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1.
Cancers (Basel) ; 16(16)2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-39199591

RESUMO

Hepatocellular carcinoma (HCC) has emerged as a major contributor to the worldwide cancer burden. Improved methods are needed for early cancer detection and image-guided surgery. Peptides have small dimensions that can overcome delivery challenges to achieve high tumor concentrations and deep penetration. We used phage display methods to biopan against the extra-cellular domain of the purified EpCAM protein, and used IRDye800 as a near-infrared (NIR) fluorophore. The 12-mer sequence HPDMFTRTHSHN was identified, and specific binding to EpCAM was validated with HCC cells in vitro. A binding affinity of kd = 67 nM and onset of k = 0.136 min-1 (7.35 min) were determined. Serum stability was measured with a half-life of T1/2 = 2.6 h. NIR fluorescence images showed peak uptake in vivo by human HCC patient-derived xenograft (PDX) tumors at 1.5 h post-injection. Also, the peptide was able to bind to foci of local and distant metastases in liver and lung. Peptide biodistribution showed high uptake in tumor versus other organs. No signs of acute toxicity were detected during animal necropsy. Immunofluorescence staining of human liver showed specific binding to HCC compared with cirrhosis, adenoma, and normal specimens.

2.
Oral Oncol ; 157: 106985, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39126750

RESUMO

BACKGROUND: Immune-related characteristics can serve as reliable prognostic biomarkers in various cancers. Herein, we aimed to construct an individualized immune prognostic signature in nasopharyngeal carcinoma (NPC). METHODS: This study retrospectively included 455 NPC samples and 39 normal healthy nasopharyngeal tissue specimens. Samples from Gene Expression Omnibus (GEO) were obtained as discovery cohort to screen candidate prognostic immune-related gene pairs based on relative expression ordering of the genes. Quantitative real-time reverse transcription-PCR was used to detect the selected genes to construct an immune-related gene pair signature in training cohort, which comprised 118 clinical samples, and was then validated in validation cohort 1, comprising 92 clinical samples, and validation cohort 2, comprising 88 samples from GEO. RESULTS: We identified 26 immune-related gene pairs as prognostic candidates in discovery cohort. A prognostic immune signature comprising 11 immune gene pairs was constructed in training cohort. In validation cohort 1, the immune signature could significantly distinguish patients with high or low risk in terms of progression-free survival (PFS) (hazard ratio [HR] 2.66, 95 % confidence interval (CI) 1.17-6.02, P=0.015) and could serve as an independent prognostic factor for PFS in multivariate analysis (HR 2.66, 95 % CI 1.17-6.02, P=0.019). Similar results were obtained using validation cohort 2, in which PFS was significantly worse in high risk group than in low risk group (HR 3.02, 95 % CI 1.12-8.18, P=0.022). CONCLUSIONS: The constructed immune signature showed promise for estimating prognosis in NPC. It has potential for translation into clinical practice after prospective validation.


Assuntos
Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/imunologia , Carcinoma Nasofaríngeo/mortalidade , Masculino , Feminino , Prognóstico , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/imunologia , Neoplasias Nasofaríngeas/patologia , Estudos Retrospectivos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Adulto , Idoso , Regulação Neoplásica da Expressão Gênica
3.
Int J Biol Macromol ; 273(Pt 1): 132931, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38942665

RESUMO

PCP-W1, the Poria cocos polysaccharide with the strong immunomodulatory activity, was isolated through column chromatography and screened for in vitro immune activity in RAW 264.7 cells in this study. The structure analysis results revealed that the PCP-W1 were composed of galactose, glucose, fucose and mannose in a molar percentage of 35.87: 28.56: 21.77: 13.64. And it exhibited a random coil and branched conformational features with a molecular weight of 18.38 kDa. The main chain consisted of residues→3)-ß-D-Glcp-(1 â†’ 3,6)-ß-D-Glcp-(1 â†’ 3)-ß-D-Glcp-(1 â†’ 6)-ß-D-Glcp-(1 â†’ 6)-α-D-Galp-(1 â†’ 6)-α-D-Galp-(1 â†’ 2,6)-α-D-Galp-(1→6)-α-D-Galp-(1 â†’ 6)-α-D-Galp-(1 â†’ , while branching occurred at ß-D-Glcp-(1→, α-D-Manp-(1→, and α-L-Fucp-(1 â†’ 3)- α-L-Fucp-(1→. The pharmacodynamic studies demonstrated that PCP-W1 activated the release of NO, IL-6, IL-ß, TNF-α, CD86, and ROS to induce polarization of RAW 264.7 murine macrophages towards M1-type through modulation of the TLR4/MD2/NF-κB pathway. The molecular docking results showed that PCP-W1 could primarily dock onto the hydrophobic binding site of TLR4/MD2 complex via its galactose chain. Furthermore, molecular dynamics simulation displayed stable modeling for TLR4-MD2-PCP-W1 complex. Overall, we screened the most immunoactive components of the polysaccharide, analyzed its structure, demonstrated its impact on TLR4/MD2/NF-kB pathway, and studied the interaction between TLR4/MD2 and the polysaccharide fragments. These results provide further support for the structure-activity relationship study of the immunomodulatory effects of Poria cocos polysaccharide.


Assuntos
NF-kappa B , Polissacarídeos , Transdução de Sinais , Receptor 4 Toll-Like , Wolfiporia , Animais , Camundongos , Receptor 4 Toll-Like/metabolismo , Células RAW 264.7 , NF-kappa B/metabolismo , Polissacarídeos/farmacologia , Polissacarídeos/química , Transdução de Sinais/efeitos dos fármacos , Wolfiporia/química , Antígeno 96 de Linfócito/metabolismo , Antígeno 96 de Linfócito/química , Fatores Imunológicos/farmacologia , Fatores Imunológicos/química , Simulação de Acoplamento Molecular
4.
BMJ Open ; 14(5): e083213, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38772884

RESUMO

BACKGROUND: Randomised controlled trials (RCTs) are the predominant type in acupuncture clinical research, and the publications have increased rapidly in recent years, but there is a prevalence of the high risk of bias and poor methodological design in acupuncture RCTs. Clinical trial registration can improve the transparency and credibility of studies by disclosing key information in advance. However, the registration in acupuncture RCTs is not satisfactory, as there is widespread of the under-registration, inconsistency with published studies and insufficient disclosure of key methodological information. Whether registration can reduce the risk of bias in acupuncture RCTs and improve data transparency has not been fully explored. Therefore, we constructed this study to investigate the association between registration and risk of bias and data sharing level in acupuncture RCTs. METHODS: Seven databases including MEDLINE, EMBASE, CENTRAL, CBM, CNKI, Wanfang and VIP databases will be systematically searched between 1 January 2014 and 31 March 2024, for acupuncture RCTs. Two reviewers will independently extract data using a predefined standardised format and perform secondary validation. The characteristics and data sharing level of the included studies will be summarised. The risk of bias of included RCTs will be assessed by the revised Cochrane risk-of-bias tool for randomised trials. The risk of bias and registration in acupuncture RCTs will be analysed by logistic or quantile regression analyses (depending on the number of minimum events). The data sharing level and registration will be analysed by quantile regression analyses. ETHICS AND DISSEMINATION: As the systematic review aims to consolidate info from published sources, ethical approval is not necessary for this study. The study's findings will be submitted to a peer-reviewed academic journal and disseminated via conference presentations. This protocol has been registered in Open Science Framework Registries.


Assuntos
Terapia por Acupuntura , Viés , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto , Humanos , Terapia por Acupuntura/métodos , Projetos de Pesquisa , Sistema de Registros
5.
Environ Res ; 252(Pt 4): 119135, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38740291

RESUMO

Cyhalofop-butyl (CB) poses a significant threat to aquatic organisms, but there is a discrepancy in evidence about hepatotoxicity after prolonged exposure to environmental levels. The aim of this study was to investigate long-term hepatotoxicity and its effects on the gut-liver axis through the exposure of zebrafish to environmental concentrations of CB (0.1,1,10 µg/L) throughout their life cycle. Zebrafish experienced abnormal obesity symptoms and organ index after a prolonged exposure of 120 days. The gut-liver axis was found to be damaged both morphologically and functionally through an analysis of histology, electron microscopy subcellular structure, and liver function. The disruption of the gut-liver axis inflammatory process by CB is suggested by the rise in inflammatory factors and the alteration of inflammatory genes. Furthermore, there was a noticeable alteration in the blood and gut-liver axis biochemical parameters as well as gene expression linked to lipid metabolism, which may led to an imbalance in the gut flora. In conclusion, the connection between the gut-liver axis, intestinal microbiota, and liver leads to the metabolic dysfunction of zebrafish exposed to long-term ambient concentrations of CB, and damaged immune system and liver lipid metabolism. This study gives another knowledge into the hepatotoxicity component of long haul openness to ecological centralization of CB, and might be useful to assess the potential natural and wellbeing dangers of aryloxyphenoxypropionate herbicides.


Assuntos
Fígado , Poluentes Químicos da Água , Peixe-Zebra , Animais , Fígado/efeitos dos fármacos , Fígado/patologia , Poluentes Químicos da Água/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/patologia , Microbioma Gastrointestinal/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos
6.
J Gen Virol ; 105(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38814698

RESUMO

Transmissible gastroenteritis virus (TGEV), an enteropathogenic coronavirus, has caused huge economic losses to the pig industry, with 100% mortality in piglets aged 2 weeks and intestinal injury in pigs of other ages. However, there is still a shortage of safe and effective anti-TGEV drugs in clinics. In this study, phloretin, a naturally occurring dihydrochalcone glycoside, was identified as a potent antagonist of TGEV. Specifically, we found phloretin effectively inhibited TGEV proliferation in PK-15 cells, dose-dependently reducing the expression of TGEV N protein, mRNA, and virus titer. The anti-TGEV activity of phloretin was furthermore refined to target the internalization and replication stages. Moreover, we also found that phloretin could decrease the expression levels of proinflammatory cytokines induced by TGEV infection. In addition, we expanded the potential key targets associated with the anti-TGEV effect of phloretin to AR, CDK2, INS, ESR1, ESR2, EGFR, PGR, PPARG, PRKACA, and MAPK14 with the help of network pharmacology and molecular docking techniques. Furthermore, resistant viruses have been selected by culturing TGEV with increasing concentrations of phloretin. Resistance mutations were reproducibly mapped to the residue (S242) of main protease (Mpro). Molecular docking analysis showed that the mutation (S242F) significantly disrupted phloretin binding to Mpro, suggesting Mpro might be a potent target of phloretin. In summary, our findings indicate that phloretin is a promising drug candidate for combating TGEV, which may be helpful for developing pharmacotherapies for TGEV and other coronavirus infections.


Assuntos
Antivirais , Simulação de Acoplamento Molecular , Floretina , Vírus da Gastroenterite Transmissível , Replicação Viral , Vírus da Gastroenterite Transmissível/efeitos dos fármacos , Animais , Suínos , Floretina/farmacologia , Replicação Viral/efeitos dos fármacos , Linhagem Celular , Antivirais/farmacologia , Gastroenterite Suína Transmissível/tratamento farmacológico , Gastroenterite Suína Transmissível/virologia , Citocinas/metabolismo , Citocinas/genética , Internalização do Vírus/efeitos dos fármacos
7.
Chempluschem ; 89(6): e202400047, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38517224

RESUMO

The carboxyl-terminal (C-terminal) S-[(Z)-2-aminovinyl]-cysteine (AviCys) analogs have been identified in four families of ribosomally synthesized and post-translationally modified peptides (RiPPs): lanthipeptides, linaridins, thioamitides, and lipolanthines. Within identified biosynthetic pathways, a highly reactive enethiol intermediate, formed through an oxidative decarboxylation catalyzed by a LanD-like flavoprotein, can undergo two types of cyclization: a Michael addition with a dehydroamino acid or a coupling reaction initiated by a radical species. The collaborative actions of LanD-like proteins with diverse enzymes involved in dehydration, dethiolation or cyclization lead to the construction of structurally distinct peptide natural products with analogous C-terminal macrocyclic moieties. This concept summarizes existing knowledge regarding biosynthetic pathways of AviCys analogs to emphasize the diversity of biosynthetic mechanisms that paves the way for future genome mining explorations into diverse peptide natural products.


Assuntos
Produtos Biológicos , Cisteína , Peptídeos , Ribossomos , Produtos Biológicos/química , Produtos Biológicos/metabolismo , Cisteína/química , Cisteína/metabolismo , Peptídeos/química , Peptídeos/metabolismo , Ribossomos/metabolismo , Ribossomos/química , Processamento de Proteína Pós-Traducional
8.
Front Public Health ; 12: 1305303, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38327568

RESUMO

The use of human aging markers, which are physiological, biochemical and molecular indicators of structural or functional degeneration associated with aging, is the fundamental basis of individualized aging assessments. Identifying methods for selecting markers has become a primary and vital aspect of aging research. However, there is no clear consensus or uniform principle on the criteria for screening aging markers. Therefore, we combine previous research from our center and summarize the criteria for screening aging markers in previous population studies, which are discussed in three aspects: functional perspective, operational implementation perspective and methodological perspective. Finally, an evaluation framework has been established, and the criteria are categorized into three levels based on their importance, which can help assess the extent to which a candidate biomarker may be feasible, valid, and useful for a specific use context.


Assuntos
Envelhecimento , Projetos de Pesquisa , Humanos , Envelhecimento/fisiologia , Biomarcadores
9.
BMJ Open ; 14(2): e079218, 2024 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326262

RESUMO

INTRODUCTION: Patient-reported outcomes (PROs) are health reports that come directly from the patients themselves and represented the experience and insights of the patient's perspective on the impact of the intervention. PROs were increasingly emphasised in acupuncture randomised controlled trials (RCTs). However, the reporting quality of PROs in acupuncture RCTs has not been investigated to date. Therefore, we constructed this study to reveal the basic characteristics and reporting quality of PROs in acupuncture RCTs, and explore the relationship between concealment, blinding and RROs. We hope our findings can provide guidance for the reporting standards and future development of PROs in acupuncture RCTs in reverse. METHODS AND ANALYSIS: RCTs using acupuncture treatment as the intervention and PROs as primary outcomes or secondary outcomes will be systematically searched through seven databases MEDLINE, EMBASE, CENTRAL, CBM, CNKI, Wanfang and VIP between 1 January 2012 and 15 October 2022. The basic characteristics, concealment, blinding design and the characteristics of PROs in included RCTs will be summarised. The reporting quality of PROs will be assessed based on the CONSORT PRO extension. Logistic analysis will be performed to identify the association between concealment, blinding and RROs. ETHICS AND DISSEMINATION: Ethical approval is not required for this study. This protocol has been registered in Open Science Framework (OSF) Registries. The findings of this study will be submitted to a peer-reviewed academic journal.


Assuntos
Terapia por Acupuntura , Humanos , Estudos Transversais , Terapia por Acupuntura/métodos , Padrões de Referência , Medidas de Resultados Relatados pelo Paciente , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto
10.
Sleep Breath ; 28(1): 133-149, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37428351

RESUMO

PURPOSE: This study evaluated the effects of chronic intermittent hypoxia (CIH) at different times on the mitochondria of mouse hearts and H9C2 cardiomyocytes to determine the role of the cannabinoid receptor 1 (CB1R)/adenosine 5'-monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) signaling pathway. METHODS: Animal and cellular CIH models were prepared in an intermittent hypoxia chamber at different times. The cardiac function of mice was determined, and heart tissue and ultrastructural changes were observed. Apoptosis, reactive oxygen species (ROS), and mitochondrial membrane potential were detected, and MitoTracker™ staining was performed to observe cardiomyocyte mitochondria. Western blot, immunohistochemistry, and cellular immunofluorescence were also performed. RESULTS: In the short-term CIH group, increases in mouse ejection fraction (EF) and heart rate (HR); mitochondrial division; ROS and mitochondrial membrane potential; and the expression levels of CB1R, AMPK, and PGC-1α were observed in vivo and in vitro. In the long-term CIH group, the EF and HR increased, the myocardial injury and mitochondrial damage were more severe, mitochondrial synthesis decreased, the apoptosis percentage and ROS increased, mitochondrial fragmentation increased, membrane potential decreased, CB1R expression increased, and AMPK and PGC-1α expression levels decreased. Targeted blocking of CB1R can increase AMPK and PGC-1α, reduce damage attributed to long-term CIH in mouse hearts and H9C2 cells, and promote mitochondrial synthesis. CONCLUSION: Short-term CIH can directly activate the AMPK/PGC-1α pathway, promote mitochondrial synthesis in cardiomyocytes, and protect cardiac structure and function. Long-term CIH can increase CB1R expression and inhibit the AMPK/PGC-1α pathway, resulting in structural damage, the disturbance of myocardial mitochondria synthesis, and further alterations in the cardiac structure. After targeted blocking of CB1R, levels of AMPK and PGC-1α increased, alleviating damage to the heart and cardiomyocytes caused by long-term CIH.


Assuntos
Proteínas Quinases Ativadas por AMP , Miócitos Cardíacos , Camundongos , Animais , Miócitos Cardíacos/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Mitocôndrias/metabolismo , Transdução de Sinais , Hipóxia/metabolismo
11.
Cancers (Basel) ; 15(19)2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37835489

RESUMO

Colorectal cancer is a leading cause of cancer-related morbidity and mortality worldwide. Premalignant lesions that are flat and subtle in morphology are often missed in conventional colonoscopies. Patient-derived adenoma colonoids with high and low cMet expression and normal colonoids were implanted orthotopically in the colon of immunocompromised mice to serve as a preclinical model system. A peptide specific for cMet was labeled with IRDye800, a near-infrared (NIR) fluorophore. This peptide was administered intravenously, and in vivo imaging was performed using a small animal fluorescence endoscope. Quantified intensities showed a peak target-to-background ratio at ~1 h after intravenous peptide injection, and the signal cleared by ~24 h. The peptide was stable in serum with a half-life of 3.6 h. Co-staining of adenoma and normal colonoids showed a high correlation between peptide and anti-cMet antibody. A human-specific cytokeratin stain verified the presence of human tissues implanted among surrounding normal mouse colonic mucosa. Peptide biodistribution was consistent with rapid renal clearance. No signs of acute toxicity were found on either animal necropsy or serum hematology and chemistries. Human colonoids provide a clinically relevant preclinical model to evaluate the specific uptake of a NIR peptide to detect premalignant colonic lesions in vivo.

12.
Angew Chem Int Ed Engl ; 62(35): e202308733, 2023 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-37431841

RESUMO

LanD flavoproteins catalyze oxidative decarboxylation of the C-terminal Cys residue of a peptide to produce an enethiol. This enethiol is highly reactive and can be coupled with an upstream dehydroamino acid through Michael addition to form S-[2-aminovinyl](3-methyl)cysteine, an unsaturated thioether residue known to be characteristic of an array of C-terminally macrocyclized, ribosomally synthesized and posttranslationally modified peptides (RiPPs). Based on a two-stage bioinformatics mining of posttranslational modifications (PTMs) related to C-terminal Cys processing, we report herein that LanD activity can couple with radical S-adenosylmethionine chemistry to provide a new unsaturated thioether residue, S-[2-aminovinyl]-3-carbamoylcysteine, by conjugating the resultant enethiol with Cß of the Asn residue in the C-terminal NxxC motif of a peptide for macrocyclization. This study furthers our understanding of the variety of PTMs involved in creating the structure diversity of macrocyclic RiPPs.


Assuntos
Flavoproteínas , Sulfetos , Sequência de Aminoácidos , Sulfetos/química , Flavoproteínas/metabolismo , Peptídeos/química , Oxirredução , Processamento de Proteína Pós-Traducional
13.
Int J Biol Macromol ; 249: 125953, 2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37517750

RESUMO

The function of the intestinal tract is critical to human health. Poria cocos is a widely used functional edible fungus in Asia and has been reported to modulate gastrointestinal function. However, the effects of polysaccharides, the main active constituents of Poria cocos, on the intestinal tract remains unclear and is the focus of the study. Poria cocos polysaccharides (PCP) were extracted, characterized, and administered to mice by gavage. The results show that PCP used in this study has a typical polysaccharide peak with a molecular weight of 11.583 kDa and is composed primarily of mannose, D-glucosamine hydrochloride, glucose, galactose, and fucose with a molar ratio of 15.308: 0.967: 28.723: 31.631: 23.371. The methylation results suggest that the PCP backbone may be t-Gal(p), 6-Gal(p) and 2,6-Gal(p). The effects of PCP on the mucosal barrier function of the mouse intestine (duodenum, jejunum, and ileum) were examined in terms of intestinal physiological status, physical barrier, biochemical barrier, immune barrier, and microbial barrier. The results showed that PCP significantly improved the physiological state of mouse intestine. Moreover, PCP strengthened the intestinal physical barrier by upregulating the expression of intestinal Occludin and ZO-1 and downregulating the levels of serum endotoxin, DAO, D-lactate, and intestinal MPO. Regarding biochemical barrier, PCP could upregulate the expression of MUC2, ß-defensin, and SIgA in intestinal tissues. In addition, PCP modulated the immune barrier by increasing IL-2, IL-4, IL-6, IL-10, TGF-ß, and IFN-γ expression. Besides, PCP increased the level of SCFAs in small intestinal contents. PCP modulates intestinal barrier function by altering the microbial composition of the gut. We also found that PCP could maintain intestinal barrier function by increasing the expression of Wnt/ß-Catenin and Lrp5 proteins. Generally, our findings suggested that PCP may be used as a functional food to regulate intestinal mucosal function, thereby enhancing the health of the intestinal and host.


Assuntos
Poria , Wolfiporia , Humanos , Animais , Camundongos , Wolfiporia/química , Polissacarídeos/farmacologia , Polissacarídeos/química , Antioxidantes/farmacologia , Poria/química
14.
BMJ Open ; 13(6): e070545, 2023 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-37344108

RESUMO

INTRODUCTION: Randomised controlled trials (RCTs) play an important role in evidence-based medicine. However, an article with low reporting quality may mislead both experts and the general public into an erroneous decision. Data sharing can contribute to the truthfulness and transparency of trials. Acupuncture RCTs have been increasing rapidly these years, but the reporting quality and data-sharing level of acupuncture RCTs are not clear. Thus, this study will provide the current status of the reporting quality and data-sharing level of acupuncture RCTs. METHODS AND ANALYSIS: A cross-sectional study will be conducted. The seven databases including MEDLINE, EMBASE, CENTRAL, CBM, CNKI, Wanfang Database and VIP will be searched between 1 January 2012 and 15 October 2022 to identify acupuncture RCTs. The basic characteristics of included trials will be summarised. The reporting quality for included RCTs will be assessed by the Consolidated Standards for Reporting Trials 2010 statement and the Standards for Reporting Interventions in Controlled Trials of Acupuncture. The data-sharing level will be assessed by open science practices. ETHICS AND DISSEMINATION: Ethical approval is not required for this study. This protocol has been registered in Open Science Framework Registries. The findings of this study will be submitted to a peer-reviewed academic journal.


Assuntos
Terapia por Acupuntura , Humanos , Estudos Transversais , MEDLINE , Bases de Dados Factuais , Padrões de Referência , Projetos de Pesquisa , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Front Public Health ; 11: 1074274, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37124811

RESUMO

Biological age (BA) is a common model to evaluate the function of aging individuals as it may provide a more accurate measure of the extent of human aging than chronological age (CA). Biological age is influenced by the used biomarkers and standards in selected aging biomarkers and the statistical method to construct BA. Traditional used BA estimation approaches include multiple linear regression (MLR), principal component analysis (PCA), Klemera and Doubal's method (KDM), and, in recent years, deep learning methods. This review summarizes the markers for each organ/system used to construct biological age and published literature using methods in BA research. Future research needs to explore the new aging markers and the standard in select markers and new methods in building BA models.


Assuntos
Envelhecimento , Modelos Biológicos , Humanos , Modelos Lineares , Biomarcadores , Análise Multivariada
16.
Ann Transl Med ; 11(8): 299, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37181344

RESUMO

Background: Tourette syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics. Recurrent respiratory tract infection (RRTI), a commonly occurring disease in childhood, correlates with recurrent and severe course of tic symptoms. Qiangzhi decoction (QZD) is a traditional Chinese medicine that can alleviate TS symptoms while reducing the recurrence of RRTI. However, the mechanism of QZD on TS and RRTI remains unclear. This study aimed to determine the treatment effect of QZD on comorbid TS and RRTI by integrating ultrahigh-performance liquid chromatography mass spectrometry (UPLC-MS), network pharmacology, and intestinal flora analysis. Methods: The components of QZD were first identified by UPLC-quadrupole (Q)-orbitrap-MS/MS. The mechanism of QZD on comorbid RRTI and TS was investigated by a series of network pharmacological methods, including target prediction and bioinformatics analysis. Finally, a comorbid TS and RRTI rat model was established by intraperitoneal injection of 3,3-iminodipropionitrile (IDPN), cyclophosphamide (CTX), and lipopolysaccharide (LPS). Alteration of gut microbiota in the alleviation of TS and RRTI by QZD was investigated via intestinal flora analysis. Results: The results of UPLC-Q-orbitrap-MS/MS showed that QZD had 96 types of chemical components. The network pharmacology results demonstrated that targets of QZD involved in the treatment of TS and RRTI involved 1045 biological processes (BPs), 109 cellular components (CCs), and 133 molecular functions (MFs), including synaptic and transsynaptic signaling, chemical synaptic transmission, neurotransmitter receptor activity, G protein-coupled amine receptor activity, and serotonin receptor activity, among others. Firmicutes, Bacteroidetes, Coprococcus, and Lachnospiraceae played crucial roles in gut microbiota of a QZD-treated comorbid TS and RRTI model. Conclusions: Our results revealed QZD provided a multicomponent, multitarget, and multipathway synergistic treatment of comorbid TS and RRTI.

17.
Artigo em Inglês | MEDLINE | ID: mdl-37065634

RESUMO

Purpose: Screening questionnaires can help identify individuals at a high risk of COPD. This study aimed to compare the performance of the COPD population screener (COPD-PS) and COPD screening questionnaire (COPD-SQ) on the general population as a full cohort and stratified by urbanization. Methods: We recruited subjects who underwent a health checkup at urban and rural community health centers in Beijing. All eligible subjects completed the COPD-PS and COPD-SQ, then spirometry. Spirometry-defined COPD was defined as a post-bronchodilator FEV1/FVC<70%. Symptomatic COPD was defined as a post-bronchodilator FEV1/FVC<70% and respiratory symptoms. Receiver operating characteristic (ROC) curve analysis compared the discriminatory power of the two questionnaires, and stratified by urbanization. Results: We identified 129 spirometry-defined and 92 symptomatic COPD cases out of 1350 enrolled subjects. The optimal cut-off score for the COPD-PS was 4 for spirometry-defined and 5 for symptomatic COPD. The optimum cut-off score for the COPD-SQ was 15 for both spirometry-defined and symptomatic COPD. The COPD-PS and COPD-SQ had similar AUC values for spirometry-defined (0.672 vs 0.702) and symptomatic COPD (0.734 vs 0.779). The AUC of the COPD-SQ tended to be higher in rural areas than that of the COPD-PS for spirometry-defined COPD (0.700 vs 0.653, P = 0.093). Conclusion: The COPD-PS and COPD-SQ had comparable discriminatory power for detecting COPD in the general population while the COPD-SQ performed better in rural areas. A pilot study for validating and comparing the diagnostic accuracy of different questionnaires is required when screening for COPD in a new environment.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Inquéritos e Questionários , Humanos , Broncodilatadores , População do Leste Asiático , Volume Expiratório Forçado , Programas de Rastreamento , Projetos Piloto , Valor Preditivo dos Testes , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Espirometria
18.
Heliyon ; 9(1): e12819, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36647359

RESUMO

As a new natural antioxidant with high safety and non-toxic side effects, polysaccharide can also be used as a critical macromolecular carrier to form a stable iron complex with Fe3+. Our previous study has extracted and purified the homogeneous polysaccharide (PCP1C) from Poria cocos. In this study, the PCP1C-iron (III) complex was synthesized by co-thermal synthesis with PCP1C and ferric trichloride. The chelating capacity, iron releasing capacity, and qualitative identification of complex were evaluated. The complex was characterized by scanning electron microscope-energy dispersive spectrometer (SEM-EDS) analysis, particle size distribution, and fourier transform infrared (FTIR) spectroscopy. The antioxidant and iron supplement effects of the complex were also studied in vitro and in the iron deficiency anemia (IDA) rat model. The results showed that the iron content in the PCP1C-iron (III) complex was 28.14% with no free iron, and the iron release rate was 95.3%. The structure analysis showed that the iron core of the PCP1C-iron (III) complex existed in the form of ß-FeOOH and the surface of the complex become smooth and particle size increased, which indicated the high iron content of polysaccharide iron and slow release. Furthermore, we found that the PCP1C iron (III) complex had positive scavenging effect on DPPH, ABTS, MDA, and hydroxyl radical in vitro study and significantly increased the levels of red blood cell (RBC), Hemoglobin (Hb), and red blood cell specific volume (HCT) in IDA rat model. Therefore, our results suggested that the PCP1C-iron (III) complex is expected to develop into a new comprehensive iron supplement and antioxidant.

19.
BMC Med Res Methodol ; 23(1): 20, 2023 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-36670375

RESUMO

BACKGROUND: Reporting quality is a critical issue in health sciences. Adopting the reporting guidelines has been approved to be an effective way of enhancing the reporting quality and transparency of clinical research. In 2012, we found that only 7 (7/1221, 0.6%) journals adopted the Consolidated Standards of Reporting Trials (CONSORT) statement in China. The aim of the study was to know the implementation status of CONSORT and other reporting guidelines about clinical studies in China. METHODS: A cross-sectional bibliometric study was conducted. Eight medical databases were systematically searched, and 1039 medical journals published in mainland China, Hong Kong, Macau, and Taiwan were included. The basic characteristics, including subject, language, publication place, journal-indexed databases, and journal impact factors were extracted. The endorsement of reporting guidelines was assessed by a modified 5-level evaluation tool, namely i) positive active, ii) positive weak, iii) passive moderate, iv) passive weak and v) none. RESULTS: Among included journals, 24.1% endorsed CONSORT, and 0.8% endorsed CONSORT extensions. For STROBE (STrengthening the Reporting of Observational Studies in Epidemiology), PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), STARD (An Updated List of Essential Items for Reporting Diagnostic Accuracy Studies), CARE (CAse REport guidelines), the endorsement proportion were 17.2, 16.6, 16.4, and 14.8% respectively. The endorsement proportion for SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials), TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis), AGREE (Appraisal of Guidelines, Research, and Evaluation), and RIGHT (Reporting Items for Practice Guidelines in Healthcare) were below 0.7%. CONCLUSIONS: Our results showed that the implementation of reporting guidelines was low. We suggest the following initiatives including i) enhancing the level of journal endorsement for reporting guidelines; ii) strengthening the collaboration among authors, reviewers, editors, and other stakeholders; iii) providing training courses for stakeholders; iv) establishing bases for reporting guidelines network in China; v) adopting the endorsement of reporting guidelines in the policies of the China Periodicals Association (CPA); vi) promoting Chinese medical journals into the international evaluation system and publish in English.


Assuntos
Publicações Periódicas como Assunto , China , Estudos Transversais , Padrões de Referência
20.
Arch Gerontol Geriatr ; 107: 104905, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36542874

RESUMO

BACKGROUND: Biological age (BA) may reflect the actual aging state in humans better than chronological age (CA). The study aimed to construct BA models suitable for the Chinese Han population by selecting appropriate aging markers and evaluation methods. METHODS: A total of 1207 individuals (21∼91 years) from the Han Chinese population in Beijing were examined for essential organ functions, and 156 cardiovascular, pulmonary function, and atherosclerotic indices and clinical and genetic factors were used as candidate markers of aging. BA models were constructed using multiple linear regression (MLR), principal component analysis (PCA), and the Klemera and Doubal method (KDM). Models were internally and externally validated using cross-validation and disease populations. RESULTS: Nine aging markers were selected. Two MLR, three PCA, and three KDM models were successfully constructed. External validation showed that the difference between CA and BA was most significant in the PCA3 and KDM2 models, while there was no significant difference in the MLR1 and MLR2 models; the fitted lines for BA in the disease population were higher than those in the healthy population in the MLR1, MLR2, KDM1, and KDM2 models, while the other models showed the opposite. CONCLUSIONS: Based on a healthy population in Beijing, nine markers representing multiple organ/system functions were screened from the candidate markers, eight methods were successfully used to construct BA models, and the KDM2 model was found to potentially be more appropriate for assessing BA in the Chinese Han population.


Assuntos
Envelhecimento , População do Leste Asiático , Humanos , Modelos Lineares , Pressão Sanguínea , Análise Multivariada , Modelos Biológicos
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