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1.
Int J Oncol ; 2021 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-33650668

RESUMEN

Patients with a variety of malignancies can develop malignant pleural effusion (MPE). MPE can cause significant symptoms and result in a marked decrease in quality of life and a poor prognosis. MPE is primarily considered as an immune and vascular manifestation of pleural metastases. In the present review, the existing evidence supporting the applicability of anti­angiogenic therapy and immunotherapy for the treatment of MPE was summarized. Patients with MPE have benefited from anti­angiogenic agents, including bevacizumab and endostar; however, no relevant prospective phase III trial has, thus far, specifically analyzed the benefit of anti­angiogenic therapy in MPE. Immunotherapy for MPE may be sufficient to turn a dire clinical situation into a therapeutic advantage. Similar to anti­angiogenic therapy, more clinical data on the efficiency and safety of immunotherapy for controlling MPE are urgently required. The combined use of anti­angiogenic therapy and immunotherapy may be a promising strategy for MPE, which requires to be further understood.

2.
Theranostics ; 11(7): 3348-3358, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33537091

RESUMEN

Pin1 belongs to the peptidyl-prolyl cis-trans isomerases (PPIases) superfamily and catalyzes the cis-trans conversion of proline in target substrates to modulate diverse cellular functions including cell cycle progression, cell motility, and apoptosis. Dysregulation of Pin1 has wide-ranging influences on the fate of cells; therefore, it is closely related to the occurrence and development of various diseases. This review summarizes the current knowledge of Pin1 in disease pathogenesis.

3.
Mol Plant Pathol ; 2021 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-33559339

RESUMEN

Histone-3-lysine-4 (H3K4) methylation is catalysed by the multiprotein complex known as the Set1/COMPASS or MLL/COMPASS-like complex, an element that is highly evolutionarily conserved from yeast to humans. However, the components and mechanisms by which the COMPASS-like complex targets the H3K4 methylation of plant-pathogenic genes in fungi remain elusive. Here we present a comprehensive analysis combining biochemical, molecular, and genome-wide approaches to characterize the roles of the COMPASS-like family in the rice blast fungus Magnaporthe oryzae, a model plant pathogen. We purified and identified six conserved subunits of COMPASS from M. oryzae: MoBre2 (Cps60/ASH2L), MoSpp1 (Cps40/Cfp1), MoSwd2 (Cps35), MoSdc1 (Cps25/DPY30), MoSet1 (MLL/ALL), and MoRbBP5 (Cps50), using an affinity tag on MoBre2. We determined the sequence repeat in dual-specificity kinase splA and ryanodine receptors domain of MoBre2 can interact directly with the DPY30 domain of MoSdc1 in vitro. Furthermore, we found that deletion of the genes encoding COMPASS subunits of MoBre2, MoSPP1, and MoSwd2 caused similar defects regarding invasive hyphal development and pathogenicity. Genome-wide profiling of H3K4me3 revealed that it has remarkable co-occupancy at the transcription start site regions of target genes. Significantly, these target genes are often involved in spore germination and pathogenesis. Decreased gene expression caused by the deletion of MoBre2, MoSwd2, or MoSpp1 was highly correlated with a decrease in H3K4me3. These results suggest that MoBre2, MoSpp1, and MoSwd2 function as a whole COMPASS complex, contributing to fungal development and pathogenesis by regulating H3K4me3-targeted genes in M. oryzae.

4.
Plasmid ; 114: 102555, 2021 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-33472047

RESUMEN

To analyze characteristics and underlying evolutionary processes of IncC and IncI1 plasmids in a multidrug-resistant avian E. coli strain, antibiotic susceptibility testing, PCR, conjugation assays, and next-generation sequencing were performed. The type 1 IncC plasmid pEC009.1 harbored three antimicrobial resistance regions including ISEcp1-blaCMY-2-blc-sugE, ARI-B resistance island, and ARI-A island that was a mosaic multidrug resistance region (MRR) comprised of a class 1 integron with cassette array |aac(6')-II(aacA7)|qacE∆1|sul1|, IS26-mphR(A)-mrx-mph(A)-IS26, IS26-fosA3-IS26, and mercury resistance cluster merRTPABDE. It is the first report of three different size circular forms derived from IS26-mphR(A)-mrx-mph(A)-IS26-fosA3-IS26 in ARI-A of type 1 IncC plasmid. In IncI1/ST136 pEC009.2, the truncated transposon Tn1722 carrying blaTEM-1b, rmtB, aac(3)-IId(aacC2d), and a class 1 integron with cassette array |dfrA12|orfF|aadA2|, inserted into the plasmid backbone generating 5-bp direct repeats (DRs, TATAA) at the boundaries of the region, which was highly similar to that of other IncI1 plasmids, and differed by the arrangements of resistance determinants. Comparison among two epidemic plasmid lineages showed complex MRRs respectively located in the specific position in type 1 IncC and IncI1/ST136 plasmids with conserved backbones, and these have evolved via multiple events involved in mobile elements-mediated loss and gain of resistance genes and accessory genes. Strains harboring these plasmids may serve as a reservoir for antibiotic resistance genes, thereby contributing to the rapid spread of resistance genes and posing a public health threat.

5.
J Glob Antimicrob Resist ; 24: 215-219, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33460843

RESUMEN

Fusarium species cause many diseases in plants and humans, which results in a great number of economic losses every year. The management of plant diseases and related human diseases caused by Fusarium is challenging as many kinds of Fusarium may be intrinsically resistant to antifungal drugs, not to mention the fact that they can acquire drug resistance, which is common in clinical practice. To date, the drug resistance of Fusarium is mainly related to target alterations, drug efflux and biofilm formation. This article reviews recent studies related to the mechanism of Fusarium resistance, and summarizes the key molecules affecting resistance.

6.
Mar Drugs ; 19(2)2021 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-33498781

RESUMEN

Macroalgae polysaccharides are phytochemicals that are beneficial to human health. In this study, response surface methodology was applied to optimize the extraction procedure of Pyropia yezoensis porphyran (PYP). The optimum extraction parameters were: 100 °C (temperature), 120 min (time), and 29.32 mL/g (liquid-solid ratio), and the maximum yield of PYP was 22.15 ± 0.55%. The physicochemical characteristics of PPYP, purified from PYP, were analyzed, along with its lipid-lowering effect, using HepG2 cells and Drosophila melanogaster larvae. PPYP was a ß-type sulfated hetero-rhamno-galactan-pyranose with a molecular weight of 151.6 kDa and a rhamnose-to-galactose molar ratio of 1:5.3. The results demonstrated that PPYP significantly reduced the triglyceride content in palmitic acid (PA)-induced HepG2 cells and high-sucrose-fed D. melanogaster larvae by regulating the expression of lipid metabolism-related genes, reducing lipogenesis and increasing fatty acid ß-oxidation. To summarize, PPYP can lower lipid levels in HepG2 cells and larval fat body (the functional homolog tissue of the human liver), suggesting that PPYP may be administered as a potential marine lipid-lowering drug.

7.
Artículo en Inglés | MEDLINE | ID: mdl-33452640

RESUMEN

The development and utilization of energy in the Loess Plateau has caused a wide range of ecological security issues, and Yan'an has become a typical area for ecological security research on the Loess Plateau. Ecological security evaluation research can provide data support and scientific reference value for the sustainable development, which is of great significance to the overall social and economic development of the region. In this study, the pressure-state-response (PSR) model was used to establish the evaluation index system in the evaluation of ecological security in Yan'an region (YAR), then the fuzzy analytic hierarchy process (FAHP) was used to determine the internal index weight of each element, and finally the ecological security index value (ESI) was calculated. The GIS technology was used to simulate the distribution map of ecological security in YAR and then analyzed the temporal and spatial changes and evolution of ecological security in YAR. The results showed that from 1997 to 2016, the ecological security in the western part of Luochuan County and the eastern part of Yanchuan County was still very high, while the ecological security index was relatively low in the southern part of Huanglong County. The ecological security index of Baota District had increased significantly, from 1.85 in 1997 to 2.76 in 2016. The proportion of III and IV ecological security regions had increased significantly, and the ecological security of the entire YAR was generally in a good situation. This study could clarify the temporal and spatial characteristics of ecological security and provided some reference for the study of ecological security evolution in typical regions of the Loess Plateau.

8.
J Air Waste Manag Assoc ; : 1-12, 2021 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-33428540

RESUMEN

To eliminate nitrogen oxides (NOx), composite carrier-supported catalysts (Mn-Ce/MWCNT-W) and traditional catalysts (Mn-Ce/MWCNT and W-Mn-Ce/MWCNT) were prepared using an ultrasonic impregnation method that preformed low-temperature ammonia-selective catalytic reduction (SCR) removal of NOx. The promotion effects of MWCNT-W composite carriers for low temperature SCR activities and SO2 tolerance of the catalysts were systematically investigated. Compared to traditional catalyst, Mn-Ce/MWCNT-W catalyst, with a 30% WOx/MWCNT mass ratio, demonstrated improved SCR activity and high N2-selectivity from 100°C to 200°C. A series of characterizations were carried out and it was found that there were more redox sites and the stronger the NH3 adsorption capacity over the composite carrier-supported catalysts than traditional catalysts. Also, with this composite carrier-supported catalyst, the improvement of SCR reaction was considered to be from the abundance of high valence state Mn and well dispersed active components. Notably, compared to traditional catalyst, the composite carrier-supported catalyst exhibited the stronger sulfur resistance. Thus, using MWCNT-W composite carriers to prepare Mn-Ce/MWCNT-W catalysts resulted in excellent NOx conversion and SO2 resistance at low temperatures. Implications: LT NH3-SCR of NOx is an effective way to remove NOx from stationary sources. The physicochemical properties of the support not only affect a catalyst's LT SCR activity but also affect the catalyst's anti-poisoning performance. The modified carriers could promote active component dispersion, which is conducive to SCR reaction. However, for LT SCR reactions, few reports have addressed the design and preparation of composite carrier-supported catalysts. The goal of this study was to design and synthesize Mn-Ce/MWCNT-W catalysts and to observe the influence of composite support in Mn-based catalysts on LT SCR activity and sulfur resistance.

9.
Ann Clin Transl Neurol ; 8(2): 498-503, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33400852

RESUMEN

Paraneoplastic autoimmune encephalitis (PAE) represents a group of rare neurological syndromes associated with neoplastic diseases. Here, we report a case that multiple anti-neuronal antibodies were present in a patient with PAE who developed both small cell lung cancer and colorectal adenocarcinoma. Furthermore, the immunopathological investigation of the colorectal adenocarcinoma revealed the formation of abnormal neuronal antigens and a massive infiltration of plasma cells in the tumor tissue. These findings support the hypothesis that expression of neuronal antigens in neoplasm initiates autoimmune responses in PAE.

10.
Phytomedicine ; 80: 153402, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33203590

RESUMEN

BACKGROUND: Although great achievements have been made in the field of cancer therapy, chemotherapy and radiotherapy remain the mainstay cancer therapeutic modalities. However, they are associated with various side effects, including cardiocytotoxicity, nephrotoxicity, myelosuppression, neurotoxicity, hepatotoxicity, gastrointestinal toxicity, mucositis, and alopecia, which severely affect the quality of life of cancer patients. Plants harbor a great chemical diversity and flexible biological properties that are well-compatible with their use as adjuvant therapy in reducing the side effects of cancer therapy. PURPOSE: This review aimed to comprehensively summarize the molecular mechanisms by which phytochemicals ameliorate the side effects of cancer therapies and their potential clinical applications. METHODS: We obtained information from PubMed, Science Direct, Web of Science, and Google scholar, and introduced the molecular mechanisms by which chemotherapeutic drugs and irradiation induce toxic side effects. Accordingly, we summarized the underlying mechanisms of representative phytochemicals in reducing these side effects. RESULTS: Representative phytochemicals exhibit a great potential in reducing the side effects of chemotherapy and radiotherapy due to their broad range of biological activities, including antioxidation, antimutagenesis, anti-inflammation, myeloprotection, and immunomodulation. However, since a majority of the phytochemicals have only been subjected to preclinical studies, clinical trials are imperative to comprehensively evaluate their therapeutic values. CONCLUSION: This review highlights that phytochemicals have interesting properties in relieving the side effects of chemotherapy and radiotherapy. Future studies are required to explore the clinical benefits of these phytochemicals for exploitation in chemotherapy and radiotherapy.


Asunto(s)
Antineoplásicos/efectos adversos , Fitoquímicos/farmacología , Sustancias Protectoras/farmacología , Radioterapia/efectos adversos , Animales , Antiinflamatorios no Esteroideos/farmacología , Antineoplásicos/uso terapéutico , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/radioterapia , Estrés Oxidativo/efectos de los fármacos , Traumatismos por Radiación/prevención & control
11.
Methods Mol Biol ; 2211: 57-68, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33336270

RESUMEN

Catanionic nanovesicles are attractive as a novel class of delivery vehicle because they can increase the stability, adsorption, and cellular uptake of a broad range of drugs. These hybrid lipid nanocarriers consist of solid and liquid lipids, which are biocompatible and biodegradable. Since liquid lipid is added to the nanocarrier, the lipids are present in a crystalline defect or amorphous structure state. As a result, hybrid lipid nanocarriers have a higher drug loading capability and suffer less drug leakage during preparation and storage compared to the pure lipid nanocarriers. Catanionic nanovesicles have been shown to increase stability, adsorption, cellular uptake, apoptosis induction, tumor cell cytotoxicity, and antitumorigenic effect, making it a highly desirable vehicle for drug delivery. For example, the anticancer compound curcumin (CC) have shown great promise to cure cancers such as lung cancer, breast cancer, stomach cancer, and colon cancer. However, like many potential antitumor drugs, CC on its own has poor water solubility, easy photodegradation, chemical instability, low bioavailability, rapid metabolism, and fast systematic clearance, which severely limits its clinical applications. In this chapter, we demonstrate the use of catanionic nanovesicles to improve the bioavailability and efficacy of CC for anticancer applications. This technique can be easily adapted for delivery and evaluation of other bioactive compounds.

12.
J Hazard Mater ; 406: 124596, 2020 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-33307449

RESUMEN

Microcystin-LR (MC-LR) is a high-toxic biohazard that pollutes ecological environment and agroproducts. In this study, a newly recombined genetically engineered antibody (AVHH-MVH) with higher thermal stability and binding activity was designed by chain shuffling and based on our previously obtained anti-MC-LR scFv and nanobody. Based on AVHH-MVH template, a capacity of 8.99 × 105 CFU/mL of phage display AVHH-MVH mutagenesis library was constructed by site-directed mutagenesis in MVH-CDR3 region, and then used for ultrasensitive mutants screening. Afterwards, a total of five positive AVHH-MVH mutants were isolated from the mutagenesis library, and their binding activity was higher than AVHH-MVH for MC-LR. The AVHH-MVH mutant 3 was cloned into pET-25b vector for soluble expression, and the concentration of target protein expressed in culture system was 43.5 mg/L. An indirect competitive enzyme-linked immunosorbent assay (IC-ELISA) was established based on purified AVHH-MVH mutant 3 protein, and it showed ultrasensitive binding activity for MC-LR with the detection limit of 0.0075 µg/L, which was far below the maximum residue limit standard of 1.0 µg/L in drinking water proposed by World Health Organization. The established IC-ELISA shows good accuracy, repeatability, stability and applicability for MC-LR spiked samples, and it is promising for MC-LR ultrasensitive monitoring.

13.
Life Sci ; 265: 118756, 2020 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-33189816

RESUMEN

Atherosclerosis is the primary culprit of cardiovascular and cerebrovascular diseases. Also, atherogenesis and the development of atherosclerosis involve endothelial cells, monocytes/macrophages, smooth myocytes, and others. Increasingly, studies have found that non-coding RNA (ncRNA) which can regulate apoptosis, pyroptosis, autophagy, proliferation, and monocyte migration participates in atherogenesis and progress of atherosclerosis by the above. The ncRNA networks may be essential in regulating the complicated process of atherosclerosis. Accordingly, this review delves into the regulatory roles of ncRNA, which were introduced previously. The answer above is particularly crucial to explain further the regulatory mechanism of ncRNA in cardiovascular disorders. Furthermore, we discuss the possibility and related research of ncRNAs as a biomarker and therapeutic target for the prevention, diagnosis, and treatment of atherosclerosis.

14.
Pak J Pharm Sci ; 33(3): 1033-1048, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-33191227

RESUMEN

Curcuma was the dried rhizomes of Curcuma kwangsiensis S.G. Lee et C.F. Liang (Chinese name: e zhu), have been used in China for thousands of years. There are some reports have shown that curcumin, the major component of curcuma, has a good curative effect on psoriasis, but the mechanism is still unknown, so the present study was designed to investigate the effect of curcuma's extraction on psoriasis-like mouse, and to explore the mechanisms of therapy. First, we observed that curcuma's extractions effect on mitosis of mouse vaginal epithelial cells; then making psoriasis like model and measuring the score of skin damage on days 7 and 14; finally, we observed the expression of immune factors (CK14, CK16, CK17, PCNA, TLR-2, TLR-4, TLR-9) in propranolol induced psoriasis like rats. Curcuma's extraction prohibited the mitosis of mouse vaginal epithelial cells; curcuma's extractions have a significantly efficacy and dose dependent inhibition on imiquimod induced psoriasis like rats; and the expression of immune factors (CK14, CK16, CK17, PCNA, TLR-2, TLR-4, TLR-9) was decreasing in the curcuma's extraction treated groups compared with normal groups. Our research proved that curcuma's extractions have a significantly efficacy on psoriasis like rats, thus, curcuma's extractions can be a potential novel treatment for psoriasis. Furthermore, the expression of immune factors was decreasing after treatment with curcuma's extraction suggest us cytokines has strong relation with the mechanism of therapy for psoriasis. Our results contribute towards validation of curcuma in the treatment of psoriasis and other joint disorders.

15.
Hum Genet ; 2020 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-33140241

RESUMEN

Alzheimer's disease (AD) is one of the most common neurodegeneration diseases caused by multiple factors. The mechanistic insight of AD remains limited. To disclose molecular mechanisms of AD, many studies have been proposed from transcriptome analyses. However, no analysis across multiple levels of transcription has been conducted to discover co-expression networks of AD. We performed gene-level and isoform-level analyses of RNA sequencing (RNA-seq) data from 544 brain tissues of AD patients, mild cognitive impaired (MCI) patients, and healthy controls. Gene and isoform levels of co-expression modules were constructed by RNA-seq data. The associations of modules with AD were evaluated by integrating cognitive scores of patients, Genome-wide association studies (GWAS), alternative splicing analysis, and dementia-related genes expressed in brain tissues. Totally, 29 co-expression modules were found with expressions significantly correlated with the cognitive scores. Among them, two isoform modules were enriched with AD-associated SNPs and genes whose mRNA splicing displayed significant alteration in relation to AD disease. These two modules were further found enriched with dementia-related genes expressed in four brain regions of 125 AD patients. Analyzing expressions of these two modules revealed expressions of 39 isoforms (corresponding to 35 genes) significantly correlated with cognitive scores of AD patients, in which 38 isoforms were significantly up-regulated in AD patients comparing to controls, and 33 isoforms (corresponding to 29 genes) were not reported as AD-related previously. Employing the co-expression modules and the drug-induced gene expression data from Connectivity Map (CMAP), 12 drugs were predicted as significant in restoring the gene expression of AD patients towards health, which include nine drugs reported for relieving AD. In comparison, four of the top 12 significant drugs were known for relieving AD if the drug prediction was performed by the genes expressed significantly different in AD and healthy controls. Analysis of multiple levels of the transcriptomic organization is useful in suggesting AD-related co-expression networks and discovering drugs.

16.
Mol Med Rep ; 22(6): 4601-4610, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33174000

RESUMEN

Severe invasive aspergillosis infection occurs when human immune function is impaired. The interaction between Aspergillus fumigatus (A. fumigatus) conidia and type II lung epithelial cells serves an important role in disease progression. The present study compared the proteomes of A549 human lung epithelial cells with and without A. fumigatus infection. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein interaction analyses were performed, and differential protein expression was verified by western blotting and reverse transcription­quantitative PCR (RT­qPCR). In addition, the RNA interference method, an internalization assay and ELISA were performed. Isobaric tags for relative and absolute quantification analysis detected a total of 1,582 proteins, from which 111 proteins with differential expression were obtained (fold change >1.5 or <0.75). Among them, 18 proteins were upregulated and 93 proteins were downregulated in A549 cells challenged with A. fumigatus. GO and KEGG analyses revealed that the altered proteins were mainly involved in biological functions, such as cell metabolism, synthesis, the cellular stress response, metabolic pathways and pyruvate metabolism. N­myc downstream­regulated gene 1 (NDRG1) expression was upregulated 1.88­fold, while CD44 expression was downregulated 0.47­fold following A. fumigatus infection. The expression levels of specific proteins were verified by western blotting and RT­qPCR. The internalization efficiency was affected by NDRG1 gene silencing. The secretion of IL­6 and IL­8 was affected when CD44 was inhibited. These results indicated that A. fumigatus affects lung epithelial cell metabolism and biological synthetic functions. A number of novel molecules, including NDRG1 and CD44, were found to be related to A. fumigatus infection.

17.
Artículo en Inglés | MEDLINE | ID: mdl-33098203

RESUMEN

Polar materials attract wide research interest due to their unique properties, such as ferroelectricity and the bulk photovoltaic effect (BPVE), which are not accessible with nonpolar materials. However, in general, rationally designing polar materials is difficult because nonpolar materials are more favorable in terms of dipole-dipole interactions. Here, we report a rational strategy to form polar assemblies with bowl-shaped π-conjugated molecules and a molecular design principle for this strategy. We synthesized and thoroughly characterized 12 single crystals with the help of various theoretical calculations. Furthermore, we demonstrated that it can be possible to predict whether polar assemblies become more favorable or not by estimating their lattice energies. We believe that this study contributes to the development of organic polar materials and their related studies.

18.
J Dermatol Sci ; 2020 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-33059972

RESUMEN

BACKGROUND: Radiation-induced skin injury is one of the main adverse effects and a dose-limiting factor of radiotherapy without feasible treatment. The underlying mechanism of this disease is still limited. OBJECTIVE: To investigate the potential molecular pathways and mechanisms of radiation-induced skin injury. METHODS: mRNA expression profiles were determined by Affymetrix Human HTA2.0 microarray.IFI6 overexpression and knockdown were mediated by lentivirus. The functional changes of skin cells were measured by flow cytometry, ROS probe and Edu probe. Protein distribution was detected by immunofluorescence experiment, and IFI6-interacting proteins were detected by immunoprecipitation (IP) combined with mass spectrometry. The global gene changes in IFI6-overexpressed skin cells after irradiation were detected by RNA-seq. RESULTS: mRNA expression profiling showed 50 upregulated and 13 down regulated genes and interferon alpha inducible protein 6 (IFI6) was top upregulated. Overexpression of IFI6 promoted cell proliferation and reduced cell apoptosis as well as ROS production following radiation, and conversely, increased the radiosensitivity of HaCaT and human skin fibroblast (WS1). IFI6 was translocated into nucleus in irradiated skin cells and the interacting relationship with mitochondrial single-stranded DNA-binding protein 1 (SSBP1), which could enhance the transcriptional activity of heat shock transcription factor 1 (HSF1).IFI6 augmented HSF1 activity following radiation in HaCaT and WS1 cells. RNA-seq analysis showed IFI6 modulated virus infection and cellular response to stress pathways, which may help to further explore how IFI6 regulate the transcriptional activity of HSF1. CONCLUSION: This study reveals that IFI6 is induced by ionizing radiation and confers radioprotection in skin cells.

19.
Cell Prolif ; 53(10): e12912, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32964544

RESUMEN

OBJECTIVES: Mechanical force plays an important role in modulating stem cell fate and behaviours. However, how periodontal ligament stem cells (PDLSCs) perceive mechanical stimulus and transfer it into biological signals, and thereby promote alveolar bone remodelling, is unclear. MATERIALS AND METHODS: An animal model of force-induced tooth movement and a compressive force in vitro was used. After force application, tooth movement distance, mesenchymal stem cell and osteoclast number, and proinflammatory cytokine expression were detected in periodontal tissues. Then, rat primary PDLSCs with or without force loading were isolated, and their stem cell characteristics including clonogenicity, proliferation, multipotent differentiation and immunoregulatory properties were evaluated. Under compressive force in vitro, the effects of the ERK signalling pathway on PDLSC characteristics were evaluated by Western blotting. RESULTS: Mechanical force in vivo induced PDLSC proliferation, which was accompanied with inflammatory cytokine accumulation, osteoclast differentiation and TRPV4 activation; the force-stimulated PDLSCs showed greater clonogenicity and proliferation, reduced differentiation ability, improved induction of macrophage migration, osteoclast differentiation and proinflammatory factor expression. The biological changes induced by mechanical force could be partially suppressed by TRPV4 inhibition. Mechanistically, force-induced activation of TRPV4 in PDLSCs regulated osteoclast differentiation by affecting the RANKL/OPG system via ERK signalling. CONCLUSIONS: Taken together, we show here that TRPV4 activation in PDLSCs under mechanical force contributes to changing their stem cell characteristics and modulates bone remodelling during tooth movement.


Asunto(s)
Remodelación Ósea , Ligamento Periodontal/citología , Células Madre/citología , Canales Catiónicos TRPV/metabolismo , Animales , Fenómenos Biomecánicos , Proliferación Celular , Células Cultivadas , Humanos , Masculino , Osteoclastos/citología , Osteoclastos/metabolismo , Ligamento Periodontal/metabolismo , Ratas , Ratas Sprague-Dawley , Células Madre/metabolismo , Estrés Mecánico
20.
Front Immunol ; 11: 2101, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32983166

RESUMEN

Background and Purpose: The mechanism underlying the pathology of neuromyelitis optica spectrum disorders (NMOSD) remains unclear even though antibodies to the water channel protein aquaporin-4 (AQP4) on astrocytes play important roles. Our previous study showed that dysbiosis occurred in the fecal microbiota of NMOSD patients. In this study, we further investigated whether the intestinal barrier and mucosal flora balance are also interrupted in NMOSD patients. Methods: Sigmoid mucosal biopsies were collected by endoscopy from six patients with NMOSD and compared with samples from five healthy control (HC) individuals. These samples were processed for electron microscopy and immunohistochemistry to investigate changes in ultrastructure and in the number and size of intestinal inflammatory cells. Changes in mucosal flora were also analyzed by high-throughput 16S ribosomal RNA gene amplicon sequencing. Results: The results from bacterial rRNA gene sequencing showed that bacterial diversity was decreased, but Streptococcus and Granulicatella were abundant in the colonic mucosa specimens of NMOSD patients compared to the HC individuals. The intercellular space between epithelia of the colonic mucosa was wider in NMOSD patients compared to the HC subjects (p < 0.01), and the expression of tight junction proteins [occludin, claudin-1 and zonula occludens-1 (ZO-1)] in NMOSD patients significantly decreased compared to that in the HC subjects. We also found numerous activated macrophages with many inclusions within the cytoplasm, mast cells with many particles in their cytoplasm, and enlarged plasma cells with rich developed rough endoplasmic reticulum in the lamina propria of the mucosa of the patients with NMOSD. Quantitative analysis showed that the percentages of small CD38+ and CD138+ cells (plasma cells) were lower, but the percentage of larger plasma cells was higher in NMOSD patients. Conclusion: The present study demonstrated that the intestinal barrier was disrupted in the patients with NMOSD, accompanied by dysbiosis and inflammatory activation of the gut. The mucosal microbiota imbalance and inflammatory responses might allow pathogens to cross the damaged intestinal barrier and participate in pathological process in NMOSD. However, further study on the pathological mechanism of NMOSD underlying gut dysbiosis is warranted in the future.

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