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1.
Transl Cancer Res ; 11(4): 603-614, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35571655

RESUMO

Background: Glioblastoma multiforme (GBM) is the most aggressive type of primary brain tumor. Ferroptosis is a form of cell death that is involved in regulating the biological behavior of tumors, and could become a promising potential biomarker in tumor diagnosis and treatment. Methods: We used the expression of ferroptosis related genes in the Cancer Genome Atlas (TCGA) and Chinese Glioma Cooperative Group (CGCG) datasets to construct a prognostic prediction model and verified the expression by real-time polymerase chain reaction (RT-qPCR). Using TCGA genomic and epigenetic data, we analyzed the factors that regulate the expression of these ferroptosis related genes. Results: We used 15 ferroptosis related genes related to the prognosis of GBM to establish a prognostic predictive risk model. The area under the curve (AUC) of this model was 0.907, which had good utility in predicting the prognosis of GBM, and could be used as an independent prognostic indicator for GBM patients. We verified the expression of these risk genes by RT-qPCR in 30 independent pairs of tumors and adjacent tissues. Genomic and epigenetic analysis of risk genes found that the expressions of these genes were mainly regulated by methylation, not copy number variation in GBM. Conclusions: The ferroptosis related characteristics proposed in this study can potentially predict the prognosis of GBM patients, and these prognostic-related genes are generally regulated by methylation.

2.
Theranostics ; 12(7): 3438-3455, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547774

RESUMO

Rationale: Gut barrier disruption caused by enteric pathogen infection results in activated diabetogenic T cells and accelerated type 1 diabetes (T1D). Cathelicidin-related antimicrobial peptide (CRAMP) maintains intestinal barrier integrity, regulates the microbiome, and exerts positive immune-modulatory effects on pancreatic diseases. Methods: The model enteric pathogen Citrobacter rodentium (C. rodentium) was adopted to represent clinical colonic infection with gut barrier disruption. The protective role and gut-pancreas pathophysiological mechanism of CRAMP in enteric pathogen-accelerated T1D were investigated in spontaneous non-obese diabetic (NOD) mice and streptozotocin-induced diabetic mice. Results: Colonic CRAMP production was defective in C. rodentium infection-accelerated T1D. C. rodentium infection triggered the recruitment of interferon-gamma (IFN-γ)+ T cells and accelerated T1D. In the C. rodentium-accelerated T1D mice, CRAMP deficiency further aggravated gut barrier disruption, gut dysbiosis, and diabetic phenotype, which could be reversed by CRAMP treatment. The protective effect of CRAMP may be due to CRAMP inhibiting C. rodentium-aggravated gut immune dysregulation, gut dysbiosis, and migration of gut-primed IFN-γ+ T cells to the pancreas, thus contributing to gut barrier protection and pancreatic-intestinal immune homeostasis. Conclusion: CRAMP plays a pivotal role in pancreatic-gut crosstalk during C. rodentium-accelerated T1D by gut barrier-protective, immune- and microbial-modulatory mechanisms. Cathelicidin supplementation to restore a healthy gut barrier may represent a novel therapeutic strategy for T1D.

3.
BMC Plant Biol ; 22(1): 240, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35549680

RESUMO

As high soil salinity threatens the growth and development of plants, understanding the mechanism of plants' salt tolerance is critical. The Chrysanthemum × grandiflora is a newly developed species with a strong salt resistance that possesses multiple genes controlling its quantitative salt resistance. Because of this multigene control, we chose to investigate the plant stress genes overall responses at the transcriptome level. C. grandiflora were treated with a 200 mM NaCl solution for 12 h to study its effect on the roots and leaves via Illumina RNA sequencing. PAL, CYP73A, and 4CL in the phenylpropanoid biosynthesis pathway were upregulated in roots and leaves. In the salicylic acid signal transduction pathway, TGA7 was upregulated in the roots and leaves, while in the jasmonic acid signal transduction pathway, TIFY9 was upregulated in the roots and leaves. In the ion transporter gene, we identified HKT1 that showed identical expression patterns in the roots and leaves. The impact of NaCl imposition for 12 h was largely due to osmotic effect of salinity on C. grandiflora, and most likely the transcript abundance changes in this study were due to the osmotic effect. In order to verify the accuracy of the Illumina sequencing data, we selected 16 DEGs for transcription polymerase chain reaction (qRT-PCR) analysis. qRT-PCR and transcriptome sequencing analysis revealed that the transcriptome sequencing results were reliable.

4.
Molecules ; 27(9)2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35566310

RESUMO

Daylily is a valuable plant resource with various health benefits. Its main bioactive components are phenolic compounds. In this work, four extraction methods, ultrasonic-assisted water extraction (UW), ultrasonic-assisted ethanol extraction (UE), enzymatic-assisted water extraction (EW), and enzymatic-assisted ethanol extraction (EE), were applied to extract phenolic compounds from daylily. Among the four extracts, the UE extract exhibited the highest total phenolic content (130.05 mg/100 g DW) and the best antioxidant activity. For the UE extract, the DPPH value was 7.75 mg Trolox/g DW, the FRAP value was 14.54 mg Trolox/g DW, and the ABTS value was 15.37 mg Trolox/g DW. A total of 26 phenolic compounds were identified from the four extracts, and the UE extract exhibited a higher abundance range of phenolic compounds than the other three extracts. After multivariate statistical analysis, six differential compounds were selected and quantified, and the UE extract exhibited the highest contents of all six differential compounds. The results provided theoretical support for the extraction of phenolic compounds from daylily and the application of daylily as a functional food.

5.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 38(3): 268-274, 2022 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-35365993

RESUMO

Objective To prepare murine monoclonal antibody (mAb) against enterovirus 71 (EV71) capsid protein VP1. Methods VP1 protein was expressed and purified. BALB/c mice were immunized with inactivated and purified EV71 virus, and mAb specific to EV71 VP1 was generated by hybridoma technique. Indirect ELISA was used to test antibody titer and antibody subclass identification. The expression of VP1 protein was detected by Western blot in EV71-infected RD cells. The expression and distribution of VP1 protein was detected by immunofluorescence cytochemistry in EV71-infected RD cells. Results Six antibody strains were obtained, among which three were IgG2a and three were IgG2b, all of which could be used for ELISA, Western blot and immunofluorescence cytochemical staining. 2D7 exhibited neutralization capacity with 50% inhibitory concentrations(IC50) of 9.892 µg/mL. Conclusion Six strains of monoclonal antibodies with excellent reactivity were obtained, which laid a foundation for the further studies on the identification and diagnosis of EV71 as well as the functional of VP1 protein.


Assuntos
Enterovirus Humano A , Enterovirus , Animais , Anticorpos Monoclonais , Proteínas do Capsídeo , Hibridomas , Camundongos
6.
Front Psychiatry ; 13: 837774, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35444569

RESUMO

Objective: This study aimed to explore transcranial electrical stimulation (tES) to relieve peripartum anxiety and depressive symptoms in women undergoing cesarean section with combined spinal-epidural anesthesia. Methods: This double-blind, randomized, sham-controlled trial was conducted in the Affiliated Hospital of Xuzhou Medical University from March 2021 and May 2021. One hundred and forty-eight full-term parturients giving birth by elective cesarean section were selected, and 126 were included in the intent-to-treat analysis. Parturients were provided standardized anesthesia and randomized to the active-tES (a-tES) group and sham-tES group. Parturients and outcome assessors were blinded to treatment allocation. The primary outcome was the changes in peripartum mental health disorders, including anxiety, assessed by the Pregnancy-Related Anxiety Questionnaire-Revised 2 (PRAQ-R2). Secondary outcomes included peripartum depressive symptoms, assessed by the Edinburgh Postnatal Depression Scale (EPDS), maternal satisfaction, fatigue level, sleep quality index, and pain score during and after operation. Data were collected before entering the operating room (T0), between post-anesthesia and pre-surgery (T1), before leaving the operating room (T2), and at 24 h post-surgery (T3). Results: One hundred and twenty-six eligible parturients were enrolled in the two groups: a-tES group (N = 62) and sham-tES group (N = 64). Treatment with tES resulted in significantly lower scores of anxiety compared with sham-tES (T2: P < 0.001; T3: P = 0.001). Moreover, the a-tES groups showed a significant reduction in depression scores (T2: P = 0.003; T3: P = 0.032). Conclusion: In this randomized pilot study, tES treatment is efficacious in alleviating peripartum anxiety and depressive symptoms in women undergoing cesarean section and has been demonstrated to be a novel strategy for improving peripartum mental health disorders. Clinical Trial Registration: [www.chictr.org.cn], identifier [ChiCTR2000040963].

7.
Cell Death Dis ; 13(4): 299, 2022 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-35379776

RESUMO

A high plasma level of the choline-derived metabolite trimethylamine N-oxide (TMAO) is closely related to the development of cardiovascular disease. However, the underlying mechanism remains unclear. In the present study, we demonstrated that a positive correlation of protein arginine methyltransferase 5 (PRMT5) expression and TMAO-induced vascular inflammation, with upregulated vascular cell adhesion molecule-1 (VCAM-1) expression in primary rat and human vascular smooth muscle cells (VSMC) in vitro. Knockdown of PRMT5 suppressed VCAM-1 expression and the adhesion of primary bone marrow-derived macrophages to TMAO-stimulated VSMC. VSMC-specific PRMT5 knockout inhibited vascular inflammation with decreased expression of VCAM-1 in mice. We further identified that PRMT5 promoted VCAM-1 expression via symmetrical demethylation of Nuclear factor-κB p65 on arginine 30 (R30). Finally, we found that TMAO markedly induced the expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) and production of reactive oxygen species, which contributed to PRMT5 expression and subsequent VCAM-1 expression. Collectively, our data provide novel evidence to establish a Nox4-PRMT5-VCAM-1 in mediating TMAO-induced VSMC inflammation. PRMT5 may be a potential target for the treatment of TMAO-induced vascular diseases.


Assuntos
Músculo Liso Vascular , Molécula 1 de Adesão de Célula Vascular , Animais , Inflamação/genética , Inflamação/metabolismo , Metilaminas/metabolismo , Metilaminas/farmacologia , Camundongos , Músculo Liso Vascular/metabolismo , Ratos , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo
8.
Sci Rep ; 12(1): 6692, 2022 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-35461324

RESUMO

The crosstalk between osteosarcoma (OS) development and abnormally expressed microRNA (miR)-601 is not explored explicitly. Here, we identified the downregulated miR-601 in osteosarcoma (OS) through a comprehensive bioinformatics analysis of GEO Datasets. The results indicated that miR-601 was downregulated in both OS cells and tissues. The OS patients with reduced expression of miR-601 displayed worse prognosis. The results of in vitro and in vivo assay revealed that elevated miR-601 inhibited the proliferative, migratory and invasive capacities in OS cells. Mechanically, miR-601 exerted its function via targeting oncogene protein kinase membrane associated tyrosine/threonine 1 (PKMYT1) at post-transcriptional level. Moreover, miR-601 was attenuated by c-Myb at transcriptional level. Taken together, our studies reveal that miR-601 is a suppressive gene negatively correlated with malignancy of OS.


Assuntos
Neoplasias Ósseas , MicroRNAs , Osteossarcoma , Proteínas Tirosina Quinases , Proteínas Proto-Oncogênicas c-myb , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas de Membrana/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Osteossarcoma/genética , Osteossarcoma/patologia , Prognóstico , /metabolismo , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-myb/genética , Proteínas Proto-Oncogênicas c-myb/metabolismo
9.
Int J Biol Macromol ; 209(Pt B): 1900-1913, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35487379

RESUMO

In this work, short rod-like cationic cellulose nanocrystals (AH-CNCs) were prepared by sodium periodate oxidation combined with deep eutectic solvent method. The effects of different content AH-CNCs on the properties of the emulsion were studied. With the increase of AH-CNCs content, the diameter of emulsion droplets decreased and the stabilization time prolonged. The electrostatic attraction between the negative charge accumulated at the oil-water interface and AH-CNCs with positive charge improved the stability of the emulsion. Then, the rheological properties showed the interaction of nanocellulose in the continuous phase increased the viscosity of the emulsion. In addition, the droplet diameter of emulsion of 120 s was smaller at different ultrasonic time, the particle size distribution of emulsion changed from monodisperse to polydisperse with the increase of oil volume, the salt concentration had little effect on the droplet size of emulsion, and the preparation of emulsion under acidic conditions was more stable.

10.
Hum Exp Toxicol ; 41: 9603271221089000, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35363093

RESUMO

BACKGROUND: LINC00511 has been reported as a biomarker related to the prognosis of non-small cell lung cancer (NSCLC), but the molecular mechanism and exact functions of LINC00511 in chemoresistance of NSCLC remain to be elucidated. METHODS: RT-qPCR was used to evaluate the mRNA expression of LINC00511, miR-625, and leucine rich repeat containing 8 volume-regulated anion channel subunit E (LRRC8E). Western blotting detected the protein levels of Ki-67, MMP-9, cleaved-caspase-3. The interaction between miR-625 and LINC00511 or LRRC8E was verified by luciferase reporter assays. CCK-8, TUNEL, and Transwell assays were used to evaluate IC50 value, proliferation, migration, and invasion of NSCLC cells. RESULTS: In our study, it was discovered that the levels of LINC00511 and LRRC8E were increased, while miR-625 expression was decreased in NSCLC tissues, DDP-resistant NSCLC cells, and non-resistant NSCLC cells. LINC00511 depletion significantly curbed cell growth, IC50 value, and metastasis in DDP-resistant NSCLC cells. In addition, the influence of LINC00511 deficiency on the DDP resistance in NSCLC was overturned by suppressing miR-625. Furthermore, LRRC8E overexpression abolished the promotive effect of miR-625 abundance on the DDP sensitivity in DDP-resistant NSCLC cells. CONCLUSION: Our results demonstrated that LINC00511 increased DDP resistance in NSCLC by suppressing miR-625 to upregulate LRRC8E.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Ânions/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Leucina/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo
11.
Front Bioeng Biotechnol ; 10: 810880, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35433652

RESUMO

At present, bone nonunion and delayed union are still difficult problems in orthopaedics. Since the discovery of bone morphogenetic protein (BMP), it has been widely used in various studies due to its powerful role in promoting osteogenesis and chondrogenesis. Current results show that BMPs can promote healing of bone defects and reduce the occurrence of complications. However, the mechanism of BMP in vivo still needs to be explored, and application of BMP alone to a bone defect site cannot achieve good therapeutic effects. It is particularly important to modify implants to carry BMP to achieve slow and sustained release effects by taking advantage of the nature of the implant. This review aims to explain the mechanism of BMP action in vivo, its biological function, and how BMP can be applied to orthopaedic implants to effectively stimulate bone healing in the long term. Notably, implantation of a system that allows sustained release of BMP can provide an effective method to treat bone nonunion and delayed bone healing in the clinic.

12.
Ultrason Sonochem ; 84: 105975, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35276515

RESUMO

Sterilization plays an important role in extending the shelf-life of apple juice; however, it also affects the nutritional and flavor profile of the juice. This study was initiated to evaluate the effects of several common sterilization methods (conventional pasteurization, microwave sterilization, ultrasonic sterilization, and ultra-high-pressure sterilization) on some important quality parameters of apple juice. The results showed that the content of soluble pectin and soluble protein in juice decreased significantly after ultra-high-pressure sterilization. Sonication was found to be effective in increasing the level of ascorbic acid in apple juice. The sugar:acid ratio increased significantly after pasteurization, microwave sterilization, and ultra-high-pressure sterilization, which changed the taste of juice. Microwave sterilization caused the highest volatile compound loss, while ultra-high-pressure sterilization led to a higher retention rate of volatile compounds in juice. This study could be helpful in seeking suitable sterilization methods retaining the quality of cloudy apple juice.


Assuntos
Malus , Sucos de Frutas e Vegetais , Esterilização , Paladar , Ultrassom
13.
Front Bioeng Biotechnol ; 10: 850110, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35299643

RESUMO

With the development of three-dimensional (3D) printed technology, 3D printed alloy implants, especially titanium alloy, play a critical role in biomedical fields such as orthopedics and dentistry. However, untreated titanium alloy implants always possess a bioinert surface that prevents the interface osseointegration, which is necessary to perform surface modification to enhance its biological functions. In this article, we discuss the principles and processes of chemical, physical, and biological surface modification technologies on 3D printed titanium alloy implants in detail. Furthermore, the challenges on antibacterial, osteogenesis, and mechanical properties of 3D-printed titanium alloy implants by surface modification are summarized. Future research studies, including the combination of multiple modification technologies or the coordination of the structure and composition of the composite coating are also present. This review provides leading-edge functionalization strategies of the 3D printed titanium alloy implants.

14.
Materials (Basel) ; 15(5)2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-35269193

RESUMO

(1) Background: The EndoSequence BC Sealer HiFlow (Brasseler, Savannah, GA, USA) has recently been introduced in clinical applications. Thus, the aims of the present study are to determine its biocompatibility in vivo and to examine its ability to drive macrophage polarization in vitro and in vivo. (2) Methods: HiFlow was implanted into rat connective tissue for 7, 30 and 150 days. The microstructures and elemental compositions were determined by scanning electron microscopy-energy-dispersive X-ray spectroscopy (SEM-EDX). Hematoxylin-eosin, immunofluorescence, RT-qPCR and flow cytometry were used to elucidate the effects on inflammatory responses and macrophage polarization. (3) Results: SEM-EDX revealed the formation of surface hydroxyapatite crystal layers. Histological evaluation showed that HiFlow exhibited long-term biocompatibility because it decreased inflammatory responses and reduced the number of macrophages over time; however, tissue necrosis was observed in all the groups. RT-qPCR verified that HiFlow regulated the expression of inflammatory factors to inhibit the inflammatory response. Immunofluorescence analysis performed on in vivo samples revealed that HiFlow promoted M2-like macrophage polarization, and these results were confirmed by flow cytometry in vitro. (4) Conclusion: After 150 days of investigation, HiFlow was considered biologically acceptable, and the formation of apatite crystal layers and the promotion of M2-like macrophage polarization may contribute to its favorable biocompatibility.

15.
Bioact Mater ; 12: 257-277, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35310382

RESUMO

Regenerative endodontic procedures have been rapidly evolving over the past two decades and are employed extensively in clinical endodontics. These procedures have been perceived as valuable adjuvants to conventional strategies in the treatment of necrotic immature permanent teeth that were deemed to have poor prognosis. As a component biological triad of tissue engineering (i.e., stem cells, growth factors and scaffolds), biomaterial scaffolds have demonstrated clinical potential as an armamentarium in regenerative endodontic procedures and achieved remarkable advancements. The aim of the present review is to provide a broad overview of biomaterials employed for scaffolding in regenerative endodontics. The favorable properties and limitations of biomaterials organized in naturally derived, host-derived and synthetic material categories were discussed. Preclinical and clinical studies published over the past five years on the performance of biomaterial scaffolds, as well as current challenges and future perspectives for the application of biomaterials for scaffolding and clinical evaluation of biomaterial scaffolds in regenerative endodontic procedures were addressed in depth.

16.
Bot Stud ; 63(1): 5, 2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-35247135

RESUMO

BACKGROUND: Salt stress is often associated with excessive production of reactive oxygen species (ROS). Oxidative stress caused by the accumulation of ROS is a major factor that negatively affects crop growth and yield. Root is the primary organ that senses and transmits the salt stress signal to the whole plant. How oxidative stress affect redox sensitive proteins in the roots is not known. RESULTS: In this study, the redox proteome of sugar beet M14 roots under salt stress was investigated. Using iTRAQ reporters, we determined that salt stress caused significant changes in the abundance of many proteins (2305 at 20 min salt stress and 2663 at 10 min salt stress). Using iodoTMT reporters, a total of 95 redox proteins were determined to be responsive to salt stress after normalizing again total protein level changes. Notably, most of the differential redox proteins were involved in metabolism, ROS homeostasis, and stress and defense, while a small number play a role in transport, biosynthesis, signal transduction, transcription and photosynthesis. Transcription levels of 14 genes encoding the identified redox proteins were analyzed using qRT-PCR. All the genes were induced by salt stress at the transcriptional level. CONCLUSIONS: Based on the redox proteomics results, we construct a map of the regulatory network of M14 root redox proteins in response to salt stress. This study further refines the molecular mechanism of salt resistance at the level of protein redox regulation.

17.
Ying Yong Sheng Tai Xue Bao ; 33(2): 369-377, 2022 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-35229510

RESUMO

Reasonable nutrient and water management is effective ways to improve productivity and biodiversity of degraded grasslands. However, little is known about the effects of nutrient and water addition on soil inorganic phosphorus (P) fractions in old-field grasslands. Based on a field experiment with nutrient addition (N: 10 g·m-2·a-1, P: 10 g·m-2·a -1) and water addition (180 mm water irrigated during plant growing season) in Duolun County, Inner Mongolia in 2005, we examined the changes of inorganic P fractions and Olsen-P contents in the topsoil (0-10 cm). Results showed that 11-year P addition significantly increased total inorganic P (TIP) content, and that exogenous P was mostly transformed into calcium phosphate (Ca-P: 62.6%-69.2%), and then into aluminium phosphate (Al-P: 19.9%-25.1%), ferric phosphate (Fe-P) and occluded P (O-P). Phosphorus incorporated with nitrogen (N) addition significantly increased Fe-P and Al-P contents by declining soil pH and activating Fe3+ and Al3+ in soil. Water addition alone significantly increased Fe-P, Al-P, and decalcium phosphate (Ca10-P) fractions, and the contents of Fe-P, Al-P, octacalcium phosphate (Ca8-P), and Ca10-P were greater in P incorporated with water treatment than in P addition alone. There was no difference of each inorganic P fraction between P incorporated with N and water treatment and P incorporated with N treatment. Phosphorus and P incorporated with N additions significantly increased soil Olsen-P content, while water addition significantly decreased soil Olsen-P content under P addition alone and P incorporated with N treatment. In the calcareous soils, calcium superphosphate addition could enhance soil inorganic P pool through increasing Ca-P fraction.


Assuntos
Pradaria , Solo , Nitrogênio , Nutrientes , Fósforo/química , Solo/química
18.
Pharm Biol ; 60(1): 326-333, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35167426

RESUMO

CONTEXT: Studies have shown that tanshinone IIA (TIIA) has an anti-inflammatory effect, but the effect on allergic rhinitis (AR) is unclear. OBJECTIVE: In this study, we explore the effect of TIIA on AR. MATERIALS AND METHODS: AR mice model was established by the intraperitoneal (ip) injection of 50 µg ovalbumin (OVA). AR mice in the dose tested groups were treated with TIIA (10 mg/kg/d, ip) or dexamethasone (Dex) (2.5 mg/kg/d, oral). The number of nasal rubbing in mice was counted. Inflammatory, goblet and mast cells in nasal mucosal tissue were detected. The contents of histamine, OVA-immunoglobulin E (IgE), OVA-immunoglobulin G1 (IgG1), tumour necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-5, interferon-γ (IFN-γ) and IL-12 in nasal lavage fluid (NALF) or serum were measured. Human mast cells (HMC-1) were treated with C48/80 to release histamine or TIIA for therapeutic effect, and the cell viability, histamine content and mast cell degranulation were examined. RESULTS: OVA promoted the number of nasal rubbings in mice (78 times/10 min, p< 0.001), increased the inflammatory, goblet and mast cells in nasal mucosal tissue, and significantly (p< 0.001) elevated the levels of histamine (120 ng/mL), OVA-IgE (2 pg/mL), OVA-IgG1 (90 ng/mL), TNF-α (2.3 pg/mL), IL-4 (150 pg/mL) and IL-5 (65 pg/mL) in serum or NALF of OVA-induced AR mice. However, both TIIA and Dex inhibited the effect of OVA on AR mice. Besides, TIIA reversed the promotion of histamine release (30%) and mast cell degranulation induced by C48/80. DISCUSSION AND CONCLUSIONS: TIIA alleviates OVA-induced AR symptoms in AR mice, and may be applied as a therapeutic drug for patients with Th2-, or mast cell-allergic disorders.


Assuntos
Abietanos/farmacologia , Liberação de Histamina/efeitos dos fármacos , Rinite Alérgica/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Dexametasona/farmacologia , Modelos Animais de Doenças , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina , Células Th2/imunologia
19.
J Inflamm Res ; 15: 1047-1061, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35210811

RESUMO

BACKGROUND: GIMAP, a GTP enzyme of immune-related proteins, plays a crucial role in immune mechanisms. Investigating GIMAP7 expression in pan-cancer can provide efficient guidance for predicting clinical prognosis and identifying novel immunotherapy targets. METHODS: Gene expression in different tumour types and stages was analysed based on The Cancer Genome Atlas and the Genotype-Tissue Expression database. An immunohistochemical assay was used to explore the differences in GIMAP7 protein levels in different tumour types and stages. Further, the cBioPortal was used to obtain the genetic variation characteristics of GIMAP7. Kaplan-Meier analysis and multivariable Cox regression analysis were performed to assess the prognostic value of GIMAP7. The pathways affected by GIMAP7 were studied based on gene set enrichment analysis, and the correlation between GIMAP7 expression and immune infiltration was determined using the TIMER2 database and the CIBERSORT method. ESTIMATE was used to analyse the correlation between GIMAP7 expression and ESTIMATE, immune and stromal scores. In addition, the correlation between GIMAP7 and immunoregulators was analysed. Furthermore, tumour mutational burden and microsatellite instability were evaluated using Spearman correlation assay. RESULTS: GIMAP7 expression was significantly low and predicted better survival status in most tumour types. GIMAP7 was positively correlated with the abundance of CD8 + and CD4 + T cells in the tumour microenvironment. However, the high expression of GIMAP7 was negatively correlated with tumour mutations in uveal melanoma and colon adenocarcinoma. A correlation between GIMAP7 and microsatellite instability was found in rectal adenocarcinoma. Additionally, GIMAP7 presented a robust correlation between immune modulators and immunotherapeutic markers. Moreover, high GIMAP7 expression was significantly related to immune-relevant pathways. CONCLUSION: This study suggests the potential role of GIMAP7 as a prognostic and immunotherapeutic marker in pan-cancer, laying the groundwork for prospective functional and mechanistic experiments and their impact in the clinical setting.

20.
Free Radic Res ; 56(1): 63-76, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35109721

RESUMO

Oxidative stress is an important contributor to the development of osteoporosis. Melatonin, an indoleamine secreted by the pineal gland, has antioxidant properties. This study aims to explore whether melatonin can promote bone formation and elucidate the mechanisms underlying this process. In this study, we used an in vitro hydrogen peroxide (H2O2)-induced oxidative stress model in MC3T3-E1 cells and an in vivo ovariectomized osteoporotic bone defect model in rats to explore the protective effects of melatonin against osteoporotic bone defects along with the mechanism underlying these effects. We found that melatonin significantly increased alkaline phosphatase activity, mineralization capacity, and the expression of BMP2, RUNX2, and OPN in MC3T3-E1 cells treated with H2O2. Furthermore, melatonin was found to activate SIRT1, SIRT3 and inhibit p66Shc, reduce the intracellular reactive oxygen species levels, stabilize mitochondria, reduce malondialdehyde levels, increase superoxide dismutase activity, and reduce apoptosis in MC3T3-E1 cells treated with H2O2. Intriguingly, these effects could be reversed by the SIRT1 inhibitor EX527. In vivo experiments confirmed that melatonin improves the microstructure and bone mineral density of the distal femoral bone trabecula and promotes bone formation. Meanwhile, melatonin activated SIRT1, inhibited p66Shc and increased SIRT3 expression. Taken together, our findings showed that melatonin can restrain oxidative damage in MC3T3-E1 cells and promote osteogenesis by activating SIRT1 which regulate the activity of SIRT3 and inhibit the expression of p66Shc, suggesting that melatonin could be a potential therapeutic agent for osteoporosis-related bone metabolic diseases.


Assuntos
Melatonina , Osteoporose , Sirtuína 3 , Animais , Peróxido de Hidrogênio/metabolismo , Melatonina/farmacologia , Melatonina/uso terapêutico , Osteoblastos/metabolismo , Osteogênese , Osteoporose/induzido quimicamente , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Estresse Oxidativo , Ratos , Sirtuína 1/genética , Sirtuína 1/metabolismo , Sirtuína 3/genética , Sirtuína 3/metabolismo , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/metabolismo , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/farmacologia , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/uso terapêutico
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