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1.
Front Pharmacol ; 15: 1304502, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38487163

RESUMO

The tumor microenvironment (TME) plays an important role in dynamically regulating the progress of cancer and influencing the therapeutic results. Targeting the tumor microenvironment is a promising cancer treatment method in recent years. The importance of tumor immune microenvironment regulation by ultrasound combined with microbubbles is now widely recognized. Ultrasound and microbubbles work together to induce antigen release of tumor cell through mechanical or thermal effects, promoting antigen presentation and T cells' recognition and killing of tumor cells, and improve tumor immunosuppression microenvironment, which will be a breakthrough in improving traditional treatment problems such as immune checkpoint blocking (ICB) and himeric antigen receptor (CAR)-T cell therapy. In order to improve the therapeutic effect and immune regulation of TME targeted tumor therapy, it is necessary to develop and optimize the application system of microbubble ultrasound for organs or diseases. Therefore, the combination of ultrasound and microbubbles in the field of TME will continue to focus on developing more effective strategies to regulate the immunosuppression mechanisms, so as to activate anti-tumor immunity and/or improve the efficacy of immune-targeted drugs, At present, the potential value of ultrasound combined with microbubbles in TME targeted therapy tumor microenvironment targeted therapy has great potential, which has been confirmed in the experimental research and application of breast cancer, colon cancer, pancreatic cancer and prostate cancer, which provides a new alternative idea for clinical tumor treatment. This article reviews the research progress of ultrasound combined with microbubbles in the treatment of tumors and their application in the tumor microenvironment.

2.
Mol Plant ; 17(4): 614-630, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38454602

RESUMO

The infection of host plants by many different viruses causes reactive oxygen species (ROS) accumulation and yellowing symptoms, but the mechanisms through which plant viruses counteract ROS-mediated immunity to facilitate infection and symptom development have not been fully elucidated. Most plant viruses are transmitted by insect vectors in the field, but the molecular mechanisms underlying virus‒host-insect interactions are unclear. In this study, we investigated the interactions among wheat, barley yellow dwarf virus (BYDV), and its aphid vector and found that the BYDV movement protein (MP) interacts with both wheat catalases (CATs) and the 26S proteasome ubiquitin receptor non-ATPase regulatory subunit 2 homolog (PSMD2) to facilitate the 26S proteasome-mediated degradation of CATs, promoting viral infection, disease symptom development, and aphid transmission. Overexpression of the BYDV MP gene in wheat enhanced the degradation of CATs, which leading to increased accumulation of ROS and thereby enhanced viral infection. Interestingly, transgenic wheat lines overexpressing BYDV MP showed significantly reduced proliferation of wingless aphids and an increased number of winged aphids. Consistent with this observation, silencing of CAT genes also enhanced viral accumulation and reduced the proliferation of wingless aphids but increased the occurrence of winged aphids. In contrast, transgenic wheat plants overexpressing TaCAT1 exhibited the opposite changes and showed increases in grain size and weight upon infection with BYDV. Biochemical assays demonstrated that BYDV MP interacts with PSMD2 and promotes 26S proteasome-mediated degradation of TaCAT1 likely in a ubiquitination-independent manner. Collectively, our study reveals a molecular mechanism by which a plant virus manipulates the ROS production system of host plants to facilitate viral infection and transmission, shedding new light on the sophisticated interactions among viruses, host plants, and insect vectors.


Assuntos
Afídeos , Luteovirus , Complexo de Endopeptidases do Proteassoma , Viroses , Animais , Triticum , Afídeos/genética , Catalase , Proteínas Virais , Espécies Reativas de Oxigênio , Luteovirus/genética , Plantas Geneticamente Modificadas , Doenças das Plantas
3.
Proc Natl Acad Sci U S A ; 121(12): e2319582121, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38483998

RESUMO

The presence of viruses that spread to both plant and fungal populations in nature has posed intriguingly scientific question. We found a negative-strand RNA virus related to members of the family Phenuiviridae, named Valsa mali negative-strand RNA virus 1 (VmNSRV1), which induced strong hypovirulence and was prevalent in a population of the phytopathogenic fungus of apple Valsa canker (Valsa mali) infecting apple orchards in the Shaanxi Province of China. Intriguingly, VmNSRV1 encodes a protein with a viral cell-to-cell movement function in plant tissue. Mechanical leaf inoculation showed that VmNSRV1 could systemically infect plants. Moreover, VmNSRV1 was detected in 24 out of 139 apple trees tested in orchards in Shaanxi Province. Fungal inoculation experiments showed that VmNSRV1 could be bidirectionally transmitted between apple plants and V. mali, and VmNSRV1 infection in plants reduced the development of fungal lesions on leaves. Additionally, the nucleocapsid protein encoded by VmNSRV1 is associated with and rearranged lipid droplets in both fungal and plant cells. VmNSRV1 represents a virus that has adapted and spread to both plant and fungal hosts and shuttles between these two organisms in nature (phyto-mycovirus) and is potential to be utilized for the biocontrol method against plant fungal diseases. This finding presents further insights into the virus evolution and adaptation encompassing both plant and fungal hosts.


Assuntos
Ascomicetos , Micovírus , Malus , Micoses , Vírus de RNA , Ascomicetos/genética , Vírus de RNA/genética , Doenças das Plantas/microbiologia , Malus/metabolismo
4.
Mol Plant Pathol ; 25(2): e13437, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38393681

RESUMO

Phytoplasmas are phloem-restricted plant-pathogenic bacteria transmitted by insects. They cause diseases in a wide range of host plants, resulting in significant economic and ecological losses worldwide. Research on phytoplasmas has a long history, with significant progress being made in the past 30 years. Notably, with the rapid development of phytoplasma research, scientists have identified the primary agents involved in phytoplasma transmission, established classification and detection systems for phytoplasmas, and 243 genomes have been sequenced and assembled completely or to draft quality. Multiple possible phytoplasma effectors have been investigated, elucidating the molecular mechanisms by which phytoplasmas manipulate their hosts. This review summarizes recent advances in phytoplasma research, including identification techniques, host range studies, whole- or draft-genome sequencing, effector pathogenesis and disease control methods. Additionally, future research directions in the field of phytoplasma research are discussed.


Assuntos
Phytoplasma , Animais , Phytoplasma/genética , Sequência de Bases , Insetos/microbiologia , Doenças das Plantas/microbiologia
5.
Plant Dis ; 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38319628

RESUMO

Based on our previous finding that polysaccharide peptide (PSP) has substantial antiviral activity, we cultured strawberry plants infected with strawberry mild yellow edge virus (SMYEV) or strawberry vein banding virus (SVBV) in Murashige and Skoog (MS) media supplemented with PSP to test its ability to eliminate these viruses. PSP not only improved the elimination of SMYEV and SVBV but also promoted the growth and rooting of strawberry plants in tissue culture. On the 45th day, the average height of the 'Ningyu' strawberry plants in the 1 mg/mL PSP treatment group was 1.91 cm, whereas that of the plants in the control group was 1.51 cm. After the same time point, the number of new leaves on the tissue culture media supplemented with 1 mg/mL and 500 µg/mL PSP and without PSP were 4.92, 4.41, and 3.53, respectively. PSP also promoted strawberry rooting and significantly increased both the length and number of roots. In addition, after treatment with 1 mg/mL PSP treatment in tissue culture for 45 days followed by meristem-shoot-tip culture, the elimination rates of SMYEV and SVBV in regenerated 'Ningyu' strawberry plants ranged from 60% to 100%. This study investigated the use of the antiviral agent PSP for virus elimination. PSP has a low production cost and thus has great application potential for virus elimination in crop plants.

7.
Recent Pat Anticancer Drug Discov ; 19(2): 188-198, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38214358

RESUMO

BACKGROUND: Giant cell tumor of bone (GCTB) is a locally aggressive bone tumour aggravated by stromal cell proliferation and metastasis. OBJECTIVE: We investigated the mechanism of action of human chorionic gonadotropin (HCG) in mediating GCTB proliferation and invasion. METHODS: The expression of HCG was quantified using quantitative real-time PCR. After the primary stromal cells were isolated and identified, the function of HCG in GCTB was estimated using the cell counting kit-8, flow cytometry, scratch experiment, transwell assay, Western blot, and immunofluorescence. Moreover, the mechanism of HCG was assessed through western blotting. RESULTS: HCG expression was decreased in clinical tissue samples from patients with GCTB. We validated that HCG repressed stromal cell proliferation, migration, invasion, autophagy, and epithelial- mesenchymal transition (EMT) and promoted cell apoptosis in GCTB. We also verified that HCG repressed the autophagy and EMT of stromal cells through the Smad signaling axis in GCTB. HCG inhibited the transduction of the Smad signaling pathway by restraining the binding of the TGF-ß II receptor to ligand Activin A. CONCLUSION: HCG restrained the Smad signaling pathway by antagonizing TGF-ß signaling in GCTB. HCG may serve as a useful patent to treat GCTB.


Assuntos
Tumor de Células Gigantes do Osso , Fator de Crescimento Transformador beta , Humanos , Tumor de Células Gigantes do Osso/tratamento farmacológico , Tumor de Células Gigantes do Osso/metabolismo , Linhagem Celular Tumoral , Patentes como Assunto , Transdução de Sinais , Gonadotropina Coriônica
8.
Ultrason Imaging ; 46(2): 102-109, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38098206

RESUMO

This study aimed to compare the value of ultrasound elastography combined with contrast-enhanced ultrasound (CEUS) quantitative analysis in the differentiation of nodular fibrocystic breast change (FBC) from breast invasive ductal carcinoma (BIDC). We selected 50 patients each with nodular FBC and BIDC, who were admitted to the Affiliated Hospital of Zunyi Medical University from January 2018 to December 2021. Their ultrasonic elastic images and CEUS videos were collected, their ultrasound elastography scores and the ratio of strain rate (SR) of the lesions were determined, and the exported DICOM format videos of CEUS were quantitatively analyzed using VueBox software to obtain quantitative perfusion parameters. The differences between the ultrasound elastography score and SR while comparing nodular FBC and BIDC cases were statistically significant (p < .05). The sensitivity, specificity, and accuracy of ultrasound elastography scores in the differential diagnoses of nodular FBC and BIDC were 74%, 88%, and 81%, respectively. Additionally, the sensitivity, specificity, and accuracy of SR in the differential diagnosis of nodular FBC and BIDC were 94%, 78%, and 86%, respectively. Statistically significant differences were observed in the CEUS quantitative perfusion parameters PE, AUC (WiAUC, WoAUC, WiWoAUC), and WiPI in both nodular FBC and BIDC according to the VueBox software (p < .05). The sensitivity, specificity, and accuracy of CEUS quantitative analysis in the differential diagnoses of nodular FBC and BIDC were 66%, 82%, and 74%, respectively. Using the pathological findings as the gold standard, ROC curves were established, and the area under the curve (AUC) of the CEUS quantitative analysis, elasticity score, SR, and ultrasound elastography combined with CEUS quantitative analysis were 0.731, 0.838, and 0.892, as well as 0.945, respectively. Ultrasound elasticity scoring, SR and CEUS quantitative analysis have certain application value for differentiating nodular FBC cases from BIDC; however, ultrasound elasticity imaging combined with CEUS quantitative analysis can help in improving the differential diagnostic efficacy of nodular FBC cases from BIDC.


Assuntos
Carcinoma Ductal , Técnicas de Imagem por Elasticidade , Humanos , Técnicas de Imagem por Elasticidade/métodos , Meios de Contraste , Ultrassonografia/métodos , Mama/diagnóstico por imagem , Diagnóstico Diferencial , Sensibilidade e Especificidade
9.
J Pak Med Assoc ; 73(10): 2096-2099, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37876080

RESUMO

A 52 year old woman presented to the emergency department of Affiliated Hospital of Zunyi Medical University, Zunyi, China in May 2022, complaining of a palpable lower abdominal mass since two days. She denied haematuria, umbilical drainage, or any other urinary symptoms. Previous health record indicated that the patient was diagnosed with urachal inflammatory pseudotumour. Inflammatory pseudotumourous masses of the urachal canal are rare chronic inflammatory disorders with only a few case reports. Ultrasonography is the preferred method for diagnosing urachal lesions. Contrast- enhanced ultrasonography (CEUS) allows real-time visualization of the microvascular blood flow within the solid lesion, reducing the probability of misdiagnosis of the disease. We have reported a case of urachal inflammatory pseudotumour and analyzed its ultrasonographic findings from two-dimensional conventional ultrasonography and CEUS to provide support for the diagnosis of urachal inflammatory pseudotumour in the clinic and to assist clinical selection of effective treatment modalities.


Assuntos
Granuloma de Células Plasmáticas , Úraco , Feminino , Humanos , Pessoa de Meia-Idade , Úraco/diagnóstico por imagem , Úraco/patologia , Granuloma de Células Plasmáticas/diagnóstico por imagem , Resultado do Tratamento , Diagnóstico Diferencial , Ultrassonografia
10.
Mol Plant ; 16(10): 1564-1589, 2023 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-37671604

RESUMO

Wheat (Triticum aestivum) is a staple food for about 40% of the world's population. As the global population has grown and living standards improved, high yield and improved nutritional quality have become the main targets for wheat breeding. However, wheat production has been compromised by global warming through the more frequent occurrence of extreme temperature events, which have increased water scarcity, aggravated soil salinization, caused plants to be more vulnerable to diseases, and directly reduced plant fertility and suppressed yield. One promising option to address these challenges is the genetic improvement of wheat for enhanced resistance to environmental stress. Several decades of progress in genomics and genetic engineering has tremendously advanced our understanding of the molecular and genetic mechanisms underlying abiotic and biotic stress responses in wheat. These advances have heralded what might be considered a "golden age" of functional genomics for the genetic improvement of wheat. Here, we summarize the current knowledge on the molecular and genetic basis of wheat resistance to abiotic and biotic stresses, including the QTLs/genes involved, their functional and regulatory mechanisms, and strategies for genetic modification of wheat for improved stress resistance. In addition, we also provide perspectives on some key challenges that need to be addressed.


Assuntos
Melhoramento Vegetal , Triticum , Triticum/genética , Mudança Climática , Plantas , Estresse Fisiológico/genética
11.
Clin Lab ; 69(8)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37560874

RESUMO

BACKGROUND: The aim of the study was to conduct a comprehensive performance evaluation of the Mindray CX-9000 fully automated coagulation analyzer for the detection of the seven coagulation items. METHODS: The performance of activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (FIB), thrombin time (TT), D-dimer (D-D), fibrinogen degradation product (FDP), and antithrombin Ⅲ (AT) was validated for precision, linear range, carryover contamination rate, reference interval validation, inter-method agreement, and anti-interference ability. RESULTS: The intra- and inter-precision (coefficient of variation, CV%) of all seven items was less than the target CV%; the carryover contamination rates for different concentrations and between items were < 10%. The slope of the linear regression equation for the theoretical and measured values of the linear range was within 1 ± 0.05 and R ≥ 0.975. The reference interval quoted from the manufacturer's reference interval passed ≥ 95%. The CX-9000 was compared with the results of the reference instrument STAGO R MAX (STA-R MAX) and the p-values for all items ranged from 0.822 to 0.987. Within the concentration range claimed by the manufacturer, the interference errors produced by all items met the manufacturer's claimed criteria, except for triglycerides which produced interference errors > 10% for the FIB, D-D, FDP, and bilirubin which produced interference errors for the FIB and D-D assays. CONCLUSIONS: The CX-9000 automatic coagulation analyzer has good stability and repeatability, a wide linear range of detection, low carryover contamination rate, and high resistance to interference, making it suitable for the testing of clinical specimens.


Assuntos
Coagulação Sanguínea , Fibrinogênio , Humanos , Testes de Coagulação Sanguínea/métodos , Tempo de Protrombina , Tempo de Tromboplastina Parcial , Fibrinogênio/análise
12.
Plant Physiol Biochem ; 200: 107771, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37247558

RESUMO

Barley yellow dwarf virus-GAV (BYDV-GAV) is a highly destructive virus that is transmitted by aphids and can cause substantial yield losses in crops such as wheat (Triticum aestivum), barley (Hordeum vulgare) and oat (Avena sativa). Autophagy is an evolutionarily conserved degradation process that eliminates damaged or harmful intracellular substances during stress conditions or specific developmental processes. However, the mechanism of autophagy involved in disease resistance in wheat remains unknown. In this study, we demonstrate that BYDV-GAV infection could induces the upregulation of genes related to the autophagy pathway in wheat, accompanied by the production of autophagosomes. Furthermore, we confirmed the direct interaction between the viral movement protein (MP) and wheat autophagy-related gene 6 (TaATG6) both in vivo and in vitro. Through yeast function complementation experiments, we determined that TaATG6 can restore the autophagy function in a yeast mutant, atg6. Additionally, we identified the interaction between TaATG6 and TaATG8, core factors of the autophagic pathway, using the yeast two-hybrid system. TaATG6 and TaATG8-silenced wheat plants exhibited a high viral content. Overall, our findings suggest that wheat can recognize BYDV-GAV infection and activate the MP-TaATG6-TaATG8 regulatory network of defense responses through the induction of the autophagy pathway.


Assuntos
Hordeum , Luteovirus , Triticum/genética , Saccharomyces cerevisiae , Antivirais , Doenças das Plantas , Luteovirus/genética , Autofagia
13.
PLoS One ; 18(4): e0282692, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37058543

RESUMO

The long R&D process, the high risk, and the externalities of technological innovation are challenges that enterprises have to meet when making decisions on R&D investment. Governments share this risk with enterprises through preferential tax policies. We summarized China's preferential tax policies related to enterprises and R&D innovation, and used panel data of listed enterprises from 2013 to 2018 in the Growth Enterprises Market (GEM) of the Shenzhen Stock Exchange to explore the incentive effects of current tax policies on the R&D innovation of enterprises. Through empirical analysis, we found that tax incentives significantly motivate R&D innovation input and promote output. In addition, we found that the income tax incentives are greater than that of the circulation tax, since the profitability of enterprise has a positive correlation with R&D investment. Meanwhile, the size of the enterprise is negatively correlated with the intensity of R&D investment.


Assuntos
Invenções , Motivação , Tomada de Decisões , Governo , China
14.
J Biol Chem ; 299(4): 103052, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36813236

RESUMO

Phytoplasmas are insect-borne bacterial pathogens capable of secreting effectors into host cells and interfering with host plant defense response processes. Previous studies have found that the Candidatus Phytoplasma tritici effector SWP12 binds to and destabilizes the wheat transcription factor TaWRKY74, increasing wheat susceptibility to phytoplasmas. Here, we used a Nicotiana benthamiana transient expression system to identify two key functional sites of SWP12 and screened a series of truncated mutants and amino acid substitution mutants to determine whether they inhibit Bax-induced cell death. Using a subcellular localization assay and online structure analysis websites, we found that structure rather than intracellular localization probably affects the function of SWP12. D33A and P85H are two inactive substitution mutants, neither of which interacts with TaWRKY74, and P85H does not inhibit Bax-induced cell death, suppress flg22-triggered reactive oxygen species (ROS) bursts, degrade TaWRKY74, or promote phytoplasma accumulation. D33A can weakly suppress Bax-induced cell death and flg22-triggered ROS bursts and degrade a portion of TaWRKY74 and weakly promote phytoplasma accumulation. S53L, CPP, and EPWB are three SWP12 homolog proteins from other phytoplasmas. Sequence analysis revealed that D33 was conserved in these proteins, and they exhibited the same polarity at P85. Transient expression in N. benthamiana showed that these proteins could inhibit Bax-induced cell death and suppress ROS bursts. Our findings clarified that P85 and D33 of SWP12 play critical and minor roles, respectively, in suppressing the plant defense response and that they play a preliminary role in determining the functions of homologous proteins.


Assuntos
Phytoplasma , Phytoplasma/química , Phytoplasma/metabolismo , Proteínas de Bactérias/metabolismo , Aminoácidos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteína X Associada a bcl-2/metabolismo , Plantas/metabolismo , Doenças das Plantas/microbiologia
15.
Sci Rep ; 13(1): 1699, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36717697

RESUMO

The Immersed Boundary Method (IBM) has an advantage in simulating fluid-structure interaction, owning to its simplicity, intuitiveness, and ease of handling complex object boundaries. The interpolation function plays a vital role in IBM and it is usually computationally intensive. For moving or deforming solids, the interpolation weights of all the immersed boundary points ought to be updated every time step, which takes quite a lot CPU time. Since the interpolation procedure within all uniform structured grids is highly repetitive and very similar, we propose a simple and generalized Discretized Immersed Boundary Method (DIBM), which significantly improves efficiency by discretizing the interpolation functions onto subgrid points within each control volume and reusing a predefined universal interpolation stencil. The accuracy and performance of DIBM are analyzed using both theoretical estimation and simulation tests. The results show speedup ratios of 30-40 or even higher using DIBM when compared with conventional IBM for typical moving boundary simulations like particle-laden flows, while the error is estimated to be under 1% and can be further decreased by using finer subgrid stencils. By balancing the performance and accuracy demands, DIBM provides an efficient alternative framework for handling moving boundaries in incompressible viscous flows.

16.
Plant Dis ; 107(1): 34-37, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35787011

RESUMO

In this study, methods of Actinidia chlorotic ringspot-associated virus (AcCRaV) elimination by shoot tip culture, thermotherapy followed by shoot tip culture, and chemotherapy followed by shoot tip culture were explored. The results showed that the AcCRaV elimination rate was 23.3% when the secondary shoot tip culture method was used and when the shoot tip length was less than 0.5 mm. The AcCRaV elimination rate was 100% when thermotherapy (36°C [day] and 32°C [night]) was applied for 20 days followed by shoot tip culture (shoot tip length less than 1.0 mm). When shoot segments were treated with ribavirin at 15 µg/ml for 2 months followed by shoot tip culture, the elimination rate of AcCRaV was 100% (shoot tip length less than 1.0 mm). When shoot segments were treated with ribavirin at 25 µg/ml for 2 months followed by shoot tip culture, the elimination rate of AcCRaV was 100% (shoot tip length less than 1.5 mm). This is the first report on kiwifruit virus elimination methods.


Assuntos
Actinidia , Vírus , Ribavirina/farmacologia , Brotos de Planta , Frutas
17.
J Drug Target ; 31(2): 217-224, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36214127

RESUMO

OBJECTIVE: To design and construct a hydrogel drug-controlled release system loaded with gentamicin on a titanium surface, and to evaluate the in vitro drug release behaviour and antibacterial properties and biocompatibility of the controlled release system. METHODS: Titanium (Ti) surface was coated with poly dopamine (PDA) substrate, and then polyethylene glycol (PEG) was attached to PDA. The composite drug microsphere controlled release layer formed by gentamicin (GEN) and cross-linked starch (CSt) were subsequently covered with poly lactic⁃co⁃glycolic acid (PLGA) as a barrier to construct a Ti-GEN-Cst-PLGA anti-infective drug controlled release system. RESULTS: The hydrogel drug release system was successfully constructed. The results of in vitro anti-staphylococcus aureus (SAU) assay, anti-staphylococcus epidermidis (SEP) assay and anti-Escherichia coli (ECO) assay showed that Ti-GEN-Cst-PLGA could effectively inhibit the growth of three bacteria. Assay in the New Zealand rabbit found that Ti-GEN-Cst-PLGA could promote wound healing at the 3rd week after implantation, and the pathology assay found that the Ti-GEN-Cst-PLGA group had less inflammatory reactions and significant tissue proliferation at the endophyte contact surface. CONCLUSION: Ti-GEN-Cst-PLGA can effectively inhibit the inflammatory response and promote wound healing, or may be a potential treatment for orthopaedic endophytes.


Assuntos
Gentamicinas , Titânio , Animais , Coelhos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Titânio/farmacologia , Gentamicinas/farmacologia , Preparações de Ação Retardada , Microesferas , Materiais Biocompatíveis , Polietilenoglicóis/química , Hidrogéis , Amido/química
18.
BMC Musculoskelet Disord ; 23(1): 1020, 2022 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-36435763

RESUMO

Steroid-induced osteonecrosis of femoral head (SANFH) involves impaired differentiation of bone marrow mesenchymal stem cells (BMSC), the mechanism of which is regulated by multiple microRNAs. Studies have shown that miR-145 is a key regulatory molecule of BMSC cells, but its mechanism in steroid-induced femur head necrosis remains unclear. The present study mainly explored the specific mechanism of miR-145 involved in SANFH. In this study dexamethasone, a typical glucocorticoid, was used to induce osteogenic differentiation of BMSC cells. Western blot, qPCR, CCK8 and flow cytometry were used to investigate the effects of miR-145 on the proliferation and differentiation of BMSC. The relationship between miR-145 and GABA Type A Receptor Associated Protein Like 1(GABARAPL1) was identified using dual luciferase reports and the effects of the two molecules on BMSC were investigated in vitro. The results showed that miR-145 was up-regulated in SANFH patients, while GABARAPL1 was down-regulated. Inhibition of miR-145 can improve apoptosis and promote proliferation and activation of BMSC. GABARAPL1 is a downstream target gene of miR-145 and is negatively regulated by miR-145. In conclusion, miR-145 regulates the proliferation and differentiation of glucocorticoid-induced BMSC cells through GABARAPL1 and pharmacologically inhibit targeting miR-145 may provide new aspect for the treatment of SANFH.


Assuntos
Necrose da Cabeça do Fêmur , Células-Tronco Mesenquimais , MicroRNAs , Humanos , Osteogênese , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/metabolismo , Cabeça do Fêmur/metabolismo , Glucocorticoides/efeitos adversos , Medula Óssea , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismo , Esteroides , Proliferação de Células , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Associadas aos Microtúbulos/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/genética
19.
Plant J ; 112(6): 1473-1488, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36380696

RESUMO

'Candidatus Phytoplasma tritici' ('Ca. P. tritici') is an insect-borne obligate pathogen that infects wheat (Triticum aestivum) causing wheat blue dwarf disease, and leads to yield losses. SWP12 is a potential effector secreted by 'Ca. P. tritici' that manipulates host processes to create an environment conducive to phytoplasma colonization, but the detailed mechanism of action remains to be investigated. In this study, the expression of SWP12 weakened the basal immunity of Nicotiana benthamiana and promoted leaf colonization by Phytophthora parasitica, Sclerotinia sclerotiorum, and tobacco mild green mosaic virus. Moreover, the expression of SWP12 in wheat plants promoted phytoplasma colonization. Triticum aestivum WRKY74 and N. benthamiana WRKY17 were identified as host targets of SWP12. The expression of TaWRKY74 triggered reactive oxygen species bursts, upregulated defense-related genes, and decreased TaCRR6 transcription, leading to reductions in NADH dehydrogenase complex (NDH) activity. Expression of TaWRKY74 in wheat increased plant resistance to 'Ca. P. tritici', and silencing of TaWRKY74 enhanced plant susceptibility, which indicates that TaWRKY74 is a positive regulator of wheat resistance to 'Ca. P. tritici'. We showed that SWP12 weakens plant resistance and promotes 'Ca. P. tritici' colonization by destabilizing TaWRKY74.


Assuntos
Phytoplasma , Fatores de Transcrição , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Triticum/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Doenças das Plantas , Resistência à Doença/genética
20.
Front Immunol ; 13: 888891, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389695

RESUMO

Sepsis is a disease with a high morbidity and mortality rate. At present, there is a lack of ideal biomarker prognostic models for sepsis and promising studies using prognostic models to predict and guide the clinical use of medications. In this study, 71 differentially expressed genes (DEGs) were obtained by analyzing single-cell RNA sequencing (scRNA-seq) and transcriptome RNA-seq data, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analyses were performed on these genes. Then, a prognosis model with CCL5, HBD, IFR2BP2, LTB, and WFDC1 as prognostic signatures was successfully constructed after univariate LASSO regression analysis and multivariate Cox regression analysis. Kaplan-Meier (K-M) survival analysis, receiver operating characteristic (ROC) time curve analysis, internal validation, and principal component analysis (PCA) further validated the model for its high stability and predictive power. Furthermore, based on a risk prediction model, gene set enrichment analysis (GSEA) showed that multiple cellular functions and immune function signaling pathways were significantly different between the high- and low-risk groups. In-depth analysis of the distribution of immune cells in healthy individuals and sepsis patients using scRNA-seq data revealed immunosuppression in sepsis patients and differences in the abundance of immune cells between the high- and low-risk groups. Finally, the genetic targets of immunosuppression-related drugs were used to accurately predict the potential use of clinical agents in high-risk patients with sepsis.


Assuntos
Sepse , Análise de Célula Única , Humanos , RNA-Seq , Prognóstico , Sequenciamento do Exoma , Sepse/tratamento farmacológico , Sepse/genética , Proteínas
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