is an herb medicine which has been utilized to treat malignant diseases for decades. The
extract (MTE) shows significant anti-proliferation activity against non-small cell lung cancer (NSCLC) cells, ...but the underlying mechanisms remain unclear. In this study, we explored the potential anti-proliferation mechanisms of MTE in NSCLC cells in relation to apoptosis as well as autophagy, which are two critical forms to control cancer cell survival and death.
The proliferation of H1975 and A549 cells was evaluated by MTT assay. Cell apoptosis was assessed by Annexin V and PI staining, Caspase 3 expression and activity. Autophagy flux proteins were detected by Western blot with or without autophagy inducer and inhibitor. Endogenous LC3-II puncta and LysoTracker staining were monitored by confocal microscopy. The formation of autophagic vacuoles was measured by acridine orange staining. ERK is a crucial molecule to interplay with cell autophagy and apoptosis. The role of ERK on cell apoptosis and autophagy influenced by MTE was determined in the presence of MEK/ERK inhibitor U0126.
The significant growth inhibition and apoptosis induction were observed in MTE treated NSCLC cells. MTE induced cell apoptosis coexisted with elevated Caspase 3 activity. MTE also impaired autophagic flux by upregulated LC3-II and p62 expression. Autophagy inducer EBSS could not abolish the impaired autophagic flux by MTE, while it was augmented in the presence of autophagy inhibitor Baf A1. The autophagosome-lysosome fusion was blocked by MTE via affecting lysosome function as evidenced by decreased expression of LAMP1 and Cathepsin B. The molecule ERK became hyperactivated after MTE treatment, but the MEK/ERK inhibitor U0126 abrogated autophagy inhibition and apoptosis induction caused by MTE, suggested that ERK signaling pathways partially contributed to cell death caused by MTE.
Our results demonstrate that MTE caused apoptosis induction as well as autophagy inhibition in NSCLC cells. The activated ERK is partially associated with NSCLC apoptotic and autophagic cell death in response to MTE treatment. The present findings reveal new mechanisms for the anti-tumor activity of MTE against NSCLC.
•NaCl endosmosis induces gelation of egg yolks, plasmas and granules.•The schematic behaviours of the plasmas and granules during salting are proposed.•Granule plays a role in the higher hardness ...texture of salted egg yolk gels.•Lipoproteins were disrupted into liberated constituents under NaCl treatment.•Phospholipids, neutral lipids and proteins interact with each other.
Changes in physico-chemical properties, microstructure, protein structures and intermolecular force of egg yolk, plasma and granule gels during salting were investigated, using low-field nuclear magnetic resonance (LF-NMR), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR) and chemical analysis. The results showed that the contents of soluble protein and free sulfhydryl increased and, with D2O treatment, T21 and T22 decreased in egg yolks and plasma salted for 2 d. The particles of egg yolks, plasma and granules in the later stage of salting were disrupted and they liberated their constituents (phospholipids, neutral lipids and proteins), which randomly aggregated. The treatment with NaCl changed the spatial structure of egg yolk proteins. The results suggested that the oil exudation of salted egg yolks was mainly due to structural changes in the low-density lipoproteins. Granules were shown to contribute to the higher hardness and gelation of salted egg yolks.
Type 2 diabetes mellitus (T2DM) is an important risk factor for Alzheimer's disease (AD). Glucagon‐like peptide‐1 (GLP‐1) and glucose‐dependent insulinotropic polypeptide (GIP) have been identified ...to be effective in T2DM treatment and neuroprotection. In this study, we further explored the effects of a novel unimolecular GLP‐1/GIP/Gcg triagonist on the cognitive behavior and cerebral pathology in the 7‐month‐old triple transgenic mouse model of AD (3xTg‐AD), and investigated its possible electrophysiological and molecular mechanisms. After chronic administration of the GLP‐1/GIP/Gcg triagonist (10 nmol/kg bodyweight, once daily, i.p.) for 30 days, open field, Y maze and Morris water maze tests were performed, followed by in vivo electrophysiological recording, immunofluorescence and Western blotting experiments. We found that the chronic treatment with the triagonist could improve long‐term spatial memory of 3xTg‐AD mice in Morris water maze, as well as the working memory in Y maze task. The triagonist also alleviated the suppression of long‐term potentiation (LTP) in the CA1 region of hippocampus. In addition, the triagonist significantly reduced hippocampal pathological damages, including amyloid‐β (Aβ) and phosphorylated tau aggregates, and upregulated the expression levels of S133p‐CREB, T286p‐CAMKII and S9p‐GSK3β in the hippocampus of the 3xTg‐AD mice. These results demonstrate for the first time that the novel GLP‐1/GIP/Gcg triagonist is efficacious in ameliorating cognitive deficits and pathological damages of 3xTg‐AD mice, suggesting that the triagonist might be potentially beneficial in the treatment of AD.
A new Ag
36
nanocluster with a closed electronic structure and eight valence electrons is reported, which has a similar structure to that of an open-shell Ag
34
nanocluster with three valence ...electrons, except that in the shell two (Ag-PPh
3
)
+
cations replace two S
2−
anions specifically. The fine structural modulation leads to various levels of activity for singlet oxygen photogeneration due to the distinct optical gaps of the nanoclusters.
A fine structural modulation occurred from a
Ag
34
nanocluster (3e) to a
Ag
36
nanocluster (8e), leading to varying levels of activity for singlet oxygen photogeneration due to the distinct optical gaps of the nanoclusters.
•Ultrasound can improve the gel properties of duck egg white protein gel.•Ultrasound can promote the hydrophobic interaction and hydrogen bond of egg white.•Synergetic phosphorylation/ultrasound can ...promote the crosslinking of egg white.•The secondary structures and gel structure of SUDEP become more stable.•Effect of synergetic phosphorylation/ultrasound is better than that of ultrasound.
To improve the gel properties of duck egg white gel and increase the industrial value of duck egg white, the mechanisms of ultrasound and synergetic phosphorylation/ultrasound treatments were examined in this study. It was found that as the ultrasound power increased, the surface hydrophobicity, hardness, and cohesiveness of the gel system increased, and the ζ-potential and water mobility decreased. Of the two treatments, phosphorylation/ultrasound had the strongest impact on the conformation and crystallinity of the gel system and promoted the formation of high molecular polymers. Both gel systems displayed enhanced compactness, stability, and gel strength because of the enhanced protein–protein interactions via hydrogen bonds and protein aggregation, and increased the content of intramolecular β-sheets following ultrasound treatment, and synergetic phosphorylation/ultrasound further improved the stability, water binding and gel properties. This experiment showed that ultrasound and, particularly, phosphorylation/ultrasound are effective methods to improve the gel properties of duck egg white. This study enhanced our understanding of the interactions of sodium pyrophosphate and egg white under ultrasound treatment, and promote the potential application of sodium pyrophosphate and ultrasound treatment of novel food products.
TG-rich lipoprotein (TRL)-related biomarkers, including TRL-cholesterol (TRL-C), remnant-like lipoprotein particle-cholesterol (RLP-C), and apoC-III have been associated with atherosclerosis. ...However, their prognostic values have not been fully determined, especially in patients with previous CAD. This study aimed to examine the associations of TRL-C, RLP-C, and apoC-III with incident cardiovascular events (CVEs) in the setting of secondary prevention of CAD. Plasma TRL-C, RLP-C, and total apoC-III were directly measured. A total of 4,355 participants with angiographically confirmed CAD were followed up for the occurrence of CVEs. During a median follow-up period of 5.1 years (interquartile range: 3.9–6.4 years), 543 (12.5%) events occurred. Patients with incident CVEs had significantly higher levels of TRL-C, RLP-C, and apoC-III than those without events. Multivariable Cox analysis indicated that a log unit increase in TRL-C, RLP-C, and apoC-III increased the risk of CVEs by 49% (95% CI: 1.16–1.93), 21% (95% CI: 1.09–1.35), and 40% (95% CI: 1.11–1.77), respectively. High TRL-C, RLP-C, and apoC-III were also independent predictors of CVEs in individuals with LDL-C levels ≤1.8 mmol/l (n = 1,068). The addition of RLP-C level to a prediction model resulted in a significant increase in discrimination, and all three TRL biomarkers improved risk reclassification. Thus, TRL-C, RLP-C, and apoC-III levels were independently associated with incident CVEs in Chinese CAD patients undergoing statin therapy.
Whether prediabetes mellitus (Pre-DM) alone or combined with hypertension is an independent risk factor for cardiovascular disease has not been fully clarified. This study aimed to further confirm ...whether the relation of Pre-DM to cardiovascular disease differs between individuals with or without hypertension. A total of 7121 consecutive patients with angina-like chest pain who received coronary angiography were evaluated and 4193 patients with angiography-proven stable, new-onset coronary artery disease were enrolled into the study. They were divided into 3 groups according to diabetes mellitus status and further stratified by hypertension. The severity of coronary artery disease was assessed by number of diseased vessels and Gensini score. All subjects were regularly followed up for the occurrence of the composite end points. Comparisons of coronary artery disease severity and outcomes were performed among these groups. During an average of 11 338 patient-years of follow-up, 434 (10.35%) cardiovascular events occurred. No significant difference was observed in coronary severity and composite end point events between Pre-DM and normal glucose regulation groups (both P>0.05). However, when hypertension was also incorporated as a stratifying factor, cardiovascular disease risk, assessed by coronary severity and clinical prognosis, was significantly elevated in Pre-DM plus hypertension and diabetes mellitus plus hypertension groups, compared with the reference group with normal glucose regulation and normal blood pressure (all P<0.05). The present study indicated that among patients with stable, new-onset coronary artery disease, the increased cardiovascular risk with Pre-DM is largely driven by the coexistence of hypertension rather than Pre-DM per se.
Objectives
Elevated thioredoxin‐interacting protein (TXNIP)‐induced pyroptosis contributes to the pathology of diabetic kidney disease (DKD). However, the molecular mechanisms in dysregulated TXNIP ...in DKD remain largely unclear.
Materials and methods
Transcriptomic analysis identified a novel long noncoding RNA—Prader Willi/Angelman region RNA, SNRPN neighbour (PWARSN)—which was highly expressed in a proximal tubular epithelial cell (PTEC) under high glucose conditions. We focused on revealing the functions of PWARSN in regulating TXNIP‐mediated pyroptosis in PTECs by targeting PWARSN expression via lentivirus‐mediated overexpression and CRISPR‐Cas9‐based knockout in vitro and overexpressing PWARSN in the renal cortex by AAV‐9 targeted injection in vivo. A number of molecular techniques disclosed the mechanisms of PWARSN in regulating TXNIP induced‐pyroptosis in DKD.
Results
TXNIP‐NOD‐like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome and PTEC pyroptosis were activated in the renal tubules of patients with DKD and in diabetic mice. Then we explored that PWARSN enhanced TXNIP‐driven PTECs pyroptosis in vitro and in vivo. Mechanistically, cytoplasmic PWARSN sponged miR‐372‐3p to promote TXNIP expression. Moreover, nuclear PWARSN interacted and facilitated RNA binding motif protein X‐linked (RBMX) degradation through ubiquitination, resulting in the initiation of TXNIP transcription by reducing H3K9me3‐enrichment at the TXNIP promoter. Further analysis indicated that PWARSN might be a potential biomarker for DKD.
Conclusions
These findings illustrate distinct dual molecular mechanisms for PWARSN‐modulated TXNIP and PTECs pyroptosis in DKD, presenting PWARSN as a promising therapeutic target for DKD.
Pyroptosis mediated by thioredoxin‐interacting protein (TXNIP) aggravates diabetic kidney disease (DKD), thus clarifying the key regulator of TXNIP‐induced cell pyroptosis may delay DKD progression. We unveiled a new long non‐coding RNA, Prader Willi/Angelman region RNA, SNRPN neighbour (PWARSN), which is especially expressed in proximal tubular epithelial cell (PTEC), plasma and urinary sediments samples from patients with DKD and regulated TXNIP‐induced PTECs pyroptosis in DKD. Mechanistically, PWARSN regulates TXNIP expression via a dual pathway: both by sponging cytoplasmic miR‐372‐3p and by interacting with nuclear RNA binding motif protein X‐linked (RBMX). Our findings suggest that PWARSN can be used as a biomarker and may be a potential target for DKD diagnosis and treatment.
The influence of high hydrostatic pressure (HHP) treatment at 150, 300, 450, and 600 MPa for 25 min on the physicochemical properties, structural properties, and in vitro digestibility of pea starch ...was studied. Compared to native and pea starch treated at 150–450 MPa, the morphology of pea starch at 600 MPa was completely destroyed and the particle size became larger, indicating complete gelatinization. The X‐ray diffraction results showed that the native pea starch was gradually changed from the C‐type into the B‐type pattern after 150–600 MPa HHP treatment. At 30–70°C, pea starch treated at 600 MPa had a higher water absorption index (p < 0.05), swelling power, and solubility than other samples did, but opposite results were obtained at 90°C. The rapid visco analyzer (RVA) results indicated that pea starch treated with high pressure at 600 MPa showed lower values of peak viscosity, trough, breakdown, final viscosity, and setback (p < 0.05), reflecting lower retrogradation. Gelatinization temperatures and enthalpy determined by differential scanning calorimetry (DSC) decreased with the increase of pressure. Furthermore, the in vitro digestibility of HHP treated pea starches was lower than that of native pea starch (p < 0.05). Therefore, it is an effective method for HHP treatment to modify the properties of pea starches.
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