ABSTRACT
We previously described the role of low-density lipoprotein (LDL) in aggressiveness in papillary thyroid cancer (PTC). Moreover, the MAPK signaling pathway in the presence of BRAF V600E mutation is associated with more aggressive PTC. Although the link between MAPK cascade and LDL receptor (LDLR) expression has been previously described, it is unknown whether LDL can potentiate the adverse effects of PTC through it. We aimed to investigate whether the presence of LDL might accelerate the oncogenic processes through MAPK pathway in presence or absence of BRAF V600E in two thyroid cell lines: TPC1 and BCPAP (wild-type and BRAF V600E, respectively). LDLR, PI3K-AKT and RAS/RAF/MAPK (MEK)/ERK were analyzed via Western blot; cell proliferation was measured via MTT assay, cell migration was studied through wound-healing assay and LDL uptake was analyzed by fluorometric and confocal analysis. TPC1 demonstrated a time-specific downregulation of the LDLR, while BCPAP resulted in a receptor deregulation after LDL exposition. LDL uptake was increased in BCPAP over-time, as well as cell proliferation (20% higher) in comparison to TPC1. Both cell lines differed in migration pattern with a wound closure of 83.5 ± 9.7% after LDL coculture in TPC1, while a loss in the adhesion capacity was detected in BCPAP. The siRNA knockdown of LDLR in LDL-treated BCPAP cells resulted in a p-ERK expression downregulation and cell proliferation modulation, demonstrating a link between LDLR and MAPK pathway. The modulation of BRAF-V600E using vemurafenib-impaired LDLR expression decreased cellular proliferation. Our results suggest that LDLR regulation is cell line-specific, regulating the RAS/RAF/MAPK (MEK)/ERK pathway in the LDL-signaling cascade and where BRAF V600E can play a critical role. In conclusion, targeting LDLR and this downstream signaling cascade, could be a new therapeutic strategy for PTC with more aggressive behavior, especially in those harboring BRAF V600E.
Subject(s)
Proto-Oncogene Proteins B-raf , Thyroid Neoplasms , Humans , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins B-raf/metabolism , Phosphatidylinositol 3-Kinases/genetics , Mutation , Thyroid Neoplasms/pathology , Thyroid Cancer, Papillary/genetics , Thyroid Cancer, Papillary/pathology , Receptors, LDL/genetics , Lipoproteins, LDL/genetics , Mitogen-Activated Protein Kinase Kinases/genetics , Cell Line, TumorABSTRACT
Salt tolerance and the possible functions of suberization on salt exclusion and secretion were examined in a dominant mangrove plant, Avicennia marina. The results showed that low salinities (10 and 20) almost has no negative effect on A. marina, however significant growth inhibitions were observed in the seedlings grown in higher salinities (30 and 40). With the increases of salinity, increased tissue Na+ content and enhanced salt secretion by glands were observed. Obvious suberization thickening were detected both in the exodermis and endodermis of the roots after salt pretreatment when compared to the roots without salt treatment. More importantly, the present data further confirmed that these root apoplastic barriers would directly decrease Na+ loading into xylem. Higher salt tolerance was observed in the seedlings pre-cultivated by salty tide when compared to fresh water cultivated A. marina. In summary, this study suggests a barrier property of suberization in dealing with salt exclusion in mangroves, a moderate salt pre-treatment may benefit plant withstanding high salinity.
Subject(s)
Avicennia/physiology , Salt Tolerance/physiology , Ions , Plant Roots , Salinity , Seedlings , Sodium , XylemABSTRACT
A short term pot trail was employed to evaluate the exposure of mixed heavy metals (Cu, Pb and Zn) on growth, radial oxygen loss (ROL) and root anatomy in Bruguiera gymnorrhiza. The possible function of BgC4H, a cytochrome P450 gene, on root lignification was also discussed. The exposures of mixed Cu, Pb and Zn directly reduce O2 leakage at root surface. The reduced ROL inhibited by heavy metals was mainly ascribed by the changes in root anatomical features, such as decreased root porosity together with increased lignification within the exodermis. BgC4H was found to be up-regulated after 0.5-day metal exposure, and remained higher transcript levels within 3-day metal exposure when compared to control roots. Besides, the inhibited photosynthesis may also result in less oxygen can be transported to the underground roots. In summary, the mangrove B. gymnorrhiza appeared to react to external mixed metal contaminants by developing a lignified and impermeable exodermis, and such a root barrier induced by mixed Cu, Pb and Zn appeared to be an adaptive response to block metal ions enters into the roots.
Subject(s)
Metals, Heavy/toxicity , Oxygen/metabolism , Plant Roots/drug effects , Rhizophoraceae , Water Pollutants, Chemical/toxicity , Wetlands , Copper , Lead , Plant Roots/physiology , ZincABSTRACT
Tidal flooding can directly result in oxygen (O2) shortage, however the functions of root aeration in flooding tolerance and O2 dynamics within mangroves are still poorly understood. Thus, in this study, the correlations among waterlogging tolerance, root porosity and O2 movement within the plants were investigated using two mangrove species (Aegiceras corniculatum and Bruguiera gymnorrhiza) and a semi-mangrove Heritiera littoralis. Based on the present data, the species A. corniculatum and B. gymnorrhiza, which possessed higher root porosity, exhibited higher waterlogging tolerance, while H. littoralis is intolerant. Increased root porosity, leaf stoma, and total ROL were observed in the roots of A. corniculatum and B. gymnorrhiza growing in stagnant solution when compared to respective aerated controls. As for ROL spatial pattern along roots, external anaerobic condition could promote ROL from apical root regions but reduce ROL from basal roots, leading to a 'tighter barrier'. In summary, the present study indicated that the plants (e.g., A. corniculatum and B. gymnorrhiza) prioritized to ensure O2 diffusion towards root tips under waterlogging by increasing aerenchyma formation and reducing O2 leakage at basal root regions.
Subject(s)
Primulaceae , Rhizophoraceae , Wetlands , Eutrophication , Oxygen/metabolism , Plant Roots/physiologyABSTRACT
In this study, we demonstrate a bottom-up assembly of a monomeric copper complex and a two-dimensional (2-D) heterometallic metal-organic framework (MOF) from a carboxylate-functionalized tridentate Schiff base ligand and metal ions. The obtained 2-D MOF features a unique bimetallic copper center which is different from its monometallic precursor and acts as an efficient heterogeneous catalyst for the Friedel-Crafts reaction and Henry reaction. The MOF catalyst shows a remarkably superior activity compared to its homogeneous counterparts in a wide range of substrates. It is presumably ascribed to the dual activation of the substrates by the active bimetallic copper center confined in the MOF network, which is supported by the significant changes in catalytic activity at low catalyst/substrates ratios when using the 2-D MOF and its precursor as catalysts, respectively. Moreover, the MOF catalyst also shows an excellent stability and recyclability. Our work, therefore, provides a stepwise strategy to design a heterogeneous cooperative catalyst, by taking advantage of the modulated structure of MOF and tunable functionality of the tridentate Schiff base, with high performance in a variety of organic synthesis.
ABSTRACT
Climate change provides an opportunity for the northward expansion of mangroves, and thus, the afforestation of mangroves at higher latitude areas presents an achievable way for coastal restoration, especially where invasive species S. alterniflora needs to be clipped. However, it is unclear whether replacing S. alterniflora with northward-afforested mangroves would benefit carbon sequestration. In the study, we examined the key CO2 and CH4 exchange processes in a young (3 yr) northward-afforested wetland dominated by K. obovata. We also collected soil cores from various ages (3, 15, 30, and 60 years) to analyze the carbon storage characteristics of mangrove stands using a space-for-time substitution approach. Our findings revealed that the young northward mangroves exhibited obvious seasonal variations in net ecosystem CO2 exchange (NEE) and functioned as a moderate carbon sink, with an average annual NEE of -107.9 g C m-2 yr-1. Additionally, the CH4 emissions from the northward mangroves were lower in comparison to natural mangroves, with the primary source being the soil. Furthermore, when comparing the vertical distribution of soil carbon, it became evident that both S. alterniflora and mangroves contributed to organic carbon accumulation in the upper soil layers. Our study also identified a clear correlation that the biomass and carbon stocks of mangroves increased logarithmically with age (R2 = 0.69, p < 0.001). Notably, both vegetation and soil carbon stocks (especially in the deeper layers) of the 15 yr northward mangroves, were markedly higher than those of S. alterniflora. This suggests that replacing S. alterniflora with northward-afforested mangroves is an effective long-term strategy for future coasts to enhance blue carbon sequestration.
Subject(s)
Carbon , Ecosystem , Carbon/analysis , Carbon Dioxide , Wetlands , Poaceae , Soil , Carbon Sequestration , ChinaABSTRACT
Objective: To investigate the early effectiveness of transiliac-transsacral screws internal fixation assisted by augmented reality navigation system HoloSight (hereinafter referred to as "computer navigation system") in the treatment of posterior pelvic ring injuries. Methods: A retrospective analysis was made in the 41 patients with posterior pelvic ring injuries who had been treated surgically with transiliac-transsacral screws between June 2022 and June 2023. The patients were divided into navigation group (18 cases, using computer navigation system to assist screw implantation) and freehand group (23 cases, using C-arm X-ray fluoroscopy to guide screw implantation) according to the different methods of transiliac-transsacral screws placement. There was no significant difference in gender, age, body mass index, causes of injuries, Tile classification of pelvic fracture, days from injury to operation, usage of unlocking closed reduction technique between the two groups ( P>0.05). The time of screw implantation, the fluoroscopy times, the guide wire adjustment times of each screw, and the incidence of complications were recorded and compared between the two groups. The position of the transiliac-transsacral screw was scanned by CT within 2 days after operation, and the position of the screw was classified according to Gras standard. Results: The operation was successfully completed in both groups. The time of screw implantation, the fluoroscopy times, and the guide wire adjustment times of each screw in the navigation group were significantly less than those in the freehand group ( P<0.05). There were 2 cases of incision infection in the freehand group, and the incision healed by first intention after active dressing change; there was no screw-related complication in the navigation group during operation and early period after operation; the difference in incidence of complications between the two groups (8.7% vs. 0) was not significant ( P=0.495). According to the Gras standard, the screw position of the navigation group was significantly better than that of the freehand group ( P<0.05). Conclusion: Compared with the traditional freehand method, the computer navigation system assisted transiliac-transsacral screws internal fixation in the treatment of posterior pelvic ring injuries has advantages of improving the accuracy of screw implantation and reducing radiation damage and the time of screw implantation.
Subject(s)
Replantation , Surgical Wound Infection , Humans , Retrospective Studies , Body Mass IndexABSTRACT
BACKGROUND: Lenvatinib, a tyrosine kinase inhibitor (TKI) approved for the treatment of progressive and radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), is associated with significant adverse effects that can be partially mitigated through the development of novel drug formulations. The utilization of nanoparticles presents a viable option, as it allows for targeted drug delivery, reducing certain side effects and enhancing the overall quality of life for patients. This study aimed to produce and assess, both in vitro and in vivo, the cytotoxicity, biodistribution, and therapeutic efficacy of lenvatinib-loaded PLGA nanoparticles (NPs), both with and without decoration using antibody conjugation (cetuximab), as a novel therapeutic approach for managing aggressive thyroid tumors. METHODS: Poly(lactic-co-glycolic acid) nanoparticles (NPs), decorated with or without anti-EGFR, were employed as a lenvatinib delivery system. These NPs were characterized for size distribution, surface morphology, surface charge, and drug encapsulation efficiency. Cytotoxicity was evaluated through MTT assays using two cellular models, one representing normal thyroid cells (Nthy-ori 3-1) and the other representing anaplastic thyroid cells (CAL-62). Additionally, an in vivo xenograft mouse model was established to investigate biodistribution and therapeutic efficacy following intragastric administration. RESULTS: The NPs demonstrated success in terms of particle size, polydispersity index (PDI), zeta potential, morphology, encapsulation efficiency, and cetuximab distribution across the surface. In vitro analysis revealed cytotoxicity in both cellular models with both formulations, but only the decorated NPs achieved an ID50 value in CAL-62 cells. Biodistribution analysis following intragastric administration in xenografted thyroid mice demonstrated good stability in terms of intestinal barrier function and tumor accumulation. Both formulations were generally well tolerated without inducing pathological effects in the examined organs. Importantly, both formulations increased tumor necrosis; however, decorated NPs exhibited enhanced parameters related to apoptotic/karyolytic forms, mitotic index, and vascularization compared with NPs without decoration. CONCLUSIONS: These proof-of-concept findings suggest a promising strategy for administering TKIs in a more targeted and effective manner.
Subject(s)
Nanoparticles , Thyroid Neoplasms , Humans , Animals , Mice , Polylactic Acid-Polyglycolic Acid Copolymer , Cetuximab , Lactic Acid , Polyglycolic Acid , Glycols , Tissue Distribution , Iodine Radioisotopes , Quality of Life , Cell Line, Tumor , Thyroid Neoplasms/drug therapy , ErbB Receptors , Drug CarriersABSTRACT
BACKGROUND: To describe the characteristics of clinical manifestations of children with 2019 novel coronavirus (2019-nCoV) infection in Chongqing. METHODS: All 25 children with laboratory-confirmed 2019-nCoV infection by real-time reverse transcription-PCR (RNA-PCR) were admitted from the 4 designated treatment hospitals of 2019-nCoV in Chongqing from January 19 to March 12, 2020. Clinical data and epidemiologic history of these patients were retrospectively collected and analyzed. RESULTS: The diagnosis was confirmed through RNA-PCR testing. Among the 25 cases, 14 were males and 11 were females. The median age was 11.0 (6.3-14.5) years (range 0.6-17.0 years). All children were related to a family cluster outbreak, and 7 children (28%) with a travel or residence history in Hubei Province. These patients could be categorized into different clinical types, including 8 (32%) asymptomatic, 4 (16%) very mild cases and 13 (52%) common cases. No severe or critical cases were identified. The most common symptoms were cough (13 cases, 52%) and fever (6 cases, 24%). The duration time of clinical symptoms was 13.0 (8.0-25.0) days. In the 25 cases, on admission, 21 cases (84%) had normal white blood cell counts, while only 2 cases (8%) more than 10 × 10/L and 2 cases (8%) less than 4 × 10/L, respectively; 22 cases(88%) had normal CD4+ T lymphocyte counts, while in the remaining 3 cases(8%) this increased mildly; 23 cases had normal CD8+ T lymphocyte counts, while in the remaining 2 cases (8%) CD8+ T lymphocyte counts were mildly increased as well. All Lymphocyte counts were normal. There were no statistical differences of lab results between the groups of asymptomatic cases, mild cases and common cases. There were only 13 cases with abnormal CT imaging, most of which were located in the subpleural area of the bottom of the lung. All patients were treated with interferon, 6 cases combined with Ribavirin, and 12 cases combined with lopinavir or ritonavir. The days from onset to RNA turning negative was 15.20 ± 6.54 days. There was no significant difference of RNA turning negative between the groups of interferon, interferon plus ribavirin and interferon plus lopinavir or ritonavir treatment. All the cases recovered and were discharged from hospital. CONCLUSIONS: The morbidity of 2019-nCoV infection in children is lower than in adults and the clinical manifestations and inflammatory biomarkers in children are nonspecific and milder than that in adults. RNA-PCR test is still the most reliable diagnostic method, especially for asymptomatic patients.