phase and was able to effectively inhibit cell motility to achieve potent anti-tumor effects. In addition, compound 2 can effectively induce apoptosis by activating the Bax/Bcl-2/Caspase-3 signaling pathway.


Assuntos
Alcaloides , Delphinium , Diterpenos , Humanos , Delphinium/química , Estrutura Molecular , Células CACO-2 , Alcaloides/farmacologia , Alcaloides/química , Diterpenos/farmacologia , Diterpenos/química
3.
Adv Mater ; : e2304846, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38252896

RESUMO

Decellularized extracellular matrix (dECM)-based hydrogels are widely applied to additive biomanufacturing strategies for relevant applications. The extracellular matrix components and growth factors of dECM play crucial roles in cell adhesion, growth, and differentiation. However, the generally poor mechanical properties and printability have remained as major limitations for dECM-based materials. In this study, heart-derived dECM (h-dECM) and meniscus-derived dECM (Ms-dECM) bioinks in their pristine, unmodified state supplemented with the photoinitiator system of tris(2,2-bipyridyl) dichlororuthenium(II) hexahydrate and sodium persulfate, demonstrate cytocompatibility with volumetric bioprinting processes. This recently developed bioprinting modality illuminates a dynamically evolving light pattern into a rotating volume of the bioink, and thus decouples the requirement of mechanical strengths of bioprinted hydrogel constructs with printability, allowing for the fabrication of sophisticated shapes and architectures with low-concentration dECM materials that set within tens of seconds. As exemplary applications, cardiac tissues are volumetrically bioprinted using the cardiomyocyte-laden h-dECM bioink showing favorable cell proliferation, expansion, spreading, biomarker expressions, and synchronized contractions; whereas the volumetrically bioprinted Ms-dECM meniscus structures embedded with human mesenchymal stem cells present appropriate chondrogenic differentiation outcomes. This study supplies expanded bioink libraries for volumetric bioprinting and broadens utilities of dECM toward tissue engineering and regenerative medicine.

4.
Biomater Res ; 27(1): 117, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37978399

RESUMO

BACKGROUND: There is a great clinical need and it remains a challenge to develop artificial soft tissue constructs that can mimic the biomechanical properties and bioactivity of natural tissue. This is partly due to the lack of suitable biomaterials. Hydrogels made from human placenta offer high bioactivity and represent a potential solution to create animal-free 3D bioprinting systems that are both sustainable and acceptable, as placenta is widely considered medical waste. A combination with silk and gelatin polymers can bridge the biomechanical limitations of human placenta chorion extracellular matrix hydrogels (hpcECM) while maintaining their excellent bioactivity. METHOD: In this study, silk fibroin (SF) and tyramine-substituted gelatin (G-TA) were enzymatically crosslinked with human placental extracellular matrix (hpcECM) to produce silk-gelatin-ECM composite hydrogels (SGE) with tunable mechanical properties, preserved elasticity, and bioactive functions. The SGE composite hydrogels were characterized in terms of gelation kinetics, protein folding, and bioactivity. The cyto- and biocompatibility of the SGE composite was determined by in vitro cell culture and subcutaneous implantation in a rat model, respectively. The most cell-supportive SGE formulation was then used for 3-dimensional (3D) bioprinting that induced chemical crosslinking during extrusion. CONCLUSION: Addition of G-TA improved the mechanical properties of the SGE composite hydrogels and inhibited crystallization and subsequent stiffening of SF for up to one month. SGE hydrogels exhibit improved and tunable biomechanical properties and high bioactivity for encapsulated cells. In addition, its use as a bioink for 3D bioprinting with free reversible embedding of suspended hydrogels (FRESH) has been validated, opening the possibility to fabricate highly complex scaffolds for artificial soft tissue constructs with natural biomechanics in future.

5.
Adv Mater Technol ; 8(7)2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37693798

RESUMO

Blood vessel chips are bioengineered microdevices, consisting of biomaterials, human cells, and microstructures, which recapitulate essential vascular structure and physiology and allow a well-controlled microenvironment and spatial-temporal readouts. Blood vessel chips afford promising opportunities to understand molecular and cellular mechanisms underlying a range of vascular diseases. The physiological relevance is key to these blood vessel chips that rely on bioinspired strategies and bioengineering approaches to translate vascular physiology into artificial units. Here, we discuss several critical aspects of vascular physiology, including morphology, material composition, mechanical properties, flow dynamics, and mass transport, which provide essential guidelines and a valuable source of bioinspiration for the rational design of blood vessel chips. We also review state-of-art blood vessel chips that exhibit important physiological features of the vessel and reveal crucial insights into the biological processes and disease pathogenesis, including rare diseases, with notable implications for drug screening and clinical trials. We envision that the advances in biomaterials, biofabrication, and stem cells improve the physiological relevance of blood vessel chips, which, along with the close collaborations between clinicians and bioengineers, enable their widespread utility.

6.
Front Bioeng Biotechnol ; 11: 1252499, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37744248

RESUMO

Silk spinning, observed in spiders and insects, exhibits a remarkable biological source of inspiration for advanced polymer fabrications. Because of the systems design, silk spinning represents a holistic and circular approach to sustainable polymer fabrication, characterized by renewable resources, ambient and aqueous processing conditions, and fully recyclable "wastes." Also, silk spinning results in structures that are characterized by the combination of monolithic proteinaceous composition and mechanical strength, as well as demonstrate tunable degradation profiles and minimal immunogenicity, thus making it a viable alternative to most synthetic polymers for the development of advanced biomedical devices. However, the fundamental mechanisms of silk spinning remain incompletely understood, thus impeding the efforts to harness the advantageous properties of silk spinning. Here, we present a concise and timely review of several essential features of silk spinning, including the molecular designs of silk proteins and the solvent cues along the spinning apparatus. The solvent cues, including salt ions, pH, and water content, are suggested to direct the hierarchical assembly of silk proteins and thus play a central role in silk spinning. We also discuss several hypotheses on the roles of solvent cues to provide a relatively comprehensive analysis and to identify the current knowledge gap. We then review the state-of-the-art bioinspired fabrications with silk proteins, including fiber spinning and additive approaches/three-dimensional (3D) printing. An emphasis throughout the article is placed on the universal characteristics of silk spinning developed through millions of years of individual evolution pathways in spiders and silkworms. This review serves as a stepping stone for future research endeavors, facilitating the in vitro recapitulation of silk spinning and advancing the field of bioinspired polymer fabrication.

7.
bioRxiv ; 2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37503226

RESUMO

Expansion microscopy (ExM) is a promising technology that enables nanoscale imaging on conventional optical microscopes by physically magnifying the specimens. Here, we report the development of a strategy that enables i) on-demand labeling of subcellular organelles in live cells for ExM through transfection of fluorescent proteins that are well-retained during the expansion procedure; and ii) non-fluorescent chromogenic color-development towards efficient bright-field and photoacoustic imaging in both planar and volumetric formats, which is applicable to both cultured cells and biological tissues. Compared to the conventional ExM methods, our strategy provides an expanded toolkit, which we term as expansion fluorescence and photoacoustic microscopy (ExFLPAM), by allowing on-demand fluorescent protein labeling of cultured cells, as well as non-fluorescent absorption contrast-imaging of biological samples.

8.
Bioorg Chem ; 138: 106623, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37295240

RESUMO

Fangchinoline (Fan) are extracted from the traditional Chinese medicine Stephania tetrandra S., which is a bis-benzyl isoquinoline alkaloids with anti-tumor activity. Therefore, 25 novel Fan derivatives have been synthesized and evaluated for their anti-cancer activity. In CCK-8 assay, these fangchinoline derivatives displayed higher proliferation inhibitory activity on six tumor cell lines than the parental compound. Compared to the parent Fan, compound 2h presented the anticancer activity against most cancer cells, especially A549 cells, with an IC50 value of 0.26 µM, which was 36.38-fold, and 10.61-fold more active than Fan and HCPT, respectively. Encouragingly, compound 2h showed low biotoxicity to the human normal epithelial cell BEAS-2b with an IC50 value of 27.05 µM. The results indicated compound 2h remarkably inhibited the cell migration by decreasing MMP-2 and MMP-9 expression and inhibited the proliferation of A549 cells by arresting the G2/M cell cycle. Meanwhile, compound 2h could also induce A549 cell apoptosis by promoting endogenous pathways of mitochondrial regulation. In nude mice presented that the growth of tumor tissues was markedly inhibited by the consumption of compound 2h in a dose-dependent manner, and it was found that compound 2h could inhibit the mTOR/PI3K/AKT pathway in vivo. In docking analysis, high affinity interaction between 2h and PI3K was responsible for drastic kinase inhibition by the compound. To conclude, this derivative compound may be useful as a potent anti-cancer agent for treatment of NSCLC.


Assuntos
Antineoplásicos , Benzilisoquinolinas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Camundongos , Animais , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Camundongos Nus , Neoplasias Pulmonares/metabolismo , Proliferação de Células , Benzilisoquinolinas/farmacologia , Benzilisoquinolinas/uso terapêutico , Linhagem Celular Tumoral , Apoptose , Proteínas Proto-Oncogênicas c-akt/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
9.
Phytomedicine ; 112: 154702, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36764096

RESUMO

BACKGROUND: Nervonic acid (C24:1∆15, 24:1 ω-9, cis-tetracos-15-enoic acid; NA), a long-chain monounsaturated fatty acid, plays an essential role in prevention of metabolic diseases, and immune regulation, and has anti-inflammatory properties. As a chronic, immune-mediated inflammatory disease, ulcerative colitis (UC) can affect the large intestine. The influences of NA on UC are largely unknown. PURPOSE: The present study aimed to decipher the anti-UC effect of NA in the mouse colitis model. Specifically, we wanted to explore whether NA can regulate the levels of inflammatory factors in RAW264.7 cells and mouse colitis model. METHODS: To address the above issues, the RAW264.7 cell inflammation model was established by lipopolysaccharide (LPS), then the inflammatory factors tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), Interleukin-1ß (IL-1ß), and Interleukin-10 (IL-10) were detected by Enzyme-linked immunosorbent assay (ELISA). The therapeutic effects of NA for UC were evaluated using C57BL/6 mice gavaged dextran sodium sulfate (DSS). Hematoxylin and eosin (H&E) staining, Myeloperoxidase (MPO) kit assay, ELISA, immunofluorescence assay, and LC-MS/MS were used to assess histological changes, MPO levels, inflammatory factors release, expression and distribution of intestinal tight junction (TJ) protein ZO-1, and metabolic pathways, respectively. The levels of proteins involved in the nuclear factor kappa-B (NF-κB) pathway in the UC were investigated by western blotting and RT-qPCR. RESULTS: In vitro experiments verified that NA could reduce inflammatory response and inhibit the activation of key signal pathways associated with inflammation in LPS-induced RAW264.7 cells. Further, results from the mouse colitis model suggested that NA could restore intestinal barrier function and suppress NF-κB signal pathways to ameliorate DSS-induced colitis. In addition, untargeted metabolomics analysis of NA protection against UC found that NA protected mice from colitis by regulating citrate cycle, amino acid metabolism, pyrimidine and purine metabolism. CONCLUSION: These results suggested that NA could ameliorate the secretion of inflammatory factors, suppress the NF-κB signaling pathway, and protect the integrity of colon tissue, thereby having a novel role in prevention or treatment therapy for UC. This work for the first time indicated that NA might be a potential functional food ingredient for preventing and treating inflammatory bowel disease (IBD).


Assuntos
Colite Ulcerativa , Colite , Animais , Camundongos , Cromatografia Líquida , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colo/patologia , Sulfato de Dextrana , Modelos Animais de Doenças , Ácidos Graxos Monoinsaturados/farmacologia , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Transdução de Sinais , Espectrometria de Massas em Tandem
10.
Nat Commun ; 14(1): 210, 2023 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-36639727

RESUMO

Volumetric additive manufacturing (VAM) enables fast photopolymerization of three-dimensional constructs by illuminating dynamically evolving light patterns in the entire build volume. However, the lack of bioinks suitable for VAM is a critical limitation. This study reports rapid volumetric (bio)printing of pristine, unmodified silk-based (silk sericin (SS) and silk fibroin (SF)) (bio)inks to form sophisticated shapes and architectures. Of interest, combined with post-fabrication processing, the (bio)printed SS constructs reveal properties including reversible as well as repeated shrinkage and expansion, or shape-memory; whereas the (bio)printed SF constructs exhibit tunable mechanical performances ranging from a few hundred Pa to hundreds of MPa. Both types of silk-based (bio)inks are cytocompatible. This work supplies expanded bioink libraries for VAM and provides a path forward for rapid volumetric manufacturing of silk constructs, towards broadened biomedical applications.


Assuntos
Bioimpressão , Fibroínas , Seda , Tinta , Bioimpressão/métodos , Impressão Tridimensional , Engenharia Tecidual/métodos , Alicerces Teciduais
11.
Small ; 19(50): e2205078, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36587991

RESUMO

Three-dimensional (3D) bioprinting is driving significant innovations in biomedicine over recent years. Under certain scenarios such as in intraoperative bioprinting, the bioinks used should exhibit not only cyto/biocompatibility but also adhesiveness in wet conditions. Herein, an adhesive bioink composed of gelatin methacryloyl, gelatin, methacrylated hyaluronic acid, and skin secretion of Andrias davidianus is designed. The bioink exhibits favorable cohesion to allow faithful extrusion bioprinting in wet conditions, while simultaneously showing good adhesion to a variety of surfaces of different chemical properties, possibly achieved through the diverse bonds presented in the bioink formulation. As such, this bioink is able to fabricate sophisticated planar and volumetric constructs using extrusion bioprinting, where the dexterity is further enhanced using ergonomic handheld bioprinters to realize in situ bioprinting. In vitro experiments reveal that cells maintain high viability; further in vivo studies demonstrate good integration and immediate injury sealing. The characteristics of the bioink indicate its potential widespread utility in extrusion bioprinting and will likely broaden the applications of bioprinting toward situations such as in situ dressing and minimally invasive tissue regeneration.


Assuntos
Bioimpressão , Alicerces Teciduais , Alicerces Teciduais/química , Engenharia Tecidual/métodos , Adesivos , Gelatina/química , Pele , Cicatrização , Impressão Tridimensional , Hidrogéis/química , Bioimpressão/métodos
12.
Life Sci Space Res (Amst) ; 35: 150-157, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36336360

RESUMO

The spaceflight environment, including microgravity and radiation, may have considerable effects on the health and performance of astronauts, especially for long-duration and Martian missions. Conventional on-ground and in-space experimental approaches have been employed to investigate the comprehensive biological effects of the spaceflight environment. As a class of recently emerging bioengineered in vitro models, tissue chips are characterized by a small footprint, potential automation, and the recapitulation of tissue-level physiology, thus promising to help provide molecular and cellular insights into space medicine. Here, we briefly review the technical advantages of tissue chips and discuss specific on-chip physiological recapitulations. Several tissue chips have been launched into space, and more are poised to come through multi-agency collaborations, implying an increasingly important role of tissue chips in space medicine.


Assuntos
Medicina Aeroespacial , Marte , Voo Espacial , Ausência de Peso , Humanos , Meio Ambiente Extraterreno , Astronautas
13.
Food Chem X ; 15: 100432, 2022 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-36211743

RESUMO

The study aimed to characterize physicochemical, thermal, and rheological properties of cashew nut starch (CNS) and then compare the obtained results with the properties of potato and corn starches. CNS showed higher gelatinization temperatures (112.29 °C) than those noted for potato and maize starches (78.44-94.65 °C). In addition, CNS had higher peak viscosity (19.03 mPa·s) than high amylose corn starch. The static shear rheological test indicated that the CNS followed a pseudoplastic behavior. In addition, CNS sample showed a thixotropic patter, which was less pronounced than that observed for potato starch, but higher than the value reported for high amylose corn starch. These results demonstrated that the shear resistance of CNS was lower than high amylose corn starch, but higher than potato starch. The storage and loss modulus (G' and G", respectively) of the CNS were higher than those reported for the rest of samples. In this line, elastic properties were predominant in CNS sample. In conclusion, results from this study provided insight into physicochemical and structural properties of cashew nut starch, which could represent a preliminary step for its future application in food processing.

14.
ACS Nano ; 16(10): 15977-15993, 2022 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-36190834

RESUMO

The number of patients who benefit from acquired immunotherapy is limited. Stimulator of interferon genes (STING) signal activation is a significant component to enhance innate immunity, which has been used to realize broad-spectrum immunotherapy. Here, M@P@HA nanoparticles, as a STING signal amplifier, are constructed to enhance innate immunotherapy. Briefly, when M@P@HA was targeted into tumor cells, the nanoparticles decomposed with Mn2+ and activated the release of protoporphyrin (PpIX). Under light irradiation, the generated reactive oxygen species disrupt the cellular redox homeostasis to lead cytoplasm leakage of damaged mitochondrial double-stranded (ds) DNA, which is the initiator of the STING signal. Simultaneously, Mn2+ as the immunoregulator could significantly increase the activity of related protein of a STING signal, such as cyclic GMP-AMP synthase (cGAS) and STING, to further amplify the STING signal of tumor cells. Subsequently, the STING signal of tumor-associated macrophages (TAM) is also activated by capturing dsDNA and Mn2+ that escaped from tumor cells, so as to enhance innate immunity. It is found that, by amplifying the STING signal of tumor tissue, M@P@HA could not only activate innate immunity but also cascade to activate CD8+ T cell infiltration even in a tumor with low immunogenicity.


Assuntos
Proteínas de Membrana , Protoporfirinas , Humanos , Espécies Reativas de Oxigênio , Proteínas de Membrana/metabolismo , Transdução de Sinais , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Imunidade Inata , Imunoterapia , DNA/metabolismo , Interferons
15.
Eur J Pharmacol ; 930: 175157, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-35870480

RESUMO

Hyperuricemia is a common metabolic disease and is one of the factors that could induce chronic kidney disease (CKD). Geniposide (GEN) is a typical natural iridoid glucoside compound with a series of biological activities, but the poor bioavailability of GEN limits its clinical application. In this context, the pharmacological activity of the geniposide-phospholipid complex (GEN-PLC) in ameliorating posthyperuricemia CKD was evaluated by in vitro and in vivo experiments in this study. In vitro cell experiments showed that GEN-PLC treatment markedly decreased inflammatory cytokine levels and reactive oxygen species levels compared with those of GEN in uric acid-treated HKC cells. In vivo research results confirmed that a high concentration of uric acid could cause CKD by increasing inflammatory cytokines and reactive oxygen species in hyperuricemic mice. At the same time, GEN-PLC could regulate the PI3K/AKT/NF-κB and Keap1/Nrf2/HO-1 signaling pathways to effectively inhibit the inflammatory response and oxidative stress, thereby ameliorating posthyperuricemia CKD, and the therapeutic effect was better than that of GEN. In addition, the preparation technology of GEN-PLC was optimized, and the physiochemical analysis explained the intermolecular interactions of the two components. Based on the research results, GEN-PLC could enhance the bioavailability of GEN and become a promising candidate for clinical drug development.


Assuntos
Fator 2 Relacionado a NF-E2 , Insuficiência Renal Crônica , Animais , Inflamação/tratamento farmacológico , Iridoides/farmacologia , Iridoides/uso terapêutico , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Fosfatidilinositol 3-Quinases/metabolismo , Fosfolipídeos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Insuficiência Renal Crônica/tratamento farmacológico , Ácido Úrico/farmacologia
16.
Biomaterials ; 287: 121672, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35835001

RESUMO

3D printing has experienced swift growth for biological applications in the field of regenerative medicine and tissue engineering. Essential features of bioprinting include determining the appropriate bioink, printing speed mechanics, and print resolution while also maintaining cytocompatibility. However, the scarcity of bioinks that provide printing and print properties and cell support remains a limitation. Silk Fibroin (SF) displays exceptional features and versatility for inks and shows the potential to print complex structures with tunable mechanical properties, degradation rates, and cytocompatibility. Here we summarize recent advances and needs with the use of SF protein from Bombyx mori silkworm as a bioink, including crosslinking methods for extrusion bioprinting using SF and the maintenance of cell viability during and post bioprinting. Additionally, we discuss how encapsulated cells within these SF-based 3D bioprinted constructs are differentiated into various lineages such as skin, cartilage, and bone to expedite tissue regeneration. We then shift the focus towards SF-based 3D printing applications, including magnetically decorated hydrogels, in situ bioprinting, and a next-generation 4D bioprinting approach. Future perspectives on improvements in printing strategies and the use of multicomponent bioinks to improve print fidelity are also discussed.

17.
Nat Commun ; 13(1): 3317, 2022 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-35680907

RESUMO

Digital light processing bioprinting favors biofabrication of tissues with improved structural complexity. However, soft-tissue fabrication with this method remains a challenge to balance the physical performances of the bioinks for high-fidelity bioprinting and suitable microenvironments for the encapsulated cells to thrive. Here, we propose a molecular cleavage approach, where hyaluronic acid methacrylate (HAMA) is mixed with gelatin methacryloyl to achieve high-performance bioprinting, followed by selectively enzymatic digestion of HAMA, resulting in tissue-matching mechanical properties without losing the structural complexity and fidelity. Our method allows cellular morphological and functional improvements across multiple bioprinted tissue types featuring a wide range of mechanical stiffness, from the muscles to the brain, the softest organ of the human body. This platform endows us to biofabricate mechanically precisely tunable constructs to meet the biological function requirements of target tissues, potentially paving the way for broad applications in tissue and tissue model engineering.


Assuntos
Bioimpressão , Bioimpressão/métodos , Gelatina/química , Humanos , Ácido Hialurônico , Hidrogéis/química , Metacrilatos/química , Impressão Tridimensional , Engenharia Tecidual/métodos , Alicerces Teciduais/química
18.
Bioorg Chem ; 126: 105916, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35687986

RESUMO

Hyperuricemia is a common metabolic disease with a series of complications. Nuciferine, a typical aporphine alkaloid natural compound extracted from the leaves of Nelumbo nucifera Gaertn., was confirmed to have an antihyperuricemia effect. In the present study, 30 novel nuciferine derivatives were designed and synthesized. The effects of all derivatives on the regulation of URAT1 were studied in a uric acid-induced HK-2 cell model with benzbromarone as a positive control. The results indicated that Compound 1j showed the optimal URAT1 inhibitory activity through repressing PI3K/Akt pathway in HK-2 cells and the inhibitory effect was similar to that of benzbromarone. In addition, in vivo experiments demonstrated that Compound 1j could reduce uric acid levels and ameliorate kidney damage in hyperuricemic mice. On the one hand, Compound 1j could inhibit the expression of URAT1 and GLUT9 to increase the uric acid excretion index. On the other hand, Compound 1j could regulate the TLR4/IκBα/NF-κB signaling pathway to reduce the levels of inflammatory cytokines, thereby alleviating kidney damage. Meanwhile, a molecular docking assay revealed the potential molecular binding power (-9.79 kcal/mol) between Compound 1j and URAT1, which was more tightly bound than the lead compound nuciferine (-7.44 kcal/mol). Based on these results, Compound 1j may be a future drug for the development of new potential antihyperuricemia and nephroprotective drug candidates.


Assuntos
Aporfinas , Hiperuricemia , Transportadores de Ânions Orgânicos , Animais , Aporfinas/farmacologia , Benzobromarona/efeitos adversos , Hiperuricemia/tratamento farmacológico , Camundongos , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases/metabolismo , Ácido Úrico
19.
Angew Chem Int Ed Engl ; 61(33): e202207066, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35674195

RESUMO

In the electronics industry, the efficient recovery and capture of sulfur hexafluoride (SF6 ) from SF6 /N2 mixtures is of great importance. Herein, three metal-organic frameworks with fine-tuning pore structures, Cu(peba)2 , Ni(pba)2 , and Ni(ina)2 , were designed for SF6 capture. Among them, Ni(ina)2 has perfect pore sizes (6 Å) that are comparable to the kinetic diameter of sulfur hexafluoride (5.2 Å), affording the benchmark binding affinity for SF6 gas. Ni(ina)2 exhibits the highest SF6 /N2 selectivity (375.1 at 298 K and 1 bar) and ultra-high SF6 uptake capacity (53.5 cm3 g-1 at 298 K and 0.1 bar) at ambient conditions. The remarkable separation performance of Ni(ina)2 was verified by dynamic breakthrough experiments. Theoretical calculations and the SF6 -loaded single-crystal structure provided critical insight into the adsorption/separation mechanism. This porous coordination network has the potential to be used in industrial applications.

20.
PLoS One ; 17(5): e0268531, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35584139

RESUMO

Xanthine oxidase (XO) is a key enzyme in the generation and development of hyperuricemia. Thiazolidine-2-thione, a typical heterocyclic compound, have been widely used in the field of drug synthesis. In this study, a series of novel thiazolidine-2-thione derivatives were synthesized as XO inhibitors, and the XO inhibitory potencies of obtained compounds were evaluated by in vitro enzyme catalysis. The result shown that compound 6k behaved the strongest XO inhibitory activity with an IC50 value of 3.56 µmol/L, which was approximately 2.5-fold more potent than allopurinol. The structure-activity relationship revealed that the phenyl-sulfonamide group was indispensable for thiazolidine-2-thione derivatives to produce XO inhibitory activity. The enzyme inhibition kinetics analyses confirmed that compound 6k exerted a mixed-type XO inhibition. Additionally, the molecular docking results suggested that the 4-fluorophenyl-sulfonyl moiety could interact with Gly260 and Ile264 in the innermost part of the active pocket through 2 hydrogen bonds, while the thiazolidinethione moiety could form two hydrogen bonds with Glu263 and Ser347 in hydrophobic pockets. In summary, the results described above suggested that compound 6k could be a valuable lead compound for the treatment of hyperuricemia as a novel XO inhibitor.


Assuntos
Hiperuricemia , Xantina Oxidase , Inibidores Enzimáticos/química , Humanos , Hiperuricemia/tratamento farmacológico , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Tiazolidinas
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