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1.
J Fungi (Basel) ; 10(4)2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38667919

RESUMO

Aspergillus oryzae, a biosafe strain widely utilized in bioproduction and fermentation technology, exhibits a robust hydrolytic enzyme secretion system. Therefore, it is frequently employed as a cell factory for industrial enzyme production. Moreover, A. oryzae has the ability to synthesize various secondary metabolites, such as kojic acid and L-malic acid. Nevertheless, the complex secretion system and protein expression regulation mechanism of A. oryzae pose challenges for expressing numerous heterologous products. By leveraging synthetic biology and novel genetic engineering techniques, A. oryzae has emerged as an ideal candidate for constructing cell factories. In this review, we provide an overview of the latest advancements in the application of A. oryzae-based cell factories in industrial production. These studies suggest that metabolic engineering and optimization of protein expression regulation are key elements in realizing the widespread industrial application of A. oryzae cell factories. It is anticipated that this review will pave the way for more effective approaches and research avenues in the future implementation of A. oryzae cell factories in industrial production.

2.
J Microbiol Biotechnol ; 34(5): 1-10, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38563100

RESUMO

Cordyceps militaris is a significant edible fungus that produces a variety of bioactive compounds. We have previously established a uridine/uracil auxotrophic mutant and a corresponding Agrobacterium tumefaciens-mediated transformation (ATMT) system for genetic characterization in C. militaris using pyrG as a screening marker. In this study, we constructed an ATMT system based on a dual pyrG and hisB auxotrophic mutant of C. militaris. Using the uridine/uracil auxotrophic mutant as the background and pyrG as a selection marker, the hisB gene encoding imidazole glycerophosphate dehydratase, required for histidine biosynthesis, was knocked out by homologous recombination to construct a histidine auxotrophic C. militaris mutant. Then, pyrG in the histidine auxotrophic mutant was deleted to construct a ΔpyrG ΔhisB dual auxotrophic mutant. Further, we established an ATMT transformation system based on the dual auxotrophic C. militaris by using GFP and DsRed as reporter genes. Finally, to demonstrate the application of this dual transformation system for studies of gene function, knock out and complementation of the photoreceptor gene CmWC-1 in the dual auxotrophic C. militaris were performed. The newly constructed ATMT system with histidine and uridine/uracil auxotrophic markers provides a promising tool for genetic modifications in the medicinal fungus C. militaris.

3.
Front Neurol ; 15: 1378276, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38595846

RESUMO

Inner ear disorders have a variety of causes, and many factors can contribute to the exacerbation of cochlear and vestibular pathology. This systematic review aimed to analyze clinical data on the coexistence and potential causal interaction between allergic diseases and inner ear conditions. A search of PubMed and Web of Science identified 724 articles, of which 21 were selected for full-text analysis based on inclusion and exclusion criteria. The epidemiologic evidence found overwhelmingly supports an association between allergic disease and particular inner ear disorders represented by a high prevalence of allergic reactions in some patients with Ménière's disease (MD), idiopathic sudden sensorineural hearing loss (ISSHL), and acute low-tone hearing loss (ALHL). In addition, patients with MD, ISSHL, and ALHL had higher levels of total serum IgE than healthy subjects. Finally, in some cases, changes in cochlear potential may have been induced by antigen exposure, while desensitization alleviated allergy and inner ear-related symptoms. The exact mechanism of interaction between the auditory/vestibular and immune systems is not fully understood, and further clinical and basic research is needed to understand the relationship between the two systems fully.

4.
Pestic Biochem Physiol ; 200: 105837, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38582599

RESUMO

Susceptibility to insecticides is one of the limiting factors preventing wider adoption of natural enemies to control insect pest populations. Identification and selective breeding of insecticide tolerant strains of commercially used biological control agents (BCAs) is one of the approaches to overcome this constraint. Although a number of beneficial insects have been selected for increased tolerance to insecticides the molecular mechanisms underpinning these shifts in tolerance are not well characterised. Here we investigated the molecular mechanisms of enhanced tolerance of a lab selected strain of Orius laevigatus (Fieber) to the commonly used biopesticide spinosad. Transcriptomic analysis showed that spinosad tolerance is not a result of overexpressed detoxification genes. Molecular analysis of the target site for spinosyns, the nicotinic acetylcholine receptor (nAChR), revealed increased expression of truncated transcripts of the nAChR α6 subunit in the spinosad selected strain, a mechanism of resistance which was described previously in insect pest species. Collectively, our results demonstrate the mechanisms by which some beneficial biological control agents can evolve insecticide tolerance and will inform the development and deployment of insecticide-tolerant natural enemies in integrated pest management strategies.


Assuntos
Inseticidas , Receptores Nicotínicos , Tisanópteros , Animais , Tisanópteros/metabolismo , Inseticidas/toxicidade , Resistência a Inseticidas/genética , Agentes de Controle Biológico/farmacologia , Receptores Nicotínicos/genética , Receptores Nicotínicos/metabolismo , Insetos/genética , Macrolídeos/farmacologia , Combinação de Medicamentos
5.
Bioeng Transl Med ; 9(2): e10623, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38435823

RESUMO

The biological barriers of the body, such as the blood-brain, placental, intestinal, skin, and air-blood, protect against invading viruses and bacteria while providing necessary physical support. However, these barriers also hinder the delivery of drugs to target tissues, reducing their therapeutic efficacy. Extracellular vesicles (EVs), nanostructures with a diameter ranging from 30 nm to 10 µm secreted by cells, offer a potential solution to this challenge. These natural vesicles can effectively pass through various biological barriers, facilitating intercellular communication. As a result, artificially engineered EVs that mimic or are superior to the natural ones have emerged as a promising drug delivery vehicle, capable of delivering drugs to almost any body part to treat various diseases. This review first provides an overview of the formation and cross-species uptake of natural EVs from different organisms, including animals, plants, and bacteria. Later, it explores the current clinical applications, perspectives, and challenges associated with using engineered EVs as a drug delivery platform. Finally, it aims to inspire further research to help bioengineered EVs effectively cross biological barriers to treat diseases.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38551442

RESUMO

Background: Previous studies link overweight/obesity to reduced fertility, highlighting weight intervention as vital for better pregnancy outcomes. However, clarity on the role and efficacy of weight loss in enhancing pregnancy is inconsistent. Objective: This study aimed to assess the impact of individualized weight intervention on pregnancy among Chinese overweight/obese infertile women and explore body composition indexes influencing pregnancy outcomes. Methods: This retrospective study involved 363 overweight/obese infertile women admitted to the First Affiliated Hospital of Guangxi Medical University, Guangxi, China, from June 2017 to November 2020. Among them, 249 received personalized weight intervention (intervention group), while 114 did not (control group). Pregnancy outcomes were compared between the two groups, and changes in body composition before and after intervention were measured. Multivariate logistic regression was employed to analyze factors influencing pregnancy outcomes. Results: The intervention group exhibited significantly higher clinical pregnancy rates, natural pregnancy rates, assisted reproductive pregnancy rates, and induced ovulation (IO) pregnancy rates compared to the control group (all P < .05). Following weight intervention, there were significant decreases in body weight, body mass index (BMI), visceral fat area, and body fat (all P < .01). Logistic regression analysis identified polycystic ovary syndrome as the reason for infertility (OR=3.446, P = .016), ∆body weight %≥10% (OR=2.931, P = .014), and ∆visceral fat area% (OR=1.025, P = .047) as positive factors for a successful pregnancy. Conversely, age≥35 years old (OR=0.337, P = .001), BMI≥25 kg/m2 after intervention (OR=0.279, P < .001), and visceral fat area≥100 cm2 after intervention (OR=0.287, P = .007) were identified as negative factors. Conclusions: Individualized weight management enhances pregnancy outcomes in overweight/obese infertile women. Achieving a reduction in body weight by 10% or more, combined with effective control of visceral fat, proves important in improving pregnancy outcomes. Excess visceral fat emerges as an adverse factor impacting successful pregnancy.

7.
Front Oncol ; 14: 1331815, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38549939

RESUMO

Tendon Sheath Giant Cell Tumor (TGCT) is a benign tumor that primarily grows within joints and bursae. However, it has a high postoperative recurrence rate, ranging from 15% to 45%. Although radiotherapy may reduce this recurrence rate, its applicability as a standard treatment is still controversial. Furthermore, the pathogenic mechanisms of TGCT are not clear, which limits the development of effective treatment methods. The unpredictable growth and high recurrence rate of TGCT adds to the challenges of disease management. Currently, our understanding of TGCT mainly depends on pathological slice analysis due to a lack of stable cell models. In this study, we first reviewed the medical records of two female TGCT patients who had undergone radiotherapy. Then, by combining bioinformatics and machine learning, we interpreted the pathogenesis of TGCT and its associations with other diseases from multiple perspectives. Based on a deep analysis of the case data, we provided empirical support for postoperative radiotherapy in TGCT patients. Additionally, our further analysis revealed the signaling pathways of differentially expressed genes in TGCT, as well as its potential associations with osteoarthritis and synovial sarcomas.

8.
Comput Biol Med ; 171: 108198, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38417385

RESUMO

Cuproptosis, a recently characterized programmed cell death mechanism, has emerged as a potential contributor to tumorigenesis, metastasis, and immune modulation. Long non-coding RNAs (lncRNAs) have demonstrated diverse regulatory roles in cancer and hold promise as biomarkers. However, the involvement and prognostic significance of cuproptosis-related lncRNAs (CRLs) in oral squamous cell carcinoma (OSCC) remain poorly understood. Based on TCGA-OSCC data, we integrated single-sample gene set enrichment analysis (ssGSEA), the LASSO algorithm, and the tumor immune dysfunction and exclusion (TIDE) algorithm. We identified 11 CRLs through differential expression, Spearman correlation, and univariate Cox regression analyses. Two distinct CRL-related subtypes were unveiled, delineating divergent survival patterns, tumor microenvironments (TME), and mutation profiles. A robust CRL-based signature (including AC107027.3, AC008011.2, MYOSLID, AC005785.1, AC019080.5, AC020558.2, AC025265.1, FAM27E3, and LINC02367) prognosticated OSCC outcomes, immunotherapy responses, and anti-tumor strategies. Superior predictive power compared to other lncRNA models was demonstrated. Functional assessments confirmed the influence of FAM27E3, LINC02367, and MYOSLID knockdown on OSCC cell behaviors. Remarkably, the CRLs-based signature maintained stability across OSCC patient subgroups, underscoring its clinical potential for survival prediction. This study elucidates CRLs' roles in TME of OSCC and establishes a potential signature for precision therapy.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , RNA Longo não Codificante , Humanos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , RNA Longo não Codificante/genética , Neoplasias Bucais/genética , Neoplasias Bucais/terapia , Imunoterapia , Apoptose , Microambiente Tumoral/genética
10.
Surg Endosc ; 38(4): 2027-2040, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38424283

RESUMO

BACKGROUND: Surgical quality control is a crucial determinant of evaluating the tumor efficacy. OBJECTIVE: To assess the ClassIntra grade for quality control and oncological outcomes of robotic radical surgery for gastric cancer (GC). METHODS: Data of patients undergoing robotic radical surgery for GC at a high-volume center were retrospectively analyzed. Patients were categorized into two groups, the intraoperative adverse event (iAE) group and the non-iAE group, based on the occurrence of intraoperative adverse events. The iAEs were further classified into five sublevels (ranging from I to V according to severity) based on the ClassIntra grade. Surgical performance was assessed using the Objective Structured Assessment of Technical Skill (OSATS) and the General Error Reporting Tool. RESULTS: This study included 366 patients (iAE group: n = 72 [19.7%] and non-iAE group: n = 294 [80.3%]). The proportion of ClassIntra grade II patients was the highest in the iAE group (54.2%). In total and distal gastrectomies, iAEs occurred most frequently in the suprapancreatic area (50.0% and 54.8%, respectively). In total gastrectomy, grade IV iAEs were most common during lymph node dissection in the splenic hilum area (once for bleeding [grade IV] and once for injury [grade IV]). The overall survival (OS) and disease-free survival of the non-iAE group were significantly better than those of the iAE group (Log rank P < 0.001). Uni- and multi-variate analyses showed that iAEs were key prognostic indicators, independent of tumor stage and adjuvant chemotherapy (P < 0.001). CONCLUSION: iAEs in patients who underwent robotic radical gastrectomy significantly correlated with the occurrence of postoperative complications and a poor long-term prognosis. Therefore, utilization and inclusion of ClassIntra grading as a crucial surgical quality control and prognostic indicator in the routine surgical quality evaluation system are recommended.


Assuntos
Procedimentos Cirúrgicos Robóticos , Neoplasias Gástricas , Humanos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Gastrectomia/efeitos adversos , Intervalo Livre de Doença
11.
Phytother Res ; 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38400575

RESUMO

Thrombotic disorders, such as myocardial infarction and stroke, are the leading cause of death in the global population and have become a health problem worldwide. Drug therapy is one of the main antithrombotic strategies, but antithrombotic drugs are not completely safe, especially the risk of bleeding at therapeutic doses. Recently, natural products have received widespread interest due to their significant efficacy and high safety, and an increasing number of studies have demonstrated their antithrombotic activity. In this review, articles from databases, such as Web of Science, PubMed, and China National Knowledge Infrastructure, were filtered and the relevant information was extracted according to predefined criteria. As a result, more than 100 natural products with significant antithrombotic activity were identified, including flavonoids, phenylpropanoids, quinones, terpenoids, steroids, and alkaloids. These compounds exert antithrombotic effects by inhibiting platelet activation, suppressing the coagulation cascade, and promoting fibrinolysis. In addition, several natural products also inhibit thrombosis by regulating miRNA expression, anti-inflammatory, and other pathways. This review systematically summarizes the natural products with antithrombotic activity, including their therapeutic effects, mechanisms, and clinical applications, aiming to provide a reference for the development of new antithrombotic drugs.

12.
BMC Bioinformatics ; 25(1): 78, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378437

RESUMO

BACKGROUND: In recent years, the extensive use of drugs and antibiotics has led to increasing microbial resistance. Therefore, it becomes crucial to explore deep connections between drugs and microbes. However, traditional biological experiments are very expensive and time-consuming. Therefore, it is meaningful to develop efficient computational models to forecast potential microbe-drug associations. RESULTS: In this manuscript, we proposed a novel prediction model called GARFMDA by combining graph attention networks and bilayer random forest to infer probable microbe-drug correlations. In GARFMDA, through integrating different microbe-drug-disease correlation indices, we constructed two different microbe-drug networks first. And then, based on multiple measures of similarity, we constructed a unique feature matrix for drugs and microbes respectively. Next, we fed these newly-obtained microbe-drug networks together with feature matrices into the graph attention network to extract the low-dimensional feature representations for drugs and microbes separately. Thereafter, these low-dimensional feature representations, along with the feature matrices, would be further inputted into the first layer of the Bilayer random forest model to obtain the contribution values of all features. And then, after removing features with low contribution values, these contribution values would be fed into the second layer of the Bilayer random forest to detect potential links between microbes and drugs. CONCLUSIONS: Experimental results and case studies show that GARFMDA can achieve better prediction performance than state-of-the-art approaches, which means that GARFMDA may be a useful tool in the field of microbe-drug association prediction in the future. Besides, the source code of GARFMDA is available at https://github.com/KuangHaiYue/GARFMDA.git.


Assuntos
Antibacterianos , Algoritmo Florestas Aleatórias , Probabilidade , Software
13.
RSC Adv ; 14(6): 4252-4263, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38292269

RESUMO

Yttrium is an important rare earth element and is widely used in fields such as special glass preparation, metallurgy, and materials science. However, it is difficult to recover yttrium ion waste from dilute solutions with traditional processes, resulting in a significant waste of rare earth resources. The simple, effective, and easy-to-operate adsorption method is the most promising method for recovering yttrium, which is of great significance for sustainable development of the rare earth industry. In this study, activated carbon was prepared from Camellia oleifera fruit shells (COS) using phosphoric acid activation, and efficient recovery of Y(iii) from the Camellia oleifera fruit shell activated carbon was studied. Adsorption equilibrium data showed that this activated carbon had a Y(iii) adsorption capacity of 35.41 mg g-1, indicating significant potential for recovery of yttrium ions. The adsorption of Y(iii) by the activated carbon prepared from COS was consistent with the Langmuir model, and the adsorption data were consistent with the pseudo second-order kinetic model, indicating that the adsorption process was primarily chemical adsorption. After adsorption, the surface of the activated carbon contained large amounts of N, O, and Y, indicating that Y(iii) was stably adsorbed. The mechanisms for adsorption of Y(iii) on three types of activated carbon were studied through DFT calculations. The results showed that Y(iii) interacted with the carbon atoms on the surfaces to form new chemical bonds. The yttrium ion adsorption capacities for the three different activated carbons decreased in the order C I > C II > C.

14.
BMC Plant Biol ; 24(1): 12, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38163883

RESUMO

ABC (ATP-binding cassette) transporter proteins are one of the most extensive protein families known to date and are ubiquitously found in animals, plants, and microorganisms. ABCs have a variety of functions, such as plant tissue development regulation, hormone transport, and biotic and abiotic stress resistance. However, the gene characterization and function of the ABC gene family in almond (Prunus dulcis) have not been thoroughly studied. In this study, we identified 117 PdABC genes using the whole genome of 'Wanfeng' almond obtained by sequencing and explored their protein characterization. The PdABC family members were classified into eight subfamilies. The members of the same subfamily had conserved motifs but poorly conserved numbers of exons and introns and were unevenly distributed among the eight subfamilies and on the eight chromosomes. Expression patterns showed that PdABC family members were significantly differentially expressed during almond development, dormant freezing stress, and salt stress. We found that PdABC59 and PdABC77 had extremely high expression levels in pollen. PdABC63 and PdABC64 had high expression levels during almond petal development and multiple stages of flower development. PdABC98 was highly expressed in annual dormant branches after six temperature-freezing stress treatments. PdABC29, PdABC69, and PdABC98 were highly expressed under different concentrations of salt stress. This study preliminarily investigated the expression characteristics of ABC genes in different tissues of almond during flower development, freezing stress and salt stress, and the results will provide a reference for further in-depth research and breeding of almond in the future.


Assuntos
Prunus dulcis , Animais , Prunus dulcis/genética , Congelamento , Melhoramento Vegetal , Estresse Fisiológico/genética , Estresse Salino/genética , Flores/genética , Flores/metabolismo , Filogenia , Regulação da Expressão Gênica de Plantas , Família Multigênica , Proteínas de Plantas/metabolismo
15.
Sci Rep ; 14(1): 650, 2024 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-38182635

RESUMO

The prediction of potential microbe-drug associations is of great value for drug research and development, especially, methods, based on deep learning, have been achieved significant improvement in bio-medicine. In this manuscript, we proposed a novel computational model named NMGMDA based on the nuclear norm minimization and graph attention network to infer latent microbe-drug associations. Firstly, we created a heterogeneous microbe-drug network in NMGMDA by fusing the drug and microbe similarities with the established drug-microbe associations. After this, by using GAT and NNM to calculate the predict scores. Lastly, we created a fivefold cross validation framework to assess the new model NMGMDA's progressiveness. According to the simulation results, NMGMDA outperforms some of the most advanced methods, with a reliable AUC of 0.9946 on both MDAD and aBioflm databases. Furthermore, case studies on Ciprofloxacin, Moxifoxacin, HIV-1 and Mycobacterium tuberculosis were carried out in order to assess the effectiveness of NMGMDA even more. The experimental results demonstrated that, following the removal of known correlations from the database, 16 and 14 medications as well as 19 and 17 microbes in the top 20 predictions were validated by pertinent literature. This demonstrates the potential of our new model, NMGMDA, to reach acceptable prediction performance.


Assuntos
Soropositividade para HIV , HIV-1 , Humanos , Ciprofloxacina , Simulação por Computador , Bases de Dados Factuais
16.
Pestic Biochem Physiol ; 198: 105743, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38225086

RESUMO

The alkaloid, nicotine, produced by tobacco and other Solanaceae as an anti-herbivore defence chemical is one of the most toxic natural insecticides in nature. However, some insects, such as the whitefly species, Trialeurodes vaporariorum and Bemisia tabaci show strong tolerance to this allelochemical and can utilise tobacco as a host. Here, we used biological, molecular and functional approaches to investigate the role of cytochrome P450 enzymes in nicotine tolerance in T. vaporariorum and B. tabaci. Insecticide bioassays revealed that feeding on tobacco resulted in strong induced tolerance to nicotine in both species. Transcriptome profiling of both species reared on tobacco and bean hosts revealed profound differences in the transcriptional response these host plants. Interrogation of the expression of P450 genes in the host-adapted lines revealed that P450 genes belonging to the CYP6DP subfamily are strongly upregulated in lines reared on tobacco. Functional characterisation of these P450s revealed that CYP6DP1 and CYP6DP2 of T. vaporariorum and CYP6DP3 of B. tabaci confer resistance to nicotine in vivo. These three genes, in addition to the B. tabaci P450 CYP6DP5, were also found to confer resistance to the neonicotinoid imidacloprid. Our data provide new insight into the molecular basis of nicotine resistance in insects and illustrates how divergence in the evolution of P450 genes in this subfamily in whiteflies may have impacted the extent to which different species can tolerate a potent natural insecticide.


Assuntos
Hemípteros , Inseticidas , Animais , Nicotina/farmacologia , Nicotina/metabolismo , Inseticidas/farmacologia , Inseticidas/metabolismo , Resistência a Inseticidas/genética , Neonicotinoides/farmacologia , Neonicotinoides/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Tabaco/genética , Hemípteros/metabolismo , Nitrocompostos/farmacologia , Nitrocompostos/metabolismo
17.
Int J Surg ; 110(2): 1215-1223, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37994715

RESUMO

BACKGROUND: Botulinum toxin type A (BTX-A) is a potential treatment for cancer pain. This study aimed to analyze the effectiveness and safety of BTX-A in the treatment of pain after cancer treatment. PATIENTS AND METHODS: Systematic searches of PubMed, Cochrane Library, and Embase databases were conducted. Randomized controlled trials evaluating the efficacy and safety of BTX-A compared with either placebo or active treatment in patients with pain after cancer treatment were included. The outcomes included pain intensity, quality of life, and adverse events. RESULTS: This systematic review included four studies of which two were included in the meta-analysis. Compared with a placebo, BTX-A injection in patients with pain after cancer treatment had a clinically meaningful reduction in self-reported pain post-treatment [mean difference=-1.79 (95% CI: -2.14--1.43), P <0.00001, I ²=0%]. CONCLUSION: This systematic review and meta-analysis demonstrated that BTX-A is safe and effective for pain relief in patients with pain after cancer treatment.


Assuntos
Toxinas Botulínicas Tipo A , Neoplasias , Humanos , Toxinas Botulínicas Tipo A/efeitos adversos , Qualidade de Vida , Dor , Neoplasias/complicações , Manejo da Dor , Resultado do Tratamento
18.
Cell Biochem Biophys ; 82(1): 127-137, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37801199

RESUMO

LAMB3, a major extracellular matrix and basal membrane component, is involved in wound healing. We aimed to understand its role in Asherman's syndrome (AS), which is associated with infertility, by using bioinformatics analysis and cultured endometrial stromal cells (ESCs). MRNAs extracted from tissues obtained from control subjects and patients with severe intrauterine adhesion were sequenced and subjected to bioinformatics analysis and the RhoA/ROCK1/MYL9 pathway was implicated and this subsequently studied using cultured primary ESCs. The effects of overexpression and knockdown and activation and inhibition of LAMB3 on the mesenchymal to myofibroblastic phenotypic transformation of ECCs were assessed using PCR and western blot analysis. Phalloidin was used to localize the actin cytoskeletal proteins. Silencing of LAMB3 reversed the TGF-ß-induced ESC myofibroblast phenotype conversion, whereas overexpression of LAMB3 promoted this process. Activation and silencing of LAMB3 led to remodeling of the ESC cytoskeleton. Overexpression and silencing of LAMB3 caused activation and inhibition of ESCs, respectively. Y-27632 and LPA reversed the activation and inhibition of the RhoA/ROCK1/MYL9 pathway after overexpression and silencing, respectively. These results suggest that LAMB3 can regulate ESC fibrosis transformation and cytoskeleton remodeling via the RhoA/ROCK1/MYL9 pathway. This study provides a potential new target for gene therapy and drug intervention of AS.


Assuntos
Citoesqueleto , Quinases Associadas a rho , Humanos , Quinases Associadas a rho/genética , Quinases Associadas a rho/metabolismo , Actinas/metabolismo , Proteína rhoA de Ligação ao GTP/genética , Proteína rhoA de Ligação ao GTP/metabolismo , Transdução de Sinais , Células Estromais/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Cadeias Leves de Miosina/metabolismo
19.
PLoS Pathog ; 19(12): e1011828, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38091367

RESUMO

Buprofezin, a chitin synthesis inhibitor, is widely used to control several economically important insect crop pests. However, the overuse of buprofezin has led to the evolution of resistance and exposed off-target organisms present in agri-environments to this compound. As many as six different strains of bacteria isolated from these environments have been shown to degrade buprofezin. However, whether insects can acquire these buprofezin-degrading bacteria from soil and enhance their own resistance to buprofezin remains unknown. Here we show that field strains of the brown planthopper, Nilaparvata lugens, have acquired a symbiotic bacteria, occurring naturally in soil and water, that provides them with resistance to buprofezin. We isolated a symbiotic bacterium, Serratia marcescens (Bup_Serratia), from buprofezin-resistant N. lugens and showed it has the capacity to degrade buprofezin. Buprofezin-susceptible N. lugens inoculated with Bup_Serratia became resistant to buprofezin, while antibiotic-treated N. lugens became susceptible to this insecticide, confirming the important role of Bup_Serratia in resistance. Sequencing of the Bup_Serratia genome identified a suite of candidate genes involved in the degradation of buprofezin, that were upregulated upon exposure to buprofezin. Our findings demonstrate that S. marcescens, an opportunistic pathogen of humans, can metabolize the insecticide buprofezin and form a mutualistic relationship with N. lugens to enhance host resistance to buprofezin. These results provide new insight into the mechanisms underlying insecticide resistance and the interactions between bacteria, insects and insecticides in the environment. From an applied perspective they also have implications for the control of highly damaging crop pests.


Assuntos
Hemípteros , Inseticidas , Animais , Humanos , Inseticidas/farmacologia , Inseticidas/metabolismo , Resistência a Inseticidas/genética , Hemípteros/metabolismo , Bactérias , Solo
20.
Acta Cardiol ; : 1-9, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37961871

RESUMO

BACKGROUND: Thyroid-stimulating hormone (TSH) has been regarded as a predictor of poor outcomes in patients with acute myocardial infarction (AMI). AMI complicated by diabetes mellitus (DM) tends to have a high prevalence and a worse prognosis. We aim to evaluate the association between thyroid dysfunction and in-hospital outcomes and short- and medium-term mortality in diabetic patients with AMI. METHODS: From January 2017 to November 2020, a total of 432 patients with AMI were included in this study, including 209 DM patients and 223 non-DM patients. Baseline characteristics, medical history, and laboratory parameters of patients were recorded after admission. In-hospital outcomes and 30-day mortality were recorded, and long-term mortality was recorded with a median follow-up of 34.2 ± 5.6 months. RESULTS: Subclinical hypothyroidism (SCH) was defined as an elevated TSH level of more than with a normal range of circulating thyroid hormones. In AMI with DM group, 26/209 (12.4%) patients were complicated with SCH, these patients tend to be older and experienced worse in-hospital outcomes compared to patients without SCH, including higher rates of acute heart failure, acute kidney injury, and atrial fibrillation. Moreover, patients with SCH had a higher prevalence of 30-day mortality and long-term mortality, compared with patients without SCH. CONCLUSIONS: Diabetic AMI patients with SCH had worse in-hospital outcomes and higher 30-day and long-term mortality. Patients with diabetic AMI should pay attention to thyroid function, and SCH is an independent risk factor for short-term and long-term mortality in diabetic AMI patients.

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