ARTICLE | doi:10.20944/preprints202309.1748.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Glioma; peroxisome; PEX5; prognosis; immune microenvironment
Online: 26 September 2023 (07:16:44 CEST)
Gliomas, the most prevalent and lethal form of brain cancer, are known to exhibit metabolic alterations that facilitate tumor growth, invasion, and resistance to therapies. Peroxisomes, essential organelles responsible for fatty acid oxidation and reactive oxygen species (ROS) homeostasis, rely on the receptor PEX5 for the import of metabolic enzymes into their matrix. However, the prognostic significance of PEX5 for glioma patients remains unclear. We developed a robust prognosis model based on PEX5-dependent signature. This signature not only serves as a robust prognosis model capable of accurately predicting outcomes for glioma patients but also effectively distinguishes several clinicopathological features, including the grade, isocitrate dehydrogenase (IDH) mutation, and 1p19q codeletion status. Furthermore, we developed a nomogram that integrates the prognostic model with other clinicopathological factors, demonstrating highly accurate performance in estimating patient survival. Patients classified into the high-risk group based on our prognostic model exhibit an immunosuppressive microenvironment. Finally, we validated that the peroxisomal localization of the signature genes depends on PEX5 and demonstrated that PEX5 is required for cell growth, migration and invasion of glioma cells. These findings identify the PEX5-dependent signature as a promising prognostic tool for gliomas.
Subject: Biology And Life Sciences, Plant Sciences Keywords: physiological indicators; reflectance spectra; Suaeda salsa; salt stress; coastal wetland
Online: 17 March 2020 (04:17:29 CET)
In order to understand the response mechanism between plant stress, physiological indicators and hyperspectral indices, pot experiments were conducted on Suaeda salsa seedlings collected from a coastal wetland area to reveal the effects of salt stress on the physiological indicators and reflectance spectra of Suaeda salsa at the canopy and leaf level. The Suaeda salsa seedlings were exposed to seven salt treatments of different concentrations (0 mmol/L (control), 50 mmol/L, 100 mmol/L, 200 mmol/L, 300 mmol/L, 400 mmol/L, and 600 mmol/L) in natural conditions. The physiological indicators of plant height, fresh weight, dry weight, leaf succulence, chlorophyll content, and carotenoid content were measured, in addition to the reflectance spectra of Suaeda salsa at both the canopy and leaf level. Firstly, the effects of salt stress on the physiological indicators and reflectance spectra were analyzed by the qualitative and quantitative methods. Then, physiological indicators sensitive to salt stress were further retrieved. Afterwards hyperspectral indices such as a/b and ((a-b)/(a+b) ) sensitive to salt stress were also extracted by one-way analysis of variance (ANOVA) and Student-Newman-Keuls (S-N-K) comparison test. Our results showed that plant height, root length, leaf succulence, biomass, Chl-a, and Chl-b were sensitive to salt stress, while carotenoids (Car) and relative water content on the root were not significantly affected by salt stress. At the salt concentration of 200 mmol/L, plant height, biomass, relative water content, leaf succulence peaked. With enhanced salt stress, physiological indicators decreased. The first-order derivative spectral reflectance has the highest correlation with salt stress, compared to the control. The spectral index most sensitive to the salt stress at the canopy level is (D903−D851)/(D903+D851), for which the multiple determination coefficient (r2) is 0.9216. While the most sensitive spectral index to the salt stress is (D442−D667)/(D442+D667) at the leaf level, for which the r2 is −0.898. In summary, the results indicated that there exists the quantitative relationship between the physiological indicators and spectra reflectance under salt stress and hyperspectral plant indices can effectively estimate the degree of salt stress. The inconsistency between the diagnostic hyperspectral plant indices at the canopy and leaf levels may be caused by the observation conditions, canopy structure.
ARTICLE | doi:10.20944/preprints201810.0489.v1
Subject: Physical Sciences, Biophysics Keywords: diabetes mellitus; blood glucose; kidney; diabetic neuropathy; pancreas
Online: 22 October 2018 (10:45:08 CEST)
This present study was designed to find out whether the acankoreagenin showed the antidiabetic and renoprotective effects in streptozotocin (STZ)-induced diabetic nephropathy (DN) rats. Type I diabetes was induced by a single intraperitoneal injection of STZ (70 mg/kg). At the end of the experiment, rats were euthanized and serum/plasma was separated for the determination of glucose, insulin, glycated hemoglobin A1c (HbA1c), C-peptide, biochemical parameters, and kidney function. One kidney was used for determining glutathione, superoxide dismutas, malondialdehyde, and tumor necrosis factor-alpha levels. The other kidney and pancreas were used for histopathological studies and immunohistochemical measurement of transforming growth factor beta (TGF-β) or NF-κB. Acankoreagenin (2 mg/kg) treatments led to a significant reduction in blood glucose assessed via oral glucose tolerance test (OGTT) in diabetic rats at 2 h. The treatment also resulted in improved body weight, decreased HbA1c, restored lipid profile, and renal oxidative stress. By inhibiting NF-κB, the release of proinflammatory cytokines was suppressed and by inhibiting TGF-β, the renal fibrosis was suppressed in STZ-induced diabetic rat model. Histopathological injury was also observed in pancreatic and renal tissues. These findings support the beneficial effect of acankoreagenin treatment in DN, which could be attributed to its antidiabetic and renoprotective effects.
ARTICLE | doi:10.20944/preprints202209.0442.v1
Subject: Biology And Life Sciences, Biophysics Keywords: TDP-43; Liquid-liquid phase separation; Solution-state NMR
Online: 28 September 2022 (12:22:40 CEST)
Liquid-liquid phase separation (LLPS) of proteins has been found ubiquitously in eukaryotic cells, critical in the controlling of many biological processes through forming a temporary condensed phase with different bimolecular components. TDP-43 is recruited to stress granules in cells and is the main component of TDP-43 granules and proteinaceous amyloid inclusions in patients with amyotrophic lateral sclerosis (ALS). TDP-43 low complexity domain (LCD) is able to demix in solution forming the protein condensed droplets. The molecular interactions regulating its LLPS were investigated at the protein fusion equilibrium stage, where the droplets stopped growing. We found the molecules in the droplet were still liquid-like but with enhanced intermolecular helix-helix interaction in the LCD. The protein would start to aggregate after about 200 minutes of lag time and aggregate slower than at the condition when the protein does not phase separate or the molecules have a reduced intermolecular helical interaction. A structural transition intermediate towards protein aggregation was also discovered involving a decrease of the intermolecular helix-helix interaction and a reduction in the helicity. Therefore, LLPS and the intermolecular helical interaction could help maintain the stability of TDP-43 LCD.