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1.
Phys Med Biol ; 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36096129

RESUMO

Cone beam CT (CBCT) in preclinical small animal irradiation platforms provides essential information for image guidance and radiation dose calculation for experiment planning. This project developed a photon-counting detector (PCD)-based multi(3)-energy (ME-)CBCT on a small animal irradiator to improve accuracy of material differentiation and hence dose calculation, and compared to conventional flat panel detector (FPD)-based CBCT. APPROACH: We constructed a mechanical structure to mount a PCD to an existing preclinical irradiator platform and built a data acquisition pipeline to acquire x-ray projection data with a 100 kVp x-ray beam using three different energy thresholds in a single gantry rotation. We implemented an energy threshold optimization scheme to determine optimal thresholds to balance signal-to-noise ratios (SNRs) among energy channels. Pixel-based detector response calibration was performed to remove ring artifacts in reconstructed CBCT images. Feldkamp-Davis-Kress (FDK) method was employed to reconstruct CBCT images and a total-variance regularization-based optimization model was used to decompose CBCT images into bone and water material images. We compared dose calculation results using PCD-based ME-CBCT with that of FPD-based CBCT. MAIN RESULTS: The optimal nominal energy thresholds were determined as 26, 56, and 90 keV, under which SNRs in a selected region-of-interest in water region were 6.11, 5.91 and 5.93 in the three energy channels, respectively. Comparing with dose calculation results using FPD-based CBCT, using PCD-based ME-CBCT reduced mean relative error from 49.5\% to 16.4\% in bone regions and from 7.5\% to 6.9\% in soft tissue regions. SIGNIFICANCE: PCD-based ME-CBCT is beneficial in improving radiation dose calculation accuracy in experiment planning of preclinical small animal irradiation researches.

2.
Front Pediatr ; 10: 943320, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36147817

RESUMO

Aims: To examine the predictive value of serum biomarkers combined with other indicators for necrotizing enterocolitis (NEC) surgery decision-making. Methods: Clinical data, including baseline information, clinical features, imaging presentation and serum assessment, of the infants enrolled were collected, and the serum concentrations of HBD2, HMGB-1, Claudin-3 and Relmß were determined. Student's t test, the Mann-Whitney U test, the chi-square test and logistic regression analysis were used. Receiver operating characteristic (ROC) curves were also generated. Results: Forty-nine infants were enrolled, with 23 in the surgical NEC group and 26 in the medical NEC group. There were no differences in the baseline clinical information, including birth weight, gestational age, admission age and risk factors, during pregnancy and before enrollment (P > 0.05). Peritonitis, intestinal adhesion and sepsis were more common in the surgical group (P < 0.05). The incidences of abdominal distention, abdominal wall tenseness, abdominal tenderness and absent bowel sounds in the surgical group were significantly higher when NEC occurred (P < 0.05). There were no differences between the two groups in the imaging presentation (P > 0.05). The concentration of Relmß {[8.66 (4.29, 19.28) vs. 20.65 (9.51, 44.65)]} in the surgical group was significantly higher (P < 0.05). Abdominal wall tenseness, abdominal tenderness and a Relmß concentration > 19.7 µmol/L were included in the predictive model, and the AUC of the predictive score was 0.943 (95% CI: 0.891-1.000) (P < 0.05). Conclusion: Serum Relmß concentration combined with abdominal wall tenseness and abdominal tenderness may be useful in determining surgical timing in neonates with NEC.

3.
Vet Sci ; 9(8)2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-36006314

RESUMO

Fecal microbiota transplantation (FMT) is an emerging therapeutic option for a variety of diseases, and is characterized as the transfer of fecal microorganisms from a healthy donor into the intestinal tract of a diseased recipient. In human clinics, FMT has been used for treating diseases for decades, with promising results. In recent years, veterinary specialists adapted FMT in canine patients; however, compared to humans, canine FMT is more inclined towards research purposes than practical applications in most cases, due to safety concerns. Therefore, in order to facilitate the application of fecal transplant therapy in dogs, in this paper, we review recent applications of FMT in canine clinical treatments, as well as possible mechanisms that are involved in the process of the therapeutic effect of FMT. More research is needed to explore more effective and safer approaches for conducting FMT in dogs.

4.
J Inflamm Res ; 15: 4763-4784, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36032938

RESUMO

Purpose: This study aimed to investigate the improvement effect of Sini Decoction plus Ginseng Soup (SNRS) on the LPS/D-GalN-induced acute liver failure (ALF) mouse model and the molecular mechanism of the SNRS effect. Methods: To study the protective effect of SNRS on ALF mice, the ICR mice were firstly divided into 4 groups: Control group (vehicle-treated), Model group (LPS/D-GalN), SNRS group (LPS/D-GalN+SNRS), and Silymarin group (LPS/D-GalN+Silymarin), the therapeutic drug was administered by gavage 48h, 24h before, and 10 min after LPS/D-GalN injection. On this basis, the peroxisome proliferator-activated receptor (PPAR) α agonist (WY14643) and inhibitor (GW6471) were added to verify whether the therapeutic mechanism of SNRS is related to its promoting effect on PPARα. The animals are grouped as follows: Control group (vehicle-treated), Model group (LPS/D-GalN+DMSO), SNRS group (LPS/D-GalN+SNRS+DMSO), Inhibitor group (LPS/D-GalN+GW6471), Agonist group (LPS/D-GalN+WY14643), and Inhibitor+SNRS group (LPS/D-GalN+GW6471+SNRS). Results: The protective effect of SNRS on the ALF model is mainly reflected in the reduction of serum alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST) as well as the ameliorated pathology of the liver tissue. The survival rate of ALF mice treated with SNRS was significantly increased. Further mechanism studies showed that SNRS significantly promoted the protein expression of PPARα and decreased the expression of necroptosis proteins (RIP3, MLKL, p-MLKL) in ALF mice. Reduced necroptosis resulted in decreased HMGB1 release, which in turn inhibited the activation of TLR4-JNK and NLRP3 inflammasome signaling pathways and the expression of NF-κB protein induced by LPS/D-GalN. The expression of CPT1A, a key enzyme involved in fatty acid ß-oxidation, was found to be significantly up-regulated in the SNRS treated group, accompanied by an increased adenosine-triphosphate (ATP) level, which may be the relevant mechanism by which SNRS reduces necroptosis. Conclusion: The potential therapeutic effect of SNRS on ALF may be through promoting the expression of PPARα and increasing the level of ATP in liver tissue, thereby inhibiting necroptosis of hepatocytes, reducing hepatocyte damage, and improving liver function.

5.
Angew Chem Int Ed Engl ; 61(37): e202209849, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-35876073

RESUMO

Electrochemical reduction of biomass-derived 5-hydroxymethylfurfural (HMF) represents an elegant route toward sustainable value-added chemicals production that circumvents the use of fossil fuel and hydrogen. However, the reaction efficiency is hampered by the high voltage and low activity of electrodes (Cu, Bi, Pb). Herein, we report a Ru1 Cu single-atom alloy (SAA) catalyst with isolated Ru atoms on Cu nanowires that exhibits an electrochemical reduction of HMF to 2,5-dihydroxymethylfuran (DHMF) with promoted productivity (0.47 vs. 0.08 mmol cm-2 h-1 ) and faradic efficiency (FE) (85.6 vs. 71.3 %) at -0.3 V (vs. RHE) compared with Cu counterpart. More importantly, the FE (87.5 %) is largely retained at high HMF concentration (100 mM). Kinetic studies by using combined electrochemical techniques suggest disparate mechanisms over Ru1 Cu and Cu, revealing that single-atom Ru promotes the dissociation of water to produce H* species that effectively react with HMF via an electrocatalytic hydrogenation (ECH) mechanism.


Assuntos
Ligas , Furaldeído , Furaldeído/análogos & derivados , Hidrogenação , Cinética
6.
Sci Adv ; 8(28): eabo3064, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35857512

RESUMO

Alveolar macrophages (AMs) are critical mediators of pulmonary inflammation. Given the unique lung tissue environment, whether there exist AM-specific mechanisms that control inflammation is not known. Here, we found that among various tissue-resident macrophage populations, AMs specifically expressed Lepr, encoding receptor for a key metabolic hormone leptin. AM-intrinsic Lepr signaling attenuated pulmonary inflammation in vivo, manifested as subdued acute lung injury yet compromised host defense against Streptococcus pneumoniae infection. Lepr signaling protected AMs from necroptosis and thus constrained neutrophil recruitment and tissue damage secondary to release of proinflammatory cytokine interleukin-1α. Mechanistically, Lepr signaling sustained activation of adenosine monophosphate-activated protein kinase in a Ca2+ influx-dependent manner and rewired cellular metabolism, thus preventing excessive lipid droplet formation and overloaded metabolic stress in a lipid-rich alveolar microenvironment. In conclusion, our results defined AM-expressed Lepr as a metabolic checkpoint of pulmonary inflammation and exemplified a macrophage tissue adaptation strategy for maintenance of immune homeostasis.


Assuntos
Macrófagos Alveolares , Pneumonia , Humanos , Inflamação/metabolismo , Leptina/metabolismo , Pulmão/metabolismo , Pneumonia/metabolismo , Receptores para Leptina/genética
7.
Microorganisms ; 10(8)2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35893553

RESUMO

Subacute ruminal acidosis (SARA) is a common metabolic disease in ruminants. In the early stage of SARA, ruminants do not exhibit obvious clinical symptoms. However, SARA often leads to local inflammatory diseases such as laminitis, mastitis, endometritis and hepatitis. The mechanism by which SARA leads to inflammatory diseases is largely unknown. The gut microbiota is the totality of bacteria, viruses and fungi inhabiting the gastrointestinal tract. Studies have found that the gut microbiota is not only crucial to gastrointestinal health but also involved in a variety of disease processes, including metabolic diseases, autoimmune diseases, tumors and inflammatory diseases. Studies have shown that intestinal bacteria and their metabolites can migrate to extraintestinal distal organs, such as the lung, liver and brain, through endogenous pathways, leading to related diseases. Combined with the literature, we believe that the dysbiosis of the rumen microbiota, the destruction of the rumen barrier and the dysbiosis of liver function in the pathogenesis of SARA lead to the entry of rumen bacteria and/or metabolites into the body through blood or lymphatic circulation and place the body in the "chronic low-grade" inflammatory state. Meanwhile, rumen bacteria and/or their metabolites can also migrate to the mammary gland, uterus and other organs, leading to the occurrence of related inflammatory diseases. The aim of this review is to describe the mechanism by which SARA causes inflammatory diseases to obtain a more comprehensive and profound understanding of SARA and its related inflammatory diseases. Meanwhile, it is also of great significance for the joint prevention and control of diseases.

8.
Microb Pathog ; 169: 105671, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35811022

RESUMO

Staphylococcus aureus (S. aureus) is a gram-positive pathogen that can cause infectious diseases in mammals. S. aureus-induced host innate immune responses have a relationship with Toll-like receptor 2 (TLR2), TLR4, and Nod-like receptor pyrin domain-containing protein 3 (NLRP3). However, the detailed roles of TLR2, TLR4, and NLRP3 in regulating the host inflammatory response to S. aureus infection remain unclear. Our data indicated that the S. aureus-induced mortality was aggravated by deficiency of TLR2, TLR4, and NLRP3 in mice. In the subsequent experiment, we found that during S. aureus infection, the roles of TLR2, TLR4, and NLRP3 seemed to be different at multiple timepoints. The deficiency of TLR2, TLR4, or NLRP3 attenuated the expression of High-mobility group box protein 1 (HMGB1) and Hyaluronic acid-binding protein 2 (HABP2), which is accompanied by decreased proinflammatory cytokine (TNF-α), chemokine (RANTES), and anti-inflammatory cytokine (IL-10) production in lungs and serum at 3 h and 6 h post-infection. However, with S. aureus infection prolonged (24 h post-infection), the trend was diametrically opposite. The results showed that deficiency of TLR2, TLR4, or NLRP3 aggravated HABP2 and HMGB1 expression, which is accompanied by enhanced proinflammatory cytokine (TNF-α), chemokine (RANTES), and anti-inflammatory cytokine (IL-10) production in lungs and serum. These results were consistent with the data observed in S. aureus-infected bone marrow-derived macrophages (BMDMs). All these results suggested that during S. aureus infection, TLR2, TLR4, and NLRP3 has time-dependent effect in regulating the balance between immune-driven resistance and tolerance.


Assuntos
Proteína HMGB1 , Infecções Estafilocócicas , Animais , Quimiocina CCL5 , Citocinas , Interleucina-10 , Mamíferos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Staphylococcus aureus/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
9.
Front Psychol ; 13: 935506, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35874345

RESUMO

There is no denying that there is ample evidence of numerous factors that influence language learners' success. Recently, there is a critical call to embrace positive psychology that is more open and appreciative of the positive influences in learning English as a foreign language (EFL). Set against this burgeoning area of study in language learning, this paper puts forward the findings of a study that aimed to examine the mediating roles of grit and foreign language enjoyment in the relationship between growth mindset and English language performance. The study employed a correlational research design involving 388 EFL students from one university in China. The data were collected through a questionnaire and an English language performance test. Using the structural equation modeling, this study found that the association between growth mindset and English language performance was partially mediated by grit and foreign language enjoyment. This indicates that students with a growth mindset tend to possess a higher level of grit as well as experience more enjoyment in learning English, which consequently can lead to students becoming more successful language learners. These findings provide significant implications for language teachers, educational material developers, and school administrators in China to embrace the affective domain postulated by positive psychology.

10.
Microorganisms ; 10(6)2022 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-35744708

RESUMO

Allergic diseases are becoming a major healthcare issue in many developed nations, where living environment and lifestyle are most predominantly distinct. Such differences include urbanized, industrialized living environments, overused hygiene products, antibiotics, stationary lifestyle, and fast-food-based diets, which tend to reduce microbial diversity and lead to impaired immune protection, which further increase the development of allergic diseases. At the same time, studies have also shown that modulating a microbiocidal community can ameliorate allergic symptoms. Therefore, in this paper, we aimed to review recent findings on the potential role of human microbiota in the gastrointestinal tract, surface of skin, and respiratory tract in the development of allergic diseases. Furthermore, we addressed a potential therapeutic or even preventive strategy for such allergic diseases by modulating human microbial composition.

11.
FEMS Microbiol Ecol ; 98(7)2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35648454

RESUMO

The colonization and virulence production of Staphylococcus aureus (S. aureus), a known pathogen that induces mastitis, depend on its quorum-sensing (QS) system and biofilm formation. It has been reported that Bacillus can inhibit the QS system of S. aureus, thereby reducing S. aureus colonization in the intestine. However, whether Bacillus affects S. aureus biofilm formation and consequent colonization during mastitis is still unknown. In this study, the differences in the colonization of S. aureus and Bacillus were first analyzed by isolating and culturing bacteria from milk samples. It was found that the colonization of Bacillus and S. aureus in cow mammary glands was negatively correlated. Secondly, we found that although Bacillus did not affect S. aureus growth, it inhibited the biofilm formation of S. aureus by interfering its QS signaling. The most significant anti-biofilm effect was found in Bacillus subtilis H28 (B. subtilis H28). Finally, we found that B. subtilis H28 treatment alleviated S. aureus-induced mastitis in a mice model. Our results rerealed that bovine milk derived commensal Bacillus inhibited S. aureus colonization and alleviated S. aureus-induced mastitis by influencing biofilm formation, suggesting a potential targeted strategy to limit the colonization of S. aureus in vivo.


Assuntos
Bacillus , Mastite Bovina , Infecções Estafilocócicas , Animais , Bacillus subtilis , Biofilmes , Bovinos , Feminino , Humanos , Mastite Bovina/microbiologia , Mastite Bovina/prevenção & controle , Camundongos , Leite/microbiologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/prevenção & controle , Staphylococcus aureus
12.
Microbiol Spectr ; 10(4): e0081122, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-35727038

RESUMO

Intestinal microbiota-mediated aryl hydrocarbon receptor (AhR) activation plays an important role in host-microbiota interactions and disease development. However, whether AhR activation mediates infection-induced inflammation in remote organs is not clear. The purpose of this study is to assess the effects and underlying mechanism of AhR activation and gut microbiota-mediated dietary tryptophan (Trp) metabolism on infection-induced inflammation using an Escherichia coli (E. coli)-induced endometritis model in mice. We found that AhR activation by 6-formylindolo (3,2-b) carbazole (Ficz), which is an AhR agonist derived from the photooxidation of Trp, alleviated E. coli-induced endometritis by repairing barrier function and inhibiting inflammatory responses, while inhibition of AhR by CH223191, which is a synthetic AhR antagonist, aggravated E. coli-induced endometritis. Gut dysbiosis damaged AhR activation and exacerbated E. coli-induced endometritis in mice, which responded to the reduced abundance of AhR ligand producers, such as Lactobacillus spp. Supplementation with dietary Trp ameliorated E. coli-induced endometritis in a microbiota-dependent manner, which was associated with the production of AhR ligands. Administration of AhR ligands, including indole and indole aldehyde, but not indole-3-propionic acid, rescued the protective effect of Trp on E. coli-induced endometritis in dysbiotic mice. Moreover, consumption of Lactobacillus reuteri (L. reuteri) containing AhR ligand-producing capability also alleviated E. coli-induced endometritis in mice in an AhR-dependent manner. Our results demonstrate that microbiota-mediated AhR activation is a key factor in fighting pathogen-caused inflammation, which leads to a potential strategy to regulate the gut microbiota and metabolism by dietary Trp or probiotics for the intervention of infectious diseases and reproductive health. IMPORTANCE Infection-induced endometritis is a common and frequently occurring disease in humans and animals. Accumulating evidence suggests an important role of the gut microbiota in the development of infection-induced inflammation. Whether and how gut microbiota-mediated AhR activation regulates the pathogenesis of pathogen-induced endometritis remains unknown. The current study found that AhR activation ameliorated E. coli-induced endometritis, and inhibition of AhR produced negative results. Gut dysbiosis reduced the abundance of AhR ligand producers including Lactobacillus spp., damaged AhR activation, and exacerbated E. coli-induced endometritis. Supplementation with dietary Trp, AhR ligands, and L. reuteri containing AhR ligand-producing capability alleviated E. coli-induced endometritis in mice. Our results suggest an important role of microbiota-mediated AhR activation in the pathogenesis of endometritis and provide potential strategies for the intervention of infectious diseases and reproductive health by regulating the gut microbiota and metabolism.


Assuntos
Endometrite , Microbioma Gastrointestinal , Lactobacillus reuteri , Animais , Disbiose/terapia , Endometrite/terapia , Escherichia coli/metabolismo , Feminino , Humanos , Inflamação , Lactobacillus reuteri/metabolismo , Ligantes , Camundongos , Receptores de Hidrocarboneto Arílico/metabolismo , Triptofano/metabolismo
13.
Food Funct ; 13(13): 7144-7156, 2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35699056

RESUMO

Ketosis, a common metabolic disorder in dairy cattle, occurs during early lactation and leads to higher concentrations of non-esterified fatty acids (NEFAs) and ß-hydroxybutyrate (BHBA), and is generally believed to be caused by excessive negative energy balance (NEB). Propylene glycol (PG), a gluconeogenic precursor, has been proved to promote gluconeogenesis and alleviate NEB. Oral administration of PG is widely considered one of the most effective therapeutic options for treating ketosis. Thus, in this study, we assessed the effects of PG on rumen microbiota via 16S rDNA analysis. The results show that one dose (500 mL) of PG treatment could rapidly reduce the blood BHBA level in ketosis cows by increasing the level and proportion of propionate in the rumen. Meanwhile, PG also had certain effects on the rumen bacterial community. Compared with before treatment, the relative abundances of Prevotella, Succinivibrionaceae_UCG-001 and Prevotellaceae_UCG-001 increased significantly, while those of Christensenellaceae_R-7_group, Butyrivibrio and Saccharofermentans significantly decreased. LEfSe analysis revealed that after PG treatment, only Rikenellaceae_RC9_gut_group was enriched in the rumen fluid at the genus level. In conclusion, the present study indicates that ketosis is accompanied by alterations in the rumen microbiota community. PG treatment changes the composition of rumen microbiota to a healthier state and contributes to rapid recovery from ketosis. These results support the usage of PG for treating such metabolic diseases that challenge high-yield cows due to their minimized cost and maximized safety without any adverse events.


Assuntos
Doenças dos Bovinos , Cetose , Microbiota , Ácido 3-Hidroxibutírico/metabolismo , Ácido 3-Hidroxibutírico/uso terapêutico , Animais , Bovinos , Doenças dos Bovinos/tratamento farmacológico , Dieta , Feminino , Cetose/tratamento farmacológico , Cetose/veterinária , Lactação , Leite/metabolismo , Propilenoglicol , Rúmen/metabolismo , Rúmen/microbiologia
14.
Bioengineered ; 13(6): 14094-14106, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35734856

RESUMO

Periodontitis is a risk factor for the development of oral squamous cell carcinomas (OSCC). Both DNA damage response (DDR) and activation of inflammasomes induced by the microbiome might play important roles in the development of tumors, in relation to genome stability of tumor cells. Herein, we explored whether periodontitis negative-associated bacteria (Neisseria sicca and Corynebacterium matruchotii, namely called 'PNB'), which were highly abundant in healthy populations, could inhibit OSCC by promoting genome stability. Firstly, a murine SCC-7 tumor-bearing model that colonized with PNB was designed and used in this study. Then, cyclin D1 was detected by immunohistochemistry. Levels of DDR, NLRP3 inflammasomes and pro-inflammatory cytokines in tumors were detected by RT-qPCR or Western blot. Immune cells in spleens were detected by immunohistochemistry or immunofluorescence. Finally, the anti-cancer activity of PNB was assessed in vitro using CCK-8 assays and flow cystometry. Compared with the control, PNB decreased tumor weights from 0.77 ± 0.26 g to 0.42 ± 0.15 g and downregulated the expression of Cyclin D1. PNB activated the DDR by up-regulating γ-H2AX, p-ATR, and p-CHK1. PNB activated NLRP3 inflammasome-mediated pyroptosis via increases of NLRP3, gasdermin D, and mRNA levels of apoptosis-associated speck-like protein, Caspase-1. PNB suppressed the inflammatory response by down-regulating mRNA levels of NF-κΒ and IL-6 in tumors as well as the populations of CD4+ T cells and CD206+ immune cells in spleens. PNB inhibited proliferation and promoted cell death of HSC-3 cells. In conclusion, Neisseria sicca and Corynebacterium matruchotii showed a 'probiotic bacterial' potential to inhibit OSCC by regulating genome stability.


Assuntos
Corynebacterium , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Neisseria sicca , Carcinoma de Células Escamosas de Cabeça e Pescoço , Animais , Ciclina D1/genética , Instabilidade Genômica , Inflamassomos/metabolismo , Camundongos , Neoplasias Bucais/genética , Neoplasias Bucais/terapia , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , RNA Mensageiro , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia
15.
Front Chem ; 10: 842208, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35646819

RESUMO

Background: A series of α-Mangostin (α-M) derivatives were designed and synthesized. α-M and four analogues were evaluated for their multifunctional anti-Alzheimer's disease (anti-AD) effects on fibrillogenesis, microglial uptake, microglial degradation, and anti-neurotoxicity of Aß, as well as LPS-induced neuroinflammation. The differences in bioactivities were analyzed to understand the structure-activity relationship for further modifications. Purpose: This study aims to investigate the anti-AD effects of α-M and elucidate its structure-activity relationship by comparing difference between α-M and several analogues. Methods: Aß fibrillogenesis was detected by Thioflavin T fluorometric assay. The levels of Aß1-42 and inflammatory cytokines were evaluated by enzyme-linked immunosorbent assay. Neuron viability was examined by the CCK-8 assay. The morphology of ZO-1 of bEnd.3 cultured in BV-2-conditioned medium was evaluated by immunofluorescence staining. Results: Aß fibrillogenesis was significantly inhibited by co-incubation with α-M, Zcbd-2 or Zcbd-3. α-M, Zcbd-2, Zcbd-3, and Zcbd-4 decreased the levels of Aß1-42 and inflammatory cytokines, and promoted Aß uptake, degradation and anti-inflammation effects inflammation in microglia. α-M and Zcbd-3 protected neuron viability from Aß-induced neurotoxicity, and preserved tight junction integrity of bEnd.3 against LPS-induced neuroinflammation. Conclusion: Zcbd-3 acted as α-M almost in all effects. The structure-activity analysis indicated that the 3-methyl-2-butenyl group at C-8 is essential for the bioactivity of α-M, while modifying the double hydroxylation at the C-2 position may improve the multifunctional anti-AD effects.

16.
Beilstein J Org Chem ; 18: 429-437, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35529891

RESUMO

Herein, we have designed and fabricated a simple and efficient supramolecular self-assembled nanosystem based on host-guest interactions between water-soluble tetraphenylethylene-embedded pillar[5]arene ( m -TPEWP5) and ammonium benzoyl-ʟ-alaninate (G) in an aqueous medium. The obtained assembly of m -TPEWP5 and G showed aggregation-induced emission (AIE) via the blocking of intramolecular phenyl-ring rotations and functioned as an ideal donor. After the loading of eosin Y (EsY) as acceptor on the surface of the assembly of m -TPEWP5 and G, the worm-like nanostructures changed into nanorods, which facilitates a Förster resonance energy transfer (FRET) from the m -TPEWP5 and G assembled donor to the EsY acceptor present in the nanorod assembly. The system comprising m -TPEWP5, G and EsY displayed moderate FRET efficiency (31%) at a 2:1 molar ratio of donor-to-acceptor. Moreover, the obtained supramolecular nanorod assembly could act as a nanoreactor mimicking natural photosynthesis and exhibited a high catalytic efficiency for the photocatalytic dehalogenation reaction of various bromoketone derivatives with good yields in short reaction time in water.

17.
Front Oncol ; 12: 756811, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35530332

RESUMO

Background: We aimed to investigate clinical implications of specific soluble immune checkpoint molecules (sICMs) in locally advanced rectal cancer (LARC) patients treated with neoadjuvant chemoradiotherapy (nCRT). Methods: We prospectively enrolled 30 LARC patients treated with nCRT and collected blood samples from them before, during, and after nCRT for prospective studies. Immune checkpoints often refer to T cell surface molecules influencing the immune response. Immune checkpoints, in the form of a soluble monomeric form, is widely present in blood. In the study, eight immune checkpoint-related plasma proteins, including programmed death-ligand 1 (PD-L1), CD80, CD86, CD28, CD27, glucocorticoid-induced tumor necrosis factor receptor (GITR), GITR ligand (GITRL), and inducible T-cell costimulator (ICOS), were measured using the Luminex platform. Two independent pathologists categorized patients as the good responders and the poor responders according to Dworak tumor regression grade (TRG). Results: Of the 30 patients, the levels of sPD-L1, sCD80, sCD86, sCD28, sGITR, sGITRL, sCD27, and sICOS decreased during nCRT (Pre-nCRT vs. During-nCRT, all p<0.05) but were restored after nCRT treatment (Pre-nCRT vs. Post-nCRT, all p>0.05). In the 14 good responders, the levels of sICMs, other than sGITR (p=0.081) and sGITRL (p=0.071), decreased significantly during nCRT (Pre-nCRT vs. During-nCRT, p<0.05), but they were all significantly increased after nCRT (During-nCRT vs. Post-nCRT, all p<0.05). In the 16 poor responders, only sCD80 was significantly reduced during nCRT (Pre-nCRT vs. During-nCRT, p<0.05), and none was significantly increased after nCRT (During-nCRT vs. Post-nCRT, all p<0.05). High levels of sICMs before nCRT were associated with poor response (all OR≥1). The Pre-model that incorporated the 8 sICMs before nCRT yielded a good predictive value (AUC, 0.848) and was identified as an independent predictor of treatment response (OR, 2.62; 95% CI, 1.11-6.18; p=0.027). Conclusion: Our results suggest chemoradiotherapy could influence the change of sPD-L1, sCD80, sCD86, sCD28, sGITR, sGITRL, sCD27, and sICOS in patients with LARC. The levels of the majority of soluble immune checkpoint molecules were reduced during nCRT and then restored at the end of nCRT, particularly in patients who responded well to nCRT. Combined baseline sICMs can be developed to predict treatment response.

18.
Chem Commun (Camb) ; 58(42): 6196-6199, 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35506735

RESUMO

Transformation of [15]paracyclophanes ([15]PCP) into fluorophores has been achieved by embedding tetraphenylethene (TPE) units into their skeletons at the meso-positions. The obtained two hosts demonstrated distinct aggregation-induced emission (AIE) properties and their fluorescence could be selectively quenched by Ni2+ ions.

19.
PLoS One ; 17(5): e0269111, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35617324

RESUMO

We performed a meta-analysis to evaluate the efficacy of alprostadil in the treatment of hypertensive nephropathy. Seven online databases (PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure [CNKI] database, Wanfang Data Knowledge Service Platform, VIP Information Resource Integration Service Platform [cqVIP], and China Biology Medicine Disc [SinoMed]) were searched from inception to January 31, 2022, and a set of clinical indicators for hypertensive nephropathy was selected. The main indicators were 24-h urinary protein, serum creatinine, endogenous serum creatinine clearance rate, blood urea nitrogen, cystatin C, and mean arterial pressure. The methodological quality of the included trials was analyzed using a risk of bias assessment according to the Cochrane Manual guidelines, and a meta-analysis was performed. A random-effects model was implemented to pool the results. A total of 20 randomized controlled trials involving 1441 patients with hypertensive nephropathy were included in this review. Our findings showed that alprostadil had a positive effect on 24-h urinary protein (mean difference [MD] = -0.79, 95% confidence interval [CI] [-1.16, -0.42], P < 0.0001), serum creatinine (MD = -13.83, 95% CI [-19.34, -8.32], P < 0.00001), endogenous serum creatinine clearance rate (MD = 6.09, 95% CI [3.59, 8.59], P < 0.00001), blood urea nitrogen (MD = -6.42, 95% CI [-8.63, -4.21], P < 0.00001), cystatin C (MD = -0.26, 95% CI [-0.34, -0.18], P < 0.00001), and mean arterial pressure levels(MD = -13.65, 95% CI [-16.08, -11.21], P < 0.00001). Compared to conventional treatment alone, alprostadil combined with conventional treatment can improve renal function in patients with hypertensive nephropathy more effectively. However, additional large-scale, multicenter, rigorously designed randomized controlled trials are needed to verify these results. This is the first meta-analysis to evaluate the efficacy of alprostadil for hypertensive nephropathy, and the results may guide clinical practice.


Assuntos
Alprostadil , Cistatina C , Creatinina , Humanos , Hipertensão Renal , Estudos Multicêntricos como Assunto , Nefrite , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
Adv Mater ; 34(27): e2201843, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35509216

RESUMO

Spider dragline silk is draw-spun from soluble, ß-sheet-crosslinked spidroin in aqueous solution. This spider silk has an excellent combination of strength and toughness, which originates from the hierarchical structure containing ß-sheet crosslinking points, spiral nanoassemblies, a rigid sheath, and a soft core. Inspired by the spidroin structure and spider spinning process, a soluble and crosslinked nanogel is prepared and crosslinked fibers are drew spun with spider-silk-like hierarchical structures containing cross-links, aligned nanoassemblies, and sheath-core structures. Introducing nucleation seeds in the nanogel solution, and applying prestretch and a spiral architecture in the nanogel fiber, further tunes the alignment and assembly of the polymer chains, and enhances the breaking strength (1.27 GPa) and toughness (383 MJ m-3 ) to approach those of the best dragline silk. Theoretical modeling provides understanding for the dependence of the fiber's spinning capacity on the nanogel size. This work provides a new strategy for the direct spinning of tough fiber materials.


Assuntos
Fibroínas , Aranhas , Animais , Fibroínas/química , Nanogéis , Seda/química , Água
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