Differentially expressed long-chain noncoding RNAs in human neuroblastoma cell line (SH-SY5Y): Alzheimer's disease cell model.

A number of complex human diseases including neurological diseases is characterized by dysregulation of long-chain noncoding RNA (lncRNA). The pathogenesis of Alzheimer's disease (AD), a neurodegenerative disorder is believed to involve alterations in lncRNAs. However, the specific lncRNAs modified in AD remain to be determined. The aim of this study was to identify lncRNAs associated with AD using human neuroblastoma cell line (SH-SY5Y) treated with beta-amyloid (Aß) as a model of this disease. The differential expressions of lncRNA were compared between beta-amyloid (Aß) SH-SY5Y cells and normal SH-SY5Y cells utilizing Illumina X10 gene sequencing. The differential expression profiles of amyloid (Aß)-treated SH-SY5Y cells were determined and verified by qRT-PCR method. The expression levels of lncRNA were expressed by calculating the abundance of FPKM (measure gene expression). The differential expression of log2 (multiple change) >1 or log2 (multiple change) < -1 had statistical significance (P< .05). The differential expression profiles of amyloid (Aß)-treated SH-SY5Y cells showed 40 lncRNA were up-regulated, while 60 lncRNA were down-regulated. GO and KEGG analysis demonstrated that differentially expressed genes were predominantly involved in the mitogen-activated protein kinase (MAPK) signaling pathway, p53 signaling pathway, hepatitis B, cell cycle, post-translational protein modification, and regulation. In conclusion, approximately 100 dysregulated lncRNA transcripts were found in amyloid (Aß)-treated SH-SY5Y cells and these lncRNAs may play an important role in the occurrence and development of AD through altered signal pathways.

The protective underlying mechanisms of Schisandrin on SH-SY5Y cell model of Alzheimer's disease.

The extract of Schisandrin a traditional Chinese medicine was postulated to be effective in prevention and treatment of Alzheimer's disease (AD). The aim of this study was to examine the underlying protective actions of Schizandrin using a human neuroblastoma cell line (SH-SY5Y). In particular Schizandrin-mediated effects on expression of glycogen synthase kinase (GSK)-3ß, protein kinase B (Akt) and Tau protein, known to be altered in AD were determined. In preliminary assays, various concentrations of Schisandrin were incubated SH-SY5Y cells to establish effects on cell viability and potential toxicity in further experimentation. Amyloid-ß (Aß1-42) peptide 10 µmol/L was used to induce in vitro AD model in SH-SY5Y. Exposure to Aß1-42 significantly reduced cell viability. Treatment with Schisandrin to Aß1-42 exposed cells increased cell viability compared to amyloid peptide; however only the 10 µmol/L Schisandrin concentration was effective in restoring cell viability to control. Western blot analysis demonstrated that Aß1-42 produced a significant decrease in p-Akt protein expression levels accompanied by marked elevation in p-tau and p-GSK-3ß protein expression levels. Addition of 10 µmol/L Schisandrin to amyloid-treated SH-SY5Y cells was found to significantly increase protein expression levels of p-Akt associated with reduction in expression levels of p-tau and p-GSK-3ß protein. Treatment with 10 µmol/L Schisandrin of SH-SY5Y cells with the p-Akt inhibitor LY294002 demonstrated that the herbal-induced rise in p-Akt protein expression was diminished by this inhibitor indicating that signal transduction occurred in the observed cellular effects. Evidence indicates that Schisandrin inhibition of Aß1-42 -mediated cellular damage in AD neurons may involve activation of the PI3K/Akt signaling pathway where up-regulation of p-Akt activity consequently leads downstream to decreased activity of p-GSK-3ß phosphorylation accompanied by reduced tau protein. Consequently, restoration of neuronal cell viability was noted. Our findings suggest that the use of Schisandrin may be considered beneficial as a therapeutic agent in AD.

Apelin-13 inhibits lipoprotein lipase expression via the APJ/PKCα/miR-361-5p signaling pathway in THP-1 macrophage-derived foam cells.

Atherosclerotic lesions are characterized by the accumulation of abundant lipids and chronic inflammation. Previous researches have indicated that macrophage-derived lipoprotein lipase (LPL) promotes atherosclerosis progression by accelerating lipid accumulation and pro-inflammatory cytokine secretion. Although apelin-13 has been regarded as an atheroprotective factor, it remains unclear whether it can regulate the expression of LPL. The aim of this study was to explore the effects of apelin-13 on the expression of LPL and the underlying mechanism in THP-1 macrophage-derived foam cells. Apelin-13 significantly decreased cellular levels of total cholesterol, free cholesterol, and cholesterol ester at the concentrations of 10 and 100 nM. ELISA analysis confirmed that treatment with apelin-13 reduced pro-inflammatory cytokine secretion, such as interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and tumor necrosis factor-alpha (TNF-α). It was also found that apelin-13 inhibited the expression of LPL as revealed by western blot and real-time PCR analyses. Bioinformatics analyses and dual-luciferase reporter assay indicated that miR-361-5p directly downregulated the expression of LPL by targeting the 3'UTR of LPL. In addition, apelin-13 + miR-361-5p mimic significantly downregulated the expression of LPL in cells. Finally, we demonstrated that apelin-13 downregulated the expression of LPL through activating the activity of PKCα. Taken together, our results showed that apelin-13 downregulated the expression of LPL via activating the APJ/PKCα/miR-361-5p signaling pathway in THP-1 macrophage-derived foam cells, leading to inhibition of lipid accumulation and pro-inflammatory cytokine secretion. Therefore, our studies provide important new insight into the inhibition of lipid accumulation and pro-inflammatory cytokine secretion by apelin-13, and highlight apelin-13 as a promising therapeutic target in atherosclerosis.

Comparison of post-resection survival between hepatocellular carcinoma patients in BCLC stage A or B who experience tumor rupture and patients in BCLC stage C who do not.

Background and aim: Spontaneous rupture of hepatocellular carcinoma (HCC) is a life-threatening complication, and patients who experience it are formally assigned to stage T4 in the TNM system, while many clinicians informally assign them to stage C in the more widely used Barcelona Clinic Liver Cancer (BCLC) system. The present study explored whether these re-staging practices are appropriate for HCC patients who suffer tumor rupture. Methods: We retrospectively reviewed the records of 1952 HCC patients who underwent hepatic resection at our hospital between January 2017 and June 2021. We compared recurrence-free and overall survival between 143 patients who had BCLC stage A or B disease at the time of spontaneous rupture and 449 patients who had BCLC stage C disease without rupture. Results: Overall survival rate was significantly higher among the 143 patients (1, 3, 5-year survival rate was 80.3%, 60.4%, 51.4%) with rupture than among the 449 (1, 3, 5-year survival rate was 69.5%, 41.5%, 32.4%) with BCLC stage C disease (hazard ratio 1.65, 95% confidence interval 1.29 to 2.12). The two groups had similar recurrence-free survival (hazard ratio 1.19, 95% confidence interval 0.92 to 1.53), but most patients with rupture were able to receive interventional and potentially curative treatments after recurrence, whereas most patients in BCLC stage C received interventional or supportive care. Similar results were obtained after propensity score matching. Conclusion: HCC patients who experience spontaneous rupture tumor while in BCLC stage A or B have better prognosis than patients in BCLC stage C without rupture. Our results suggest that HCC patients who suffer rupture in BCLC stage A or B should not be assigned to BCLC stage C.

Neurexin and neuroligins jointly regulate synaptic degeneration at the Drosophila neuromuscular junction based on TEM studies.

The Drosophila larval neuromuscular junction (NMJ) is a well-known model system and is often used to study synapse development. Here, we show synaptic degeneration at NMJ boutons, primarily based on transmission electron microscopy (TEM) studies. When degeneration starts, the subsynaptic reticulum (SSR) swells, retracts and folds inward, and the residual SSR then degenerates into a disordered, thin or linear membrane. The axon terminal begins to degenerate from the central region, and the T-bar detaches from the presynaptic membrane with clustered synaptic vesicles to accelerate large-scale degeneration. There are two degeneration modes for clear synaptic vesicles. In the first mode, synaptic vesicles without actin filaments degenerate on the membrane with ultrafine spots and collapse and disperse to form an irregular profile with dark ultrafine particles. In the second mode, clear synaptic vesicles with actin filaments degenerate into dense synaptic vesicles, form irregular dark clumps without a membrane, and collapse and disperse to form an irregular profile with dark ultrafine particles. Last, all residual membranes in NMJ boutons degenerate into a linear shape, and all the residual elements in axon terminals degenerate and eventually form a cluster of dark ultrafine particles. Swelling and retraction of the SSR occurs prior to degradation of the axon terminal, which degenerates faster and with more intensity than the SSR. NMJ bouton degeneration occurs under normal physiological conditions but is accelerated in Drosophila neurexin (dnrx) dnrx273, Drosophila neuroligin (dnlg) dnlg1 and dnlg4 mutants and dnrx83;dnlg3 and dnlg2;dnlg3 double mutants, which suggests that both neurexin and neuroligins play a vital role in preventing synaptic degeneration.

Color medical image cryptography technology based on segmentation and fractional-order hyperchaotic system.

This paper proposes a novel color medical image encryption method based on mean shift algorithm and fractional-order hyperchaotic system. Firstly, color medical images were divided into lesion area, detection area, and edge area by using mean shift clustering. Low-value pixels and zero-value pixels in the edge region are abandoned to improve the encryption efficiency. Secondly, the doctor-patient information is embedded into the pixel matrix of the lesion region by using discrete wavelet transform and singular value decomposition. Thirdly, the pixels of the lesion region and the detection region are processed by using fractional-order hyperchaotic system. Finally, the color medical image embedded with doctor-patient information can be quickly encrypted. Security analysis shows that the encryption method has not only strong robustness and security, but also good performance against various attacks. SPNA and CA results: (a) s1-DE-SPNA, (b) s2-DE-SPNA, (c) s3-DE-SPNA, (d) s4-DE-SPNA; (e) s1-DE-CA, (f) s2-DE-CA, (g) s3-DE-CA, (h) s4-DE-CA.

Eltrombopag in patients with chronic immune thrombocytopenia in Asia-Pacific, the Middle East, and Turkey: final analysis of CITE.

CITE was a prospective, noninterventional study in adult patients with chronic immune thrombocytopenia treated with eltrombopag under routine clinical care in Asia-Pacific, the Middle East, and Turkey. Data to assess eltrombopag usage, compliance, and outcomes were collected from May 2017 to December 2020. Platelet response was defined as platelet count ≥50 × 103/µL in the absence of rescue medications and splenectomy. Quality of life was evaluated using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire. Noncompliance was defined as the number of missed doses and number of days where the patient did not follow food instructions. A total of 231 patients were enrolled; the median (range) duration of eltrombopag treatment was 484.5 (1-642) days. Compliance to prescribed eltrombopag dose since the previous routine visit was high at ≥96.0%. Baseline median platelet count was 19.0 × 103/µL, which increased to ≥50 × 103/µL at month 2 and mostly fluctuated between 70 × 103/µL and 100 × 103/µL thereafter. The median time to first platelet response was 1.05 (95% confidence interval: 0.92-1.28) months, and the median (interquartile range) maximum duration of platelet response was 193 (57-456) days. FACIT-F scores improved from a mean (standard deviation) 34.4 (12.1) at baseline to 38.5 (9.1) at month 18. Adverse events occurred in 50.9% of patients (n = 116), the most common being upper respiratory tract infection (8.3%) and headache (6.6%). These findings confirmed the effectiveness of eltrombopag treatment in routine practice and reassured that real-world compliance to eltrombopag-prescribed doses and dietary instructions in Asia-Pacific, the Middle East, and Turkey were in line with current recommendations.

Laparoscopic spleen-preserving No. 10 lymph node dissection for advanced proximal gastric cancer in left approach: a new operation procedure.

BACKGROUND: To explore the feasibility of laparoscopic spleen-preserving No. 10 lymph node dissection in a left-sided approach for advanced proximal gastric cancer. METHODS: The clinical data of 32 patients with advanced proximal gastric cancer who underwent laparoscopic spleen-preserving No. 10 lymph node dissection from June 2010 to December 2011 were analyzed. RESULTS: Laparoscopic spleen-preserving No. 10 lymph node dissection using a left-sided approach was successfully performed for all patients without open conversion. The mean operation time was 206.4±54.3 minutes, mean intraoperative blood loss was 68.2±34.1 ml, mean number of No. 10 lymph nodes dissected was 2.8±2.1, mean number of positive No. 10 lymph nodes was 0.6±1.2, and the incidence of No. 10 lymph node metastasis was 11.6%. The mean postoperative hospital stay was 11.3±1.5 days. The postoperative morbidity rate was 9.4%, and there was no postoperative death. Splenic lobar vessels of all 32 patients were anatomically classified and divided into three types: 4 patients had a single lobar vessel, 22 had two lobar vessels and 6 had three lobar vessels. CONCLUSIONS: Laparoscopic spleen-preserving No. 10 lymph node dissection for advanced proximal gastric cancer using a left-sided approach is technically feasible. It simplifies the complicated surgical procedure of No. 10 lymph node dissection and leads to the popularization and promotion of this technique.

Degradation of mixed typical odour gases via non-thermal plasma catalysis.

The simultaneous treatment of H2S and NH3 typical odours by plasma was investigated and the co-treatment of both was found to have a facilitating effect the conversion. The degradation efficiency and by-product emissions of single plasma technology and plasma co-catalytic two-stage technology were compared and the degradation mechanism was further analyzed. The results show that in the single plasma technology conversion experiment, the conversion rate of the treated odours mixture is higher than that of the treated single odours, and the by-product emissions of SO2 and NOx are also reduced due to the reaction of intermediate products and by-products during the reaction process. The absolute removal of the odours mixture is optimal when treating at a gas flow rate of 6 L/min, a voltage of 16 kV and a frequency of 200 Hz. The M(Ce,Cu)-Mn/13X loaded catalyst was synthesized by co-precipitation method. Under the conditions of gas flow rate of 3-7 L/min, the efficiency of H2S and NH3 removal and the reduction of by-product emission were ranked as: uncatalyzed > Cu-Mn/13X > Ce-Mn/13X, which proved that Ce-Mn/13X showed better catalytic activity and application value.

Improved analysis method of neuromuscular junction in Drosophila larvae by transmission electron microscopy.

The Drosophila neuromuscular junction is an excellent model for neuroscience research. However, the distribution of neuromuscular junctions is very diffuse, and it is not easy to accurately locate during ultrathin sectioning, which seriously interferes with the ultrastructural analysis under electron microscopy that only has a small field of view. Here, we reported an efficient method for acquiring the ultrastructural picture of neuromuscular junctions in Drosophila larva under electron microscopy. The procedure was as follows: first, the larval sample of body wall muscle was placed between the metal mesh and was dehydrated with alcohol and infiltrated with epoxy resin to prevent the sample from curling or bending, after it was dissected and fixed into thin slices. Second, the sample was embedded in resin into a flat sheet to facilitate the positioning of the muscles. Third, carefully and gradually remove the excess resin and the cuticle of the larvae, cut off both ends of the special body segment, and trim the excess specific muscles according to the recommended ratio of trimming muscles, which would reduce the workload exponentially. At last, the trimmed sample were prepared into serial about 1000 ultrathin sections that was about total 80 microns thickness, and 30-40 sections were gathered into a grid to stain with lead citrate and uranyl acetate. This method could also be applied to the other small and thin samples such as the Drosophila embryo, ventral nerve cord and brain.

Neurexin and Neuroligins Maintain the Balance of Ghost and Satellite Boutons at the Drosophila Neuromuscular Junction.

Neurexins and neuroligins are common synaptic adhesion molecules that are associated with autism and interact with each other in the synaptic cleft. The Drosophila neuromuscular junction (NMJ) bouton is a well-known model system in neuroscience, and ghost and satellite boutons, respectively, indicate the poor development and overgrowth of the NMJ boutons. However, the Drosophila neurexin (DNrx) and Drosophila neuroligins (DNlgs) are mainly observed in type Ib boutons, indicating the ultrastructural and developmental phenotypes of the Drosophila NMJ. Here, we identified the ultrastructural and developmental features of ghost and satellite boutons by utilizing dneurexin (dnrx) and dneuroligins (dnlgs) fly mutants and other associated fly strains. Ghost boutons contain synaptic vesicles with multiple diameters but very rarely contain T-bar structures and swollen or thin subsynaptic reticulum (SSR) membranes. The muscle cell membrane is invaginated at different sites, stretches to the ghost bouton from different directions, forms several layers that enwrap the ghost bouton, and then branches into the complex SSR. Satellite boutons share a common SSR membrane and present either a typical profile in which a main bouton is encircled by small boutons or two atypical profiles in which the small boutons are grouped together or distributed in beads without a main bouton. Electron and confocal microscopy data showed that dnrx, dnlg1, dnlg2, dnlg3, and dnlg4 mutations led to ghost boutons; the overexpression of dnrx, dnlg1, dnlg2, dnlg3, and dnlg4 led to satellite boutons; and the dnlg2;dnlg3 double mutation also led to satellite boutons. These results suggested that DNrx and DNlgs jointly maintain the development and function of NMJ boutons by regulating the balance of ghost and satellite boutons in Drosophila.

Oligotrophic Nitrification and Denitrification Bacterial Communities in a Constructed Sewage Treatment Ecosystem and Nitrogen Removal of Delftia tsuruhatensis NF4.

Oligotrophic nitrifiers and denitrifiers play important roles in the removal of nitrogen from wastewater. Here, we studied the dominant bacterial populations of the sewage treatment ecosystem (STE) water from different processes and those of culture on oligotrophic heterotrophic nitrification (OHN) medium and oligotrophic aerobic denitrification (OAD) medium, using co-analysis of Illumina HiSeq DNA sequencing and traditional culture methods. The results showed that the STE water had no dominant population of oligotrophic nitrifiers or oligotrophic denitrifiers. However, after culturing on OHN medium and OAD medium, the core genera Pseudomonas, Aeromonas, and Acinetobacter that have the nitrogen removal capacity in oligotrophic environments, dominated in the bacterial community. The principal component analysis (PCA) showed that the bacterial community in the constructed rapid infiltration (CRI) effluent water of STE had high similarity with those of cultures on OHN medium and OAD medium, which prompt the special purification role of nitrogen in the CRI system. The sodium alginate immobilized OAD bacteria strain Delftia tsuruhatensis NF4 was isolated from the CRI system, with total nitrogen (TN) removal efficiency of 43.3% in sterilized STE influent water, and 60.1% in OAD medium on day three. The immobilization significantly influenced the TN and nitrate removal efficiency in OAD medium (p < 0.05), but not in sterilized STE influent water (p > 0.05). This study would lay the foundation for resource discovery of oligotrophic heterotrophic nitrifiers and aerobic denitrifiers in STE and further functional application of them on the bioremediation of wastewater.Oligotrophic nitrifiers and denitrifiers play important roles in the removal of nitrogen from wastewater. Here, we studied the dominant bacterial populations of the sewage treatment ecosystem (STE) water from different processes and those of culture on oligotrophic heterotrophic nitrification (OHN) medium and oligotrophic aerobic denitrification (OAD) medium, using co-analysis of Illumina HiSeq DNA sequencing and traditional culture methods. The results showed that the STE water had no dominant population of oligotrophic nitrifiers or oligotrophic denitrifiers. However, after culturing on OHN medium and OAD medium, the core genera Pseudomonas, Aeromonas, and Acinetobacter that have the nitrogen removal capacity in oligotrophic environments, dominated in the bacterial community. The principal component analysis (PCA) showed that the bacterial community in the constructed rapid infiltration (CRI) effluent water of STE had high similarity with those of cultures on OHN medium and OAD medium, which prompt the special purification role of nitrogen in the CRI system. The sodium alginate immobilized OAD bacteria strain Delftia tsuruhatensis NF4 was isolated from the CRI system, with total nitrogen (TN) removal efficiency of 43.3% in sterilized STE influent water, and 60.1% in OAD medium on day three. The immobilization significantly influenced the TN and nitrate removal efficiency in OAD medium (p < 0.05), but not in sterilized STE influent water (p > 0.05). This study would lay the foundation for resource discovery of oligotrophic heterotrophic nitrifiers and aerobic denitrifiers in STE and further functional application of them on the bioremediation of wastewater.

In vivo performance of implantable biodegradable preparations delivering Paclitaxel and Etanidazole for the treatment of glioma.

Drug-releasing implants delivering chemotherapeutic and radio-sensitizing agents are beginning to play a major role in the post-surgical eradication of residual glioma in the brain. Benefits from early arresting of tumor growth and tumor recovery dynamics stress the impact of drug release profiles of the implants on the efficacy of the treatment. This paper examines responses of BALB/c nude mice, bearing C6 glioma tumors subcutaneously, to treatments by PLGA microspheres, microparticles and discs-delivering Paclitaxel and Etanidazole. The experimental results are used to correlate the efficacy of treatment to in vitro release profiles from the various formulations. Our study demonstrates that radio-sensitizing effects during irradiation could be achieved by double burst profiles from Etanidazole-loaded discs, when compared to controls 17 days after implantation despite the short half-life of Etanidazole (1.4h) in vivo. These results also showed inhibited tumor growth on tumor volumes of 59%, 65% and 70% over the blank placebo groups after 21 days of tumor growth for spray-dried microspheres, electrohydrodynamic atomization microparticles and spray-dried discs, respectively.