[Baicalin improves inflammatory response of human microglia by regulating cAMP-PKA-NF-κB/CREB pathway].

This study aims to investigate the effects of baicalein(BAI) on lipopolysaccharide(LPS)-induced human microglial clone 3(HMC3) cells, with a focus on suppressing inflammatory responses and elucidating the potential mechanism underlying the therapeutic effects of BAI on ischemic stroke via modulating the cAMP-PKA-NF-κB/CREB pathway. The findings have significant implications for the application of traditional Chinese medicine in treating cerebral ischemic diseases. First, the safe dosage of BAI was screened, and then an inflammation model was established with HMC3 cells by induction with LPS for 24 h. The cells were assigned into a control group, a model group, and high-, medium-, and low-dose(5, 2.5, and 1.25 µmol·L~(-1), respectively) BAI groups. The levels of superoxide dismutase(SOD) and malondialdehyde(MDA) in cell extracts, as well as the levels of interleukin-1ß(IL-1ß), IL-6, tumor necrosis factor-α(TNF-α), and cyclic adenosine monophosphate(cAMP) in the cell supernatant, were measured. Western blot was performed to determine the expression of protein kinase A(PKA), phosphorylated cAMP-response element binding protein(p-CREB), and nuclear factor-kappa B p65(NF-κB p65). Hoechst 33342/PI staining was employed to assess cell apoptosis. High and low doses of BAI were used for treatment in the research on the mechanism. The results revealed that BAI at the concentrations of 10 µmol·L~(-1) and below had no impact on normally cultured HMC3 cells. LPS induction at 200 ng·mL~(-1) for 24 h reduced the SOD activity and increased the MDA content in HMC3 cells. However, 5, 2.5, and 1.25 µmol·L~(-1) BAI significantly increased the SOD activity and 5 µmol·L~(-1) BAI significantly decreased the MDA content. In addition, BAI ameliorated the M1 polarization of HMC3 cells induced by LPS, as indicated by cellular morphology. The results of ELISA demonstrated that BAI significantly lowered the levels of TNF-α, IL-1ß, IL-6, and cAMP in the cell supernatant. Western blot revealed that BAI up-regulated the protein levels of PKA and p-CREB while down-regulating the expression of NF-κB p65. Hoechst 33342/PI staining results indicated that BAI mitigated the apoptosis of HMC3 cells. Overall, the results indicated that BAI had protective effects on the HMC3 cells induced by LPS, and could inhi-bit inflammatory response and improve cell apoptosis, which might be related to the regulation of the cAMP-PKA-NF-κB/CREB pathway.

Distribution of multiple chalazia in eyelids of pediatrics requiring surgery in southeast China: a hospital-based cross-sectional study.

Background: Multiple chalazia are common in children, and many are treated by surgery. However, the distribution of different types of multiple chalazia has not been studied. This research aimed to investigate the location and number of multiple chalazia in pediatrics who need surgical treatments. Methods: Patients with multiple chalazia treated by incision and curettage surgery (I&C) in a tertiary children's hospital between June and December 2016 were reviewed. Demographic data, locations, and numbers of chalazia were recorded. Data were analyzed using generalized linear models of the counts and the occurrences of chalazia. Hypotheses were tested using likelihood ratio tests appropriate for each type of data. Results: The study included 128 subjects, most of which were 1-3 years old. The majority of patients had bilateral chalazia (95.3%), and the proportions of patients with internal, external, and marginal chalazion differed dramatically (99.2%, 61.7%, and 2.3%, respectively). The number of internal and external chalazia did not vary significantly with gender, age, or residence of the patients. Internal chalazia were located more frequently in the upper lids (p<0.001). External chalazia showed no preference of localization. The average number of internal chalazia in each eyelid did not relate to the presence of external chalazia. Conclusions: Multiple chalazia are common among younger children in southeast China. The anatomical distribution varies depending on the type of chalazion. Multiple chalazia often occur bilaterally and internally. If doctors are more aware of the anatomical distribution of chalazia, this might result in a higher success rate of I&C.

Spatial analysis of metformin use compared with nicotine and caffeine consumption through wastewater-based epidemiology in China.

Monitoring the consumption of pharmaceuticals and licit drugs is important for assessing the needs of public health owing to the impact on individuals as well as society. The present work applied wastewater-based epidemiology to profile the spatial patterns of metformin, nicotine, and caffeine use and their correlations. Influent wastewater samples were collected from 27 wastewater treatment plants in 22 typical Chinese cities that covered all geographic regions of the country. The consumption of metformin ranged from 0.02 g/d/1000 inh to 8.92 g/d/1000 inh, whereas caffeine and nicotine consumption ranged from 4.33 g/d/1000 inh to 394 g/d/1000 inh and 0.17 g/d/1000 inh to 1.88 g/d/1000 inh, respectively. There were significant regional differences in the consumption of caffeine, with the highest consumption in East China and the lowest consumption in Northeast China. The consumption and concentration of caffeine were related to the gross domestic product and per capita disposable income of urban residents, respectively. There was a correlation between the concentrations of caffeine and cotinine (a nicotine metabolite), thereby indicating that individuals that use one of these substances are likely to use the other substance. A significant relationship was found between the concentration of metformin and cotinine, thereby implying that the use of tobacco may be correlated with type 2 diabetes. Co-analysis of these substances in wastewater may provide a more accurate picture of substance use situations within different communities and provide more information on human health, human behavior, and the economy. This report describes the newest study related to the consumption of metformin among the general population in China.

EGFR enhances the stemness and progression of oral cancer through inhibiting autophagic degradation of SOX2.

Epidermal growth factor receptor (EGFR) is highly expressed in head and neck squamous cell carcinoma (HNSCC) and correlates with poor prognosis. EGFR has been demonstrated to be associated with cancer stem cell traits in HNSCC. However, the underlying molecular mechanism is far from elucidated. Here, SOX2, one of the most important stem cell markers, was identified as a binding partner and substrate of EGFR. EGFR signaling inhibition decreases SOX2 expression by promoting its autophagic degradation. Mechanistically, EGFR activation induces SOX2 phosphorylation at the Y277 site and reduces its ubiquitination, which inhibits its association with p62 and subsequent autophagic degradation. Gefitinib, an EGFR tyrosine kinase inhibitor, shows in vitro and in vivo protective effects against oral cancer cells that can be reversed through autophagy inhibition. Our study suggests that EGFR plays an important role in the development of cancer stem cells by stabilizing SOX2. Targeting EGFR in combination with conventional chemotherapy might be a promising strategy for the treatment of HNSCC through elimination of cancer stem cells.

Amniotic Mesenchymal Stem Cells Decrease Aß Deposition and Improve Memory in APP/PS1 Transgenic Mice.

Transplantation of human amniotic mesenchymal stem cells (hAM-MSCs) seems to be a promising strategy for the treatment of neurodegenerative disorders, including Alzheimer's disease (AD). However, the clinical therapeutic effects of hAM-MSCs and their mechanisms of action in AD remain to be determined. Here, we used amyloid precursor protein (APP) and presenilin1 (PS1) double-transgenic mice to evaluate the effects of hAM-MSC transplantation on AD-related neuropathology and cognitive dysfunction. We found that hAM-MSC transplantation into the hippocampus dramatically reduced amyloid-ß peptide (Aß) deposition and rescued spatial learning and memory deficits in APP/PS1 mice. Interestingly, these effects were associated with increasing in Aß-degrading factors, elevations in activated microglia, and the modulation of neuroinflammation. Furthermore, enhanced hippocampal neurogenesis in the subgranular zone (SGZ) of the dentate gyrus (DG) and enhanced synaptic plasticity following hAM-MSC treatment could be another important factor in reversing the cognitive decline in APP/PS1 mice. Instead, the mechanism underlying the improved cognition apparently involves a robust increase in hippocampal synaptic density and neurogenesis that is mediated by brain-derived neurotrophic factor (BDNF). In conclusion, our data suggest that hAM-MSCs may be a new and effective therapy for the treatment of AD.

Meta-analysis of the effects of oral and intravenous dexamethasone premedication in the prevention of paclitaxel-induced allergic reactions.

BACKGROUND: Dexamethasone premedication is required to prevent paclitaxel-related hypersensitivity reactions (HSRs). Oral dexamethasone (PO-D) has been considered the standard premedication regimen. However, whether intravenous dexamethasone (IV-D) is feasible for preventing paclitaxel-related HSRs is still unclear. We conducted a meta-analysis to compare these two regimens. METHODS: We performed a systematic search in the PubMed, China National Knowledge Infrastructure, and Web of Science databases for relevant articles published before June 2016. Outcomes included HSRs and severe HSRs. Statistical analyses were performed using RevMan 5.2 software. RESULT: Six studies comprising 1347 patients were included in the meta-analysis. The PO-D premedication regimen showed a significantly decreased incidence of severe HSRs compared with the IV-D regimen with an OR of 0.53 (95% CI 0.28-0.99, p = 0.05). However, there was no difference in the overall paclitaxel-related HSR rates between the two premedication regimens (OR 0.76, 95% CI 0.55-1.06, p = 0.11). Subgroup analyses according to study type and country of origin showed similar statistical results between the two premedication regimens. CONCLUSION: Our meta-analysis showed that the PO-D premedication regimen is superior to the IV-D regimen in preventing paclitaxel-related HSRs. Additional randomized controlled trials are needed to confirm our findings.

Frosted Branch Angiitis in Pediatric Dyskeratosis Congenita: A Case Report.

Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome, usually presented with abnormal skin pigmentation, nail dystrophy, and oral leukoplakia. The main cause of mortality in DC is immunodeficiency and vital infection. DC involves multisystem, but retinal involvements are rare.Herein, we report an unusual case of pediatric DC suffering from frosted branch angiitis (FBA) after recovery of mycoplasma pneumonia. Cytomegalovirus infection and cytokine changes were found relevant to the onset of FBA. Despite corticosteroids, antiviral medication, and hematopoietic stem cell transplantation, the patient ended in poor vision with optic atrophy.This case implies that pediatricians should be aware of FBA as a rare retinal manifestation in children with DC and bone marrow failure. Cytomegalovirus may be one of the common causes and cytokines could be triggering factors.

Low concentrations of chloroquine and 3-methyladenine suppress the viability of retinoblastoma cells synergistically with vincristine independent of autophagy inhibition.

BACKGROUND: To study the inhibition of retinoblastoma cell viability by two commonly used autophagy inhibitors, chloroquine (CQ) and 3-methyladenine (3-MA), alone or in combination with the conventional chemotherapeutic drug vincristine (VCR), and to investigate whether the mechanisms of these drugs are related to inhibition of autophagy. METHODS: On retinoblastoma cell line HXO-Rb44, VCR, CQ and 3-MA were used individually or combined. The cell viability was determined by CCK8 method, and the cellular autophagic activity was determined by Western blotting of LC3 and p62. Caspase 3 fragmentation and Akt activation was also determined by Western blotting. RESULTS: VCR induced cell cycle arrest and apoptosis in HXO-Rb44 cells, but only inhibited autophagy at relatively high doses. Both CQ and 3-MA were synergistic with VCR to inhibit the growth of retinoblastoma cells and the combinational use significantly reduced the dosage of each drug. The lowest effective dose of CQ and 3-MA was most efficient to add on VCR; however, such dose was not sufficient to suppress autophagy in these cells. CQ could directly induce caspase activation, while 3-MA significantly inhibited Akt phosphorylation. CONCLUSIONS: CQ and 3-MA were synergistic with VCR to inhibit retinoblastoma cells. Our result suggested a novel strategy to combine CQ or 3-MA with VCR to reduce the side effects of each drug. However, lack of change in the autophagic activity when using the two drugs at lower doses suggests multiple mechanisms of action of the same drug at different doses. At higher doses, the drugs could inhibit autophagy, while at lower doses, they suppress tumor growth via autophagy-independent mechanisms.

Spatial and temporal regulation of biosynthesis of the plant immune signal salicylic acid.

The plant hormone salicylic acid (SA) is essential for local defense and systemic acquired resistance (SAR). When plants, such as Arabidopsis, are challenged by different pathogens, an increase in SA biosynthesis generally occurs through transcriptional induction of the key synthetic enzyme isochorismate synthase 1 (ICS1). However, the regulatory mechanism for this induction is poorly understood. Using a yeast one-hybrid screen, we identified two transcription factors (TFs), NTM1-like 9 (NTL9) and CCA1 hiking expedition (CHE), as activators of ICS1 during specific immune responses. NTL9 is essential for inducing ICS1 and two other SA synthesis-related genes, phytoalexin-deficient 4 (PAD4) and enhanced disease susceptibility 1 (EDS1), in guard cells that form stomata. Stomata can quickly close upon challenge to block pathogen entry. This stomatal immunity requires ICS1 and the SA signaling pathway. In the ntl9 mutant, this response is defective and can be rescued by exogenous application of SA, indicating that NTL9-mediated SA synthesis is essential for stomatal immunity. CHE, the second identified TF, is a central circadian clock oscillator and is required not only for the daily oscillation in SA levels but also for the pathogen-induced SA synthesis in systemic tissues during SAR. CHE may also regulate ICS1 through the known transcription activators calmodulin binding protein 60g (CBP60g) and systemic acquired resistance deficient 1 (SARD1) because induction of these TF genes is compromised in the che-2 mutant. Our study shows that SA biosynthesis is regulated by multiple TFs in a spatial and temporal manner and therefore fills a gap in the signal transduction pathway between pathogen recognition and SA production.

Porous Pd nanoparticles with high photothermal conversion efficiency for efficient ablation of cancer cells.

Nanoparticle (NP) mediated photothermal effect shows great potential as a noninvasive method for cancer therapy treatment, but the development of photothermal agents with high photothermal conversion efficiency, small size and good biocompatibility is still a big challenge. Herein, we report Pd NPs with a porous structure exhibiting enhanced near infrared (NIR) absorption as compared to Pd nanocubes with a similar size (almost two-fold enhancement with a molar extinction coefficient of 6.3 × 10(7) M(-1) cm(-1)), and the porous Pd NPs display monotonically rising absorbance from NIR to UV-Vis region. When dispersed in water and illuminated with an 808 nm laser, the porous Pd NPs give a photothermal conversion efficiency as high as 93.4%, which is comparable to the efficiency of Au nanorods we synthesized (98.6%). As the porous Pd NPs show broadband NIR absorption (650-1200 nm), this allows us to choose multiple laser wavelengths for photothermal therapy. In vitro photothermal heating of HeLa cells in the presence of porous Pd NPs leads to 100% cell death under 808 nm laser irradiation (8 W cm(-2), 4 min). For photothermal heating using 730 nm laser, 70% of HeLa cells were killed after 4 min irradiation at a relative low power density of 6 W cm(-2). These results demonstrated that the porous Pd nanostructure is an attractive photothermal agent for cancer therapy.

[Immunological regulation and treatment of Brucea javanica and Fructus Psoraleae on rats with Pneumocystis carinii pneumonia].

OBJECTIVE: To study the immunological regulation and treatment of Brucea javanica and Fructus Psoraleae, traditional Chinese medicine, on rats with Pneumocystis carinii pneumonia (PCP). METHODS: Rats were injected subcutaneously by dexamethasone. When the rats got Pc infected, they were divided into two groups: rats in one group were treated with the mixture of Brucea javanica and Fructus Psoraleae and another group was used as infected control. Control with normal rats was also established. Observations were made on the number of cysts in lungs and the changes of CD4+ T cells, CD8+ T cells and TNF-alpha in the serum to demonstrate the immunological regulation and killing effect of the medicine on cysts in the infected rats. RESULTS: The body weight of the rats treated with Brucea javanica and Fructus Psoraleae increased considerably than that of immunosuppressed rats and the normal control. The damaged lung got improved and repaired, and a significant cyst reduction was shown in the treated group. The CD4+ T cells, CD8+ T cells and level of TNF-alpha in serum also increased in the treated group significantly. CONCLUSION: The mixture of Brucea javanica and fructus psoraleae plays an immunological regulation on rats with Pneumocystis carinii pneumonia and shows certain killing effect on the cysts.