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1.
Curr Issues Mol Biol ; 44(9): 3930-3947, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36135182

##### RESUMO

Bat plasminogen activators α2 (DSPAα2) has extremely high medicinal value as a powerful natural thrombolytic protein. However, wild-type DSPAα2 has two N-glycosylation sites (N185 and N398) and its non-human classes of high-mannose-type N-glycans may cause immune responses in vivo. By mutating the N-glycosylation sites, we aimed to study the effect of its N-glycan chain on plasminogen activation, fibrin sensitivity, and to observe the physicochemical properties of DSPAα2. A logical structure design was performed in this study. Four single mutants and one double mutant were constructed and expressed in Pichia pastoris. When the N398 site was eliminated, the plasminogen activator in the mutants had their activities reduced to ~40%. When the N185 site was inactivated, there was a weak decrease in the plasminogen activation of its mutant, while the fibrin sensitivity significantly decreased by ~10-fold. Neither N-glycosylation nor deglycosylation mutations changed the pH resistance or heat resistance of DSPAα2. This study confirms that N-glycosylation affects the biochemical function of DSPAα2, which provides a reference for subsequent applications of DSPAα2.

2.
Int J Biol Macromol ; 221: 1228-1237, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36087756

##### RESUMO

It was investigated that the rheology, starch-gluten-surimi network, thermal properties, and water distribution of surimi-wheat dough, and texture characteristics, cooking properties, and microscopic characteristics of the surimi-wheat noodles with konjac glucomannan (KGM) of different viscosities in different concentrations. The results showed that the storage (G'), loss (Gâ³), and complex (Gâ) moduli of dough increased with adding KGM. With the increase of KGM viscosity, the reduction in the free sulfhydryl (SH) content to 0.84 µmol/g and the increase in the free water content to 8.25 % led to significantly improved enthalpy and the microstructure density. The hardness and tensile length of noodles were substantially increased by adding 3 % KGM. In addition, the KGM enhanced the starch-gluten-surimi network and improved the cooking qualities and textural properties of noodles. More importantly, the application of KGM in the wheat flour composite system also showed better performance. Thus, the introduction of KGM into the surimi-wheat dough had a significant effect on the optimization of the macro- and micro-characteristics of dough and noodles.

3.
Microb Pathog ; 172: 105768, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36096456

##### RESUMO

The probiotic E. coli Nissle 1917 (EcN) plays an important role in regulating the microbial components of the gut and preventing inflammation of the gastrointestinal tract. Currently, the long-term use of antibiotics for the treatment of lethal white diarrhea in chicks caused by Salmonella has led to increased morbidity and mutation rates. Therefore, we want to use EcN as an antibiotic alternative as an alternative approach to prevent Salmonella-induced white diarrhea in chickens. To date, there are no reports of EcN being used for the prevention and control of Salmonella pullorum (S. pullorum) in chickens. In vitro, pretreatment with EcN significantly decreased the cellular invasion of S. pullorum CVCC533 in a chicken fibroblast (DF-1) cell model. Then, 0-day-old egg-laying chickens were orally inoculated with EcN at a dose of 109 CFU/100 µL at either Day 1 (EcN1) or both Day 1 and Day 4 (EcN2). Then, S. pullorum CVCC533 was used to challenge the cells at a dose of 1.0 × 107 CFU/100 µL on Day 8. Next, the body weights and survival rates were recorded for 14 consecutive days, and the colonization of S. pullorum in the spleen and liver at 7 days post-challenge (dpc) was determined. Chicken feces were also collected at 2, 4, 6 and 8 dpc to evaluate the excretion of pathogenic bacteria in feces. The liver, duodenum and rectum samples were collected and analyzed by pathological histology at 7 dpc to evaluate the protective effect of EcN on the mucosa, villi and crypts of the small intestine. The spleen and bursa were collected, and the immune organ index was calculated. In addition, the contents of the cecum of chicks were collected at 7 dpc for 16S rRNA sequencing to detect the distribution of microbial communities in the intestine. The results showed that EcN was able to protect against CVCC533 challenge, as shown by decreased body weight loss, mortality and shedding of pathogenic bacteria in fecal samples in the EcN1 plus Salmonella challenge group (EcN1S) but not the EcN2 plus Salmonella challenge group (EcN2S). The pathogenic changes in the liver, duodenum and rectum also demonstrated that one dose but not two doses of EcN effectively prolonged the length of the pilus with decreased crypt depth, indicating its protective effects against S. pullorum. In addition, the 16S rRNA sequencing results suggested that EcN could enlarge the diversity of intestinal flora, decrease the abundance of pathogenic bacteria and increase the abundance of beneficial bacteria, such as Lactobacillus. In conclusion, EcN has shown moderate protection against S. pullorum challenge in chickens.

4.
Int J Biol Macromol ; 220: 1329-1344, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36116592

##### RESUMO

Biodegradable natural polymers are receiving increasing attention as potential candidates for wound dressing. In the present study, composite microspheres (mCSB) based on calcium alginate (CA), silk fibroin peptide (SP), and Bletilla striata polysaccharide (BSP) were prepared by the reverse emulsion method. The excellent swelling properties of microspheres enable them to rapidly promote thrombosis. Microspheres can increase the platelet aggregation index to 1.5 and the aggregation rate of red blood cells to as high as 80 %. Furthermore, tannic acid (TA)-loaded microspheres demonstrate a slow-release effect on TA; this allows the microspheres to exhibit good long-lasting antibacterial properties. Due to the synergistic effects of SP and TA, the cell senescence was delayed, with a 126.69 % survival rate of fibroblasts after 3 days of incubation. In addition, TA led to a rapid reduction in inflammation levels, with a wound closure rate of >92.80 % within 7 days. The multifunctional TA-loaded mCSB has great application potential for rapid wound healing and the treatment of wound hemostasis.

5.
Sci Rep ; 12(1): 15839, 2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36151271

##### RESUMO

Fracture nonunion is a common and challenging complication. Although direct current stimulation has been suggested to promote fracture healing, differences in cell density near the positive and negative electrodes have been reported during direct current stimulation. This study aimed to explore the effects of these differences on osteoblast proliferation and fracture healing. MC3T3-E1 cells were stimulated by positive and negative charges to observe cell proliferation, apoptosis, and osteogenic factor expression in vitro, while positive and negative charges were connected to the Kirschner wires of the fractures in an in vivo double-toe fracture model in New Zealand white rabbits and fracture healing was assessed in digital radiography (DR) examinations performed on days 1, 15, 30. Bone tissue samples of all rabbits were analysed histologically after the last examination. The results showed that in comparison with the control group, after DC stimulation, the number of cells near the positive electrode decreased significantly (P < 0.05), apoptosis increased (P < 0.05), the expression of osteocalcin, osteoblast-specific genes, and osteonectin decreased significantly near the positive electrode (P < 0.05) and increased significantly at the negative electrode (P < 0.05). The fracture at the positive electrode junction of New Zealand white rabbits did not heal. Histomorphological analysis showed more bone trabeculae and calcified bone in the bone tissue sections of the control group and the negative electrode group than in the positive electrode group. The bone trabeculae were thick and showed good connections. However, positive charge inhibited osteoblast proliferation and a positive charge at fracture sites did not favour fracture healing. Thus, a positive charge near the fracture site may be a reason for fracture nonunion.

6.
New Phytol ; 2022 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-36151918

##### RESUMO

·Receptor-like proteins (RLPs) lacking the cytoplasmic kinase domain play crucial roles in plant growth, development and immunity. However, what remains largely elusive is whether RLP protein levels are fine-tuned by E3 ubiquitin ligases, which are employed by receptor-like kinases for signaling attenuation. Nicotiana benthamiana NbEIX2 is a leucine-rich repeat RLP (LRR-RLP) that mediates fungal xylanase-triggered immunity. ·Here we show that NbEIX2 associates with an F-box protein NbPFB1, which promotes NbEIX2 degradation likely by forming an SCF E3 ubiquitin ligase complex, and negatively regulates NbEIX2-mediated immune responses. ·NbEIX2 undergoes ubiquitination and proteasomal degradation in planta. Interestingly, NbEIX2 without its cytoplasmic tail is still associated with and destabilized by NbPFB1. In addition, NbPFB1 also associates with and destabilizes NbSOBIR1, a co-receptor of LRR-RLPs, and fails to promote NbEIX2 degradation in the sobir1 mutant. ·Our findings reveal a distinct model of NbEIX2 degradation, in which an F-box protein destabilizes NbEIX2 indirectly in a SOBIR1-dependent manner.

7.
Biosensors (Basel) ; 12(9)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36140099

##### RESUMO

This paper presents the development of a compact, three-electrode electrochemical device functionalized by a biocompatible layer of hyaluronic acid methacrylate (HAMA) hydrogel for the adsorptive removal of detrimental lead (Pb(II)) ions in aqueous solutions. An adsorption mechanism pertaining to the observed analytical performance of the device is proposed and further experimentally corroborated. It is demonstrated that both the molecular interactions originating from the HAMA hydrogel and electrochemical accumulation originating from the electrode beneath contribute to the adsorption capability of the device. Infrared spectral analysis reveals that the molecular interaction is mainly induced by the amide functional group of the HAMA hydrogel, which is capable of forming the Pb(II)-amide complex. In addition, inductively coupled plasma mass spectrometric (ICP-MS) analysis indicates that the electrochemical accumulation is particularly valuable in facilitating the adsorption rate of the device by maintaining a high ion-concentration gradient between the solution and the hydrogel layer. ICP-MS measurements show that 94.08% of Pb(II) ions present in the test solution can be adsorbed by the device within 30 min. The HAMA hydrogel-modified electrochemical devices exhibit reproducible performance in the aspect of Pb(II) removal from tap water, with a relative standard deviation (RSD) of 1.28% (for n = 8). The experimental results suggest that the HAMA hydrogel-modified electrochemical device can potentially be used for the rapid, on-field remediation of Pb(II) contamination.

8.
Thromb Res ; 219: 1-13, 2022 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-36084517

##### RESUMO

Neutrophil extracellular traps (NETs) are known to play a role in various diseases affecting coagulation. As of now, it is unclear whether NETs are present in hematoma samples collected from patients who have suffered an intracranial hemorrhage (ICH). The objective of this was to determine whether NETs are present in circulation and hematoma samples from ICH patients and to evaluate the procoagulant activity (PCA) of NETs during the ICH process. The expression of NET markers in samples from 78 ICH patients and 35 healthy donners was detected by ELISA and flow cytometry. Immunostaining for neutrophil markers (neutrophil CD66b) and NET markers (citrullinated histone H3 [H3Cit] and extracellular DNA) was performed on hematoma samples obtained from ICH patients undergoing intracranial hematoma evacuation. Our findings suggest that plasma and hematoma samples from patients with ICH showed high levels of NETs. Furthermore, using DNase I to target NETs enhanced ex vivo hematoma lysis. In conclusion, NETs play an important role in the ICH process and may be a novel therapeutic target for treatment of ICH patients.

9.
ACS Omega ; 7(36): 32131-32152, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36120034

##### RESUMO

The pathogenesis of Alzheimer's disease (AD) is very complex, and there are many hypotheses. Therefore, the development of a multi-target-directed-ligand may be an effective therapeutic strategy. Our previous study showed that notopterol (a natural product from Notopterygium) is a dual BACE1/GSK3ß inhibitor. In this study, we designed and synthesized 48 notopterol derivatives with furacoumarin as a scaffold in order to enhance their balanced AChE/BACE1/GSK3ß inhibitory activity. Fortunately, 1c showed effective inhibitory activity against AChE (58.7% at 1.0 µM), BACE1 (48.3% at 20 µM), and GSK3ß (40.3% at 10 µM). Furthermore, 1c showed good blood-brain barrier penetrability, suitable bioavailability, and oral safety. More importantly, 1c could ameliorate the impaired learning and memory in Aß-induced AD mice. In conclusion, we reported the triple inhibitor of AChE/BACE1/GSK3ß lead compounds based on a furocoumarin scaffold of notopterol for the first time, which provides a potential new strategy for the treatment of AD.

10.
Brief Bioinform ; 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36124759

##### RESUMO

Microbial community classification enables identification of putative type and source of the microbial community, thus facilitating a better understanding of how the taxonomic and functional structure were developed and maintained. However, previous classification models required a trade-off between speed and accuracy, and faced difficulties to be customized for a variety of contexts, especially less studied contexts. Here, we introduced EXPERT based on transfer learning that enabled the classification model to be adaptable in multiple contexts, with both high efficiency and accuracy. More importantly, we demonstrated that transfer learning can facilitate microbial community classification in diverse contexts, such as classification of microbial communities for multiple diseases with limited number of samples, as well as prediction of the changes in gut microbiome across successive stages of colorectal cancer. Broadly, EXPERT enables accurate and context-aware customized microbial community classification, and potentiates novel microbial knowledge discovery.

11.
Magn Reson Med ; 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36128892

##### RESUMO

PURPOSE: To develop an MR multitasking-based dynamic imaging for cerebrovascular evaluation (MT-DICE) technique for simultaneous quantification of permeability and leakage-insensitive perfusion with a single-dose contrast injection. METHODS: MT-DICE builds on a saturation-recovery prepared multi-echo fast low-angle shot sequence. The k-space is randomly sampled for 7.6 min, with single-dose contrast agent injected 1.5 min into the scan. MR multitasking is used to model the data into six dimensions, including three spatial dimensions for whole-brain coverage, a saturation-recovery time dimension, and a TE dimension for dynamic T 1 $${\mathrm{T}}_1$$ and T 2 * $${\mathrm{T}}_2^{\ast }$$ quantification, respectively, and a contrast dynamics dimension for capturing contrast kinetics. The derived pixel-wise T 1 / T 2 * $${\mathrm{T}}_1/{\mathrm{T}}_2^{\ast }$$ time series are converted into contrast concentration-time curves for calculation of kinetic metrics. The technique was assessed for its agreement with reference methods in T 1 $${\mathrm{T}}_1$$ and T 2 * $${\mathrm{T}}_2^{\ast }$$ measurements in eight healthy subjects and, in three of them, inter-session repeatability of permeability and leakage-insensitive perfusion parameters. Its feasibility was also demonstrated in four patients with brain tumors. RESULTS: MT-DICE T 1 / T 2 * $${\mathrm{T}}_1/{\mathrm{T}}_2^{\ast }$$ values of normal gray matter and white matter were in excellent agreement with reference values (intraclass correlation coefficients = 0.860/0.962 for gray matter and 0.925/0.975 for white matter ). Both permeability and perfusion parameters demonstrated good to excellent intersession agreement with the lowest intraclass correlation coefficients at 0.694. Contrast kinetic parameters in all healthy subjects and patients were within the literature range. CONCLUSION: Based on dynamic T 1 / T 2 * $${\mathrm{T}}_1/{\mathrm{T}}_2^{\ast }$$ mapping, MT-DICE allows for simultaneous quantification of permeability and leakage-insensitive perfusion metrics with a single-dose contrast injection.

12.
Plant Physiol ; 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36111856

##### RESUMO

The integrity of pollen wall structures is essential for pollen development and maturity in rice (Oryza sativa L.). In this study, we isolated and characterized the rice male-sterile mutant pwa1 (pollen wall abortion 1), which exhibits a defective pollen wall structure and has sterile pollen. Map-based cloning, genetic complementation, and gene knockout experiments revealed that PWA1 corresponds to the gene LOC_Os01g55094 encoding a coiled-coil domain-containing protein. PWA1 localized to the nucleus, and PWA1 was expressed in the tapetum and microspores. PWA1 interacted with the transcription factor TDR INTERACTING PROTEIN2 (TIP2, also named bHLH142) in vivo and in vitro. The tip2-1 mutant, which we obtained by CRISPR/Cas9-mediated gene editing, showed delayed tapetum degradation, sterile pollen, and defective pollen walls. We determined that TIP2/bHLH142 regulates PWA1 expression by binding to its promoter. Analysis of the phenotype of the tip2-1 pwa1 double mutant indicated that TIP2/bHLH142 functions upstream of PWA1. Further studies suggested that PWA1 has transcriptional activation activity and participates in pollen intine development through the ß-glucosidase Os12BGlu38. Therefore, we identified a sterility factor, PWA1, and uncovered a regulatory network underlying the formation of the pollen wall and mature pollen in rice.

13.
Front Mol Biosci ; 9: 966843, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060266

##### RESUMO

Cuproptosis is a new type of cell death that is associated with mitochondrial respiration of the tricarboxylic acid cycle. Previous studies showed that long non-coding RNAs (lncRNAs) regulated low-grade glioma (LGG) progression. However, the potential applications of cuproptosis-related lncRNAs (CRLs) in LGG were not explored. A comprehensive analysis was performed in The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) cohorts. We first screened two distinct cuproptosis subtypes based on prognostic CRLs using consensus clustering. To facilitate individualized survival prediction in LGG, we constructed a prognostic signature (including CRNDE, HAR1A, and FAM181A-AS1) in the TCGA dataset. The prognostic signature exhibited excellent predictive ability and reliability, which was validated in the CGGA_325 and CGGA_693 datasets. Notably, patients in the high-risk group had increased immune cell infiltration and expression of immune checkpoints, which indicated that they may benefit more from immune checkpoint blockade (ICB) therapy. Finally, the prognostic signature screened the population with sensitivity to chemotherapy and ICB therapy. In summary, this study initially explored the mechanism of CRLs in LGG and provides some insights into chemotherapy and ICB therapy of LGG.

14.
J Clin Pharm Ther ; 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36053892

##### RESUMO

WHAT IS KNOWN AND OBJECTIVE: Linezolid is an alternative first-line agent for MRSA pneumonia. This study assessed whether dose adjustments of linezolid against methicillin-resistant Staphylococcus aureus (MRSA) infections were needed based on renal function in populations with different body weight. METHODS: Monte Carlo simulations were conducted to evaluate renal function in relation to the probability of target attainment (PTA) in three population groups with different body weight. Area under the concentration time curve (AUC)/ minimum inhibitory concentration (MIC) ratio and percentage of time above the MIC (%T > MIC) were regarded as pharmacokinetic/pharmacodynamic targets. The PTA and cumulative fractions of response (CFR) were calculated to assess the efficacy. Regarding safety, trough plasma concentration (Cmin ) > 8 mg/L was used as target for toxicity. RESULTS AND DISCUSSION: Using AUC/MIC >100 as the target pharmacodynamic (PD) index, the CFR of linezolid at the standard dose (600 mg every 12 h [q12h]) were 57.01%, 93.22%, and 99.93% in patients with normal renal function, patients with renal dysfunction and low body weight patients with renal dysfunction, respectively. Using 100%T > MIC as the target PD index, all the CFR of three population groups were more than 90% at the standard dose. The percentages of Cmin > 8 mg/L at the standard dose of linezolid were 24.16%, 53.24%, and 90.10% in three population groups on day 7. WHAT IS NEW AND CONCLUSION: The risk of thrombocytopenia of linezolid was extremely higher in low body weight patients with renal impairment when receiving standard linezolid dose compared with patients with normal renal function. 450 mg q12h and 300 mg q12h might be effective and safe against MRSA infection in patients with renal dysfunction and low body weight patients with renal dysfunction, respectively.

15.
Front Mol Biosci ; 9: 942966, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36090045

##### RESUMO

Epithelial-mesenchymal transition (EMT) confers high invasive and migratory capacity to cancer cells, which limits the effectiveness of tumor therapy. Long non-coding RNAs (lncRNAs) can regulate the dynamic process of EMT at different levels through various complex regulatory networks. We aimed to comprehensively analyze and screen EMT-related lncRNAs to characterize lower-grade glioma (LGG) tumor biology and provide new ideas for current therapeutic approaches. We retrieved 1065 LGG samples from the Cancer Genome Atlas and Chinese Glioma Genome Atlas by machine learning algorithms, identified three hub lncRNAs including CRNDE, LINC00665, and NEAT1, and established an EMT-related lncRNA signature (EMTrLS). This novel signature had strong prognostic value and potential clinical significance. EMTrLS described LGG genomic alterations and clinical features including gene mutations, tumor mutational burden, World Health Organization (WHO) grade, IDH status, and 1p/19q status. Notably, stratified analysis revealed activation of malignancy-related and metabolic pathways in the EMTrLS-high cohort. Moreover, the population with increased EMTrLS scores had increased cells with immune killing function. However, this antitumor immune function may be suppressed by increased Tregs and macrophages. Meanwhile, the relatively high expression of immune checkpoints explained the immunosuppressive state of patients with high EMTrLS scores. Importantly, we validated this result by quantifying the course of antitumor immunity. In particular, EMTrLS stratification enabled assessment of the responsiveness of LGG to chemotherapeutic drug efficacy and PD1 blockade. In conclusion, our findings complement the foundation of molecular studies of LGG, provide valuable insight into our understanding of EMT-related lncRNAs, and offer new strategies for LGG therapy.

16.
Curr Zool ; 68(4): 489-498, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36090147

##### RESUMO

Deciphering the role of climatic oscillations in species divergence helps us understand the mechanisms that shape global biodiversity. The cold-adapted species may have expanded their distribution with the development of glaciers during glacial period. With the retreat of glaciers, these species were discontinuously distributed in the high-altitude mountains and isolated by geographical barriers. However, the study that focuses on the speciation process of cold-adapted species is scant. To fill this gap, we combined population genetic data and ecological niche models (ENMs) to explore divergence process of snow partridge (Lerwa lerwa). Lerwa lerwa is a cold-adapted bird that is distributed from 4,000 to 5,500 m. We found 2 genetic populations within L. lerwa, and they diverged from each other at about 0.40-0.44 million years ago (inter-glacial period after Zhongliangan glaciation). The ENMs suggested that L. lerwa expanded to the low elevations of the Himalayas and Hengduan mountains during glacial period, whereas it contracted to the high elevations, southern of Himalayas, and Hengduan mountains during inter-glacial periods. Effective population size trajectory also suggested that L. lerwa expanded its population size during the glacial period. Consistent with our expectation, the results support that inter-glacial isolation contributed to the divergence of cold-adapted L. lerwa on Qinghai-Tibetan Plateau. This study deepens our understanding of how climatic oscillations have driven divergence process of cold-adapted Phasianidae species distributed on mountains.

17.
J Inflamm Res ; 15: 5075-5088, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091333

##### RESUMO

Background: Altered lipid metabolism is associated with gastric cancer (GC) progression. Comprehensive analysis to identify critical lipid metabolic drivers for predicting overall survival (OS) is not fully elucidated in GC. Our study aim to explore a novel lipid metabolism-related prognostic marker for GC. Methods: Transcriptional status and clinical features were obtained from the TCGA-STAD database. The differentially expressed lipid metabolic genes and the risk prognostic model were developed by using bioinformatics and Cox regression analyses. ROC and Kaplan-Meier analysis were established to assess the performance of the risk predictive score model. GSE84437 dataset was used for external validation. Immunochemistry (IHC) was used to examine the expression of CYP19A1 in GC patients. Gene Set Enrichment Analysis (GSEA) was conducted to elucidate the underlying enriched mechanisms. TIMER and CIBERSORT analysis were performed to explore the relationship between CYP19A1 and immune microenvironment. Results: A novel lipid metabolic gene signature (including MTTP, CYP19A1, MYB, SERPINE1), and specifically CYP19A1, might be a promising prognostic factor for GC. Using the validation cohort, ROC curves indicate a good showing of our risk model. Based on the signature yielded a significant difference OS time between the low- and high-risk groups. Cox regression indicates that the signature is an independent prognostic variable. ROC curves present better and reliability predictive accuracy. The IHC data validate that high expression of CYP19A1 was found in GC tissues. GSEA analysis reveals that higher expression of CYP19A1 may significantly up-regulate genes involved in fatty acid metabolism and glycerolipid metabolism. CIBERSORT analysis suggests that CYP19A1 is related to the infiltration of multiple immune cells. Conclusion: CYP19A1 could be an independent prognostic factor and a novel metabolic-targeted treatment strategy for gastric cancer.

18.
Front Bioeng Biotechnol ; 10: 937803, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091431

##### RESUMO

Although bone tissue has the ability to heal itself, beyond a certain point, bone defects cannot rebuild themselves, and the challenge is how to promote bone tissue regeneration. Iron oxide nanoparticles (IONPs) are a magnetic material because of their excellent properties, which enable them to play an active role in bone regeneration. This paper reviews the application of IONPs in bone tissue regeneration in recent years, and outlines the mechanisms of IONPs in bone tissue regeneration in detail based on the physicochemical properties, structural characteristics and safety of IONPs. In addition, a bibliometric approach has been used to analyze the hot spots and trends in the field in order to identify future directions. The results demonstrate that IONPs are increasingly being investigated in bone regeneration, from the initial use as magnetic resonance imaging (MRI) contrast agents to later drug delivery vehicles, cell labeling, and now in combination with stem cells (SCs) composite scaffolds. In conclusion, based on the current research and development trends, it is more inclined to be used in bone tissue engineering, scaffolds, and composite scaffolds.

19.
Artigo em Inglês | MEDLINE | ID: mdl-36091601

##### RESUMO

Objective: The aim of this study was to analyze the clinical effect of the proximal femoral nail on elderly patients with unstable intertrochanteric fracture and the effect of the proximal femoral nail on serum levels of matrix metalloproteinases (MMPs) and osteoprotegerin (OPG). Methods: The elderly patients with unstable intertrochanteric fracture of the femur admitted to our hospital from January 2017 to January 2021 were studied. 100 patients were randomly divided into two groups: the control group (n = 50) and the observation group (n = 50). The patients in the control group were treated with a proximal femoral locking compression plate. The patients in the observation group were treated with the proximal femoral antirotation intramedullary nail. The clinical therapeutic effects of the two groups and the changes in serum MMPs and OPG levels before and after treatment were analyzed. Results: Compared with the control group, the operation time, postoperative landing time, and fracture healing time of the observation group were significantly shortened, and intraoperative blood loss was significantly reduced (P < 0.05). Compared with the control group, the total effective rate of patients in the observation group was significantly higher (P < 0.05). After treatment, the levels of CRP, IL1ß, IL2, MMP-2, MMP-6, TIMP-1, and RANKL decreased significantly in both groups (P < 0.05), while the levels of OPG increased significantly (P < 0.05). Compared with the control group, the changes in the above indexes were more obvious in the observation group (P < 0.05). Conclusion: The proximal femoral antirotation intramedullary nail has a better therapeutic effect on elderly patients with unstable intertrochanteric fracture, and the level of MMPs and OPG may be related to the treatment process.

20.
Front Pharmacol ; 13: 893244, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091836

##### RESUMO

Yuan-Zhi Decoction (YZD) is a traditional Chinese medical formulation with demonstrated clinical benefits in Alzheimer's disease (AD). We used liquid chromatography coupled with mass spectrometry to identify 27 unique chemical components of YZD. Analyzing these using network pharmacology and molecular docking models identified 34 potential interacting molecular targets involved in 26 biochemical pathways. When tested in an animal model of AD, the APP/PS1 transgenic mice showed measurable improvements in spatial orientation and memory after the administration of YZD. These improvements coincided with significantly reduced deposition of Aß plaques and tau protein in the hippocampi in the treated animals. In addition, a decreased BACE1 and beta-amyloid levels, a downregulation of the p-GSK-3ß/GSK-3ß, and an upregulation of the PI3K and p-AKT/AKT pathway was seen in YZD treated animals. These in vivo changes validated the involvement of molecular targets and pathways predicted in silico analysis of the chemical components of YZD. This study provides scientific support for the clinical use of YZD and justifies further investigations into its effects in AD. Furthermore, it demonstrates the utility of network pharmacology in elucidating the biochemical mechanisms underlying the beneficial effects of traditional Chinese medicines (TCM).

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