Low-level laser therapy with 850 nm recovers salivary function via membrane redistribution of aquaporin 5 by reducing intracellular Ca2+ overload and ER stress during hyperglycemia.

The overall goal is to study the effect of low-level laser therapy (LLLT) on membrane distribution of major water channel protein aquaporin 5 (AQP5) in salivary gland during hyperglycemia. Par C10 cells treated with high glucose (50 mM) showed a reduced membrane distribution of AQP5. The functional expression of AQP5 was downregulated due to intracellular Ca2+ overload and ER stress. This reduction in AQP5 expression impairs water permeability and therefore results in hypo-salivation. A reduced salivary flow was also observed in streptozotocin (STZ)-induced diabetic mice model and the expression of AQP5 and phospho-AQP5 was downregulated. Low-level laser treatment with 850 nm (30 mW, 10 min = 18 J/cm2) reduced ER stress and recovered AQP5 membrane distribution via serine phosphorylation in the cells. In the STZ-induced diabetic mouse, LLLT with 850 nm (60 J/cm2) increased salivary flow and upregulated of AQP5 and p-AQP5. ER stress was also reduced via downregulation of caspase 12 and CHOP. In silico analysis confirmed that the serine 156 is one of the most favorable phosphorylation sites of AQP5 and may contribute to the stability of the protein. Therefore, this study suggests high glucose inhibits phosphorylation-dependent AQP5 membrane distribution. High glucose induces intracellular Ca2+ overload and ER stress that disrupt AQP5 functional expression. Low-level laser therapy with 850 nm improves salivary function by increasing AQP5 membrane distribution in hyperglycemia-induced hyposalivation.

Opuntia humifusa modulates morphological changes characteristic of asthma via IL-4 and IL-13 in an asthma murine model.

Asthma is a chronic pulmonary disease that affects an estimated 235 million people worldwide, but asthma drugs have many adverse effects. Opuntia humifusa (eastern prickly pear) has been used as a food and traditional medicine worldwide; however, its anti-asthmatic effects have not been reported. We evaluated O. humifusa as a potential therapeutic or preventive component of anti-asthmatic drugs. We divided ovalbumin-sensitized mice into the following groups: normal control, asthma-induced control, dexamethasone-treated group (positive control), 50 mg/kg O. humifusa-treated group, 100 mg/kg O. humifusa-treated group, and 500 mg/kg O. humifusa-treated group. Levels of Th1/Th2/Th17-related cytokines were evaluated using RT-PCR, ELISA, and immunohistochemistry. O. humifusa dose-dependently suppressed the morphological changes typically observed in asthma, such as goblet cell hyperplasia, inflammatory cell infiltration, mucous hypersecretion, and relative basement membrane thickening in the respiratory system. These results may be attributable to regulation of Th1-/Th2-/Th17-related factors, especially interleukin (IL)-4 and IL-13. We conclude that O. humifusa is a potential anti-asthmatic functional food. Abbreviations: O. humifusa: Opuntia humifusa; Th: helper T; RT-PCR: real-time polymerase chain reaction; ELISA: enzyme-linked immunosorbent assay; IL: interleukin; WHO: World Health Organization; IFN-γ: interferon gamma; TNF-α: tumor necrosis factor-alpha; IgE: immunoglobulin E; CD: cluster of differentiation; OVA: ovalbumin; DEX: dexamethasone; BALF: bronchoalveolar fluid; H&E: hematoxylin and eosin; PAS: periodic acid-schiff; PBS: phosphate-buffered saline; BM: basement membrane; cDNA: complementary deoxyribonucleic acid; RNA: ribo nucleic acid; RIPA: radioimmunoprecipitation assay; IHC: immunohistochemistry; HPLC: high-performance liquid chromatography; SD: standard deviation; WBC: white blood cells; APCs: antigen-presenting cells.

Radiologic findings as a determinant and no effect of macrolide resistance on clinical course of Mycoplasma pneumoniae pneumonia.

BACKGROUND: With the emergence of macrolide resistance, concerns about the efficacy of macrolides for the treatment of Mycoplasma pneumoniae (MP) pneumonia in children have been raised. This study aimed to determine the effect of macrolide resistance on the outcome of children who were hospitalized with MP pneumonia. METHODS: Between 2010 and 2015, we performed culture of MP from nasopharyngeal samples obtained from children who were hospitalized with pneumonia at five hospitals in Korea. Macrolide resistance was determined by the analysis of 23S rRNA gene transition and the minimal inhibitory concentrations of four macrolides. Medical records were reviewed to analyze the clinical response to treatment with macrolides. RESULTS: MP was detected in 116 (4.8%) of the 2436 children with pneumonia. MP pneumonia was prevalent in 2011 and 2015. Of the 116 patients with MP pneumonia, 82 (70.7%) were macrolide-resistant. There were no differences in the age distribution, total duration of fever, and chest x-ray patterns between the macrolide-susceptible and macrolide-resistant groups. After macrolide initiation, mean days to defervescence were longer in the macrolide-resistant group than in macrolide-susceptible group (5.7 days vs. 4.1 days, P = 0.021). However, logistic regression analysis revealed that the presence of extrapulmonary signs (P = 0.039), homogeneous lobar consolidation (P = 0.004), or parapneumonic effusion (P < 0.001) were associated with fever duration of ≥7 days after the initiation of macrolides, regardless of macrolide resistance. CONCLUSIONS: This study demonstrated that fever duration in MP pneumonia was determined by the radiologic findings of chest x-ray, not by the presence of macrolide resistance. The results highlight the need for future studies to assess therapeutic benefit from macrolides in the treatment of children with MP pneumonia.

In vitro structure-activity relationship and in vivo studies for a novel class of cyclooxygenase-2 inhibitors: 5-aryl-2,2-dialkyl-4-phenyl-3(2H)furanone derivatives.

5-Aryl-2,2-dialkyl-4-phenyl-3(2H)furanone derivatives were studied as a novel class of selective cyclooxygenase-2 inhibitors with regard to synthesis, in vitro SAR, antiinflammatory activities, pharmacokinetic considerations, and gastric safety. 1f, a representative compound for methyl sulfone derivatives, showed a COX-2 IC(50) comparable to that of rofecoxib. In case of 20b, a representative compound for sulfonamide derivatives, a potent antiinflammatory ED(50) of 0.1 mg kg(-1) day(-1) was observed against adjuvant-induced arthritis by a preventive model, positioning 20b as one of the most potent COX-2 inhibitors ever reported. Furthermore, 20b showed strong analgesic activity as indicated by its ED(50) of 0.25 mg/kg against carrageenan-induced thermal hyperalgesia in the Sprague-Dawley rat. 3(2H)Furanone derivatives showed due gastric safety profiles as selective COX-2 inhibitors upon 7-day repeat dosing. A highly potent COX-2 inhibitor of the 3(2H)furanone scaffold could be considered suitable for a future generation COX-2 selective arthritis medication with improved safety profiles.