H(2)S level may be negatively correlated with the process of inflammation and positively correlated with expression of CSE in nasal mucosa. The endogenous H(2)S pathway is down-regulated in AR.

The objective of this study is to evaluate the effect of exhaled CO (eCO) on the development of asthma and allergic rhinitis (AR) by means of reviewing published literature. The literatures published between January 1997 and December 2008 from the US National Library of Medicine (NLM) Database were obtained according to inclusion criteria. Meta-analysis of randomized controlled trials (RCTs) was performed. CO levels of asthma and AR patients were compared with that of normal controls. HO-1(heme oxygenase-1) expression and effect of corticosteroids on eCO levels were also analyzed. Fifteen studies concerning asthma and four studies concerning AR were included in this analysis. Heterogeneity from different studies was evident (P < 0.0001), so a random-effects model was preferred. The meta-analysis revealed that asthmatic patients had significantly higher levels of eCO compared to normal controls. There was significant difference between asthma and control groups in terms of eCO (combined weighted mean difference (WMD) 1.33 (95% confidence interval 0.72 to 1.95), P < 0.0001), and no significant difference between AR and control (combined WMD 0.93 (95% confidence interval -0.54 to 2.40), P = 0.22). HO-1 expression were also reviewed, asthma group produced greater expression of HO-1 than control group with significant difference (combined standardized mean difference (SMD) 2.98 (95% confidence interval 1.13 to 4.84), P = 0.002). After corticosteroid therapy, significantly different levels of eCO were produced after corticosteroid therapy than did asthma group (combined WMD -1.23 (95% confidence interval -2.43 to -0.03), P = 0.04). The analysis reveals that eCO levels were significantly raised in asthma and it may attribute to high expression of HO-1, but there were no significantly high eCO levels between AR and control groups. Due to sensitivity to corticosteroid inhibition, eCO may be used as a practical marker to detect and monitor exacerbation of asthma.

Background: The mechanisms responsible for the development of allergic rhinitis(AR) are not fully understood. The present study was designed to explore the possible roles of carbon monoxide(CO) on the pathogenesis of AR.

High-grade B-cell lymphoma with concurrent MYC and BCL2 rearrangements (HGBL-DHL) is a rare, aggressive mature B-cell malignancy with a high likelihood of treatment failure following front-line immunochemotherapies. Patients with HGBL-DHL who develop a relapsed or refractory disease have little effective therapeutic strategies and show very poor clinical outcomes, thus calling for development of novel therapies for this specific patient population. In this study, we investigated the preclinical anti-lymphoma efficacies and potential mechanism of action of a novel treatment approach, combining the BCL2 inhibitor venetoclax with CS2164, a new orally active multitarget inhibitor, in HGBL-DHL models. This combination therapy exhibited a robust synergistic cytotoxicity against HGBL-DHL cells, evidenced by cooperatively inducing loss of cell viability and promoting cell apoptosis. Moreover, coadministration of CS2164 and venetoclax resulted in significant superior suppression of HGBL-DHL cell growth and remarkably abrogated tumor burden in a HGBL-DHL-xenografted mouse model. The synergistic lethality of CS2164 and venetoclax in HGBL-DHL cells was associated with induction of DNA damage and impairment of DNA repair ability. Of importance, the combined treatment almost abolished the expression of both BCL2 and MYC, two hallmark proteins of HGBL-DHL, and substantially blunted the activity of PI3K/AKT/mTOR signaling cascade. In addition, MCL1 and BCL-XL, two well-characterized contributors for venetoclax resistance, were significantly lessened in the presence of CS2164 and venetoclax, thus leading to the accumulation of proapoptotic proteins BAX and PUMA and then initiating the intrinsic apoptosis pathway. Taken together, these findings suggest that the regimen of CS2164 and venetoclax is highly effective to eliminate HGBL-DHL cells in the preclinical setting, warranting further clinical investigations of this regimen for the treatment of unfavorable HGBL-DHL patients.