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1.
Appl Intell (Dordr) ; : 1-43, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34764621

RESUMO

Salp swarm algorithm (SSA) is a relatively new and straightforward swarm-based meta-heuristic optimization algorithm, which is inspired by the flocking behavior of salps when foraging and navigating in oceans. Although SSA is very competitive, it suffers from some limitations including unbalanced exploration and exploitation operation, slow convergence. Therefore, this study presents an improved version of SSA, called OOSSA, to enhance the comprehensive performance of the basic method. In preference, a new opposition-based learning strategy based on optical lens imaging principle is proposed, and combined with the orthogonal experimental design, an orthogonal lens opposition-based learning technique is designed to help the population jump out of a local optimum. Next, the scheme of adaptively adjusting the number of leaders is embraced to boost the global exploration capability and improve the convergence speed. Also, a dynamic learning strategy is applied to the canonical methodology to improve the exploitation capability. To confirm the efficacy of the proposed OOSSA, this paper uses 26 standard mathematical optimization functions with various features to test the method. Alongside, the performance of the proposed methodology is validated by Wilcoxon signed-rank and Friedman statistical tests. Additionally, three well-known engineering optimization problems and unknown parameters extraction issue of photovoltaic model are applied to check the ability of the OOSA algorithm to obtain solutions to intractable real-world problems. The experimental results reveal that the developed OOSSA is significantly superior to the standard SSA, currently popular SSA-based algorithms, and other state-of-the-artmeta-heuristic algorithms for solving numerical optimization, real-world engineering optimization, and photovoltaic model parameter extraction problems. Finally, an OOSSA-based path planning approach is developed for creating the shortest obstacle-free route for autonomous mobile robots. Our introduced method is compared with several successful swarm-based metaheuristic techniques in five maps, and the comparative results indicate that the suggested approach can generate the shortest collision-free trajectory as compared to other peers.

2.
Front Oncol ; 11: 760429, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722315

RESUMO

Cyclin-dependent kinase 5 (CDK5) regulatory subunit associated protein 3 (CDK5RAP3, also named as C53 or LZAP) was initially identified as a binding protein of CDK5 activator p35. To date, CDK5RAP3 has been reported to interact with a range of proteins involved in cellular events ranging from cell cycle, apoptosis, and invasion to UFMylation modification and endoplasmic reticulum stress. Owing to its crucial roles in cellular processes, CDK5RAP3 is demonstrated to be not only an active participant in embryonic and mammalian tissue development, but also a key regulator in the onset and progress of human cancers such as head and neck squamous cell carcinoma, gastric cancer, hepatocellular cancer, lung cancer, kidney cancer and breast cancer. Notwithstanding, the detailed function of CDK5RAP3 and its mechanism remain poorly defined. Here, we briefly described a history of the discovery of CDK5RAP3, and systematically overviewed its gene structural and distribution features. We also focused on the known functions of this protein and its implications for embryogenesis and tissue development, as well as diseases especially carcinoma. This review may facilitate to understand the molecular and functional basis of CDK5RAP3 and its association with development and disease, and provide a reasonable idea for novel therapeutic opportunities targeting CDK5RAP3.

3.
Crit Rev Food Sci Nutr ; : 1-21, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34613845

RESUMO

Alzheimer's disease (AD) is the most common form of dementia in elderly people with a high incidence rate and complicated pathogenesis, and causes progressive cognitive deficit and memory impairment. Some natural products and bioactive compounds from natural sources show great potential in the prevention and treatment of AD, such as apple, blueberries, grapes, chili pepper, Monsonia angustifolia, cruciferous vegetables, Herba epimedii, Angelica tenuissima, Embelia ribes, sea cucumber, Cucumaria frondosa, green tea, Puer tea, Amanita caesarea and Inonotus obliquus, via reducing amyloid beta (Aß) deposition, decreasing Tau hyperphosphorylation, regulating cholinergic system, reducing oxidative stress, inhibiting apoptosis and ameliorating inflammation. This review mainly summarizes the effects of some natural products and their bioactive compounds on AD with the potential molecular mechanisms.

4.
Materials (Basel) ; 14(19)2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34640262

RESUMO

In this paper, a simple method to fulfill the ideal microstructural design of particle reinforced tungsten (W) alloys with promising mechanical properties is presented. W-0.5 wt.% TiC powders with core-shell (TiC/W) structure are prepared by ball-milling and controlled hydrogen reduction processes. TEM observation demonstrates that the nano TiC particles are well coated by tungsten. The W-TiC powders are sintered by spark plasma sintering (SPS) under 1600 °C. The sintered microstructures are characterized by FESEM and TEM. It is found that the W-0.5TiC alloys obtain an ultra-fine-sized tungsten grain of approximately 0.7 µm. The TiC particles with the original nano sizes are uniformly distributed both in tungsten grain interiors and at tungsten grain boundaries with a high number density. No large agglomerates of TiC particles are detected in the microstructure. The average diameter of the TiC particles in the tungsten matrix is approximately 47.1 nm. The mechanical tests of W-0.5 TiC alloy show a significantly high microhardness and bending fracture strength of 785 Hv0.2 and 1132.7 MPa, respectively, which are higher than the values obtained in previous works. These results indicate that the methods used in our work are very promising to fabricate particle-dispersion-strengthened tungsten-based alloys with high performances.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34650613

RESUMO

Background: Huangqi Sijunzi decoction (HQSJZD) is a commonly used conventional Chinese herbal medicine prescription for invigorating Qi, tonifying Yang, and removing dampness. Modern pharmacology and clinical applications of HQSJZD have shown that it has a certain curative effect on Alzheimer's disease (AD). Methods: The active components and targets of HQSJZD were searched in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The genes corresponding to the targets were retrieved using UniProt and GeneCard database. The herb-compound-target network and protein-protein interaction (PPI) network were constructed by Cytoscape. The core targets of HQSJZD were analysed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The main active compounds of HQSJZD were docked with acetylcholinesterase (AChE). In vitro experiments were conducted to detect the inhibitory and neuroprotective effects of AChE. Results: Compound-target network mainly contained 132 compounds and 255 corresponding targets. The main compounds contained quercetin, kaempferol, formononetin, isorhamnetin, hederagenin, and calycosin. Key targets contained AChE, PTGS2, PPARG, IL-1B, GSK3B, etc. There were 1708 GO items in GO enrichment analysis and 310 signalling pathways in KEGG, mainly including the cAMP signalling pathway, the vascular endothelial growth factor (VEGF) signalling pathway, serotonergic synapses, the calcium signalling pathway, type II diabetes mellitus, arginine and proline metabolism, and the longevity regulating pathway. Molecular docking showed that hederagenin and formononetin were the top 2 compounds of HQSJZD, which had a high affinity with AChE. And formononetin has a good neuroprotective effect, which can improve the oxidative damage of nerve cells. Conclusion: HQSJZD was found to have the potential to treat AD by targeting multiple AD-related targets. Formononetin and hederagenin in HQSJZD may regulate multiple signalling pathways through AChE, which might play a therapeutic role in AD.

6.
Eur J Pharm Sci ; 167: 106029, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34601069

RESUMO

The co-penetration of micellar vehicles and the encapsulated drugs into the skin layers, as well as the mechanisms underlying the penetration enhancement have not been clearly elucidated. We developed licochalcone A (LA)-loaded glycyrrhiza acid (GA) (GA+LA) micelles for topical delivery of LA into the epidermis. The in vitro co-penetration, penetration pathways, mechanism of interaction between skin and the micelles, and the in vitro and in vivo whitening effect of GA+LA micelles were evaluated. Co-penetration and penetration pathways were visualized on the abdominal skin of rats model with confocal laser scanning microscopy (CLSM) using a nile blue A-labeled GA (GA-NB). We found that GA significantly increased the transport of LA into the skin predominantly via the hair follicles and GA mainly accumulated in the SC and epidermis, while LA was localized in the epidermis and dermis. Moreover, 73.4% of the LA deposited into the epidermis within 12 h and approximately 9.32% of the LA permeated across the SC in the form of entire micelles within 24 h. GA-NB+LA micelles disaggregated and accumulated in the specific skin layers, and the LA released from the carrier penetrated into deeper layers. Moreover, the GA+LA micelles promoted drug penetration via intracellular or intercellular routes by loosening the skin surface and enhancing fluidization through lipid distortion and keratin denaturation. Furthermore, GA+LA micelles exhibited synergistic whitening effect on B16 cells and UVB-exposed C57BL/6 mice. Collectively, GA micelles can enhance penetration of LA to the epidermis mainly via the hair follicles following topical application, and reduce skin pigmentation.


Assuntos
Glycyrrhiza , Micelas , Animais , Chalconas , Portadores de Fármacos , Ácido Glicirrízico , Melaninas , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Pele
7.
Pharmaceutics ; 13(9)2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34575511

RESUMO

Peptides are strings of approximately 2-50 amino acids, which have gained huge attention for theranostic applications in cancer research due to their various advantages including better biosafety, customizability, convenient process of synthesis, targeting ability via recognizing biological receptors on cancer cells, and better ability to penetrate cell membranes. The conjugation of peptides to the various nano delivery systems (NDS) has been found to provide an added benefit toward targeted delivery for cancer therapy. Moreover, the simultaneous delivery of peptide-conjugated NDS and nano probes has shown potential for the diagnosis of the malignant progression of cancer. In this review, various barriers hindering the targeting capacity of NDS are addressed, and various approaches for conjugating peptides and NDS have been discussed. Moreover, major peptide-based functionalized NDS targeting cancer-specific receptors have been considered, including the conjugation of peptides with extracellular vesicles, which are biological nanovesicles with promising ability for therapy and the diagnosis of cancer.

8.
Am J Transl Res ; 13(6): 5851-5865, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34306330

RESUMO

SRY (sex determining region Y)-box 2 (SOX2) plays a key role in the maintenance of stemness and resistance to drugs, whereas tumor necrosis factor (TNF)-α is essential for maintaining cancer cell proliferation and metastasis. Accumulation of muscle segment homeobox 2 (MSX2) leads to downregulation of SOX2 expression. Here, we explored the MSX2-SOX2-TNF-α signaling axis and its function in the tumor phenotypes of osteosarcoma cells. Colony formation assay, cell counting kit (CCK)-8 assay, and Flow cytometry were used to examine cell growth, viability, and death, respectively. Wound healing and Transwell invasive assay were employed to examine cell migratory and invasive activities, respectively. Western blotting and RT-qPCR were used to determine the protein and mRNA expressions of MSX2, SOX2, TNF-α, Bax, and matrix metalloproteinase-2 (MMP-2). Osteosarcoma clinical samples and cells showed lower levels of MSX2 than normal healthy control samples. Overexpression of MSX2 led to a reduced activity of SOX2 and TNF-α, whereas MSX2 depletion did not contribute to upregulated SOX2 levels. A gain-of-function experiment showed that osteosarcoma cell viability and growth were reduced, cell death was increased, and migration and invasion were inhibited in the MSX2 overexpression group compared with those in the non-transfected group. Furthermore, co-overexpression of MSX2 and SOX2 counteracted the inhibitory effects of MSX2 on the abovementioned tumor phenotypes of osteosarcoma cells. An in vivo tumor growth assay showed that MSX2 overexpression slowed the growth rate of osteosarcoma xenograft tumors. Thus, MSX2 loss plays a crucial role in the osteosarcoma phenotype by elevating SOX2 and TNF-α levels.

9.
Cell Rep ; 36(2): 109344, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34260905

RESUMO

Although peripheral B cell dysfunction in early HIV infection is established, how B cell subsets are altered by HIV infection is poorly understood. While investigating B cell subsets among individuals recently infected with HIV, we observe an accumulation of CD27-CD38+ B cells and find that these cells can directly facilitate HIV infection of primary CD4+ T cells in vitro. Comprehensive analyses of the phenotype, function, and transcriptome of the CD27-CD38+ B cell subset is conducted compared with memory and naive B cells. We find that the CD27-CD38+ B cells exhibit a transitional B cell phenotype and an extremely high turnover rate. Importantly, individuals with higher proportions of CD27-CD38+ B cells during early HIV infection tend to become rapid progressors in the chronic infection stage. In this study, we identify a peripheral transitional B cell subset that accumulates during early HIV infection and may contribute to disease progression.

10.
Materials (Basel) ; 14(9)2021 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-34065157

RESUMO

The hot deformation behaviors of a new Ti-6Al-2Nb-2Zr-0.4B titanium alloy in the strain rate range 0.01-10.0 s-1 and temperature range 850-1060 °C were evaluated using hot compressing testing on a Gleeble-3800 simulator at 60% of deformation degree. The flow stress characteristics of the alloy were analyzed according to the true stress-strain curve. The constitutive equation was established to describe the change of deformation temperature and flow stress with strain rate. The thermal deformation activation energy Q was equal to 551.7 kJ/mol. The constitutive equation was ε Ë™=e54.41[sinh (0.01σ)]2.35exp(-551.7/RT). On the basis of the dynamic material model and the instability criterion, the processing maps were established at the strain of 0.5. The experimental results revealed that in the (α + ß) region deformation, the power dissipation rate reached 53% in the range of 0.01-0.05 s-1 and temperature range of 920-980 °C, and the deformation mechanism was dynamic recovery. In the ß region deformation, the power dissipation rate reached 48% in the range of 0.01-0.1 s-1 and temperature range of 1010-1040 °C, and the deformation mechanism involved dynamic recovery and dynamic recrystallization.

11.
Medicine (Baltimore) ; 100(25): e26400, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160424

RESUMO

BACKGROUND: Femur Head Necrosis (FHN) is a common clinical joint orthopedic-related disease, and its incidence is increasing year by year. Symptoms include dull pain and dull pain in the affected hip joint or its surrounding joints. More severely, it can lead to limited joint movement and inability to walk autonomously. Surgical treatment has many sequelae. The high cost makes it unaffordable for patients, and the side effects of drug treatment are unknown. A large number of clinical studies have shown that acupuncture is effective in treating femoral head necrosis. Therefore, this systematic review aims to explore the safety and effectiveness of acupuncture in the treatment of femoral head necrosis. METHODS: We will conduct a comprehensive literature search in Medline, PubMed, Cochrane Database of Systematic Reviews, Embase, Chinese Biomedical Literatures Database (CBM), China National Knowledge Infrastructure (CNKI), Wang FangDatabase (WF), Chinese Scientific Journal Database (VIP) from inception to May 2021 without any language restriction. In addition, we will retrieve the unpublished studies and the references of initially included literature manually. The two reviewers will identify studies, extract data, and assess the quality independently. The outcomes of interest include: total effective rate; the total nasal symptom score; Hip function (Hip Harris joint score, WOMAC hip score, hip joint Lequesne index score, Merle D 'Aubigne and hip joint Postel score); Adverse events. Randomized clinical trials will be collected, methodological quality will be evaluated using the Cochrane risk-of-bias assessment tool, and the level of evidence will be rated using the Grading of Recommendations, Assessment, Development and Evaluation approach. Meta-analysis will be performed using RevMan 5.4.0 software. The heterogeneity test will be conducted between the studies, P < .1 and I2 > 50% are the thresholds for the tests. We will utilize the fixed effects model or the random effects model according to the size of heterogeneity. RESULTS: The meta-analysis program will systematically evaluate the efficacy and safety of acupuncture in the treatment of FHN patients. CONCLUSION: This study will investigate whether acupuncture can be used as one of the non-surgical and non-pharmacological therapies for the prevention or treatment of FHN. TRIAL REGISTRATION NUMBER: INPLASY202150035.


Assuntos
Terapia por Acupuntura/efeitos adversos , Necrose da Cabeça do Fêmur/terapia , Dor Musculoesquelética/terapia , Manejo da Dor/métodos , Estudos de Viabilidade , Necrose da Cabeça do Fêmur/complicações , Necrose da Cabeça do Fêmur/diagnóstico , Humanos , Metanálise como Assunto , Dor Musculoesquelética/diagnóstico , Dor Musculoesquelética/etiologia , Manejo da Dor/efeitos adversos , Medição da Dor/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Revisões Sistemáticas como Assunto , Resultado do Tratamento
12.
Environ Sci Pollut Res Int ; 28(42): 59640-59651, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34143387

RESUMO

Copper mine road dust is the major source of dust in mine operations. The dust produced on the road surface is a great hazard to the workers. Aiming at the road dust of an open-pit mine, this paper conducts a physical and chemical analysis of a new type of chemical dust suppressant. It is prepared by using sodium polyacrylate as a binder, sodium carbonate as a moisture absorbent, polyethylene glycol as a water-retaining agent, and alkyl glycoside as a surfactant. Physical and chemical characteristics and dust suppression performance of dust suppressant were tested. The results show that the dust suppressant has a pH of 11.03, a viscosity of 18.5 mPa·s, and a surface tension of 28.1 mN/m. The content of heavy metal ions contained is less than the maximum concentration defined by "The norms for the integrated treatment of copper mine acidic waste water." Under the same temperature condition, the greater the humidity, the stronger the hygroscopicity. Especially when the humidity is 30%, the hygroscopic effect is contrary to water. The dust suppressant also has good anti-evaporation properties, and it could maintain a moisture content of 4% to 5% after being placed at room temperature for 10 days. Compared with water, the dust suppressant has better performance of wind erosion, water erosion, and compression resistance. Under the same conditions, the loss rate of water is 2 times that of the dust suppressant, and the pressure of the dust suppressant sample is about 3 times that of water. The dust suppressant has a much higher dust removal efficiency for all dust and respirable dust than water under the same conditions. Finally, the test results and mechanism of the dust suppression mechanism of the dust suppressant are described and analyzed, which shows that the dust suppressant studied in this paper has good performance and is suitable for road dust prevention.


Assuntos
Poeira , Metais Pesados , Cobre , Poeira/análise , Humanos , Metais Pesados/análise , Mineração , Vento
13.
Front Pharmacol ; 12: 654714, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34045964

RESUMO

Postmenopausal osteoporosis (PMOP) is a type of bone metabolism disease-related to estrogen deficiency with an increasing incidence. Traditional Chinese (TCM) has always been used and showed effectiveness in treating PMOP. In the current study, Bu-Yang herbs were considered to be the most frequently used and efficient TCM herbs in PMOP treatment. However, chemical and pharmacological profiles were not elucidated. Network pharmacology was conducted on representative Bu-Yang herbs (Yin-Yang-Huo. Du-Zhong, Bu-Gu-Zhi, Tu-Si-Zi) to investigate the mechanism of Bu-Yang herbs on PMOP. Chemical compounds, potential targets, and disease related genes were available from the corresponding database. Results showed that Bu-Yang herbs could interact with ESR1 and estrogen signaling pathways. For further validation, the Bu-Yang decoction (BYD), formula consisted of the above-mentioned 4 Bu-Yang herbs was presented for experimental validation. In vivo, BYD significantly reversed ovariectomy (OVX)-induced osteoporosis progress in a dose-dependent manner by up-regulation of bone mineral density and amelioration of bone microarchitecture. In vitro, BYD dramatically improved the proliferation and mineral nodules formation of osteoblasts. Both in vitro and in vivo results illustrated that the phenotype change induced by BYD is correlated with up-regulated of ESR1 and activation of the ß-catenin pathway. Meanwhile, inhibition of ESR1 by ICI182, 780 blocked the osteogenic phenotype and ß-catenin pathway activation induced by BYD. In conclusion, the current study suggested that Bu-Yang herbs are the most useful TCM herbs in treating PMOP. Furthermore, the integrated strategy of network pharmacology prediction with experimental validation suggested that BYD exerted its anti-PMOP via ESR1 and the downstream mechanism might be activation of the ß-catenin signaling pathway.

14.
Am J Transl Res ; 13(4): 2694-2701, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34017430

RESUMO

OBJECTIVE: The purpose of this study was to analyze the efficacy of platelet-rich plasma (PRP) injection combined with arthroscopic microfracture technique for knee cartilage injury. METHODS: Seventy-nine patients with knee cartilage injury were randomly divided into a control group (CG, n=39) and an observation group (OBG, n=40). Both of the groups were treated with the arthroscopic microfracture technique, and the OBG was additionally treated with PRP injection. RESULTS: The VAS scores for pain in the affected area of the OBG were lower than those of the CG at 1, 3, 5, and 7 days after surgery (P < 0.05). Knee flexion, hyperextension, and rotation angles in the OBG were greater than those in the CG at 1 month after surgery (P < 0.05). IKDC scores in the OBG were lower than those in the CG at 1, 2, and 3 weeks after surgery (P < 0.05). The Tegner and Lysholm scores in the OBG were higher than those in the CG at 1, 2, and 3 months after surgery (P < 0.05). The complication rate in the OBG was 10.00%, which was lower than that of 28.21% in the CG (P < 0.05). CONCLUSION: The efficacy of microfracture technique combined with PRP injection in the treatment of knee joint cartilage injury is significantly improved compared with that of microfracture technique alone, which can reduce postoperative complications and improve the range of motion and function of the knee joint.

15.
Spectrochim Acta A Mol Biomol Spectrosc ; 259: 119826, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33965890

RESUMO

Cysteine (Cys) is an effective biomarker in life systems and is closely related to a variety of diseases, so developing a specific and efficient detection method for Cys is of great significance. To date, extensive work has been undertaken toward this goal. However, the differentiation of Cys from other biothiols still represents a challenge from an experimental point of view. Toward this end, a selective and sensitive red-emitting probe (TMN-NCS) with an isothiocyanate (ITC)-based structure was proposed in this paper. A large Stokes shift (210 nm) was observed upon addition of Cys to a solution of TMN-NCS. In addition, TMN-NCS showed low toxicity, a low detection limit (120 nM), and excellent cell permeability. The results suggested that TMN-NCS holds great promise for biological applications.


Assuntos
Cisteína , Corantes Fluorescentes , Glutationa , Células HeLa , Humanos , Isotiocianatos , Limite de Detecção
16.
Molecules ; 26(6)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799765

RESUMO

Extracellular vesicles (EVs) play major roles in intracellular communication and participate in several biological functions in both normal and pathological conditions. Surface modification of EVs via various ligands, such as proteins, peptides, or aptamers, offers great potential as a means to achieve targeted delivery of therapeutic cargo, i.e., in drug delivery systems (DDS). This review summarizes recent studies pertaining to the development of EV-based DDS and its advantages compared to conventional nano drug delivery systems (NDDS). First, we compare liposomes and exosomes in terms of their distinct benefits in DDS. Second, we analyze what to consider for achieving better isolation, yield, and characterization of EVs for DDS. Third, we summarize different methods for the modification of surface of EVs, followed by discussion about different origins of EVs and their role in developing DDS. Next, several major methods for encapsulating therapeutic cargos in EVs have been summarized. Finally, we discuss key challenges and pose important open questions which warrant further investigation to develop more effective EV-based DDS.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/fisiologia , Exossomos/metabolismo , Exossomos/fisiologia , Humanos , Lipossomos/isolamento & purificação , Lipossomos/metabolismo
17.
Int J Gen Med ; 14: 967-981, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33790626

RESUMO

Purpose: The dysregulation of arrestin domain containing 3 (ARRDC3) has an important effect on oncogenesis and tumor progression in many cancers, including renal cell carcinoma and breast cancer. However, the role of ARRDC3 in ovarian cancer (OC) has not been reported. Methods: The present study explored the diagnostic and prognostic roles of ARRDC3 in ovarian cancer using GEPIA, ONCOMINE, GEO, and Kaplan-Meier Plotter databases for training and validation. Then, we conducted a stratified analysis for clinicopathological factors using Kaplan-Meier Plotter and GEPIA databases. To further explore the mechanisms, we also used the MIST database to visualize the protein-protein interaction network of ARRDC3 associated with OC. The gene-gene interaction network was visualized by GeneMANIA plugin in Cytoscape 3.8.0 software, and the associated co-expression genes of ARRDC3 were analyzed by the cBioPortal database. The 100 top co-expression genes chosen for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used by the DAVID website. Results: A significant difference in ARRDC3 mRNA expression was found between OC and normal ovary tissues. ARRDC3 could potentially be implicated in the diagnosis of OC. A high ARRDC3 mRNA expression level was associated with poor overall survival and progression-free survival. However, no significance was reported in respect to post progression survival. Except for histology, which had no prognostic value for PPS in stratified analysis, stratified analysis of other factors had prognostic value for OS, PFS, and PPS. Interestingly, we found a positive correlation between ARRDC3 expression and CD8+ T cells, macrophages, neutrophils, and dendritic cells, indicating that ARRDC3 might be associated with immune infiltration of these immune cells. Co-expression genes enrichment analysis found that they were involved in the Renin-angiotensin system pathway. Conclusion: Differentially expressed ARRDC3 might be a potential prognostic and diagnostic marker in Ovarian Cancer.

18.
AAPS J ; 23(2): 38, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33665728

RESUMO

Bioequivalence (BE) is usually hard to achieve for extended-release (ER) dosage form products due to not only its complicated formulation but also to the BCS classification of the investigated drugs. Considering the difficulties in establishing full-scale IVIVC and limited in vivo pharmacokinetics data in the early stage of formulation development, we have selected BCS III drug metformin as a model drug to demonstrate a novel approach for the selection of BE formulations. Firstly, dissolution tests in both standard and biorelevant media were performed followed by identification of the most similar formulation WM to the reference product (GXR) based on principal component analysis (PCA) of the dissolution data. Then, we developed an IVIVC model using the reported GXR pharmacokinetics profiles via a convolution-based approach. Based on our established IVIVC and in vitro dissolution profiles of generic metformin ER products, we were able to predict their in vivo pharmacokinetic profiles and quantitatively compare the differences in AUC and Cmax to ensure the correct selection of BE product. Finally, the selection of WM as the BE formulation of GXR was confirmed with a pilot BE study in healthy volunteers under fasting state. Moreover, the in vivo data from the fed state study were further integrated into our IVIVC model to identify FeSSIF-V2 as the biorelevant media for WM. Our novel integrative approach of PCA with a convolution-based IVIVC was successfully adopted for the screening of the BE metformin ER formulation and such an approach could be further utilized for the effective selection of BE formulation for other drugs/formulations with complex in vivo absorption processes.


Assuntos
Metformina/farmacocinética , Modelos Biológicos , Administração Oral , Área Sob a Curva , Disponibilidade Biológica , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacocinética , Liberação Controlada de Fármacos , Jejum , Absorção Gastrointestinal , Voluntários Saudáveis , Humanos , Metformina/administração & dosagem , Projetos Piloto , Análise de Componente Principal , Solubilidade , Comprimidos , Equivalência Terapêutica
19.
Stem Cell Res Ther ; 12(1): 128, 2021 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-33579360

RESUMO

BACKGROUND: Recently, growing evidence has indicated an important role of the complement system, a crucial component of immunity, in mediating neuroinflammation and promoting neuronal apoptosis following closed head injury (CHI). We previously reported that transplanted induced neural stem cells (iNSCs) pre-treated with CHI mouse serum could enhance complement receptor type 1-related protein y (Crry) expression and ameliorate complement-mediated damage in mouse CHI models. However, the mechanism underlying the elevated levels of Crry expression remains elusive. METHODS: CHI models were established using a standardized weight-drop device. We collected CHI mouse serum at 12 h post-trauma. RT-QPCR assay, western blot analysis, complement deposition assay, Akt inhibition assay, flow cytometry, cell transplantation, and functional assay were utilized to clarify the mechanism of Crry expression in iNSCs receiving CHI mouse serum treatment. RESULTS: We observed dramatic increases in the levels of Crry expression and Akt activation in iNSCs receiving CHI mouse serum treatment. Remarkably, Akt inhibition led to the reduction of Crry expression in iNSCs. Intriguingly, the treatment of iNSC-derived neurons with recombinant complement receptor 2-conjugated Crry (CR2-Crry), which inhibits all complement pathways, substantially enhanced Crry expression and Akt activation in neurons after CHI mouse serum treatment. In subsequent in vitro experiments of pre-treatment of iNSCs with CR2-Crry, we observed significant increases in the levels of Crry expression and Akt activation in iNSCs and iNSC-derived astrocytes and neurons post-treatment with CHI mouse serum. Additionally, an in vivo study showed that intracerebral-transplanted iNSCs pre-treated with CR2-Crry markedly enhanced Crry expression in neurons and protected neurons from complement-dependent damage in the brains of CHI mice. CONCLUSION: INSCs receiving CR2-Crry pre-treatment increased the levels of Crry expression in iNSCs and iNSC-derived astrocytes and neurons and attenuated complement-mediated injury following CHI.


Assuntos
Traumatismos Cranianos Fechados , Células-Tronco Neurais , Animais , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Neurais/transplante , Neuroproteção , Proteínas Proto-Oncogênicas c-akt/genética , Receptores de Complemento 3b , Proteínas Recombinantes de Fusão
20.
Acta Ophthalmol ; 99(8): 885-891, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33565242

RESUMO

PURPOSE: Spontaneous cerebrospinal fluid (CSF) rhinorrhea is related to intracranial pressure (ICP) and dynamic changes. This study investigated CSF dynamics along the optic nerve (ON) in patients with spontaneous CSF rhinorrhea. METHODS: The computed tomographic (CT) cisternographies of 66 patients (132 eyes) with spontaneous CSF rhinorrhea were analysed. The contrast-loaded CSF (CLCSF) density was measured in Hounsfield units (HU) at three regions of interest (ROIs) along the ON and adjusted by the basal cistern density. The CLCSF density and ON sheath diameter (ONSD) were analysed between both sides in the different ICP groups. RESULTS: When comparing the density of CLCSF along the ON, no significant differences were found between the ipsilateral and contralateral sides of the leakage. The distribution of CLCSF along the ON showed a highly significant density reduction from the canalicular segment to the bulbar segment on both sides. The CLCSF density significantly decreased on the ipsilateral ON in the canalicular segment and tended to decrease on the ipsilateral ON in the bulbar and canal segments compared with that on the contralateral ON in the low-ICP group. The ONSD tended to decrease on the ipsilateral side of leakage. CONCLUSIONS: According to the CLCSF density on CT cisternography, CSF dynamics along the ON may bilaterally decrease from the optic canal to the retrobulbar segment. Cerebrospinal fluid (CSF) dynamics are possibly influenced by differences in ICP, and a lower ICP may cause more obvious differences or impairments in CSF dynamics along the ipsilateral ON.

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