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1.
J Photochem Photobiol B ; 254: 112893, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38531303

RESUMO

An aromatic ring-containing compound with a wide range of biological activities, 9-methylacridine (AD-9-Me) is a precursor for the synthesis of various drugs. However, its photoactivation properties and mechanism of damage as a photo activator against Aedes aegypti are unknown. The toxic effects of AD-9-Me on Aedes aegypti mosquitoes were determined under light and non-light conditions. The results showed that the toxicity of AD-9-Me to mosquito larvae was significantly higher than that of the dark treatment after 24 h of light exposure; AD-9-Me was mainly distributed in the midgut of larvae, after 24 h of treatment, it can cause an increase in calcium ion concentration, reactive oxygen species (ROS) eruption and ROS accumulation by blocking the ROS elimination pathway in midgut cells. This in turn caused an increase in protein carbonyl and malondialdehyde (MDA) content, a decrease in mitochondrial membrane potential (MMP), a disruption of the barrier function of midgut tissues, a significant decrease in midgut weight and chitin content, which induced the up-regulation of AeDronc, AeCaspase8 and AeCaspase7 genes, leading to apoptotic cell death. In this study, we confirmed that AD-9-Me has photoactivation activity and mainly acts on the midgut of mosquito larvae, which can generate a large amount of ROS in the cells of the midgut and induce apoptosis to occur, resulting in the disruption of the function of the tissues of mosquito larvae, accelerating the death and delaying the development of the mosquito larvae.


Assuntos
Aedes , Animais , Espécies Reativas de Oxigênio/metabolismo , Larva , Mitocôndrias/metabolismo , Apoptose
2.
Insects ; 15(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38392515

RESUMO

The red imported fire ant (Solenopsis invicta Buren) is one of the 100 worst invasive alien species in the world. At present, the control of red imported fire ants is still mainly based on chemical control, and the most commonly used is indoxacarb bait. In this study, the contact and feeding toxicity of 16 kinds of nanomaterials to workers, larvae, and reproductive ants were evaluated after 24 h, 48 h, and 72 h. The results showed that the mortality of diatomite, Silica (raspberry-shaped), and multi-walled carbon nanotubes among workers reached 98.67%, 97.33%, and 68%, respectively, after contact treatment of 72 h. The mortality of both larval and reproductive ants was less than 20% after 72 h of treatment. All mortality rates in the fed treatment group were below 20% after 72 h. Subsequently, we evaluated the digging, corpse-removal, and foraging behaviors of workers after feeding with diatomite, Silica (raspberry-shaped), and multi-walled carbon nanotubes for 24 h, which yielded inhibitory effects on the behavior of red imported fire ants. The most effective was diatomite, which dramatically decreased the number of workers that dug, extended the time needed for worker ant corpse removal and foraging activities, decreased the number of workers that foraged, and decreased the weight of the food carried by the workers. In addition, we also evaluated the contact and feeding toxicity of these three nanomaterials in combination with indoxacarb on red imported fire ants. According to contact toxicity, after 12 h of contact treatment, the death rate among the red imported fire ants exposed to the three materials combined with indoxacarb reached more than 97%. After 72 h of exposure treatment, the mortality rate of larvae was more than 73% when the nanomaterial content was above 1% and 83% when the diatomite content was 0.5%, which was significantly higher than the 50% recorded in the indoxacarb control group. After 72 h of feeding treatment, the mortality of diatomite, Silica (raspberry-shaped), and multi-walled carbon nanotubes combined with indoxacarb reached 92%, 87%, and 98%, respectively. The death rates of the three kinds of composite ants reached 97%, 67%, and 87%, respectively. The three kinds of composite food had significant inhibitory effects on the behavior of workers, and the trend was largely consistent with the effect of nanomaterials alone. This study provides technical support for the application of nanomaterials in red imported fire ant control.

3.
BMC Med Genomics ; 17(1): 58, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383415

RESUMO

BACKGROUND: Ischemic stroke (IS) is a common and serious neurological condition that is highly fatal but so far no early diagnostic markers are available. Myocardial infarction-associated transcript (MIAT) is a long non-coding RNA (lncRNA) that could lead to IS by inducing autophagy and apoptosis in neuronal cells. However, there has been no report on the link between susceptibility to IS and the single-nucleotide polymorphisms (SNPs) of MIAT. This study aimed to investigate the association between MIAT gene polymorphisms and IS risk. METHODS: A total of 320 IS patients and 310 age-, sex- and race-matched controls were included in this study. Four polymorphisms (rs2157598, rs5761664, rs1894720, and rs9625066) were genotyped by using SNPscan technique. RESULTS: Among the 4 polymorphisms of MIAT, only rs9625066 was associated with IS risk (CA vs. CC: adjusted OR = 0.55, 95% CI, 0.37-0.85, P = 0.006; AA vs. CC: adjusted OR = 0.39, 95% CI, 0.16-0.94, P = 0.036; (AA + CA vs. CC: adjusted OR = 0.53, 95% CI, 0.35-0.80, P = 0.002; A vs. C adjusted OR = 0.59, 95% CI, 0.42-0.82, P = 0.002). Haplotype analysis showed a 1.32-fold increase (95% CI, 1.05-1.67, P = 0.017) in IS risk for rs2157598-rs5761664-rs1894720-rs9625066 (A-C-G-C). Logistic regression analysis identified some independent impact factors for IS including rs9625066 AA/AC, TC, TG, HDL-C (P < 0.05). CONCLUSION: The rs9625066 polymorphism of MIAT might be associated with IS susceptibility in Chinese population, in which AA/CA plays a protective role in IS, whereas the CC genotype increases the risk of developing IS, suggesting it might be a marker predictive of IS risk.


Assuntos
AVC Isquêmico , Infarto do Miocárdio , RNA Longo não Codificante , Acidente Vascular Cerebral , Humanos , Biomarcadores , Predisposição Genética para Doença , AVC Isquêmico/genética , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/genética , Acidente Vascular Cerebral/genética
4.
Mol Plant ; 17(3): 409-422, 2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38335958

RESUMO

Plant high-affinity K+ transporters (HKTs) mediate Na+ and K+ uptake, maintain Na+/K+ homeostasis, and therefore play crucial roles in plant salt tolerance. In this study, we present cryoelectron microscopy structures of HKTs from two classes, class I HKT1;1 from Arabidopsis thaliana (AtHKT1;1) and class II HKT2;1 from Triticum aestivum (TaHKT2;1), in both Na+- and K+-bound states at 2.6- to 3.0-Å resolutions. Both AtHKT1;1 and TaHKT2;1 function as homodimers. Each HKT subunit consists of four tandem domain units (D1-D4) with a repeated K+-channel-like M-P-M topology. In each subunit, D1-D4 assemble into an ion conduction pore with a pseudo-four-fold symmetry. Although both TaHKT2;1 and AtHKT1;1 have only one putative Na+ ion bound in the selectivity filter with a similar coordination pattern, the two HKTs display different K+ binding modes in the filter. TaHKT2;1 has three K+ ions bound in the selectivity filter, but AtHKT1;1 has only two K+ ions bound in the filter, which has a narrowed external entrance due to the presence of a Ser residue in the first filter motif. These structures, along with computational, mutational, and electrophysiological analyses, enable us to pinpoint key residues that are critical for the ion selectivity of HKTs. The findings provide new insights into the ion selectivity and ion transport mechanisms of plant HKTs and improve our understanding about how HKTs mediate plant salt tolerance and enhance crop growth.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Simportadores , Proteínas de Arabidopsis/metabolismo , Microscopia Crioeletrônica , Arabidopsis/metabolismo , Transporte de Íons , Íons/metabolismo , Potássio/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
5.
Nat Commun ; 15(1): 113, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38168103

RESUMO

Mast cells are phenotypically and functionally heterogeneous, and their state is possibly controlled by local microenvironment. Therefore, specific analyses are needed to understand whether mast cells function as powerful participants or dispensable bystanders in specific diseases. Here, we show that degranulation of mast cells in inflammatory synovial tissues of patients with rheumatoid arthritis (RA) is induced via MAS-related G protein-coupled receptor X2 (MRGPRX2), and the expression of MHC class II and costimulatory molecules on mast cells are upregulated. Collagen-induced arthritis mice treated with a combination of anti-IL-17A and cromolyn sodium, a mast cell membrane stabilizer, show significantly reduced clinical severity and decreased bone erosion. The findings of the present study suggest that synovial microenvironment-influenced mast cells contribute to disease progression and may provide a further mast cell-targeting therapy for RA.


Assuntos
Artrite Reumatoide , Sinoviócitos , Humanos , Camundongos , Animais , Mastócitos/metabolismo , Artrite Reumatoide/metabolismo , Sinoviócitos/metabolismo , Membrana Sinovial/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Receptores de Neuropeptídeos/metabolismo
6.
Insects ; 15(1)2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38249048

RESUMO

Solenopsis invicta, often known as the red imported fire ants (RIFAs), is a well-known global invasive ant species that can be found in agricultural, urban, and natural environments worldwide. Simultaneously, it also inhabits the soil. Biochar is generated by the pyrolysis of organic matter under high-temperature anoxic environments and widely used in agricultural ecosystems and soil amendment. However, to date, it remains unknown as to whether soil application of biochar has a negative effect on RIFAs. In our study, we investigated the toxicity and irritability effects of different amounts of biochar (0%, 1%, 2%, 5%, 10%, and 20%) introduced into the soil on red fire ants; upon comparison with the control soil (0% biochar), the application of 1%, 2%, and 5% biochar did not result in significantly different results. But the utilization of biochar at a concentration over 10% effectively repelled the RIFAs, resulting in their departure from the treated soils. High doses of biochar were able to cause death of red fire ants; the mortality rate of red fire ants reached 55.56% after 11 days of 20% biochar treatment. We also evaluated the effects of biochar on four behaviors of red fire ants, namely aggregation, walking, grasping, and attacking; 20% of the biochar treatment group reduced aggregation by 64.22% and this value was 55.22%, 68.44%, and 62.36% for walking, grasping, and attacking. Finally, we measured the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) enzyme activity and malondialdehyde (MDA) content in red fire ants; the results showed that the activities of the three enzymes increased with the increase in biochar addition, which indicated that a high dose of biochar induced oxidative stress in red fire ants. Our results indicate that biochar has the potential to cause toxicity and repel red imported fire ants (RIFAs) in a manner that is dependent on the concentration. We propose that biochar could be utilized in the control and manufacturing of baits for red fire ant management. This work establishes a foundation for the prevention and management of red fire ants and the logical utilization of biochar.

7.
Exp Hematol Oncol ; 12(1): 98, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38012722

RESUMO

Natural killer (NK) cells are promising alternatives for the production of "off-the-shelf" CAR products, posing a lower risk of cytokine release syndrome (CRS) than CAR-T cells. We synthesized four single VHH-directed anti-BCMA CARs, incorporating various intracellular regions (2B4 versus CD28) and hinge domains (CD28 versus IgG1) and ectopically producing IL-15. NK cells derived from peripheral blood (PB) were expanded ex vivo by K562-mbIL21 feeder cells. Stable CAR transduction was obtained through lentiviral transduction with the BaEV-Rless pseudotyped lentiviral vector. BCMA-CD28-IL15 CAR-NK cells with ectopic expression of IL-15 exhibited superior cytotoxicity were compared to BCMA-CD28 CAR-NK cells lacking IL-15 and BCMA-hIgG1-IL15 CAR-NK cells with an IgG1 hinge domain. We further assessed the cytotoxic capabilities of BCMA-2B4-IL15 CAR-NK cells with 2B4 intracellular domain. The BCMA-CD28-IL15 CAR-NK cells revealed stronger cytotoxicity and higher cytokine secretion against BCMA+ tumor cells than BCMA-2B4-IL15 CAR-NK cells in vitro. In the MM.1S-Luc mouse model, BCMA-CD28-IL15 CAR-NK inhibited the growth of tumor cells and prolonged mouse survival. These results show that the single VHH-directed BCMA CAR-NK cells exhibited remarkable specific killing ability, making them a potential candidate for immunotherapy in multiple myeloma treatment.

8.
Mol Immunol ; 163: 174-180, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37812989

RESUMO

Psoriatic arthritis (PsA) is a disease that transformed from psoriasis (PsO), and its underlying mechanisms are still not fully understood. Overactivation of the immune system is a key factor driving inflammatory diseases. Our goal is to define the unbalanced subsets of peripheral blood CD4 +T cells between PsO and PsA patients. Blood samples from 43 patients (23 PsA and 20 PsO) and 36 healthy donors (HD) were studied. Peripheral blood mononuclear cells (PBMC) were separated from blood and underwent fluorescent staining to assess CD4+T cell subsets by flow cytometry. We found that frequencies of various CD4+T cells including Th1, Th2, Th17, and Tfh were higher in the patients with PsO or PsA than those of healthy donors, indicating the general expansion of CD4+T cells in inflammatory conditions. More importantly, we observed the significant imbalance of Th1/Th2 between patients with PsO and PsA. Pearson correlation analysis showed that Th1/Th2 ratio was positively correlated with disease activity in psoriatic arthritis (DAPSA), Tfh/Tfr ratio was positively correlated with DAPSA score and visual analogue scale (VAS) score in PsA patients. Together, our results highlight the CD4+T cell changes in the transition from PsO to PsA, may contribute to early assessment and intervention.


Assuntos
Artrite Psoriásica , Psoríase , Humanos , Leucócitos Mononucleares , Linfócitos T CD4-Positivos , Subpopulações de Linfócitos T
9.
Front Neurol ; 14: 1260230, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37840919

RESUMO

Background: Ischemic stroke (IS) represents a major cause of morbidity and mortality across the globe. The aberrant expression of miR-365 has been found to be implicated in a wide array of human diseases, including atherosclerosis and cancer. Studies on single-nucleotide polymorphisms (SNPs) in miRNA genes can help gain insight into the susceptibility to the condition. This study aimed to examine the relationship between miR-365 SNPs and the risk of IS. Methods: The study recruited 215 IS patients and 220 controls. The SNPscans genotyping was employed to genotype three polymorphic loci (rs121224, rs30230, and rs178553) of miR-365. The relative expression of miR-365 in peripheral blood mononuclear cells of the patients and controls was determined by using real-time quantitative PCR. Results: The miR-365 rs30230 polymorphism exhibited a significant association with the risk of developing IS (TC vs. CC: adjusted OR = 0.55, 95% CI: 0.33-0.92, P = 0.022; TT vs. CC: adjusted OR = 0.34, 95% CI: 0.14-0.85, P = 0.021; TC +TT vs. CC: adjusted OR = 0.51, 95% CI: 0.31-0.83, P = 0.007; T vs. C: adjusted OR = 0.57, 95% CI: 0.39-0.83, P = 0.004). Haplotype analysis revealed that the C-T-G haplotype was associated with a decreased risk of IS (OR = 0.68, 95% CI: 0.46-1.00, P = 0.047). Furthermore, miR-365 expression was significantly higher in IS patients than in controls (P < 0.001). Interestingly, patients with rs30230 TC or TT genotypes had lower miR-365 levels compared to their counterparts with CC genotypes (P < 0.001). Conclusions: The miR-365 rs30230 polymorphism might bear an association with IS susceptibility in the Chinese population, and the rs30230 TC/TT genotype might be a protective factor against IS.

10.
Insect Mol Biol ; 32(6): 738-747, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37646607

RESUMO

Cucurbits are important economic plants that are attacked by numerous pests, among which the melon fly Zeugodacus cucurbitae is extremely problematic. New sustainable pest control strategies are necessary to replace chemical insecticides that are harmful to the environment, human health and nontarget species. The RNA interference (RNAi) technology is one of the most promising tools due to high efficiency and species specificity. We developed an RNAi strategy targeting the ecdysone receptor (ECR) of Z. cucurbitae, which plays an important role in moulting and reproduction. We identified, described and isolated the ECR gene of Z. cucurbitae and measured its expression pattern across developmental stages and tissues. ZcECR knockdown via dsZcECR ingestion caused a significant larval mortality and abnormal phenotypes in pupae and adults. About 68% of larvae fed with a dsZcECR-treated diet failed to enter the pupal stage and died. In addition, ZcECR knockdown dramatically reduced pupal weight (by 3.24 mg on average) and fecundity (by about 23%). RNAi targeting the ECR gene is therefore a promising method to control Z. cucurbitae, paving the way for the development of novel sustainable and highly specific control strategies.


Assuntos
Cucurbitaceae , Receptores de Esteroides , Tephritidae , Humanos , Animais , Cucurbitaceae/metabolismo , Tephritidae/genética , Larva , Receptores de Esteroides/genética , Pupa/metabolismo
11.
BMC Med Genomics ; 16(1): 176, 2023 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-37525251

RESUMO

BACKGROUND: The miR-208 gene is one of the microRNAs now under active studies, and has been found to play significant roles in an array of cardiovascular diseases. Nevertheless, until now, no studies have examined the relationship between the susceptibility to ischemic stroke (IS) and genetic variations in miR-208. This study explored the association between the miR-208 polymorphisms (rs178642, rs8022522, and rs12894524) and the risk of IS. METHODS: A total of 205 cases of IS and 211 control subjects were included. The SNPscans genotyping test was employed to determine the genotypes of the three polymorphisms. RESULTS: Significant correlation was observed between rs8022522 polymorphism and risk of IS on the basis of analyses of genotypes, models and alleles (GA vs. GG: adjusted OR = 2.159, 95% CI: 1.052-4.430, P = 0. 036; AA vs. GG: adjusted OR = 5.154, 95% CI: 1.123-23.660, P = 0.035; dominant model: adjusted OR = 1.746, 95% CI, 1.075-2.838, P = 0.025; G vs. A: adjusted OR = 2.451, 95% CI: 1.374-4.370, P = 0.002). CONCLUSIONS: The rs8022522 polymorphism of the miR-208 gene is significantly associated with an elevated risk of ischemic stroke in Chinese.


Assuntos
AVC Isquêmico , MicroRNAs , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , MicroRNAs/genética
12.
Inorg Chem ; 62(32): 12920-12930, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37523448

RESUMO

Hierarchical porosity of carbonates can facilitate their performance in massive applications as compared to their corresponding bulk samples. Traditional solution-based precipitation is typically utilized to fabricate porous carbonates. However, this tactic is generally employed under humid conditions, which demand soluble metal precursors, solvents, and extended dry periods. A salt-assisted mechanochemistry is exploited in contemporary work to settle the shortcomings. Enlighted by solid-state technology, this approach eliminates the utilization of solvents, and the process of ball milling can create pores in 5 min. A range of highly porous carbonates and their derivatives are acquired, with several materials surpassing recording surface areas (e.g., H-CaCO3: 108 m2/g, SrCO3: 125 m2/g, BaCO3: 172 m2/g, Pd/H-CaCO3 catalyst: 101 m2/g). The results display that Pd/H-CaCO3 shows superior catalytic efficiency in the synthesis of aniline (turnover frequency [TON] = 1.33 × 104/h-1, yield ≥ 99%, and recycle stability: 11 cycles) and dye degradation. Combining mechanochemistry and salt-assisted tactic provides a facile and efficient pathway for processing porous materials.

13.
Environ Sci Pollut Res Int ; 30(26): 68677-68690, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37126171

RESUMO

The red imported fire ant (RIFA), Solenopsis invicta Buren (Hymenoptera: Formicidae), is an invasive species that is considered to be among the 100 most dangerous species to human health and the environment. RIFA is currently controlled primarily by chemical insecticides. However, human health concerns and environmental problems require environment friendly, green insect pest control technology. In this study, the HS-SPME-GC/MS method was used to determine the volatile components of six essential oils, namely Illicium verum Burm, Blumea balsamifera (L.) DC., Citrus limon Burm, Acorus tatarinowii Schott, Mosla chinensis Maxim, and Cinnamomum cassia Presl, as well as their fumigation activity against RIFA. D-Limonene was identified as a core volatile in all six essential oils. The effects of volatile substances from essential oils on the fumigation activity and behavior of RIFA workers were studied by closed fumigation method. Except for C. limon essential oil, all other five plant essential oils exhibit excellent fumigation activity under the treatment of a concentration at 10 µL/ cm3 within 24 h. All plant essential oils are capable of causing the death of all red fire ants, while C. limon essential oil exhibited the lowest fumigation activity at 63.25%. Significant reductions in RIFA aggregation, aggressiveness, and gripping abilities were observed with all plant essential oils, and antenna sensilla appeared to bend or break. Moreover, after treating red ant fire ants with essential oil for 24 h, three protective enzyme activities were assessed. All six plant essential oils were shown to have enhanced enzyme activities for superoxide dismutase (SOD), glutathione S-transferase (GST), and catalase (CAT). It has been shown that plant essential oils have the capability of reducing the viability of red fire ants via receptor and behavioral factors, ultimately causing them to die off. As a conclusion, plant oils were demonstrated to be negatively affecting RIFA and providing a green and environmentally sustainable control method in this study.


Assuntos
Formigas , Inseticidas , Óleos Voláteis , Animais , Humanos , Óleos Voláteis/farmacologia , Inseticidas/farmacologia , Controle de Insetos , Óleos de Plantas/farmacologia
14.
Braz J Microbiol ; 54(2): 1115-1125, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37118055

RESUMO

There are many problems that result from the use of a large number of chemical pesticides to control plant diseases, including pathogenic bacteria resistance, environmental contamination, and human health effects. Recently, endophytic fungi have become a significant source of bioactive fungicide products and an invaluable resource for excavating microbial pesticides. In this study, endophytic fungi with biocontrol potential were isolated and screened from Mikania micrantha leaves, stems, and roots. Fifty endophytic fungi were isolated and their antagonistic activity was studied in vitro using the confrontation culture method. The J2-3 strains from stems exhibit broad-spectrum and high activity. The strain's biological characteristics were determined by various culture conditions, and it was identified as Fusarium proliferatum by both morphological and ITS sequence analysis. Biological characteristics of the J2-3 strain were also tested. The optimum temperature for mycelium growth and sporulation was 25 °C and 30 °C, respectively. For mycelium growth, starch was the optimum carbon source, and peptone was the optimum nitrogen source for sucrose, mycelium growth, and sporulation. Mycelium growth was killed by a temperature of 60 °C, and sporulation was killed by a temperature of 55 °C. The light aided mycelium growth, and the light alternated between light and dark cycles for sporulation. Further, pot experiments were conducted to determine the antagonistic and viable effects of highly antagonistic strains on cucumber. The spore suspension's final control efficacy on cucumber wilt disease was up to 62.79% and it also promoted cucumber growth significantly. The results show that the entophytic fungus J2-3 from M. micrantha can protect cucumbers from wilt disease and promote growth.


Assuntos
Cucumis sativus , Fusarium , Praguicidas , Humanos , Cucumis sativus/microbiologia , Fungos , Praguicidas/farmacologia , Doenças das Plantas/prevenção & controle , Doenças das Plantas/microbiologia
15.
Int Immunopharmacol ; 119: 110163, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37060808

RESUMO

Fibroblast-like synoviocytes (FLS) mediate many pathological processes in rheumatoid arthritis (RA), including pannus formation, bone erosion, and inflammation. RA FLS have unique aggressive phenotypes and exhibit several tumor cell-like characteristics, including hyperproliferation, excessive migration and invasion. Casein kinase 2 (CK2) is reportedly overexpressed in numerous tumor types, and targeted inhibition of CK2 has therapeutic benefits for tumors. However, the expression level of CK2 and its functions in RA FLS remain unclear. Herein, we aimed to elucidate whether CK2 is responsible for the aggressive phenotypes of RA FLS and whether targeted therapy can alleviate the severity of RA. We found that CK2 subunits were elevated in RA FLS compared with osteoarthritis FLS, and the activity of CK2 also markedly increased in RA FLS. Targeted inhibition of CK2 using CX-4945 suppressed RA FLS proliferation through cell cycle arrest. Cell migration and invasion were also inhibited by CX-4945 treatment. Moreover, CX-4945 reduced Interleukin-6 (IL-6), CC motif chemokine ligand 2 (CCL2) and Matrix metalloproteinase-3 (MMP-3) secretion in RA FLS. Further proteomic investigation revealed that p53 signaling pathway significantly changes after CX-4945 treatment in RA FLS. The siRNA-mediated p53 knockdown partly abolished the anti-proliferation and reduced IL-6, MMP-3 secretion effects of CX-4945. Furthermore, CX-4945 administration alleviates arthritis severity in CIA mice. Collectively, our results demonstrated the abnormal elevation of CK2 and its positive association with abnormal phenotypes in RA FLS. Our novel findings suggest the possible therapeutic potential of CX-4945 for RA.


Assuntos
Artrite Reumatoide , Sinoviócitos , Camundongos , Animais , Caseína Quinase II/metabolismo , Caseína Quinase II/farmacologia , Caseína Quinase II/uso terapêutico , Metaloproteinase 3 da Matriz/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Interleucina-6/metabolismo , Proteômica , Proliferação de Células , Células Cultivadas , Artrite Reumatoide/metabolismo , Fibroblastos , Gravidade do Paciente , Membrana Sinovial/patologia
16.
Front Physiol ; 14: 1112548, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36733910

RESUMO

Irradiation can be used as an insect pest management technique to reduce post-harvest yield losses. It causes major physiological changes, impairing insect development and leading to mortality. This technique is used to control the melon fly Zeugodacus cucurbitae, a major pest of Cucurbitaceae in Asia. Here, we applied irradiation to melon fly eggs, and the larvae emerged from irradiated eggs were used to conduct comparative transcriptomics and thereby identify key genes involved in the development and survival. We found 561 upregulated and 532 downregulated genes in irradiated flies compared to non-irradiated flies. We also observed abnormal small-body phenotypes in irradiated flies. By screening the 532 downregulated genes, we selected eight candidate genes putatively involved in development based in described functions in public databases and in the literature. We first established the expression profile of each candidate gene. Using RNA interference (RNAi), we individually knocked down each gene in third instar larvae and measured the effects on development. The knockdown of ImpE2 ecdysone-inducible gene controlling life stage transitions-led to major body size reductions in both pupae and adults. The knockdown of the tyrosine-protein kinase-like tok (Tpk-tok) caused severe body damage to larvae, characterized by swollen and black body parts. Adults subject to knockdown of the eclosion hormone (Eh_1) failed to shed their old cuticle which remained attached to their bodies. However, no obvious developmental defects were observed following the knockdown of the heat shock protein 67B1-like (Hsp67), the insulin receptor (Insr), the serine/threonine-protein kinase Nek4 (Nek4), the tyrosine-protein kinase transmembrane receptor Ror (Ror_1) and the probable insulin-like peptide 1 (Insp_1). We argue that irradiation can be successfully used not only as a pest management technique but also for the screening of essential developmental genes in insects via comparative transcriptomics. Our results demonstrate that ImpE2 and Eh_1 are essential for the development of melon fly and could therefore be promising candidates for the development of RNAi-based pest control strategies.

17.
Chemosphere ; 316: 137863, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36649895

RESUMO

Glufosinate-ammonium, the second largest transgene crop resistant herbicide, is classified as a mobile persistent pollutant by the U.S. Environmental Protection Agencybecause of its slow decomposition and easy mobile transfer in a water environment. The chronic and multigeneration toxicity of this compound to environmental organisms are alarming. In this study, racemic glufosinate-ammonium and the effective isomer, l-glufosinate-ammonium, were used as the test agents. The developmental, neurotoxic and reproductive toxicities of Caenorhabditis elegans to their parents and progeny were studied by continuous exposure in water at concentrations of 0.1, 1, 10 and 100 µg/L. The causes of toxicity differences were analysed from oxidative stress and transcription levels. Through oxidative stress of C. elegans, racemic glufosinate-ammonium and l-glufosinate-ammonium both mediated the developmental toxicity (shortened developmental cycle, reduced body length and width, promoted ageingand decreased longevity), neurotoxicity (inhibited head swinging, body bending frequency and acetylcholinesterase [AchE] activity) and reproductive toxicity (significant reductions in the number of eggs and offspring in vivo and induced apoptosis of gonadal cells). These phenomena caused oxidative damage (protein and membrane lipid peroxidation) and further induced apoptosis. The changes in various indicators caused by racemic glufosinate-ammonium exposure were more significant than those caused by l-glufosinate-ammonium exposure, and the reproduction-related indicators were more significant than the developmental and neurological indicators. A continuous accumulation of toxicity was observed after multiple generations of continuous exposure. These research results provide a data reference for the ecotoxicological evaluation and risk assessment of glufosinate-ammonium and contribute to the revision and improvement of the related environmental policies of glufosinate-ammonium.


Assuntos
Acetilcolinesterase , Caenorhabditis elegans , Animais , Caenorhabditis elegans/genética , Aminobutiratos/toxicidade , Reprodução
18.
Asia Pac J Clin Oncol ; 19(4): 434-438, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36448565

RESUMO

Prostate cancer morbidity and mortality are increasing globally and in China, and the rate of metastasis is also rising, limiting the therapeutic effect and clinical prognosis of prostate cancer. CD151 is considered to be the first promoter of tumor metastasis in the tetraspanin superfamily. Previous research has linked CD151 to the progression of a number of malignancies, including prostate cancer. However, a recent study found that CD151 can inhibit the progression of prostate cancer. As a result, this paper examines existing research on CD151 and prostate cancer progression in order to clarify the relationship and provide a possible reference for future studies.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Tetraspanina 24 , Próstata/patologia , Tetraspaninas , Prognóstico , China
19.
J Orthop Surg Res ; 17(1): 571, 2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36577990

RESUMO

BACKGROUND: As one of the major diagnostic criteria in Musculoskeletal Infection Society, the microbiological diagnosis of periprosthetic joint infection (PJI) performed by analyzing periprosthetic tissue culture is recommended. The goal of this study was to determine if methylene blue (MB) has antibacterial effects that might interfere with microbial culture in vitro. METHODS: Eight isolates of reference strains of Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Streptococcus pyogenes, and Candida albicans were incubated appropriately on blood agar, China blue agar, or Sabouraud's agar plates at 35 â„ƒ. (Streptococci were cultured in a CO2-rich atmosphere.) Each bacterial suspension was formed by 50-fold dilution before the test MB was added. For each strain, bacterial suspension was divided into 3 groups (5 samples each) exposed either MB 0.1%, MB 0.05% or sterile non-bacteriostatic 0.45% saline. The antimicrobial property of MB was determined by measuring the bacterial density on agar plates incubated for 24 h and comparing it with controls unexposed to MB. RESULTS: Exposure to MB 0.1% or MB 0.05% negatively affected microbial viability in vitro. Of the diluted form of MB exposure, reference strains of S. hominis and A. baumannii resulted in fewer colony-forming units compared with the sterile saline control. MB concentration was significantly negatively correlated with CFU counts of S. hominis and A. baumannii strains. The antibacterial property of MB 0.1% or MB 0.05% appears to affect the ability to culture the organism in in vitro assays. CONCLUSION: MB 0.1% or MB 0.05% has strong antimicrobial activities against some commonly encountered bacterial strains in PJI in vitro. To further evaluate its potential antibacterial usefulness in clinical applications, the next studies are needed to assess the ability of MB to affect the ability to culture the pathogens in vivo, especially in periprosthetic tissue.


Assuntos
Anti-Infecciosos , Artrite Infecciosa , Infecções Relacionadas à Prótese , Humanos , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/microbiologia , Azul de Metileno/farmacologia , Ágar/farmacologia , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Bactérias , Escherichia coli
20.
Front Microbiol ; 13: 1008274, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439797

RESUMO

Echinococcus multilocularis, the causative agent of alveolar echinococcosis (AE), severely threats human health and livestock farming. The first line of chemotherapeutic drug for AE is albendazole, which limits rapid extension of E. multilocularis metacestodes, but is rarely curative for AE, with severe side effects in long-term use, thus development of new anti-echinococcal drugs is mandated. Pseudolaric acid B (PAB) has long been used to treat fungal-infected dermatosis, and exerted anti-tumor, -fertility, -angiogenesis, -tubulin and antiparasitic activity. However, the effect of PAB against Echinococcus spp. remains unclear. The present study is to understand the effect of PAB against E. multilocularis in vitro and in vivo, and identify potential anti-echinococcal mechanism, as well as its toxicity. After exposure to PAB at 20 µg/ml, significant reduction of the survival rate and substantial ultrastructural destructions in E. multilocularis protoscoleces were observed in vitro. Furthermore, the wet weight of E. multilocularis cysts in the infected mice was significantly decreased after treatment with PAB (40, 20 or 10 mg/kg) for 12 weeks. Meanwhile, significant increase of both protein and mRNA expression of transforming growth factor beta 1 (TGF-ß1) was detected in the serum and liver of the infected mice, whereas PAB administration lowered its expression significantly. The toxicity tests demonstrated that PAB displayed lower cytotoxicity to human liver and kidney cells (HL-7702 and HK-2 cell) with IC50 = 25.29 and 42.94 µg/ml than albendazole with IC50 = 3.71 and 21.22 µg/ml in vitro, and caused lower hepatoxicity and nephrotoxicity in mice than ABZ. Our findings indicated that PAB possesses potent anti-echinococcal effect, with lower toxicity than albendazole, implying a potential chemotherapeutic agent for AE. Additionally, the present study demonstrated that the suppressive effect of PAB on the parasite may involve down-regulation of TGF-ß1 signaling.

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