RESUMEN
Populus pseudo-cathayana × Populus deltoides is a crucial artificial forest tree species in Northeast China. The presence of the fall webworm (Hyphantria cunea) poses a significant threat to these poplar trees, causing substantial economic and ecological damage. This study conducted an insect-feeding experiment with fall webworm on P. pseudo-cathayana × P. deltoides, examining poplar's physiological indicators, transcriptome, and metabolome under different lengths of feeding times. Results revealed significant differences in phenylalanine ammonia-lyase activity, total phenolic content, and flavonoids at different feeding durations. Transcriptomic analysis identified numerous differentially expressed genes, including AP2/ERF, MYB, and WRKY transcription factor families exhibiting the highest expression variations. Differential metabolite analysis highlighted flavonoids and phenolic acid compounds of poplar's leaves as the most abundant in our insect-feeding experiment. Enrichment analysis revealed significant enrichment in the plant hormone signal transduction and flavonoid biosynthetic pathways. The contents of jasmonic acid and jasmonoyl-L-isoleucine increased with prolonged fall webworm feeding. Furthermore, the accumulation of dihydrokaempferol, catechin, kaempferol, and naringenin in the flavonoid biosynthesis pathway varied significantly among different samples, suggesting their crucial role in response to pest infestation. These findings provide novel insights into how poplar responds to fall webworm infestation.
Asunto(s)
Populus , Populus/genética , Populus/metabolismo , Animales , Flavonoides/metabolismo , Escarabajos/fisiología , Escarabajos/metabolismo , Oxilipinas/metabolismo , Fenilanina Amoníaco-Liasa/metabolismo , Fenilanina Amoníaco-Liasa/genética , Ciclopentanos/metabolismo , Hojas de la Planta/metabolismo , Transcriptoma , Regulación de la Expresión Génica de las Plantas , Mariposas Nocturnas/genética , Mariposas Nocturnas/fisiología , Reguladores del Crecimiento de las Plantas/metabolismoRESUMEN
Digital microfluidic biochips (DMFBs), which are used in various fields like DNA analysis, clinical diagnosis, and PCR testing, have made biochemical experiments more compact, efficient, and user-friendly than the previous methods. However, their reliability is often compromised by their inability to adapt to all kinds of errors. Errors in biochips can be categorized into two types: known errors, and unknown errors. Known errors are detectable before the start of the routing process using sensors or cameras. Unknown errors, in contrast, only become apparent during the routing process and remain undetected by sensors or cameras, which can unexpectedly stop the routing process and diminish the reliability of biochips. This paper introduces a deep reinforcement learning-based routing algorithm, designed to manage not only known errors but also unknown errors. Our experiments demonstrated that our algorithm outperformed the previous ones in terms of the success rate of the routing, in the scenarios including both known errors and unknown errors. Additionally, our algorithm contributed to detecting unknown errors during the routing process, identifying the most efficient routing path with a high probability.
Asunto(s)
Técnicas Analíticas Microfluídicas , Microfluídica , Microfluídica/métodos , Técnicas Analíticas Microfluídicas/métodos , Reproducibilidad de los Resultados , Análisis por Micromatrices , AlgoritmosRESUMEN
In this work, we propose a method for estimating depth for an image of a monocular camera in order to avoid a collision for the autonomous flight of a drone. The highest flight speed of a drone is generally approximate 22.2 m/s, and long-distant depth information is crucial for autonomous flights since if the long-distance information is not available, the drone flying at high speeds is prone to collisions. However, long-range, measurable depth cameras are too heavy to be equipped on a drone. This work applies Pix2Pix, which is a kind of Conditional Generative Adversarial Nets (CGAN). Pix2Pix generates depth images from a monocular camera. Additionally, this work applies optical flow to enhance the accuracy of depth estimation. In this work, we propose a highly accurate depth estimation method that effectively embeds an optical flow map into a monocular image. The models are trained with taking advantage of AirSim, which is one of the flight simulators. AirSim can take both monocular and depth images over a hundred meter in the virtual environment, and our model generates a depth image that provides the long-distance information than images captured by a common depth camera. We evaluate accuracy and error of our proposed method using test images in AirSim. In addition, the proposed method is utilized for flight simulation to evaluate the effectiveness to collision avoidance. As a result, our proposed method is higher accuracy and lower error than a state of work. Moreover, our proposed method is lower collision than a state of work.
Asunto(s)
Flujo Optico , Dispositivos Aéreos No TripuladosRESUMEN
S-(-)-trans-Verbenol (1) and its antipode, R-(+)-trans-verbenol (1') have been confirmed as the critical pheromone components of bark beetles. Synthesis of these two active secondary alcohols (1 and 1') from commercially available starting materials S-α-pinene and R-α-pinene was reported. The key steps were mainly depended on the effective SN2 stereo-inversion of the hydroxy group of sterically hindered alcohols (3 and 3'), using Mitsunobu reaction or hydrolysis of mesylate ester, alternatively. Our results provide a new and stereo-selectivity way to obtain optically active insect pheromones.
Asunto(s)
Alcoholes , Gorgojos , Animales , Monoterpenos Bicíclicos , Estructura Molecular , FeromonasRESUMEN
RNA interference (RNAi) technology is a promising approach used in pest control. The efficiency of RNAi varies considerably among different insect species, and growing evidence suggests that degradation of double-stranded RNA (dsRNA) prior to uptake is an important factor that limits RNAi efficiency in insects. Our recent work on fall webworm (Hyphantria cunea), an important invasive pest in China, showed a relatively low silencing efficiency of RNAi through dsRNA injection, which is considered the most feasible dsRNA delivery method for inducing RNAi, and the factors involved in the mechanism remain unknown. Herein, we first detected the dsRNA-degrading activity in the hemolymph and gut content of H. cunea in ex vivo assays and observed rapid degradation of dsRNA, especially in the hemolymph, which was complete within only 10 min. To determine whether dsRNA degradation could contribute to the low effectiveness of RNAi in H. cunea, four dsRNA nuclease (dsRNase) genes, HcdsRNase1, HcdsRNase2, HcdsRNase3, and HcdsRNase4, were identified by homology searching against the H. cunea transcriptome database, and their transcript levels were subsequently investigated in different tissues, developmental stages, and after dsRNA injection. Our results show that HcdsRNases are highly expressed mainly in gut tissues and hemolymph, and the expression of HcdsRNase3 and HcdsRNase4 were significantly upregulated by dsGFP induction. RNAi-of-RNAi studies, using HcCht5 as a reporter gene, demonstrated that silencing HcdsRNase3 and HcdsRNase4 significantly increases RNAi efficacy via dsHcCht5 injection, and co-silencing these two HcdsRNase genes results in a more significant improvement in efficacy. These results confirm that the RNAi efficacy in H. cunea through dsRNA injection is certainly impaired by dsRNase activity, and that blocking HcdsRNases could potentially improve RNAi, providing a reference for related studies on insects where RNAi has low efficiency.
Asunto(s)
Mariposas Nocturnas , ARN Bicatenario , Animales , Endonucleasas/metabolismo , Hemolinfa/metabolismo , Insectos/metabolismo , Mariposas Nocturnas/genética , Mariposas Nocturnas/metabolismo , Interferencia de ARN , ARN Bicatenario/genética , ARN Bicatenario/metabolismoRESUMEN
The symbiosis between the bark beetle (Ips subelongatus) and its fungal symbiont (Endoconidiophora fujiensis) poses a serious threat to larch forests. However, the signaling pathways between these symbiotic partners and their host/non-host trees are not fully understood. Inoculation of the host larch (Larix principis-rupprechtii) with two strains of E. fujiensis induced a rapid and long-term release of monoterpenes. Although the fungi had a level of tolerance to these compounds, many monoterpenes inhibited fungal growth in culture. Moreover, monoterpenes with stronger inhibitory effects on fungal growth exhibited weaker synergistic effects on the attraction of I. subelongatus to aggregation pheromone. Surprisingly, individual isomers of aggregation pheromone components promoted fungal symbiont growth in a culture medium. Non-host volatiles (NHVs) were tested and shown to completely inhibit the growth of fungal symbionts in culture but had no effects on beetle responses to aggregation pheromone, with the exception of (Z)-3-hexen-1-ol. These results reveal convergence and mutualism patterns in the evolution of I. subelongatus and E. fujiensis with respect to host tree volatiles but not in response to NHVs. Ultimately, we put forward a hypothesis that host plants are ecological and evolutionary determinants of bark beetle-fungus symbioses in terms of their complex signaling interactions.
Asunto(s)
Escarabajos , Animales , Ascomicetos , Hongos , Corteza de la Planta , Simbiosis , ÁrbolesRESUMEN
BACKGROUND: Immune-related genes (IRGs) were linked to the prognosis of head and neck squamous cell carcinoma (HNSCC). This study aimed to identify the effects of an immune-related gene signature (IRGS) that can predict the of HNSCC prognosis. METHODS: The expression data of 770 HNSCC patients from the TCGA database and the GEO database were used. To explore a predictive model, the Cox proportional hazards model was applied. The Kaplan-Meier survival analysis, as well as univariate and multivariate analyses were performed to evaluate the independent predictive value of IRGS. To explore biological functions of IRGS, enrichment analyses and pathway annotation for differentially expressed genes (DEGs) in different immune groups were applied, as well as the immune infiltration. RESULTS: A prognostic signature comprising 27 IRGs was generated. IRGS significantly stratified HNSCC patients into high and low immune risk groups in regard to overall survival in the training cohort (HR = 3.69, 95% CI 2.73-4.98, P < 0.001). Likewise, IRGS could be linked to the prognosis of HNSCC in patients of the validation cohort (HR = 1.84, 95% CI 1.21-2.81, P < 0.01). Even after adjusting for TNM stage, IRGS was maintained as an independent predictor in the multivariate analysis (HR = 3.62, 95% CI 2.58-5.09, P < 0.001), and in the validation cohort (HR = 1.73, 95% CI 1.12-2.67, P = 0.014). The IFN-α response, the IFN-γ response, IL-2/STAT5 signaling, and IL-6/JAK/STAT3 signaling were all negatively correlated with the immune risk (P < 0.01). Immune infiltration of the high-risk group was significantly lower than that of the low-risk group (P < 0.01). Most notably, the infiltration of CD8 T cells, memory-activated CD4 T cells, and regulatory T cells was strongly upregulated in the low immune risk groups, while memory resting CD4 T cell infiltration was downregulated (P < 0.01). CONCLUSION: Our analysis provides a comprehensive prognosis of the immune microenvironments and outcomes for different individuals. Further studies are needed to evaluate the clinical application of this signature.
RESUMEN
BACKGROUND: Periodontitis was reported to be associated with inflammatory bowel disease (IBD). However, the association between them has not been firmly established in the existing literature. Therefore, this meta-analysis was conducted to evaluate the relationship between periodontitis and IBD. METHODS: Electronic databases were searched for publications up to August 1, 2019 to include all eligible studies. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated to determine the association between periodontal disease and IBD using a random or fixed effects model according to heterogeneity. RESULTS: Six eligible studies involving 599 IBD patients and 448 controls were included. The pooled OR between periodontitis and IBD was 3.17 (95% CI: 2.09-4.8) with no heterogeneity observed (I2 = 0.00%). The pooled ORs were 3.64 (95% CI: 2.33-5.67) and 5.37 (95% CI: 3.30-8.74) for the associations between periodontitis and the two sub-categories of IBD, Crohn' s disease and ulcerative colitis, respectively. CONCLUSIONS: The results demonstrated that periodontitis was significantly associated with IBD. However, the mechanisms underlying periodontitis and IBD development are undetermined. Further studies are needed to elucidate this relationship.
Asunto(s)
Colitis Ulcerosa/epidemiología , Enfermedad de Crohn/epidemiología , Enfermedades Inflamatorias del Intestino/epidemiología , Periodontitis/epidemiología , Adulto , Humanos , Persona de Mediana Edad , Higiene Bucal , Prevalencia , Factor de Necrosis Tumoral alfa , Adulto JovenRESUMEN
OBJECTIVE: We have previously demonstrated the effect of alpha-2-macroglobulin (α2M) in the remediation of radiation-induced cellular damage. Here, we investigated the protective effects of α2M in a preclinical rat model of jaw osteoradionecrosis (ORN). METHODS: Eighteen rats were divided randomly into three groups: the control group, the radiation therapy (RT) alone group, and the radiated mandibles pretreated with α2M (α2M + RT) group. One month after radiation, all left molar teeth were extracted. After another 3 months, the animals were sacrificed and body weight, histopathology, microcomputed tomography and immunofluorescence were evaluated in all groups. RESULTS: The RT group showed serious alopecia, bone exposure, inflammation, necrosis, fibrosis, and the absence of new bone formation within the socket. The α2M + RT group exhibited less alopecia than the RT group and slight inflammation and fibrosis in the bone marrow cavity. The cortical bone was similar to normal bone tissue. Interestingly, compared with RT group, serum superoxide dismutase levels in the α2M + RT group increased at the 1th day (P = 0.037), 14th day (P = 0.012), while reactive oxygen species levels clearly decreased at the 1th day (P< 0.001), 14th day (P = 0.007), and 28th day (P = 0.013). CONCLUSIONS: A clinically translational model of jaw ORN was successfully established and the application of α2M prior to radiation protected the bone from being injured by the radiation, possibly related to oxidative stress.
Asunto(s)
Enfermedades Maxilomandibulares/prevención & control , Osteorradionecrosis/prevención & control , alfa 2-Macroglobulinas Asociadas al Embarazo/administración & dosificación , Protectores contra Radiación/farmacología , Animales , Modelos Animales de Enfermedad , Inyecciones Intralesiones , Enfermedades Maxilomandibulares/etiología , Enfermedades Maxilomandibulares/metabolismo , Masculino , Osteorradionecrosis/etiología , Osteorradionecrosis/metabolismo , Estrés Oxidativo , alfa 2-Macroglobulinas Asociadas al Embarazo/farmacología , Radioterapia/efectos adversos , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
Vision-based fall-detection methods have been previously studied but many have limitations in terms of practicality. Due to differences in rooms, users do not set the camera or sensors at the same height. However, few studies have taken this into consideration. Moreover, some fall-detection methods are lacking in terms of practicality because only standing, sitting and falling are taken into account. Hence, this study constructs a data set consisting of various daily activities and fall events and studies the effect of camera/sensor height on fall-detection accuracy. Each activity in the data set is carried out by eight participants in eight directions and taken with the depth camera at five different heights. Many related studies heavily depended on human segmentation by using Kinect SDK but this is not reliable enough. To address this issue, this study proposes Enhanced Tracking and Denoising Alex-Net (ETDA-Net) to improve tracking and denoising performance and classify fall and non-fall events. Experimental results indicate that fall-detection accuracy is affected by camera height, against which ETDA-Net is robust, outperforming traditional deep learning based fall-detection methods.
RESUMEN
Syntheses of (11Z,13Z)-hexadecadienal (1), (11Z,13Z)-hexadecadienol (2), (11Z,13Z)-hexadecadien-1-yl acetate (3), and (Z)-13-hexadecen-11-ynal (4) from commercially available starting material 10-bromo-1-decanol are reported. These (Z,Z)-dienes and conjugated en-yne moieties are common in sex pheromone and attractant components for many Notodontide insect pests. The synthetic scheme, using the C10 + C3 + C3 strategy, was mainly based on three key steps: alkylation of lithium alkyne under a low temperature, cis-Wittig olefination of the aldehyde with propylidentriphenylphosphorane, and hydroboration-protonolysis of alkyne. This synthetic route provided (11Z,13Z)-hexadecadienal (1) in a 23.0% total yield via an eight-step sequence, alcohol (2) in a 21.9% total yield, acetate (3) in a 21.4% total yield, and (Z)-13-hexadecen-11-ynal (4) in a 34.7% total yield. This simple strategy provides a new way to achieve syntheses of the key sex pheromones of Notodontide insect pests.
Asunto(s)
Aldehídos/síntesis química , Mariposas Nocturnas/química , Atractivos Sexuales/síntesis química , Aldehídos/química , Animales , Atractivos Sexuales/químicaRESUMEN
Orthaga achatina (Lepidoptera: Pyralidae) is the most serious pest in south China of camphor trees, Cinnamomum camphora (L.) Presl, an important urban tree species. Gas chromatography-electroantennographic detection (GC-EAD) of the sex pheromone of O. achatina showed three EAD-active components. Coupled gas chromatography/mass spectrometry analyses identified these as (Z)-11-hexadecenol (Z11-16:OH), (Z)-11-hexadecenyl acetate (Z11-16:OAc), and (3Z,6Z,9Z,12Z,15Z)-tricosapentaene (Z3,Z6,Z9,Z12,Z15-23:H). In field tests using different combinations of the three compounds, male moths were attracted to a mixture of Z11-16:OAc and Z3,Z6,Z9,Z12,Z15-23:H, but less attracted to other blends. Further field tests with different ratios of the two compounds determined the optimal ratio of the binary blend as 500:250. The addition of Z11-16:OH to Z11-16:OAc, or to the binary mixture of Z11-16: OAc and the pentaene did not yield higher catches. This shows that O. achatina uses a mixture of Type I and Type II sex pheromone components. Orthaga achatina is the third Pyraloidea species found to utilize Z3,Z6,Z9,Z12,Z15-23:H as a sex pheromone component.
Asunto(s)
Lepidópteros/química , Lepidópteros/efectos de los fármacos , Atractivos Sexuales/química , Atractivos Sexuales/farmacología , Animales , Femenino , Cromatografía de Gases y Espectrometría de Masas , Masculino , Conducta Sexual Animal/efectos de los fármacosRESUMEN
BACKGROUND: Although triptorelin is increasingly used in China for biochemical castration, its effects on primary prostate cancer symptoms remain unclear. This study aimed to assess the prevalence of lower urinary tract symptoms (LUTS) in Chinese prostate cancer patients and the effectiveness of triptorelin on LUTS. METHODS: In this 48-week multicenter, non-interventional, prospective study, we enrolled patients with locally advanced or metastatic prostate cancer. Patients received triptorelin (15 mg) intramuscularly at baseline and at weeks 12, 24, and 36 with symptom assessment using the International Prostate Symptoms Score (IPSS). The primary endpoints were the prevalence of LUTS at baseline per IPSS categories and the percentage of patients with moderate to severe LUTS (IPSS > 7) at baseline, having at least a 3-point reduction of IPSS score at week 48. RESULTS: A total of 398 patients were included; 211 (53.0%) and 160 (40.2%) among them had severe and moderate LUTS, respectively. Of the patients with IPSS scores available at baseline and at week 48 (n = 213), 81.2% achieved a reduction in IPSS of at least 3 points. Of the patients with moderate to severe LUTS at baseline and IPSS scores available at baseline and at week 48 (n = 194), 86.6% achieved a total IPSS reduction of at least 3 points. CONCLUSIONS: The vast majority of Chinese patients with locally advanced or metastatic prostate cancer scheduled to receive triptorelin as part of their standard treatment have severe or moderate LUTS. Triptorelin therapy resulted in sustained improvement of LUTS in these patients.
Asunto(s)
Antineoplásicos Hormonales/administración & dosificación , Síntomas del Sistema Urinario Inferior/tratamiento farmacológico , Síntomas del Sistema Urinario Inferior/epidemiología , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/epidemiología , Pamoato de Triptorelina/administración & dosificación , Anciano , Anciano de 80 o más Años , China/epidemiología , Humanos , Inyecciones Intramusculares , Síntomas del Sistema Urinario Inferior/diagnóstico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Neoplasias de la Próstata/diagnósticoRESUMEN
BACKGROUND: Pine moths (Lepidoptera; Bombycoidea; Lasiocampidae: Dendrolimus spp.) are among the most serious insect pests of forests, especially in southern China. Although COI barcodes (a standardized portion of the mitochondrial cytochrome c oxidase subunit I gene) can distinguish some members of this genus, the evolutionary relationships of the three morphospecies Dendrolimus punctatus, D. tabulaeformis and D. spectabilis have remained largely unresolved. We sequenced whole mitochondrial genomes of eight specimens, including D. punctatus wenshanensis. This is an unambiguous subspecies of D. punctatus, and was used as a reference for inferring the relationships of the other two morphospecies of the D. punctatus complex. We constructed phylogenetic trees from this data, including twelve published mitochondrial genomes of other Bombycoidea species, and examined the relationships of the Dendrolimus taxa using these trees and the genomic features of the mitochondrial genome. RESULTS: The eight fully sequenced mitochondrial genomes from the three morphospecies displayed similar genome structures as other Bombycoidea species in terms of gene content, base composition, level of overall AT-bias and codon usage. However, the Dendrolimus genomes possess a unique feature in the large ribosomal 16S RNA subunits (rrnL), which are more than 60 bp longer than other members of the superfamily and have a higher AC proportion. The eight mitochondrial genomes of Dendrolimus were highly conservative in many aspects, for example with identical stop codons and overlapping regions. But there were many differences in start codons, intergenic spacers, and numbers of mismatched base pairs of tRNA (transfer RNA genes). Our results, based on phylogenetic trees, genetic distances, species delimitation and genomic features (such as intergenic spacers) of the mitochondrial genome, indicated that D. tabulaeformis is as close to D. punctatus as is D. punctatus wenshanensis, whereas D. spectabilis evolved independently from D. tabulaeformis and D. punctatus. Whole mitochondrial DNA phylogenies showed that D. spectabilis formed a well-supported monophyletic clade, with a clear species boundary separating it from the other congeners examined here. However, D. tabulaeformis often clustered with D. punctatus and with the subspecies D. punctatus wenshanensis. Genetic distance analyses showed that the distance between D. tabulaeformis and D. punctatus is generally less than the intraspecific distance of D. punctatus and its subspecies D. punctatus wenshanensis. In the species delimitation analysis of Poisson Tree Processes (PTP), D. tabulaeformis, D. punctatus and D. punctatus wenshanensis clustered into a putative species separated from D. spectabilis. In comparison with D. spectabilis, D. tabulaeformis and D. punctatus also exhibit a similar structure in intergenic spacer characterization. These different types of evidence suggest that D. tabulaeformis is very close to D. punctatus and its subspecies D. punctatus wenshanensis, and is likely to be another subspecies of D. punctatus. CONCLUSIONS: Whole mitochondrial genomes possess relatively rich genetic information compared with the traditional use of single or multiple genes for phylogenetic purposes. They can be used to better infer phylogenetic relationships and degrees of relatedness of taxonomic groups, at least from the aspect of maternal lineage: caution should be taken due to the maternal-only inheritance of this genome. Our results indicate that D. spectabilis is an independent lineage, while D. tabulaeformis shows an extremely close relationship to D. punctatus.
Asunto(s)
Genoma Mitocondrial , Mitocondrias/genética , Mariposas Nocturnas/genética , Animales , Disparidad de Par Base , China , Codón Iniciador/genética , ADN Mitocondrial/análisis , ADN Mitocondrial/aislamiento & purificación , Evolución Molecular , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Mariposas Nocturnas/clasificación , Filogenia , ARN Ribosómico 16S/genética , ARN Ribosómico 16S/metabolismo , ARN de Transferencia/genética , ARN de Transferencia/metabolismo , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: Matrix metalloproteinase 1 (MMP1) has been shown as a novel unique biomarker of bladder cancer in urine. MMP1 can only be detected using conventional and time-consuming methods, such as ELISA and Western. Refolded MMP1 has been achieved and used in probe screen for many years, while there is no clinical application for MMP1 detection until now. Soluble expression of MMP1 is necessary in urine detection. METHODS: cDNA of MMP1 has been isolated from human embryonic kidney 293(HEK293) cells. The catalytic domain of MMP1 is expressed as fusion protein with Escherichia coli thioredoxin (TrxA). The 30 kDa recombinant proteins were purified by Ni-chelating chromatography. The activity of soluble MMP1 was determined and compared with refolded MMP1 by zymography. RESULTS: Compared with refolded MMP1, TrxA can increase the solubility of MMP1. The soluble MMP1 has the same protein sequences with refolded MMP1 and increased 1.54-fold of gelatin-degradation activities than refolded MMP1. CONCLUSION: Successfully soluble expression of MMP1 has been achieved by fusion expression and will make progress in discovering specific molecular probes against MMP1.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Metaloproteinasa 1 de la Matriz/metabolismo , Neoplasias de la Vejiga Urinaria/enzimología , Vectores Genéticos/metabolismo , Células HEK293 , Humanos , Cuerpos de Inclusión/metabolismo , Metaloproteinasa 1 de la Matriz/aislamiento & purificación , SolubilidadRESUMEN
Diabetes-induced testicular cell death is due predominantly to oxidative stress. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is an important transcription factor in controlling the antioxidative system and is inducible by sulforaphane (SFN). To test whether SFN prevents diabetes-induced testicular cell death, an insulin-defective stage of type 2 diabetes (IDS-T2DM) was induced in mice. This was accomplished by feeding them a high-fat diet (HFD) for 3 mo to induce insulin resistance and then giving one intraperitoneal injection of streptozotocin to induce hyperglycemia while age-matched control mice were fed a normal diet (ND). IDS-T2DM and ND-fed control mice were then further subdivided into those with or without 4-mo SFN treatment. IDS-T2DM induced significant increases in testicular cell death presumably through receptor and mitochondrial pathways, shown by increased ratio of Bax/Bcl2 expression and cleavage of caspase-3 and caspase-8 without significant change of endoplasmic reticulum stress. Diabetes also significantly increased testicular oxidative damage and inflammation. All of these diabetic effects were significantly prevented by SFN treatment with upregulated Nrf2 expression. These results suggest that IDS-T2DM induces testicular cell death presumably through caspase-8 activation and mitochondria-mediated cell death pathways and also by significantly downregulating testicular Nrf2 expression and function. SFN upregulates testicular Nrf2 expression and its target antioxidant expression, which was associated with significant protection of the testis from IDS-T2DM-induced germ cell death.
Asunto(s)
Apoptosis/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Isotiocianatos/administración & dosificación , Factor 2 Relacionado con NF-E2/metabolismo , Testículo/metabolismo , Testículo/patología , Animales , Diabetes Mellitus Experimental/inducido químicamente , Masculino , Ratones , Ratones Endogámicos C57BL , Oxidación-Reducción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Sulfóxidos , Testículo/efectos de los fármacos , Resultado del Tratamiento , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Renal cell carcinoma (RCC) is the most common types among kidney cancers. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) strongly induces apoptosis in RCC. However, TRAIL therapy also leads to hepatotoxicity. To improve the biosafety, we inserted miRNA response elements (MREs) of miR-138, miR-199, and miR-122 into an adenoviral vector, Ad-TRAIL-3MREs, to restrict TRAIL expression within RCC cells. Luciferase assays showed that MREs can regulate the expression of exogenous gene in RCC cells. Ad-TRAIL-3MREs selectively expressed TRAIL and induce apoptosis in RCC cells, but not in normal cells. MTT assays revealed that Ad-TRAIL-3MREs reduced viability of RCC cells without cytotoxicity to normal cells. Ad-TRAIL-3MREs suppressed the growth of ACHN tumors and exerted no hepatotoxicity in vivo. Collectively, we generated a TRAIL-expressing adenoviral vector under the regulation of MREs. This miRNA-based gene therapy may be a promising strategy for RCC treatment.
Asunto(s)
Carcinoma de Células Renales/patología , Neoplasias Renales/patología , MicroARNs/fisiología , Ligando Inductor de Apoptosis Relacionado con TNF/fisiología , Adenoviridae/genética , Secuencia de Bases , Carcinoma de Células Renales/metabolismo , Cartilla de ADN , Vectores Genéticos , Humanos , Neoplasias Renales/metabolismo , MicroARNs/genética , Reacción en Cadena de la Polimerasa , Ligando Inductor de Apoptosis Relacionado con TNF/genéticaRESUMEN
Odorant binding proteins (OBPs) play important roles in insect olfactory processes. The Chinese pine caterpillar moth, Dendrolimus tabulaeformis (Lepidoptera, Lasiocampidae) is a serious economic pest in China, and the pheromones of this species have been identified to monitor their presence. However, the molecular mechanisms by which D. tabulaeformis perceive pheromones and host volatiles remain unknown. In this study, we identified and characterized three new OBPs, including one pheromone binding protein (PBP1) and two general odor binding proteins (GOBPs), from antennal cDNA of D. tabulaeformis. The deduced amino acid sequences of DtabPBP1, DtabGOBP1, and DtabGOBP2 revealed mature proteins of 140, 147, and 140 amino acids, respectively. Each has six cysteine residues in conserved positions relative to other known OBPs. Amino-acid alignments indicated that the two GOBPs are more conserved (DtabGOBP1 is 52.9-67.4 % identical to orthologs from other Lepidoptera, and DtabGOBP2 is 55.2-81.8 % identical) than the PBP (32.5-46.0 %). Real-time PCR indicated tissue- and sex-specific expression patterns of the three genes. DtabPBP1 was mainly expressed in the antennae of males, whereas female antennae had only 1.09 % the expression in male antennae. Both DtabGOBP1 and DtabGOBP2 were more highly expressed in antennae than in other tissues, while DtabGOBP1 was more abundant in male antennae and DtabGOBP2 in female antennae. In addition, the binding specificities of the three proteins were investigated, and all three OBPs exhibited high binding affinities for the pheromone component (5Z,7E)-5,7-dodecadien-1-yl propionate (Z5,E7-12:OPr). This suggests a role in binding pheromone for GOBPs, as well as PBP1, in D. tabulaeformis.
Asunto(s)
Proteínas Portadoras/genética , Regulación de la Expresión Génica , Proteínas de Insectos/genética , Mariposas Nocturnas/genética , Receptores Odorantes/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Proteínas Portadoras/química , Proteínas Portadoras/metabolismo , ADN Complementario/genética , ADN Complementario/metabolismo , Femenino , Perfilación de la Expresión Génica , Proteínas de Insectos/química , Proteínas de Insectos/metabolismo , Masculino , Datos de Secuencia Molecular , Mariposas Nocturnas/metabolismo , Especificidad de Órganos , Filogenia , Receptores Odorantes/química , Receptores Odorantes/metabolismo , Alineación de SecuenciaRESUMEN
Radiation is an important modality in cancer treatment, and eighty percent of cancer patients need radiotherapy at some point during their clinical management. However, radiation-induced damage to normal tissues restricts the therapeutic doses of radiation that can be delivered to tumours and thereby limits the effectiveness of the treatment. The use of radioprotectors represents an obvious strategy to obtain better tumour control using a higher dose in radiotherapy. However, most of the synthetic radioprotective compounds studied have shown inadequate clinical efficacy owing to their inherent toxicity and high cost. Hence, the development of radioprotective agents with lower toxicity and an extended window of protection has attracted a great deal of attention, and the identification of alternative agents that are less toxic and highly effective is an absolute necessity. Recent studies have shown that alpha-2-macroglobulin (α2M) possesses radioprotective effects. α2M is a tetrameric, disulfide-rich plasma glycoprotein that functions as a non-selective inhibitor of different types of non-specific proteases and as a carrier of cytokines, growth factors, and hormones. α2M induces protein factors whose interplay underlies radioprotection, which supports the idea that α2M is the central effector of natural radioprotection in the rat. Pretreatment with α2M has also induced a significant reduction of irradiation-induced DNA damage and the complete restoration of liver and body weight. Mihailovic et al. concluded that the radioprotection provided by α2M was in part mediated through cytoprotection of new blood cells produced in the bone marrow; these authors also indicated that an important aspect of the radioprotective effect of amifostine was the result of the induction of the endogenous cytoprotective capability of α2M. The radioprotective effects of α2M are possibly due to antioxidant, anti-fibrosis, and anti-inflammatory functions, as well as the maintenance of homeostasis, and enhancement of the DNA repair and cell recovery processes. This review is the first to summarise the observations and elucidate the possible mechanisms responsible for the beneficial effects of α2M. The lacunae in the existing knowledge and directions for future research are also addressed.
RESUMEN
AIMS: A bibliometric study was conducted to gain deeper insights into the current state of research on diabetes and the biological clock (BC). METHODS: The study involved a comprehensive search for literature related to diabetes and BC published between 1992 and 2023 in the Web of Science database. RESULTS: Ninety-five articles were published in 65 journals, with six of these journals not included in the Journal Citation Reports as of 2022. Among the remaining 59 journals, 10 had an impact factor (IF) greater than 10, and 21 had an IF greater than 5. Twenty-nine journals belonged to Quartile 1, while 16 journals were part of Quartile 2. The articles were contributed by researchers from 22 countries, with the Netherlands and the USA being the most prolific contributors. However, the total number of citations for articles from the USA was significantly higher than that of the Netherlands. The co-occurrence analysis of title and abstract keywords primarily focused on investigating the mechanisms of BC. Regarding author keywords and keyword-plus, the co-occurrence analysis centered around diabetes and BC. International collaboration was prominent among developed countries, with the Netherlands, the USA, and France being major participants. Institution- wise cooperation primarily occurred between two research institutions in the Netherlands. In total, the 95 articles received 5,157 citations, averaging 54.28 citations per article. CONCLUSION: To foster advancements in this area, more attention and international cooperation are necessary. Emphasizing collaborative efforts can drive the development of novel approaches to manage diabetes and regulate blood glucose levels effectively.