Exploiting lignin-based nanomaterials for enhanced anticancer therapy: A comprehensive review and future direction.

Lignin, a renewable and abundant natural polymer, has emerged as a promising candidate for anticancer therapy due to its unique properties and biocompatibility. This review provides a comprehensive overview of recent advancements in the utilization of lignin-based nanomaterials for enhancing anticancer drug delivery and therapeutic outcomes. A detailed examination of the literature reveals several synthesis methods, including nanoprecipitation, microemulsion, and solvent exchange, which produce lignin nanoparticles with improved drug solubility and bioavailability. The anticancer mechanisms of lignin nanoparticles, such as the generation of reactive oxygen species (ROS), induction of apoptosis, and enhanced cellular uptake, are also explored. Lignin nanoparticles loaded with drugs like curcumin, doxorubicin, camptothecin, and resveratrol have demonstrated the ability to improve drug efficacy, selectively target cancer cells, overcome multidrug resistance, and minimize toxicity in both in vitro and in vivo studies. These nanoparticles have shown significant potential in suppressing tumor growth, inducing cell death through apoptotic pathways, and enhancing the synergistic effects of combination therapies, such as chemo-phototherapy. Future research directions include optimizing lignin nanoparticle formulations for clinical applications, refining targeted delivery mechanisms to cancer cells, and conducting thorough biocompatibility and toxicity assessments. Overall, this review highlights the significant progress made in utilizing lignin-based nanomaterials for cancer therapy and outlines promising areas for further exploration in this rapidly evolving field.

Aldehyde End-Capped Degradable Polyethylenes from Hydrogen-Controlled Ethylene/CO Copolymerization.

To access degradable polyolefin plastic, non-alternating copolymerization of ethylene (E) and carbon monoxide (CO) for producing polyethylene (PE) with in-chain ketones is particularly appealing; however, it still presents significant challenges such as molecular weight modulation (hydrogen response) and chain endgroup control (functional terminal). In this study, we achieved hydrogen-controlled E/CO non-alternating copolymerization using late transition metal catalysts. This process results in linear PEs containing the desired non-alternating in-chain keto groups (1.0-9.3 mol%) and with tunable molecular weights ranging from 43 to 195 kDa. In this reaction, H2 serves as a chain transfer agent, modulating the polymer's molecular weight, forming unique aldehyde endgroups and eliminating usual olefinic endgroups; CO undergoes non-alternating insertion into the PE chain, resulting in a strictly non-alternating structure (> 99%) for the keto-PE. The dispersed incorporation of in-chain keto groups retains bulk properties of PE and makes PE susceptible to photodegradation, which produces significantly lower molecular weight polymers and oligomers with unambiguous vinyl and acetyl terminals.

Artificial intelligence-based classification of breast nodules: a quantitative morphological analysis of ultrasound images.

Background: Accurate classification of breast nodules into benign and malignant types is critical for the successful treatment of breast cancer. Traditional methods rely on subjective interpretation, which can potentially lead to diagnostic errors. Artificial intelligence (AI)-based methods using the quantitative morphological analysis of ultrasound images have been explored for the automated and reliable classification of breast cancer. This study aimed to investigate the effectiveness of AI-based approaches for improving diagnostic accuracy and patient outcomes. Methods: In this study, a quantitative analysis approach was adopted, with a focus on five critical features for evaluation: degree of boundary regularity, clarity of boundaries, echo intensity, and uniformity of echoes. Furthermore, the classification results were assessed using five machine learning methods: logistic regression (LR), support vector machine (SVM), decision tree (DT), naive Bayes, and K-nearest neighbor (KNN). Based on these assessments, a multifeature combined prediction model was established. Results: We evaluated the performance of our classification model by quantifying various features of the ultrasound images and using the area under the receiver operating characteristic (ROC) curve (AUC). The moment of inertia achieved an AUC value of 0.793, while the variance and mean of breast nodule areas achieved AUC values of 0.725 and 0.772, respectively. The convexity and concavity achieved AUC values of 0.988 and 0.987, respectively. Additionally, we conducted a joint analysis of multiple features after normalization, achieving a recall value of 0.98, which surpasses most medical evaluation indexes on the market. To ensure experimental rigor, we conducted cross-validation experiments, which yielded no significant differences among the classifiers under 5-, 8-, and 10-fold cross-validation (P>0.05). Conclusions: The quantitative analysis can accurately differentiate between benign and malignant breast nodules.

Expression landscape of cancer-FOXP3 and its prognostic value in pancreatic adenocarcinoma.

FOXP3, a key identifier of Treg, has also been identified in tumor cells, which is referred to as cancer-FOXP3 (c-FOXP3). Human c-FOXP3 undergoes multiple alternative splicing events, generating several isoforms, like c-FOXP3FL and c-FOXP3Δ3. Previous research on c-FOXP3 often ignore its cellular source (immune or tumor cells) and isoform expression patterns, which may obscure our understanding of its clinical significance. Our immunohistochemistry investigations which conducted across 18 tumors using validated c-FOXP3 antibodies revealed distinct expression landscapes for c-FOXP3 and its variants, with the majority of tumors exhibited a predominantly expression of c-FOXP3Δ3. In pancreatic ductal adenocarcinoma (PDAC), we further discovered a potential link between nuclear c-FOXP3Δ3 in tumor cells and poor prognosis. Overexpression of c-FOXP3Δ3 in tumor cells was associated with metastasis. This work elucidates the expression pattern of c-FOXP3 in pan-cancer and indicates its potential as a prognostic biomarker in clinical settings, offering new perspectives for its clinical application.

Real-time imaging of ipsilateral parathyroid glands by retrograde injection of methylene blue into the superior thyroid artery: a new intraoperative parathyroid protection method.

BACKGROUND: Postoperative hypoparathyroidism caused by parathyroid injury is a problem faced by thyroid surgeons. The current technologies for parathyroid imaging all have some defects. METHODS: Patients with differentiated thyroid carcinoma (DTC) who underwent unilateral thyroidectomy plus ipsilateral central lymph node dissection were recruited. We dissected the main trunk of the superior thyroid artery entering the thyroid gland and placed the venous indwelling tube into the artery. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated. RESULTS: A total of 132 patients enrolled in this single-arm clinical trial, 105 of them completed retrograde catheterization via the superior artery. The sensitivity was 69.23 and 83.33% respectively. The specificity was 72.91 and 64.89%. The accuracy was 72.91 and 64.89%. The PPV was 85.71 and 81.08%. The NPV was 22.58 and 45.45%. There were no patients with allergic reactions to the methylene blue, or methylene blue toxicity. CONCLUSIONS: Retrograde injection of methylene blue via the superior thyroid artery is an effective and safe method to visualize parathyroid glands. This method can accurately locate the target organ by ultraselecting the blood vessel and injecting the contrast agent while avoiding background contamination and reducing the amount of contrast agent. TRIAL REGISTRATION: Clinical trial registration numbers and date of registration: ChiCTR2300077263、02/11/2023.

Single-atom iron boosts electrochemiluminescence for ultrasensitive carcinoembryonic antigen detection.

A simple and ultrasensitive sandwich-type electrochemiluminescence (ECL) immunosensor has been developed using porous three-dimensional gold nanoparticles (Au NPs) iron(Fe)-zinc(Zn) metal-organic frameworks (Au NPs-FeZn-MOFs@luminol) as high-efficiency ECL signal probes with Fe single-atom catalysts (SACs) (Fe-N-C SACs) as potentially advanced coreaction accelerators and dissolved oxygen as a coreaction agent to realize an H2O2-free amplification method for detecting carcinoembryonic antigen (CEA). The cathodic ECL of luminol, which was usually negligible, increased first. Because the Fe-N-C SACs exhibited an outstanding catalytic performance and a unique electronic structure, different reactive oxygen species (ROS) were generated via the oxygen reduction reaction. ROS oxidized the luminol anions to luminol anion radicals, preventing the time-consuming luminol electrochemical oxidation. Furthermore, the luminol anion radicals generated in situ reacted with ROS to produce potent cathodic ECL emissions. The immunosensor exhibited favorable analytical accuracy (detection range: 0.1 pg mL-1 - 80 ng mL-1), and its detection limit for serum samples was 0.031 pg mL-1 (S/N = 3). Consequently, the proposed strategy offers a new approach for early screening of CEA.

Identification of FOXP3+ epithelial cells contributing to pancreatic proliferation and angiogenesis.

Forkhead box protein 3 (FOXP3), traditionally recognized as a specific transcription factor for regulatory T cells (Tregs), has also been identified in various tumor epithelial cells (named as cancer-FOXP3, c-FOXP3). However, the natural state and functional role of FOXP3 positive tumor epithelial cells remain unknown. Monoclonal cells expressing varying levels of c-FOXP3 were isolated from established PANC-1 cells using limited dilution. Whole transcriptome sequencing and weighted gene co-expression network analysis (WGCNA) were conducted on these subsets, followed by in vitro and in vivo functional investigations. In addition, we identified c-FOXP3+E-cadherin- epithelial cells in human pancreatic cancer tissues after radical resection by immunofluorescence co-staining. We also investigated the connection between c-FOXP3+E-cadherin- epithelial cells and their clinicopathological features. Our study uncovered a distinct subset of c-FOXP3+ tumor epithelial cells characterized by reduced E-cadherin expression. C-FOXP3+E-cadherin- cells displayed significant proliferation potential and pro-angiogenic effect through the expression of chemokines, including C-X-C motif ligand 1 (CXCL1), C-X-C motif ligand 5 (CXCL5), and C-X-C motif ligand 8 (CXCL8). Notably, higher counts of c-FOXP3+E-Cadherin- cells correlated with poorer prognosis, lower tumor differentiation, lymph node metastasis, and vascular invasion in pancreatic ductal adenocarcinoma (PDAC). In conclusion, this work revealed the stable expression of FOXP3 in tumor epithelial cells, marking a distinct subset. C-FOXP3+E-cadherin- epithelial cells exhibit active proliferation and promote angiogenesis in a vascular endothelial growth factor A (VEGFA) independent manner. These findings provide novel insights into PDAC prognosis and therapeutic avenues.NEW & NOTEWORTHY In this study, we revealed a novel c-FOXP3+ tumor epithelial cell subset marked by diminished E-cadherin and stable FOXP3 expression. These subpopulations not only show robust proliferation and drive angiogenesis via CXCL1, CXCL5, and CXCL8, bypassing VEGFA pathways, but their heightened presence also correlates with adverse PDAC outcomes. By challenging traditional epithelial cell definitions and extending lymphocyte markers to these cells, our findings present innovative targets for PDAC treatment and enrich our understanding of cell biology.

Endoplasmic Reticulum Stress and Mitochondrial Stress in Drug-Induced Liver Injury.

Drug-induced liver injury (DILI) is a widespread and harmful disease closely linked to mitochondrial and endoplasmic reticulum stress (ERS). Globally, severe drug-induced hepatitis, cirrhosis, and liver cancer are the primary causes of liver-related morbidity and mortality. A hallmark of DILI is ERS and changes in mitochondrial morphology and function, which increase the production of reactive oxygen species (ROS) in a vicious cycle of mutually reinforcing stress responses. Several pathways are maladapted to maintain homeostasis during DILI. Here, we discuss the processes of liver injury caused by several types of drugs that induce hepatocyte stress, focusing primarily on DILI by ERS and mitochondrial stress. Importantly, both ERS and mitochondrial stress are mediated by the overproduction of ROS, destruction of Ca2+ homeostasis, and unfolded protein response (UPR). Additionally, we review new pathways and potential pharmacological targets for DILI to highlight new possibilities for DILI treatment and mitigation.

The Circadian System Is Essential for the Crosstalk of VEGF-Notch-mediated Endothelial Angiogenesis in Ischemic Stroke.

Ischemic stroke is a major public health problem worldwide. Although the circadian clock is involved in the process of ischemic stroke, the exact mechanism of the circadian clock in regulating angiogenesis after cerebral infarction remains unclear. In the present study, we determined that environmental circadian disruption (ECD) increased the stroke severity and impaired angiogenesis in the rat middle cerebral artery occlusion model, by measuring the infarct volume, neurological tests, and angiogenesis-related protein. We further report that Bmal1 plays an irreplaceable role in angiogenesis. Overexpression of Bmal1 promoted tube-forming, migration, and wound healing, and upregulated the vascular endothelial growth factor (VEGF) and Notch pathway protein levels. This promoting effect was reversed by the Notch pathway inhibitor DAPT, according to the results of angiogenesis capacity and VEGF pathway protein level. In conclusion, our study reveals the intervention of ECD in angiogenesis in ischemic stroke and further identifies the exact mechanism by which Bmal1 regulates angiogenesis through the VEGF-Notch1 pathway.

Effects of overexpression of histone H3K9me3 demethylase on development of porcine cloned embryos.

The abnormal modification of histone is an important factor restricting development of porcine cloned embryos. Overexpression of histone H3K9me3 demethylase KDM4 family can effectively improve the developmental efficiency of cloned embryos. In order to explore the effects of overexpression of H3K9me3 demethylase on the development of porcine cloned embryos, KDM4A mRNA and KDM4D mRNA were injected respectively into porcine cloned embryos at the 1-cell stage and 2-cell stage to detect the blastocyst rate; 2-cell stage cloned embryos injected with KDM4A mRNA and embryo injection water (the control group) at the 1-cell stage were collected to detect the expression level of H3K9me3, and 4-cell stage cloned embryos were collected for single cell transcriptome sequencing, then the sequencing data was analyzed with KEGG and GO. The results showed that the blastocyst rate of porcine cloned embryos injected with KDM4A mRNA at 1-cell stage was significantly higher than that of the control group (25.32 ± 0.74% vs 14.78 ± 0.87%), while cloned embryos injected with KDM4D mRNA had a similar blastocyst rate with cloned embryos in control group (16.27 ± 0.77% vs 14.78 ± 0.87%). Porcine cloned embryos injected with KDM4A mRNA and KDM4D mRNA at 2-cell stage had a similar blastocyst rate with cloned embryos in control group (32.18 ± 1.67%, 30.04 ± 0.91% vs 31.22 ± 1.40%). The expression level of H3K9me3 in cloned embryos injected with KDM4A mRNA at 1-cell stage was lower than that in control group. There were 133 differentially expressed genes detected by transcriptome sequencing, including 52 up-regulated genes and 81 down-regulated genes. Pathways enriched by GO analyses were mainly related to protein localization. Pathways enriched by KEGG analyses were related to cellular senescence and acute myeloid leukemia. These results suggest that overexpression of histone H3K9me3 demethylase KDM4A can significantly improve the developmental efficiency of porcine cloned embryos.

New Set of Isobaric Labeling Reagents for Quantitative 16Plex Proteomics.

Peptide labeling by isobaric tags is a powerful approach for the relative quantitative analysis of proteomes in multiple groups. There has been a revolution in the innovation of new isobaric reagents; however, great effort is being made to expand simultaneous labeling groups to identify more labeled peptides and reduce reporter ion signal suppression. We redesigned the original chemical structure of the deuterium isobaric amine-reactive tag developed in our laboratory. We optimized the synthetic pathway to create a new set of 16-plex isobaric tags (IBT-16plex). The novel reagent enabled almost complete labeling of peptides within 90 min, with all labeling reporter ions exhibiting comparable MS/MS signals. Compared to a typical 16plex reagent, TMTpro-16plex, the peptides and proteins identified by IBT-16plex in trypsinized HeLa cells were significantly increased by 14.8 and 8.6%, respectively. Moreover, differences in peptide abundance within 10-fold among multiple groups were barely suppressed in IBT-16plex, whereas the dynamic range in TMTpro-16plex-labeled groups was smaller. After quantitative examination of MCF7 cell proteins, IBT-16plex was confirmed as feasible and useful for evaluating protein responses of glucose-starved MCF7 cells to a glucose-rich medium.

Identification of Important Factors Causing Developmental Arrest in Cloned Pig Embryos by Embryo Biopsy Combined with Microproteomics.

The technique of pig cloning holds great promise for the livestock industry, life science, and biomedicine. However, the prenatal death rate of cloned pig embryos is extremely high, resulting in a very low cloning efficiency. This limits the development and application of pig cloning. In this study, we utilized embryo biopsy combined with microproteomics to identify potential factors causing the developmental arrest in cloned pig embryos. We verified the roles of two potential regulators, PDCD6 and PLK1, in cloned pig embryo development. We found that siRNA-mediated knockdown of PDCD6 reduced mRNA and protein expression levels of the pro-apoptotic gene, CASP3, in cloned pig embryos. PDCD6 knockdown also increased the cleavage rate and blastocyst rate of cloned porcine embryos. Overexpression of PLK1 via mRNA microinjection also improved the cleavage rate of cloned pig embryos. This study provided a new strategy to identify key factors responsible for the developmental defects in cloned pig embryos. It also helped establish new methods to improve pig cloning efficiency, specifically by correcting the expression pattern of PDCD6 and PLK1 in cloned pig embryos.

Amphiregulin Supplementation During Pig Oocyte In Vitro Maturation Enhances Subsequent Development of Cloned Embryos by Promoting Cumulus Cell Proliferation.

The oocyte in vitro maturation (IVM) technique is important in animal husbandry, biomedicine, and human-assisted reproduction. However, the developmental potential of in vitro matured oocytes is usually lower than that of in vivo matured (IVVM) oocytes. Amphiregulin (AREG) is an EGF-like growth factor that plays critical roles in the maturation and development of mammalian oocytes. This study investigated the effects of AREG supplementation during pig oocyte IVM on the subsequent development of cloned embryos. The addition of AREG to pig oocyte IVM medium improved the developmental competence of treated oocyte-derived cloned embryos by enhancing the expansion and proliferation of cumulus cells (CCs) during IVM. The positive effect of AREG on enhancing the quality of IVVM pig oocytes might be due to the activation of proliferation-related pathways in CCs by acting on the AREG receptor. The present study provides an AREG treatment-based method to improve the developmental competence of cloned pig embryos.

Effect of ALA-PDT on inhibition of oral precancerous cell growth and its related mechanisms.

BACKROUND: Early treatment of oral precancerous lesions is considered as a key strategy for in oral carcinogenesis prevention. Increasing evidence has suggested that the transforming growth factor beta (TGF-ß) signaling pathway is tightly involved in the process of oral-carcinogenesis. In this study, we investigated the inhibition effect and potential mechanism of 5-aminolaevulinic acid photodynamic therapy (ALA-PDT) in human oral precancerous cells via TGF-ß pathway. MATERIALS AND METHODS: Here, the dysplastic oral keratinocyte (DOK) cells were incubated with ALA concentration of 1 mM/mL for 4 h and then irradiated with a Helium-Neon (He-Ne) ion laser at 633 nm (200 mW/cm2). The control cells were cultured in Dulbecco's modified Eagle's medium (DMEM) medium. We analyzed the differentially expressed genes and correlated pathways in oral precancerous cells following ALA-PDT using Affymetrix microarrays. TGF-ß pathway was analyzed by quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting. Bioinformatics analysis was performed to evaluate the expression of TGF-ß1 in human oral cancer samples and adjacent normal samples. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), flow cytometry, 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA), and wound healing assay were used to assess the effects of ALA-PDT plus TGF-ß receptor inhibitor (LY2109761) in DOK cells. RESULTS: The TGF-ß signaling could exert in suppressive effects on DOK cells after ALA-PDT. The cell proliferation and migration rate of DOK cells was significantly reduced and apoptosis and ROS generation induced more effectively by ALA-PDT combined with LY2109761. Furthermore, cell cycle analysis revealed that the combined treatment resulted in G0/G1 phase arrest. CONCLUSIONS: ALA-PDT suppresses the growth of oral precancerous cells by regulating the TGF-ß signaling pathway, and its suppressive effect was enhanced using LY2109761. These results indicate that it could be a promising alternative treatment against oral precancerous lesions.

Response Prediction to Concurrent Chemoradiotherapy in Esophageal Squamous Cell Carcinoma Using Delta-Radiomics Based on Sequential Whole-Tumor ADC Map.

Purpose: The purpose of this study was to investigate the association between the radiomics features (RFs) extracted from a whole-tumor ADC map during the early treatment course and response to concurrent chemoradiotherapy (cCRT) in patients with esophageal squamous cell carcinoma (ESCC). Methods: Patients with ESCC who received concurrent chemoradiotherapy were enrolled in two hospitals. Whole-tumor ADC values and RFs were extracted from sequential ADC maps before treatment, after the 5th radiation, and after the 10th radiation, and the changes of ADC values and RFs were calculated as the relative difference between different time points. RFs were selected and further imported to a support vector machine classifier for building a radiomics signature. Radiomics signatures were obtained from both RFs extracted from pretreatment images and three sets of delta-RFs. Prediction models for different responders based on clinical characteristics and radiomics signatures were built up with logistic regression. Results: Patients (n=76) from hospital 1 were randomly assigned to training (n=53) and internal testing set (n=23) in a ratio of 7 to 3. In addition, to further test the performance of the model, data from another institute (n=17) were assigned to the external testing set. Neither ADC values nor delta-ADC values were correlated with treatment response in the three sets. It showed a predictive effect to treatment response that the AUC values of the radiomics signature built from delta-RFs over the first 2 weeks were 0.824, 0.744, and 0.742 in the training, the internal testing, and the external testing set, respectively. Compared with the evaluated response, the performance of response prediction in the internal testing set was acceptable (p = 0.048). Conclusions: The ADC map-based delta-RFs during the early course of treatment were effective to predict the response to cCRT in patients with ESCC.

Global Quantification of Glutathione S-Transferases in Human Serum Using LC-MS/MS Coupled with Affinity Enrichment.

The members of the glutathione S-transferase (GST) superfamily often exhibit functional overlap and can compensate for each other. Their concentrations in serum are considered as disease biomarkers. A global and quantitative evaluation of serum GSTs is therefore urgent, but there is a lack of efficient approaches due to technological limitations. GSH magnetic beads were examined for their affinity to enrich GSTs in serum, and the enriched GSTs were quantitatively targeted using a Q Exactive HF-X mass spectrometer in parallel reaction monitoring (PRM) mode. To optimize the quantification of GST peptides, sample types, trypsin digestion, and serum loading were carefully assessed; a biosynthetic method was employed to generate isotope-labeled GST peptides, and instrumental parameters were systematically optimized. A total of 134 clinical sera were collected for GST quantification from healthy donors and patients with four liver diseases. Using the new approach, GSTs in healthy sera were profiled: 14 GST peptides were quantified, and the abundance of five GST families was ranked GSTM > GSTP > GSTA > MGST1 > GSTT1, ranging from 0.1 to 4 pmol/L. Furthermore, combining the abundance of multiple GST peptides could effectively distinguish different types of liver diseases. Quantification of serum GSTs through targeted proteomics, therefore, has apparent clinical potential for disease diagnosis.

Selective branch formation in ethylene polymerization to access precise ethylene-propylene copolymers.

Polyolefins with branches produced by ethylene alone via chain walking are highly desired in industry. Selective branch formation from uncontrolled chain walking is a long-standing challenge to generate exclusively branched polyolefins, however. Here we report such desirable microstructures in ethylene polymerization by using sterically constrained α-diimine nickel(II)/palladium(II) catalysts at 30 °C-90 °C that fall into industrial conditions. Branched polyethylenes with exclusive branch pattern of methyl branches (99%) and notably selective branch distribution of 1,4-Me2 unit (86%) can be generated. The ultrahigh degree of branching (>200 Me/1000 C) enables the well-defined product to mimic ethylene-propylene copolymers. More interestingly, branch distribution is predictable and computable by using a simple statistical model of p(1-p)n (p: the probability of branch formation). Mechanistic insights into the branch formation including branch pattern and branch distribution by an in-depth density functional theory (DFT) calculation are elucidated.

N6-methyladenine- induced LINC00667 promoted breast cancer progression through m6A/KIAA1429 positive feedback loop.

Increasing evidence supports that N6-methyladenine (m6A) and long noncoding RNAs (lncRNAs) both act as master regulators involved in breast cancer (BC) tumorigenesis at epigenetic modification level. Here, our research tries to unveil the interaction of m6A and lncRNAs on BC progression and explore the underlying regulatory mechanism. In the current study, we found that LINC00667 was m6A-modified lncRNA, which was up-regulated upon the overexpression of KIAA1429. The high expression of LINC00667 was correlated with the prognosis of BC patients. Bio-functional assays indicated that LINC00667 promoted the proliferation and migration of BC cells. Mechanistic assays illustrated that KIAA1429 targeted the m6A modification site of LINC00667 and enhanced its mRNA stability. Moreover, LINC00667 positively regulated the KIAA1429 via sponging miR-556-5p, forming a KIAA1429/m6A/LINC00667/miR-556-5p feedback loop. Collectively, the central findings of our study suggest that KIAA1429-induced LINC00667 exerted its functions as an oncogene in BC progression through m6A-dependent feedback loop.

Endothelial cell-derived SSAO can increase MLC20 phosphorylation in VSMCs.

Vascular hyporesponsiveness in the shock decompensation period is an important factor leading to death. Myosin light chain 20 (MLC20) is the main effector protein that regulates vascular reactivity. However, whether the change in semicarbazide-sensitive amine oxidase (SSAO) expression during hypoxia can change the MLC20 phosphorylation level, and its underlying mechanism were not clear. The amine oxidase copper containing 3 (AOC3) overexpressing adenovirus vector was constructed and transfected into rat intestinal microvascular endothelial cells (RIMECs) to overexpress SSAO, and the RIMECs were co-cultured with rat intestinal microvascular smooth muscle cells (RIMSCs). The changes in SSAO/inducible nitric oxide synthase (iNOS)/Rho associate coiled-coil containing protein kinase 1 (ROCK1) expression levels and MLC20 phosphorylation level were detected. Here we found that the increased SSAO by AOC3 overexpression can decrease the iNOS expression level and its activity after hypoxia. In addition, RIMSCs co-cultured with RIMECs overexpressed with AOC3 gene had significantly higher ROCK1 protein level and MLC20 phosphorylation level than RIMSCs co-cultured with normal RIMECs. Our study demonstrated that SSAO overexpression can significantly inhibit iNOS activity, promote RhoA/ROCK pathway activation, and increase the phosphorylation level of MLC20, which might be the potential mechanism in relieving the vascular hyporesponsiveness during shock decompensation.

Poria cocos polysaccharide attenuates damage of nervus in Alzheimer's disease rat model induced by D-galactose and aluminum trichloride.

Poria cocos polysaccharide (PCP) is a compound from Poria cocos, and which is used as a classical tonic agent. This article aims to investigate the effects of PCP on neuronal damage of hippocampus and cognitive function in a rat model of Alzheimer's disease induced by D-galactose and aluminum trichloride. Oxiracetam (ORC) was used as a positive drug in this experiment. The rats were treated with PCP at doses of 100, 200 and 300 mg/kg/day for 30 days and ORC at dose of 346 mg/kg/day after modeling. The results of behavioral test showed that PCP could prevent cognitive decline in Alzheimer's disease rats as assessed by Y-maze test and Morris water maze test. Results of hippocampus slices showed that neurons were integrated and regularly arranged in the groups, which were administered along with PCP. Moreover, PCP could reduce neuronal apoptosis in hippocampus of Alzheimer's disease rats. Furthermore, the activities of superoxide dismutase in the hippocampus were elevated by PCP administration, while acetyl cholinesterase, reactive oxygen, malondialdehyde and inflammatory factors levels were reduced. In addition, we found PCP could attenuate MAPK/NF-κB signal pathway in the hippocampus. All results illustrated that PCP could exert neuroprotective effects at least partly through alleviating oxidative stress, apoptosis, inflammation and inhibiting the MAPK/NF-κB pathway in Alzheimer's disease rats induced by D-galactose and aluminum trichloride.