A two-photon fluorescent probe for lysosomal zinc ions

The selective detection of zinc ions in lysosomes over that in cytosol is achieved with a fluorescent probe, which enabled the fluorescence imaging of endogenous zinc ions in lysosomes of NIH 3T3 cells as well as mouse hippocampal tissues by two-photon microscopy under excitation at 900 nm.open

Anti-allergic effect of luteolin in mice with allergic asthma and rhinitis

Abstract Aim of the study : Results: after the oVa challenge, the number of eosinophils, neutrophils and lymphocytes in BaL fluid was significantly increased in group B, compared to group a (p < 0.001). mice in group C had no significant difference (p > 0.05). on the other hand, group D showed a significant decrease in all inflammatory cells compared to group B (p < 0.05). also, group D showed a significant decrease in iL-4, iL-5 and iL-13 in their lung homogenate compared to groups B and C (p < 0.05). group D also showed a significant decrease in inflammatory cell infiltration after luteolin treatment (p < 0.05). Conclusion: Luteolin had an anti-allergic effect in a murine model of allergic asthma and rhinitis

Paraprobiotic derived from Bacillus velezensis GV1 improves immune response and gut microbiota composition in cyclophosphamide-treated immunosuppressed mice

Paraprobiotics that benefit human health have the capacity to modulate innate and adaptive immune systems. In this study, we prepared the paraprobiotic from Bacillus velezensis GV1 using the heat-killing method and investigated its effects on immunity and gut microbiota in vitro and in vivo. The morphology of inactivated strain GV1 was observed using scanning electron microscopy. Treatment with GV1 promoted nitric oxide production and augmented cytokine (IL-6, IL-1β, and TNF-α) expression and secretion in RAW 264.7 macrophages. Moreover, the strain GV1 could alleviate cyclophosphamide monohydrate (CTX)-induced immunosuppression by reversing spleen damage and restoring the immune organ index, as well as by increasing the expression of immune-related cytokines (TNF-α, IL-1β, IFN-γ, and IL-2) in the spleen and thymus, respectively. Furthermore, GV1 treatment dramatically healed the CTX-damaged colon and regulated gut microbiota by increasing the relative abundance of beneficial bacterial families (Lactobacillaceae, Akkermansiaceae, and Coriobacteriaceae) and decreasing that of harmful bacterial families (Desulfovibrionaceae, Erysipelotrichaceae, and Staphylococcaceae). Thus, the heat-killed GV1 can be considered a potential immunoregulatory agent for use as a functional food or immune-enhancing medicine

Protective Effect of the Fruit Hull of Gleditsia sinensis on LPS-Induced Acute Lung Injury Is Associated with Nrf2 Activation

The fruit hull of Gleditsia sinensis (FGS) has been prescribed as a traditional eastern Asian medicinal remedy for the treatment of various respiratory diseases, but the efficacy and underlying mechanisms remain poorly characterized. Here, we explored a potential usage of FGS for the treatment of acute lung injury (ALI), a highly fatal inflammatory lung disease that urgently needs effective therapeutics, and investigated a mechanism for the anti-inflammatory activity of FGS. Pretreatment of C57BL/6 mice with FGS significantly attenuated LPS-induced neutrophilic lung inflammation compared to sham-treated, inflamed mice. Reporter assays, semiquantitative RT-PCR, and Western blot analyses show that while not affecting NF-κB, FGS activated Nrf2 and expressed Nrf2-regulated genes including GCLC, NQO-1, and HO-1 in RAW 264.7 cells. Furthermore, pretreatment of mice with FGS enhanced the expression of GCLC and HO-1 but suppressed that of proinflammatory cytokines in including TNF-α and IL-1β in the inflamed lungs. These results suggest that FGS effectively suppresses neutrophilic lung inflammation, which can be associated with, at least in part, FGS-activating anti-inflammatory factor Nrf2. Our results suggest that FGS can be developed as a therapeutic option for the treatment of ALI

A Role of Canonical Transient Receptor Potential 5 Channel in Neuronal Differentiation from A2B5 Neural Progenitor Cells

Store-operated Ca2+ entry (SOCE) channels are the main pathway of Ca2+ entry in non-excitable cells such as neural progenitor cells (NPCs). However, the role of SOCE channels has not been defined in the neuronal differentiation from NPCs. Here, we show that canonical transient receptor potential channel (TRPC) as SOCE channel influences the induction of the neuronal differentiation of A2B5+ NPCs isolated from postnatal-12-day rat cerebrums. The amplitudes of SOCE were significantly higher in neural cells differentiated from proliferating A2B5+ NPCs and applications of SOCE blockers, 2-aminoethoxy-diphenylborane (2-APB), and ruthenium red (RR), inhibited their rise of SOCE. Among TRPC subtypes (TRPC1-7), marked expression of TRPC5 and TRPC6 with turned-off TRPC1 expression was observed in neuronal cells differentiated from proliferating A2B5+ NPCs. TRPC5 small interfering RNA (siRNA) blocked the neuronal differentiation from A2B5+ NPCs and reduced the rise of SOCE. In contrast, TRPC6 siRNA had no significant effect on the neuronal differentiation from A2B5+ NPCs. These results indicate that calcium regulation by TRPC5 would play a key role as a switch between proliferation and neuronal differentiation from NPCs

Neuroprotective effects of triterpenoids from camellia japonica against amyloid beta-induced neuronal damage

Alzheimer's disease (AD), a neurocognitive impairment affecting human mental capacity, is related to the accumulation of amyloid-beta peptide (A beta) and the hyperphosphorylation of tau protein. In addition to modern therapies approved for AD treatment, natural products with antioxidant and anti-inflammatory properties have been studied for their potential to prevent AD pathogenesis. Six new noroleanane triterpenoids from the fruit peels of Camellia japonica were isolated, and their structures were determined by diverse spectroscopic methods. The APP neuroprotective effects of the six new compounds were tested against A beta-induced neurotoxicity and neuroinflammation in mouse hippocampal and microglial cells. In the model of HT22-transfected cells, compounds 1-4 showed strongly neuroprotective effects via antioxidant response element gene activation and decreased the level of glutamate uptake. Compounds 1-4 also appeared to have strong inhibitory effects on NO production in A beta(1-42)-transfected BV2 microglial cells. A docking simulation study was used to explain the inhibitory effects of compounds 1-4 on beta-secretase 1 (BACE1). Noroleanane triterpenoids 1 - 4 had potential neuroprotective and anti-inflammatory effects against A beta-induced neuronal damage. The structure-activity relationships of the 30 oleanane triterpenoids from C. japonica were assessed in a model of A beta(1-42)-transfected HT22 cells.N

Determinants of Conductive Hearing Loss in Tympanic Membrane Perforation

ObjectivesTympanic membrane perforations are common, but there have been few studies of the factors determining the extent of the resulting conductive hearing loss. The aims of this study were to determine whether the size of tympanic membrane perforation, pneumatization of middle ear & mastoid cavity, and location of perforation were correlated with air-bone gap (ABG) of patients.MethodsForty-two patients who underwent tympanoplasty type I or myringoplasty were included and preoperative audiometry were analyzed. Digital image processing was applied in computed tomography for the estimation of middle ear & mastoid pneumatization volume and tympanic membrane photograph for the evaluation of perforation size and location.ResultsPreoperative mean ABG increased with perforation size (P=0.018), and correlated inversely with the middle ear & mastoid volume (P=0.005). However, perforations in anterior versus posterior locations showed no significant differences in mean ABG (P=0.924).ConclusionThe degree of conductive hearing loss resulting from a tympanic membrane perforation would be expected with the size of perforation and pneumatization of middle ear and mastoid

Round-robin test on thermal conductivity measurement of ZnO nanofluids and comparison of experimental results with theoretical bounds

Ethylene glycol (EG)-based zinc oxide (ZnO) nanofluids containing no surfactant have been manufactured by one-step pulsed wire evaporation (PWE) method. Round-robin tests on thermal conductivity measurements of three samples of EG-based ZnO nanofluids have been conducted by five participating labs, four using accurate measurement apparatuses developed in house and one using a commercial device. The results have been compared with several theoretical bounds on the effective thermal conductivity of heterogeneous systems. This study convincingly demonstrates that the large enhancements in the thermal conductivities of EG-based ZnO nanofluids tested are beyond the lower and upper bounds calculated using the models of the Maxwell and Nan et al. with and without the interfacial thermal resistance

A retrospective analysis of second-line chemotherapy in patients with advanced gastric cancer

<p>Abstract</p> <p>Background</p> <p>Because treatment of advanced gastric cancer (AGC) patients after failure with first-line chemotherapy remains controversial, we performed this retrospective analysis based on the data obtained from 1455 patients registered in a first-line treatment cohort with respect to receiving or not receiving subsequent chemotherapy.</p> <p>Methods</p> <p>The decision for administering second-line chemotherapy was, in most cases, at the discretion of the physician. Seven-hundred twenty-five (50%) received second-line chemotherapy after first-line failure. Univariate and multivariate analyses were performed on the recognized baseline parameters for survival.</p> <p>Results</p> <p>At the time of initiating second-line chemotherapy, the patients' median age was 56 years (range, 22 to 86) and 139 (19%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or more. Seven (1%) complete and 108 (15%) partial responses to second-line chemotherapy were observed for an overall response rate of 16% (95% confidence interval [CI], 13 to 19%). The median progression-free and overall survivals, calculated from the start of second-line chemotherapy, were 2.9 months (95% CI, 2.6 to 3.3) and 6.7 months (95% CI, 5.8 to 7.5), respectively. Multivariate analysis revealed that low baseline hemoglobin level (hazard ratio [HR], 0.74; 95% CI 0.61–0.90) and a poor performance status (HR, 0.66; 95% CI, 0.52–0.83) were independent negative prognostic factors for overall survival.</p> <p>Conclusion</p> <p>Performance status, along with baseline hemoglobin level, could be used to identify the subgroup of patients most likely to benefit from second-line chemotherapy for AGC.</p