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1.
J Cell Mol Med ; 28(4): e18123, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38353470

RESUMO

Blood vessels are essential for bone development and metabolism. Type H vessels in bone, named after their high expression of CD31 and Endomucin (Emcn), have recently been reported to locate mainly in the metaphysis, exhibit different molecular properties and couple osteogenesis and angiogenesis. A strong correlation between type H vessels and bone metabolism is now well-recognized. The crosstalk between type H vessels and osteoprogenitor cells is also involved in bone metabolism-related diseases such as osteoporosis, osteoarthritis, fracture healing and bone defects. Targeting the type H vessel formation may become a new approach for managing a variety of bone diseases. This review highlighted the roles of type H vessels in bone-related diseases and summarized the research attempts to develop targeted intervention, which will help us gain a better understanding of their potential value in clinical application.


Assuntos
Doenças Ósseas Metabólicas , Osteoporose , Humanos , Osteogênese/genética , Osso e Ossos/metabolismo , Osteoporose/metabolismo , Consolidação da Fratura , Neovascularização Fisiológica
2.
J Cell Mol Med ; 28(12): e18483, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39051629

RESUMO

The development of high-throughput technologies has enhanced our understanding of small non-coding RNAs (sncRNAs) and their crucial roles in various diseases, including atrial fibrillation (AF). This study aimed to systematically delineate sncRNA profiles in AF patients. PANDORA-sequencing was used to examine the sncRNA profiles of atrial appendage tissues from AF and non-AF patients. Differentially expressed sncRNAs were identified using the R package DEGseq 2 with a fold change >2 and p < 0.05. The target genes of the differentially expressed sncRNAs were predicted using MiRanda and RNAhybrid. Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. In AF patients, the most abundant sncRNAs were ribosomal RNA-derived small RNAs (rsRNAs), followed by transfer RNA-derived small RNAs (tsRNAs), and microRNAs (miRNAs). Compared with non-AF patients, 656 rsRNAs, 45 miRNAs, 191 tsRNAs and 51 small nucleolar RNAs (snoRNAs) were differentially expressed in AF patients, whereas no significantly differentially expressed piwi-interacting RNAs were identified. Two out of three tsRNAs were confirmed to be upregulated in AF patients by quantitative reverse transcriptase polymerase chain reaction, and higher plasma levels of tsRNA 5006c-LysCTT were associated with a 2.55-fold increased risk of all-cause death in AF patients (hazard ratio: 2.55; 95% confidence interval, 1.56-4.17; p < 0.001). Combined with our previous transcriptome sequencing results, 32 miRNA, 31 snoRNA, 110 nucleus-encoded tsRNA, and 33 mitochondria-encoded tsRNA target genes were dysregulated in AF patients. GO and KEGG analyses revealed enrichment of differentially expressed sncRNA target genes in AF-related pathways, including the 'calcium signaling pathway' and 'adrenergic signaling in cardiomyocytes.' The dysregulated sncRNA profiles in AF patients suggest their potential regulatory roles in AF pathogenesis. Further research is needed to investigate the specific mechanisms of sncRNAs in the development of AF and to explore potential biomarkers for AF treatment and prognosis.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Perfilação da Expressão Gênica , Pequeno RNA não Traduzido , Humanos , Fibrilação Atrial/genética , Pequeno RNA não Traduzido/genética , Apêndice Atrial/metabolismo , Masculino , Feminino , MicroRNAs/genética , Ontologia Genética , Idoso , Pessoa de Meia-Idade , RNA Nucleolar Pequeno/genética , RNA Nucleolar Pequeno/metabolismo , Regulação da Expressão Gênica , Transcriptoma/genética , Biologia Computacional/métodos , Prognóstico
3.
Artigo em Inglês | MEDLINE | ID: mdl-38695865

RESUMO

A novel Gram-staining-positive actinobacterium with antimicrobial activity, designated CFH 90308T, was isolated from the sediment of a salt lake in Yuncheng, Shanxi, south-western China. The isolate exhibited the highest 16S rRNA gene sequence similarities to Microbacterium yannicii G72T, Microbacterium hominis NBRC 15708T and Microbacterium xylanilyticum S3-ET (98.5, 98.4 and 98.2 %, respectively), and formed a separate clade with M. xylanilyticum S3-ET in phylogenetic trees. The strain grew at 15-40 ºC, pH 6.0-8.0 and could tolerate NaCl up to a concentration of 15 % (w/v). The whole genome of strain CFH 90308T consisted of 4.33 Mbp and the DNA G+C content was 69.6 mol%. The acyl type of the peptidoglycan was glycolyl and the whole-cell sugars were galactose and mannose. The cell-wall peptidoglycan mainly contained alanine, glycine and lysine. The menaquinones of strain CFH 90308T were MK-12, MK-13 and MK-11. Strain CFH 90308T contained anteiso-C15:0, anteiso-C17:0, iso-C16:0 and iso-C15:0 as the predominant fatty acids. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between CFH 90308T and the other species of the genus Microbacterium were found to be low (ANIb <81.3 %, dDDH <25.6 %). The secondary metabolite produced by strain CFH 90308T showed antibacterial activities against Bacillus subtilis, Pseudomonas syringae, Aeromonas hydrophila and methicillin-resistant Staphylococcus aureus. Based on genotypic, phenotypic and chemotaxonomic results, the isolate is considered to represent a novel species of the genus Microbacterium, for which the name Microbacterium salsuginis sp. nov. is proposed. The type strain is CFH 90308T (=DSM 105964T=KCTC 49052T).


Assuntos
Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Sedimentos Geológicos , Microbacterium , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Vitamina K 2 , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , China , Vitamina K 2/análogos & derivados , Sedimentos Geológicos/microbiologia , Peptidoglicano , Lagos/microbiologia , Hibridização de Ácido Nucleico , Cloreto de Sódio/metabolismo , Genoma Bacteriano
4.
Exp Cell Res ; 433(2): 113854, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-37952573

RESUMO

Osteoarthritis (OA) is a common musculoskeletal disorder that impairs function and reduces the quality of life. Extracellular matrix (ECM) degradation and inflammatory mechanisms are crucial to the progression of OA. In this study, we aimed to investigate the anti-inflammatory activity, anti-ECM degradation property, and glucose transport capacity of quercitrin (QCT) on IL-1ß-treated rat primary chondrocytes. Rat primary chondrocytes were treated with IL-1ß to simulate inflammatory environmental conditions and OA in vitro. We examined the effects of QCT at concentrations ranging from 0 to 200 µM on the viability of rat chondrocytes and selected 5 µM for further study. Using qRT-PCR, immunofluorescent, immunocytochemistry, and western blotting techniques, we identified the potential molecular mechanisms and signaling pathways that are responsible for these effects. We established an OA rat model through anterior cruciate ligament transection (ACLT). The animals were then periodically injected with QCT into the knee articular cavity. Our in vivo and in vitro study showed that QCT could inhibit IL-1ß-activated inflammation and ECM degradation in chondrocyte. Furthermore, QCT could inhibit the NF-κB signal pathway and enhance glucose transport capacity in the IL-1ß-stimulated chondrocytes. In vivo study proved that QCT attenuates OA progression in rats. Overall, QCT inhibited the activation of NF-κB and enhanced glucose transport capacity to alleviate the progression of OA.


Assuntos
NF-kappa B , Osteoartrite , Ratos , Animais , NF-kappa B/metabolismo , Qualidade de Vida , Células Cultivadas , Transdução de Sinais , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Inflamação/metabolismo , Condrócitos/metabolismo , Glucose/farmacologia , Interleucina-1beta/farmacologia , Interleucina-1beta/metabolismo
5.
Dig Dis Sci ; 69(10): 3753-3759, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39261383

RESUMO

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory condition affecting the colon, with a global incidence that is rising. Despite the increasing prevalence, effective treatment options for UC remain limited. METHODS: We utilized an NF-κB promoter dual fluorescence reporter system to screen for compounds that could inhibit p65 and IκBα phosphorylation. The anti-hypertension drug lacidipine was identified as a candidate. Its efficacy was further evaluated in a murine model of dextran sulfate sodium (DSS)-induced colitis. The analysis included the assessment of colon lesions, inflammation markers, and signal pathway activation, with a focus on NF-κB and Notch signaling. RESULTS: Lacidipine effectively inhibited p65 and IκBα phosphorylation in the reporter system. In the DSS-induced colitis murine model, lacidipine treatment led to a reduction in colon lesions and inflammatory markers. Target analysis showed significant enrichment of the Notch signaling pathway. Additionally, lacidipine inhibited both NF-κB and Notch activation in DSS-stimulated colons. CONCLUSION: Lacidipine demonstrated a protective effect in UC, reducing inflammation and modulating key signaling pathways. These findings suggest that lacidipine could be a promising candidate for the treatment of UC.


Assuntos
Sulfato de Dextrana , Di-Hidropiridinas , NF-kappa B , Receptores Notch , Transdução de Sinais , Animais , Di-Hidropiridinas/farmacologia , Di-Hidropiridinas/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , NF-kappa B/metabolismo , Camundongos , Receptores Notch/metabolismo , Receptores Notch/genética , Receptores Notch/antagonistas & inibidores , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Masculino , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colite/patologia , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Fosforilação/efeitos dos fármacos , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia
6.
Angew Chem Int Ed Engl ; 63(25): e202318991, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38252658

RESUMO

ß-Tertiary amino acid derivatives constitute one of the most frequently occurring units in natural products and bioactive molecules. However, the efficient asymmetric synthesis of this motif still remains a significant challenge. Herein, we disclose a cobalt-catalyzed enantioselective reductive addition reaction of ketimine using α-chloro carbonyl compound as a radical precursor, providing expedient access to a diverse array of enantioenriched ß-quaternary amino acid analogues. This protocol exhibits outstanding enantioselectivity and broad substrate scope with excellent functional group tolerance. Preliminary mechanism studies rule out the possibility of Reformatsky-type addition and confirm the involvement of radical species in stereoselective addition process. The synthetic utility has been demonstrated through the rapid assembly of iterative amino acid units and oligopeptide, showcasing its versatile platform for late-stage modification of drug candidates.

7.
Angew Chem Int Ed Engl ; 63(7): e202316012, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38164694

RESUMO

Chromium-catalyzed enantioselective Nozaki-Hiyama-Kishi (NHK) reaction represents one of the most powerful approaches for the formation of chiral carbon-heteroatom bond. However, the construction of sterically encumbered tetrasubstituted stereocenter through NHK reaction still posts a significant challenge. Herein, we disclose a cobalt-catalyzed aza-NHK reaction of ketimine with alkenyl halide to provide a convenient synthetic approach for the manufacture of enantioenriched tetrasubstituted α-vinylic amino acid. This protocol exhibits excellent functional group tolerance with excellent 99 % ee in most cases. Additionally, this asymmetric reductive method is also applicable to the aldimine to access the trisubstituted stereogenic centers.

8.
Biochem Biophys Res Commun ; 640: 164-172, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36512848

RESUMO

Osteoarthritis (OA) places a significant burden on society and finance, and there is presently no effective treatment beside late replacement surgery and symptomatic relief. The therapy of OA requires additional research. Gardenoside is a naturally compound extracted from Gardenia jasminoides Ellis, which has a variety of anti-inflammatory effects. However, few studies have been conducted to determine the role of gardenoside in OA. This study aimed to explore whether gardenoside has effect in OA treatment. Rat primary chondrocytes were treated with IL-1ß to simulate inflammatory environmental conditions and OA in vitro. We examined the effects of gardenoside at concentrations ranging from 0 to 200 µM on the viability of rat chondrocytes and selected 10 µM for further study. Via in vitro experiments, our study found that gardenoside lowers the gene expression of COX-2, iNOS, IL-6, and reduced the ROS production of chondrocytes induced by IL-1ß. Moreover, it effectively alleviates ECM degradation caused by IL-1ß and promotes the ECM synthesis in chondrocytes by upregulating collagen-II and the ACAN expression, downregulating the expression of MMP-3, MMP-13, and ADAMTS-5 expression. Further, our study showed that gardenoside inhibits NF-κB signaling pathway activated by IL-1ß in chondrocytes. We established an OA rat model by anterior cruciate ligament transection (ACLT). The animals were then periodically injected with gardenoside into the knee articular cavity. In vivo study suggested that gardenoside attenuates OA progression in rats. As a whole, in vitro and in vivo results highlight gardenoside is a promising OA treatment agent.


Assuntos
Matriz Extracelular , Iridoides , NF-kappa B , Osteoartrite , Animais , Ratos , Células Cultivadas , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Inflamação/tratamento farmacológico , Interleucina-1beta/metabolismo , Iridoides/farmacologia , Iridoides/uso terapêutico , NF-kappa B/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Transdução de Sinais , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo
9.
Small ; 19(40): e2302799, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37264755

RESUMO

Effective treatments for cartilage defects are currently lacking. Gene delivery using proper delivery systems has shown great potential in cartilage regeneration. However, the inflammatory microenvironment generated by the defected cartilage severely affects the system's delivery efficiency. Therefore, this study reports a silk fibroin microcapsule (SFM) structure based on layer-by-layer self-assembly, in which interleukin-4 (IL-4) is modified on silk by click chemistry and loaded with lysyl oxidase plasmid DNA (LOX pDNA). The silk microcapsules display good biocompatibility and the release rate of genes can be adjusted by controlling the number of self-assembled layers. Moreover, the functionalized SFMs mixed with methacrylated gelatin (GelMA) exhibit good injectability. The IL-4 on the outer layer of the SFM can regulate macrophages to polarize toward the M2 type, thereby promoting cartilage matrix repair and inhibiting inflammation. The LOX pDNA loaded inside can be effectively delivered into cells to promote extracellular matrix generation, significantly promoting cartilage regeneration. The results of this study provide a promising biomaterial for cartilage repair, and this novel silk-based microcapsule delivery system can also provide strategies for the treatment of other diseases.


Assuntos
Fibroínas , Fibroínas/química , Cápsulas , Interleucina-4 , Cartilagem , Seda/química , DNA , Regeneração , Alicerces Teciduais/química , Engenharia Tecidual
10.
Cytokine ; 162: 156114, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36603482

RESUMO

Acute respiratory distress syndrome (ARDS) is a syndrome of acute respiratory failure caused by infection, trauma, shock, aspiration or drug reaction. The pathogenesis of ARDS is characterized as an unregulated inflammatory storm, which causes endothelial and epithelial layer damage, leading to alveolar fluid accumulation and pulmonary edema. Previous studies have shown the potential role of mesenchymal stem cells (MSC) in combating the inflammatory cascade by increasing the anti-inflammatory mediator interleukin-10 (IL-10). However, the involved mechanisms are unclear. Here we investigated whether a key immunomodulatory regulator, stanniocalcin-1 (STC-1), was secreted by MSC to activate phosphoinositide 3-kinase/protein kinase B (PI3K/AKT)/ mammalian target of rapamycin (mTOR) signaling pathway to increase IL-10 expression in alveolar macrophages. Lipopolysaccharide (LPS)-stimulated alveolar macrophages co-cultured with human umbilical mesenchymal stem cells (HUMSC) secreted high levels of IL-10. HUMSC co-cultured with alveolar macrophages expressed high STC-1 levels and increased PI3K, AKT and mTOR phosphorylation after LPS activation in alveolar macrophages. STC-1 knockdown in HUMSC decreased the phosphorylation of PI3K, AKT and mTOR and suppressed IL-10 expression in alveolar macrophages. Rapamycin (an mTOR inhibitor) reduced IL-10 secretion in alveolar macrophages. These results, together with our previous study and others, indicate that the PI3K/AKT/mTOR pathway is involved in the regulation of IL-10 production by STC-1 secreted by HUMSC in alveolar macrophages.


Assuntos
Células-Tronco Mesenquimais , Síndrome do Desconforto Respiratório , Humanos , Fatores Imunológicos/metabolismo , Interleucina-10/metabolismo , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Macrófagos Alveolares/metabolismo , Células-Tronco Mesenquimais/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Síndrome do Desconforto Respiratório/metabolismo , Serina-Treonina Quinases TOR/metabolismo
11.
Helicobacter ; 28(5): e13005, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37382428

RESUMO

BACKGROUND: Urease subunit B (UreB), a conserved and key virulence factor of Helicobacter pylori (H. pylori), can induce the host CD4+ T cell immune responses to provide protection, but less is known regarding CD8+ T cell responses. The characteristics of H. pylori-specific CD8+ T cell responses and the mechanism underlying antigen processing and presentation pathways remain unclear. This study was focus on protective antigen recombinant UreB (rUreb) to detect specific CD8+ T cell responses in vitro and elucidate the mechanism of UreB antigen processing and presentation. METHODS: The peripheral blood mononuclear cells (PBMCs) collected from H. pylori-infected individuals were stimulated with rUreB in vitro to detect specific CD8+ T cell responses after co-culture with rUreB-pulsed autologous hMDCs. Through blocking assay, we investigated the potential pathway of UreB antigen processing and presentation via the cytosolic pathway or vacuolar pathway. The cytokines production of UreB specific CD8+ T cell were evaluated as well. RESULTS: We demonstrated UreB can induce specific CD8+ T cell immune responses in H. pylori infected individuals. Importantly, we characterized that UreB were mainly processed by proteasome instead of lysosomal proteases and presented through cytosolic pathway of cross-presentation, which requires endoplasmic reticulum-Golgi transport and newly synthesized MHC-I molecules, to induce functional-specific CD8+ T cell (IFN-γ + TNF-α + Grz A+ Grz B+) responses. CONCLUSIONS: These results suggest that H. pylori UreB induces specific CD8+ T cell responses through cytosolic pathway of cross-presentation in infected individuals.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Humanos , Animais , Camundongos , Urease , Apresentação Cruzada , Leucócitos Mononucleares , Infecções por Helicobacter/prevenção & controle , Linfócitos T CD8-Positivos , Vacinas Bacterianas , Camundongos Endogâmicos BALB C
12.
Exp Cell Res ; 417(2): 113230, 2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-35667466

RESUMO

Intervertebral disc degeneration (IVDD) is a main contributor to induce low back pain, and the pathogenic mechanism of IVDD remains unclear. The nucleus pulposus (NP) is a component of the intervertebral disc (IVD) that provides protection from mechanical stimuli. The matrix stiffness of NP tissue increases during the process of disc degeneration. Although several studies have found that pathological mechanical stimuli induce NP cell senescence, which is relevant for NP degeneration, however, the effect of matrix stiffness on NP cell senescence is not clear. Therefore, in the present study, we used polyvinyl alcohol (PVA) hydrogel with controllable stiffness to mimic the matrix stiffness of normal (4 kPa) and severely degenerated (20 kPa) NP tissue. Rat NP cells were isolated and cultured on substrates with different stiffness, and the cell proliferation, SA-ß-gal activity, cell cycle, telomerase activity and the phenotype markers of NP cells were analyzed. Moreover, cytoskeleton staining and NP cellular Young's modulus on different substrates were also measured. To further investigate how substrate stiffness affects NP cell senescence, lysyl oxidase (LOX) was used to restore the extracellular matrix (ECM) synthesis of NP cells. The expression levels of integrin ß1 and p38 MAPK were then measured. Our results showed that the 20 kPa substrate significantly induced NP cell senescence compared to the 4 kPa substrate. NP cells cultured on the 20 kPa substrate failed to maintain the expression of their phenotype markers. Furthermore, the 20 kPa substrate induced an increase of Young's modulus of NP cells, which possibly through up regulating the expressions of integrin ß1 and p38 MAPK. These results indicated that the integrin ß1-p38 MAPK signaling pathway may participated in substrate stiffness induced senescence of NP cells. LOX significantly increased ECM synthesis and inhibited substrate stiffness induced NP cell senescence, which indicated that matrix mechanics may be essential for maintaining the function of NP cell. Our results may provide a new perspective on the mechanism of IVDD by pathological matrix mechanics.


Assuntos
Degeneração do Disco Intervertebral , Núcleo Pulposo , Animais , Células Cultivadas , Senescência Celular , Integrina beta1/genética , Integrina beta1/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Núcleo Pulposo/metabolismo , Proteína-Lisina 6-Oxidase/genética , Proteína-Lisina 6-Oxidase/metabolismo , Proteína-Lisina 6-Oxidase/farmacologia , Ratos , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
13.
Biosci Biotechnol Biochem ; 88(1): 26-36, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-37950567

RESUMO

This study aimed to explore the function of nucleolar protein interacting with the FHA domain of MKI67 (NIFK) on colorectal cancer (CRC) and its associated molecular mechanisms. NIFK was upregulated in CRC tissues and cells. NIFK silencing resulted in reduced cell growth and metastasis, as well as in promoted apoptosis in CRC cells. Moreover, NIFK silencing was also confirmed to inhibit lipid accumulation and decrease fatty acid synthesis via downregulating lipogenic enzymes in CRC cells. Gene set enrichment analysis and western blot co-verified that NIFK silencing inhibited MYC proto-oncogene, bHLH transcription factor (MYC) pathway in CRC cells. In addition, we also revealed that NIFK silencing function on cell growth, apoptosis, metastasis, and fatty acid metabolism in CRC might be cancelled after c-MYC overexpression. Silencing NIFK could inhibit cell growth and metastasis, and promoted apoptosis, as well as regulated fatty acid metabolism by inhibiting MYC pathway in CRC.


Assuntos
Neoplasias Colorretais , Humanos , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Colorretais/patologia , Ácidos Graxos , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genética
14.
Int J Clin Pract ; 2023: 3473603, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36874383

RESUMO

Objective: Atrial fibrillation (AF) is one of the most common complications of acute coronary syndrome (ACS) patients. Possible risk factors related to new-onset AF (NOAF) in ACS patients have been reported in some studies, and several prediction models have been established. However, the predictive power of these models was modest and lacked independent validation. The aim of this study is to define risk factors of NOAF in patients with ACS during hospitalization and to develop a prediction model and nomogram for individual risk prediction. Methods: Retrospective cohort studies were conducted. A total of 1535 eligible ACS patients from one hospital were recruited for model development. External validation was performed using an external cohort of 1635 ACS patients from another hospital. The prediction model was created using multivariable logistic regression and validated in an external cohort. The discrimination, calibration, and clinical utility of the model were evaluated, and a nomogram was constructed. A subgroup analysis was performed for unstable angina (UA) patients. Results: During hospitalization, the incidence of NOAF was 8.21% and 6.12% in the training and validation cohorts, respectively. Age, admission heart rate, left atrial diameter, right atrial diameter, heart failure, brain natriuretic peptide (BNP) level, less statin use, and no percutaneous coronary intervention (PCI) were independent predictors of NOAF. The AUC was 0.891 (95% CI: 0.863-0.920) and 0.839 (95% CI: 0.796-0.883) for the training and validation cohort, respectively, and the model passed the calibration test (P > 0.05). The clinical utility evaluation shows that the model has a clinical net benefit within a certain range of the threshold probability. Conclusion: A model with strong predictive power was constructed for predicting the risk of NOAF in patients with ACS during hospitalization. It might help with the identification of ACS patients at risk and early intervention of NOAF during hospitalization.


Assuntos
Síndrome Coronariana Aguda , Fibrilação Atrial , Intervenção Coronária Percutânea , Humanos , Estudos Retrospectivos , Átrios do Coração
15.
J Integr Neurosci ; 22(6): 157, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-38176929

RESUMO

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by misfolding of α-synuclein. Clinical manifestations include slowly developing resting tremor, muscle rigidity, bradykinesia and abnormal gait. The pathological mechanisms underlying PD are complex and yet to be fully elucidated. Clinical studies suggest that the onset of gastrointestinal symptoms may precede motor symptoms in PD patients. The microbiota-gut-brain axis plays a bidirectional communication role between the enteric nervous system and the central nervous system. This bidirectional communication between the brain and gut is influenced by the neural, immune and endocrine systems related to the gut microbiome. A growing body of evidence indicates a strong link between dysregulation of the gut microbiota and PD. In this review, we present recent progress in understanding the relationship between the microbiota-gut-brain axis and PD. We focus on the role of the gut microbiota, the unique changes observed in the microbiome of PD patients, and the impact of these changes on the progression of PD. Finally, we evaluate the role of current treatment strategies for PD, including probiotics, fecal microbial transplants, dietary modifications, and related drug therapies.


Assuntos
Microbioma Gastrointestinal , Doença de Parkinson , Probióticos , Humanos , Doença de Parkinson/terapia , Eixo Encéfalo-Intestino , Encéfalo/patologia
16.
Ultraschall Med ; 44(2): e126-e135, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34820796

RESUMO

PURPOSE: To prospectively study the influence of the volume of the uterine junctional zone (JZ) as a novel predictor of reproductive outcomes in frozen embryo transfer cycles. METHODS: Among the first 30 patients, intra- and interobserver repeatability was evaluated and expressed as a coefficient of repeatability. The same classification system was used to evaluate the JZ of 142 infertility patients undergoing in vitro fertilization (IVF). Ultrasonography was performed on the day before transplantation. The three-dimensional (3D) volume images were then analyzed to obtain the volume of the endometrium (EV), the average thickness of the JZ on the coronal plane, and the volume of the JZ (JZV). The JZV was then divided by the EV. These parameters were compared with the outcomes of clinical pregnancy. RESULTS: The 3D image showed that the JZ achieved a good intra- and interobserver consistency (k = 0.862, k = 0.694). The total pregnancy rate was 47%. There was a highly significant difference between pregnant and non-pregnant women with respect to age (p < 0.001), JZV (p = 0.003), and JZV/EV (p < 0.001) on the day before transplantation. Age and JZV/EV were independent factors for predicting the success of IVF transplantation (p = 0.010, p = 0.016). The area under the ROC curve of JZV/EV in predicting clinical pregnancy was 0.688, the cut-off value was 0.54, the sensitivity was 83.8%, and the specificity was 50.0%. CONCLUSION: Age and JZV/EV are independent factors for predicting the success of frozen embryo transfer cycles in IVF. A smaller JZV/EV was more beneficial for clinical pregnancy.


Assuntos
Transferência Embrionária , Útero , Gravidez , Feminino , Humanos , Útero/diagnóstico por imagem , Fertilização in vitro , Endométrio/diagnóstico por imagem , Ultrassonografia
17.
Women Health ; 63(2): 73-82, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36581403

RESUMO

Endometriosis (EMS) is a challenging gynecological disorder prevalent in reproductive-aged women, and Th1/Th2 cytokines are implicated in EMS progression. This study probed the serum levels and clinical values of Th1/Th2 cytokines in EMS patients. Firstly, the clinic characteristics of EMS and control patients were recorded. The levels of interferon (IFN)-γ, interleukin (IL)-2, IL-4, and IL-10 in the serum of EMS and control patients were identified, respectively. The correlations between Th1 and Th2 cytokines and the diagnostic values of these cytokines in EMS were analyzed. We observed that EMS patients had obvious differences from the controls in dysmenorrhea, dyspareunia, pelvic pain, nulliparous, and CA125 levels. Serum IFN-γ and IL-2 were lower while IL-4 and IL-10 were higher in EMS patients. Serum IFN-γ, IL-4 were negatively correlated with serum IL-2, and IL-10 in EMS patients. Th1/Th2 cytokines may help the diagnosis of EMS. Serum IFN-γ and IL-2 were independent protective factors for EMS while dysmenorrhea, dyspareunia, nulliparous, and serum IL-4 and IL-10 were independent risk factors for EMS. Collectively, serum Th1/Th2 cytokine levels helped the diagnosis of EMS, with IFN-γ and IL-2 serving as independent protective factors whilst IL-4 and IL-10 serving as independent risk factors.


Assuntos
Dispareunia , Endometriose , Humanos , Feminino , Adulto , Citocinas , Interleucina-10 , Interleucina-2 , Interleucina-4 , Relevância Clínica , Dismenorreia , Células Th1 , Células Th2
18.
J Am Chem Soc ; 144(18): 8389-8398, 2022 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-35482430

RESUMO

Enantioselective transformations of olefins are among the most important strategies for the asymmetric synthesis of organic compounds. Chemo-, diastereo-, and stereoselective control of reactions with internal acyclic alkenes for the construction of functionalized acyclic alkanes still remain a persistent challenge. Here, we report a palladium-catalyzed asymmetric regiodivergent Heck-type diarylation of internal acyclic alkenes. The 1,2-diarylation of two accessible acyclic alkenes, cinnamyl carbamates and enamides with diazonium salts and aromatic boronic acids, furnishes products containing vicinal stereogenic centers via the stereospecific formation of carbonyl coordination-assisted transient palladacycles. Moreover, the asymmetric migratory diarylation of enamides enables the formation of incontiguous stereocenters by an interrupted diastereoselective 1,3-chain-walking process. This protocol streamlines access to highly functionalized multisubstituted enantioenriched carbamates and amine derivatives which are embedded in the key biologically active motifs.


Assuntos
Alcenos , Estirenos , Carbamatos , Catálise , Estereoisomerismo
19.
Arch Microbiol ; 204(6): 305, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35532844

RESUMO

A novel Gram-stain-negative, non-motile, short rod-shaped and aerobic bacterial strain, designated as CFH 74456 T, was isolated from sediment of a hot spring, Tengchong, Yunnan Province, south-western China. Growth occurred at 20-53 ºC (optimum 45 ºC), pH 7.0-9.0 (optimum pH 8.0) and up to 2.0% (w/v) NaCl (optimum 0-1.0%, w/v). The predominant respiratory quinone was ubiquinone 10 (Q-10). The major fatty acids (> 10%) were C17:1 ω6c (17.9%) and summed feature 8 (38.6%). The polar lipid profile of strain CFH 74456 T was identified as diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, sphingoglycolipid, three unidentified glycolipids and three unidentified polar lipids. Phylogenetic analysis based on 16S rRNA gene sequence indicated that strain CFH 74456 T belongs to the genus Qipengyuania, and was most closely related to Qipengyuania sediminis CGMCC 1.12928 T (95.7%). The draft genome size of the isolate was 2.29 Mb with G + C content of 68.5%. The amino acid identity, average nucleotide identity and the digital DNA-DNA hybridization values between strain CFH 74456 T and the closest relatives ranged from 67.0 to 67.9%, 73.0 to 74.2% and 18.2-19.3%, respectively. On the basis of phenotypic, phylogenetic and genotypic analyses, it is concluded that strain CFH 74456 T represents a new species of the genus Qipengyuania, for which the name Qipengyuania thermophila sp. nov. is proposed. The type strain is CFH 74456 T (= KCTC 62921 T = CCTCC AB 2018237 T).


Assuntos
Fontes Termais , Técnicas de Tipagem Bacteriana , China , DNA Bacteriano/genética , Ácidos Graxos/química , Fontes Termais/microbiologia , Fosfolipídeos/química , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
20.
Artigo em Inglês | MEDLINE | ID: mdl-35085062

RESUMO

A novel actinobacterium, designated strain CFH 90414T, was isolated from sediment sampled at a saline lake in Yuncheng, Shanxi, PR China. The taxonomic position of the strain was investigated by using a polyphasic approach. Cells of strain CFH 90414T were Gram-reaction-positive, aerobic and non-motile. Growth occured at 4-40 °C, pH 5.0-9.0 and in the presence of up to 0-3.0 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CFH 90414T was a member of the genus Agromyces. The 16S rRNA gene sequence similarity analysis indicated that strain CFH 90414T was most closely related to Agromyces italicus JCM 14320T (98.07 %) and Agromyces lapidis JCM 14321T (97.18 %). The whole genome of CFH 90414T was 3.64 Mb, and showed a G+C content of 71.5 mol%. The average nucleotide identity (ANI) values and digital DNA-DNA hybridization (dDDH) values between CFH 90414T and the other species of the genus Agromyces were found to be low (ANI <78.99 % and dDDH <22.9 %). The whole-cell sugars were rhamnose, mannose, ribose, glucose and galactose. The isolate contained l-2,4-diaminobutyric acid, d-alanine, d-glutamic acid and glycine in the cell-wall peptidoglycan. The predominant menaquinone was MK-12. The major cellular fatty acids were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. The polar lipid profile contained diphosphatidylglycerol, phosphatidylglycerol and an unidentified glycolipid. On the basis of phenotypic, genotypic and phylogenetic data, strain CFH 90414T is considered to represent a novel species of the genus Agromyces, for which the name Agromyces agglutinans sp. nov. is proposed. The type strain is CFH 90414T (=DSM 105966T=KCTC 49062T).


Assuntos
Actinobacteria/classificação , Ácidos Graxos , Sedimentos Geológicos/microbiologia , Lagos , Filogenia , Águas Salinas , Actinobacteria/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Lagos/microbiologia , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/química
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