Treatment with onion bulb extract both prevents and reverses allergic inflammation in a murine model of asthma.

CONTEXT: Asthma presents a global health challenge. The main pharmacotherapy is synthetic chemicals and biological-based drugs that are costly, and have significant side effects. In contrast, use of natural products, such as onion (Allium cepa L., Amaryllidaceae) in the treatment of airway diseases has increased world-wide because of their perceived efficacy and little safety concerns. However, their pharmacological actions remain largely uncharacterized. OBJECTIVE: We investigated whether onion bulb extract (OBE) can (1) reverse established asthma phenotype (therapeutic treatment) and/or (2) prevent the development of the asthma phenotype, if given before the immunization process (preventative treatment). MATERIALS AND METHODS: Six groups of male Balb/c mice were established for the therapeutic (21 days) and five groups for the preventative (19 days) treatment protocols; including PBS and house dust mite (HDM)-challenged mice treated with vehicle or OBE (30, 60, and 100 mg/kg/i.p.). Airways inflammation was determined using cytology, histology, immunofluorescence, Western blot, and serum IgE. RESULTS: Therapeutic (60 mg/kg/i.p.) and preventative (100 mg/kg/i.p.) OBE treatment resulted in down-regulation of HDM-induced airway cellular influx, histopathological changes and the increase in expression of pro-inflammatory signaling pathway EGFR, ERK1/2, AKT, pro-inflammatory cytokines and serum IgE. DISCUSSION AND CONCLUSION: Our data show that OBE is an effective anti-inflammatory agent with both therapeutic and preventative anti-asthma effects. These findings imply that onion/OBE may be used as an adjunct therapeutic agent in established asthma and/or to prevent development of allergic asthma. However, further studies to identify the active constituents, and demonstrate proof-of-concept in humans are needed.

Minocycline synergizes with corticosteroids in reducing colitis severity in mice via the modulation of pro-inflammatory molecules.

Background: A few studies have highlighted the anti-inflammatory properties of minocycline in reducing colitis severity in mice, but its molecular mechanism is not fully understood. The aim of this study was to determine the anti-inflammatory properties of minocycline and the expression/activity profiles of molecules involved in pro-inflammatory signaling cascades, cytokines, and molecules involved in the apoptotic machinery. The synergistic effect between minocycline and corticosteroids was also evaluated. Methods: The effects of various treatment approaches were determined in mice using the dextran sulfate sodium (DSS) colitis model at gross and microscopic levels. The expression/activity profiles of various pro- or anti-inflammatory molecules were determined using Western blotting and polymerase chain reaction (PCR). Results: Minocycline treatment significantly reduced colitis severity using prophylactic and treatment approaches and produced a synergistic effect with budesonide and methylprednisolone in reducing the active state of colitis. This was mediated in part through reduced colonic expression/activity of pro-inflammatory molecules, cytokines, proteins involved in the apoptotic machinery, and increased expression of the anti-inflammatory cytokine IL-10. Conclusion: Minocycline synergizes with corticosteroids to reduce colitis severity, which could reduce their dose-dependent side effects and treatment cost. The reduction in colitis severity was achieved by modulating the expression/activity profiles of various pro- and anti-inflammatory signaling molecules, cytokines, and molecules involved in the apoptotic machinery.

A Novel ANO1 Gene Variant is Associated with Intestinal Dysmotility Syndrome Masquerading as Hirschsprung Disease: A Case Report.

Anoctamin 1 (ANO1)-related intestinal dysmotility syndrome (OMIM: 620045) is an extremely rare disorder with only 2 cases reported in the medical literature. We present the clinical scenario of a 2-month-old male infant that presented to our center with diarrhea, vomiting, and abdominal distension. Routine investigations did not yield a clear diagnosis. Whole-exome sequencing showed a novel homozygous nonsense ANO1 pathogenic variant (c.1273G>T) with a protein alternation of p.Glu425Ter that fits the patient's phenotype. Sanger sequencing revealed the same ANO1 variant in both parents in a heterozygous form confirming an autosomal recessive mode of inheritance. The patient experienced multiple bouts of diarrhea-related metabolic acidosis, dehydration, and severe electrolyte imbalances that required intensive care unit monitoring. The patient was managed conservatively and being followed regularly in an outpatient setting.

An aqueous Commiphora myrrha extract ameliorates paclitaxel-induced peripheral neuropathic pain in mice.

Background: Chemotherapy-induced neuropathic pain (CINP) is a debilitating side effect in individuals undergoing cancer treatment. Treatment of CINP with the current available classes of drugs is limited and often yields unsatisfactory results. Finding therapeutic alternatives of plant origin could provide a new way for the management of CINP. Commiphora myrrha (CM) resin extract has been reported to have anti-inflammatory and analgesic activities, but the effect of CM on neuropathic pain is yet to be investigated in CINP. Objectives: The aim of this study was to investigate the antinociceptive effect of CM extract in a mouse model of paclitaxel-induced neuropathic pain (PINP). Methods: The effects of CM on thermal hyperalgesia and mechanical allodynia were assessed in female BALB/c mice with PINP using a hot plate and a plantar aesthesiometer, respectively. Motor coordination was evaluated using a rotarod apparatus. The involvement of transient receptor potential vanilloid channel 1 (TRPV1) in CM actions was investigated using a capsaicin (a TRPV1 agonist)-induced nociception test. The genetic expression of Trpv1, Nrf2, Sod2, and Hmox1 was assessed using real-time PCR, while protein expression of TRPV1, Iba-1, and CD11b was assessed using Wes™. Results: Administration of CM to mice with established PINP produced a dose-dependent reduction in thermal hyperalgesia. Prophylactic treatment of mice with CM prevented the development of paclitaxel-induced thermal hyperalgesia and mechanical allodynia. CM did not change the motor coordination of mice, as the reaction latency and the rotational velocity of animals pretreated with CM extract were similar to those of animals pretreated with vehicle. CM significantly decreased the number and duration of the flick responses following capsaicin injection into the dorsal surface of the hind paw of mice. The protein expression of TRPV1 was upregulated in the spinal cord of paclitaxel-treated animals compared to vehicle-only-treated control animals, while CM-treated animals had values similar to vehicle-only-treated control animals. The mRNA expression of Nrf2, a major antioxidant transcription factor, was upregulated in the paw skin of mice treated with CM compared to those treated with paclitaxel alone. Conclusion: These results indicate that CM may both treat established and prevent the development of paclitaxel-induced thermal hyperalgesia and mechanical allodynia without any impairment in the motor activity of mice. CM may mediate its action through the peripheral inhibition of TRPV1 channel activity, restoration of normal TRPV1 protein expression in the spinal cord, and elevation of cellular antioxidant defenses. CM has the potential to be used as a therapeutic alternative to treat CINP.

Correlations of C-Reactive Protein and Folate with Smoking, Sport, Hematological Inflammation Biomarkers and Anthropometrics in Syrian University Female Students Cross-Sectional Study.

In Syria, high-Sensitive C-Reactive (hsCRP), folate, and, other health risk data in young women are limited. This cross-sectional study evaluates hsCRP and folate levels along with anthropometric characteristics, lifestyle factors and some biomarkers linked to cardiovascular disease (CVD) risk factors in healthy female students (n = 207, 18-25 years old). Among participants, hsCRP level was at average or high risk of CVD in 20.7% and 2.5% respectively and it was significantly higher in participants who had high body mass index (BMI) (Nonparametric statistical tests, p value < 0.05). Unexpectedly, it did not vary significantly between smokers and nonsmokers. And, it correlated positively with anthropometric and erythrocyte sedimentation rate (ESR) measurements. While folate level was low in 3.4% of participants, no association between hsCRP and folate levels was found. Finally, low hemoglobin level and habit of waterpipe smoking are spreading; and, sport practicing is shrinking. After reviewing similar works, this study suggests that the possible correlation between hsCRP and folate could be displayed in patients older than 30 years. Also, the marked decrease in hemoglobin level needs more attention. Finally, young females in Syria are advised to consider a lifestyle free of smoking and packed with physical activity.

A study of innate and adaptive immune responses in beta-thalassemic patients with chronic hepatitis C virus infection.

Thalassemia major is an inherited disorder particularly common in people of Mediterranean, African, and Southeast Asian ancestry. Hepatitis C virus (HCV) is responsible for 80 - 90% of post transfusion hepatitis in beta-Thalassemic patients. Marked liver iron overload, which is often inevitable in patients on regular blood transfusion, and HCV infection have been shown to have a potentiating effect on hepatic fibrogenesis in thalassemic patients. This study aimed at investigating the impact of combined chronic hepatitis C and beta-Thalassemia on innate and adaptive immune responses. The study was conducted on 60 patients and 15 apparently healthy controls. Patients were dived into three groups: group 1: 35 patients with combined beta-thalassemia and chronic hepatitis C (CHC) (betaTH/CHC), group II: 15 beta-thalassemia patients without HCV infection (betaTH), group III: 10 patients with chronic hepatitis C infection (CHC). Assessment of the number of CD3+, CD4+, CD8+ T cells, NK cells, and NKT cells was done by flowcytometry. Human IFN-delta and IL-15 levels were estimated by Enzyme -Linked Immunosorbent Assay (ELISA). betaTH/CHC patients had significantly reduced numbers of conventional T lymphocytes, NK, NKT, CD4+, and CD8+ T cells when compared to betaTH patients. Serum IFN-gamma levels were significantly reduced in betaTH/CHC patients (2.57 pg/ml) in comparison to CHC patients (6.89pg/ml) and normal controls (4.73 pg/ml). A significant elevation of serum IL-15 levels in betaTH/CHC patients (38.04pg/ml) was found when compared to betaTH patients (16.22 pg/ml). Splenectomized patients showed reduced numbers of NK cells, NK T cells and lower CD4:CD8 ratio in comparison to non-splenectomized ones among betaTH/CHC patients. In conclusion our data show an obvious defective cellular innate immunity (NK & NKT cells) and cellular adaptive immunity (CD4+ T cells, CD8+ T cells, & INF-gamma) in (betaTH/CHC) patients, in comparison to (betaTH) patients. This observation suggests a potentiating effect of both CHC and beta-thalassemia on depression of innate and adaptive immune status in these patients