Recent advances in membrane technologies applied in oil-water separation.

Effective treatment of oily wastewater, which is toxic and harmful and causes serious environmental pollution and health risks, has become an important research field. Membrane separation technology has emerged as a key area of investigation in oil-water separation research due to its high separation efficiency, low costs, and user-friendly operation. This review aims to report on the advances in the research of various types of separation membranes around emulsion permeance, separation efficiency, antifouling efficiency, and stimulus responsiveness. Meanwhile, the challenges encountered in oil-water separation membranes are examined, and potential research avenues are identified.

Lotus Leaf Extract Alleviates Lipopolysaccharide-Induced Intestinal Injury in Mice by Regulating Oxidative Stress and Inflammation.

Inflammatory bowel disease, a disease featured by intestinal epithelial barrier destruction and dysfunction, has been a constant threat to animal health. The primary objective of this research was to assess the impact of the extract derived from lotus leaves (LLE) on lipopolysaccharide (LPS) induced damage to the intestines in mice, as well as to investigate the fundamental mechanism involved. The LLE was prepared using ultrasonic extraction in this experiment, and the LLE total flavonoid content was 117.02 ± 10.73 mg/g. The LLE had strong antioxidant activity in vitro, as assessed by 2, 2-diphenyl-1-picrylhydrazyl, ferric reducing antioxidant power, and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) methods. In the vivo experiment, different doses of LLE (50, 100, and 200 mg/kg) were administered for 2 weeks before LPS treatment in mice. The results revealed that LLE alleviates intestinal tissue damage in LPS-induced mice. In the jejunum tissue, LLE significantly upregulated mRNA and protein expression levels of tight junction proteins, such as ZO-1, occludin, and claudin-1, and decreased the contents of the inflammatory cytokines, interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α. Furthermore, the malondialdehyde and lactate dehydrogenase contents increased by LPS in the liver were significantly reduced after administration of LLE, and the total antioxidant capacity, superoxide dismutase, and reduced glutathione decreased by LPS were remarkably increased by LLE. It was found that LLE could relieve LPS-induced oxidative stress by upregulating mRNA and protein expression of Nrf2 and HO-1 in jejunum tissue. In conclusion, LLE alleviates LPS-induced intestinal damage through regulation of the Nrf2/HO-1 signal pathway to alleviate oxidative stress, reducing inflammatory factors and increasing the expression of tight junction proteins in mice.

Impact of thermal treatment on proanthocyanidin-pectin binary complexes: Insights from structural, rheological, antioxidant, and astringent properties.

In this study, the effects of thermal treatments on the structural, rheological, water mobility, antioxidant, and astringency properties of proanthocyanidin (PA)-pectin binary complexes were investigated. Thermal treatments (25, 63, or 85 °C) significantly decreased the particle size but increased the molecular weight of PA-pectin complexes, which indicated that heating altered the intermolecular and intramolecular interactions between PA and pectin. The thermal treatments reduced the apparent viscosity of both pectin and PA-pectin complexes, but the presence of proanthocyanidins (PAs) increased the apparent viscosity and water mobility of the PA-pectin complexes. Antioxidant activity analysis showed that the presence of pectin slightly reduced the antioxidant activity of the PAs, but there were no significant changes in the total phenolic content and antioxidant activity after thermal treatment. Finally, we found that pectin reduced the astringency of the PAs by forming PA-pectin complexes. Moreover, the thermal treatments also significantly reduced the astringency of the PA-pectin complexes.

Human umbilical cord-derived mesenchymal stem cell transplantation supplemented with curcumin improves the outcomes of ischemic stroke via AKT/GSK-3ß/ß-TrCP/Nrf2 axis.

BACKGROUND: Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) engraftment is a promising therapy for acute ischemic stroke (AIS). However, the harsh ischemic microenvironment limits the therapeutic efficacy of hUC-MSC therapy. Curcumin is an anti-inflammatory agent that could improve inflammatory microenvironment. However, whether it enhances the neuroprotective efficacy of hUC-MSC transplantation is still unknown. In the present study, we investigated the therapeutic efficacy and the possible mechanism of combined curcumin and hUC-MSC treatment in AIS. METHODS: Middle cerebral artery occlusion (MCAO) mice and oxygen glucose deprivation (OGD) microglia were administrated hUC-MSCs with or without curcumin. Neurological deficits assessment, brain water content and TTC were used to assess the therapeutic effects of combined treatment. To elucidate the mechanism, MCAO mice and OGD microglia were treated with AKT inhibitor MK2206, GSK3ß activator sodium nitroprusside (SNP), GSK3ß inhibitor TDZD-8 and Nrf2 gene knockout were used. Immunofluorescence, flow cytometric analysis, WB and RT-PCR were used to evaluate the microglia polarization and the expression of typical oxidative mediators, inflammatory cytokines and the AKT/GSK-3ß/ß-TrCP/Nrf2 pathway protein. RESULTS: Compared with the solo hUC-MSC-grafted or curcumin groups, combined curcumin-hUC-MSC therapy significantly improved the functional performance outcomes, diminished the infarct volumes and the cerebral edema. The combined treatment promoted anti-inflammatory microglia polarization via Nrf2 pathway and decreased the expression of ROS, oxidative mediators and pro-inflammatory cytokines, while elevating the expression of the anti-inflammatory cytokines. Nrf2 knockout abolished the antioxidant stress and anti-inflammation effects mediated with combined treatment. Moreover, the combined treatment enhanced the phosphorylation of AKT and GSK3ß, inhibited the ß-TrCP nucleus translocation, accompanied with Nrf2 activation in the nucleus. AKT inhibitor MK2206 activated GSK3ß and ß-TrCP and suppressed Nrf2 phosphorylation in nucleus, whereas MK2206 with the GSK3ß inhibitor TDZD-8 reversed these phenomena. Furthermore, combined treatment followed by GSK3ß inhibition with TDZD-8 restricted ß-TrCP nucleus accumulation, which facilitated Nrf2 expression. CONCLUSIONS: We have demonstrated that combined curcumin-hUC-MSC therapy exerts anti-inflammation and antioxidant stress efficacy mediated by anti-inflammatory microglia polarization via AKT/GSK-3ß/ß-TrCP/Nrf2 axis and an improved neurological function after AIS.

A Novel Nomogram for Predicting Malignant Cerebral Edema After Endovascular Thrombectomy in Acute Ischemic Stroke: A Retrospective Cohort Study.

BACKGROUND: Malignant cerebral edema (MCE) is a common and feared complication after endovascular thrombectomy (EVT) in acute ischemic stroke (AIS). This study aimed to establish a nomogram to predict MCE in anterior circulation large vessel occlusion stroke (LVOS) patients receiving EVT in order to guide the postoperative medical care in the acute phase. METHODS: In this retrospective cohort study, 381 patients with anterior circulation LVOS receiving EVT were screened from 636 hospitalized patients with LVOS at 2 stroke medical centers. Clinical baseline data and imaging data were collected within 2-5 days of admission to the hospital. The patients were divided into 2 groups based on whether MCE occurred after EVT. Multivariate logistic regression analysis was used to evaluate the independent risk factors for MCE and to establish a nomogram. RESULTS: Sixty-six patients out of 381 (17.32%) developed MCE. The independent risk factors for MCE included admission National Institutes of Health Stroke Scale (NIHSS) ≥16 (odds ratio [OR] 1.851; 95% CI 1.029-3.329; P = 0.038), ASPECT score (OR 0.621; 95% CI 0.519-0.744; P < 0.001), right hemisphere (OR 1.636; 95% CI 0.941-2.843; P = 0.079), collateral circulation (OR 0.155; 95% CI 0.074-0.324; P < 0.001), recanalization (OR 0.223; 95% CI 0.109-0.457; P < 0.001), hematocrit (OR, 0.937; 95% CI: 0.892-0.985; P =0.010), and glucose (OR 1.118; 95% CI 1.023-1.223; P = 0.036), which were adopted as parameters of the nomogram. The receiver operating characteristic curve analysis showed that the area under the curve of the nomogram in predicting MCE was 0.901(95% CI 0.848-0.940; P < 0.001). The Hosmer-Lemeshow test results were not significant (P = 0.685), demonstrating a good calibration of the nomogram. CONCLUSIONS: The novel nomogram composed of admission NIHSS, ASPECT scores, right hemisphere, collateral circulation, recanalization, hematocrit, and serum glucose provide a potential predictor for MCE in patients with AIS after EVT.

Application value of whole exome sequencing in screening and identifying novel mutations of hypopharyngeal cancer.

The research on targeted therapy of hypopharyngeal cancer is very scarce. The discovery of new targeted driver genes will promote the progress of hypopharyngeal cancer therapy to a great extent. In our research, whole-exome sequencing in 10 patients with hypopharyngeal cancer was performed to identify single nucleotide variations (SNVs) and insertions and deletions (INDELs). American College of Medical Genetics and Genomics (ACMG) guidelines were used to evaluate the pathogenicity of the selected variants. 8113 mutation sites in 5326 genes were identified after strict screening. We identified 72 pathogenic mutations in 53 genes according to the ACMG guidelines. Gene Ontology (GO) annotation and KEGG enrichment analysis show the effect of these genes on cancer. Protein-protein interaction (PPI) was analyzed by string online software. The validation results of the ualcan database showed that 22 of the 53 genes may be related to the poor prognosis of patients with hypopharyngeal cancer. RBM20 has the most significant correlation with hypopharyngeal cancer, and it is likely to be the driver gene of hypopharyngeal cancer. In conclusion, we found possible therapeutic targets for hypopharyngeal cancer, especially RBM20 and KMT2C. Our study provides a basis for the pathogenesis and targeted therapy of hypopharyngeal cancer.

Regulating the Expression of HIF-1α or lncRNA: Potential Directions for Cancer Therapy.

Previous studies have shown that tumors under a hypoxic environment can induce an important hypoxia-responsive element, hypoxia-induced factor-1α (HIF-1α), which can increase tumor migration, invasion, and metastatic ability by promoting epithelial-to-mesenchymal transition (EMT) in tumor cells. Currently, with the deeper knowledge of long noncoding RNAs (lncRNAs), more and more functions of lncRNAs have been discovered. HIF-1α can regulate hypoxia-responsive lncRNAs under hypoxic conditions, and changes in the expression level of lncRNAs can regulate the production of EMT transcription factors and signaling pathway transduction, thus promoting EMT progress. In conclusion, this review summarizes the regulation of the EMT process by HIF-1α and lncRNAs and discusses their relationship with tumorigenesis. Since HIF-1α plays an important role in tumor progression, we also summarize the current drugs that inhibit tumor progression by modulating HIF-1α.

Physicochemical characterization, emulsifying and antioxidant properties of the polysaccharide conjugates from Chin brick tea (Camellia sinensis).

Tea polysaccharide conjugate fractions (TPCs) with different molecular weights (TPC-40, TPC-60, and TPC-80, MW = 1355 to 204 kDa) were prepared from Chin brick tea using graded alcohol precipitation. The physiochemical and functional properties of TPCs were investigated. Results showed that TPC-80 (204 kDa) had the highest antioxidant activity attributed to its higher phenolic and theabrownin contents. Moreover, this fraction had the highest surface pressure (16.2 ± 0.9 mN/m), but the lowest interfacial dilatational modulus (30.3 ± 2.2 mN/m) than TPC-40 (1355 kDa) and TPC-60 (955 kDa). As a result, TPC-80 had the highest emulsifying activity but the lowest emulsion stabilizing properties due to its fastest adsorption kinetics but the relatively thin interfacial coating on the oil droplets. Overall, our results indicate that the chemical compositions and structural characteristics of TPCs significantly impact their functional attributes. TPCs have the potential to be a novel natural antioxidant emulsifier in food industry.

Antioxidant potential of Pediococcus pentosaceus strains from the sow milk bacterial collection in weaned piglets.

BACKGROUND: In modern animal husbandry, breeders pay increasing attention to improving sow nutrition during pregnancy and lactation to favor the health of neonates. Sow milk is a main food source for piglets during their first three weeks of life, which is not only a rich repository of essential nutrients and a broad range of bioactive compounds, but also an indispensable source of commensal bacteria. Maternal milk microorganisms are important sources of commensal bacteria for the neonatal gut. Bacteria from maternal milk may confer a health benefit on the host. METHODS: Sow milk bacteria were isolated using culturomics followed by identification using 16S rRNA gene sequencing. To screen isolates for potential probiotic activity, the functional evaluation was conducted to assess their antagonistic activity against pathogens in vitro and evaluate their resistance against oxidative stress in damaged Drosophila induced by paraquat. In a piglet feeding trial, a total of 54 newborn suckling piglets were chosen from nine sows and randomly assigned to three treatments with different concentrations of a candidate strain. Multiple approaches were carried out to verify its antioxidant function including western blotting, enzyme activity analysis, metabolomics and 16S rRNA gene amplicon sequencing. RESULTS: The 1240 isolates were screened out from the sow milk microbiota and grouped into 271 bacterial taxa based on a nonredundant set of 16S rRNA gene sequencing. Among 80 Pediococcus isolates, a new Pediococcus pentosaceus strain (SMM914) showed the best performance in inhibition ability against swine pathogens and in a Drosophila model challenged by paraquat. Pretreatment of piglets with SMM914 induced the Nrf2-Keap1 antioxidant signaling pathway and greatly affected the pathways of amino acid metabolism and lipid metabolism in plasma. In the colon, the relative abundance of Lactobacillus was significantly increased in the high dose SMM914 group compared with the control group. CONCLUSION: P. pentosaceus SMM914 is a promising probiotic conferring antioxidant capacity by activating the Nrf2-Keap1 antioxidant signaling pathway in piglets. Our study provided useful resources for better understanding the relationships between the maternal microbiota and offspring. Video Abstract.

The potential, analysis and prospect of ctDNA sequencing in hepatocellular carcinoma.

Background: The genome map of hepatocellular carcinoma (HCC) is complex. In order to explore whether circulating tumor cell DNA (ctDNA) can be used as the basis for sequencing and use ctDNA to find tumor related biomarkers, we analyzed the mutant genes of ctDNA in patients with liver cancer by sequencing. Methods: We used next-generation targeted sequencing technology to identify mutations in patients with liver cancer. The ctDNA from 10 patients with hepatocellular carcinoma (including eight cases of primary hepatocellular carcinoma and two cases of secondary hepatocellular carcinoma) was sequenced. We used SAMtools to detect and screen single nucleotide polymorphisms (SNPs) and insertion deletion mutations (INDELs) and ANNOVAR to annotate the structure and function of the detected mutations. Screening of pathogenic and possible pathogenic genes was performed using American College of Medical Genetics and Genomics (ACMG) guidelines. GO analysis and KEGG analysis of pathogenic and possible pathogenic genes were performed using the DAVID database, and protein-protein interaction network analysis of pathogenic and possible pathogenic genes was performed using the STRING database. Then, the Kaplan-Meier plotter database, GEPIA database and HPA database were used to analyse the relationship between pathogenic and possible pathogenic genes and patients with liver cancer. Results: Targeted capture and deep sequencing of 560 cancer-related genes in 10 liver cancer ctDNA samples revealed 8,950 single nucleotide variation (SNV) mutations and 70 INDELS. The most commonly mutated gene was PDE4DIP, followed by SYNE1, KMT2C, PKHD1 and FN1. We compared these results to the COSMIC database and determined that ctDNA could be used for sequencing. According to the ACMG guidelines, we identified 54 pathogenic and possible pathogenic mutations in 39 genes in exons and splice regions of 10 HCC patients and performed GO analysis, KEGG analysis, and PPI network analysis. Through further analysis, four genes significantly related to the prognosis of liver cancer were identified. Conclusion: In this study, our findings indicate that ctDNA can be used for sequencing. Our results provide some molecular data for the mapping of genetic variation in Chinese patients with liver cancer, which enriches the understanding of HCC pathogenesis and provides new ideas for the diagnosis and prognosis of HCC patients.

Corrigendum: Adenosine A2A Receptor Suppressed Astrocyte-Mediated Inflammation through the Inhibition of STAT3/YKL-40 Axis in Mice with Chronic Cerebral Hypoperfusion-Induced White Matter Lesions.

[This corrects the article DOI: 10.3389/fimmu.2022.841290.].

Adenosine A2A Receptor Suppressed Astrocyte-Mediated Inflammation Through the Inhibition of STAT3/YKL-40 Axis in Mice With Chronic Cerebral Hypoperfusion-induced White Matter Lesions.

White matter lesions are an important pathological manifestation of cerebral small vessel disease, with inflammation playing a pivotal role in their development. The adenosine A2a receptor (ADORA2A) is known to inhibit the inflammation mediated by microglia, but its effect on astrocytes is unknown. Additionally, although the level of YKL-40 (expressed mainly in astrocytes) has been shown to be elevated in the model of white matter lesions induced by chronic cerebral hypoperfusion, the specific regulatory mechanism involved is not clear. In this study, we established in vivo and in vitro chronic cerebral hypoperfusion models to explore whether the ADORA2A regulated astrocyte-mediated inflammation through STAT3/YKL-40 axis and using immunohistochemical, western blotting, ELISA, PCR, and other techniques to verify the effect of astrocytes ADORA2A on the white matter injury. The in vivo experiments showed that activation of the ADORA2A decreased the expression of both STAT3 and YKL-40 in the astrocytes and alleviated the white matter injury, whereas its inhibition had the opposite effects. Similarly, ADORA2A inhibition significantly increased the expression of STAT3 and YKL-40 in astrocytes in vitro, with more proinflammatory cytokines being released by astrocytes. STAT3 inhibition enhanced the inhibitory effect of ADORA2A on YKL-40 synthesis, whereas its activation reversed the phenomenon. These results suggest that the activation of ADORA2A in astrocytes can inhibit the inflammation mediated by the STAT3/YKL-40 axis and thereby reduce white matter injury in cerebral small vessel disease.

The effect of surgery plus intensity-modulated radiotherapy on treatment in laryngeal cancer: A clinical retrospective study.

PURPOSE: As a common head and neck tumor, laryngeal cancer has attracted heightened attention for its treatment and prognosis. Surgery and radiotherapy were mainly therapeutic approaches in laryngeal cancer, and intensity-modulated radiotherapy (IMRT) was a precision treatment way in radiotherapy. However, the therapeutic effect of surgery plus IMRT in laryngeal cancer was rarely reported. This study aims to determine the effect of IMRT on the treatment of patients with laryngeal cancer. METHODS: A total of 125 patients with laryngeal cancer were collected and retrospectively analyzed based on their clinical data and follow-up results. These patients had a clear treatment plan for surgery and intensity-modulated radiotherapy. RESULTS: Smoking, lymph node metastasis, TNM staging and therapeutic approaches could affect the survival of patients with laryngeal cancer. It was shown that the laryngeal function retention rate in the simple IMRT group was significantly higher than the simple surgery group and surgery plus IMRT group. The 5-year survival rate of surgery plus IMRT, simple surgery and simple IMRT were 82.86%, 53.85% and 43.33%, respectively. The locoregional recurrences rate of surgery plus IMRT, simple surgery and simple IMRT were 14.29%, 34.62% and 43.33%. CONCLUSION: Surgery plus IMRT was a feasible and efficacious treatment technique for patients with laryngeal cancer, which effectively prolong the survival time of patients.

TiO2 nanoparticles negatively impact the bioavailability and antioxidant activity of tea polyphenols.

This study was to investigate the influence of TiO2 nanoparticles (NPs) on the stability, bioavailability, and antioxidant activity of co-ingested tea polyphenols extract using an in vitro digestion model. The tea polyphenol contents decreased significantly after addition of 0.5 % (w/w) TiO2 NPs. The gallocatechin gallate level decreased the most, changing from 101.9 to 27.2 µg/mL (about 73.3%). The TiO2 NPs also reduced the bioavailability of the tea polyphenols in a dose-dependent manner, which was ascribed to the formation of large polyphenol-TiO2 NP complex aggregates that could not pass through the pores in the dialysis tube used to simulate the gut wall. Additionally, the TiO2 NPs decreased the antioxidant activity of the tea polyphenols within the simulated gastrointestinal tract. In summary, our results show that high levels of TiO2 NPs (but within the current legal limits in many countries) may negatively impact the bioavailability and bioactivity of polyphenols in foods.

Research Progress and Direction of Novel Organelle-Migrasomes.

Migrasomes are organelles that are similar in structure to pomegranates, up to 3 µm in diameter, and contain small vesicles with a diameter of 50-100 nm. These membranous organelles grow at the intersections or tips of retracting fibers at the back of migrating cells. The process by which cells release migrasomes and their contents outside the cell is called migracytosis. The signal molecules are packaged in the migrasomes and released to the designated location by migrasomes to activate the surrounding cells. Finally, the migrasomes complete the entire process of information transmission. In this sense, migrasomes integrate time, space, and specific chemical information, which are essential for regulating physiological processes such as embryonic development and tumor invasion and migration. In this review, the current research progress of migrasomes, including the discovery of migrasomes and migracytosis, the structure of migrasomes, and the distribution and functions of migrasomes is discussed. The migratory marker protein TSPAN4 is highly expressed in various cancers and is associated with cancer invasion and migration. Therefore, there is still much research space for the pathogenesis of migratory bodies and cancer. This review also makes bold predictions and prospects for the research directions of the combination of migrasomes and clinical applications.

Single-Cell RNA Sequencing Analysis of the Immunometabolic Rewiring and Immunopathogenesis of Coronavirus Disease 2019.

Although immune dysfunction is a key feature of coronavirus disease 2019 (COVID-19), the metabolism-related mechanisms remain elusive. Here, by reanalyzing single-cell RNA sequencing data, we delineated metabolic remodeling in peripheral blood mononuclear cells (PBMCs) to elucidate the metabolic mechanisms that may lead to the progression of severe COVID-19. After scoring the metabolism-related biological processes and signaling pathways, we found that mono-CD14+ cells expressed higher levels of glycolysis-related genes (PKM, LDHA and PKM) and PPP-related genes (PGD and TKT) in severe patients than in mild patients. These genes may contribute to the hyperinflammation in mono-CD14+ cells of patients with severe COVID-19. The mono-CD16+ cell population in COVID-19 patients showed reduced transcription levels of genes related to lysine degradation (NSD1, KMT2E, and SETD2) and elevated transcription levels of genes involved in OXPHOS (ATP6V1B2, ATP5A1, ATP5E, and ATP5B), which may inhibit M2-like polarization. Plasma cells also expressed higher levels of the OXPHOS gene ATP13A3 in COVID-19 patients, which was positively associated with antibody secretion and survival of PCs. Moreover, enhanced glycolysis or OXPHOS was positively associated with the differentiation of memory B cells into plasmablasts or plasma cells. This study comprehensively investigated the metabolic features of peripheral immune cells and revealed that metabolic changes exacerbated inflammation in monocytes and promoted antibody secretion and cell survival in PCs in COVID-19 patients, especially those with severe disease.

Abnormal alternative splicing promotes tumor resistance in targeted therapy and immunotherapy.

Abnormally alternative splicing events are common hallmark of diverse types of cancers. Splicing variants with aberrant functions play an important role in cancer development. Most importantly, a growing body of evidence has supported that alternative splicing might play a significant role in the therapeutic resistance of tumors. Targeted therapy and immunotherapy are the future directions of tumor therapy; however, the loss of antigen targets on the tumor cells surface and alterations in drug efficacy have resulted in the failure of targeted therapy and immunotherapy. Interestingly, abnormal alternative splicing, as a strategy to regulate gene expression, is reportedly involved in the reprogramming of cell signaling pathways and epitopes on the tumor cell surface by changing splicing patterns of genes, thus rendering tumors resisted to targeted therapy and immunotherapy. Accordingly, increased knowledge regarding abnormal alternative splicing in tumors may help predict therapeutic resistance during targeted therapy and immunotherapy and lead to novel therapeutic approaches in cancer. Herein, we provide a brief synopsis of abnormal alternative splicing events in cancer progression and therapeutic resistance.

Progress in the Understanding of the Mechanism of Tamoxifen Resistance in Breast Cancer.

Tamoxifen is a drug commonly used in the treatment of breast cancer, especially for postmenopausal patients. However, its efficacy is limited by the development of drug resistance. Downregulation of estrogen receptor alpha (ERα) is an important mechanism of tamoxifen resistance. In recent years, with progress in research into the protective autophagy of drug-resistant cells and cell cycle regulators, major breakthroughs have been made in research on tamoxifen resistance. For a better understanding of the mechanism of tamoxifen resistance, protective autophagy, cell cycle regulators, and some transcription factors and enzymes regulating the expression of the estrogen receptor are summarized in this review. In addition, recent progress in reducing resistance to tamoxifen is reviewed. Finally, we discuss the possible research directions into tamoxifen resistance in the future to provide assistance for the clinical treatment of breast cancer.

Down-regulation of PCK2 inhibits the invasion and metastasis of laryngeal carcinoma cells.

Laryngeal carcinoma is one of the common malignancies of head and neck. However, the pathogenesis of laryngeal cancer has been not completely clear. To identify the effects of hypoxia on the invasion, metastasis, and metabolism of laryngeal carcinoma, iTRAQ-labeling-with-LC-MS/MS analysis was performed to identify differentially expressed proteins of the SCC10A cells under hypoxia and normoxia, while metabolites were examined by metabolic profiling. 155 proteins and 180 metabolites were identified and the PCK2 protein was selected for validation by Western Blotting. Immunohistochemistry (IHC) was performed to analyze the expression of PCK2 in formalin-fixed paraffin-embedded (FFPE) tissue sections, including laryngeal squamous cell carcinoma tissues from various stages. Collectively, we report that down-regulation of PCK2 inhibits the invasion, migration, and proliferation of laryngeal cancer under hypoxia and down-regulation of PCK2 may be used as a new strategy for laryngeal cancer therapy.

Adenosine A2A Receptors in Bone Marrow-Derived Cells Attenuate Cognitive Impairment in Mice After Chronic Hypoperfusion White Matter Injury.

The mechanism of cognitive dysfunction caused by ischemic white matter lesions is unclear. To explore the effect and mechanism of different cell-derived adenosine A2A receptor (A2AR) in cognitive impairment caused by chronic hypoperfusion white matter lesions (CHWMLs), we destroyed the bone marrow hematopoietic capacity of the recipient mice using radiation irradiation followed by establishing the selectively inactivated or reconstituted A2AR models with the transplanting bone marrow from global A2AR gene knockout or wild-type mice into wild-type or gene knockout mice, respectively. Then Morris Water Maze (MWM), ELISA, immunohistochemistry, and Bielschowsky silver staining were used to assess the effect and mechanism of the cognitive function in chronic cerebral blood flow hypoperfusion (CCH) model. Selectively reconstructing bone marrow-derived cells (BMDCs) A2AR (WT → KO group) and activated total adenosine A2AR with CGS21680 (CCH + CGS group) improved the cognitive related index. Activation of BMDC A2AR suppressed expression of inflammatory cytokines in peripheral blood and reduced the number of activated microglia cells co-localized with cystatin F in local brain, consequently inhibited white matter lesions. On the contrary, selective inactivation of adenosine A2AR (KO → WT group) and activation of non-BMDC A2AR with CGS21680 (KO → WT + CGS group) served the opposite effects. These results suggested that BMDC A2AR could inhibit white matter lesions and attenuate cognitive impairment after CHWMLs, whereas non-BMDC A2ARs aggravate cognitive impairment. The systemic inflammatory response and local activated microglia with cystatin F high expression were involved in the process of cognitive function recovery with BMDC A2AR. The overall trend is that BMDC A2ARs play a leading role.