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1.
Proc Natl Acad Sci U S A ; 121(28): e2403581121, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38968108

RESUMO

Adverse cardiac outcomes in COVID-19 patients, particularly those with preexisting cardiac disease, motivate the development of human cell-based organ-on-a-chip models to recapitulate cardiac injury and dysfunction and for screening of cardioprotective therapeutics. Here, we developed a heart-on-a-chip model to study the pathogenesis of SARS-CoV-2 in healthy myocardium established from human induced pluripotent stem cell (iPSC)-derived cardiomyocytes and a cardiac dysfunction model, mimicking aspects of preexisting hypertensive disease induced by angiotensin II (Ang II). We recapitulated cytopathic features of SARS-CoV-2-induced cardiac damage, including progressively impaired contractile function and calcium handling, apoptosis, and sarcomere disarray. SARS-CoV-2 presence in Ang II-treated hearts-on-a-chip decreased contractile force with earlier onset of contractile dysfunction and profoundly enhanced inflammatory cytokines compared to SARS-CoV-2 alone. Toward the development of potential therapeutics, we evaluated the cardioprotective effects of extracellular vesicles (EVs) from human iPSC which alleviated the impairment of contractile force, decreased apoptosis, reduced the disruption of sarcomeric proteins, and enhanced beta-oxidation gene expression. Viral load was not affected by either Ang II or EV treatment. We identified MicroRNAs miR-20a-5p and miR-19a-3p as potential mediators of cardioprotective effects of these EVs.


Assuntos
Angiotensina II , COVID-19 , Vesículas Extracelulares , Células-Tronco Pluripotentes Induzidas , Miócitos Cardíacos , SARS-CoV-2 , Humanos , Angiotensina II/farmacologia , COVID-19/virologia , COVID-19/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/virologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Vesículas Extracelulares/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Apoptose/efeitos dos fármacos , Dispositivos Lab-On-A-Chip , MicroRNAs/metabolismo , MicroRNAs/genética , Citocinas/metabolismo
2.
PLoS Genet ; 17(8): e1009724, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34398892

RESUMO

Feeding is essential for animal survival and reproduction and is regulated by both internal states and external stimuli. However, little is known about how internal states influence the perception of external sensory cues that regulate feeding behavior. Here, we investigated the neuronal and molecular mechanisms behind nutritional state-mediated regulation of gustatory perception in control of feeding behavior in the brown planthopper and Drosophila. We found that feeding increases the expression of the cholecystokinin-like peptide, sulfakinin (SK), and the activity of a set of SK-expressing neurons. Starvation elevates the transcription of the sugar receptor Gr64f and SK negatively regulates the expression of Gr64f in both insects. Interestingly, we found that one of the two known SK receptors, CCKLR-17D3, is expressed by some of Gr64f-expressing neurons in the proboscis and proleg tarsi. Thus, we have identified SK as a neuropeptide signal in a neuronal circuitry that responds to food intake, and regulates feeding behavior by diminishing gustatory receptor gene expression and activity of sweet sensing GRNs. Our findings demonstrate one nutritional state-dependent pathway that modulates sweet perception and thereby feeding behavior, but our experiments cannot exclude further parallel pathways. Importantly, we show that the underlying mechanisms are conserved in the two distantly related insect species.


Assuntos
Comportamento Alimentar/fisiologia , Percepção Gustatória/genética , Animais , Encéfalo/metabolismo , Metabolismo dos Carboidratos/fisiologia , Carboidratos/fisiologia , Colecistocinina/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/fisiologia , Comportamento Alimentar/psicologia , Expressão Gênica/genética , Regulação da Expressão Gênica/genética , Hemípteros/genética , Hemípteros/fisiologia , Neurônios/metabolismo , Neuropeptídeos/metabolismo , Receptores de Superfície Celular/genética , Inanição/metabolismo , Açúcares/metabolismo , Paladar/fisiologia , Percepção Gustatória/fisiologia
3.
Int Wound J ; 21(2): e14733, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38339798

RESUMO

Keloids, pathological scars resulting from skin trauma, have traditionally posed significant clinical management challenges due to their persistence and high recurrence rates. Our research elucidates the pivotal roles of lipids and their derivatives in keloid development, driven by underlying mechanisms of abnormal cell proliferation, apoptosis, and extracellular matrix deposition. Key findings suggest that abnormalities in arachidonic acid (AA) synthesis and non-essential fatty acid synthesis are integral to keloid formation. Further, a complex interplay exists between lipid derivatives, notably butyric acid (BA), prostaglandin E2 (PGE2), prostaglandin D2 (PGD2), and the regulation of hyperfibrosis. Additionally, combinations of docosahexaenoic acid (DHA) with BA and 15-deoxy-Δ12,14-Prostaglandin J2 have exhibited pronounced cytotoxic effects. Among sphingolipids, ceramide (Cer) displayed limited pro-apoptotic effects in keloid fibroblasts (KFBs), whereas sphingosine 1-phosphate (S1P) was found to promote keloid hyperfibrosis, with its analogue, FTY720, demonstrating contrasting benefits. Both Vitamin D and hexadecylphosphorylcholine (HePC) showed potential antifibrotic and antiproliferative properties, suggesting their utility in keloid management. While keloids remain a prevalent concern in clinical practice, this study underscores the promising potential of targeting specific lipid molecules for the advancement of keloid therapeutic strategies.


Assuntos
Queloide , Humanos , Queloide/tratamento farmacológico , Queloide/patologia , Matriz Extracelular , Fibrose , Apoptose , Lipídeos/farmacologia , Lipídeos/uso terapêutico , Fibroblastos
4.
Acc Chem Res ; 55(11): 1533-1545, 2022 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-35413187

RESUMO

Nature provides abundant inspiration and elegant paradigms for the development of smart materials that can actuate, morph, and move on demand. One remarkable capacity of living organisms is to adapt their shapes or positions in response to stimuli. Programmed deformations or movements in plant organs are mainly driven by water absorption/dehydration of cells, while versatile motions of mollusks are based on contraction/extension of muscles. Understanding the general principles of these morphing and motion behaviors can give rise to disruptive technologies for soft robotics, flexible electronics, biomedical devices, etc. As one kind of intelligent material, hydrogels with high similarity to soft biotissues and diverse responses to external stimuli are an ideal candidate to construct soft actuators and robots.The objective of this Account is to give an overview of the fundamental principles for controllable deformations and motions of hydrogels, with a focus on the structure designs and responsive functions of the corresponding soft actuators and robots. This field has been rapidly developed in recent years with a growing understanding of working principles in natural organisms and a substantial revolution of manufacturing technologies to devise bioinspired hydrogel systems with desired structures. Diverse morphing hydrogels and soft actuators/robots have been developed on the basis of several pioneering works, ranging from bending and folding deformations of bilayer hydrogels to self-shaping of non-Euclidean hydrogel surfaces, and from thermoactuated bilayer gel "hands" to electrodriven polyelectrolyte gel "worms". These morphing hydrogels have demonstrated active functions and versatile applications in biomedical and engineering fields.In this Account, we discuss recent progress in morphing hydrogels and highlight the design principles and relevant applications. First, we introduce the fundamentals of basic deformation modes, together with generic structure features, actuation strategies, and morphing mechanisms. The advantages of in-plane gradient structures are highlighted for programmable deformations by harnessing the out-of-plane buckling with bistability nature to obtain sophisticated three-dimensional configurations. Next, we give an overview of soft actuators and robots based on morphing hydrogels and focus on the working principles of the active systems with different structure designs. We discuss the advancements of hydrogel-based soft robots capable of swift locomotion with different gaits and emphasize the significances of structure control and dynamic actuation. Then we summarize versatile applications of hydrogel-based actuators and robots in biomedicines, cargo delivery, soft electronics, information encryption, and so forth. Some hydrogel robots with a built-in feedback loop and self-sensing system exhibit collaborative functions and advanced intelligence that are informative for the design of next-generation hydrogel machines. Finally, concluding remarks are given to discuss future opportunities and remaining challenges in this field. For example, miniature hydrogel-based actuators/robots with therapeutic or diagnostic functions are highly desired for biomedical applications. The morphing mechanisms summarized in this Account should be applicable to other responsive materials. We hope that this Account will inspire more scientists to be involved in this emerging area and make contributions to reveal novel working principles, design multifunctional soft machines, and explore applications in diverse fields.


Assuntos
Robótica , Materiais Inteligentes , Hidrogéis/química , Movimento (Física) , Robótica/métodos , Água
5.
Org Biomol Chem ; 20(19): 3902-3906, 2022 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-35502883

RESUMO

A photoexcited sulfenylation of C(sp3)-H bonds in amides is developed for the synthesis of sulfenyl amides using thiosulfonates as a sulfur source. In the presence of easily available and inexpensive Na2-eosin Y, TBHP and K2CO3, various sulfenyl amides can be obtained under the irradiation of blue light at room temperature.


Assuntos
Amidas , Enxofre , Amidas/química , Enxofre/química
6.
Inorg Chem ; 60(14): 10535-10549, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34232620

RESUMO

Trinuclear aluminum complexes bearing bipyrazoles were synthesized, and their catalytic activity for ε-caprolactone (CL) polymerization was investigated. DBu2Al3Me5 exhibited higher catalytic activity than did the dinuclear aluminum complex LBu2Al2Me4 (16 times as high for CL polymerization; [CL]:[DBu2Al3Me5]:[BnOH] = 100:0.5:5, [DBu2Al3Me5] = 10 mM, conversion 93% after 18 min at room temperature). Density functional theory calculations revealed a polymerization mechanism in which CL first approached the central Al atom and then moved to an external Al. The coordinated CL ring was opened because the repulsion of two tert-butyl groups on the ligands pushed an alkoxide initiator on an external Al to initiate CL. In these trinuclear Al catalysts, the central Al plays a role in monomer capture and then collaborates with the external Al to activate CL, accelerating polymerization.

7.
Zhongguo Zhong Yao Za Zhi ; 46(24): 6558-6567, 2021 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-34994149

RESUMO

In this study, the evidence mapping methodology was used to systematically retrieve and sort out the clinical research evidence of Chinese patent medicines in the treatment of tension-type headache(TTH), and to understand the distribution of evidence in this field and the basis and quality of evidence. Chinese and English articles on the 28 Chinese patent medicines for TTH, which were recorded in National Essential Medicines List(2018), Medicine Catalogue for National Basic Medical Insurance, Work Injury Insurance, and Maternity Insurance(2020), and Chinese Pharmacopoeia(2020), were retrieved from China National Knowledge Infrastructure(CNKI), Wanfang, VIP, China Biology Medicine disc(CBMdisc), PubMed, EMbase, and Cochrane Library from the establishment to June 2021, followed by descriptive analysis. Then, tables and bubble charts were plotted to analyze the distribution characteristics of evidence. A total of 129 eligible articles were yielded: 126 randomized/non-randomized controlled trials, and 3 systematic reviews. The functions, indications, and composition of the 28 medicines, as well as the proportion of related articles, publication trends, intervention measures, and outcome indicators were compared and analyzed. The results showed that the 28 Chinese patent medicines, composed of 128 Chinese medicinals, can be classified into six categories in terms of function: reinforcing healthy Qi, tranquilizing mind, dispelling stasis, regulating Qi, treating wind, and resuscitating. There are ongoing efforts to study the treatment of TTH with Chinese patent medicine in China, despite of little evidence. The clinical positioning of Chinese patent medicine for TTH is not clear, and clinical research fails to highlight the advantages of Chinese medicine. In addition, the outcome indicators have not been standardized and unified, and there is a lack of evidence on the long-term efficacy of Chinese patent medicine for TTH. This study is the first exploratory application of evidence maps to compare the characteristics and clinical research progress of 28 Chinese patent medicines for TTH, which can provide a reference for research on the optimization of Chinese medicine strategies for TTH.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional do Leste Asiático , Cefaleia do Tipo Tensional , Povo Asiático , Feminino , Humanos , Medicina Tradicional Chinesa , Medicamentos sem Prescrição , Gravidez
8.
Angew Chem Int Ed Engl ; 60(36): 19949-19956, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34128303

RESUMO

Carbodicarbene (CDC), unique carbenic entities bearing two lone pairs of electrons are well-known for their strong Lewis basicity. We demonstrate herein, upon introducing a weak Brønsted acid benzyl alcohol (BnOH) as a co-modulator, CDC is remolded into a Frustrated Lewis Pair (FLP)-like reactivity. DFT calculation and experimental evidence show BnOH loosely interacting with the binding pocket of CDC via H-bonding and π-π stacking. Four distinct reactions in nature were deployed to demonstrate the viability of proof-of-concept as synergistic FLP/Modulator (CDC/BnOH), demonstrating enhanced catalytic reactivity in cyclotrimerization of isocyanate, polymerization process for L-lactide (LA), methyl methacrylate (MMA) and dehydrosilylation of alcohols. Importantly, the catalytic reactivity of carbodicarbene is uniquely distinct from conventional NHC which relies on only single chemical feature of nucleophilicity. This finding also provides a new spin in diversifying FLP reactivity with co-modulator or co-catalyst.

9.
Cytogenet Genome Res ; 160(10): 565-578, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33022677

RESUMO

The excessive production of inflammatory mediators by vascular endothelial cells (ECs) greatly contributes to the development of atherosclerosis. In this study, we explored the potential effect of lncRNA MALAT1 on endothelial inflammation. First, the EC inflammation model was constructed by treating human umbilical vein ECs (HUVECs) and human coronary artery ECs (HCAECs) with oxidized low-density lipoprotein (ox-LDL), which confirmed the role of MALAT1 in the inflammatory activity. Then MALAT1 was overexpressed in HUVECs and HCAECs, and the levels of inflammatory mediators and nitric oxide (NO) were examined by Western blotting, ELISA, and NO detection assay. The migration ability was confirmed by wound healing assay. The interactions among MALAT1, miR-590, and STAT3 were predicted by bioinformatics analysis and verified by qRT-PCR, Western blotting, or dual-luciferase reporter assay. MALAT1 was upregulated in ECs treated with ox-LDL, and knockdown of MALAT1 significantly inhibited ox-LDL-induced inflammation. MALAT1 overexpression potentiated the inflammatory activities of ECs, including enhanced production of inflammatory cytokines (IL-6, IL-8, and TNF-α) and adhesion molecules (VCAM1 and ICAM1), and decreased NO level and cell migratory ability. Mechanistically, MALAT1 could directly downregulate miR-590, and miR-590 could bind to the 3'-UTR of STAT3 to repress its expression. Additionally, overexpression of MALAT1-mediated inflammation was largely abrogated by the concomitant overexpression of miR-590. miR-590 knockdown activated the inflammatory response, which was reversed by STAT3 inhibition. Thus, MALAT1 serves as a proinflammatory lncRNA in ECs through regulating the miR-590/STAT3 axis, suggesting that MALAT1 may be a promising therapeutic target during the treatment of atherosclerosis.


Assuntos
Células Endoteliais/metabolismo , Células Endoteliais/patologia , Inflamação/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Fator de Transcrição STAT3/metabolismo , Regiões 3' não Traduzidas/genética , Sequência de Bases , Células Endoteliais/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Inflamação/patologia , Lipoproteínas LDL/farmacologia , MicroRNAs/genética , Modelos Biológicos , Fenótipo , Ligação Proteica/genética , RNA Longo não Codificante/genética
10.
Hepatology ; 69(2): 498-512, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30070724

RESUMO

The gender disparity of hepatocellular carcinoma (HCC) is most striking in hepatitis B virus (HBV)-related cases. The majority of such HCC cases contain integrated HBV, and some hotspot integrations, such as those in the telomerase reverse transcriptase gene (TERT) promoter, activate gene expression to drive carcinogenesis. As the HBV genome contains both androgen-responsive and estrogen-responsive motifs, we hypothesized that the integrated HBV DNA renders a similar regulation for downstream gene expression and thus contributes to male susceptibility to HCC. To test this hypothesis, the HBV integration sites and the common mutations in the TERT promoter and tumor protein P53 (TP53) coding region were analyzed in 101 HBV-related HCC cases using a capture-next-generation sequencing platform. The results showed that both HBV integration and -124G>A mutation in the TERT promoter region, occurring in a mutually exclusive manner, were more frequent in male than in female patients with HCC (integration: 22/58 male patients with HCC, 6/36 female patients with HCC, P = 0.0285; -124G>A: 17/62 male patients with HCC, 3/39 female patients with HCC, P = 0.0201; in combination, 39/62 male patients with HCC, 9/39 female patients with HCC, P < 0.0001). The effects of sex hormone pathways on the expression of TERT with both genetic changes were investigated using a reporter assay. HBV integration in the TERT promoter rendered the TERT transcription responsive to sex hormones, with enhancement by androgen receptor (AR) but suppression by estrogen receptor, both of which were dependent on hepatocyte nuclear factor 4 alpha. Besides, AR also increased TERT expression by targeting TERT promoter mutations in a GA binding protein transcription factor subunit alpha-dependent manner. Conclusion: TERT elevation by AR through integrated HBV and point mutation at the TERT promoter region was identified as a mechanism for the male dominance of HBV-related HCCs; telomerase and AR thus may be targets for intervention of HCC.


Assuntos
Carcinoma Hepatocelular/etiologia , Regulação Neoplásica da Expressão Gênica , Hepatite B/complicações , Neoplasias Hepáticas/etiologia , Receptores Androgênicos/metabolismo , Androgênios/metabolismo , Carcinoma Hepatocelular/metabolismo , Estrogênios/metabolismo , Feminino , Fator de Transcrição de Proteínas de Ligação GA/metabolismo , Vírus da Hepatite B/fisiologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Oncogenes , Mutação Puntual , Regiões Promotoras Genéticas , Caracteres Sexuais , Telomerase/genética , Telomerase/metabolismo , Integração Viral
11.
Yi Chuan ; 42(1): 112-125, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31956101

RESUMO

Alcohol abuse causes tissue and organ damage, and may participate neuropsychiatric diseases. Studies have shown that DNA methylation plays an important role in gene expression and behavioral changes induced by alcohol, however the causative neurobiological mechanisms have not been clarified. In this study, 32 healthy adult male SD rats were randomly divided into a drinking water control group (n=16) and a chronic alcohol exposure group (n=16). The alcohol preference and locomotor activity of rats were evaluated by two-bottle choice test (TBCT) and open-field test (OFT). DNA methylation in the medial prefrontal cortex (mPFC) tissue was detected by the reduced representative bisulfite sequencing (RRBS) technology. The methylation differential genes closely related to alcohol abuse were screened. qRT-PCR was used to verify the mRNA expression patterns of differential genes. qRT-PCR and Western blot were used to detect the expression of DNA methyltransferases (DNMTs) and methyl CpG binding protein 2 (MeCP2). Furthermore, the effect of short-term alcohol exposure (7 days) on DNMTs and MeCP2 in the mPFC of rats was tested (n=8/group). The results indicated that the methylation level of promoter region in the mPFC of rats exposed to chronic alcohol was significantly increased. In addition, the increased methylation levels in the promoter of Ntf3 and Ppm1G were accompanied by down-regulated mRNA levels in the chronic alcohol exposure group. The decreased methylation levels in the promoter of Hap1 and DUSP1 were accompanied by up-regulated mRNA levels. Furthermore, chronic alcohol exposure increased the mRNA and protein levels of DNMT3B and MeCP2. However, short term alcohol exposure did not affect their expression. This present study provides evidence that DNA methylation is associated with the development of alcohol abuse, which may be regulated by DNMT3B and MeCP2. The target genes Ntf3, Ppm1G, Hap1, and DUSP1 related to alcohol abuse were discovered as well, providing new insights into the neurobiological mechanism of alcohol abuse and the potential pharmacological targets for the treatment of alcohol abuse.


Assuntos
Alcoolismo/fisiopatologia , Comportamento Animal , Metilação de DNA , Córtex Pré-Frontal/fisiopatologia , Animais , DNA (Citosina-5-)-Metiltransferases/genética , Locomoção , Masculino , Proteína 2 de Ligação a Metil-CpG/genética , Regiões Promotoras Genéticas , Ratos , Ratos Sprague-Dawley , DNA Metiltransferase 3B
12.
Nano Lett ; 16(7): 4665-9, 2016 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-27324157

RESUMO

Because of their hollow interior, transmembrane channels are capable of opening up pathways for ions across lipid membranes of living cells. Here, we demonstrate ion conduction induced by a single DNA duplex that lacks a hollow central channel. Decorated with six porpyrin-tags, our duplex is designed to span lipid membranes. Combining electrophysiology measurements with all-atom molecular dynamics simulations, we elucidate the microscopic conductance pathway. Ions flow at the DNA-lipid interface as the lipid head groups tilt toward the amphiphilic duplex forming a toroidal pore filled with water and ions. Ionic current traces produced by the DNA-lipid channel show well-defined insertion steps, closures, and gating similar to those observed for traditional protein channels or synthetic pores. Ionic conductances obtained through simulations and experiments are in excellent quantitative agreement. The conductance mechanism realized here with the smallest possible DNA-based ion channel offers a route to design a new class of synthetic ion channels with maximum simplicity.


Assuntos
DNA/química , Canais Iônicos/química , Bicamadas Lipídicas/química , Simulação de Dinâmica Molecular , Ativação do Canal Iônico , Transporte de Íons
13.
Front Immunol ; 15: 1393852, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38711526

RESUMO

Different eukaryotic cell organelles (e.g., mitochondria, endoplasmic reticulum, lysosome) are involved in various cancer processes, by dominating specific cellular activities. Organelles cooperate, such as through contact points, in complex biological activities that help the cell regulate energy metabolism, signal transduction, and membrane dynamics, which influence survival process. Herein, we review the current studies of mechanisms by which mitochondria, endoplasmic reticulum, and lysosome are related to the three major malignant gynecological cancers, and their possible therapeutic interventions and drug targets. We also discuss the similarities and differences of independent organelle and organelle-organelle interactions, and their applications to the respective gynecological cancers; mitochondrial dynamics and energy metabolism, endoplasmic reticulum dysfunction, lysosomal regulation and autophagy, organelle interactions, and organelle regulatory mechanisms of cell death play crucial roles in cancer tumorigenesis, progression, and response to therapy. Finally, we discuss the value of organelle research, its current problems, and its future directions.


Assuntos
Neoplasias dos Genitais Femininos , Mitocôndrias , Organelas , Humanos , Feminino , Neoplasias dos Genitais Femininos/patologia , Neoplasias dos Genitais Femininos/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Organelas/metabolismo , Sobrevivência Celular , Animais , Lisossomos/metabolismo , Retículo Endoplasmático/metabolismo , Autofagia , Metabolismo Energético , Transdução de Sinais
14.
Regen Biomater ; 11: rbae032, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38779347

RESUMO

The substantial economic impact of non-healing wounds, scarring, and burns stemming from skin injuries is evident, resulting in a financial burden on both patients and the healthcare system. This review paper provides an overview of the skin's vital role in guarding against various environmental challenges as the body's largest protective organ and associated developments in biomaterials for wound healing. We first introduce the composition of skin tissue and the intricate processes of wound healing, with special attention to the crucial role of immunomodulation in both acute and chronic wounds. This highlights how the imbalance in the immune response, particularly in chronic wounds associated with underlying health conditions such as diabetes and immunosuppression, hinders normal healing stages. Then, this review distinguishes between traditional wound-healing strategies that create an optimal microenvironment and recent peptide-based biomaterials that modulate cellular processes and immune responses to facilitate wound closure. Additionally, we highlight the importance of considering the stages of wounds in the healing process. By integrating advanced materials engineering with an in-depth understanding of wound biology, this approach holds promise for reshaping the field of wound management and ultimately offering improved outcomes for patients with acute and chronic wounds.

16.
Methods Mol Biol ; 2639: 113-128, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37166714

RESUMO

Building on the recent technological advances, all-atom molecular dynamics (MD) simulations have become an indispensable tool to study the molecular behavior at nanoscale. Molecular simulations have been used to characterize the structure, dynamics, and mechanical and electrical properties of DNA origami objects. In this chapter we describe a method to build all-atom model of lipid-spanning DNA origami nanopores and perform molecular dynamics simulations in explicit electrolyte solutions.


Assuntos
Simulação de Dinâmica Molecular , Nanoporos , DNA/química
17.
Adv Mater ; 35(15): e2211802, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36680376

RESUMO

Joints, as a flexing element to connect different parts, are widespread in natural systems. Various joints exist in the body and play crucial roles to execute gestures and gaits. These scenarios have inspired the design of mechanical joints with passive, hard materials, which usually need an external power supply to drive the transformations. The incorporation of soft and active joints provides a modular strategy to devise soft actuators and robots. However, transformations of responsive joints under external stimuli are usually in uni-mode with a pre-determined direction. Here, hydrogel joints capable of folding and twisting transformation in bi-mode are reported, which enable the composite hydrogel to form multiple configurations under constant conditions. These joints have an in-plane gradient structure and comprise stiff, passive gel as the frame and soft, active gel as the actuating unit. Under external stimuli, the response mismatch between different gels leads to out-of-plane folding or twisting deformation with the feature of bistability. These joints can be modularly integrated with other gels to afford complex deformations and multistable configurations. This approach favors selective control of hydrogel's architectures and versatile design of hydrogel devices, as demonstrated by proof-of-concept examples. It shall also merit the development of metamaterials, soft actuators, and robots, etc.

18.
World J Gastroenterol ; 29(29): 4557-4570, 2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37621756

RESUMO

BACKGROUND: Hydrogen sulfide (H2S) is a recently discovered gaseous neurotransmitter in the nervous and gastrointestinal systems. It exerts its effects through multiple signaling pathways, impacting various physiological activities. The nucleus tractus solitarius (NTS), a vital nucleus involved in visceral sensation, was investigated in this study to understand the role of H2S in regulating gastric function in rats. AIM: To examine whether H2S affects the nuclear factor kappa-B (NF-κB) and transient receptor potential vanilloid 1 pathways and the neurokinin 1 (NK1) receptor in the NTS. METHODS: Immunohistochemical and fluorescent double-labeling techniques were employed to identify cystathionine beta-synthase (CBS) and c-Fos co-expressed positive neurons in the NTS during rat stress. Gastric motility curves were recorded by inserting a pressure-sensing balloon into the pylorus through the stomach fundus. Changes in gastric motility were observed before and after injecting different doses of NaHS (4 nmol and 8 nmol), physiological saline, Capsazepine (4 nmol) + NaHS (4 nmol), pyrrolidine dithiocarbamate (PDTC, 4 nmol) + NaHS (4 nmol), and L703606 (4 nmol) + NaHS (4 nmol). RESULTS: We identified a significant increase in the co-expression of c-Fos and CBS positive neurons in the NTS after 1 h and 3 h of restraint water-immersion stress compared to the expressions observed in the control group. Intra-NTS injection of NaHS at different doses significantly inhibited gastric motility in rats (P < 0.01). However, injection of saline, first injection NF-κB inhibitor PDTC or transient receptor potential vanilloid 1 (TRPV1) antagonist Capsazepine or NK1 receptor blockers L703606 and then injection NaHS did not produce significant changes (P > 0.05). CONCLUSION: NTS contains neurons co-expressing CBS and c-Fos, and the injection of NaHS into the NTS can suppress gastric motility in rats. This effect may be mediated by activating TRPV1 and NK1 receptors via the NF-κB channel.


Assuntos
Sulfeto de Hidrogênio , Animais , Ratos , Sulfeto de Hidrogênio/farmacologia , NF-kappa B , Núcleo Solitário , Desidratação
19.
RSC Adv ; 13(44): 30771-30776, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37869386

RESUMO

In this work, a 2-(2'-hydroxyphenyl)benzimidazole derived fluorescent probe, 2-(2'-hydroxy-4'-aminophenyl)benzimidazole (4-AHBI), was synthesized and its fluorescent behavior toward triphosgene were evaluated. The results showed that 4-AHBI exhibited high sensitivity (limit of detection, 0.08 nM) and excellent selectivity for triphosgene over other acyl chlorides including phosgene in CH2Cl2 solution. Moreover, 4-AHBI loaded test strips were prepared for the practical sensing of triphosgene.

20.
Chin J Physiol ; 55(6): 421-7, 2012 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-23286450

RESUMO

Microwave radiations can be encountered regularly in daily lives. When WHO announced that microwave radiations were a kind of environmental energy which interfere with the physiological functions of the human body, great concerns have been raised over the damages microwave frequencies can do to human physiology. The immunological performance and the activities of the cellular inflammatory factor NFκB have been closely related in monocyte. Due to the effect of phorbol 12-myristate 13-acetate (PMA) on THP-1 monocytes, THP-1 monocytes would differentiate into macrophages and would then react with lipopolysaccharides (LPS), and the amount of NFκB increased in the THP-1 monocytes. Expression of cytokine is affected when cells are exposed to a frequency of 2450 MHz and at 900 W. Thus, in our experiments, an observation was made when THP-1 monocytes were stimulated with PMA and LPS to differentiate into macrophage, the amount of NFκB in cells increased exponentially, and the levels of NFκB expression were decreased by the exposure of microwave radiation. In conclusion, microwave radiations were found to inhibit the activity functions of THP-1 monocytes stimulated with PMA and LPS.


Assuntos
Lipopolissacarídeos , Monócitos , Humanos , Lipopolissacarídeos/farmacologia , Macrófagos , Micro-Ondas , NF-kappa B/metabolismo , Acetato de Tetradecanoilforbol/farmacologia
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