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1.
Genome Res ; 33(8): 1354-1368, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37491077

RESUMO

The interactome networks at the DNA, RNA, and protein levels are crucial for cellular functions, and the diverse variations of these networks are heavily involved in the establishment of different cell states. We have developed a diffusion-based method, Hi-C to geometry (CTG), to obtain reliable geometric information on the chromatin from Hi-C data. CTG produces a consistent and reproducible framework for the 3D genomic structure and provides a reliable and quantitative understanding of the alterations of genomic structures under different cellular conditions. The genomic structure yielded by CTG serves as an architectural blueprint of the dynamic gene regulatory network, based on which cell-specific correspondence between gene-gene and corresponding protein-protein physical interactions, as well as transcription correlation, is revealed. We also find that gene fusion events are significantly enriched between genes of short CTG distances and are thus close in 3D space. These findings indicate that 3D chromatin structure is at least partially correlated with downstream processes such as transcription, gene regulation, and even regulatory networking through affecting protein-protein interactions.


Assuntos
Cromatina , Redes Reguladoras de Genes , Cromatina/genética , Regulação da Expressão Gênica , Cromossomos , DNA
2.
J Nanobiotechnology ; 22(1): 197, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38644475

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial inflammation, causing substantial disability and reducing life quality. While macrophages are widely appreciated as a master regulator in the inflammatory response of RA, the precise mechanisms underlying the regulation of proliferation and inflammation in RA-derived fibroblast-like synoviocytes (RA-FLS) remain elusive. Here, we provide extensive evidence to demonstrate that macrophage contributes to RA microenvironment remodeling by extracellular vesicles (sEVs) and downstream miR-100-5p/ mammalian target of rapamycin (mTOR) axis. RESULTS: We showed that bone marrow derived macrophage (BMDM) derived-sEVs (BMDM-sEVs) from collagen-induced arthritis (CIA) mice (cBMDM-sEVs) exhibited a notable increase in abundance compared with BMDM-sEVs from normal mice (nBMDM-sEVs). cBMDM-sEVs induced significant RA-FLS proliferation and potent inflammatory responses. Mechanistically, decreased levels of miR-100-5p were detected in cBMDM-sEVs compared with nBMDM-sEVs. miR-100-5p overexpression ameliorated RA-FLS proliferation and inflammation by targeting the mTOR pathway. Partial attenuation of the inflammatory effects induced by cBMDM-sEVs on RA-FLS was achieved through the introduction of an overexpression of miR-100-5p. CONCLUSIONS: Our work reveals the critical role of macrophages in exacerbating RA by facilitating the transfer of miR-100-5p-deficient sEVs to RA-FLS, and sheds light on novel disease mechanisms and provides potential therapeutic targets for RA interventions.


Assuntos
Artrite Reumatoide , Macrófagos , MicroRNAs , Transdução de Sinais , Serina-Treonina Quinases TOR , Animais , Humanos , Masculino , Camundongos , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Artrite Experimental/genética , Artrite Reumatoide/metabolismo , Artrite Reumatoide/genética , Artrite Reumatoide/patologia , Proliferação de Células , Vesículas Extracelulares/metabolismo , Inflamação/metabolismo , Macrófagos/metabolismo , Camundongos Endogâmicos DBA , MicroRNAs/genética , MicroRNAs/metabolismo , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia , Sinoviócitos/metabolismo , Serina-Treonina Quinases TOR/metabolismo
3.
J Chem Inf Model ; 63(14): 4355-4363, 2023 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-37386792

RESUMO

Virtual screening, including molecular docking, plays an essential role in drug discovery. Many traditional and machine-learning-based methods are available to fulfill the docking task. However, the traditional docking methods are normally extensively time-consuming, and their performance in blind docking remains to be improved. Although the runtime of docking based on machine learning is significantly decreased, their accuracy is still limited. In this study, we take advantage of both traditional and machine-learning-based methods and present a method, deep site and docking pose (DSDP), to improve the performance of blind docking. For traditional blind docking, the entire protein is covered by a cube, and the initial positions of ligands are randomly generated in this cube. In contrast, DSDP can predict the binding site of proteins and provide an accurate searching shape and initial positions for further conformational sampling. The sampling task of DSDP makes use of the score function and a similar but modified searching strategy of AutoDock Vina, accelerated by implementation in GPUs. We systematically compare its performance in redocking, blind docking, and virtual screening tasks with state-of-the-art methods, including AutoDock Vina, GNINA, QuickVina, SMINA, and DiffDock. In the blind docking task, DSDP reaches a 29.8% top-1 success rate (root-mean-squared deviation < 2 Å) on an unbiased and challenging test dataset with 1.2 s wall-clock computational time per system. Its performances on the DUD-E dataset and the time-split PDBBind dataset used in EquiBind, TANKBind, and DiffDock are also evaluated, presenting a 57.2 and 41.8% top-1 success rate with 0.8 and 1.0 s per system, respectively.


Assuntos
Descoberta de Drogas , Proteínas , Simulação de Acoplamento Molecular , Proteínas/química , Sítios de Ligação , Aprendizado de Máquina , Ligantes , Ligação Proteica
4.
Pharmacogenet Genomics ; 32(7): 247-256, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35852868

RESUMO

OBJECTIVE: Gut dysbiosis contributes to multiple autoimmune diseases, including ankylosing spondylitis, which is commonly treated with tumor necrosis factor (TNF)-α inhibitors (TNFis). Because host TNF-α levels are considered to interact with gut microbiota, we aimed to systematically investigate the microbiota profile of ankylosing spondylitis patients with anti-TNF-α-based treatment and identify potential key bacteria. METHODS: Fecal samples were collected from 11 healthy controls and 24 ankylosing spondylitis patients before/after anti-TNF-α treatment, the microbiota profiles of which were evaluated by 16S ribosomal DNA amplicon sequencing and subsequent bioinformatic analysis. RESULTS: Significantly different microbial compositions were observed in samples from ankylosing spondylitis patients compared with healthy controls, characterized by a lower abundance of short-chain fatty acid (SCFA)-producing bacteria. All patients exhibited a positive response after anti-TNF-α treatment, accompanied by a trend of restoration in the microbiota compositions and functional profile of ankylosing spondylitis patients to healthy controls. In particular, the abundance of SCFA-producing bacteria (e.g. Megamonsa and Lachnoclostridium ) was not only significantly lower in ankylosing spondylitis patients than in healthy controls and restored after anti-TNF-α treatment but also negatively correlated with disease severity (e.g. cor = -0.52, P = 8 × 10 -5 for Megamonsa ). In contrast, Bacilli and Haemophilus may contribute to ankylosing spondylitis onset and severity. CONCLUSIONS: Microbiota dysbiosis in ankylosing spondylitis patients can be restored after anti-TNF-α treatment, possibly by impacting SCFA-producing bacteria.


Assuntos
Microbioma Gastrointestinal , Espondilite Anquilosante , Bactérias/genética , Disbiose/microbiologia , Microbioma Gastrointestinal/genética , Humanos , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/microbiologia , Espondilite Anquilosante/patologia , Inibidores do Fator de Necrose Tumoral , Fator de Necrose Tumoral alfa
5.
Nanotechnology ; 33(41)2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35728516

RESUMO

Gold nanorods (AuNRs) possess a high optical nonlinear coefficient, ultrafast optical response speed and widely tunable localized surface plasmon resonance (LSPR) wavelength covering the visible and near infrared region. Therefore, they are extensively investigated for many optical applications. However, the poor thermal stability of the AuNRs seriously restricts their practical performance. In addition, for many applications, such as optical communication or laser modulation, AuNRs have to be combined with transparent solids, for example polymers, glass or crystals to make devices. Here, we report on the preparation of 0.23 mg AuNR dispersed methyl silicone resin (MSR) with longitudinal LSPR (L-LSPR) wavelength (1450 nm) in the optical communication window. We found that AuNR-silicone composites possess high thermal stability. After calcination in ambient environment at a temperature of 250 °C for 10 h, the L-LSPR peak of the sample can remain longer than 1380 nm, implying that the NR shape of the Au particles was well maintained. Using the open-aperture Z-scan technique, the nonlinear absorption coefficient of the composites was measured as -11.71 cm GW-1, higher than many nonlinear materials. Thus, the thermally stable AuNR@SiO2-MSR composite with high nonlinearity is promising for practical applications in the optical communication window.

6.
Phys Chem Chem Phys ; 24(38): 23840-23848, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36165176

RESUMO

Diffusion-based translocation along DNA or RNA molecules is essential for genome regulatory proteins to execute their biological functions. The reduced dimensionality of the searching process makes the proteins bind specific target sites at a "faster-than-diffusion-controlled rate". We herein report a photoresponsive slider-track diffusion system capable of self-assembly rate acceleration, which consists of (-)-camphorsulfonic acid, 4-(4'-n-octoxylphenylazo)benzenesulfonic acid, and isotactic poly(2-vinylpyridine). The protonated pyridine rings act as the footholds for anionic azo sliders to diffusively bind and slide along polycationic tracks via electrostatic interactions. Ultraviolet light triggers the trans to cis isomerization and aggregation of azo sliders, which can be monitored by multiple spectroscopic methods without labeling. The presence of vinyl polymer track increases the aggregation rate of cis azobenzene up to ∼20 times, depending on the stereoregularity of the polymer chain, the acid/base ratio and the addition of salt. This system has a feature of simplicity, monitorability, controllability, and could find applications in designing molecular machines with desired functionalities.


Assuntos
Compostos Azo , DNA , Compostos Azo/química , DNA/química , Polímeros/química , Piridinas , RNA , Raios Ultravioleta
7.
J Clin Lab Anal ; 36(9): e24605, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35837962

RESUMO

INTRODUCTION: We performed a cross-sectional study to investigate the clinical usefulness of YKL-40 in patients with dermatomyositis (DM) and conducted a systematic review to summarize the clinical value of YKL-40 in patients with polymyositis (PM)/DM. MATERIALS AND METHODS: A cross-sectional study and a systematic review were performed to study the clinical value of YKL-40 in patients with PM/DM. Serum YKL-40 level was detected using enzyme-linked immunosorbent assay, and its association with clinical and laboratory parameters was analyzed. In the systematic review, electronic databases of OVID Embase, OVID Medline, and web of science were searched to collect studies that reported clinical use of YKL-40 in patients with PM/DM. RESULTS: In the cross-sectional study, serum YKL-40 level was higher in patients with DM than in healthy controls (median [interquartile range]: 84.09 [52.72-176.4] ng/ml versus 27.37 [12.30-53.58] ng/ml, p < 0.0001). Serum levels of YKL-40 were associated with the course of DM (r = -0.469, p < 0.001), CRP (r = 0.303, p = 0.043), CK (r = 0.263, p = 0.037), and global disease activity (r = 0.628, p < 0.001). The area under the ROC curve was 0.835 (95% confidence interval 0.751-0.920). In the systematic review, a total of four studies were included with moderate to high quality. Serum level of YKL-40 has the possibility for diagnosing PM/DM, identifying PM/DM patients with interstitial lung disease (ILD) or rapid progress ILD, and predicting death. CONCLUSION: Serum YKL-40 level is a possible useful biomarker for PM/DM diagnosis and may be used to predict prognosis.


Assuntos
Proteína 1 Semelhante à Quitinase-3/metabolismo , Dermatomiosite , Doenças Pulmonares Intersticiais , Polimiosite , Estudos Transversais , Humanos , Prognóstico
8.
J Cell Biochem ; 120(3): 4613-4619, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30552709

RESUMO

BACKGROUND: Recently, the role of α-adducin rs4961 polymorphism in hypertension (HTN) was intensively analyzed, but the results of these studies were inconsistent. Therefore, we performed this study to better assess the relationship between α-adducin rs4961 polymorphism and the likelihood of HTN. METHODS: Eligible studies were searched in PubMed, Medline, Embase, and Web of Science. Odds ratios with 95% confidence intervals were used to assess the relationship between α-adducin rs4961 polymorphism and HTN. RESULTS: A total of 33 studies with 40 432 participants were analyzed. Significant associations with the likelihood of HTN were detected for the α-adducin rs4961 polymorphism with fixed effect models (FEM) (dominant model: P = 0.003; allele model: P = 0.003), but not with random effect models (REM). Further subgroup analysis according to ethnicity of participants revealed that the α-adducin rs4961 polymorphism was significantly associated with the likelihood of HTN in Asians (7721 cases and 8299 controls) with both FEMs (dominant model: P < 0.0001; additive model: P = 0.01; allele model: P < 0.0001) and REMs (dominant model: P = 0.0005; additive model: P = 0.03; allele model: P = 0.0006). CONCLUSIONS: Our findings indicate that the α-adducin rs4961 polymorphism may serve as a genetic biomarker of HTN in Asians.


Assuntos
Povo Asiático/genética , Proteínas de Ligação a Calmodulina/genética , Hipertensão , Polimorfismo Genético , Feminino , Humanos , Hipertensão/etnologia , Hipertensão/genética , Masculino
9.
Fish Shellfish Immunol ; 91: 216-222, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31121288

RESUMO

In the present study, a monoclonal antibody (mAb) against large yellow croaker IgM was produced by immunizing mice with purified large yellow croaker serum IgM. Western blotting showed that this mAb could specifically react with the heavy chain of large yellow croaker serum IgM. Indirect immunofluorescence assay (IFA) analysis suggested that the resulting mouse anti-IgM mAb could recognize membrane-bound IgM (mIgM) molecules of large yellow croaker. This mouse anti-IgM mAb also can be used for sorting of large yellow croaker IgM+ B cells through the magnetic-activated cell sorting (MACS) method, which was further confirmed by RT-PCR analysis of specific marker genes for B cells. Flow cytometry analysis showed that the percentages of IgM+ B cells in head kidney, spleen and peripheral blood lymphocytes were 29.00 ±â€¯1.58%, 33.00 ±â€¯1.64%, and 16.50 ±â€¯2.39%, respectively. Additionally, the phagocytosis rates of IgM+ B cells for 0.5 µm beads in head kidney, spleen and peripheral blood were calculated to be 7.56 ±â€¯0.58%, 4.053 ±â€¯0.62% and 23.17 ±â€¯2.26%, respectively, while only 2.36 ±â€¯0.23%, 1.16 ±â€¯0.44% and 6.41 ±â€¯0.45 of IgM+ B cells in these three tissues ingested 1 µm beads. Taken together, our data demonstrated that the mouse anti-IgM mAb produced in this study could be used as a tool to characterize IgM+ B cells and to study functions of IgM in large yellow croaker.


Assuntos
Anticorpos Monoclonais/imunologia , Linfócitos B/imunologia , Imunoglobulina M/imunologia , Perciformes/imunologia , Animais , Western Blotting/veterinária , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Técnica Indireta de Fluorescência para Anticorpo/veterinária , Camundongos , Camundongos Endogâmicos BALB C
10.
Angew Chem Int Ed Engl ; 58(12): 3859-3864, 2019 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-30637898

RESUMO

Theoretical calculations reveal that intrinsic pentagons in the basal plane can contribute to the local electronic redistribution and the contraction of band gap, making the carbon matrix possess superior binding affinity and electrochemical reactivity. To experimentally verify this, a pentagon-defect-rich carbon nanomaterial was constructed by means of in situ etching of fullerene molecules (C60 ). The electrochemical tests show that, relative to hexagons, such a carbon-based material with abundant intrinsic pentagon defects makes much greater contribution to the electrocatalytic oxygen reduction activity and electric double layer capacitance. It shows a four-electron-reaction mechanism similar to commercial Pt/C and other transition-metal-based catalysts, and a higher specific capacitance than many reported metal-free carbon materials. These results show the influence of intrinsic pentagon defects for developing carbon-based nanomaterials toward energy conversion and storage devices.

11.
J Chem Theory Comput ; 20(2): 832-841, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38196086

RESUMO

Slab geometric systems are widely utilized in molecular simulations. However, an efficient, straightforward, and accurate method for calculating electrostatic interactions in these systems for molecular dynamics (MD) simulations is still needed. This review introduces a PME-like approach called PMC-IZ, specifically designed for slab geometric systems. Traditional approaches for long-range electrostatic interaction calculations in slab geometry typically involve Ewald summation, where the Gaussian charge density is summed within 3D unit cells and then integrated in the 2D periodic space. In the proposed approach here, the Poisson equation was solved for a single Gaussian charge density within 2Dl periodic space, followed by convolution within 3D unit cells using an effective potential as the convolution kernel for summation. The effective potential ensures that the solution within the region of interest adheres strictly to 2D periodic boundary conditions while inherently possessing 3D periodic boundary condition properties. The PMC-IZ method provides for such systems accurate treatment of electrostatic interactions, overcomes limitations associated with finite vacuum layers, and offers improved computational efficiency. We thus postulate that this method provides a valuable tool for studying electrostatic interactions in slab geometric system MD simulations. It has promising applications in various areas such as surface science, catalysis, and materials research, where accurate modeling of slab geometric electrostatic interactions is essential.

12.
Nat Nanotechnol ; 19(4): 479-484, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38049594

RESUMO

The permeability and selectivity of biological and artificial ion channels correlate with the specific hydration structure of single ions. However, fundamental understanding of the effect of ion-ion interaction remains elusive. Here, via non-contact atomic force microscopy measurements, we demonstrate that hydrated alkali metal cations (Na+ and K+) at charged surfaces could come into close contact with each other through partial dehydration and water rearrangement processes, forming one-dimensional chain structures. We prove that the interplay at the nanoscale between the water-ion and water-water interaction can lead to an effective ion-ion attraction overcoming the ionic Coulomb repulsion. The tendency for different ions to become closely packed follows the sequence K+ > Na+ > Li+, which is attributed to their different dehydration energies and charge densities. This work highlights the key role of water molecules in prompting close packing and concerted movement of ions at charged surfaces, which may provide new insights into the mechanism of ion transport under atomic confinement.

13.
J Phys Chem B ; 127(22): 5034-5045, 2023 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-37252724

RESUMO

Cyclic GMP-AMP synthase (cGAS) has been widely investigated as a drug target for its crucial role in innate immunity. However, the inhibitors designed using mouse model were often shown to be ineffective for humans. This outcome indicates that the activation mechanisms of human and mouse cGAS (mcGAS) are different. The cGAS activation is achieved by dimerization via binding to DNA, the detailed mechanism of which, however, is not entirely clear. To investigate these mechanisms, molecular dynamics (MD) simulations were performed on several states of four types of cGAS, namely, the mcGAS, the wild-type and A- and C-type mutations of human cGAS (hcGAS). We find that sequence differences between hcGAS and mcGAS can directly affect the protein structure stability, especially that of the siteB domain. The sequence and structural differences also contribute to DNA-binding differences. In addition, the conformational fluctuations of cGAS are found to correlate with the regulation of catalytic capacity. More importantly, we illustrate that dimerization enhances the correlation among distant residues and significantly reinforces the allosteric signal transmission among the DNA-binding interfaces and the catalytic pocket, which facilitates rapid immune response to cytosolic DNA. We conclude that siteB domain plays a prominent role in mcGAS activation, while siteA domain is key to hcGAS activation.


Assuntos
Simulação de Dinâmica Molecular , Nucleotidiltransferases , Humanos , Animais , Camundongos , Nucleotidiltransferases/química , DNA/química
14.
Heart Lung ; 57: 110-116, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36182861

RESUMO

BACKGROUND: Interstitial lung disease (ILD) is a common pulmonary complication of connective tissue disease (CTD) that can lead to poor quality of life and prognosis. OBJECTIVES: To explore the screening value of lung ultrasound (LUS) for connective tissue disease-associated interstitial lung disease (CTD-ILD). METHODS: Data of patients with CTD were collected, and each patient underwent LUS, high-resolution computed tomography (HRCT), and pulmonary function tests. Considering HRCT is the gold standard for diagnosing CTD-ILD, patients were divided into CTD-ILD and CTD-non-ILD groups. The LUS and HRCT results were assessed using semiquantitative and Warrick scores, respectively. Pulmonary function results were also collected. Receiver operating characteristic (ROC) curves were used to evaluate the accuracy of LUS diagnosis. Spearman correlation analysis was used to analyze the correlation between LUS, HRCT, and lung function indices. RESULTS: A total of 88 patients (65 with CTD-ILD and 23 with CTD-non-ILD) were included in this study. The sensitivity and specificity of LUS for the diagnosis of CTD-ILD were 86.60% and 82.60%, respectively, which was consistent with the HRCT results (P < 0.05). The LUS results (total number of B-lines, frequency of B-line, pleural thickness, and pleural-line irregularity) were positively correlated with the HRCT Warrick score (r = 0.77, 0.76, 0.65 and 0.71, P < 0.05). CONCLUSIONS: LUS may be a promising tool for screening patients with CTD-ILD.


Assuntos
Doenças do Tecido Conjuntivo , Doenças Pulmonares Intersticiais , Humanos , Qualidade de Vida , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/etiologia , Pulmão/diagnóstico por imagem , Doenças do Tecido Conjuntivo/complicações , Doenças do Tecido Conjuntivo/diagnóstico por imagem , Ultrassonografia/métodos
15.
Adv Sci (Weinh) ; 10(33): e2303421, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37822163

RESUMO

Broadband near-infrared (NIR) photonic materials have wide applications. Although extensive studies on rare-earth, transition-metal, and even semiconductor-activated materials have enabled the development of a rich NIR material pool, developing broadband and efficient photonic candidates covering the NIR I and II regions from 750 to 1500 nm has been met with limited success. Here, it is reported that a subnano Te cluster with a characteristic configuration different from that of the ion state may fill the aforementioned gap. Further, a strategy is proposed for the in situ generation and stabilization of Te clusters by tuning the cluster evolution in glass. A novel active photonic glass embedded with a Te cluster is fabricated; it exhibits intense and broadband short-wave NIR luminescence with a central wavelength at 1030 nm and a bandwidth exceeding 330 nm. Interestingly, the glass exhibited a full visible-spectrum conversion ability from 300 to 800 nm. The application of this unique broadband excitation feature for night vision and tissue penetration is demonstrated using a smartphone as the excitation source. These findings demonstrate a fundamental principle of cluster design in glass for creating new properties and provide a new direction for developing novel cluster-derived functional composite materials.

16.
J Chem Theory Comput ; 19(14): 4338-4350, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37358079

RESUMO

Molecular simulations, which simulate the motions of particles according to fundamental laws of physics, have been applied to a wide range of fields from physics and materials science to biochemistry and drug discovery. Developed for computationally intensive applications, most molecular simulation software involves significant use of hard-coded derivatives and code reuse across various programming languages. In this Review, we first align the relationship between molecular simulations and artificial intelligence (AI) and reveal the coherence between the two. We then discuss how the AI platform can create new possibilities and deliver new solutions to molecular simulations, from the perspective of algorithms, programming paradigms, and even hardware. Rather than focusing solely on increasingly complex neural network models, we introduce various concepts and techniques brought about by modern AI and explore how they can be transacted to molecular simulations. To this end, we summarized several representative applications of molecular simulations enhanced by AI, including from differentiable programming and high-throughput simulations. Finally, we look ahead to promising directions that may help address existing issues in the current framework of AI-enhanced molecular simulations.

17.
Adv Rheumatol ; 62(1): 22, 2022 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-35761320

RESUMO

BACKGROUND: This systematic review and meta-analysis aimed to investigate the incidence and risk of knee and hip replacement in patients with osteoarthritis (OA) treated with different medications. METHODS: OVID MEDLINE, OVID EMBASE, Cochrane and Web of Science electronic databases were searched from inception to May 4th, 2022. Clinical trials, including randomized controlled trials, cohort studies and case-control studies, were selected. The meta-analysis effect size was estimated using either incidence with 95% confidence intervals (CIs) or odds ratio (OR)/relative risk (RR) with 95% CIs. The risk of bias and heterogeneity among studies were assessed and analyzed. RESULTS: Forty studies were included, involving 6,041,254 participants. The incidence of joint replacement in patients with OA varied according to the study design and treatments. The incidence of knee arthroplasty varied from 0 to 70.88%, while the incidence of hip arthroplasty varied from 11.71 to 96.43%. Compared to non-users, bisphosphonate users had a reduced risk of knee replacement (RR = 0.71, 95% CI: 0.66-0.77; adjusted hazard ratio [aHR] = 0.76, 95% CI: 0.70-0.83). Compared to intra-articular corticosteroid users, hyaluronic acid (HA) users had a higher risk of knee arthroplasty (RR = 1.76, 95% CI: 1.38-2.25). No publication bias was observed. CONCLUSIONS: Bisphosphonate treatment is associated with a reduced risk of knee replacement. More studies are needed to validate our results due to the limited number of eligible studies and high heterogeneity among studies.


Assuntos
Artroplastia de Substituição , Osteoartrite do Joelho , Difosfonatos/uso terapêutico , Humanos , Incidência , Articulação do Joelho , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/cirurgia
18.
Rev Sci Instrum ; 93(1): 014705, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35104965

RESUMO

To study the damage and protection mechanism of the transient electromagnetic pulse to the cables of the electronic equipment under test, an all-solid-state pulsed current injection source with light initiated multi-gate semiconductor switches is developed. The output peak current range of the prepared all-solid-state pulsed current injection source was 0.1-1 kA, the risetime was 18 ns, and the pulse width was 520 ns. In addition, the waveforms of the output peak current were consistent.

19.
J Pharm Sci ; 111(11): 3047-3053, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35779664

RESUMO

Betulinic acid (BA) is a natural pentacyclic triterpenoid with broad-spectrum anticancer activity, which has great development potential as an anti-cancer drug. In this study, a novel hyaluronic acid (HA)-modified BA liposome (BA-L) was developed for use in targeted liver cancer therapy. The size, polymer dispersity index (PDI), zeta potential, and entrapment efficiency were measured. Cell viability, cell migration and clonogenicity, cellular uptake, immunohistochemistry of CD44, and protein expression of ROCK1/IP3/RAS were also investigated. BA, BA-L, and HA-BA-L had no inhibitory effect on the activity of LO2 normal hepatocytes, but they inhibited the proliferation of HepG2 and SMMC-7721 cells in a dose- and time-dependent manner, with HA-BA-L exhibiting the most prominent inhibitory effect. Compared with the BA-L group, the expression of CD44 in HepG2 cells in the HA-BA-L group was decreased. The results of WB showed that BA, BA-L, and HA-BA-L downregulated the expression of ROCK1, IP3, and RAS in HepG2 cells, and the expression level in the HA-BA-L group was significantly decreased. The easily prepared HA-BA-L was demonstrated to be an excellent CD44-mediated intracellular delivery system capable of targeting effects. Further mechanistic research revealed that the inhibition of HA-BA-L on HepG2 cells may be mediated by blocking the ROCK1/IP3/RAS signaling pathways.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Linhagem Celular Tumoral , Humanos , Receptores de Hialuronatos/metabolismo , Ácido Hialurônico/uso terapêutico , Lipossomos , Triterpenos Pentacíclicos/farmacologia , Triterpenos Pentacíclicos/uso terapêutico , Polímeros , Quinases Associadas a rho/uso terapêutico , Ácido Betulínico
20.
Dis Markers ; 2022: 9223883, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35356065

RESUMO

Background: Insulin-like growth factor-binding proteins (IGFBPs) and connective tissue growth factor (CTGF) participate in angiogenesis. Dermatomyositis (DM) is characterized by microvasculopathy-derived skin lesions. Here, we investigated the clinical significance of serum IGFBP and CTGF levels in DM patients. Methods: In this study, 65 DM patients and 30 healthy controls were enrolled. Serum IGFBP and CTGF levels were examined by ELISA, and their correlation with clinical and laboratory findings was analyzed by Spearman's correlation. Results: Serum IGFBP-2, IGFBP-4, and CTGF levels were higher in DM patients than in healthy controls (median (quartile): 258.9 (176.4-326.1) ng/mL vs. 167.7 (116.1-209.4) ng/mL, p < 0.0001; 450.4 (327.3-631.8) ng/mL vs. 392.2 (339.0-480.2) ng/mL, p = 0.04; and 45.71 (38.54-57.45) ng/mL vs. 35.52 (30.23-41.52) ng/mL, p = 0.001, respectively). IGFBP-2 and CTGF levels were positively correlated with cutaneous (r = 0.257, p = 0.040 and r = 0.427, p = 0.015, respectively) and global (r = 0.380, p = 0.002 and r = 0.292, p = 0.019, respectively) disease activity in DM patients. Conclusion: Serum IGFBP-2 and CTGF levels were increased in patients with DM and correlated with cutaneous and global disease activity.


Assuntos
Dermatomiosite , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Humanos , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina , Fator de Crescimento Insulin-Like I/metabolismo
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