Hesperidin inhibits the epithelial to mesenchymal transition induced by transforming growth factor-β1 in A549 cells through Smad signaling in the cytoplasm

Hesperidin, a natural compound, suppresses the epithelial-to-mesenchymal transition through the TGF-β1/ Smad signaling pathway. However, studies on the detailed effects and mechanisms of hesperidin are rare. The present study showed that, for A549 alveolar epithelial cells, the anti-proliferative effects of hesperidin occurred in a dose-dependent manner, with an IC50= 216.8 μM at 48 h. TGF-β1 was used to activate the Smad signaling pathway and induce the epithelial to mesenchymal transition in cells. Treatment with hesperidin or SB431542 was used for antagonism of Smad pathway activation. Hesperidin inhibited the increase in ɑ-SMA and Col1ɑ-1 and the decrease in E-cadherin in a dose-dependent manner from concentration of 20 μM to 60 μM, as assessed by both ELISA and Western blotting assays; however, there was no significant effect on cellular morphological alterations. Moreover, the Western blotting assay showed that, in the cytoplasm, hesperidin and SB431542 had no significant effect on the protein expression of Smad 2, 3, 4, or 7 as well as 2/3. However, 60 μM hesperidin and SB431542 significantly decreased p-Smad2/3 protein expression. From the above results, it is concluded that hesperidin can partly inhibit the epithelial to mesenchymal transition in human alveolar epithelial cells; the effect accounts for the blockage of the phosphorylation of Smad2/3 in the cytoplasm rather than a change in Smad protein production in the cytoplasm

Investigation of mycotoxins in grain and its products in Henan Province

Objective To understand the types and extent of mycotoxins in grains and its products sold in Henan Province. Methods During 2018-2019, 16 kinds of mycotoxins were detected by isotope dilution ultra high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The results were evaluated and analyzed according to GB 2761-2017 national food safety standard mycotoxin limit in food. Results Fumonisin, zearalenone, aflatoxin and deoxynivalenol were the main mycotoxins in 100 corn flour, corn dregs and corn kernels, the detection rate ranged from 0.0% to 95.7%. The detection rates of deoxynivalenol in 220 wheat flour, noodles and steamed bread were 78.0% (124/159), 64.3% (18/28) and 87.9% (29/33) respectively, and the content of other mycotoxins was very low or not detected. Conclusion There were different levels of mycotoxin pollution in grain and its products in Henan Province, especially fumonisin in corn and its products. It is necessary to carry out traceability investigation in time and take corresponding control measures as soon as possible

Prevalence of A2143G mutation of H. pylori-23S rRNA in Chinese subjects with and without clarithromycin use history

<p>Abstract</p> <p>Background</p> <p>A2143G mutation of <it>23S rRNA </it>gene of <it>H. pylori </it>results in clarithromycin (CLR) resistance. To investigate the prevalence of the CLR resistance-related A2143G mutation of the <it>H. pylori</it>-specific <it>23S rRNA </it>gene in Chinese subjects with and without CLR use history, 307 subjects received the treatment with amoxicillin and omeprazole (OA) and 310 subjects received a placebo in 1995, and 153 subjects received a triple therapy with OA and CLR (OAC) in 2000. DNA was extracted from fasting gastric juice at the end of the intervention trial in 2003. <it>H. pylori </it>infection was determined by <it>H. pylori</it>-specific <it>23S rRNA </it>PCR, ELISA, and¹³C-urea breath test assays. Mutations of the <it>23S rRNA </it>gene were detected by RFLP assays.</p> <p>Results</p> <p>The presence of <it>23S rRNA </it>due to <it>H. pylori </it>infection in the OA group remained lower than that in the placebo group 7.3 yrs after OA-therapy [51.1% (157/307) vs. 83.9% (260/310), p = 0.0000]. In the OAC group, the <it>23S rRNA </it>detection rate was 26.8% (41/153) three yrs after OAC-treatment. The A2143G mutation rate among the <it>23S rRNA</it>-positive subjects in the OAC group [31.7% (13/41)] was significantly higher than that in the OA group [10.2% (16/157)] and the placebo group [13.8% (36/260)]. The frequency of the AAGGG → CTTCA (2222–2226) and AACC → GAAG (2081–2084) sequence alterations in the OAC group was also significantly higher than those in the OA group and the placebo group.</p> <p>Conclusion</p> <p>Primary prevalence of the A2143G mutation was 10~14% among Chinese population without history of CLR therapy. Administration of CLR to eliminate <it>H. pylori </it>infection increased the prevalence of the A2143G mutation in Chinese subjects (32%) significantly.</p

Mechanisms of action of the BCL-2 inhibitor venetoclax in multiple myeloma: a literature review

Abnormal cellular apoptosis plays a pivotal role in the pathogenesis of Multiple Myeloma (MM). Over the years, BCL-2, a crucial anti-apoptotic protein, has garnered significant attention in MM therapeutic research. Venetoclax (VTC), a small-molecule targeted agent, effectively inhibits BCL-2, promoting the programmed death of cancerous cells. While VTC has been employed to treat various hematological malignancies, its particular efficacy in MM has showcased its potential for broader clinical applications. In this review, we delve into the intricacies of how VTC modulates apoptosis in MM cells by targeting BCL-2 and the overarching influence of the BCL-2 protein family in MM apoptosis regulation. Our findings highlight the nuanced interplay between VTC, BCL-2, and MM, offering insights that may pave the way for optimizing therapeutic strategies. Through this comprehensive analysis, we aim to lay a solid groundwork for future explorations into VTC’s clinical applications and the profound effects of BCL-2 on cellular apoptosis

Spin pinning effect to reconstructed oxyhydroxide layer on ferromagnetic oxides for enhanced water oxidation.

Producing hydrogen by water electrolysis suffers from the kinetic barriers in the oxygen evolution reaction (OER) that limits the overall efficiency. With spin-dependent kinetics in OER, to manipulate the spin ordering of ferromagnetic OER catalysts (e.g., by magnetization) can reduce the kinetic barrier. However, most active OER catalysts are not ferromagnetic, which makes the spin manipulation challenging. In this work, we report a strategy with spin pinning effect to make the spins in paramagnetic oxyhydroxides more aligned for higher intrinsic OER activity. The spin pinning effect is established in oxideFM/oxyhydroxide interface which is realized by a controlled surface reconstruction of ferromagnetic oxides. Under spin pinning, simple magnetization further increases the spin alignment and thus the OER activity, which validates the spin effect in rate-limiting OER step. The spin polarization in OER highly relies on oxyl radicals (O∙) created by 1st dehydrogenation to reduce the barrier for subsequent O-O coupling

The role of PALLD-STAT3 interaction in megakaryocyte differentiation and thrombocytopenia treatment

Impaired differentiation of megakaryocytes constitutes the principal etiology of thrombocytopenia. The signal transducer and activator of transcription 3 (STAT3) is a crucial transcription factor in regulating megakaryocyte differentiation, yet the precise mechanism of its activation remains unclear. PALLD, an actin-associated protein, has been increasingly recognized for its essential functions in multiple biological processes. This study revealed that megakaryocyte/plateletspecific knockout of PALLD in mice exhibited thrombocytopenia due to diminished platelet biogenesis. In megakaryocytes, PALLD deficiency led to impaired proplatelet formation and polyploidization, ultimately weakening their differentiation for platelet production. Mechanistic studies demonstrated that PALLD bound to STAT3 and interacted with its DNA-binding domain (DBD) and Src homology 2 (SH2) domain via Immunoglobulin domain 3 (Ig3). Moreover, the absence of PALLD attenuated STAT3 Y705 phosphorylation and impeded STAT3 nuclear translocation. Based on the PALLD-STAT3 binding sequence, we designed a peptide C-P3, which can facilitate megakaryocyte differentiation and accelerate platelet production in vivo. In conclusion, this study highlights the pivotal role of PALLD in megakaryocyte differentiation and proposes a novel approach for treating thrombocytopenia by targeting the PALLD-STAT3 interaction