A critical review on the use of flue gas desulfurization gypsum to ameliorate saline-alkali soils and its prospect for reducing carbon emissions.

Flue gas desulfurization gypsum (FGDG), a solid waste produced during sulfur removal in coal-fired power plants, has applications in saline-alkali soil amelioration due to its function of calcium­sodium ion exchange. Existing research has focused on the use of gypsum to improve saline-alkali soils in non-coastal areas. However, coastal areas are not only extensively salinized, but an important source of methane, and surprisingly, FGDG may assist to decrease methane formation mainly by the action of sulfate radical. This is the first critical review to systematically discuss the effects of FGDG on both saline-alkali soil improvement and carbon emission control in tidal flats, including application status, amendment principles, environmental risks and methane emission control. After adding FGDG, soil salinization degree was weakened via adjusting soil structure, pH, exchangeable sodium percentage and electric conductivity, introduction of nutrients also promotes crop growth. The optimal FGDG dosage in tidal flats seems to be higher (>2 %) than that in non-coastal areas (<1 %). Its environmental risks regarding heavy metals and eutrophication are evaluated safe. In tidal areas, more methane is produced in hot seasons and ebb tides. Plants and invertebrates also promote methane release. FGDG controls methane production by promoting the activity of sulfate-reducing bacteria and inhibiting methanogens. Considering methane flux levels and seawater erosion, FGDG use in low tidal beach needs more research, while that in high and middle tidal beach is recommended. This review will expand applications and appropriate use of FGDG for reducing carbon emission and improving ecological services in coastal areas.

Altered synaptic currents, mitophagy, mitochondrial dynamics in Alzheimer's disease models and therapeutic potential of Dengzhan Shengmai capsules intervention.

Emerging research suggests a potential association of progression of Alzheimer's disease (AD) with alterations in synaptic currents and mitochondrial dynamics. However, the specific associations between these pathological changes remain unclear. In this study, we utilized Aß42-induced AD rats and primary neural cells as in vivo and in vitro models. The investigations included behavioural tests, brain magnetic resonance imaging (MRI), liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis, Nissl staining, thioflavin-S staining, enzyme-linked immunosorbent assay, Golgi-Cox staining, transmission electron microscopy (TEM), immunofluorescence staining, proteomics, adenosine triphosphate (ATP) detection, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) assessment, mitochondrial morphology analysis, electrophysiological studies, Western blotting, and molecular docking. The results revealed changes in synaptic currents, mitophagy, and mitochondrial dynamics in the AD models. Remarkably, intervention with Dengzhan Shengmai (DZSM) capsules emerged as a pivotal element in this investigation. Aß42-induced synaptic dysfunction was significantly mitigated by DZSM intervention, which notably amplified the frequency and amplitude of synaptic transmission. The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions, including the hippocampal CA3, primary cingular cortex, prelimbic system, and dysgranular insular cortex. DZSM intervention led to increased IDE levels, augmented long-term potential (LTP) amplitude, and enhanced dendritic spine density and length. Moreover, DZSM intervention led to favourable changes in mitochondrial parameters, including ROS expression, MMP and ATP contents, and mitochondrial morphology. In conclusion, our findings delved into the realm of altered synaptic currents, mitophagy, and mitochondrial dynamics in AD, concurrently highlighting the therapeutic potential of DZSM intervention.

Neuroendocrine pathogenesis of perimenopausal depression.

With the development of social economics and the increase of working pressure, more and more women are suffering from long-term serious stress and showing symptoms of perimenopausal depression (PMD). The incidence rate of PMD is increasing, and the physical and mental health are seriously affected. However, due to the lack of accurate knowledge of pathophysiology, its diagnosis and treatment cannot be accurately executed. By consulting the relevant literature in recent years, this paper elaborates the neuroendocrine mechanism of perimenopausal depression from the aspects of epigenetic changes, monoamine neurotransmitter and receptor hypothesis, glial cell-induced neuroinflammation, estrogen receptor, interaction between HPA axis and HPG axis, and micro-organism-brain gut axis. The purpose is to probe into new ways of treatment of PMD by providing new knowledge about the neuroendocrine mechanism and treatment of PMD.

PolyReco: A Method to Automatically Label Collinear Regions and Recognize Polyploidy Events Based on the K S Dotplot.

Polyploidization plays a critical role in producing new gene functions and promoting species evolution. Effective identification of polyploid types can be helpful in exploring the evolutionary mechanism. However, current methods for detecting polyploid types have some major limitations, such as being time-consuming and strong subjectivity, etc. In order to objectively and scientifically recognize collinearity fragments and polyploid types, we developed PolyReco method, which can automatically label collinear regions and recognize polyploidy events based on the K S dotplot. Combining with whole-genome collinearity analysis, PolyReco uses DBSCAN clustering method to cluster K S dots. According to the distance information in the x-axis and y-axis directions between the categories, the clustering results are merged based on certain rules to obtain the collinear regions, automatically recognize and label collinear fragments. According to the information of the labeled collinear regions on the y-axis, the polyploidization recognition algorithm is used to exhaustively combine and obtain the genetic collinearity evaluation index of each combination, and then draw the genetic collinearity evaluation index graph. Based on the inflection point on the graph, polyploid types and related chromosomes with polyploidy signal can be detected. The validation experiments showed that the conclusions of PolyReco were consistent with the previous study, which verified the effectiveness of this method. It is expected that this approach can become a reference architecture for other polyploid types classification methods.

Molecular Mechanisms of Glutamate Toxicity in Parkinson's Disease.

Parkinson's disease (PD) is a common neurodegenerative disease, the pathological features of which include the presence of Lewy bodies and the neurodegeneration of dopaminergic neurons in the substantia nigra pars compacta. However, until recently, research on the pathogenesis and treatment of PD have progressed slowly. Glutamate and dopamine are both important central neurotransmitters in mammals. A lack of enzymatic decomposition of extracellular glutamate results in glutamate accumulating at synapses, which is mainly absorbed by excitatory amino acid transporters (EAATs). Glutamate exerts its physiological effects by binding to and activating ligand-gated ion channels [ionotropic glutamate receptors (iGluRs)] and a class of G-protein-coupled receptors [metabotropic glutamate receptors (mGluRs)]. Timely clearance of glutamate from the synaptic cleft is necessary because high levels of extracellular glutamate overactivate glutamate receptors, resulting in excitotoxic effects in the central nervous system. Additionally, increased concentrations of extracellular glutamate inhibit cystine uptake, leading to glutathione depletion and oxidative glutamate toxicity. Studies have shown that oxidative glutamate toxicity in neurons lacking functional N-methyl-D-aspartate (NMDA) receptors may represent a component of the cellular death pathway induced by excitotoxicity. The association between inflammation and excitotoxicity (i.e., immunoexcitotoxicity) has received increased attention in recent years. Glial activation induces neuroinflammation and can stimulate excessive release of glutamate, which can induce excitotoxicity and, additionally, further exacerbate neuroinflammation. Glutamate, as an important central neurotransmitter, is closely related to the occurrence and development of PD. In this review, we discuss recent progress on elucidating glutamate as a relevant neurotransmitter in PD. Additionally, we summarize the relationship and commonality among glutamate excitotoxicity, oxidative toxicity, and immunoexcitotoxicity in order to posit a holistic view and molecular mechanism of glutamate toxicity in PD.

Piperine Attenuates TBI-Induced Seizures via Inhibiting Cytokine-Activated Reactive Astrogliosis.

Peppers have been used in clinics for a long time and its major component, piperine (PPR), has been proven to be effective in the treatment of seizures. The purpose of this study was to investigate the effects of piperine on early seizures in mice after a traumatic brain injury (TBI) and to explore the mechanism of the drug against the development on TBI. Specific-pathogen-free-grade mice were randomly divided into six dietary groups for a week: control group, TBI group, three piperine groups (low PPR group with 10 mg/kg PPR, medium PPR group with 20 mg/kg PPR, and high PPR group with 40 mg/kg PPR), and a positive control group (200 mg/kg valproate). Except for the control group, all the other groups used Feeney free weight falling method to establish the TBI of closed brain injury in mice, and the corresponding drugs were continuously injected intraperitoneally for 7 days after the brain injury. The results from behavior and electroencephalogram showed that piperine attenuated the subthreshold dose of pentylenetetrazole-induced seizures compared with the TBI group. The western blot results showed that the expression levels of inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were reduced by piperine. The immunostaining results showed that the brain-derived neurotrophic factor (BDNF) was also reduced by piperine. In addition, positive cell counts of astrocytic fibrillary acidic protein (GFAP) in immuno-fluorescence showed that they were also reduced. Our data show that piperine treatment can reduce the degree of cerebral edema, down-regulate TNF-α, IL-1ß, and BDNF, decrease the reactivity of GFAP in the hippocampus, and inhibit TBI-induced seizures.

Identification of a panel of genes as a prognostic biomarker for glioblastoma.

BACKGROUND: Glioblastoma multiforme (GBM) is a fatal disease without effective therapy. Identification of new biomarkers for prognosis would enable more rational selections of strategies to cure patients with GBM and prevent disease relapse. METHODS: Seven datasets derived from GBM patients using microarray or next generation sequencing in R2 online database (http://r2.amc.nl) were extracted and then analyzed using JMP software. The survival distribution was calculated according to the Kaplan-Meier method and the significance was determined using log-rank statistics. The sensitivity of a panel of GBM cell lines in response to temozolomide (TMZ), salinomycin, celastrol, and triptolide treatments was evaluated using MTS and tumor-sphere formation assay. FINDINGS: We identified that CD44, ATP binding cassette subfamily C member 3 (ABCC3), and tumor necrosis factor receptor subfamily member 1A (TNFRSF1A) as highly expressed genes in GBMs are associated with patients' poor outcomes and therapy resistance. Furthermore, these three markers combined with MGMT, a conventional GBM marker, can classify GBM patients into five new subtypes with different overall survival time in response to treatment. The four-gene signature and the therapy response of GBMs to a panel of therapeutic compounds were confirmed in a panel of GBM cell lines. INTERPRETATION: The data indicate that the four-gene panel can be used as a therapy response index for GBM patients and potential therapeutic targets. These results provide important new insights into the early diagnosis and the prognosis for GBM patients and introduce potential targets for GBM therapeutics. FUND: Baylor Scott & White Health Startup Fund (E.W.); Collaborative Faculty Research Investment Program (CFRIP) of Baylor University, Baylor Scott & White Health, and Baylor College of Medicine (E.W., T.S., J.H.H.); NIH R01 NS067435 (J.H.H.); Scott & White Plummer Foundation Grant (J.H.H.); National Natural Science Foundation of China 816280007 (J.H.H. and Fu.W.).

Remnant preservation technique versus standard technique for anterior cruciate ligament reconstruction: a meta-analysis of randomized controlled trials.

BACKGROUND: This meta-analysis was performed to compare the clinical outcomes of primary anterior cruciate ligament (ACL) reconstruction using the ACL remnant preservation technique versus the standard technique. METHODS: PubMed, Embase, and the Cochrane Library were searched through December 24, 2017, to identify randomized controlled studies that compared the use of the ACL remnant preservation technique versus the standard technique for primary ACL reconstruction. Statistical heterogeneity among the trials was evaluated with chi-square and I-square tests. A sensitivity analysis was conducted to explore sources of heterogeneity. Subgroup analysis was performed to identify potential differences according to type of ACL remnant tissue (remnant bundle or remnant fibers). RESULTS: Seven studies with a combined 412 patients (208 in the remnant preservation technique group and 204 in the standard technique group) were included in the meta-analysis. There was a significant difference between the groups in Lysholm score (mean difference (MD), 2.20; 95% confidence interval (CI), 0.95-3.45; P = 0.0006) and side-to-side difference (MD, - 0.71; 95% CI, - 0.87 to - 0.55; P < 0.01). There was no significant difference between the groups in subjective International Knee Documentation Committee (IKDC) score, complications, pivot shift test, Lachman test, or overall IKDC score. Subgroup analysis demonstrated that for primary ACL reconstruction with preservation of remnant fibers, the remnant preservation technique was superior to the standard technique based on Lysholm scores (P < 0.01) and side-to-side difference (P < 0.01). CONCLUSIONS: Based on the current literature, using the remnant preservation technique showed a better clinical outcome than using the standard technique for patients undergoing primary ACL reconstruction with respect to Lysholm score and side-to-side difference. However, it remains unclear that there is a definite advantage to use the remnant preservation technique compared with the standard technique.

Stress Induced Hormone and Neuromodulator Changes in Menopausal Depressive Rats.

Objective: Previously, we showed that neuromodulators are important factors involved in depression, here we aim to further investigate the interactions between neuromodulators and sex hormone involved in menopause related depression in rats. Methods: Menopausal depression was made with bilateral ovariectomies in female SD rats followed by chronic mild unpredictable stress treatment for 21 days. Thirty six rats were randomly divided into four groups: sham surgery group, sham/stress group, surgery group, surgery/stress group. Then open-field locomotor scores and sucrose intake were employed to observe behavior changes. The levels of norepinephrine (NE), dopamine (DA), serotonin (5-HT) in the cerebral spinal fluid and serum adrenocorticotropic hormone (ACTH), cortisone were determined with High-performance liquid chromatography (HPLC). Serum estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured with radioimmunoassay. Results: The open-field locomotor scores and sucrose intake were significantly decreased after the surgery and stress treatment (p < 0.01). The Serum E2 level decreased significantly after the surgery (p < 0.01), but serum LH, FSH levels increased significantly in the surgery group than the sham surgery group (p < 0.01). The cortisone levels increased significantly in sham/stress group than that in the sham surgery group during the first 2 weeks at stressful treatment, but decrease afterwards. The monoamine levels in the surgery/stress group were much lower than those in the sham surgery group (p < 0.01). The correlation analysis found that LH and FSH are related more to the neurotransmitter release than E2. Conclusion: Ovary removal rats showed depression-like behaviors, with LH and FSH increase and monoamine decrease, and the levels of these monoamines in the stress treated groups changed only after the stressful treatment. The LH, FSH hormone increasing might be the reason for the lower monoamine release, which in turn might be the reason for depressed syndromes in the menopause. The cortisone and ACTH in the serum in the surgery/stress group were much higher than that in the sham surgery group.

Comparison of clinical outcomes after anterior cruciate ligament reconstruction with hamstring tendon autograft versus soft-tissue allograft: A meta-analysis of randomised controlled trials.

BACKGROUND: Hamstring tendon autografts and soft-tissue allograft are commonly used for anterior cruciate ligament (ACL) reconstruction. However, the clinical outcomes between these two grafts are controversial. This meta-analysis was performed to compare clinical outcomes of primary ACL reconstruction with hamstring tendon autografts versus soft-tissue allografts. MATERIALS AND METHODS: PubMed, Embase, and the Cochrane Library were searched through 8 September 2017 to identify randomized controlled studies that compared hamstring tendon autografts with soft-tissue allografts for primary ACL reconstruction. Two authors independently graded the methodological quality of each eligible study using the Cochrane Collaboration tool and extracted relevant data. Statistical heterogeneity among the trials was evaluated with chi-square and I-square tests. A sensitivity analysis was conducted to explore sources of heterogeneity. Subgroup analysis was performed to identify potential differences according to type of reconstruction technique (single-bundle or double-bundle). RESULTS: Eight studies with 785 combined patients (396 hamstring tendon autografts and 389 soft-tissue allografts) were included. Two studies had a high risk of bias. The other six studies had unclear risk of bias. There were significant differences between the groups in subjective International Knee Documentation Committee (IKDC) score (mean difference [MD], 2.43; 95%CI, 0.69-4.18; p = 0.006), Tegner score (MD, 0.24; 95%CI, 0.03-0.45; p = 0.03), and side-to-side difference (MD, -1.37; 95%CI, -2.44 to -0.30; p = 0.01). There was no significant difference between the groups in Lysholm score, complications, pivot shift test, anterior drawer test, Lachman test, overall IKDC score, or range of motion. Subgroup analysis demonstrated that for primary ACL reconstruction using the single-bundle technique, soft-tissue allografts were inferior to hamstring tendon autografts in subjective IKDC score, anterior drawer test, and side-to-side difference. CONCLUSION: Soft-tissue allografts are inferior to hamstring tendon autografts with respect to subjective patient evaluation and knee stability but superior in the complication of hypoesthesia for patients undergoing primary ACL reconstruction.

Human glia can both induce and rescue aspects of disease phenotype in Huntington disease.

The causal contribution of glial pathology to Huntington disease (HD) has not been heavily explored. To define the contribution of glia to HD, we established human HD glial chimeras by neonatally engrafting immunodeficient mice with mutant huntingtin (mHTT)-expressing human glial progenitor cells (hGPCs), derived from either human embryonic stem cells or mHTT-transduced fetal hGPCs. Here we show that mHTT glia can impart disease phenotype to normal mice, since mice engrafted intrastriatally with mHTT hGPCs exhibit worse motor performance than controls, and striatal neurons in mHTT glial chimeras are hyperexcitable. Conversely, normal glia can ameliorate disease phenotype in transgenic HD mice, as striatal transplantation of normal glia rescues aspects of electrophysiological and behavioural phenotype, restores interstitial potassium homeostasis, slows disease progression and extends survival in R6/2 HD mice. These observations suggest a causal role for glia in HD, and further suggest a cell-based strategy for disease amelioration in this disorder.

Outcome after pancreaticoduodenectomy for malignancy in elderly patients.

BACKGROUND/AIMS: To evaluate short-term outcomes and long-term survival after pancreaticoduodenectomy for malignancy in elderly Chinese patients (aged 70 years or older) compared with younger patients. METHODOLOGY: Between January 2005 and December 2013, 216 consecutive patients who underwent a PD with pancreatic cancer or periampullary cancers in our institution were recruited in this study. Sixty-eight patients aged 70 years or older when they underwent PD, while 148 patients younger than 70. RESULTS: There were no significant differences in postoperative mortality (p = 0.104), overall morbidity (p = 0.057) and surgical complications (p = 0.200) between the elderly patients and the younger patients. Elderly patients had a significantly higher incidence of cardiac events (p = 0.008) and pneumonia (p = 0.041) postoperatively. The postoperative hospital stay in the older age group was significantly longer (p = 0.013). The overall survival did not differ between the two age groups both when patients with pancreatic cancer were analyzed (p = 0.836) and when patients with periampullary cancers were analyzed (p = 0.817). CONCLUSIONS: Our results showed that pancreaticoduodenectomy for malignancy in Chinese patients over 70 years old could be performed safely. Age should not be considered as a contraindication to pancreaticoduodenectomy.

G-protein coupled receptor 34 knockdown impairs the proliferation and migration of HGC-27 gastric cancer cells in vitro.

BACKGROUND: Overexpression of G-protein coupled receptor 34 (GPR34) affects the progression and prognosis of human gastric adenocarcinoma, however, the role of GPR34 in gastric cancer development and progression has not been well-determined. The current study aimed to investigate the effect of GPR34 knockdown on the proliferation, migration, and apoptosis of HGC-27 gastric cancer cells and the underlying mechanisms. METHODS: The expression of GPR34 in gastric cancer cell line HGC-27 was detected by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. HGC-27 cells were employed to construct the stable GPR34 knockdown cell model in this study. Real-time RT-PCR and Western blotting were applied to validate the effect of short hairpin RNA (ShRNA) on the expression of GPR34 in HGC-27 gastric cells. The proliferation, migration of these cells were examined by Cell Counting Kit-8 and transwell. We also measured expression profile of PI3K/PDK1/AKT and ERK using Western blotting. RESULTS: The ShRNA directed against GPR34 effectively inhibited both endogenous mRNA and protein expression levels of GPR34, and significantly down-regulated the expression of PIK3CB (P < 0.01), PIK3CD (P < 0.01), PDK1 (P < 0.01), phosphorylation of PDK1 (P < 0.01), Akt (P < 0.01), and ERK (P < 0.01). Furthermore, GPR34 knockdown resulted in an obvious reduction in HGC-27 cancer cell proliferation and migration activity (P < 0.01). CONCLUSIONS: GPR34 knockdown impairs the proliferation and migration of HGC-27 gastric cancer cells in vitro and provides a potential implication for therapy of gastric cancer.

Establishment and characterization of an immortalized rat hepatic stellate cell line.

Hepatic stellate cells (HSCs) play an important role in liver fibrosis and portal hypertension. This study established a new rat HSC cell line LSC-1. Liver ex vivo perfusion with collagenase IV and density gradient centrifugation were used to isolate rat HSC. Cells have been maintained in culture for multiple passages. LSC-1 cell biological characteristics were studied. LSC-1 cell have been maintained in culture over 100 passages. This new HSC cell line express telomerase reverse transcriptase (TRT) and p53, suggesting that it is immortalized spontaneously. LSC-1 cells have a doubling time of 46 hours and their growth is serum-dependent. Karyotypic analysis revealed that LSC-1 cells possess normal chromosome phenotype. Moreover, LSC-1 cells do not grow in soft agar or induce tumors in nude mice, suggesting that they are not transformed. LSC-1 cells express desmin, glial fibrillary acidic proteins (GFAP), collagen type I and III, α-smooth muscle actin (α-SMA), transforming growth factor ß1 (TGF-ß1), platelet derived growth factor B (PDGF-B) and inducible nitric oxide synthase (iNOS). TGF-ß1 stimulation increased collagen type I and III expression in LSC-1 cells. Additionally, LSC-1 cells proliferate in response to PDGF-BB, and contract in response to endothelin-1 (ET-1). In summary, LSC-1 cells exhibit activated HSC phenotype characteristics, and therefore are useful tool to study the pathogenesis of liver cirrhosis and portal hypertension.

Blockade of the OX40/OX40L pathway and induction of PD-L1 synergistically protects mouse islet allografts from rejection.

BACKGROUND: OX40/OX40 ligand (OX40/OX40L) and programmed death-1/programmed death ligand-1 (PD-1/PD-L1) costimulatory signals play important roles in T cell-induced immune responses. The aim of this study was to investigate the roles of OX40/OX40L and PD-1/PD-L1 costimulatory pathways in mouse islet allograft rejection. METHODS: Lentiviral vectors containing OX40L siRNA sequences and an adenovirus vector containing the PD-L1 gene were constructed. The streptozotocin-induced model of diabetes was established in C57BL/6 (H-2(b)) mice. Diabetic C57BL/6 mice were randomly allocated into five groups: group 1, untreated control; group 2, Ad-EGFP treatment; group 3, Ad-PD-L1 treatment; group 4, OX40L-RNAi-LV treatment; group 5, OX40L-RNAi-LV combined with Ad-PD-L1 treatment. Lentiviral vector and the adenovirus vector were injected, singly or combined, into the caudal vein one day before islet transplantation. The islets of DBA/2 (H-2(d)) mice were transplanted into the renal subcapsular space of the diabetic recipients. Recipient blood glucose and the survival time of the allografts were monitored. Antigen-specific mixed lymphocyte reaction was also evaluated. RESULTS: The recombinant lentiviral RNA interference vector OX40L-RNAi-LV reduced OX40L protein expression by 70%. The recombinant adenovirus vector Ad-PD-L1 increased PD-L1 protein expression in vivo in C57BL/6 recipient mice. Combined OX40L-RNAi-LV/Ad-PD-L1 treatment induced a synergistic protective effect in pancreatic islet allografts. Allograft survival time in the combined treatment group was (92.27±9.65) days, not only longer than that of the control ((6.51±0.27) days) and Ad-EGFP groups ((7.09±0.13) days) (P < 0.01), but also significantly longer than that of Ad-PD-L1 and OX40L-RNAi-LV single treatment groups ((40.64±3.95) days and (55.14±5.48) days respectively, P < 0.01). The blood glucose concentration of recipient mice in the combined treatment group was also stable and kept within the normal range. Flow cytometry analysis showed that combined OX40L-RNAi-LV/Ad-PD-L1 treatment significantly decreased proliferation in an antigen-specific mixed lymphocyte reaction. After donor DBA/2 lymphocyte stimulation, 89.71% of lymphocytes from recipient combination treatment C57BL/6 mice were not split and proliferated. In contrast, after stimulation with third party Lewis rat lymphocytes, only 45.84% lymphocytes of C57BL/6 mice were not split and proliferated. CONCLUSIONS: This study demonstrates the successful construction of the recombinant lentivirus vector OX40L-RNAi-LV and adenovirus vector Ad-PD-L1 for the blockade of OX40/OX40L and activation of PD-1/PD-L1 costimulatory pathways simultaneously in pancreatic islet allografts in diabetic mice. Combination therapy with these two vectors resulted in inhibition of T cell activation, synergistically prolonging the survival time of pancreatic islet allografts.

Ileo-colonic intussusception secondary to small-bowel lipomatosis: a case report.

Intestinal lipomatosis is a rare disease with an incidence at autopsy ranging from 0.04% to 4.5%. Because the lipomas are diffusely distributed in the intestine, most patients are symptom-free, and invasive intervention is not advised by most doctors. Here, we describe a case with intussusception due to small-bowel lipomatosis. Partial small bowel resection and anastomosis were performed because the intestinal wall was on the verge of perforation. This case indicates that regular follow-up is necessary and endoscopic treatment should be considered to avoid surgical procedures if the lipoma is large enough to cause intestinal obstruction.

[Effect of erythromycin on electrical activity and gastric emptying of the intrathoracic stomach after esophagectomy for esophageal cancer].

OBJECTIVE: To investigate the effect of erythromycin on electrical activity and emptying of the intrathoracic stomach after esophagectomy for esophageal cancer. METHODS: Thirty patients undergoing esophagectomy for cancer and esophagogastrostomy above the aortic arch were divided into the study group (n=15) and the control group (n=15). Electrogastrography and radionuclide gastric emptying were examined for these patients before and 1, 3, 6, 12 months after surgery. Patients in the study group received erythromycin (0.25 g tid po) for 1 week before examination. RESULTS: The wave amplitude (Uv), dominant frequency (CPM) and percentage of normal slow wave (%) of electrogastrogram decreased after surgery and returned to normal at the first postoperative month in the study group and the 12th postoperative month in the control group (P>0.05). Gastric emptying was significantly delayed after esophagectomy, and returned to normal one year after operation in the study group (P>0.05). However, gastric emptying remained abnormal in the control group (P<0.01). CONCLUSIONS: Erythromycin improves electrical activity and emptying of the stomach after esophagectomy for cancer. Gastric emptying recovery later than the recovery of electrical activity, which may be related to gastric ischemia and edema.

Sustained mobilization of endogenous neural progenitors delays disease progression in a transgenic model of Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disease characterized in part by the loss of striatopallidal medium spiny projection neurons (MSNs). Expression of BDNF and noggin via intracerebroventricular (ICV) delivery in an adenoviral vector triggers the addition of new neurons to the neostriatum. In this study, we found that a single ICV injection of the adeno-associated viruses AAV4-BDNF and AAV4-noggin triggered the sustained recruitment of new MSNs in both wild-type and R6/2 mice, a model of HD. Mice treated with AAV4-BDNF/noggin or with BDNF and noggin proteins actively recruited subependymal progenitor cells to form new MSNs that matured and achieved circuit integration. Importantly, the AAV4-BDNF/noggin-treated R6/2 mice showed delayed deterioration of motor function and substantially increased survival. In addition, squirrel monkeys given ICV injections of adenoviral BDNF/noggin showed similar addition of striatal neurons. Induced neuronal addition may therefore represent a promising avenue for disease amelioration in HD.

Astrocytes modulate neural network activity by Ca²+-dependent uptake of extracellular K+.

Astrocytes are electrically nonexcitable cells that display increases in cytosolic calcium ion (Ca²+) in response to various neurotransmitters and neuromodulators. However, the physiological role of astrocytic Ca²+ signaling remains controversial. We show here that astrocytic Ca²+ signaling ex vivo and in vivo stimulated the Na+,K+-ATPase (Na+- and K+-dependent adenosine triphosphatase), leading to a transient decrease in the extracellular potassium ion (K+) concentration. This in turn led to neuronal hyperpolarization and suppressed baseline excitatory synaptic activity, detected as a reduced frequency of excitatory postsynaptic currents. Synaptic failures decreased in parallel, leading to an increase in synaptic fidelity. The net result was that astrocytes, through active uptake of K+, improved the signal-to-noise ratio of synaptic transmission. Active control of the extracellular K+ concentration thus provides astrocytes with a simple yet powerful mechanism to rapidly modulate network activity.

Extracellular Ca²âº acts as a mediator of communication from neurons to glia.

Defining the pathways through which neurons and astrocytes communicate may contribute to the elucidation of higher central nervous system functions. We investigated the possibility that decreases in extracellular calcium ion concentration ([Ca(2+)](e)) that occur during synaptic transmission might mediate signaling from neurons to glia. Using noninvasive photolysis of the photolabile Ca(2+) buffer diazo-2 {N-[2-[2-[2-[bis(carboxymethyl)amino]-5-(diazoacetyl)phenoxy]ethoxy]-4-methylphenyl]-N-(carboxymethyl)-, tetrapotassium salt} to reduce [Ca(2+)](e) or caged glutamate to simulate glutamatergic transmission, we found that a local decline in extracellular Ca(2+) triggered astrocytic adenosine triphosphate (ATP) release and astrocytic Ca(2+) signaling. In turn, activation of purinergic P2Y1 receptors on a subset of inhibitory interneurons initiated the generation of action potentials by these interneurons, thereby enhancing synaptic inhibition. Thus, astrocytic ATP release evoked by an activity-associated decrease in [Ca(2+)](e) may provide a negative feedback mechanism that potentiates inhibitory transmission in response to local hyperexcitability.