RESUMEN
BACKGROUND: The optimal primary debulking surgery outcome of serous ovarian carcinoma (SOC) is greatly affected by primary ovarian neoplasm or metastatic lesion close to the rectum. PURPOSE: To study the risk factors affecting postoperative residual primary ovarian neoplasm or metastatic lesion close to the rectum of SOC. MATERIAL AND METHODS: The clinical and MRI data of 164 patients with SOC eligible from institution A (training and test groups) and 36 patients with SOC eligible from institution B (external validation group) were collected and retrospectively analyzed. The clinical data included age, serum carbohydrate antigen 125 (CA-125), human epididymis protein 4, and neutrophil-to-lymphocyte ratio (NLR). Magnetic resonance imaging (MRI) data included ovarian mass distribution, maximum diameter of ovarian mass, ovarian mass features, degree of rectal invasion of the primary ovarian neoplasm or metastatic lesion, and amount of ascites. A model was established using multivariate logistic regression. RESULTS: By univariate and multivariate logistic regressions, CA-125 (P = 0.024, odds ratio [OR] = 3.798, 95% confidence interval [CI] = 1.24-13.32), NLR (P = 0.037, OR = 3.543, 95% CI = 1.13-12.72), and degree of rectal invasion of the primary ovarian neoplasm or metastatic lesion (P < 0.001, OR = 37.723, 95% CI = 7.46-266.88) were screened as independent predictors. The area under the curve values of the model in the training, test, and external validation groups were 0.860, 0.764, and 0.778, respectively. CONCLUSION: The clinical-radiological model based on T1-weighted dual-echo MRI can be used non-invasively to predict postoperative residual ovarian neoplasm or metastasis close to SOC in the rectum.
RESUMEN
Low-light stress compromises photosynthetic and energy efficiency and leads to spikelet sterility; however, the effect of low-light stress on pollen tube elongation in the pistil remains poorly understood. The gene RGA1, which encodes a Gα-subunit of the heterotrimeric G-protein, enhanced low-light tolerance at anthesis by preventing the cessation of pollen tube elongation in the pistil of rice plants. In this process, marked increases in the activities of acid invertase (INV), sucrose synthase (SUS) and mitochondrial respiratory electron transport chain complexes, as well as the relative expression levels of SUTs (sucrose transporter), SWEETs (sugars will eventually be exported transporters), SUSs, INVs, CINs (cell-wall INV 1), SnRK1A (sucrose-nonfermenting 1-related kinase 1) and SnRK1B, were observed in OE-1 plants. Accordingly, notable increases in contents of ATP and ATPase were presented in OE-1 plants under low-light conditions, while they were decreased in d1 plants. Importantly, INV and ATPase activators (sucrose and Na2 SO3 , respectively) increased spikelet fertility by improving the energy status in the pistil under low-light conditions, and the ATPase inhibitor Na2 VO4 induced spikelet sterility and decreased ATPase activity. These results suggest that RGA1 could alleviate the low-light stress-induced impairment of pollen tube elongation to increase spikelet fertility by promoting sucrose unloading in the pistil and improving the metabolism and allocation of energy.
Asunto(s)
Infertilidad , Oryza , Azúcares/metabolismo , Tubo Polínico , Plantas/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Sacarosa/metabolismo , Adenosina Trifosfatasas/metabolismo , Oryza/genéticaRESUMEN
BACKGROUND: The purpose of this study was to explore the short-term efficacy and safety of neoadjuvant chemotherapy combined with arterial chemoembolization for locally advanced gastric cancer (LAGC). METHODS: We retrospectively analyzed the clinical data of 203 patients with LAGC who received neoadjuvant therapy from June 2019 to December 2021. The patients were divided into a neoadjuvant chemotherapy combined with arterial chemoembolization group (combined group, n = 102) and a neoadjuvant chemotherapy group (conventional group, n = 101). The adverse events of chemotherapy, postoperative complications and pathological complete response (pCR) rate were compared between the two groups. Univariate and multivariate analyses were performed to evaluate the potential factors affecting pCR. RESULTS: A total of 78.8% of the patients were in clinical stage III before neoadjuvant therapy. A total of 52.2% of the patients underwent surgery after receiving two cycles of neoadjuvant therapy. There were 21.2% patients with ≥ grade 3 (CTCAE 4.0) adverse events of chemotherapy and 11.3% patients with Clavien-Dindo classification ≥ grade 3 postoperative complications. Compared with the conventional group, the combination group did not experience an increase in the adverse events of chemotherapy or postoperative complications. The pCR rate in the combined group was significantly higher than that in the conventional group (16.7% vs. 4.95%, P = 0.012). The multivariate analysis showed that arterial chemoembolization, pre-treatment neutrophil-to-lymphocyte ratio (NLR) and pre-treatment platelet-to-lymphocyte ratio (PLR) were independent factors affecting pCR. CONCLUSION: Neoadjuvant chemotherapy combined with arterial chemoembolization contributed to improving the pCR rate of LAGC patients. Arterial chemoembolization, pre-treatment NLR and pre-treatment PLR were also predictors of pCR.
Asunto(s)
Terapia Neoadyuvante , Neoplasias Gástricas , Humanos , Estudios Retrospectivos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Linfocitos/patología , Complicaciones Posoperatorias/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
Life-like hierarchical architecture shows great potential for advancing intelligent biosensing, but modular expansion of its sensitivity and functionality remains a challenge. Drawing inspiration from intracellular liquid-liquid phase separation, we discovered that a DNA-encoded artificial cell with a liquid core (LAC) can enhance peroxidase-like activity of Hemin and its DNA G-quadruplex aptamer complex (DGAH) without substrate-selectivity, unlike its gelled core (GAC) counterpart. The LAC is easily engineered as an ultrasensitive biosensing system, benefiting from DNA's high programmability and unique signal amplification capability mediated by liquid-liquid phase separation. As proof of concept, its versatility was successfully demonstrated by coupling with two molecular recognition elements to monitor tumor-related microRNA and profile cancer cell phenotypes. This scalable design philosophy offers new insights into the design of next generation of artificial cells-based biosensors.
Asunto(s)
Aptámeros de Nucleótidos , Células Artificiales , Técnicas Biosensibles , ADN Catalítico , G-Cuádruplex , MicroARNs , Neoplasias , Humanos , ADN/genética , Hemina , ADN Catalítico/metabolismoRESUMEN
Heat stress that occurs during the flowering stage severely decreases the rice (Oryza sativa L.) seed-setting rate. This damage can be reversed by abscisic acid (ABA), through effects on reactive oxygen species, carbohydrate metabolism, and heat shock proteins, but the exact role of trehalose and ATP in this process remains unclear. Two rice genotypes, namely, Zhefu802 (heat-resistant plant, a recurrent parent) and its near-isogenic line (faded green leaf, Fgl, heat-sensitive plant), were subjected to 38 °C heat stress after being sprayed with ABA or its biosynthetic inhibitor, fluridone (Flu), at the flowering stage. The results showed that exogenous ABA significantly increased the seed-setting rate of rice under heat stress, by 14.31 and 22.40% in Zhefu802 and Fgl, respectively, when compared with the H2O treatment. Similarly, exogenous ABA increased trehalose content, key enzyme activities of trehalose metabolism, ATP content, and F1Fo-ATPase activity. Importantly, the opposite results were observed in plants treated with Flu. Therefore, ABA may improve rice thermo-tolerance by affecting trehalose metabolism and ATP consumption.
Asunto(s)
Ácido Abscísico , Oryza , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacología , Adenosina Trifosfatasas/metabolismo , Adenosina Trifosfato/metabolismo , Metabolismo de los Hidratos de Carbono , Regulación de la Expresión Génica de las Plantas , Proteínas de Choque Térmico/metabolismo , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Estrés Fisiológico , Trehalosa/metabolismoRESUMEN
Sugar content is an important trait of fleshy fruit, and elevating Suc levels is a major goal in horticultural crop breeding. Here, we examined the sugar content in two varieties of the Ussurian pear (Pyrus ussuriensis), 'Nanguo' (NG) and its bud sport (BNG), and we found that Suc content was higher in BNG fruit than in NG fruit. We compared the transcriptomes of the two varieties using RNA sequencing and identified a SWEET (Sugars Will Eventually be Exported Transporter) gene, PuSWEET15, expressed at higher levels in BNG fruit. Heterologous expression of PuSWEET15 in a SUSY7/ura yeast (Saccharomyces cerevisiae) strain showed that PuSWEET15 is an active Suc transporter. Overexpression of PuSWEET15 in NG pear fruit increased Suc content, while silencing of PuSWEET15 in BNG fruit decreased Suc content. The WRKY transcription factor PuWRKY31 was also expressed more highly in BNG fruit than in NG fruit, and we found that PuWRKY31 bound to the PuSWEET15 promoter and induced its transcription. The histone acetylation level of the PuWRKY31 promoter was higher in BNG fruit, suggesting a mechanism by which Suc levels can be elevated.
Asunto(s)
Frutas/metabolismo , Histonas/metabolismo , Proteínas de Plantas/metabolismo , Pyrus/metabolismo , Factores de Transcripción/metabolismo , Acetilación , Frutas/genética , Regulación de la Expresión Génica de las Plantas/genética , Regulación de la Expresión Génica de las Plantas/fisiología , Histonas/genética , Proteínas de Plantas/genética , Regiones Promotoras Genéticas/genética , Pyrus/genética , Sacarosa/metabolismo , Factores de Transcripción/genéticaRESUMEN
Isoquinoline alkaloids, an important class of N-based heterocyclic compounds, have attracted considerable attention from researchers worldwide since the early 19th century. Over the past 200 years, many compounds from this class were isolated, and most of them and their analogs possess various bioactivities. In this review, we survey the updated literature on bioactive alkaloids and highlight research achievements of this alkaloid class during the period of 2014-2018. We reviewed over 400 molecules with a broad range of bioactivities, including antitumor, antidiabetic and its complications, antibacterial, antifungal, antiviral, antiparasitic, insecticidal, anti-inflammatory, antioxidant, neuroprotective, and other activities. This review should provide new indications or directions for the discovery of new and better drugs from the original naturally occurring isoquinoline alkaloids.
Asunto(s)
Alcaloides , Antiinfecciosos , Alcaloides/farmacología , Antiinfecciosos/farmacología , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Humanos , Isoquinolinas/farmacologíaRESUMEN
Flavonoid accumulation in most fruits is enhanced by ethylene and jasmonate. However, little is known about the hormone functions related to red pear fruit coloration or their combined effects and potential underlying mechanisms. Various treatments were used to investigate the flavonoid metabolite profile and pear transcriptome to verify the effects of ethylene and jasmonate on flavonoid biosynthesis in red pear fruits as well as the mechanism behind this. Ethylene inhibits anthocyanin biosynthesis in red Chinese pear fruits, whereas jasmonate increases anthocyanin and flavone/isoflavone biosyntheses. The branching of the jasmonate-induced flavonoid biosynthesis pathway is determined by ethylene. Co-expression network and Mfuzz analyses revealed 4,368 candidate transcripts. Additionally, ethylene suppresses PpMYB10 and PpMYB114 expression via TF repressors, ultimately decreasing anthocyanin biosynthesis. Jasmonate induces anthocyanin accumulation through transcriptional or post-translational regulation of TFs-like MYB and bHLH in the absence of ethylene. However, jasmonate induces ethylene biosynthesis and the associated signalling pathway in pear, thereby decreasing anthocyanin production, increasing the availability of the precursors for flavone/isoflavone biosynthesis and enhancing deep yellow fruit coloration. We herein present new phenotypes and fruit coloration regulatory patterns controlled by jasmonate and ethylene, and confirm that the regulation of fruit coloration is complex.
Asunto(s)
Pyrus , Antocianinas , Ciclopentanos , Etilenos , Frutas/genética , Frutas/metabolismo , Regulación de la Expresión Génica de las Plantas , Oxilipinas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Pyrus/genética , Pyrus/metabolismoRESUMEN
In this paper, the nitrogen atom was inserted into the anthracycline system of the isocryptolepine nucleus to obtain the "Aza"-type structure benzo[4,5]imidazo[1,2-c] quinazoline. A series of "Aza"-type derivatives were designed, synthesized and evaluated for their antifungal activity against six plant fungi in vitro. Among all derivatives, compounds A-0, B-1 and B-2 showed significant antifungal activity against B. cinerea with the EC50 values of 2.72⯵g/mL, 5.90⯵g/mL and 4.00⯵g/mL, respectively. Compound A-2 had the highest activity against M. oryzae with the EC50 values of 8.81⯵g/mL, and compound A-1 demonstrated the most control efficacy against R. solani (EC50, 6.27⯵g/mL). Moreover, compound A-0 was selected to investigate the in vivo tests against B. cinerea and the results indicated that the preventative efficacy of it up to 72.80% at 100⯵g/mL. Preliminary mechanism studies revealed that after treatment with A-0 at 5⯵g/mL, the B. cinerea mycelia appeared curved, collapsed and the cell membrane integrity may be damaged. The reactive oxygen species production, mitochondrial membrane potential and nuclear morphometry of mycelia have been changed, and the membrane function and cell proliferation of mycelia were destroyed. Compounds A-0, A-1, B-1 and B-2 presented weaker toxicities against two cells lines than isocryptolepine. This study lays the foundation for the future development of isocryptolepine derivatives as environmentally friendly and safe agricultural fungicides.
Asunto(s)
Antifúngicos/farmacología , Diseño de Fármacos , Hongos/efectos de los fármacos , Fungicidas Industriales/farmacología , Alcaloides Indólicos/farmacología , Quinolinas/farmacología , Antifúngicos/síntesis química , Antifúngicos/química , Relación Dosis-Respuesta a Droga , Fungicidas Industriales/síntesis química , Fungicidas Industriales/química , Alcaloides Indólicos/síntesis química , Alcaloides Indólicos/química , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Plantas/microbiología , Quinolinas/síntesis química , Quinolinas/química , Relación Estructura-ActividadRESUMEN
Isoquinoline alkaloids possess broad pharmacological activities. In this study, the antifungal activity of twelve isoquinoline alkaloids, including berberine (1), jatrorrhizine (2), coptisine (3), corydaline (4), tetrahydroberberine (5), chelidonine (6), dihydrosanguinarine (7), chelerythrine (8), sanguinarine (9), palmatine (10), tetrahydropalmatine (11) and columbamine (12) were evaluated against eight plant pathogenic fungi in vitro. All the tested compounds showed varying degrees of inhibition against the eight tested plant fungi. Among them, sanguinarine exhibited high antifungal activity (EC50 ranging from 6.96-59.36⯵g/mL). It displayed the best inhibitory activity against Magnaporthe oryzae (EC50â¯=â¯6.96⯵g/mL), compared with azoxystrobin (EC50â¯=â¯12.04⯵g/mL), and significantly suppressed spore germination of M. oryzae with the inhibition rate reaching 100% (50⯵g/mL). The optical microscopy and scanning electron microscopy observations revealed that after treating M. oryzae mycelia with sanguinarine at 10⯵g/mL, the mycelia appeared curved, collapsed and the cell membrane integrity was eventually damaged. Furthermore, the reactive oxygen species production, mitochondrial membrane potential and nuclear morphometry of mycelia had been changed, and the membrane function and cell proliferation of mycelia were destroyed. These results will enrich our insights into action mechanisms of antifungal activity of sanguinarine against M. oryzae.
Asunto(s)
Alcaloides/farmacología , Antifúngicos/farmacología , Benzofenantridinas/farmacología , Isoquinolinas/farmacología , Berberina/análogos & derivados , Berberina/farmacología , Alcaloides de Berberina/farmacología , Magnaporthe/metabolismo , Magnaporthe/patogenicidad , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Pruebas de Sensibilidad Parasitaria , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Quinoline and quinazoline alkaloids, two important classes of N-based heterocyclic compounds, have attracted tremendous attention from researchers worldwide since the 19th century. Over the past 200 years, many compounds from these two classes were isolated from natural sources, and most of them and their modified analogs possess significant bioactivities. Quinine and camptothecin are two of the most famous and important quinoline alkaloids, and their discoveries opened new areas in antimalarial and anticancer drug development, respectively. In this review, we survey the literature on bioactive alkaloids from these two classes and highlight research achievements prior to the year 2008 (Part I). Over 200 molecules with a broad range of bioactivities, including antitumor, antimalarial, antibacterial and antifungal, antiparasitic and insecticidal, antiviral, antiplatelet, anti-inflammatory, herbicidal, antioxidant and other activities, were reviewed. This survey should provide new clues or possibilities for the discovery of new and better drugs from the original naturally occurring quinoline and quinazoline alkaloids.
Asunto(s)
Alcaloides/farmacología , Quinazolinas/farmacología , Quinolinas/farmacología , Alcaloides/química , Animales , Humanos , Factores Inmunológicos/química , Factores Inmunológicos/farmacología , Sustancias Protectoras/química , Sustancias Protectoras/farmacología , Quinazolinas/química , Quinolinas/químicaRESUMEN
To follow-up on our prior Part I review, this Part II review summarizes and provides updated literature on novel quinoline and quinazoline alkaloids isolated during the period of 2009-2016, together with the biological activity and the mechanisms of action of these classes of natural products. Over 200 molecules with a broad range of biological activities, including antitumor, antiparasitic and insecticidal, antibacterial and antifungal, cardioprotective, antiviral, anti-inflammatory, hepatoprotective, antioxidant, anti-asthma, antitussive, and other activities, are discussed. This survey should provide new clues or possibilities for the discovery of new and better drugs from the original naturally occurring quinoline and quinazoline alkaloids.
Asunto(s)
Alcaloides/farmacología , Quinazolinas/farmacología , Quinolinas/farmacología , Alcaloides/química , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Humanos , Sustancias Protectoras/química , Sustancias Protectoras/farmacología , Quinazolinas/química , Quinolinas/químicaRESUMEN
In recent years, laser cladding technology has been widely used in surface modification of titanium alloys. To improve the wear resistance of titanium alloys, ceramic-reinforced nickel-based composite coatings were prepared on a TC4 alloy substrateusing coaxial powder feeding laser cladding technology. Ti (C, N) ceramic was synthesized in situ by laser cladding by adding different contents (10%, 20%, 30%, and 40%) of TiN, pure Ti powder, graphite, and In625 powder. Thisestudy showed that small TiN particles were decomposed and directly formed the Ti (C, N) phase, while large TiN particles were not completely decomposed. The in situ synthetic TiCxN1-x phase was formed around the large TiN particles. With the increase in the proportion of powder addition, the wear volume of the coating shows a decreasing trend, and the wear resistance of the surface coating is improving. The friction coefficient of the sample with 40% TiN, pure Ti powder, and graphite powder is 0.829 times that of the substrate. The wear volume is 0.145 times that of the substrate. The reason for this is that with the increase in TiN, Ti, and graphite in the powder, there are more ceramic phases in the cladding layer, and the hard phases such as TiC, Ti(C, N) and Ti2Ni play the role in the structure of the "backbone", inhibit the damage caused by micro-cutting, and impede the movement of the tearing point of incision, so that the coating has a higher abrasion resistance.
RESUMEN
Objectives: Water-saving and drought-resistance rice (WDR) plays a vital role in the sustainable development of agriculture. Nevertheless, the impacts and processes of water and nitrogen on grain yield in WDR remain unclear. Methods: In this study, Hanyou 73 (WDR) and Hyou 518 (rice) were used as materials. Three kinds of nitrogen fertilizer application rate (NFAR) were set in the pot experiment, including no NFAR (nitrogen as urea applied at 0 g/pot), medium NFAR (nitrogen as urea applied at 15.6 g/pot), and high NFAR (nitrogen as urea applied at 31.2 g/pot). Two irrigation regimes, continuous flooding cultivation and water stress, were set under each NFAR. The relationships between root and shoot morphophysiology and grain yield in WDR were explored. Results: The results demonstrated the following: 1) under the same irrigation regime, the grain yield of two varieties increased with the increase of NFAR. Under the same NFAR, the reduction of irrigation amount significantly reduced the grain yield in Hyou 518 (7.1%-15.1%) but had no substantial influence on the grain yield in Hanyou 73. 2) Under the same irrigation regime, increasing the NFAR could improve the root morphophysiology (root dry weight, root oxidation activity, root bleeding rate, root total absorbing surface area, root active absorbing surface area, and zeatin + zeatin riboside contents in roots) and aboveground physiological indexes (leaf photosynthetic rate, non-structural carbohydrate accumulation in stems, and nitrate reductase activity in leaves) in two varieties. Under the same NFAR, increasing the irrigation amount could significantly increase the above indexes in Hyou 518 (except root dry weight) but has little effect on Hanyou 73. 3) Analysis of correlations revealed that the grain yield of Hyou 518 and Hanyou 73 was basically positively correlated with aboveground physiology and root morphophysiology, respectively. Conclusion: The grain yield could be maintained by water stress under medium NFAR in WDR. The improvement of root morphophysiology is a major factor for high yield under the irrigation regime and NFAR treatments in WDR.
RESUMEN
PURPOSE: To develop and validate a model for predicting suboptimal debulking surgery (SDS) of serous ovarian carcinoma (SOC) using radiomics method, clinical and MRI features. METHODS: 228 patients eligible from institution A (randomly divided into the training and internal validation cohorts) and 45 patients from institution B (external validation cohort) were collected and retrospectively analyzed. All patients underwent abdominal pelvic enhanced MRI scan, including T2-weighted imaging fat-suppressed fast spin-echo (T2FSE), T1-weighted dual-echo magnetic resonance imaging (T1DEI), diffusion weighted imaging (DWI), and T1 with contrast enhancement (T1CE). We extracted, selected and eliminated highly correlated radiomic features for each sequence. Then, Radiomic models were made by each single sequence, dual-sequence (T1CE + T2FSE), and all-sequence, respectively. Univariate and multivariate analyses were performed to screen the clinical and MRI independent predictors. The radiomic model with the highest area under the curve (AUC) was used to combine the independent predictors as a combined model. RESULTS: The optimal radiomic model was based on dual sequences (T2FSE + T1CE) among the five radiomic models (AUC = 0.720, P < 0.05). Serum carbohydrate antigen 125, the relationship between sigmoid colon/rectum and ovarian mass or mass implanted in Douglas' pouch, diaphragm nodules, and peritoneum/mesentery nodules were considered independent predictors. The AUC of the radiomic-clinical-radiological model was higher than either the optimal radiomic model or the clinical-radiological model in the training cohort (AUC = 0.908 vs. 0.720/0.854). CONCLUSIONS: The radiomic-clinical-radiological model has an overall algorithm reproducibility and may help create individualized treatment programs and improve the prognosis of patients with SOC.
RESUMEN
Seed dormancy and germination play pivotal roles in the agronomic traits of plants, and the degree of dormancy intuitively affects the yield and quality of crops in agricultural production. Seed priming is a pre-sowing seed treatment that enhances and accelerates germination, leading to improved seedling establishment. Seed priming technologies, which are designed to partially activate germination, while preventing full seed germination, have exerted a profound impact on agricultural production. Conventional seed priming relies on external priming agents, which often yield unstable results. What works for one variety might not be effective for another. Therefore, it is necessary to explore the internal factors within the metabolic pathways that influence seed physiology and germination. This review unveils the underlying mechanisms of seed metabolism and germination, the factors affecting seed dormancy and germination, as well as the current seed priming technologies that can result in stable and better germination.
RESUMEN
Long noncoding RNAs (lncRNA) have a critical role in colorectal cancer (CRC) development and progression. However, the role of the lncRNA HOXB-AS4 in CRC remains unclear. In this study, we found that HOXB-AS4 was markedly upregulated in tumor tissues compared to precancerous tissues. Loss-of-function assays in HT29 and SW480 cells confirmed that knockdown of HOXB-AS4 inhibited proliferation, migration, and promoted apoptosis. In addition, HOXB-AS4 was shown to regulate histone deacetylase 7 (HDAC7) expression by acting as a molecular sponge to bind to and adsorb miR-140-5p. These findings were confirmed by the dual-luciferase reporter assay. Functional recovery experiments further demonstrated the crucial role of the HOXB-AS4/miR-140-5p/HDAC7 axis in modulating the malignant phenotype of CRC cells. Collectively, our data suggested that HOXB-AS4 regulated the malignant tumor aggression of HT29 and SW480 cells through the miR-140-5p/HDAC7 axis and PI3K/AKT signaling pathway. Our study provides novel insights into the mechanism of action of HOXB-AS4 in CRC and highlights its potential use as a targeted therapy.
RESUMEN
Cancer-associated fibroblasts (CAFs) influence many aspects of pancreatic adenocarcinoma (PAAD) carcinogenesis, including tumor cell proliferation, angiogenesis, invasion, and metastasis. A six-gene prognostic signature was constructed for PAAD based on the 189 CAF marker genes identified in single-cell RNA-sequencing data. Multivariate analyses showed that the risk score was independently prognostic for survival in the TCGA (P < 0.001) and ICGC (P = 0.004) cohorts. Tumor infiltration of CD8 T (P = 0.005) cells and naïve B cells (P = 0.001) was greater in the low-risk than in the high-risk group, with infiltration of these cells negatively correlated with risk score. Moreover, the TMB score was lower in the low-risk than in the high-risk group (P = 0.0051). Importantly, patients in low-risk group had better immunotherapy responses than in the high-risk group in an independent immunotherapy cohort (IMvigor210) (P = 0.039). The CAV1 and SOD3 were highly expressed in CAFs of PAAD tissues, which revealed by immunohistochemical staining. In summary, this comprehensive analysis resulted in the development of a novel prognostic signature, which was associated with immune cell infiltration, drug sensitivity, and TMB, and could predict the prognosis and immunotherapy response of patients with PAAD.
Asunto(s)
Adenocarcinoma , Fibroblastos Asociados al Cáncer , Neoplasias Pancreáticas , Humanos , Adenocarcinoma/genética , Adenocarcinoma/terapia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Pronóstico , Inmunoterapia , ARN , Microambiente Tumoral/genética , Neoplasias PancreáticasRESUMEN
Colorectal cancer (CRC) is regarded as one of the most prevalent neoplasms worldwide, and ubiquitination and N6-methyladenosine (m6A) modification regulate the outgrowth of multiple cancers. This study attempted to explore the effect of ubiquitin-specific peptidases 29 (USP29) on the malignant proliferation of CRC cells via stabilizing Vir-like m6A methyltransferase associated (VIRMA/KIAA1429). First, upregulations of USP29, KIAA1429, and SRY-box transcription factor 8 (SOX8) were found in CRC tissues and cells through real-time quantitative polymerase chain reaction and Western blotting. After transfection of si-USP29, the proliferation of CRC cells was evaluated by the cell counting kit-8, colony formation and 5-ethynyl-2'-deoxyuridine assays, and we observed that depletion of USP29 inhibited the proliferation of CRC cells. Co-immunoprecipitation confirmed the binding of USP29 to KIAA1429. Mechanically, USP29 mediated deubiquitination to stabilize the protein levels of KIAA1429, and KIAA1429 promoted the stability of SOX8 mRNA through m6A modification. Moreover, overexpression of KIAA1429 or SOX8 reversed the inhibitory effects of USP29 depletion on CRC cell proliferation. Finally, the xenograft tumor model revealed the promotive role of USP29 in the proliferation of CRC cells in vivo. Altogether, USP29 facilitates the malignant proliferation of CRC cells via upregulating the KIAA1429/SOX8 axis.
Asunto(s)
Neoplasias Colorrectales , Animales , Humanos , Línea Celular Tumoral , Modelos Animales de Enfermedad , Regulación hacia Arriba , Proliferación Celular/genética , Neoplasias Colorrectales/genética , Factores de Transcripción SOXE/genética , Proteasas Ubiquitina-Específicas/genéticaRESUMEN
BACKGROUND: Signal transduction mediated by heterotrimeric G proteins, which comprise the α, ß, and γ subunits, is one of the most important signaling pathways in rice plants. RGA1, which encodes the Gα subunit of the G protein, plays an important role in the response to various types of abiotic stress, including salt, drought, and cold stress. However, the role of RGA1 in the response to heat stress remains unclear. RESULTS: The heat-resistant mutant ett1 (enhanced thermo-tolerance 1) with a new allele of the RGA1 gene was derived from an ethane methyl sulfonate-induced Zhonghua11 mutant. After 45 °C heat stress treatment for 36 h and recovery for 7 d, the survival rate of the ett1 mutants was significantly higher than that of wild-type (WT) plants. The malondialdehyde content was lower, and the maximum fluorescence quantum yield of photosystem II, peroxidase activity, and hsp expression were higher in ett1 mutants than in WT plants after 12 h of exposure to 45 °C. The RNA-sequencing results revealed that the expression of genes involved in the metabolism of carbohydrate, nicotinamide adenine dinucleotide, and energy was up-regulated in ett1 under heat stress. The carbohydrate content and the relative expression of genes involved in sucrose metabolism indicated that carbohydrate metabolism was accelerated in ett1 under heat stress. Energy parameters, including the adenosine triphosphate (ATP) content and the energy charge, were significantly higher in the ett1 mutants than in WT plants under heat stress. Importantly, exogenous glucose can alleviate the damages on rice seedling plants caused by heat stress. CONCLUSION: RGA1 negatively regulates the thermo-tolerance in rice seedling plants through affecting carbohydrate and energy metabolism.