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1.
Cell ; 151(1): 96-110, 2012 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-23021218

RESUMO

PGC1α is a key transcriptional coregulator of oxidative metabolism and thermogenesis. Through a high-throughput chemical screen, we found that molecules antagonizing the TRPVs (transient receptor potential vanilloid), a family of ion channels, induced PGC1α expression in adipocytes. In particular, TRPV4 negatively regulated the expression of PGC1α, UCP1, and cellular respiration. Additionally, it potently controlled the expression of multiple proinflammatory genes involved in the development of insulin resistance. Mice with a null mutation for TRPV4 or wild-type mice treated with a TRPV4 antagonist showed elevated thermogenesis in adipose tissues and were protected from diet-induced obesity, adipose inflammation, and insulin resistance. This role of TRPV4 as a cell-autonomous mediator for both the thermogenic and proinflammatory programs in adipocytes could offer a target for treating obesity and related metabolic diseases.


Assuntos
Metabolismo Energético , Canais de Cátion TRPV/metabolismo , Termogênese , Adipócitos/metabolismo , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Feminino , Técnicas de Silenciamento de Genes , Canais Iônicos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Mitocondriais/metabolismo , Obesidade/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/genética , Transativadores/metabolismo , Fatores de Transcrição , Proteína Desacopladora 1
2.
J Cell Mol Med ; 28(14): e18375, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39039796

RESUMO

Celastrol, a bioactive molecule extracted from the plant Tripterygium wilfordii Hook F., possesses anti-inflammatory, anti-obesity and anti-tumour properties. Despite its efficacy in improving erythema and scaling in psoriatic mice, the specific therapeutic mechanism of celastrol in atopic dermatitis (AD) remains unknown. This study aims to examine the role and mechanism of celastrol in AD using TNF-α-stimulated HaCaT cells and DNCB-induced Balb/c mice as in vitro and in vivo AD models, respectively. Celastrol was found to inhibit the increased epidermal thickness, reduce spleen and lymph node weights, attenuate inflammatory cell infiltration and mast cell degranulation and decrease thymic stromal lymphopoietin (TSLP) as well as various inflammatory factors (IL-4, IL-13, TNF-α, IL-5, IL-31, IL-33, IgE, TSLP, IL-17, IL-23, IL-1ß, CCL11 and CCL17) in AD mice. Additionally, celastrol inhibited Ezrin phosphorylation at Thr567, restored mitochondrial network structure, promoted translocation of Drp1 to the cytoplasm and reduced TNF-α-induced cellular reactive oxygen species (ROS), mitochondrial ROS (mtROS) and mitochondrial membrane potential (MMP) production. Interestingly, Mdivi-1 (a mitochondrial fission inhibitor) and Ezrin-specific siRNAs lowered inflammatory factor levels and restored mitochondrial reticular formation, as well as ROS, mtROS and MMP production. Co-immunoprecipitation revealed that Ezrin interacted with Drp1. Knocking down Ezrin reduced mitochondrial fission protein Drp1 phosphorylation and Fis1 expression while increasing the expression of fusion proteins Mfn1 and Mfn2. The regulation of mitochondrial fission and fusion by Ezrin was confirmed. Overall, celastrol may alleviate AD by regulating Ezrin-mediated mitochondrial fission and fusion, which may become a novel therapeutic reagent for alleviating AD.


Assuntos
Citocinas , Proteínas do Citoesqueleto , Dermatite Atópica , Camundongos Endogâmicos BALB C , Dinâmica Mitocondrial , Triterpenos Pentacíclicos , Triterpenos , Animais , Dinâmica Mitocondrial/efeitos dos fármacos , Triterpenos Pentacíclicos/farmacologia , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/patologia , Dermatite Atópica/metabolismo , Humanos , Triterpenos/farmacologia , Camundongos , Citocinas/metabolismo , Proteínas do Citoesqueleto/metabolismo , Proteínas do Citoesqueleto/genética , Linfopoietina do Estroma do Timo , Modelos Animais de Doenças , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Células HaCaT , Fosforilação/efeitos dos fármacos
3.
J Org Chem ; 89(3): 1681-1691, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38207100

RESUMO

Pyrene-based derivatives have been widely deployed in organic luminescent materials because of their bright fluorescence, high charge carrier mobility, and facile modification. Nevertheless, the fluorescence output of conventional pyrenes is prone to quenching upon aggregation due to extensive intermolecular π-π stacking interactions. To address this issue, a set of new Y-shaped pyrene-containing luminogens are synthesized from a new bromopyrene chemical precursor, 2-hydroxyl-7-tert-butyl-1,3-bromopyrene, where the bromo and hydroxyl groups at the pyrene core can be readily modified to obtain the target products and provide great flexibility in tuning the photophysical performances. When the hydroxy group at the 2-position of pyrene was replaced by a benzyl group, the steric hindrance of the benzyl group not only efficiently inhibits the detrimental intermolecular π-π stacking interactions but also rigidifies the molecular conformation, resulting in a narrow-band blue emission. Moreover, the TPE-containing compounds 2c and 3c possessed characteristic aggregation-induced emission (AIE) properties with fluorescence quantum yields of up to 66% and 38% in the solid state, respectively. Thus, this article has methodically investigated the factors influencing the optical behavior, such as intermolecular interactions, and the steric effects of the substituent group, thereby opening up the potential to develop narrow-band pyrene-based blue emitters for OLED device applications.

4.
Macromol Rapid Commun ; 44(17): e2300180, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37379851

RESUMO

Most sheet facial masks for skincare are made of nonwovens and loaded with liquid active ingredients, which are usually opaque and require additives for long-term preservation. Herein, a Transparent Additive-Free Fibrous (TAFF) facial mask is reported for skin moisturizing. The TAFF facial mask consists of a bilayer fibrous membrane. The inner layer is fabricated by electrospinning functional components of gelatin (GE) and hyaluronic acid (HA) into a solid fibrous membrane to get rid of additives, the outer layer is an ultrathin PA6 fibrous membrane that is highly transparent, especially after absorbing water. The results indicate that the GE-HA membrane can quickly absorb water and become a transparent hydrogel film. By employing the hydrophobic PA6 membrane as the outer layer, directional water transport is achieved, which enables TAFF facial mask with excellent skin moisturizing effect. The skin moisture content is up to 84% ± 7% after placing the TAFF facial mask on the skin for 10 min. In addition, the relative transparency of the TAFF facial mask on the skin reaches 97.0% ± 1.9% when ultrathin PA6 membrane is used as the outer layer. The design of the transparent additive-free facial mask may serve as a guideline for developing new functional facial masks.


Assuntos
Face , Pele , Hidrogéis , Ácido Hialurônico
5.
Clin Anat ; 36(1): 151-160, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36349397

RESUMO

Problem-based learning (PBL) is increasingly being used in medical education globally, but its effectiveness in teaching remains controversial. A randomized controlled trial (RCT) is the method of choice for evaluating its effectiveness. The quality of an RCT has a significant effect on this evaluation, but to date we have not seen an assessment of the quality of RCTs for PBL. Two researchers searched MEDLINE and EMBASE for RCTs addressing PBL in medical education. The overall quality of each report was measured on a 28-point overall quality score (OQS) based on the 2010 revised Comprehensive Standards for Reporting and Testing (CONSORT) Statement. Furthermore, to study the key factors affecting OQS more effectively, a linear regression model of those factors was established using SPSS. After literature screening, 30 RCTs were eventually included and analyzed. The median OQS was 15 (range, 7-20), which meant that half of the items in the revised 2010 CONSORT statement were poorly reported in at least 40% of the RCTs analyzed. The regression model showed that the year of publication of RCTs and the impact factors of the journals in which they were published were the main factors affecting OQS. The overall quality of reporting of RCTs on PBL teaching in medical education was not satisfactory. Some RCTs were subjectively selective in reporting certain items, leading to heterogeneity in quality. It is expected that statisticians will develop new standards more suitable for evaluating RCTs related to teaching research and that editors and peer reviewers will be required to review the relevant RCTs more strictly.


Assuntos
Educação Médica , Aprendizagem Baseada em Problemas , Humanos , Estudos Transversais , Padrões de Referência , Modelos Lineares
6.
Biomed Chromatogr ; 31(5)2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27790733

RESUMO

A rapid, specific and high-throughput stable isotope-dilution LC-MS/MS method was developed and validated with high sensitivity for the quantification of R-phencynonate (a eutomer of phencynonate racemate) in rat and dog plasma. Plasma samples were deproteinized using acetonitrile and then separated on a C8 column with an isocratic mobile phase containing acetonitrile-water-formic acid mixture (60:40:0.1, v/v/v) at a flow rate of 0.2 mL/min. Each sample had a total run time of 3 min. Quantification was performed using triple quadrupole mass spectrometry in selected reaction monitoring mode with positive electrospray ionization. The method was shown to be highly linear (r2 > 0.99) and to have a wide dynamic range (0.1-100 ng/mL) with favourable accuracy and precision. No matrix effects were observed. The detailed pharmacokinetic profiles of R-phencynonate at therapeutic doses in rats and dogs were characterized by rapid oral absorption, quick clearance, high volume of distribution and poor absolute bioavailability. R-Phencynonate lacked dose proportionality over the oral dose range, based on the power model. However, the area under concentration-time curve and the maximum plasma concentration increased linearly in a dose-dependent manner in both animal models. The absolute bioavailability of R-phencynonate was 16.6 ± 2.75 and 4.78 ± 1.26% in dogs and rats, respectively.


Assuntos
Compostos Aza/sangue , Compostos Aza/farmacocinética , Cromatografia Líquida/métodos , Glicolatos/sangue , Glicolatos/farmacocinética , Espectrometria de Massas em Tandem/métodos , Administração Oral , Animais , Compostos Aza/administração & dosagem , Disponibilidade Biológica , Antagonistas Colinérgicos/administração & dosagem , Antagonistas Colinérgicos/sangue , Antagonistas Colinérgicos/farmacocinética , Cães , Glicolatos/administração & dosagem , Masculino , Técnica de Diluição de Radioisótopos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
7.
Molecules ; 20(9): 16266-77, 2015 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-26370951

RESUMO

Screening of anti-biofilm compounds from the burdock leaf based on metabolomics is reported here. The crystal violet assay indicated 34% ethanol elution fraction of burdock leaf could completely inhibit biofilm formation of Pseudomonas aeruginosa at 1 mg·mL(-1). Then, the chemical composition of burdock leaf fraction was analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and 11 active compounds (chlorogenic acid, caffeic acid, p-coumaric acid, quercetin, ursolic acid, rutin, cynarin, luteolin, crocin, benzoic acid, and Tenacissoside I) were identified. Lastly, UPLC-MS analysis was employed to obtain the metabolic fingerprints of burdock leaf fractions before and after inhibiting the biofilm of Pseudomonas aeruginosa. The metabolic fingerprints were transformed to data, analyzed with PLS-DA (partial least squares discriminant analysis) and the peaks whose area was significantly changed were found out. Thus, 81 compounds were screened as potential anti-biofilm ingredients. Among them, rutin, ursolic acid, caffeic acid, p-coumaric acid and quercetin were identified and confirmed as the main anti-biofilm compounds in burdock leaf. The study provided basic anti-biofilm profile data for the compounds in burdock leaf, as well as provided a convenient method for fast screening of anti-biofilm compounds from natural plants.


Assuntos
Arctium/química , Arctium/metabolismo , Biofilmes/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Folhas de Planta/metabolismo , Pseudomonas aeruginosa/efeitos dos fármacos , Metabolômica
8.
Front Public Health ; 12: 1320146, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38420033

RESUMO

Objective: During the COVID-19 pandemic, people posted help-seeking messages on Weibo, a mainstream social media in China, to solve practical problems. As viruses, policies, and perceptions have all changed, help-seeking behavior on Weibo has been shown to evolve in this paper. Methods: We compare and analyze the help-seeking messages from three dimensions: content categories, time distribution, and retweeting influencing factors. First, we crawled the help-seeking messages from Weibo, and successively used CNN and xlm-roberta-large models for text classification to analyze the changes of help-seeking messages in different stages from the content categories dimension. Subsequently, we studied the time distribution of help-seeking messages and calculated the time lag using TLCC algorithm. Finally, we analyze the changes of the retweeting influencing factors of help-seeking messages in different stages by negative binomial regression. Results: (1) Help-seekers in different periods have different emphasis on content. (2) There is a significant correlation between new daily help-seeking messages and new confirmed cases in the middle stage (1/1/2022-5/20/2022), with a 16-day time lag, but there is no correlation in the latter stage (12/10/2022-2/25/2023). (3) In all the periods, pictures or videos, and the length of the text have a significant positive effect on the number of retweets of help-seeking messages, but other factors do not have exactly the same effect on the retweeting volume. Conclusion: This paper demonstrates the evolution of help-seeking messages during different stages of the COVID-19 pandemic in three dimensions: content categories, time distribution, and retweeting influencing factors, which are worthy of reference for decision-makers and help-seekers, as well as provide thinking for subsequent studies.


Assuntos
COVID-19 , Mídias Sociais , Humanos , COVID-19/epidemiologia , Pandemias , SARS-CoV-2 , China/epidemiologia
9.
Artigo em Inglês | MEDLINE | ID: mdl-38598095

RESUMO

Ochratoxin A (OTA) is a toxic fungal metabolite that is commonly found in cereals and animal feed. It is economically damaging and potentially hazardous to human health. Herein, we propose an electrochemical immunosensor for the rapid detection of OTA using anti-OTA antibodies and diazonium-functionalized, screen-printed electrodes. We attached 4-aminobenzoic acid to an electrode surface, activated the carboxyl groups on the surface with carbodiimide, and attached an antibody to the diazo layer. Subsequently, we used bovine serum protein as a blocker to prevent non-specific antigens from binding to the antibody. We evaluated the performance of the sensor by cyclic voltammetry, electrochemical impedance spectroscopy, and differential pulse voltammetry. The sensor is highly specific and sensitive, has good linear responses in the range 20-200 ng/mL, a limit of detection of 0.5 ng/mL, and good recoveries of 90.5%-100.9% in spiked samples. It can be stored at 4 °C for approximately 2 weeks, and is highly stable, with a current response variation of no more than 4.6%.


Assuntos
Técnicas Eletroquímicas , Contaminação de Alimentos , Ocratoxinas , Ocratoxinas/análise , Contaminação de Alimentos/análise , Eletrodos , Imunoensaio/métodos , Análise de Alimentos , Compostos de Diazônio/química , Técnicas Biossensoriais , Animais
10.
Int Dent J ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38692963

RESUMO

INTRODUCTION AND AIMS: Altering the position and orientation of the root canal access cavity passway, or modifying the reduction of dentin volume, can influence the strength of dentition. This study aimed to compare the effects of different access cavities on the biomechanical performances of maxillary central incisors with a finite element analysis. METHODS: Based on the micro-computed tomography (CT) scan of a maxillary central incisor, the finite element models of the intact tooth and teeth with 4 access cavity designs: conservative incisal access cavity, incisal access cavity, conservative access cavity, and traditional access cavity were generated. Simulated occlusal forces were applied at the incisal edge of the incisor in the finite element analysis procedure. RESULTS: The maximum von Mises stress and maximum principal stress in the cervical area are highest in the traditional access cavity group, followed by the conservative access cavity group, incisal access cavity group, and conservative incisal access cavity group. CONCLUSION: The conservative access cavities minimise the extent of dentin removal from the cervical region, protecting the mechanical behaviour of the incisor. Moving the access cavity entry point to the incisal edge also improves the fracture resistance of the incisor. CLINICAL RELEVANCE: This study's findings would help clinicians select the most appropriate endodontics access cavity method when performing the root canal on maxillary central incisors.

11.
Int J Biol Macromol ; 275(Pt 2): 133088, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38880446

RESUMO

Flexible composite film has gained increasing attention in the fields of wearable devices and portable electronic products. In this work, a novel core-shell structure of cellulose nanofibers/BaTiO3@TiO2 (CNF/BTO@TiO2) was synthesized with the assistant of the biological macromolecule material of cellulose nanofiber (CNF), in which the CNF can improve the stability and dispersibility of BaTiO3 (BTO) in the aqueous phase and elevate the integrity of the core-shell structure. The core-shell structure can reduce the agglomeration of fillers in polyvinylidene fluoride (PVDF) and improve the structural defects of the composite film. Meanwhile, the core-shell structure can promote the polarization of the electric dipole and the formation of ß phase in PVDF due to the generated interface spatial polarization between the shell of TiO2 and the core of BTO. When the content of the core-shell structure was 5 wt%, the ß phase content reaches 61.89 %, and the piezoelectric coefficient of composite film reaches 84.29 pm/V. Thus the maximum output open-circuit voltage (VOC) and short-circuit current (ISC) of the piezoelectric composite film is as high as 13.10 V and 464.3 nA. In addition, its excellent pressure sensing capability allows for its application in various flexible electronic devices.


Assuntos
Compostos de Bário , Celulose , Nanofibras , Polivinil , Titânio , Titânio/química , Nanofibras/química , Polivinil/química , Compostos de Bário/química , Celulose/química , Eletricidade , Polímeros de Fluorcarboneto
12.
Nat Commun ; 15(1): 6909, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39134527

RESUMO

Late-stage specific and selective diversifications of peptides and proteins performed at target residues under ambient conditions are recognized to be the most facile route to various and abundant conjugates. Herein, we report an orthogonal modification of cysteine residues using alkyl thianthreium salts, which proceeds with excellent chemoselectivity and compatibility under mild conditions, introducing a diverse array of functional structures. Crucially, multifaceted bioconjugation is achieved through clickable handles to incorporate structurally diverse functional molecules. This "two steps, one pot" bioconjugation method is successfully applied to label bovine serum albumin. Therefore, our technique is a versatile and powerful tool for late-stage orthogonal bioconjugation.


Assuntos
Cisteína , Peptídeos , Soroalbumina Bovina , Cisteína/química , Peptídeos/química , Soroalbumina Bovina/química , Sais/química , Química Click/métodos , Animais , Proteínas/química , Bovinos
13.
ACS Appl Mater Interfaces ; 16(34): 45078-45090, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39155485

RESUMO

The advancement of intelligent and biodegradable respiratory protection equipment is pivotal in the realm of human health engineering. Despite significant progress, achieving a balance between efficient filtration and intelligent monitoring remains a great challenge, especially under conditions of high relative humidity (RH) and high airflow rate (AR). Herein, we proposed an interfacial stereocomplexation (ISC) strategy to facilitate intensive interfacial polarization for poly(lactic acid) (PLA) nanofibrous membranes, which were customized for machine learning-assisted respiratory diagnosis. Theoretical principles underlying the facilitated formation of the electroactive phase and aligned PLA chains were quantitatively depicted in the ISC-PLA nanofibers, contributing to the increased dielectric constant and surface potential (as high as 2.2 and 5.1 kV, respectively). Benefiting from the respiration-driven triboelectric mechanisms, the ISC-PLA demonstrated a high PM0.3 filtration efficiency of over 99% with an ultralow pressure drop (75 Pa), even in challenging circumstances (95 ± 5% RH, AR of 85 L/min). Furthermore, we implemented the ISC-PLA with multifunction respiratory monitoring (response time of 0.56 s and recovery time of 0.25 s) and wireless transmission technology, yielding a high recognition rate of 83% for personal breath states. This innovation has practical implications for health management and theoretical advancements in respiratory protection equipment.


Assuntos
Umidade , Aprendizado de Máquina , Nanofibras , Poliésteres , Poliésteres/química , Nanofibras/química , Humanos , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos
14.
Nat Commun ; 15(1): 2797, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38555355

RESUMO

Silent information regulator 2 (Sir2) proteins typically catalyze NAD+-dependent protein deacetylation. The recently identified bacterial Sir2 domain-containing protein, defense-associated sirtuin 2 (DSR2), recognizes the phage tail tube and depletes NAD+ to abort phage propagation, which is counteracted by the phage-encoded DSR anti-defense 1 (DSAD1), but their molecular mechanisms remain unclear. Here, we determine cryo-EM structures of inactive DSR2 in its apo form, DSR2-DSAD1 and DSR2-DSAD1-NAD+, as well as active DSR2-tube and DSR2-tube-NAD+ complexes. DSR2 forms a tetramer with its C-terminal sensor domains (CTDs) in two distinct conformations: CTDclosed or CTDopen. Monomeric, rather than oligomeric, tail tube proteins preferentially bind to CTDclosed and activate Sir2 for NAD+ hydrolysis. DSAD1 binding to CTDopen allosterically inhibits tube binding and tube-mediated DSR2 activation. Our findings provide mechanistic insight into DSR2 assembly, tube-mediated DSR2 activation, and DSAD1-mediated inhibition and NAD+ substrate catalysis in bacterial DSR2 anti-phage defense systems.


Assuntos
Sirtuínas , Sirtuínas/metabolismo , NAD/metabolismo , Proteínas Reguladoras de Informação Silenciosa de Saccharomyces cerevisiae/metabolismo , Sirtuína 2 , Hidrólise
15.
Int Dent J ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38866671

RESUMO

OBJECTIVES: With rising rates of maxillofacial fracture, postoperative infection following rigid internal fixation is an important issue that requires immediate resolution. It is important to explore an alternative antibacterial method apart from conventional antibiotics. A controlled experiment was conducted to evaluate the effectiveness of a caerin 1.9 peptide-coated titanium plate in reducing mandibular infection in New Zealand (NZ) rabbits, aiming to minimise the risk of post-metallic implantation infection. METHODS: Twenty-two NZ rabbits were randomly divided into 3 groups. The experiment group received caerin 1.9 peptide-coated titanium plates and mixed oral bacteria exposure. The control group received normal titanium plates with mixed oral bacteria exposure. The untreated group served as a control to prove that bacteria in the mouth can cause infection. Weight, temperature, hepatic function, and C-reactive protein levels were measured. Wound and bone conditions were evaluated. Further analysis included local infection, anatomic conditions, histology, and bacterial load. RESULTS: No significant differences were found in temperature, weight, blood alanine aminotransferase, and C-reactive protein levels amongst the 3 groups. The experiment group showed the lowest amount of bacterial RNA in wounds. Additionally, the experiment group had higher peripheral lymphocyte counts compared to the control group and lower neutrophil counts on the third and seventh day postoperatively. Histologic analysis revealed lower levels of inflammatory cell infiltration, bleeding, and areas of necrosis in the experimental group compared with the controls. CONCLUSIONS: A caerin 1.9-coated titanium plate is able to inhibit bacterial growth in a NZ rabbit mandibular mixed bacteria infection model and is worth further investigation.

16.
Hum Vaccin Immunother ; 20(1): 2385654, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-39193797

RESUMO

Cancer remains a major global health challenge. Immunotherapy has revolutionized the management of cancer, yet only a limited number of patients respond to such treatments. This is largely attributed to the immunosuppressive tumor microenvironment, which diminishes the effectiveness of immunotherapy. Recent studies have underscored the potential of naturally derived caerin 1 peptides, particularly caerin 1.1 and caerin 1.9, which exhibit strong antitumor effects and enhance the efficacy of immunotherapies in animal models. This review encapsulates the current research aimed at augmenting the effectiveness of immunotherapy, focusing on the role of caerin 1.1 and caerin 1.9 in boosting immunotherapeutic outcomes, elucidating possible mechanisms, and discussing their limitations and challenges.


Assuntos
Imunoterapia , Neoplasias , Microambiente Tumoral , Humanos , Neoplasias/terapia , Neoplasias/imunologia , Imunoterapia/métodos , Animais , Microambiente Tumoral/imunologia , Peptídeos Catiônicos Antimicrobianos/imunologia , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Peptídeos/imunologia , Peptídeos/uso terapêutico
17.
Infect Genet Evol ; 123: 105654, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39111344

RESUMO

Melioidosis is a zoonotic disease, with its outbreaks being rare and indicative of an unusual concurrence of extreme climate and natural environmental factors. An outbreak of melioidosis cases emerged in Hainan following Typhoon "Dianmu" from October to December 2021, presenting an opportunity to identify the environmental sources of infection for these cases due to its nature as a well-defined point-source cluster. To investigate the relationship between the occurrence of these melioidosis cases and the environment, we extracted the entire genome of 25 clinical strains and conducted MLST typing, followed by whole genome sequencing and analysis of molecular genetic information for four ST46 genotypes from these strains. Phylogenetic and evolutionary relationships between Hainan sequence types (STs) and those found in other endemic regions were analyzed using IslandPath-DIMO, PHASTER, e-BURST, PHYLOViZ, and the maximum likelihood method. Notably, a total of 25 clinical strains were identified, encompassing 12 STs (ST46, ST1105, ST1991, ST30, ST1992, ST50, ST164, ST55, ST70, ST1993, ST1545, and ST58), with ST1991, ST1992, and ST1993 being newly discovered subtypes. PHYLOViZ clustering analysis divided the strains into two groups (A and B), both closely related to the Asian region. Phylogenetic tree analysis further revealed that most of the strains in this study were closely related to those found in Australia and Thailand. Analysis of patient information and visits to their residences suggested that contaminated water sources might be the primary source of infection during this outbreak. Our findings underscore that extreme weather events, such as typhoons, significantly increase the infection rate of B. pseudomallei, along with its genetic diversity, necessitating additional prevention strategies to control these B. pseudomallei infections.


Assuntos
Burkholderia pseudomallei , Surtos de Doenças , Variação Genética , Melioidose , Tipagem de Sequências Multilocus , Filogenia , Melioidose/epidemiologia , Melioidose/microbiologia , Humanos , Burkholderia pseudomallei/genética , Burkholderia pseudomallei/classificação , Evolução Molecular , China/epidemiologia , Sequenciamento Completo do Genoma , Genótipo
18.
Adv Sci (Weinh) ; 11(21): e2308491, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38466927

RESUMO

Peptide and protein postmodification have gained significant attention due to their extensive impact on biomolecule engineering and drug discovery, of which cysteine-specific modification strategies are prominent due to their inherent nucleophilicity and low abundance. Herein, the study introduces a novel approach utilizing multifunctional 5-substituted 1,2,3-triazine derivatives to achieve multifaceted bioconjugation targeting cysteine-containing peptides and proteins. On the one hand, this represents an inaugural instance of employing 1,2,3-triazine in biomolecular-specific modification within a physiological solution. On the other hand, as a powerful combination of precision modification and biorthogonality, this strategy allows for the one-pot dual-orthogonal functionalization of biomolecules utilizing the aldehyde group generated simultaneously. 1,2,3-Triazine derivatives with diverse functional groups allow conjugation to peptides or proteins, while bi-triazines enable peptide cyclization and dimerization. The examination of the stability of bi-triazines revealed their potential for reversible peptide modification. This work establishes a comprehensive platform for identifying cysteine-selective modifications, providing new avenues for peptide-based drug development, protein bioconjugation, and chemical biology research.


Assuntos
Cisteína , Peptídeos , Proteínas , Triazinas , Cisteína/química , Triazinas/química , Peptídeos/química , Proteínas/química
20.
ACS Omega ; 8(4): 3945-3955, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36743053

RESUMO

In order to increase the number and contact probability of electric dipole on cellulose, acid and alkali treatment was employed to extract hemicellulose and lignin from original wood to gain a highly oriented cellulose frame. The combined means with 2,2,6,6-tetramethylpiperidine-1-oxyl-NaBr-NaClO oxidation and impregnation of PDMS with compression was subsequently used to enhance its mechanical performance and electromechanical conversion. The assembled wooden electromechanical device (10 mm × 10 mm × 1 mm) exhibits the maximum open-circuit voltage (V OC) of 11.75 V and short-circuit current (I SC) of 211.01 nA as stepped by foot. It can be sliced to fabricate a flexible sensor with high sensitivity displaying V OC of 2.88 V and I SC of 210.09 nA under the tapped state. Its highly oriented wood fiber makes it display significant anisotropy in terms of mechanical and electromechanical performance for multidirectional sense. This strategy will exactly provide reference for developing other high-performance piezoelectric devices.

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