The role of extended synaptotagmin at membrane contact sites in cancer research.

Membrane contact sites (MCSs) are adjacent locations between the membranes of two different organelles and play important roles in various physiological processes, including cellular calcium and lipid signaling. In cancer research, MCSs have been proposed to regulate tumor metabolism and fate, contributing to tumor progression, and this function could be exploited for tumor therapy. However, there is little evidence on how MCSs are involved in cancer progression. In this review, we use extended synaptotagmins (E-Syts) as an entry point to describe how MCSs affect cancer progression and may be used as new diagnostic biomarkers. We then introduced the role of E-Syt and its related pathways in calcium and lipid signaling, aiming to explain how MCSs affect tumor proliferation, progression, metastasis, apoptosis, drug resistance, and treatment through calcium and lipid signaling. Generally, this review will facilitate the understanding of the complex contact biology of cancer cells.

Total laparoscopic total gastrectomy and distal esophagectomy combined with reconstruction by transhiatal esophagojejunal Roux-en-y mediastinal anastomosis for Siewert II AEG.

PURPOSE: The optimal procedure is still controversial about Siewert type II AEG, We are attempt to explore the efficacy and feasibility of total laparoscopic total gastrectomy and distal esophagectomy combined with reconstruction by transhiatal esophagojejunal Roux-en-y mediastinal anastomosis for Siewert type II AEG. METHOD: Data of patients with Siewert type II AEG who received total laparoscopic total gastrectomy and distal esophagectomy combined with reconstruction by transhiatal esophagojejunal Roux-en-y mediastinal anastomosis in the Hebei General Hospital were collected from October 2020 to October 2021, The operation time, surgical blood loss, the number of dissected lymph nodes, duration of drainage tube, the length of stay in ICU, the resume oral feeding time, the length of postoperative hospital stay, postoperative complications and other related indicators of the patients were collected to evaluate the safety and feasibility of this operation. RESULT: A total of 17 patients received total laparoscopic total gastrectomy and distal esophagectomy combined with reconstruction by transhiatal esophagojejunal Roux-en-y mediastinal anastomosisin the treatment of Siewert type II AEG were analyzed in our research. The mean operation time was 253 ± 24.8 min (196-347 min); The median surgical blood loss was 250 ml (20-2400 ml); The average number of dissected lymph nodes were 28 ± 4.6 (17-36); The median duration of drainage tube was 5 days (3-7days); The median length of stay in ICU was 18 h(10-34 h); The median time of resume oral feeding was 6 days (5-7days); The median postoperative hospital stay was 11 days (8-15 days). Among the all enrolled patients, one patient underwent the conversion to laparotomy due to the massive intraoperative bleeding, one patient developed anastomotic stenosis at jejunum side-to-side anastomosis on the first month after surgery, there was no case of death during the operation and postoperative anastomotic fistula. All patients achieved R0 resection with an average distance of 6 cm (4-8.5 cm) from the upper margin of the tumor to the resection margin. CONCLUSION: The operation of total laparoscopic total gastric and distal esophagectomy combined with reconstruction by transhiatal esophagojejunal Roux-en-y mediastinal anastomosis is technically feasible and sufficiently safe in the treatment of Seiwert type II AEG from our primary clinical experience. This procedure could be one of the alternatives for the radical treatment of Siewert type II AEG.

Purely nonlinear amplified ultralow-noise transmission using hybrid second-order DRA and PPLN-based PSA.

We report ultralow-noise transmission over a 102-km single-mode fiber using a purely nonlinear amplification scheme consisting of a second-order distributed Raman amplifier (DRA) and a phase-sensitive amplifier (PSA) based on periodically poled LiNbO3 waveguides. The hybrid DRA/PSA features a broadband gain over the C and L bands and an ultralow-noise advantage, with a less than -6.3 dB effective noise figure in the DRA stage and a 1.6 dB optical signal-to-noise ratio (OSNR) improvement in the PSA stage. Compared with the unamplified link, the OSNR is improved by 10.2 dB for a 20-Gbaud 16QAM signal in the C band, resulting in error-free detection (a bit-error rate of less than 3.8 × 10-3) for the signal with a low link input power of -25 dBm. Mitigation of nonlinear distortion is also achieved by the proposed nonlinear amplified system due to the subsequent PSA.

Kukoamine A activates Akt/GSK-3ß signaling pathway to inhibit oxidative stress and relieve myocardial ischemia-reperfusion injury.

PURPOSE: Myocardial ischemia/reperfusion (MI/R) injury refers to a pathological condition of treatment of myocardial infarction. Oxidative stress and inflammation are believed to be important mechanisms mediating MI/R injury. Kukoamine A (KuA), a sperm, is the main bioactive component extracted from the bark of goji berries. In this study, we wanted to investigate the possible effects of KuA on MI/R injury. METHODS: In this experiment, all rats were divided into sham operation group, MI/R group, KuA 10 mg + MI/R group, KuA 20 mg + MI/R group. After 120 min of ischemia/reperfusion treatment, left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), maximal rates of rising and fall of left ventricular pressure (±dp/dtmax), and ischemic area were detected. Serum samples of rats in each group were collected. The enzyme activities of catalase (CAT), glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), levels of malondialdehyde (MDA), CK muscle/brain (CK-MB), tumor necrosis factor (TNF), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were detected using enzyme-linked immunosorbent assay (ELISA). The apoptosis of myocardium in each group was detected according to the instructions of the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The expressions of mammalian target of glycogen synthase kinase-3ß (GSH-3ß) and protein kinase B (Akt) mRNA level in myocardial tissues were detected via reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: MI/R rats showed a significant increase in oxidative stress and inflammation. In addition, we showed that KuA significantly improved the myocardial function such as LVSP, left ventricular ejection fraction, +dp/dt, and -dp/dt. Here, it attenuated dose-dependent histological damage in ischemia-reperfused myocardium, which is associated with the enzyme activities of SOD, GSH-PX, and levels of MDA, IL-6, TNF-α, L-1ß. CONCLUSIONS: KuA inhibited gene expression of Akt/GSK-3ß, inflammation, oxidative stress and improved MR/I injury. Taken together, our results allowed us to better understand the pharmacological activity of KuA against MR/I injury.

Effect and mechanisms of synthesis conditions on the cadmium adsorption capacity of modified fly ash.

In this study, modified coal fly ash (NMFA) was prepared by sodium hydroxide (NaOH) with low-temperature hydrothermal method. The differences of the ash to alkali mass ratio (5:3, 5:4, 5:5, 5:6), calcination temperature (100 â„ƒ, 200 â„ƒ, 300 â„ƒ), and calcination time (1 h, 3 h, 5 h) were investigated. The adsorption experiments obtained the optimal result with the ash to base ratio of 5:5, calcination temperature of 200 â„ƒ, and calcination time of 3 h, adsorbing 90.27 mg/g of Cd2+. The characterization results (SEM-EDS, FTIR, XRD, and XPS) also confirmed the effective adsorption of Cd2+ by NMFA. The functional groups of Si-O, Al-O, and Fe-O played an important role in Cd2+ removal. Meanwhile, the influences of dosage, different pH, and co-existing cations were also investigated. Quasi-secondary adsorption kinetics and Langmuir isotherm model were also referred to the Cd2+ adsorption by NMFA. Therefore, the good adsorption of NMFA-3 on Cd2+ provided new ideas for the safe utilization of fly ash and heavy metal purification in wastewater.

Which Is the Most Appropriate PI3K Inhibitor for Breast Cancer Patients with or without PIK3CA Status Mutant? A Systematic Review and Network Meta-Analysis.

OBJECTIVE: The phosphatidylinositol 3-kinase (PI3K) signaling pathway is a promising treatment target for patients with breast cancer (BC). Our study aimed to evaluate the most effective and safe PI3K inhibitor for patients with BC, especially in PIK3CA mutation. METHODS: Electronics databases were systematically searched from their inception to June 2020 for published randomized controlled trials (RCTs) comparing PI3K inhibitor therapy versus non-PI3K inhibitor therapy in patients with BC that mentioned or reported data of PIK3CA-mutated patient subgroups. Eligible RCTs had to report at least one of the following clinical outcomes: objective response rate (ORR), progression-free survival (PFS), or adverse events (AE). RESULTS: Nine eligible RCTs involving 3872 BC patients and four PI3K inhibitor therapy arms (i.e., alpelisib, buparlisib, pictilisib, and taselisib) were included. In evaluating ORR, beneficial significant results of PI3K inhibitors could be found in the PIK3CA mutated group (1.952, 1.012 to 3.766); analogous results could also be found in 6m-PFS (1.519, 1.144 to 2.018) and PFS from HR data (-0.346, -0.525 to -0.168). From pairwise and network meta-analyses, buparlisib showed the most favorable ORR, as it was significantly different from fulvestrant in the PIK3CA-mutated patient group (2.80, 1.56 to 5.03). Alpelisib ranked first in the assessment of 6m-PFS and was significantly different from fulvestrant in the PIK3CA-mutated group (2.33, 1.45 to 3.44). The above PI3K inhibitors had good safety with few serious AEs. PROSPERO registration CRD42020193932. CONCLUSION: The PI3K inhibitors alpelisib and buparlisib appear to have superior efficacy and safety therapeutic choices for patients with BC, especially in PIK3CA-mutated patients.

Exploration and analysis of the value of tumor-marker joint detection in the pathological type of lung cancer.

Lung cancer is a disease characterized by the uncontrolled growth of cells in lung tissue. If left untreated, cell growth can spread beyond the lungs to a process called metastasis and reach surrounding tissues or other organs. This experiment was set up to discuss and analyze the research value of joint detection of tumor markers including carcino-embryonic antigen (CEA), cytokeratin 19 fragments (CYFRA21-1) and neuron-specific enolase (NSE) in the diagnosis and pathological type of lung cancer. From November 2016 to February 2018, 378 cases of patients with lung cancer treated in our hospital and 200 cases of people with healthy physical examinations were collected. The electrochemical immunoluminescence method was adopted to detect the CEA, CYFRA21-1 and NSE. The detected positive rate and the concentration of CEA, CYFRA21-1 and NSE of lung cancer group were higher than that of the healthy physical examination group. The differences were of statistical significance (P<0.05); the detected positive rate of CEA and CYFRA21-1 and the concentration of CEA, CYFRA21-1 and NSE of squamous carcinoma group were higher than that of the adenocarcinoma group. The differences were of statistical significance (P<0.05). The CEA, CYFRA21-1 and NSE are related to the pathological type of lung cancer and can be regarded as related indicators to diagnose lung cancer.

Possibility of removing cadmium pollution from the environment using a newly synthesized material coal fly ash.

Coal fly ash (FA) is a solid waste produced in coal combustion. This study focused on the removal of Cd2+ from wastewater by a newly synthesized adsorbent material, the low-temperature and sodium hydroxide-modified fly ash (SHM-FA). The SEM and BET analyses of SHM-FA demonstrated that the adsorbent was porous and had a huge specific surface area. The XRF, XRD, FTIR and TGA characterization showed that SHM-FA has an amorphous structure and the Si-O and Al-O in the fly ash dissolved into the solution, which improved the adsorption capacity of Cd. The results indicated that SHM-FA has desired adsorption performance. The adsorption performance was significantly affected by the dosage, starting pH, Cd2+ initial concentrations, and temperature, as well as adsorption time. In the optimal conditions, the removal efficiency and adsorption capacity of Cd2+ by SHM-FA were 95.76% and 31.79 mg g-1, respectively. The experiment provided clearly explained adsorption kinetics and isotherms. And the results confirmed that the adsorption behavior was well described by the pseudo-second-order kinetic and Langmuir isotherm model, which means that the adsorption of Cd2+ was controlled by SHM-FA through surface reaction and external diffusion process. In addition, the recycling of SHM-FA for reuse after Cd2+ adsorption showed high removal efficiency up to six times of use. Therefore, it can be concluded that SHM-FA is a low-cost adsorbent for Cd2+ removal from wastewater.

Differential gene expression analysis in glioblastoma cells and normal human brain cells based on GEO database.

The differentially expressed genes between glioblastoma (GBM) cells and normal human brain cells were investigated to performed pathway analysis and protein interaction network analysis for the differentially expressed genes. GSE12657 and GSE42656 gene chips, which contain gene expression profile of GBM were obtained from Gene Expression Omniub (GEO) database of National Center for Biotechnology Information (NCBI). The 'limma' data packet in 'R' software was used to analyze the differentially expressed genes in the two gene chips, and gene integration was performed using 'RobustRankAggreg' package. Finally, pheatmap software was used for heatmap analysis and Cytoscape, DAVID, STRING and KOBAS were used for protein-protein interaction, Gene Ontology (GO) and KEGG analyses. As results: i) 702 differentially expressed genes were identified in GSE12657, among those genes, 548 were significantly upregulated and 154 were significantly downregulated (p<0.01, fold-change >1), and 1,854 differentially expressed genes were identified in GSE42656, among the genes, 1,068 were significantly upregulated and 786 were significantly downregulated (p<0.01, fold-change >1). A total of 167 differentially expressed genes including 100 upregulated genes and 67 downregulated genes were identified after gene integration, and the genes showed significantly different expression levels in GBM compared with normal human brain cells (p<0.05). ii) Interactions between the protein products of 101 differentially expressed genes were identified using STRING and expression network was established. A key gene, called CALM3, was identified by Cytoscape software. iii) GO enrichment analysis showed that differentially expressed genes were mainly enriched in 'neurotransmitter:sodium symporter activity' and 'neurotransmitter transporter activity', which can affect the activity of neurotransmitter transportation. KEGG pathway analysis showed that the differentially expressed genes were mainly enriched in 'protein processing in endoplasmic reticulum', which can affect protein processing in endoplasmic reticulum. The results showed that: i) 167 differentially expressed genes were identified from two gene chips after integration; and ii) protein interaction network was established, and GO and KEGG pathway analyses were successfully performed to identify and annotate the key gene, which provide new insights for the studies on GBN at gene level.

Cadmium-induced neural tube defects and fetal growth restriction: Association with disturbance of placental folate transport.

Previous studies found that maternal Cd exposure on gestational day (GD)9 caused forelimb ectrodactyly and tail deformity, the characteristic malformations. The aim of the present study was to investigate whether maternal Cd exposure on GD8 induces fetal neural tube defects (NTDs). Pregnant mice were intraperitoneally injected with CdCl2 (2.5 or 5.0mg/kg) on GD8. Neither forelimb ectrodactyly nor tail deformity was observed in mice injected with CdCl2 on GD8. Instead, maternal Cd exposure on GD8 resulted in the incidence of NTDs. Moreover, maternal Cd exposure on GD8 resulted in fetal growth restriction. In addition, maternal Cd exposure on GD8 reduced placental weight and diameter. The internal space of maternal and fetal blood vessels in the labyrinth layer was decreased in the placentas of mice treated with CdCl2. Additional experiment showed that placental PCFT protein and mRNA, a critical folate transporter, was persistently decreased when dams were injected with CdCl2 on GD8. Correspondingly, embryonic folate content was markedly decreased in mice injected with CdCl2 on GD8, whereas Cd had little effect on folate content in maternal serum. Taken together, these results suggest that maternal Cd exposure during organogenesis disturbs transport of folate from maternal circulation to the fetuses through down-regulating placental folate transporters.

Maternal serum cadmium level during pregnancy and its association with small for gestational age infants: a population-based birth cohort study.

The association between maternal cadmium (Cd) exposure during pregnancy and the increased risk of fetal growth restriction (FGR) remains controversial. The present study evaluated the association between maternal serum Cd level and risk of small for gestational age (SGA) infants in a Chinese population. The present study analyzed a subsample of the C-ABCS cohort that recruited 3254 eligible mother-and-singleton-offspring pairs. Maternal serum Cd level during pregnancy was measured by graphite furnace atomic absorption spectrometry. The rate and odds ratio (OR) for SGA infant were calculated. The rate for SGA infant was 10.6% among subjects with H-Cd (≥1.06 µg/L), significantly higher than 7.5% among subjects with L-Cd (<1.06 µg/L). OR was 1.45 (95% CI: 1.11, 1.90; P = 0.007) among subjects with H-Cd. Adjusted OR for SGA infants was 1.43 (95% CI: 1.09, 1.88; P = 0.007) among subjects with H-Cd. Taken together, we observe the fact that maternal Cd exposure at middle gestational stage, elevates the risk of SGA in contrast to early gestational stage. The present results might be interesting and worth more discussing, and guarantee to further studies.

Rosiglitazone pretreatment protects against lipopolysaccharide-induced fetal demise through inhibiting placental inflammation.

Peroxisome proliferator-activated receptor (PPAR)-γ is highly expressed in human and rodent placentas. Nevertheless, its function remains obscure. The present study investigated the effects of rosiglitazone, a PPAR-γ agonist, on LPS-induced fetal death. All pregnant mice except controls were intraperitoneally injected with LPS (150 µg/kg) daily from gestational day (GD)15 to GD17. As expected, maternal LPS injection caused placental inflammation and resulted in 63.6% fetal death in dams that completed the pregnancy. Interestingly, LPS-induced fetal mortality was reduced to 16.0% when pregnant mice were pretreated with RSG. Additional experiment showed that rosiglitazone pretreatment inhibited LPS-induced expressions of tumor necrosis factor (Tnf)-α, interleukin (Il)-1ß, Il-6, macrophage inflammatory protein (Mip)-2 and keratinocyte-derived chemokine (Kc) in mouse placenta. Although rosiglitazone had little effect on LPS-evoked elevation of IL-10 in amniotic fluid, it alleviated LPS-evoked release of TNF-α and MIP-2 in amniotic fluid. Further analysis showed that pretreatment with rosiglitazone, which activated placental PPAR-γ signaling, simultaneously suppressed LPS-evoked nuclear factor kappa B (NF-κB) activation and blocked nuclear translocation of NF-κB p65 and p50 subunits in trophoblast giant cells of the labyrinth layer. These results provide a mechanistic explanation for PPAR-γ-mediated anti-inflammatory activity in the placentas. Overall, the present study provides additional evidence for roles of PPAR-γ as an important regulator of placental inflammation.

Treatment of Benign Prostatic Hyperplasia by Ultrasound-Guided Botulinum Toxin Type A Injection.

The objective of the study was to determine the efficacy of ultrasound-guided botulinum toxin type A (BTX-A) injection in the treatment of benign prostatic hyperplasia (BPH). In the 32 patients clinically diagnosed with BPH, 200 IU BTX-A was injected into five points at the lateral and middle lobes of the prostate under the guidance of ultrasound using a balloon dilatational device. The international prostate symptom score, quality of life score, maximum flow rate, post-void residual urine volume, prostate-specific antigen, and prostate volume were determined before treatment and at 1, 3, 6, and 12 months after treatment. All clinical symptoms and indicators were remarkably improved 1 month after the treatment and reached the optimal levels at 6 months post-treatment. This improvement of clinical parameters was maintained for a period of at least 1 year. Ultrasound-guided BTX-A injection was found to be safe and effective in the management of BPH.