Gibberellic acid targeting ZBTB16 reduces NF-κB dependent inflammatory stress in sepsis-induced neuroinflammation.

OBJECTIVE: Sepsis is frequently complicated by neuroinflammation. Gibberellic acid (GA3) is recognized for its anti-inflammatory properties. In this study, our objective was to investigate whether GA3 could alleviate Nuclear factor-kappa B (NF-κB) -dependent inflammatory stress in sepsis-induced neuroinflammation. METHODS: C57BL/6 J mice were administered 10 mg/kg lipopolysaccharide (LPS) to induce sepsis. BV2 cells were pre-incubated with GA3 and subjected lipopolysaccharide stimulation to replicate the inflammatory microglia during sepsis. Subsequently, we assessed the release of IL-6, TNF-α, and IL-1ß, along with the expression of Zbtb16, NF-κB, and IκB. To investigate whether any observed anti-inflammatory effects of GA3 were mediated through a Zbtb16-dependent mechanism, Zbtb16 was silenced using siRNA. RESULTS: GA3 improved the survival of sepsis mice and alleviated post-sepsis cognitive impairment. Additionally, GA3 attenuated microglial M1 activation (pro-inflammatory phenotype), inflammation, and neuronal damage in the brain. Moreover, GA3 inhibited the release of TNF-α, IL-6, and IL-1ß in microglia stimulated with LPS. The NF-κB signaling pathway emerged as one of the key molecular pathways associated with the impact of GA3 on LPS-stimulated microglia. Lastly, GA3 upregulated Zbtb16 expression in microglia that had been downregulated by LPS. The inhibitory effects of GA3 on microglial M1 activation were partially reversed through siRNA knockdown of Zbtb16. CONCLUSIONS: Pre-incubation of microglia with GA3 led to the upregulation of the NF-κB regulator, Zbtb16. This process counteracted LPS-induced microglial M1 activation, resulting in an anti-inflammatory effect upon subsequent LPS stimulation.

Stellate Ganglion Block Improves Postoperative Sleep Quality and Analgesia in Patients with Breast Cancer: A Randomized Controlled Trial.

INTRODUCTION: Postoperative impaired sleep quality and pain are associated with adverse outcomes. Stellate ganglion block (SGB) has shown promising results in enhancing sleep quality and alleviating neuropathic pain. This study aimed to investigate the effects of ultrasound-guided SGB on postoperative sleep quality and pain in patients undergoing breast cancer surgery. METHODS: This study is a parallel-group randomized controlled clinical trial with two groups: SGB and control. Fifty female patients undergoing breast cancer surgery were randomized in a 1:1 ratio to receive preoperative ultrasound-guided single-injection SGB (SGB group) or just an ultrasound scan (control group). All participants were blinded to the group assignment. The primary outcome was postoperative sleep quality, assessed by the St. Mary's Hospital Sleep Questionnaire and actigraphy 2 days postoperatively. The secondary outcome was postoperative pain, measured by the visual analog scale. RESULTS: A total of 48 patients completed the study, with 23 patients in the control group and 25 in the SGB group. The postoperative St. Mary's Hospital Sleep Questionnaire scores were significantly higher in the SGB group than in the control group on 1 day postoperative (30.88 ± 2.44 versus 27.35 ± 4.12 points, P = 0.001). The SGB also increased the total sleep time and sleep efficiency (main actigraphy indicators) during the first two postoperative nights. Compared with the control group, preoperative SGB reduced postoperative pain and the incidence of breast cancer-related lymphedema (20% versus 52.2%, P = 0.02, odds ratio 0.229, 95% confidence interval 0.064-0.821). There were no adverse events related to SGB. CONCLUSION: Preoperative ultrasound-guided SGB improves postoperative sleep quality and analgesia in patients undergoing breast cancer surgery. SGB may be a safe and practical treatment to enhance the postoperative quality of life in patients with breast cancer. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (ChiCTR2100046620, principal investigator: Kai Zeng, date of registration: 23 May 2021).

Postoperative radiotherapy may not be necessary for locally advanced head and neck squamous cell carcinoma: a case-match multicentre study.

BACKGROUND: Some head and neck cancer surgeons found that many patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) without postoperative radiotherapy (PORT) also have a good prognosis. The purpose of this study was to determine the effect of PORT on survival in patients with LA-HNSCC. METHODS: A case-match cohort analysis was performed at two institutions on patients with LA-HNSCC. Patients who received surgery alone were case-matched 1: 1 with patients treated by surgery plus PORT based on pT, pN, tumor subsite etc. RESULTS: 114 patients were matched into 57 pairs, with a median follow-up period of 40.2 months. No difference in overall survival (OS, HR 0.88; 95% CI 0.50-1.58; P = 0.79) or disease-specific survival (DFS, 0.86; 95% CI 0.50-1.50; P = 0.76) was observed with no PORT. CONCLUSIONS: PORT isn't necessary for patients with LA-HNSCC who are treated for the first time as long as the head and neck cancer surgeon adhere to appropriate surgical concepts. The indications of PORT for patients with LA-HNSCC need to be further discussed.

Peripheral cytotoxic T lymphocyte predicts first-line progression free survival in HER2-positive advanced breast cancer.

BACKGROUND: The role of peripheral blood lymphocyte (pBL) in breast cancer has long been studied. However, the predictive role of pBL in advanced breast cancer (ABC) is poorly understood. METHODS: A total of 303 patients with ABC were consecutively recruited at our center between January 2015 and September 2019. At baseline, pBL subtypes were detected in all patients with 229 blood samples available for circulating tumor DNA (ctDNA) detection. pBL was analyzed through flow cytometry. ctDNA-based gene mutations were detected using next generation sequencing. The cutoff value of pCTL was estimated by X-tile software. Progression free survival (PFS) was estimated by Kaplan-Meier curve and Cox hazard proportion regression model, with difference detection by log-rank test. RESULTS: Median follow-up time of the study was 21.0 months. The median age of diagnosis was 52.0 years. Among the pBL subtypes, only pCTL level was found predictive for PFS in the HER2+ patients whom received anti-HER2 therapy (13.1 vs. 5.6 months, P = 0.001). However, the predictive role of pCTL was not found in HR-positive (P = 0.716) and TNBC (P = 0.202). pCTL high associated with suppressive immune indictors including lower CD4/CD8 ratio (P = 0.004) and high level of Treg cell (P = 0.004). High occurrence of FGFR1 amplification which has been reported as immune suppressor was also found in HER2+ patients with pCTL high (22.2% vs. 4.3%, P = 0.048). CONCLUSIONS: Higher pCTLs level associated with shorter PFS and FGFR1 mutation in HER2+ ABC patients.

Intraosseous venous malformation of the maxilla after enucleation of a hemophilic pseudotumor: A case report.

BACKGROUND: Hemophilic pseudotumor (HP) is a rare complication in patients with hemophilia. The lesion most frequently occurs in the long bones, pelvis, small bones of the hands and feet, or rarely in the maxillofacial region. Postoperative changes in HP are seldom arrested, whereas angiogenesis characterized by disturbed wound healing in HP may cause vascular malformations. CASE SUMMARY: We report the case of an 11-year-old boy who was affected by maxillary intraosseous venous malformation. Enucleation of an HP without factor replacement was performed initially on the right side of the maxilla 3 years ago. The patient was referred to us because of painless swelling in the same location. Factor replacement and subtotal maxillectomy were performed. Pathological examinations revealed intraosseous venous malformation. CONCLUSION: This study is the first to document the development of intraosseous venous malformation after enucleation of an HP in the maxillofacial region. Angiogenesis characterized by disturbed wound healing in patients with hemophilia may be pivotal in the pathogenesis of this condition.

Silencing of lysyl oxidase­like 2 inhibits the migration, invasion and epithelial­to­mesenchymal transition of renal cell carcinoma cells through the Src/FAK signaling pathway.

The aim of the present study was to investigate the effects of lysyl oxidase­like 2 (LOXL2) on the invasion, migration and epithelial­to­mesenchymal transition (EMT) of renal cell carcinoma (RCC) cells through the steroid receptor coactivator (Src)/focal adhesion kinase (FAK) signaling pathway. RCC tissues and adjacent normal tissues were collected from 80 patients with RCC. Immunohistochemistry was used to determine the positive expression rate of the LOXL2 protein. The expression levels of LOXL2 in the HK­2, 786­O, ACHN, Caki1 and A498 cell lines were detected by reverse transcription­quantitative polymerase chain reaction (RT­qPCR). The high LOXL2­expressing 786­O cells were selected for gene silencing experiments, whereas Caki1 cells, which exhibited low LOXL2 expression, were used for overexpression experiments. RT­qPCR and western blot analysis were applied to determine the expression of LOXL2, FAK, Src, matrix metalloproteinase (MMP)­9, epithelial (E)­cadherin, neuronal (N)­cadherin and vimentin. A MTT assay, a Transwell assay, a wound healing assay and flow cytometry were performed to detect cell proliferation, invasion, migration, cell cycle distribution and apoptosis, respectively. The protein expression rate of LOXL2 in RCC tissues was higher compared with that in adjacent normal tissues. Compared with adjacent normal tissues, the mRNA and protein expression levels of LOXL2, FAK, Src, MMP­9, N­cadherin and vimentin and the levels of FAK and Src phosphorylation were increased, while the mRNA and protein expression levels of E­cadherin were decreased in RCC tissues. Following the transfection of 786­O cells with small interfering (si) RNA against LOXL2, the mRNA and protein expression levels of FAK, Src, MMP­9, N­cadherin and vimentin and the levels of phosphorylated FAK and Src were notably decreased in the si­LOXL2 and PP2 inhibitor treated groups, while that of E­cadherin was substantially increased. Additionally, cell proliferation, invasion, migration and the percentage of RCC cells in the G1 phase were reduced, and cell apoptosis was increased. Additionally, Caki1 cells transfected with LOXL2 exhibited an opposite trend. In summary, these results indicate that LOXL2 silencing inhibits the invasion, migration and EMT in RCC cells through inhibition of the Src/FAK signaling pathway.

IL-33/ST2 axis promotes glioblastoma cell invasion by accumulating tenascin-C.

Tenascin-C (TNC), a very large multimeric glycoprotein, is overexpressed in human glioblastomas, leading to a highly motile and invasive phenotype of glioma cells. However, the regulation of TNC expression in glioma has remained unclear until now. Our data suggest that interleukin-33 (IL-33) may promote the accumulation of TNC protein by autocrine or paracrine modes of action in glioma. In the present study, the expression levels of TNC, IL-33, and ST2 were measured in glioma tissue specimens, and the impact of altered IL-33 expression on TNC was investigated in vitro and in vivo. In contrast with control treatment, IL-33 treatment increased TNC expression, and knockdown of IL-33 attenuated TNC expression in glioma cells. Furthermore, IL-33 induced the activation of nuclear factor κB (NF-κB) and increased the expression of TNC in U251 cells. In addition, blockage of the IL-33-ST2-NFκB pathway resulted in downregulation of TNC production. IL-33 promoted glioma cell invasion by stimulating the secretion of TNC. Similarly, knockdown of TNC inhibited the invasiveness of glioma cells. These findings provide a novel perspective on the role of the IL-33/NF-κB/TNC signalling pathway in supporting cancer progression. Thus, targeting the IL-33/NF-κB/TNC signalling pathway may be a useful therapeutic approach in glioma.

MicroRNA-150 suppresses epithelial-mesenchymal transition, invasion, and metastasis in prostate cancer through the TRPM4-mediated ß-catenin signaling pathway.

Prostate cancer (PCa) remains one of the leading causes of cancer-related deaths among males. The aim of the current study was to investigate the ability of microRNA-150 (miR-150) targeting transient receptor potential melastatin 4 (TRPM4) to mediate epithelial-mesenchymal transition (EMT), invasion, and metastasis through the ß-catenin signaling pathway in PCa. Microarray analysis was performed to identify PCa-related differentially expressed genes, after which both the mirDIP and TargetScan databases were employed in the prediction of the miRNAs regulating TRPM4. Immunohistochemistry and RT-qPCR were conducted to determine the expression pattern of miR-150 and TRPM4 in PCa. The relationship between miR-150 and TRPM4 expression was identified. By perturbing miR-150 and TRPM4 expression in PCa cells, cell proliferation, migration, invasion, cycle, and apoptosis as well as EMT markers were determined accordingly. Finally, tumor growth and metastasis were evaluated among nude mice. Higher TRPM4 expression and lower miR-150 expression and activation of the ß-catenin signaling pathway as well as EMT stimulation were detected in the PCa tissues. Our results confirmed TRPM4 as a target of miR-150. Upregulation of miR-150 resulted in inactivation of the ß-catenin signaling pathway. Furthermore, the upregulation of miR-150 or knockdown of TRPM4 was observed to suppress EMT, proliferation, migration, and invasion in vitro in addition to restrained tumor growth and metastasis in vivo. The evidence provided by our study highlights the involvement of miR-150 in the translational suppression of TRPM4 and the blockade of the ß-catenin signaling pathway, resulting in the inhibition of PCa progression.

ß-Bourbonene attenuates proliferation and induces apoptosis of prostate cancer cells.

Sesquiterpenes have antitumor, anti-inflammation, and anti-fungal effects. ß-bourbonene is a kind of sesquiterpene, but its pharmacological effect has not been studied. The present study was conducted in order to investigate the potential anticancer effects of ß-bourbonene on human prostate cancer PC-3M cells. PC-3M cells were incubated with 0, 25, 50, 100 µg/ml of ß-bourbonene. Cell Counting Kit-8 (CCK-8) detection showed that compared with the control group, ß-bourbonene inhibited the growth of PC-3M cells in a dose-dependent manner. G0/G1 phase arrest was observed by ß-bourbonene by using flow cytometry. TUNEL staining and Annexin V/PI dual-staining method revealed that apoptosis was found in cells with ß-bourbonene treatment, and the quantity of apoptotic cells was increased with the elevation in concentration. The mRNA and protein expression levels of Fas and FasL in the drug-treatment group were significantly elevated. Furthermore, the western blot assay also indicated that with an increase in the concentration of ß-bourbonene, the protein expression of Bax in the drug-treatment group was significantly elevated, while a decrease was identified in the protein expression of Bcl-2. Taken together, ß-bourbonene can inhibit the proliferation and simultaneously, induce apoptosis and G0/G1 arrest of prostate cancer PC-3M cells, which may be realized by upregulation of mRNA expression of Fas and FasL, increase of Bax protein expression and decrease of Bcl-2 protein expression.

Correlation of Betel Quid with Oral Cancer from 1998 to 2017: A Study Based on Bibliometric Analysis.

BACKGROUND: Betel quid chewing has been a major risk factor for oral cancer (OC) in southern China. This study aimed to analyze the scientific publications on the relationship between betel quid chewing and OC and construct a model to quantitatively and qualitatively evaluate pertinent publications from 1998 to 2017. METHODS: The publications from 1998 to 2017 were retrieved from the Web of Science Core Collection database. Microsoft Excel, Thomson Data Analyzer, VOSviewer, and CiteSpace software were used to analyze the publication outcomes, journals, countries/regions, institutions, authors, research areas, and research frontiers. RESULTS: A total of 788 publications on the relationship between betel quid chewing and OC published until October 25, 2017, were identified. The top 4 related journals were Journal of Oral Pathology Medicine, Oral Oncology, Plos One, and International Journal of Cancer. The top five countries engaged in related research included China, India, the United States, the United Kingdom, and Malaysia. The corresponding disciplines, such as oncology, oral surgery, pathology, environmental and occupational health, and toxicology, were mainly concentrated in three disciplines. The subject terms squamous cell carcinoma, OC, betel quid, expression, oral submucous fibrosis, India, and p53 ranked first among research hotspots. The burst terms squamous cell carcinoma, OC, betel quid, and expression ranked first in research frontiers. CONCLUSIONS: Research in this area emphasized hotspots such as squamous cell carcinoma, OC, oral submucosal fibrosis, betel quid, and tobacco. The annual number of publications steadily decreased from 1998 to 2017, with a lack of a systematic study from interdisciplinary perspectives, inadequate pertinent journals, limited regions with the practice of betel quid chewing, and insufficient participation of researchers, which indicate that as the prevalence of OC increases, particularly in China, research in this area warrants further expansion.

[Source and Distribution of Dissolved Metal Ions in the Backwater Area of Pengxi River in Three Gorges Reservoir].

This study uses the Gaoyang Lake section of the Pengxi River, the largest tributary on the northern bank of the Three Gorges Reservoir (TGR), as an example for exploring the distributions and dynamics of Ca, Zn, Fe, Cr, Pb, Cu, and Hg ions in the tributaries of TGR where the water level fluctuates due to dam regulation. Samples were taken 21 times, once every 17.3 days, at four sampling sites in Gaoyang Lake, which is in a perennial backwater zone of the Pengxi River, during one year from June 5, 2013 to May 29, 2014. At each sampling site, water samples were taken from the surface layer (0-0.5 m), middle layer, and bottom layer (0.5 m above the bed mud). During winter when the water was not stratified, the middle layer samples were taken at 1/2 depth, and when water was stratified in other seasons, the middle layer samples were taken from the thermal layer. Inductively coupled plasma atomic emission spectrometry (ICP-AES) and cold-vapor atomic absorption methods were adopted to determine the concentrations of the metals. Excel and SPSS were used for data analysis and Matlab for building 3-D prisms displaying concentration distributions of Hg ions in the high water level period (175 m, November-April in the ensuing year), sluicing period (May-middle June), low water level in the flooding season (145 m, June-August), and the storage period (September-November). The results provided the following observations ① Concentrations of Cr, Pb, Cu, Zn, and Hg ions were lower than those in Class Ⅲ of the water environment quality standard (GB 3838-2002). ② Cr, Pb, and Cu had high peak values during the storage and sluicing period, and the lowest values during the high water level period. Cr, Pb, and Cu were derived from the main stream of Yangtze, while Fe and Zn were from the Pengxi River locally. The concentration of Hg ions was affected by both the main stream and endogenous sources. As the water column stratified, metal ions did not mix among the stratified layers in Gaoyang Lake. ③ The conductivity was significantly lower during the high water level period than during other water level periods. The main material that affects the conductivity of Gaoyang Lake could be nonmetallic ions.

Kappa-opioid receptor agonist U50448H protects against renal ischemia-reperfusion injury in rats via activating the PI3K/Akt signaling pathway.

Renal ischemia-reperfusion injury (IRI) is regarded as a leading cause of acute kidney failure and renal dysfunction. Previous studies show that kappa opioid receptor (KOR) agonists can attenuate IRI in cardiomycytes and neuronal cells. In this study we explored the effects of a KOR agonist on renal IRI and the underlying mechanisms in vivo and in vitro. An IRI model was established in SD rats, which were intravenously pretreated with a KOR agonist U50448H (1 mg/kg), a KOR antagonist Nor-BNI (2 mg/kg) followed by U50448H (1 mg/kg), or the PI3K inhibitor wortmannin (1.4 mg/kg) followed by U50448H (1 mg/kg). U50448H pretreatment significantly decreased the serum levels of creatinine (Cr) and BUN, the renal tubular injury scores and the apoptotic index (AI) in IRI model rats. Furthermore, U50448H significantly increased SOD activity and NO levels, and reduced the MDA levels in the kidney tissues of IRI model rats. Moreover, U50448H significantly increased the phosphorylation of Akt, eNOS and PI3K in the kidney tissues of IRI model rats. All the beneficial effects of U50448H were blocked by Nor-BNI or wortmannin pre-administered. Similar results were observed in vitro in renal tubular epithelial NRK-52E cells subjected to a hypoxia-reoxygenation (HR) procedure. Our results demonstrate that the KOR agonist U50448H protects against renal IRI via activating the PI3K/Akt signaling pathway.

[Exploiture and application of an internet-based Computation Platform for Integrative Pharmacology of Traditional Chinese Medicine].

Recently, integrative pharmacology(IP) has become a pivotal paradigm for the modernization of traditional Chinese medicines(TCM) and combinatorial drugs discovery, which is an interdisciplinary science for establishing the in vitro and in vivo correlation between absorption, distribution, metabolism, and excretion/pharmacokinetic(ADME/PK) profiles of TCM and the molecular networks of disease by the integration of the knowledge of multi-disciplinary and multi-stages. In the present study, an internet-based Computation Platform for IP of TCM(TCM-IP, www.tcmip.cn) is established to promote the development of the emerging discipline. Among them, a big data of TCM is an important resource for TCM-IP including Chinese Medicine Formula Database, Chinese Medical Herbs Database, Chemical Database of Chinese Medicine, Target Database for Disease and Symptoms, et al. Meanwhile, some data mining and bioinformatics approaches are critical technology for TCM-IP including the identification of the TCM constituents, ADME prediction, target prediction for the TCM constituents, network construction and analysis, et al. Furthermore, network beautification and individuation design are employed to meet the consumer's requirement. We firmly believe that TCM-IP is a very useful tool for the identification of active constituents of TCM and their involving potential molecular mechanism for therapeutics, which would wildly applied in quality evaluation, clinical repositioning, scientific discovery based on original thinking, prescription compatibility and new drug of TCM, et al.

MicroRNA-93 inhibits apoptosis and promotes proliferation, invasion and migration of renal cell carcinoma ACHN cells via the TGF-ß/Smad signaling pathway by targeting RUNX3.

We investigated the ability of microRNA-93 (miR-93) to influence proliferation, invasion, migration, and apoptosisofrenal cell carcinoma (RCC) cells via transforming growth factor-ß/solvated metal atom dispersed (TGF-ß/Smad) signaling by targeting runt-related transcription factor 3 (RUNX3). RCC tissues with corresponding adjacent normal tissues were collected from 249 RCC patients. And normal renal tissues were collected from patients without RCC who received nephrectomy. The RCC cell line ACHN was treated with miR-93 mimic, mimic-negative control (NC), miR-93 inhibitor, inhibitor-NC, and miR-93 inhibitor + small interfering RNA (siRNA) against RUNX3 (si-RUNX3). Expression of miR-93, RUNX3, TGF-ß, and Smad4 were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Cell proliferation was assessed by the Metallothioneins (MTS) assay, cell invasion by the wound-healing assay, cell migration by the Transwell assay, and cell cycle and apoptosis by flow cytometry. Compared with normal renal tissues, the expression of miR-93 and TGF-ß were higher while that of RUNX3 and Smad4 were low in RCC and adjacent normal tissues (all P<0.05). RUNX3 was confirmed as a target of miR-93 by the dual luciferase reporter gene assay. Compared with mimic-NC group, cell proliferation, invasion, migration and cells from G0/G1 to S phase enhanced but the apoptosis decreased in the miR-93 mimic group (all P<0.05). Compared with inhibitor-NC group, proliferation, invasion, and migration reduced, while apoptosis increased, and cells at G0/G1 phase arrested in the miR-93 inhibitor group (all P<0.05). Compared with miR-93 inhibitor group, cell proliferation, invasion, and migration increased with increasing cells from G1 to S phase while the apoptosis decreased, in miR-93 inhibitor + si-RUNX3 group (all P<0.05). In conclusion, miR-93 inhibits apoptosis and promotes proliferation, invasion, and migration of RCC cells via TGF-ß/Smad signaling by inhibiting RUNX3.

Activation of the PI3K-Akt pathway promotes neuroprotection of the δ-opioid receptor agonist against cerebral ischemia-reperfusion injury in rat models.

The central objective was to identify the role of the PI3K-Akt activation pathway on the neuroprotection of δ-opioid receptor agonist (DADLE) against cerebral ischemia-reperfusion (I/R) injury in a rat model. Fifty-five male Sprague-Dawley (SD) rats were included to establish a middle cerebral artery occlusion (MCAO) model which were then divided into the sham, MCAO, LY294002 (MCAO+DADLE+LY294002 [inhibitor of PI3K-Akt pathway]), DADLE (MCAO+DADLE) and DMSO (MCAO+DADLE+DMSO [dimethyl sulphoxide]) groups. The cerebral infarction (CI) volume and nerve cell apoptosis was determined using TTC and TUNEL staining. Quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and immunohistochemistry staining were applied for the expressions of Bad, Bax, Bcl-2 and cleaved caspase-3. The MCAO group showed higher CI volume, nerve cell apoptosis and cleaved caspase-3 expressions than the DADLE and DMSO groups, which were also higher in the LY294002 group than the DADLE group. Compared with the MCAO group, the mRNA and protein expressions of PI3K and Bcl-2, and the protein expressions of p-Akt and p-Bad were elevated, while the mRNA and protein expressions of Bax were decreased in the DADLE and DMSO groups. Decreased mRNA and protein expressions of PI3K and Bcl-2, reduced protein expressions of p-Akt and p-Bad and elevated mRNA and protein expressions of Bax exhibited in the LY294002 group than the DADLE group. These results indicate that activation of PI3K-Akt pathway promotes the neuroprotection of DADLE against cerebral I/R injury in a rat model by decreasing nerve cells apoptosis.

[Temporal and Spatial Distribution of Environmental Factors and Phytoplankton During Algal Bloom Season in Pengxi River, Three Gorges Reservoir].

Planktonic algae and Related Environmental Factors were monitored during the period of algal blooms season in 2014 (Spring April 17 and summer 27 July) in Pengxi river, Three Gorges Reservoir. Mathematical statistical tools were used to analyze the community structure of planktonic algae in Pengxi River with its environmental factors. The results of sampling in spring showed that except the estuary site, S1 and the site close by, S2, the waters stratified, but without epilimnion, only had metalimnion and hypolimnion; the upstream sites had larger temperature difference between water layers than did the downstream ones; from all the 8 sampling sites from estuary to upstream, water depth, and the temperature, pH, conductivity, dissolved oxygen, chlorophyll a, TN and TP of the surface layer (0-0.5 m deep) were significantly different (ANOVA, P < 0.05). 25 species (genus) of planktonic algae were identified. The abundance of species ranged from 2.76 x 104 cell · L⁻¹ to 145.8 x 104 cell · L⁻¹. Ceratium hirundinella was the main dominant species, and Anabaena sp. was the sub-dominant species. Algal bloom in upstream sampling sites S7 (63.4 x 104cell · L⁻¹) and S8 (145.8 x 104cell · L⁻¹)were relatively serious in spring. Temperature of water, pH , conductivity, dissolved oxygen and NO3⁻ were the key regulatory factors for phytoplankton abundance based on redundancy analysis ( RDA). The results of sampling in summer showed similar stratification trends among sites; the depth of the same 8 sampling sites, and their surface layer's temperature of water, turbidity, redox potential, pH, water depth, conductivity, chlorophyll a, NH4⁺, NO3⁻, total nitrogen and total phosphorus were significantly different (ANOVA, P < 0.05). 46 species (genus) of phytoplanktonic algae were identified. The abundance ranged from 9.56 x 104 cell · L⁻¹ to 278.88 x 104 cell · L⁻¹. Phormidium sp. was the main dominant species, and Anabaena sp. was the sub- dominant algae. Algal bloom at the lower part of the river, S2 (216.44 x 104 cell · L⁻¹), S3 (278.88 x 104 cell · L⁻¹) and S4 (108.12 x 104 cell · L⁻¹) were relatively serious in summer. Turbidity, depth of water, TN, oxidation-reduction potential, conductivity and dissolved oxygen were the key regulatory factors for phytoplankton abundance based on RDA. Stratification had important effect on algal bloom formation.

MicroRNA-497 regulates cell proliferation in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver. MicroRNA-497 (miR-497) is known to be downregulated in several types of human cancer; however, the expression, function and underlying mechanisms of miR-497 in HCC remain unclear. Therefore, the present study investigated miR-497 expression in HCC samples and HCC-derived cell lines using reverse transcription-quantitative polymerase chain reaction. The protein expression of one of the predicted common targets of miR-497, insulin-like growth factor-1 receptor (IGF-1R), was assessed using western blot analyses and immunohistochemistry. The role of miR-497 in regulating the proliferation of HCC-derived cells was also investigated in vitro and in vivo. Of 60 paired specimens from HCC patients, miR-497 was downregulated in 42 cancer specimens compared with adjacent non-cancer tissues. Western blotting and immunohistochemical analyses revealed that IGF-1R expression was significantly increased in HCC compared to control tissues. In addition, overexpression of miR-497 was observed to inhibit colony formation and tumor growth in MHCC-97H human HCC cells. Conversely, SMMC-7721 human HCC cells transfected with a miR-497 inhibitor exhibited enhanced colony formation and tumor growth. Finally, IGF-1R protein, phosphoinositide 3-kinase/Akt signaling pathway-associated proteins and cyclin pathway-associated proteins were differentially expressed between miR-497-overexpressing cells and miR-497-silenced cells. These results indicate that miR-497 may be a potentially effective gene therapy target.

Non-neuronal and neuronal BACE1 elevation in association with angiopathic and leptomeningeal ß-amyloid deposition in the human brain.

BACKGROUND: Cerebral amyloid angiopathy (CAA) refers to the deposition of ß-amyloid (Aß) peptides in the wall of brain vasculature, commonly involving capillaries and arterioles. Also being considered a part of CAA is the Aß deposition in leptomeninge. The cellular origin of angiopathic Aß and the pathogenic course of CAA remain incompletely understood. METHODS: The present study was aimed to explore the pathogenic course of CAA in the human cerebrum via examination of changes in ß-secretase-1 (BACE1), the obligatory Aß producing enzyme, relative to Aß and other cellular markers, by neuroanatomical and biochemical characterizations with postmortem brain samples and primary cell cultures. RESULTS: Immunoreactivity (IR) for BACE1 was essentially not visible at vasculature in cases without cerebral amyloidosis (control group, n = 15, age = 86.1 ± 10.3 year). In cases with brain amyloid pathology (n = 15, age = 78.7 ± 12.7 year), increased BACE1 IR was identified locally at capillaries, arterioles and along the pia, localizing to endothelia, perivascular dystrophic neurites and meningeal cells, and often coexisting with vascular iron deposition. Double immunofluorescence with densitometric analysis confirmed a site-specific BACE1 elevation at cerebral arterioles in the development of vascular Aß deposition. Levels of BACE1 protein, activity and its immediate product (C99) were elevated in leptomeningeal lysates from cases with CAA relative to controls. The expression of BACE1 and other amyloidogenic proteins in the endothelial and meningeal cells was confirmed in primary cultures prepared from human leptomeningeal and arteriolar biopsies. CONCLUSION: These results suggest that BACE1 elevation in the endothelia and perivascular neurites may be involved in angiopathic Aß deposition, while BACE1 elevation in meningeal cells might contribute Aß to leptomeningeal amyloidosis.

[Nutrient Characteristics and Nitrogen Forms of Rhizosphere Soils Under Four Typical Plants in the Littoral Zone of TGR].

The Three Gorges Reservoir (TGR), which is the largest water conservancy project ever built in tne world, produced a drawdown area of about 348.93 km2 because of water level control. The biological geochemical cycle of the soil in the drawdown zone has been changed as the result of long-term winter flooding and summer drought and vegetation covering. The loss of soil nitrogen in the drawdown zone poses a threat to the water environmental in TGR. Pengxi river, is an important anabranch, which has the largest drawdown area has been selected in the present study. The four typical vegetation, contained Cynodon dactylon, Cyperus rotundus, Anthium sibiricum and Zea mays L. as the control, were studied to measure nutrient characteristics and nitrogen forms of rhizosphere and non-rhizosphere soils in three distribution areas with different soil types (paddy soil, purple soil and fluvo-aquic soils). The variables measured included organic matter (OM), total nitrogen (TN), total phosphorus (TP), total potassium (TK), hydrolysis N, available P and available K, pH, ion-exchangeable N (IEE-N), weak acid extractable N (CF-N) , iron-manganese oxides N (IMOF-N), organic matter sulfide N (OSF-N), added up four N forms for total transferable N (TF-N) and TN minus TF-N for non-transferable N (NTF-N). The results showed: (1) pH of rhizosphere soil was generally lower than that of non-rhizosphere soil under different vegetation in different type soils because the possible organic acid and H+ released form plant roots and cation absorption differences, and the OM, TP, TN and hydrolysis N of rhizosphere soil were generally higher than those of non-rhizosphere soil, and that the enrichment ratio (ER) of all the four nutrient indicators showed Cyperus rotundus > Cynodon dactylon > Zea mays L. > Anthium sibiricum. Available P showed enrichment in the rhizosphere of three natural vegetations but lose under corn, and available K, TK showed different ER in different conditions. (2) IEF-N CF-N, IMOF-N, OSF-N and TF-N of rhizosphere soil were generally higher than those of non-rhizosphere soil, but the TF-N to TN ratio in rhizosphere of Cyperus rotundus and Cynodon dactylon were lower than those of non-rhizosphere soil, and in rhizosphere of Anthium sibiricum and Zea mays L. were higher, the rhizosphere effect of different vegetations on the N cycle was significant difference. (3) the correlation between nutrient characteristics and nitrogen forms was evaluated to explore the influence factor for the N forms changing. There was a significant correlation between soil OM and four N forms, TP was significantly correlated with CF-N, OSF-N, TF-N, and soil available P content was significantly negatively correlated with IMOF-N, OSF-N, TF-N and TN. Our research could provide that the drawdown zone covered with Cyperus rotundus and Cynodon dactylon was better than Anthium sibiricum and Zea mays L. to improve soil N holding and fixation. The vegetation recovery in the drawdown zone should consider the rhizosphere effect of different vegetations on N cycle.