Cytochrome P450 enzymes, which catalyze oxygenation reactions of both exogenous and endogenous chemicals, are membrane bound proteins that require interaction with their redox partners in order to function. Those responsible for drug and foreign compound metabolism are localized primarily in the endoplasmic reticulum of liver, lung, intestine, and other tissues. More recently, the potential for P450 enzymes to exist as supramolecular complexes has been shown by the demonstration of both homomeric and heteromeric complexes. The P450 units in these complexes are heterogeneous with respect to their distribution and function, and the interaction of different P450s can influence P450-specific metabolism. The goal of this review is to examine the evidence supporting the existence of physical complexes among P450 enzymes. Additionally, the review examines the crystal lattices of different P450 enzymes derived from X-ray diffraction data to make assumptions regarding possible quaternary structures in membranes and in turn, to predict how the quaternary structures could influence metabolism and explain the functional effects of specific P450-P450 interactions.
Even when chemotherapy-induced nausea and vomiting (CINV) can be effectively controlled in the acute phase, it may still occur in the delayed phase. Identifying at risk patients is complex and requires consideration of clinical, personal, demographic, and behavioral factors. Delayed CINV has a significant detrimental effect on patients' daily life and is responsible for significant healthcare resource utilization. Patients who do not experience acute CINV are not necessarily exempt from delayed CINV, and healthcare professionals have been shown to underestimate the incidence of delayed CINV. Failure to protect against CINV during the first cycle of chemotherapy is the most significant independent risk factor for delayed CINV during subsequent cycles. Addition of a neurokinin-1 receptor antagonist to antiemetic prophylactic regimens involving a 5-hydroxytryptamine type 3 receptor antagonist and a corticosteroid helps to ameliorate delayed CINV, particularly vomiting. Netupitant and rolapitant are second generation neurokinin-1 receptor antagonists that provide effective prophylaxis against delayed chemotherapy-induced vomiting and also have an antinausea benefit. All of the neurokinin-1 receptor antagonists with the exception of rolapitant inhibit or induce cytochrome P450 3A4 (CYP3A4), and a reduced dose of dexamethasone (a CYP3A4 substrate) should be administered with aprepitant or netupitant; by contrast, this is not necessary with rolapitant. Here we review specific challenges associated with delayed CINV, its pathophysiology, epidemiology, treatment, and outcomes relative to acute CINV, and its management within the larger context of overall CINV.
Streptococcus suis (S. suis) is a zoonotic pathogen that causes severe disease symptoms in pigs and humans. Syringa oblata Lindl, distributed in the middle latitudes of Eurasia and North America were proved as the most development potential of Chinese Medicine. In this study, biofilm formation by S. suis decreased after growth with 1/2 MIC, 1/4 MIC, or 1/8 MIC of Syringa oblata Lindl. aqueous extract and rutin. Scanning electron microscopy analysis revealed the potential effect of Syringa oblata Lindl, aqueous extract and rutin against biofilm formation by S. suis. Using iTRAQ technology, comparative proteomic analyses was performed at two conditions: 1/2 MIC of Syringa oblate Lindl, aqueous extract treated and non -treated cells. The results revealed the existence of 28 proteins of varying amounts. We found that the majority of the proteins were related to cell growth and metabolism. We also found that Syringa oblata Lindl. Aqueous extract affected the synthesis enzymes. In summary, Syringa oblata Lindl. aqueous extract might be used to inhibit the biofilm formation effectively by S. suis, and the active ingredients of the Syringa oblate Lind'. aqueous extract is rutin. The content of rutin is 9.9 +/- 0.089 mg/g dry weight.