High-frequency repetitive transcranial magnetic stimulation promotes ipsilesional functional hyperemia and motor recovery in mice with ischemic stroke.

Neurovascular decoupling plays a significant role in dysfunction following an ischemic stroke. This study aimed to explore the effect of low- and high-frequency repetitive transcranial magnetic stimulation on neurovascular remodeling after ischemic stroke. To achieve this goal, we compared functional hyperemia, cerebral blood flow regulatory factors, and neurochemical transmitters in the peri-infract cortex 21 days after a photothrombotic stroke. Our findings revealed that low- and high-frequency repetitive transcranial magnetic stimulation increased the real-time cerebral blood flow in healthy mice and improved neurobehavioral outcomes after stroke. Furthermore, high-frequency (5-Hz) repetitive transcranial magnetic stimulation revealed stronger functional hyperemia recovery and increased the levels of post-synaptic density 95, neuronal nitric oxide synthase, phosphorylated-endothelial nitric oxide synthase, and vascular endothelial growth factor in the peri-infract cortex compared with low-frequency (1-Hz) repetitive transcranial magnetic stimulation. The magnetic resonance spectroscopy data showed that low- and high-frequency repetitive transcranial magnetic stimulation reduced neuronal injury and maintained excitation/inhibition balance. However, 5-Hz repetitive transcranial magnetic stimulation showed more significant regulation of excitatory and inhibitory neurotransmitters after stroke than 1-Hz repetitive transcranial magnetic stimulation. These results indicated that high-frequency repetitive transcranial magnetic stimulation could more effectively promote neurovascular remodeling after stroke, and specific repetitive transcranial magnetic stimulation frequencies might be used to selectively regulate the neurovascular unit.

The AMPK-like protein kinases Sik2 and Sik3 interact with Hipk and induce synergistic tumorigenesis in a Drosophila cancer model.

Homeodomain-interacting protein kinases (Hipks) regulate cell proliferation, apoptosis, and tissue development. Overexpression of Hipk in Drosophila causes tumorigenic phenotypes in larval imaginal discs. We find that depletion of Salt-inducible kinases Sik2 or Sik3 can suppress Hipk-induced overgrowth. Furthermore, co-expression of constitutively active forms of Sik2 or Sik3 with Hipk caused significant tissue hyperplasia and tissue distortion, indicating that both Sik2 and Sik3 can synergize with Hipk to promote tumorous phenotypes, accompanied by elevated dMyc, Armadillo/ß-catenin, and the Yorkie target gene expanded. Larvae expressing these hyperplastic growths also display an extended larval phase, characteristic of other Drosophila tumour models. Examination of total protein levels from fly tissues showed that Hipk proteins were reduced when Siks were depleted through RNAi, suggesting that Siks may regulate Hipk protein stability and/or activity. Conversely, expression of constitutively active Siks with Hipk leads to increased Hipk protein levels. Furthermore, Hipk can interact with Sik2 and Sik3 by co-immunoprecipitation. Co-expression of both proteins leads to a mobility shift of Hipk protein, suggesting it is post-translationally modified. In summary, our research demonstrates a novel function of Siks in synergizing with Hipk to promote tumour growth.

An Enriched Environment Promotes Motor Function through Neuroprotection after Cerebral Ischemia.

Stroke seriously affects human health. Many studies have shown that enriched environment (EE) can promote functional recovery after stroke, but the intrinsic mechanisms remain unclear. In order to study the internal mechanisms of EE involved in functional recovery after ischemic stroke and which mechanism plays a leading role in the recovery of limb function after cerebral infarction, key proteins potentially involved in neuronal protection and synaptic remodeling in the ischemic penumbra have been investigated. In this study, adult C57BL/6 mice after permanent middle cerebral artery occlusion (pMCAO) were assigned to the EE and standard housing (SH) groups 3 days after operation. The EE house was spacious that contained a large variety of small toys; the SH was a normal sized cage. Sham-operated mice without artery occlusion were housed under standard conditions and were fed a normal diet. On days 3, 7, 14, and 21, postoperative motor functional recovery was tested using the modified neurological severity score (mNSS) and the Rotarod test. The expression of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), growth-associated protein-43 (GAP-43), and synaptophysin (SYN) was examined by western blotting and immunofluorescence staining. The motor functional recovery (based on the mNSS and Rotarod test 3, 7, 14, and 21 days post operation) of mice in the EE group improved significantly compared to the SH group. The expression of GAP-43 and SYN and the ratio of Bcl-2/Bax were all upregulated in the EE group compared to the SH group. In addition, we also explored the relationship between neuronal protection and synaptic remodeling in the EE-mediated recovery of limb function after cerebral infarction by correlation analysis. Correlation analysis showed that compared with the increase of Bcl-2/Bax ratio, the increased expression of GAP-43 and SYN was more closely related to the recovery of limb function in ischemic mice. These data support the hypothesis that EE can promote the process of improvement of limb dysfunction induced by ischemic stroke, and this behavior restoration may, via promoting neuroprotection in the ischemic penumbra, be dependent on the regulation of the expression of GAP-43, SYN, Bcl-2, and Bax. A limitation of the study was that we only observed several representative key indicators of synaptic remodeling and neuronal apoptosis, without an in-depth study of the potential mechanisms involved.

A novel model based on necroptosis-related genes for predicting immune status and prognosis in glioma.

Background: Glioma is a highly aggressive brain cancer with a poor prognosis. Necroptosis is a form of programmed cell death occurring during tumor development and in immune microenvironments. The prognostic value of necroptosis in glioma is unclear. This study aimed to develop a prognostic glioma model based on necroptosis. Methods: A necroptosis-related risk model was constructed by Cox regression analysis based on The Cancer Genome Atlas (TCGA) training set, validated in two Chinese Glioma Genome Atlas (CGGA) validation sets. We explored the differences in immune infiltration and immune checkpoint genes between low and high risk groups and constructed a nomogram. Moreover, we compiled a third validation cohort including 43 glioma patients. The expression of necroptosis-related genes was verified in matched tissues using immunochemical staining in the third cohort, and we analyzed their relationship to clinicopathological features. Results: Three necroptosis-related differentially expressed genes (EZH2, LEF1, and CASP1) were selected to construct the prognostic model. Glioma patients with a high risk score in the TCGA and CGGA cohorts had significantly shorter overall survival. The necroptosis-related risk model and nomogram exhibited good predictive performance in the TCGA training set and the CGGA validation sets. Furthermore, patients in the high risk group had higher immune infiltration status and higher expression of immune checkpoint genes, which was positively correlated with poorer outcomes. In the third validation cohort, the expression levels of the three proteins encoded by EZH2, LEF1, and CASP1 in glioma tissues were significantly higher than those from paracancerous tissues. They were also closely associated with disease severity and prognosis. Conclusions: Our necroptosis-related risk model can be used to predict the prognosis of glioma patients and improve prognostic accuracy, which may provide potential therapeutic targets and a theoretical basis for treatment.

Long Noncoding RNA RP11-732M18.3 Promotes Glioma Angiogenesis by Upregulating VEGFA.

Gliomas are the most aggressive and common type of malignant brain tumor, with limited treatment options and a dismal prognosis. Angiogenesis, a hallmarks of cancer, is one of two critical events in the progression of gliomas. Accumulating evidence has demonstrated that in glioma dysregulated molecules like long noncoding RNAs (lncRNAs), are closely linked to tumorigenesis and prognosis. However, the effects of and mechanisms of action of lncRNAs during tumor angiogenesis are poorly understood. The effect of lncRNA RP11-732M18.3 on angiogenesis was elucidated through an intracranial orthotopic glioma model, immunohistochemistry, and an in vitro angiogenesis assay. Co-culture experiments and cell migration assays were performed to investigate the function of lncRNA RP11-732M18.3 in vitro. lncRNA RP11-732M18.3 increased CD31+ microvessel density, and overexpression of lncRNA RP11-732M18.3 resulted in poor mouse survival. lncRNA RP11-732M18.3 promoted endothelial cell migration and tube formation. Nomogram and Kaplan-Meier survival analyses indicated that higher VEGFA is correlated with a poor prognosis. Mechanistically, lncRNA RP11-732M18.3 promotes angiogenesis by increasing the nuclear level of EP300 and facilitating the transcription and secretion of VEGFA. Our study contributes to the latest understanding of glioma angiogenesis and prognosis. lncRNA RP11-732M18.3 may be a potential treatment target in glioma.

miR-338-3p Plays a Significant Role in Casticin-Induced Suppression of Acute Myeloid Leukemia via Targeting PI3K/Akt Pathway.

Objective: Casticin is generally used in traditional herbal medicine for its anti-inflammatory and anticarcinogenic pharmacological properties. Also, microRNAs are indispensable oncogenes or cancer suppressors being dysregulated in various diseases. In this study, we aimed to elucidate the mechanisms underlying effects of casticin on the progression of acute myeloid leukemia (AML). Methods: CCK-8 and flow cytometry were utilized to measure the proliferation and apoptosis of AML cell lines, respectively, after treatment with different concentrations of casticin. The alteration of several microRNA expressions in response to casticin treatment was detected by performing qRT-PCR, and the activity of PI3K/Akt pathways was evaluated through immunoblotting. Afterwards, the potential target gene of miR-338-3p was investigated by dual-luciferase reporter assay. In order to evaluate the role of miR-338-3p in the casticin-induced cellular phenotype changes, AML cells were transfected with miR-338-3p mimics or inhibitor and then subjected to proliferation and apoptosis analysis. Finally, a mouse xenograft model system was employed to investigate the role of casticin in AML progression in vivo. Results: Suppressed cellular proliferation and enhanced apoptosis were observed in HL-60 and THP-1 cells after exposure to casticin, accompanied by remarkable upregulation of the miR-338-3p expression as well as a decline in the phosphorylation of PI3K and Akt proteins. RUNX2 was identified as a direct target molecular of miR-338-3p, which might account for the findings that miR-338-3p knockdown enhanced the PI3K/Akt pathway activity, whereas the miR-338-3p overexpression inactivated this signaling pathway. In addition, the inhibition of the miR-338-3p expression attenuated severe cell apoptosis and suppressions of PI3K/Akt pathway induced by casticin. Furthermore, casticin treatment retarded tumor growth rate in mouse models, whilst elevating miR-338 expression and repressing the activity of PI3K/Akt pathway in vivo. However, miR-338-3p depletion could also abolish the phenotypic alterations caused by casticin treatment. Conclusion: Casticin promotes AML cell apoptosis but inhibits AML cell proliferation in vitro and tumor growth in vivo by upregulating miR-338-3p, which targets RUNX2 and thereafter inactivates PI3K-Akt signaling pathway. Our results provide insights into the mechanisms underlying the action of casticin in the control of AML progression.

SMG9 Serves as an Oncogene to Promote the Tumor Progression via EMT and Wnt/ß-Catenin Signaling Pathway in Hepatocellular Carcinoma.

Background/Aims: SMG9 participates in the nonsense-mediated mRNA decay process that degrades mRNA harboring nonsense mutations introduced either at the level of transcription or RNA processing. However, little is known about the role of SMG9 in hepatocellular carcinoma (HCC). The objective of this research was to clarify the effects of SMG9 expression on HCC progression. Methods: Microarray data were acquired from NCBI Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database to bioinformatically analyze the differential expression of SMG9 between HCC patients and normal controls. SMG9 mRNA level was measured in sixteen sets of fresh tumor tissues and adjacent non-cancerous liver tissues (ANLTs) via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). SMG9 protein expression was analyzed in ninety-five sets of paired formalin-fixed and paraffin-embedded tissue specimens by immunohistochemistry (IHC). In addition, clinicopathological features of SMG9 in HCC were checked. For in vitro studies, small interfering RNA (siRNA) was used to silence SMG9 expression for exploring biological functions and underlying mechanisms of SMG9 in SMMC-7721 and HepG2. Results: We found that SMG9 was upregulated in HCC tissues and SMG9 levels were closely related to TNM stage, tumor number and tumor size. Cox regression and Kaplan-Meier proportional hazards analyses showed that high expression of SMG9 was associated with poor patient survival. Furthermore, proliferation, apoptosis resistance, migration and invasion of both SMMC-7721 and HepG2 cells were suppressed by SMG9 inhibition. In addition, EMT and the Wnt/ß-catenin signaling pathway were involved in SMG9-mediated HCC progression. Conclusions: SMG9 may serve as a potential novel prognostic biomarker and therapeutic target in HCC patients.

Nonadherence in Home-Based Pulmonary Rehabilitation Program for COPD Patients.

Background: The pulmonary rehabilitation (PR) is beneficial for COPD patients. Due to the poor rate of adherence, we evaluate the factors which will predict the nonadherence of PR. Method: We analyzed the data from a retrospective study of COPD patients who were enrolled to attend the PR program. Patients were classified as the adherence group and the nonadherence group according to completion of over 50% sessions during the 8-week PR program. Demographic characteristics, 6-minute walking distance (6MWD), COPD assessment test (CAT), modified Medical Research Council scale (mMRC), and emotional function were compared between two groups. Univariate and multivariable analyses were performed to determine the factors of poor adherence of PR. Results: Among 418 patients, 170 patients (40.7%) who completed less than 50% sessions of the PR program were categorized as "nonadherence." Compared to completers, "nonadherence" patients had more cigarette consumption, higher emotional score, less 6MWD, more exacerbation, using nebulizer frequently, and higher rate of smoking at enrollment. On multivariate analysis, more exacerbation frequency (odds ratio (OR) = 1.434, 95% confidence interval (CI): 1.191∼1.796, P=0.046) and smoking at enrollment (OR = 3.349, 95% CI: 1.194∼6.302, P=0.012) were predict factors associated with nonadherence of PR. Conclusion: COPD patients with frequent exacerbation and smoking currently were more likely to be nonadherence during PR.

Long-term effect of crude oil and dispersant on denitrification and organic matter mineralization in a salt marsh sediment.

The 2010 BP oil spill has an unprecedented impact on coastal wetland ecosystem along the northern Gulf of Mexico. A two-dimensional analysis (dispersant concentration and duration of exposure) was conducted by pre-incubation of a salt marsh sediment under an open or closed condition. Denitrification activity was characterized by N2O production using an acetylene (C2H2) blockage technique, and organic matter (OM) mineralization by CO2 production. The results show that even trace amount of the dispersant could significantly inhibit the denitrification activity by 20% (p < 0.05). However, the sediment was resilient to the oil/dispersant contamination, likely due to shift of its microbial communities, by recovering the denitrification activity within 46 days in the open incubation. Inhibitory effect of the oil/dispersant on denitrification persisted beyond 46 days in the closed incubation, and the recovery could take up to 137 days depending on the dispersant concentration. The dispersant continuously stimulated OM mineralization that lowered the sediment redox status. Mobilization of N in the sediment from the OM mineralization forms a positive feedback loop, leading to deterioration of the coastal ecosystem. The study concludes that minimum dispersant should be applied for oil spill remediation, and oil cleanup operations should avoid moving the oil/dispersant from surface into deeper layers of the sediment. Synergistic interactions between the crude oil and dispersant and their biodegradation products deserves future examinations.

Dual functional roles of the MyD88 signaling in colorectal cancer development.

The myeloid differentiation factor 88 (MyD88), an adaptor protein in regulation of the innate immunity, functions to regulate immune responses against viral and bacterial infections in the human body. Toll-like receptors (TLRs) and interleukin 1 receptors (IL-1R) can recognize microbes or endogenous ligands and then recruit MyD88 to activate the MyD88-dependent pathway, while MyD88 mutation associated with lymphoma development and altered MyD88 signaling also involved in cancer-associated cell intrinsic and extrinsic inflammation progression and carcinogenesis. Detection of MyD88 expression was to predict prognosis of various human cancers, e.g., lymphoid, liver, and colorectal cancers. In human cancers, MyD88 protein acts as a bridge between the inflammatory signaling from the TLR/IL-1R and Ras oncogenic signaling pathway. However, the MyD88 signaling played dual functional roles in colorectal cancer, i.e., the tumor-promoting role that enhances cancer inflammation and intestinal flora imbalance to induce tumor invasion and tumor cell self-renewal, and the anti-tumor role that helps to maintain the host-microbiota homeostasis to induce tumor cell cycle arrest and immune responses against cancer cells. This review precisely discusses the up to date literature for these contrasting effects of MyD88 signaling on colorectal cancer development and progression.

Contribution of drugs acting on the TLRs/MyD88 signaling pathway on colitis-associated cancer.

Toll-like receptors play a particularly significant role in colitis-associated cancer (CAC). MyD88 is the mediator in TLRs signal transduction process and it is indispensable for TLRs signaling except for TLR3. The conclusion of studies about the role of TLRs/MyD88 signaling in colon cancer remains contradictory: on one hand, TLRs/MyD88 signaling contributes to colon tumor cell proliferation, invasion and metastasis and inhibition of the expression of TLRs or MyD88 could prevent the growth of colon cancer cells; on the other hand, activation of the TLRs/MyD88 signaling pathway could inhibit the proliferation of colon cancer cells. This article is based on the expression levels of TLRs or MyD88 and the activation degrees of TLRs/MyD88 signaling pathway in different periods of colon cancer and, reviews the roles of TLRs/MyD88 signaling in the tumorigenesis and procession of CAC and the clinical application of agonists and inhibitor of TLRs or MyD88. This article is intended to explore the diverse roles of TLRs/MyD88 signaling pathway in CAC and to reveal the related molecular mechanism.

Effect of temperature and dispersant (COREXIT® EC 9500A) on aerobic biodegradation of benzene in a coastal salt marsh sediment.

The coastal ecosystem in the northern Gulf of Mexico (GoM) has been seriously impacted by the 2010 BP oil spill. Two experiments were conducted to study the effect of temperature and addition of the dispersant on biodegradation of benzene, as a representative of petroleum hydrocarbon, in a coastal salt marsh sediment under aerobic conditions. The results show that benzene biodegradation was approximately 6 time faster under aerobic conditions (Eh > +300 mV) than under anaerobic iron-reduction conditions (+14 mV < Eh < +162 mV). Benzene biodegradation in response to temperature was in an order of 20 °C > 10 °C > 30 °C as expected in a saline environment. Application of the dispersant caused initial fluctuations of benzene vapor pressure during the incubation due to its hydrophobic and hydrophilic nature of the molecules. Presence of the dispersant shows an inhibitory effect on benzene biodegradation, and the inhibition increased with concentration of the dispersant. The Gulf coast sediment seems in a favorable scenario to recover from the BP oil spill with an average temperature around 20 °C in spring and fall season. Application of the dispersant may be necessary for the oil spill rescue operation, but its side effects may deserve further investigations.

Efficacy and safety of trastuzumab emtansine (T-DM1) in the treatment of HER2-positive metastatic breast cancer (MBC): a meta-analysis of randomized controlled trial.

AIMS: Trastuzumab emtansine (T-DM1), an antibody-drug conjugate against human epidermal growth factor receptor 2 (HER2), has been used in the treatment of patients with HER2-positive metastatic breast cancer (MBC). We conducted a meta-analysis to evaluate the efficacy and toxicity of T-DM1 for the treatment of patients with HER2-positive MBC. MATERIALS AND METHODS: Randomized controlled trials (RCTs), published in Pubmed, Embase, and Web of Science were systematically reviewed to assess the survival benefits and toxicity profile of HER2-positive patients with MBC who were treated with T-DM1. Outcomes included progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and toxicities. Results were expressed as the hazard ratio (HR) with 95% confidence intervals (CIs). RESULTS: A total of 5 RCTs involving 3,720 patients met the inclusion criteria and were included in this meta-analysis. T-DM1 significantly prolonged PFS (HR = 0.73, 95% CI: 0.61, 0.86; P < 0.05), OS (HR = 0.68, 95% CI: 0.62, 0.74; P < 0.05), but it did not increase ORR (RR = 1.25, 95% CI: 0.94, 1.66; P = 0.148). Subgroup analysis indicated that T-DM1 significantly improved PFS when it was used as first-line (HR = 0.86, 95% CI: 0.74, 1.00; P < 0.05) or non-first-line treatment (HR = 0.65, 95% CI: 0.53, 0.81; P < 0.05). T-DM1 was associated with more frequent adverse events, including fatigue, elevated ALT, elevated AST, and thrombocytopenia, than other anti-HER2 therapies. CONCLUSIONS: Based on the current evidence, T-DM1 significantly prolonged PFS and OS with a tolerated toxicity than other anti-HER2 therapies in patients with HER2-positive MBC. These findings confirm the use of T-DM1 for the treatment of patients with HER2-positive MBC. Further well-designed, multi-center RCTs needed to identify these findings.

Neuroprotective effect of electroacupuncture and upregulation of hypoxia-inducible factor-1α during acute ischaemic stroke in rats.

BACKGROUND: Acupuncture is a traditional method that has been widely used in various fields of medicine with therapeutic effect. However, evidence of effectiveness to support the application of electroacupuncture (EA) during the process of ischaemia is scarce. OBJECTIVES: To investigate dynamic changes in hypoxia-inducible factor (HIF)-1α expression as well as its association with neurological status in rats subjected to acute ischaemic stroke and EA intervention. METHODS: Forty adult male rats were randomly divided into three groups that received sham surgery (Control group, n=10) or underwent middle cerebral artery occlusion and EA (MCAO+EA group, n=15) or minimal acupuncture as a control treatment (MCAO+MA group, n=15). The rats in the MCAO+EA and MCAO+MA groups received EA or acupuncture without any electrical current, respectively, during 90 min of ischaemia. Rats in the Control group received the same surgical procedure but without MCAO. EA involved electrical stimulation of needles inserted into the quadriceps at 50 Hz frequency and 3 mA current intensity. Neurological status was evaluated on postoperative day 1, and cerebral infarction volume (IV) and HIF-1α expression 24 hours later. RESULTS: Neurological scores were improved and cerebral IV was decreased in the MCAO+EA group compared to the MCAO+MA group (both p<0.05). Moreover, HIF-1α expression was higher in the MCAO+EA group versus the MCAO+MA group (p<0.05). CONCLUSIONS: EA enhanced recovery of neurological function, decreased cerebral IV and increased HIF-1α expression in ischaemic rats. Further research is needed to determine whether EA is effective for stroke treatment through the stimulation of muscle contraction.

Synergistic effect of crude oil plus dispersant on bacterial community in a louisiana salt marsh sediment.

A combined effect of crude oil plus dispersant (Corexit 9500A) significantly altered indigenous bacterial communities in a Louisiana salt marsh sediment after 30 days of incubation; the crude oil and/or Corexit 9500A treatments triggered shifts in bacterial communities and the shifted bacterial structure by crude oil plus Corexit 9500A was considerably different from those by either crude oil or Corexit 9500A. However, the synergistic effect of crude oil plus Corexit 9500A was not observed after 7 days of incubation; the bacterial community was slightly shifted by Corexit 9500A and the crude oil did not trigger any bacterial community shift after 7 days of incubation. DNA sequencing data indicated that Chromobacterium species was enriched in the Corexit 9500A microcosms after 7 days of incubation, while Pseudomonas, Advenella, Acidocella and Dyella spp. were enriched after 30 days of incubation. Parvibaculum was a dominant species in the crude oil microcosms after 30 days of incubation. Rhodanobacter, Dyella and Frateuria spp. were dominant in crude oil plus Corexit 9500A microcosms after 30 days of incubation. Our data show that the effect of crude oil plus Corexit 9500A on bacterial community is synergistic, and thus the dispersant effect should be considered with the spilled oil to correctly evaluate the environmental impact.

Kanglaite injection combined with chemotherapy versus chemotherapy alone in the treatment of advanced non-small cell lung carcinoma.

OBJECTIVE: To evaluate the clinical efficacy of Kanglaite (KLT) injection combined with chemotherapy versus chemotherapy alone in the treatment of advanced non-small cell lung carcinoma (NSCLC) by meta-analysis. MATERIALS AND METHODS: Electronic search of PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases was conducted to select studies about KLT injection combined with chemotherapy versus chemotherapy alone in the treatment of advanced NSCLC. The pooled risk ratio (RR) and its 95% confidence interval (95% CI) for objective response rate (ORR), Karnofsky (KPS) score improvement and nausea and vomiting were calculated by Stata11.0 statistical software. RESULT: Finally, we included 34 clinical trials in this meta-analysis. The pooled results suggested that KLT injection combined with systematic chemotherapy can significantly increase the objective response rate (ORR) [RR = 1.35, 95% CI: 1.23-1.48, (Z = 6.43, P = 0.000)], the quality of patients' life (KSP improvement) [RR = 2.04, 95% CI: 1.79-2.33, (Z = 10.57, P = 0.000)] and decrease the risk ratio of gastrointestinal reaction [RR = 0.53, 95% CI: 0.42-0.66, (Z = 5.53, P = 0.000)] compared with chemotherapy alone. CONCLUSION: KLT injection combined with chemotherapy can improve the short-term efficacy, performance status and decrease the risk of gastrointestinal reaction compared with systematic chemotherapy alone.

Impact of exposure of crude oil and dispersant (COREXIT® EC 9500A) on denitrification and organic matter mineralization in a Louisiana salt marsh sediment.

In response to the 2010 oil spill from the explosion of the Deepwater Horizon oil rig in the Gulf of Mexico, this experiment aims to study the ecological impact of the crude oil and dispersant (COREXIT® EC 9500A) in a coastal salt marsh ecosystem. The marsh sediment was incubated under an anaerobic condition with exposure to the crude oil or/and dispersant. The experiments were conducted in two continuous phases of nitrate addition to study denitrification potential using acetylene blockage technique and organic matter mineralization potential indicated by CO2 production in the sediment. Results show that the oil slightly (with no statistical significance p>0.05) increased both the denitrification and organic matter mineralization activities, likely due to oil components serving as additional organic matter. In contrast, the dispersant significantly (p<0.05) inhibited denitrification, but stimulated organic matter mineralization activities in the sediment due to unknown mechanisms. As a consequence, redox potentials (Eh) were much lower in the dispersant treated systems. The ecological impacts from the dispersant exposure may come from two fronts. First, loss of organic matter from the coastal marsh will threaten the long-term stability of the ecosystem, and the decrease in denitrification activity will weaken the N removal efficiency. Secondly, more reducing conditions developed by the dispersant exposure will likely preserve the oil in the ecosystem for an extended period of time due to weaker oil biodegradation under anaerobic conditions.

Prior exposure to enriched environment reduces nitric oxide synthase after transient MCAO in rats.

Increasing evidence shows that exposure to an enriched environment (EE) after cerebral ischemia/reperfusion injury is neuroprotective in animal models. However, little is known about of the neuroprotective effects of EE exposure prior to injury. The current study examined the effects of prior EE exposure on inducible and neuronal nitric oxide syntheses (iNOS and nNOS) after transient middle cerebral artery occlusion (tMCAO) in rats. A total of 72 rats were exposed to EE or standard housing condition (SC) for 1 month, followed by 90-min MCAO and reperfusion or sham surgery, leading to the following three groups: (1) EE+MCAO (n=24), (2) SC+MCAO (n=24), (3) SC+sham (n=24). Rats were sacrificed at 1, 6, or 24h after MCAO (n=6/group) for iNOS and nNOS mRNA quantification by real-time PCR and at 24h after MCAO (n=6/group) for iNOS and nNOS protein quantification by Western blot or were evaluated for neurological function outcomes, then sacrificed to assess infarct volume (n=6/group). Results showed that prior exposure to EE reduced iNOS and nNOS mRNA and protein and improved neurological status after MCAO without affecting infarct volume, suggesting that EE may provide neuroprotection via ischemic preconditioning.

Kinetics of desensitization and recovery from desensitization for human alpha4beta2-nicotinic acetylcholine receptors stably expressed in SH-EP1 cells.

AIM: Studies were conducted to define the kinetics of the onset of and recovery from desensitization for human alpha4beta2-nicotinic acetylcholine receptors (nAChR) heterologously expressed in the SH-EP1 human epithelial cell line. METHODS: Whole-cell patch clamp recordings were performed to evaluate alpha4beta2-nAChR currents. RESULTS: Application of 0.1 micromol/L nicotine or 1 mmol/L acetylcholine (ACh) for 1 s or longer induced two phases, with time constants of approximately 70 and approximately 700 ms, for the onset of alpha4beta2-nAChR desensitization. For a given duration of agonist exposure, recovery from desensitization induced by nicotine was slower than recovery from ACh-induced desensitization. Comparisons with published reports indicate that time constants for the recovery of alpha4beta2-nAChRs from desensitization are smaller than those for the recovery of human muscle-type nAChRs(1) from desensitization produced by the same concentrations and durations of exposure to an agonist. Moreover, the extent of human alpha4beta2-nAChR desensitization and rate of recovery are the same, regardless of whether they are measured using whole-cell recording or based on published findings(2) using isotopic ion flux assays; this equality demonstrates the equivalent legitimacy of these techniques in the evaluation of nAChR desensitization. Perhaps most significantly, recovery from desensitization also was best fit to a biphasic process. Regardless of whether it was fit to single or double exponentials, however, half-times for recovery from desensitization grew progressively longer with an increased duration of agonist exposure during the desensitizing pulse. CONCLUSION: These findings indicate the existence of alpha4beta2-nAChRs in many distinctive states of desensitization, as well as the induction of progressively deeper states of desensitization with the increased duration of agonist exposure.

Effects of ferric iron reduction and regeneration on nitrous oxide and methane emissions in a rice soil.

A laboratory soil slurry experiment and an outdoor pot experiment were conducted to study effects of ferric iron (Fe(III)) reduction and regeneration on nitrous oxide (N(2)O) and methane (CH(4)) emissions in a rice (Oryza sativa L.) soil. The anoxic slurry experiment showed that enhancing microbial Fe(III) reduction by ferrihydrite amendment (40 mol Fe g(-1)) transitionally stimulated N(2)O production and lowered CH(4) production by 16% during an initial 33-day incubation. Increased regeneration of Fe(III) through a 4-day aeration period in the Fe-amended slurry compared to the control slurry reduced CH(4) emission by 30% in the subsequent 15-day anaerobic incubation. The pot experiment showed that ferrihydrite amendment (63 micromol Fe g(-1)) stimulated N(2)O fluxes in the days following flooding. The Fe amendment suppression on CH(4) emission was obscured in the early season but became significant upon reflooding in the mid- and late-seasons. As a result, seasonal CH(4) emission in Fe-amended pots was 26% lower than the control with a single 2-day drainage and 69% lower with a double 2-day drainage. The reduction in CH(4) emission upon reflooding from the Fe-amended pots was mainly attributed to the increased Fe(III) regeneration during drainage showing a mechanism of Fe(III) regeneration in mitigating CH(4) emission by short-term drainage in flooded soils.