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1.
Plants (Basel) ; 11(18)2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36145777

RESUMO

Populus euphratica Oliv., a pioneer species of desert riparian forest, is characterized heterophylly. To understand the adaptation strategies of the heteromorphic leaves of P. euphratica to soil drought, we assessed the structural and functional characteristics of the heteromorphic leaves at different heights in suitable soil moisture conditions (groundwater depth 1.5 m) and drought conditions (groundwater depth 5 m), which include morphology, anatomical structure, photosynthetic capacity, water use efficiency, osmotic adjustment capacity, and endogenous hormones. These results indicate that leaf area, leaf thickness, fence tissue, palisade-to-sea ratio, main vein xylem area, vessel area, net photosynthetic rate, transpiration rate, and proline, MDA, IAA, GA3, and ZR contents showed a positive correlation with the tree height under the two soil moisture conditions, but leaf shape index, leaf water potential (LWP), and ABA content showed a decreasing trend. In addition, the main vein vascular bundle area, main vein xylem area, and contents of malondialdehyde, ABA, GA3, and IAA were significantly greater under soil drought conditions than normal soil water content. Under soil drought stress, the heteromorphic leaves of P. euphratica showed more investment in anatomical structure and greater water use efficiency, proline, and hormone contents, and synergistic changes to maintain high photosynthetic efficiency. This is an adaptation strategy to water stress caused by soil drought and tree height changes.

2.
Open Life Sci ; 17(1): 839-845, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36045722

RESUMO

This study explored the correlation between peripheral blood CD3+, CD3+/CD4+, CD3+/CD8+, CD4+/CD8+, CD3-/CD16+ CD56+, and CD3-CD19+ and disease activity of different subtypes of systemic lupus erythematosus (SLE). The percentages of CD3+, CD3+/CD4+, CD3+/CD8+, CD4+/CD8+, CD3-/CD16+ CD56+, and CD3-CD19+ in the peripheral blood of patients (n = 80) classified into lupus nephritis, blood involvement, and joint involvement and SLE in different active stages were detected by flow cytometry. Their correlations with baseline clinical experimental indicators of SLE patients' SLE disease activity index score (SLEDAI) and complement C3 were analyzed. The results showed that CD3+, CD3+/CD4+, and CD3+/CD8+ at baseline level were negatively correlated with SLEDAI scores. These were positively correlated with C3. In conclusion, T-lymphocyte subpopulations are closely related to SLE activity and can be used as reference indicators to evaluate the SLE activity.

3.
World J Psychiatry ; 12(7): 904-914, 2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-36051605

RESUMO

BACKGROUND: Schizophrenia (SCZ) is a complex disease which can be affected by both genetic and environmental factors. Prenatal famine exposure may cause changes in DNA methylation levels of genes. Meanwhile, maternal nutrition during pregnancy is a pivotal environmental factor in the development of SCZ. DNA methylation may be an intermediate factor mediating exposure to famine during pregnancy and SCZ, and DNA methylation quantitative trait loci might serve as a promising tool for linking SCZ and prenatal famine. AIM: To analyze the association between prenatal famine exposure and SCZ risk in Northeast Han Chinese through analysis of DNA methylation related loci. METHODS: A total of 954 Han Chinese from Northeast China were recruited, including 443 patients with SCZ and 511 healthy controls. The participants were further divided into famine (born in 1960-1962) and non-famine (born in 1963-1965) groups to investigate the effect of prenatal famine exposure. Four single-nucleotide polymorphisms (SNPs) selected according to the relevant literature were genotyped, namely, rs11917047 in PTPRG, rs2239681 in IGF2, rs3842756 in INSIGF, and rs61955196 in ABCB9. DNA were extracted from peripheral blood samples, and the genotypes of these SNP loci were detected using the improved Multiple Ligase Detection Reaction multiple SNP typing technique. The associations of the DNA methylation related SNPs with SCZ risk and prenatal famine, and their interactions were analyzed using logistic regression analysis and generalized multifactor dimensionality reduction (GMDR) software. RESULTS: Based on the sequencing data, genotype distributions and allele frequencies of the four selected SNPs were determined. All genotype frequencies of the four SNPs in the healthy control group were tested for deviation from Hardy-Weinberg equilibrium (P > 0.05). Logistic regression analysis showed that rs61955196 was significantly associated with SCZ risk in the log-additive model [odds ratio (OR): 1.22; 95% confidence interval (CI): 1.01-1.48; P = 0.040]. We also found that the rs61955196 allele was related with an enhanced risk of SCZ (G>C, OR: 1.22; 95%CI: 1.01-1.47; P = 0.042). However, no associations were observed between rs11917047, rs2239681, or rs3842756 and SCZ risk. Under the optimal genetic model, no significant association of famine with the four SNPs was seen. Though the gene-gene interactions between rs2239681 and rs61955196 were found in GMDR analysis, none of the gene-gene interactions and gene-famine interactions were associated with the risk of SCZ. CONCLUSION: Our study suggested that rs61955196 in ABCB9 is associated with SCZ susceptibility in Northeast Han Chinese, providing insight into genetic effects on SCZ.

4.
Front Public Health ; 10: 943026, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36033742

RESUMO

Objective: To investigate the association between the structural deformity and foot pain in hallux valgus (HV) patients using a multi-variate pattern analysis (MVPA) approach. Methods: Plain radiographic metrics were calculated from 36 painful and 36 pain-free HV feet. In analysis 1, univariate analyses were performed to investigate the clinical and radiographic differences between painful and pain-free HV. In analysis 2, we investigated the pattern differences for radiographic metrics between these two groups using a MVPA approach utilizing a support vector machine. In analysis 3, sequential backward selection and exhaustive search were performed as a feature-selection procedure to identify an optimal feature subtype. In analysis 4, hierarchical clustering analysis was used to identify the optimal radiographic HV subtype associated with pain in HV. Results: We found that: (1) relative to feet with pain-free HV, the painful ones exhibited a higher hallux valgus angle, i.e., the magnitude of distal metatarsal and phalangeal deviation; (2) painful HV could be accurately differentiated from pain-free HV via MVPA. Using sequential backward selection and exhaustive search, a 5-feature subset was identified with optimal performance for classifying HV as either painful or pain-free; and (3) by applying hierarchical clustering analysis, a radiographic subtype with an 80% pain incidence was identified. Conclusion: The pain in HV is multifactorial and associated with a radiographic pattern measured by various angles on plain radiographs. The combination of hallux valgus angle, inter-phalangeal angle, distal metatarsal articular angle, metatarsal cuneiform angle and metatarsal protrusion distance showed the optimal classification performance between painful and pain-free HV.


Assuntos
Hallux Valgus , Ossos do Metatarso , Humanos , Aprendizado de Máquina , Radiografia
5.
IEEE Trans Cybern ; PP2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35930520

RESUMO

Robot learning through kinesthetic teaching is a promising way of cloning human behaviors, but it has its limits in the performance of complex tasks with small amounts of data, due to compounding errors. In order to improve the robustness and adaptability of imitation learning, a hierarchical learning strategy is proposed: low-level learning comprises only behavioral cloning with supervised learning, and high-level learning constitutes policy improvement. First, the Gaussian mixture model (GMM)-based dynamical system is formulated to encode a motion from the demonstration. We then derive the sufficient conditions of the GMM parameters that guarantee the global stability of the dynamical system from any initial state, using the Lyapunov stability theorem. Generally, imitation learning should reason about the motion well into the future for a wide range of tasks; it is significant to improve the adaptability of the learning method by policy improvement. Finally, a method based on exponential natural evolution strategies is proposed to optimize the parameters of the dynamical system associated with the stiffness of variable impedance control, in which the exploration noise is subject to stability conditions of the dynamical system in the exploration space, thus guaranteeing the global stability. Empirical evaluations are conducted on manipulators for different scenarios, including motion planning with obstacle avoidance and stiffness learning.

6.
Sci Rep ; 12(1): 14354, 2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-35999354

RESUMO

Inonotus hispidus is a valuable and rare edible and medicinal mushroom with extremely high nutritional and medicinal value. However, there is no holistic insight to elucidate the molecular basis of the differentiated usage and accurate annotation of physiological maturity to fluctuating yields and quality. This study aimed to figure out the fruiting bodies' metabolites change regulation and potential maturating indicators to distinguish different quality I. hispidus. We applied non-targeted ultra-high performance liquid chromatography and high-resolution mass spectrometry combined and with multivariate analysis and analyzed cultivated and wild mushroom I. hispidus in different growth periods (budding, mature and aging). With the fruiting bodies maturating, 1358 metabolites were annotated, 822 and 833 metabolites abundances changed greater than or equal to 1 time from the budding period to the aging period in abundance in cultivated and wild, the total polysaccharides, crude fat, total flavonoids, and total terpenes increased at first and then decreased. Total amino acids, crude protein, and total polyphenols decreased, while the total steroids increased linearly. The change of metabolites showed certain regularity. Metabolic pathways enrichment analysis showed that these metabolites are involved in glycolysis, biosynthesis of amino acids, organic acid metabolism, glycine-serine-and-threonine metabolism, tricarboxylic acid cycle, purine metabolism, and pyrimidine metabolism. In addition, ergosterol peroxide and (22E)-ergosta-4,6,8(14),22-tetraen-3-one can be used as indicator compounds, and their contents increase linearly with the fruiting bodies of I. hispidus' physiological maturation. This comprehensive analysis will help to evaluate the edible values and facilitate exploitation in mushroom I. hispidus.


Assuntos
Agaricales , Aminoácidos , Cromatografia Líquida de Alta Pressão , Inonotus
7.
Adv Mater ; : e2205303, 2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-35986557

RESUMO

To rationally design single-atom metal-organic framework (MOF)-involving photocatalysts remains an ongoing challenge for efficient CO2 conversion. Here, cuppy microstructures, consisting of a Ti(IV)-oxo node and three linked carboxylic moieties, in the single-coordination-layer Ti2 (H2 dobdc)3 MOF (NTU-9) are exploited to immobilize abundant single Ni(II) sites (Ni@MOF). The coupling of Ni@MOF with BiVO4 (BVO) nanosheets by H-bonding-induced assembly process obtains wide-spectrum 2D heterojunctions. The optimal heterojunction exhibits competitive performance and enables around 66-fold CO2 conversion of that for BVO nanoparticles by pure water, with nearly 100% CO selectivity. The exceptional photoactivity is attributed to favorable S-scheme charge transfer from BVO to MOF then to single Ni(II) sites. Noteworthily, single Ni(II) sites anchored by the Ti(IV)-oxo node and vicinal carboxylic moieties serving as a unique local microenvironment (LME) are found to synergistically catalyze CO2 conversion. Specifically, the hydroxyl groups of carboxylic moieties can form H-bonds with CO2 to promote its adsorption on single Ni(II) sites, and also can provide accessible protons to facilitate H-assisted CO2 reduction. Moreover, the CO desorption and subsequent CO2 adsorption on single Ni(II) sites with LME is proved to be thermodynamically favored, and hence dominates the high CO selectivity. This work highlights the significance of modulating the LME of single atoms to rationally design photocatalysts for realizing carbon neutralization.

8.
Oxid Med Cell Longev ; 2022: 8619275, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35979397

RESUMO

Our previous studies have shown that delicaflavone (DLL), a biocomponent extracted from Selaginella doederleinii Hieron, has antitumor activity. However, the role of DLL in the antitumor immune response is unknown. In this study, we tested the potential roles of DLL in antitumor immune response. An animal tumor model with Lewis lung cancer cell line (3LL) in C57BL/6 mice was established to determine whether DLL induced the tumor-bearing host's antitumor immune response. m6A-MeRIP-qPCR, western blot, and flow cytometry were performed to explore the underlying mechanisms. DLL inhibited the proliferation of 3LL lung cancer cells in vitro and in vivo and induced tumor cell oxidative stress. DLL significantly inhibited tumor growth in immunocompetent mice compared with nude mice. DLL treatment significantly increased Th1 cytokine production and CD8+ T cell infiltration into tumor tissues in tumor-bearing mice. DLL-mediated antitumor immune effects were reversed by overexpression of the N6-methyladenosine (m6A) transferase Mettl3/Mettl14. Mechanistically, DLL upregulated the expression of Stat1 and Irf1 and the secretion of cytokines by inhibiting Mettl3 and Mettl14 in lung cancer cells. In conclusion, DLL inhibited lung cancer cell growth by suppressing Mettl3/Mettl14 to activate antitumor immunity. These findings provided an opportunity to enhance lung cancer immunotherapy.


Assuntos
Neoplasias Pulmonares , Transferases , Adenosina/análogos & derivados , Animais , Modelos Animais de Doenças , Imunidade , Neoplasias Pulmonares/tratamento farmacológico , Metiltransferases/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Estresse Oxidativo , Transferases/metabolismo
9.
Front Immunol ; 13: 962393, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35967341

RESUMO

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with highly heterogeneous clinical symptoms and severity. There is complex pathogenesis of SLE, one of which is IFNs overproduction and downstream IFN-stimulated genes (ISGs) upregulation. Identifying the key ISGs differentially expressed in peripheral blood mononuclear cells (PBMCs) of patients with SLE and healthy people could help to further understand the role of the IFN pathway in SLE and discover potential diagnostic biomarkers. The differentially expressed ISGs (DEISG) in PBMCs of SLE patients and healthy persons were screened from two datasets of the Gene Expression Omnibus (GEO) database. A total of 67 DEISGs, including 6 long noncoding RNAs (lncRNAs) and 61 messenger RNAs (mRNAs) were identified by the "DESeq2" R package. According to Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, those DEISGs were mainly concentrated in the response to virus and immune system processes. Protein-protein interaction (PPI) network showed that most of these DEISGs could interact strongly with each other. Then, IFIT1, RSAD2, IFIT3, USP18, ISG15, OASL, MX1, OAS2, OAS3, and IFI44 were considered to be hub ISGs in SLE by "MCODE" and "Cytohubba" plugins of Cytoscape, Moreover, the results of expression correlation suggested that 3 lncRNAs (NRIR, FAM225A, and LY6E-DT) were closely related to the IFN pathway. The lncRNA NRIR and mRNAs (RSAD2, USP18, IFI44, and ISG15) were selected as candidate ISGs for verification. RT-qPCR results showed that PBMCs from SLE patients had substantially higher expression levels of 5 ISGs compared to healthy controls (HCs). Additionally, statistical analyses revealed that the expression levels of these ISGs were strongly associated to various clinical symptoms, including thrombocytopenia and facial erythema, as well as laboratory indications, including the white blood cell (WBC) count and levels of autoantibodies. The Receiver Operating Characteristic (ROC) curve demonstrated that the IFI44, USP18, RSAD2, and IFN score had good diagnostic capabilities of SLE. According to our study, SLE was associated with ISGs including NRIR, RSAD2, USP18, IFI44, and ISG15, which may contribute to the future diagnosis and new personalized targeted therapies.


Assuntos
Interferon Tipo I , Lúpus Eritematoso Sistêmico , RNA Longo não Codificante , Antivirais/metabolismo , Humanos , Interferon Tipo I/genética , Interferon Tipo I/metabolismo , Leucócitos Mononucleares/metabolismo , Lúpus Eritematoso Sistêmico/imunologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ubiquitina Tiolesterase/metabolismo
10.
J Virol ; 96(17): e0082622, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-35938868

RESUMO

Viruses evolve mechanisms to exploit cellular pathways that increase viral fitness, e.g., enhance viral replication or evade the host cell immune response. The ubiquitin-proteosome system, a fundamental pathway-regulating protein fate in eukaryotes, is hijacked by all seven classes of viruses. Members of the Cullin-RING family of ubiquitin (Ub) ligases are frequently co-opted by divergent viruses because they can target a broad array of substrates by forming multisubunit assemblies comprised of a variety of adapters and substrate receptors. For example, the linker subunit DDB1 in the cullin 4-RING (CRL4)-DDB1 Ub ligase (CRL4DDB1) interacts with an H-box motif found in several unrelated viral proteins, including the V protein of simian virus 5 (SV5-V), the HBx protein of hepatitis B virus (HBV), and the recently identified pUL145 protein of human cytomegalovirus (HCMV). In HCMV-infected cells, pUL145 repurposes CRL4DDB1 to target STAT2, a protein vital to the antiviral immune response. However, the details of how these divergent viral sequences hijack DDB1 is not well understood. Here, we use a combination of binding assays, X-ray crystallography, alanine scanning, cell-based assays, and computational analysis to reveal that viral H-box motifs appear to bind to DDB1 with a higher affinity than the H-box motifs from host proteins DCAF1 and DDB2. This analysis reveals that viruses maintain native hot-spot residues in the H-box motif of host DCAFs and also acquire favorable interactions at neighboring residues within the H-box. Overall, these studies reveal how viruses evolve strategies to produce high-affinity binding and quality interactions with DDB1 to repurpose its Ub ligase machinery. IMPORTANCE Many different viruses modulate the protein machinery required for ubiquitination to enhance viral fitness. Specifically, several viruses hijack the cullin-RING ligase CRL4DDB1 to degrade host resistance factors. Human cytomegalovirus (HCMV) encodes pUL145 that redirects CRL4DDB1 to evade the immune system through the targeted degradation of the antiviral immune response protein STAT2. However, it is unclear why several viruses bind specific surfaces on ubiquitin ligases to repurpose their activity. We demonstrate that viruses have optimized H-box motifs that bind DDB1 with higher affinity than the H-box of native binders. For viral H-boxes, native interactions are maintained, but additional interactions that are absent in host cell H-boxes are formed, indicating that rewiring CRL4DDB1 creates a selective advantage for the virus. The DDB1-pUL145 peptide structure reveals that water-mediated interactions are critical to the higher affinity. Together, our data present an interesting example of how viral evolution can exploit a weakness in the ubiquitination machinery.


Assuntos
Proteínas Culina , Infecções por Citomegalovirus , Proteínas de Ligação a DNA , Proteínas Virais , Proteínas Culina/metabolismo , Infecções por Citomegalovirus/imunologia , Proteínas de Ligação a DNA/metabolismo , Humanos , Ligação Proteica , Conformação Proteica , Fator de Transcrição STAT2/metabolismo , Complexos Ubiquitina-Proteína Ligase/metabolismo , Proteínas Virais/metabolismo
11.
Geriatr Orthop Surg Rehabil ; 13: 21514593221113533, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35832467

RESUMO

Background: We performed a meta-analysis to compare the efficacy and safety of the femoral neck system (FNS) with cannulated cancellous screws (CCSs) in treating femoral neck fractures (FNFs) in controlled clinical trials. Methods: Eligible scientific articles published prior to September 2021 were retrieved from the PubMed, Web of Science, Springer, ScienceDirect and Cochrane Library databases. The statistical analysis was performed with RevMan 5.1. Results: Seven retrospective studies met the inclusion criteria. Meta-analysis showed that there were significant differences in perioperative blood loss, the postoperative Harris score, healing time, fluoroscopy frequency, total complications, femoral head necrosis, femoral neck shortening and screw cutout. No significant differences were found regarding operation time, length of hospital stay or nonunion between the two groups. Conclusion: Compared with CCSs, the FNS showed better clinical efficacy and fewer complications in treating FNFs. Due to the limited quality and data of the currently available evidence, more high-quality randomized controlled trials are needed.

12.
Artigo em Inglês | MEDLINE | ID: mdl-35844038

RESUMO

Telitacicept, an injectable recombinant human B-lymphocyte stimulating factor receptor-antibody fusion protein, is a new dual B lymphocyte stimulator (BLyS)/APRIL (a proliferation-inducing ligand) inhibitor that effectively blocks proliferation of B lymphocytes. This study evaluates the pharmacokinetic characteristics, tolerability, and safety of a single subcutaneous injection of various doses (80, 160, and 240 mg) of telitacicept in healthy Chinese subjects. This trial is a single-center, randomized, open-label phase I clinical study that includes three dose groups (80, 160, and 240 mg) with 12 subjects in each dose group. The subjects were randomly assigned to different dose groups in a 1:1:1 ratio for a single subcutaneous administration trial. After a single dose, the maximum serum concentration (Cmax ) of total and free telitacicept was reached within 0.5-1 days. The elimination half-lives of total and free telitacicept at doses of 80-240 mg were 10.9-11.9 days and 11-12.5 days, respectively. The formation and elimination of the BLyS-telitacicept complex were much slower; the median time to Cmax was 15-57 days and was significantly prolonged with increasing dose. Only two of the 36 healthy subjects had positive antidrug antibodies with antibody titers of 1:15. The severity of adverse events was mild or moderate, and no higher treatment-emergent adverse events were reported. In conclusion, total telitacicept within a dose range of 80-240 mg and free telitacicept within a dose range of 160-240 mg had linear pharmacokinetic characteristics.

13.
Acta Pharmacol Sin ; 2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35896694

RESUMO

The current study evaluated the efficacy and safety of a denosumab biosimilar, QL1206 (60 mg), compared to placebo in postmenopausal Chinese women with osteoporosis and high fracture risk. At 31 study centers in China, a total of 455 postmenopausal women with osteoporosis and high fracture risk were randomly assigned to receive QL1206 (60 mg subcutaneously every 6 months) or placebo. From baseline to the 12-month follow-up, the participants who received QL1206 showed significantly increased bone mineral density (BMD) values (mean difference and 95% CI) in the lumbar spine: 4.780% (3.880%, 5.681%), total hip :3.930% (3.136%, 4.725%), femoral neck 2.733% (1.877%, 3.589%) and trochanter: 4.058% (2.791%, 5.325%) compared with the participants who received the placebo. In addition, QL1206 injection significantly decreased the serum levels of C-terminal crosslinked telopeptides of type 1 collagen (CTX): -77.352% (-87.080%, -66.844%), and N-terminal procollagen of type l collagen (P1NP): -50.867% (-57.184%, -45.217%) compared with the placebo over the period from baseline to 12 months. No new or unexpected adverse events were observed. We concluded that compared with placebo, QL1206 effectively increased the BMD of the lumbar spine, total hip, femoral neck and trochanter in postmenopausal Chinese women with osteoporosis and rapidly decreased bone turnover markers. This study demonstrated that QL1206 has beneficial effects on postmenopausal Chinese women with osteoporosis and high fracture risk.

14.
Oncol Res Treat ; 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35882206

RESUMO

BACKGROUND: The use of bevacizumab in patients with previously treated metastatic breast cancer (MBC) is controversial. This meta-analysis was carried out to evaluate the efficacy and safety of the regimen including bevacizumab among patients with pretreated MBC. METHODS: We systematically searched the PubMed, the Cochrane Library, Web of Science, and Embase databases for randomized controlled trials (RCTs) evaluating bevacizumab combined with chemotherapy for previously treated MBC patients. The primary endpoints were progression-free survival (PFS) and objective response rate (ORR). The secondary endpoints were overall survival (OS) and toxicity. The risk of bias was assessed by the Cochrane Collaboration tool. The pooled hazard ratio (HR) and risk ratio (RR) with 95% confidence intervals (CIs) were calculated for the identified studies. This study was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. RESULTS: Four studies involving 1640 individuals were included. Pooling results showed that the PFS of bevacizumab-containing groups (HR 0.82; 95% CI 0.73-0.93, P=0.002) was significantly better than that of the control groups, especially when bevacizumab was administered as the second-line treatment for patients with human epidermal growth factor receptor 2 (HER2)-negative MBC (HR 0.77; 95%CI 0.66-0.88, P=0.0002). The ORR in the bevacizumab-containing group was superior to that in the control group, both in the general (RR 1.45; 95%CI 1.18-1.78, P=0.0004) and HER2-negative groups (RR 1.30; 95%CI 1.03-1.63, P=0.03). However, no significant effect on OS was demonstrated for the addition of bevacizumab to the second-line treatment for HER2-negative MBC (HR 0.93; 95%CI 0.79-1.10, P=0.39). Comparatively, proteinuria was more common in the bevacizumab-containing group. In addition, the application of bevacizumab tended to result in therapy discontinuation due to treatment-related toxicity. CONCLUSIONS: Bevacizumab-containing chemotherapy, in light of its favorable effects on clinical outcomes, could be a preferred therapeutic option for patients with MBC, for whom the disease must be rapidly relieved. Further studies are warranted for exploring the advantageous patients with the receipt of bevacizumab in multiline treatment.

15.
Biomater Sci ; 10(15): 4119-4125, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35789225

RESUMO

Herein, a smart nanohydrogel with endogenous microRNA-21 toehold is developed to encapsulate gemcitabine-loaded mesoporous silica nanoparticles for targeted pancreatic cancer therapy. This toehold mediated strand displacement method can simultaneously achieve specific drug release and miRNA-21 silencing, resulting in the up-regulation of the expression of tumor suppressor genes PTEN and PDCD4.


Assuntos
MicroRNAs , Nanopartículas , DNA/genética , Regulação da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , Nanogéis
16.
Mikrochim Acta ; 189(8): 273, 2022 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-35792975

RESUMO

An integrated custom cross-response sensing array has been developed combining the algorithm module's visible machine learning approach for rapid and accurate pathogenic microbial taxonomic identification. The diversified cross-response sensing array consists of two-dimensional nanomaterial (2D-n) with fluorescently labeled single-stranded DNA (ssDNA) as sensing elements to extract a set of differential response profiles for each pathogenic microorganism. By altering the 2D-n and different ssDNA with different sequences, we can form multiple sensing elements. While interacting with microorganisms, the competition between ssDNA and 2D-n leads to the release of ssDNA from 2D-n. The signals are generated from binding force driven by the exfoliation of either ssDNA or 2D-n from the microorganisms. Thus, the signal is distinguished from different ssDNA and 2D-n combinations, differentiating the extracted information and visualizing the recognition process. Fluorescent signals collected from each sensing element at the wavelength around 520 nm are applied to generate a fingerprint. As a proof of concept, we demonstrate that a six-sensing array enables rapid and accurate pathogenic microbial taxonomic identification, including the drug-resistant microorganisms, under a data size of n = 288. We precisely identify microbial with an overall accuracy of 97.9%, which overcomes the big data dependence for identifying recurrent patterns in conventional methods. For each microorganism, the detection concentration is 105 ~ 108 CFU/mL for Escherichia coli, 102 ~ 107 CFU/mL for E. coli-ß, 103 ~ 108 CFU/mL for Staphylococcus aureus, 103 ~ 107 CFU/mL for MRSA, 102 ~ 108 CFU/mL for Pseudomonas aeruginosa, 103 ~ 108 CFU/mL for Enterococcus faecalis, 102 ~ 108 CFU/mL for Klebsiella pneumoniae, and 103 ~ 108 CFU/mL for Candida albicans. Combining the visible machine learning approach, this sensing array provides strategies for precision pathogenic microbial taxonomic identification. • A molecular response differential profiling (MRDP) was established based on custom cross-response sensor array for rapid and accurate recognition and phenotyping common pathogenic microorganism. • Differential response profiling of pathogenic microorganism is derived from the competitive response capacity of 6 sensing elements of the sensor array. Each of these sensing elements' performance has competitive reaction with the microorganism. • MRDP was applied to LDA algorithm and resulted in the classification of 8 microorganisms.


Assuntos
Escherichia coli , Nanoestruturas , DNA de Cadeia Simples , Aprendizado de Máquina , Nanoestruturas/química
17.
Ann Rheum Dis ; 2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35788493

RESUMO

OBJECTIVES: Previous studies have compared mycophenolate mofetil and azathioprine as maintenance therapy for lupus nephritis (LN). Leflunomide is an immunosuppressant widely used in the treatment of rheumatoid arthritis. The aim of this investigator-initiated study was to compare the efficacy and safety of leflunomide versus azathioprine as maintenance therapy for LN. METHODS: 270 adult patients with biopsy-confirmed active LN from 7 Chinese Rheumatology Centres were enrolled. All patients received induction therapy with 6-9 months of intravenous cyclophosphamide plus glucocorticoids. Patients who achieved complete response (CR) or partial response (PR) were randomised to receive prednisone in combination with leflunomide or azathioprine as maintenance therapy for 36 months. The primary efficacy endpoint was the time to kidney flare. Secondary outcomes included clinical parameters, extrarenal flare and adverse effects. RESULTS: A total of 215 patients were randomly allocated to the leflunomide group (n=108) and azathioprine group (n=107). Kidney flares were observed in 17 (15.7%) leflunomide-treated patients and 19 (17.8%) azathioprine-treated patients. Time to kidney flare did not statistically differ (leflunomide: 16 months vs azathioprine: 14 months, p=0.676). 24-hour proteinuria, serum creatinine, serum albumin, serum C3 and serum C4 improved similarly. Extrarenal flare occurred in two patients from the azathioprine group and one patient from the leflunomide group. The incidence of adverse events was similar in the 2 groups: leflunomide 56.5% and azathioprine 58.9%. CONCLUSIONS: The efficacy and safety profile of leflunomide are non-inferior to azathioprine for maintenance therapy of LN. Leflunomide may provide a new candidate for maintenance therapy in patients with LN. TRIAL REGISTRATION NUMBER: NCT01172002.

18.
Artigo em Inglês | MEDLINE | ID: mdl-35712878

RESUMO

The biomechanical effects of intervertebral discs and facet joints degeneration on the cervical spine are essential to understanding the mechanisms of spinal disorders to improve pathological and clinical treatment. In this study, the biomechanical effects of a progressively degenerated C5-C6 segment on the human lower cervical spine are determined by a detailed simulation of intervertebral disc degeneration. A detailed asymmetric three-dimension intact finite element model was developed using computed tomography scan data of the human lower cervical spine (C3-C7). The intact finite element model was then modified at the C5-C6 segment to build three degenerated models, such as mild, moderate, and severe degeneration. The physiological compressive load 73.6 N, and moment 1 Nm were applied at the superior endplate of the vertebra C3, and the inferior endplate of the C7 vertebra was a constraint for all degrees of freedom. Range of motion, maximum von Mises stress in the annulus, intradiscal pressure, and facet joint force of the degenerated models were computed. With progressive degeneration in the C5-C6 segment, the range of motion of degenerated and normal segments decreases in all postures. Intradiscal pressure of the degenerated segment decreases but increases in normal segments of degenerated segment C5-C6, and facet joint forces increase at both degenerated and normal segments. This study emphasizes that the degenerated disc alters the degenerated and normal segments' motion and loading patterns. The abnormal increase in facet joint force in the degenerated models threatened to accelerate the degeneration in the normal segments.

19.
Mol Imaging Biol ; 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35705779

RESUMO

PURPOSE: Sigma-1 receptor (Sig-1R), a chaperone that resides at the mitochondrion-associated endoplasmic reticulum (ER) membrane, is an ER stress biomarker. It is thought that ER stress plays a critical role in the progression of metabolic-associated fatty liver disease (MAFLD). The aim of this study was to evaluate a positron emission tomography (PET) tracer [18F]F-TZ3108 targeting Sig-1R for MAFLD. PROCEDURES: The mouse model of MAFLD was established by feeding high-fat diet (HFD) for 12 weeks. Dynamic (0-60 min) PET/CT scans were performed after intravenous injection of 2-deoxy-2[18F]fluoro-D-glucose ([18F]-FDG) and [18F]F-TZ3108. Tracer kinetic modeling was performed for quantification of the PET/CT imaging of the liver. Post-PET biodistribution, the liver tissue western blotting (WB), and immunofluorescence (IF) were performed to compare the expression of Sig-1R levels in the organs harvested from both MAFLD and age-matched control mice. RESULTS: The micro PET/CT imaging revealed a significantly decreased uptake of [18F]F-TZ3108 in the livers of the MAFLD group compared to the healthy controls, while the uptake of [18F]-FDG in the livers was not significantly different between the two groups. Based on the tracer kinetic modeling, the binding disassociate rate (k4) for [18F]F-TZ3108 was significantly increased in MAFLD group compared to healthy controls. The volume distribution (VT), and the non-displacement binding potential (BPND) revealed significantly decrease in MAFLD compared to healthy controls respectively. The post-PET biodistribution (%ID/g) of [18F]F-TZ3108 in the livers of MAFLD mice was significantly reduced nearly twofold than that in the livers of control mice. WB and IF experiments further confirmed the reduction of Sig-1R expression in the MAFLD group. CONCLUSIONS: The expression of Sig-1R in the liver, measured by the PET tracer, [18F]F-TZ3108, was significantly decreased in mouse model of MAFLD. The [18F]F-TZ3108 PET/CT imaging may provide a novel means of visualization for ER stress in MAFLD or other diseases in vivo.

20.
Dis Markers ; 2022: 7300593, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35756492

RESUMO

Purpose: Oral squamous cell carcinoma (OSCC) is the sixth leading cause of cancer-related death worldwide and is characterized by metastasis and recurrence. We aimed to evaluate the expression of AKT1 and PLK1 in OSCC and identify their correlation with the clinical and histological features and prognosis of patients with OSCC. Methods: Tissue samples were collected from 70 patients with OSCC and 50 patients with normal oral mucosa. The expression levels of AKT1 and PLK1 in OSCC tissues and normal oral mucosa were detected by immunohistochemistry. The chi-square test was used to identify correlations between the expression levels of AKT1 and PLK1 with patients' clinicopathologic characteristics. Survival analysis was assessed by the Kaplan-Meier method. Spearman's rank correlation test was used to determine the relationships between AKT1 and PLK1 expressions. The bioinformatics database GEPIA was used to verify the experimental results. Results: The chi-square test and Fisher's exact test showed that the positive expression rate of AKT1 and PLK1 in OSCC tissue was significantly higher than that in the normal oral mucosa (P < 0.05). PLK1 expression levels were significantly correlated with tumor stage and size (P < 0.05). Kaplan-Meier analysis showed that the survival time of AKT1 and PLK1 with high expression was significantly shorter than that of patients with low expression (P < 0.05). Spearman's rank correlation test showed a strong correlation between AKT1 and PLK1 expression in OSCC tissue (R = 0.53; P < 0.05). GEPIA bioinformatics database analysis results show that the expression and overall survival of AKT1 and PLK1 analysis and the correlation analysis of AKT1 and PLK1 were consistent with experimental results. Conclusion: AKT1 and PLK1 expressions are associated with the occurrence and progression of OSCC and may be used as diagnostic and prognostic indicators of OSCC. There may be a correlation between AKT1 and PLK1 in OSCC tissue.


Assuntos
Proteínas de Ciclo Celular , Neoplasias Bucais , Proteínas Serina-Treonina Quinases , Proteínas Proto-Oncogênicas c-akt , Proteínas Proto-Oncogênicas , Carcinoma de Células Escamosas de Cabeça e Pescoço , Biomarcadores Tumorais/metabolismo , Proteínas de Ciclo Celular/biossíntese , Humanos , Neoplasias Bucais/metabolismo , Prognóstico , Proteínas Serina-Treonina Quinases/biossíntese , Proteínas Proto-Oncogênicas/biossíntese , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo
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