Protective Effects of Danmu Extract Syrup on Acute Lung Injury Induced by Lipopolysaccharide in Mice through Endothelial Barrier Repair.

OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 ß in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 ß (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS: DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.

Treatment for ovarian clear cell carcinoma with combined inhibition of WEE1 and ATR.

BACKGROUND: Standard platinum-based therapy for ovarian cancer is inefficient against ovarian clear cell carcinoma (OCCC). OCCC is a distinct subtype of epithelial ovarian cancer. OCCC constitutes 25% of ovarian cancers in East Asia (Japan, Korea, China, Singapore) and 6-10% in Europe and North America. The cancer is characterized by frequent inactivation of ARID1A and 10% of cases of endometriosis progression to OCCC. The aim of this study was to identify drugs that are either FDA-approved or in clinical trials for the treatment of OCCC. RESULTS: High throughput screening of 166 compounds that are either FDA-approved, in clinical trials or are in pre-clinical studies identified several cytotoxic compounds against OCCC. ARID1A knockdown cells were more sensitive to inhibitors of either mTOR (PP242), dual mTOR/PI3K (GDC0941), ATR (AZD6738) or MDM2 (RG7388) compared to control cells. Also, compounds targeting BH3 domain (AZD4320) and SRC (AZD0530) displayed preferential cytotoxicity against ARID1A mutant cell lines. In addition, WEE1 inhibitor (AZD1775) showed broad cytotoxicity toward OCCC cell lines, irrespective of ARID1A status. CONCLUSIONS: In a selection of 166 compounds we showed that inhibitors of ATR and WEE1 were cytotoxic against a panel of OCCC cell lines. These two drugs are already in other clinical trials, making them ideal candidates for treatment of OCCC.

Targeting USP10 induces degradation of oncogenic ANLN in esophageal squamous cell carcinoma.

Anillin (ANLN) is a mitosis-related protein that promotes contractile ring formation and cytokinesis, but its cell cycle-dependent degradation mechanisms in cancer cells remain unclear. Here, we show that high expression of ANLN promotes cytokinesis and proliferation in esophageal squamous cell carcinoma (ESCC) cells and is associated with poor prognosis in ESCC patients. Furthermore, the findings of the study showed that the deubiquitinating enzyme USP10 interacts with ANLN and positively regulates ANLN protein levels. USP10 removes the K11- and K63-linked ubiquitin chains of ANLN through its deubiquitinase activity and prevents ANLN ubiquitin-mediated degradation. Importantly, USP10 promotes contractile ring assembly at the cytokinetic furrow as well as cytokinesis by stabilizing ANLN. Interestingly, USP10 and the E3 ubiquitin ligase APC/C co-activator Cdh1 formed a functional complex with ANLN in a non-competitive manner to balance ANLN protein levels. In addition, the macrolide compound FW-04-806 (F806), a natural compound with potential for treating ESCC, inhibited the mitosis of ESCC cells by targeting USP10 and promoting ANLN degradation. F806 selectively targeted USP10 and inhibited its catalytic activity but did not affect the binding of Cdh1 to ANLN and alters the balance of the USP10-Cdh1-ANLN complex. Additionally, USP10 expression was positively correlated with ANLN level and poor prognosis of ESCC patients. Overall, targeting the USP10-ANLN axis can effectively inhibit ESCC cell-cycle progression.

CircRNA and miRNA expression profiles during remote ischemic postconditioning attenuate brain ischemia/reperfusion injury.

Remote ischemic postconditioning (RIPostC) is a protective procedure for brain damage caused by ischemia/reperfusion (IR), yet the mechanism of this treatment remains to be elucidated. Circular RNAs (circRNAs) are endogenous non-coding RNAs that have recently been recognized to play vital roles in ischemic brain injury. The aim of this study was to explore the role of circRNAs in the protective mechanism of RIPostC and to analyze the circRNA-microRNA (miRNA) regulation network in RIPostC. Nine rats were assigned randomly into three groups (three rats per group): sham, IR, and RIPostC. Their brain tissues were extracted for next-generation RNA sequencing and bioinformatics analysis was performed for two comparisons: sham vs. IR and IR vs. RIPostC. The expression patterns of selected circRNAs and miRNAs were validated by quantitative real-time PCR (qPCR). We detected 82 upregulated and 51 downregulated circRNAs and 137 upregulated and 127 downregulated miRNAs in the IR group compared with the sham group, and 41 upregulated and 100 downregulated circRNAs and 45 upregulated and 64 downregulated miRNAs in the RIPostC group compared with the IR group. The proposed competitive endogenous RNA (ceRNA) network, which included 24 circRNAs, 20 miRNAs, and 145 mRNAs, indicated that the dysregulated circRNAs played important roles in brain IR injury. On the basis of the expression patterns of selected circRNAs, miRNAs, and mRNAs obtained by qPCR, we proposed a circRNA_0002286-miR-124-3p-VLCAD pathway. In PC12 cell, the expression level of miR-124-3p was significantly upregulated when the expression of circRNA_0002286 was repressed and the expression level of VLCAD (very-long chain acyl-CoA dehydrogenase) was significantly downregulated, which suggested that circRNA_0002286 may act as a miRNA sponge for miR-124-3p to regulate the expression of VLCAD. We found that upregulation of circRNA_0002286 attenuated IR injury and was associated with downregulation of miR-124-3p and upregulation of VLCAD. This is the first time that circRNAs have been shown to be closely related to brain IR injury and RIPostC and suggests that targeting the circRNA_0002286-miR-124-3p-VLCAD pathway might attenuate brain IR injury.

Neuroprotective effects of long noncoding RNAs involved in ischemic postconditioning after ischemic stroke.

During acute reperfusion, the expression profiles of long noncoding RNAs in adult rats with focal cerebral ischemia undergo broad changes. However, whether long noncoding RNAs are involved in neuroprotective effects following focal ischemic stroke in rats remains unclear. In this study, RNA isolation and library preparation was performed for long noncoding RNA sequencing, followed by determining the coding potential of identified long noncoding RNAs and target gene prediction. Differential expression analysis, long noncoding RNA functional enrichment analysis, and co-expression network analysis were performed comparing ischemic rats with and without ischemic postconditioning rats. Rats were subjected to ischemic postconditioning via the brief and repeated occlusion of the middle cerebral artery or femoral artery. Quantitative real-time reverse transcription-polymerase chain reaction was used to detect the expression levels of differentially expressed long noncoding RNAs after ischemic postconditioning in a rat model of ischemic stroke. The results showed that ischemic postconditioning greatly affected the expression profile of long noncoding RNAs and mRNAs in the brains of rats that underwent ischemic stroke. The predicted target genes of some of the identified long noncoding RNAs (cis targets) were related to the cellular response to ischemia and stress, cytokine signal transduction, inflammation, and apoptosis signal transduction pathways. In addition, 15 significantly differentially expressed long noncoding RNAs were identified in the brains of rats subjected to ischemic postconditioning. Nine candidate long noncoding RNAs that may be related to ischemic postconditioning were identified by a long noncoding RNA expression profile and long noncoding RNA-mRNA co-expression network analysis. Expression levels were verified by quantitative real-time reverse transcription-polymerase chain reaction. These results suggested that the identified long noncoding RNAs may be involved in the neuroprotective effects associated with ischemic postconditioning following ischemic stroke. The experimental animal procedures were approved by the Animal Experiment Ethics Committee of Kunming Medical University (approval No. KMMU2018018) in January 2018.

Tight junction protein 1 promotes vasculature remodeling via regulating USP2/TWIST1 in bladder cancer.

Bladder cancer (BLCA) is the most common malignant tumor of the urinary system and is characterized by high metastatic rates and poor prognosis. The expression of tight junction protein 1 (TJP1) is associated with bladder cancer invasion; however, the mechanism by which TJP1 affects vasculature remodeling remains unknown. In this study, we found that TJP1 expression correlated with tumor angiogenesis and poor overall survival in clinical samples. Furthermore, TJP1 overexpression promoted tumor angiogenesis in BLCA cells and stimulated recruitment of macrophages to tumors by upregulating CCL2 expression. Mechanistically, TJP1 interacted with TWIST1 and enhanced the transcriptional activity of CCL2. The impairment of tumor angiogenesis caused by knockdown of TJP1 was dramatically rescued by overexpression of TWIST1. Furthermore, TJP1 recruited USP2, which deubiquitinated TWIST1, thereby protecting TWIST1 from proteasome-mediated protein degradation. In conclusion, our results suggest that TJP1 controls angiogenesis in BLCA via TWIST1-dependent regulation of CCL2. We demonstrate that TJP1 functions as a scaffold for the interaction between USP2 and TWIST1 and this may provide potential therapeutic targets in bladder cancer.

Neurotrophic factors combined with stem cells in the treatment of sciatic nerve injury in rats: a meta-analysis.

Treatment of peripheral nerve regeneration with stem cells (SCs) alone has some limitations. For this reason, we evaluate the efficacy of neurotrophic factors combined with stem cell transplantation in the treatment of sciatic nerve injury (SNI) in rats. PubMed, Cochrane Library, Embase, WanFang, VIP and China National Knowledge Infrastructure databases were retrieved from inception to October 2021, and control experiments on neurotrophic factors combined with stem cells in the treatment of SNI in rats were searched. Nine articles and 551 rats were included in the meta-analysis. The results of meta-analysis confirmed that neurotrophic factor combined with stem cells for the treatment of SNI yielded more effective repair than normal rats with regard to sciatic nerve index, electrophysiological detection index, electron microscope observation index, and recovery rate of muscle wet weight. The conclusion is that neurotrophic factor combined with stem cells is more conducive to peripheral nerve regeneration and functional recovery than stem cells alone. However, due to the limitation of the quality of the included literature, the above conclusions need to be verified by randomized controlled experiments with higher quality and larger samples.

Integrated single-cell transcriptome analysis reveals heterogeneity of esophageal squamous cell carcinoma microenvironment.

The tumor microenvironment is a highly complex ecosystem of diverse cell types, which shape cancer biology and impact the responsiveness to therapy. Here, we analyze the microenvironment of esophageal squamous cell carcinoma (ESCC) using single-cell transcriptome sequencing in 62,161 cells from blood, adjacent nonmalignant and matched tumor samples from 11 ESCC patients. We uncover heterogeneity in most cell types of the ESCC stroma, particularly in the fibroblast and immune cell compartments. We identify a tumor-specific subset of CST1+ myofibroblasts with prognostic values and potential biological significance. CST1+ myofibroblasts are also highly tumor-specific in other cancer types. Additionally, a subset of antigen-presenting fibroblasts is revealed and validated. Analyses of myeloid and T lymphoid lineages highlight the immunosuppressive nature of the ESCC microenvironment, and identify cancer-specific expression of immune checkpoint inhibitors. This work establishes a rich resource of stromal cell types of the ESCC microenvironment for further understanding of ESCC biology.

Negative regulation by proBDNF signaling of peripheral neurogenesis in the sensory ganglia of adult rats.

Neurogenesis in the adult brain is well recognized and plays a critical role in the maintenance of brain function and homeostasis. However, whether neurogenesis also occurs in the adult peripheral nervous system remains unknown. Here, using sensory ganglia (dorsal root ganglia, DRGs) as a model, we show that neurogenesis also occurs in the peripheral nervous system, but in a manner different from that in the central nervous system. Satellite glial cells (SGCs) express the neuronal precursor markers Nestin, POU domain, class 4, transcription factor 1, and p75 pan-neurotrophin receptor. Following sciatic nerve injury, the suppression of endogenous proBDNF by proBDNF antibodies resulted in the transformation of proliferating SGCs into doublecortin-positive cells in the DRGs. Using purified SGCs migrating out from the DRGs, the inhibition of endogenous proBDNF promoted the conversion of SGCs into neuronal phenotypes in vitro. Our findings suggest that SGCs are neuronal precursors, and that proBDNF maintains the SGC phenotype. Furthermore, the suppression of proBDNF signaling is necessary for neuronal phenotype acquisition by SGCs. Thus, we propose that peripheral neurogenesis may occur via the direct conversion of SGCs into neurons, and that this process is negatively regulated by proBDNF.

Interplay and cooperation between SREBF1 and master transcription factors regulate lipid metabolism and tumor-promoting pathways in squamous cancer.

Squamous cell carcinomas (SCCs) comprise one of the most common histologic types of human cancer. Transcriptional dysregulation of SCC cells is orchestrated by tumor protein p63 (TP63), a master transcription factor (TF) and a well-researched SCC-specific oncogene. In the present study, both Gene Set Enrichment Analysis (GSEA) of SCC patient samples and in vitro loss-of-function assays establish fatty-acid metabolism as a key pathway downstream of TP63. Further studies identify sterol regulatory element binding transcription factor 1 (SREBF1) as a central mediator linking TP63 with fatty-acid metabolism, which regulates the biosynthesis of fatty-acids, sphingolipids (SL), and glycerophospholipids (GPL), as revealed by liquid chromatography tandem mass spectrometry (LC-MS/MS)-based lipidomics. Moreover, a feedback co-regulatory loop consisting of SREBF1/TP63/Kruppel like factor 5 (KLF5) is identified, which promotes overexpression of all three TFs in SCCs. Downstream of SREBF1, a non-canonical, SCC-specific function is elucidated: SREBF1 cooperates with TP63/KLF5 to regulate hundreds of cis-regulatory elements across the SCC epigenome, which converge on activating cancer-promoting pathways. Indeed, SREBF1 is essential for SCC viability and migration, and its overexpression is associated with poor survival in SCC patients. Taken together, these data shed light on mechanisms of transcriptional dysregulation in cancer, identify specific epigenetic regulators of lipid metabolism, and uncover SREBF1 as a potential therapeutic target and prognostic marker in SCC.

Salidroside inhibits NLRP3 inflammasome activation and apoptosis in microglia induced by cerebral ischemia/reperfusion injury by inhibiting the TLR4/NF-κB signaling pathway.

BACKGROUND: The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is an important mediator of neuroinflammatory responses that regulates inflammatory injury following cerebral ischemia and may be a potential target. Salidroside (Sal) has good anti-inflammatory effects; however, it remains unclear whether Sal can regulate NLRP3 inflammasome activation through the Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway after cerebral ischemia to alleviate inflammatory injury. METHODS: We established an oxygen-glucose deprivation and reoxygenation (OGD/R) model of BV2 cells and a middle cerebral artery occlusion/reperfusion (MCAO/R) rat model. Cell Counting Kit-8 (CCK-8), flow cytometry and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay were used to detect the viability and apoptosis of BV2 cells. Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of inflammatory factors. 2,3,5-triphenyltetrazolium chloride (TTC) staining and modified Neurological Severity Score (mNSS) were used to detect cerebral infarction volume and neurological deficit in rats. Western blot, immunohistochemistry and immunofluorescence staining were used to detect the protein expression levels. RESULTS: Our results showed that Sal increased viability, inhibited lactate dehydrogenase (LDH) release, and reduced apoptosis in OGD/R-induced BV2 cells. Sal reduced the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-8. Following induction by OGD/R, BV2 cells exhibited NLRP3 inflammasome activation and increased protein levels of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, IL-1ß, and IL-18. Protein levels of key TLR4 signaling pathway elements, such as TLR4, myeloid differentiation primary response 88 (MyD88), and phosphorylated nuclear factor kappa B p65 (p-NF-κB p65)/NF-κB p65 were upregulated. Interestingly, it was revealed that Sal could reverse these changes. In addition, TAK242, a specific inhibitor of TLR4, had the same effect as Sal treatment on BV2 cells following induction by OGD/R. In the MCAO/R rat model, Sal was also observed to inhibit NLRP3 inflammasome activation in microglia, reduce cerebral infarction volume, and inhibit apoptosis. CONCLUSIONS: In summary, we found that Sal inhibited NLRP3 inflammasome activation and apoptosis in microglia induced by cerebral ischemia/reperfusion injury by inhibiting the TLR4/NF-κB signaling pathway, thus playing a protective role. Therefore, Sal may be a promising drug for the clinical treatment of ischemic stroke.

Advances in intervention methods and brain protection mechanisms of in situ and remote ischemic postconditioning.

Ischemic postconditioning (PostC) conventionally refers to a series of brief blood vessel occlusions and reperfusions, which can induce an endogenous neuroprotective effect and reduce cerebral ischemia/reperfusion (I/R) injury. Depending on the site of adaptive ischemic intervention, PostC can be classified as in situ ischemic postconditioning (ISPostC) and remote ischemic postconditioning (RIPostC). Many studies have shown that ISPostC and RIPostC can reduce cerebral IS injury through protective mechanisms that increase cerebral blood flow after reperfusion, decrease antioxidant stress and anti-neuronal apoptosis, reduce brain edema, and regulate autophagy as well as Akt, MAPK, PKC, and KATP channel cell signaling pathways. However, few studies have compared the intervention methods, protective mechanisms, and cell signaling pathways of ISPostC and RIPostC interventions. Thus, in this article, we compare the history, common intervention methods, neuroprotective mechanisms, and cell signaling pathways of ISPostC and RIPostC.

Real-world Data on the Efficacy and Safety of Ixazomib-based Therapy in Multiple Myeloma: A Single-center Study in China.

OBJECTIVE: To assess the short-term efficacy and safety of ixazomib in Chinese multiple myeloma (MM) patients in the real world. METHODS: Fifty-nine MM patients who received at least one cycle of ixazomib-based therapy between 1 June 2018 and 30 September 2019 were retrospectively analyzed in Tianjin Medical University General Hospital. Thirteen newly diagnosed MM (NDMM), 13 refractory/relapsed MM (RRMM) and 33 continuous therapy (27 bortezomib peripheral neuritis (PN) intolerant and six maintenance therapy) MM patients were included. The indicated overall response rate (ORR), time to overall response (TOR), and adverse events (AEs) were investigated. RESULTS: The ORR in NDMM was 76.9%, with one complete response (CR), five very good partial response (VGPR), four partial response (PR), median PFS, and TOR were 122 (66-272) days and 49 (22-108) days. The ORR in RRMM was 46.2%, with one CR, two VGPR, three PR, median PFS, and TOR were 79 (28-169) days and 59 (23-88) days. The ORR in continuous therapy MM patients was 100%, with nine stringent CR, 15 CR, six VGPR and three PR, median TOR was 75 (25-141) days. There were no significant differences regarding ORR between patients with cytogenetic high risk and standard risk in three subgroups (all P>0.05). The most frequent hematological AEs were anemia (13.6%) and thrombocytopenia (10.2%). The most common nonhematological AEs were PN (25.0%) and diarrhea (13.6%). CONCLUSION: The real-world data demonstrated that ixazomib-based therapy was generally effective and safe in the short term for MM patients.

Different ischemic duration and frequency of ischemic postconditioning affect neuroprotection in focal ischemic stroke.

BACKGROUND: Many studies have confirmed that "in situ ischemia postconditioning" (ISPostC) and "remote ischemic postconditioning" (RIPostC) can reduce cerebral ischemia/reperfusion injury, but there is no comparison was made on the consistency of neuroprotection in ISPostC and RIPostC to different ischemic duration and number of cycles. NEW METHOD: We used a transient middle cerebral artery occlusion model to compare the neuroprotection of ISPostC and RIPostC. We conducted ISPostC and RIPostC via brief and repeated MCA and Femoral artery occlusion followed by different ischemic duration and number of cycles. Infarct volume, brain edema, Neurological deficit scores and Apoptosis were evaluated. RESULTS: First, the ISPostC with three cycles of 10-s occlusion/30-s release of both carotid arteries and the RIPostC with three cycles of 10-min occlusion/10-min release of the left and right femoral arteries can obviously reduce cerebral infarction size, brain edema, apoptosis, and improve behavioral deficits than other approaches. Second, three cycles of ischemia/reperfusion may be the best for RIPostC. COMPARISON WITH EXISTING METHOD(S): In this paper, we compared different ischemic duration and frequency of ISPostC and RIPostC models to determine the best method. This conclusion helps to unify the experimental methods. CONCLUSIONS: Different ischemic duration and frequency of ischemic postconditioning affect neuroprotection. three cycles of 10-s occlusion/30-s release of both carotid arteries and three cycles of 10-min occlusion/10-min release of both femoral arteries could be the first choice to study mechanisms of ischemic postconditioning and be conducive to the unification of research results.

An Observation of a Resident-as-Teacher Combined with Tutor Guided Hysteroscopy Teaching Program for Standardized Residency Training (SRT) in Obstetrics and Gynecology.

Objectives: The standardized residency training (SRT) program in China is an important link for continuing education and clinical work training for graduate students. The purpose of our study was to enable educators to maintain the effectiveness of hysteroscopy teaching techniques and make the standardized residency training students well experienced in surgery, thus demonstrating that higher efficiency of teaching can lead to better proficiency for surgery. Methods: We generated resident-as-teacher teaching round and tutor guided hysteroscopic surgery as well as a questionnaire based on the mastery degree of the basic theoretical knowledge and operational skills of hysteroscopy among seven junior residents and five senior residents of the Obstetrics and Gynecology Department, including four attending gynecologic surgeons of a hysteroscopy teaching program. Results: Senior residents felt confident to teach, while junior residents learned effectively through the teaching round. There were statistically significant differences in the whole operation time and the volume of distension fluid used between junior and senior residents (p < 0.05). Conclusions: This study acknowledges the need for new approaches to medical education for better characterization of the link between the use of teaching rounds through problem-based learning (PBL) discussion dominated by the residents themselves and overall surgical skills of teaching and learning.

Transplantation of Nurr1-overexpressing neural stem cells and microglia for treating parkinsonian rats.

BACKGROUND: Neural stem cells (NSCs) transplantation is considered a promising treatment for Parkinson's disease. But most NSCs are differentiated into glial cells rather than neurons, and only a few of them survive after transplantation due to the inflammatory environment. METHODS: In this study, neural stem cells (NSCs) and microglial cells both forced with the Nurr1 gene were transplanted into the striatum of the rat model of PD. The results were evaluated through reverse transcription polymerase chain reaction (RT-PCR), Western blot, and immunofluorescence analysis. RESULTS: The behavioral abnormalities of PD rats were improved by combined transplantation of NSCs and microglia, both forced with Nurr1. The number of tyrosine hydroxylase+ cells in the striatum of PD rats increased, and the number of Iba1+ cells decreased compared with the other groups. Moreover, the dopamine neurons differentiated from grafted NSCs could still be detected in the striatum of PD rats after 5 months. CONCLUSIONS: The results suggested that transplantation of Nurr1-overexpressing NSCs and microglia could improve the inhospitable host brain environments, which will be  a new potential strategy for the cell replacement therapy in PD.

Composition characteristics of PM2.5 metals and metalloids in a sampling point of Shanghai in winter from 2014 to 2017 / 上海预防医学

Objective To explore the composition and distribution of metal and metalloids in fine particulate metter in a certain area of Shanghai through four consecutive years of dynamic monitoring. Methods The sampling point was on the roof of a community health service center in Shanghai, with a height of 12.5 meters.In the four winters of 2014-2017 from Dec. to Feb. next year, samples were continuously collected for 7 days(from 10th to 16th) a month and 22 hours for each day.Inductively coupled plasma-mass spectrometry (ICP-MS) was used for the determination of metals and metalloids in collected samples. Results The pairwise comparisons between the total metals, Al, Be, Cr, Hg, Pb, Mn, Ni, Se and Tl in any two years were statistically different through the rank sum test.In the Cochran-Armitage trend test, Al showed an upward trend in the whole periods, while Cr, Pb and Ni was on a downward trend.In factor analysis, factor 1 in each year had relatively stable component elements (As, Cd, Pb, Mn, Se), while the internal components of the remaining factors were relatively unstable. Conclusions There may be relatively stable sources of pollution locally.Al, Cr, Pb and Ni have a significant tendency to increase or decrease.

Heat shock protein family B member 1 facilitates ezrin activation to control cell migration in esophageal squamous cell carcinoma.

Ezrin plays an important role in the development and progression of human esophageal squamous cell carcinoma (ESCC), providing a link between the cortical actin cytoskeleton and the plasma membrane to govern membrane structure and protrusions. However, the mechanism by which ezrin is activated still remains unknown in ESCC. Here, we identify a novel interaction between ezrin and heat shock protein family B (small) member 1 (HSPB1) in ESCC cells by mass spectroscopy and co-immunoprecipitation. HSPB1 only interacts with inactive ezrin and binds to the α-helical coiled coil region of ezrin. Knockdown of HSPB1 resulted to the decline of phosphorylation at ezrin Thr567, markedly suppressing the ability of ezrin to bind to the actin cytoskeleton and migration of ESCC cells. Furthermore, neither the constitutively active phosphomimetic ezrin T567D, nor inactivated ezrin T567A could restore cell migration following HSPB1 knockdown. Low HSPB1 expression was associated with favorable overall survival of ESCC patients. Taken together, HSPB1, as an important partner, participates in the activation of ezrin and merits further evaluation as a novel therapeutic target against human ESCC.

A novel primary culture method for high-purity satellite glial cells derived from rat dorsal root ganglion.

Satellite glial cells surround neurons within dorsal root ganglia. Previous studies have focused on single-cell suspensions of cultured neurons derived from rat dorsal root ganglia. At present, the primary culture method for satellite glial cells derived from rat dorsal root ganglia requires no digestion skill. Hence, the aim of the present study was to establish a novel primary culture method for satellite glial cells derived from dorsal root ganglia. Neonatal rat spine was collected and an incision made to expose the transverse protrusion and remove dorsal root ganglia. Dorsal root ganglia were freed from nerve fibers, connective tissue, and capsule membranes, then rinsed and transferred to 6-well plates, and cultured in a humidified 5% CO2 incubator at 37°C. After 3 days in culture, some cells had migrated from dorsal root ganglia. After subculture, cells were identified by immunofluorescence labeling for three satellite glial cell-specific markers: glutamine synthetase, glial fibrillary acidic protein, and S100ß. Cultured cells expressed glutamine synthetase, glial fibrillary acidic protein, and S100ß, suggesting they are satellite glial cells with a purity of > 95%. Thus, we have successfully established a novel primary culture method for obtaining high-purity satellite glial cells from rat dorsal root ganglia without digestion.

F806 Suppresses the Invasion and Metastasis of Esophageal Squamous Cell Carcinoma via Downregulating F-Actin Assembly-Related Rho Family Proteins.

Invasion and metastasis are critical pathological and mortal processes in esophageal squamous cell carcinoma (ESCC). Novel drugs, targeting the two cancer migration stages, will augment the treatment options for ESCC therapy and improve overall survival. A novel natural macrolide F806 specifically promotes apoptosis of various ESCC cells. However, whether F806 can inhibit metastasis of ESCC cells needs further evaluation. Here, our data showed that F806 inhibits dynamic F-actin assembly and then suppresses the migration of ESCC cells in vitro and their invasion and metastasis in vivo. The correlation between cancer migration and actin cytoskeleton assembly was consistent with the ability of F806 to prevent the aggregation of Paxillin, an essential protein for focal adhesion formation through binding to the ends of actin filaments. Furthermore, F806 downregulated the expression and activity of the Rho family proteins cell division cycle 42 (CDC42), RAC family small GTPase 1 (RAC1), and RAS homolog family member A (RHOA). Taken together, these results suggest that F806 can suppress cancer invasion and metastasis via interrupting the assembly of migration components involving F-actin.