Chromatographic behavior of co-eluted plasma compounds and effect on screening of drugs by APCI-LC-MS(/MS):Applications to selected cardiovascular drugs

Chromatographic behavior of co-eluted compounds from un-extracted drug-free plasma samples was studied by LC-MS and LC-MS/MS with positive APCI.Under soft gradient,total ion chromatogram（TIC） consisted of two major peaks separated by a constant lower intensity region.Early peak（0.15-0.4 min） belongs to polar plasma compounds and consisted of smaller mass ions（m/z〈 250）;late peak（3.6-4.6 min） belongs to thermally unstable phospholipids and consisted of fragments with mlz〈300.Late peak is more sensitive to variations in chromatographic and MS parameters.Screening of most targeted cardiovascular drugs at levels lower than 50 ng/mL has been possible by LC-MS for drugs with retention factors larger than three.Matrix effects and recovery,at 20 and 200 ng/mL,were evaluated for spiked plasma samples with 15 cardiovascular drugs,by MRM-LC-MS/MS.Average recoveries were above 90%and matrix effects expressed as percent matrix factor（%MF） were above 100%,indicating enhancement character for APCI.Large uncertainties were significant for drugs with smaller masses（m/z〈 250） and retention factors lower than two.

Association between common cardiovascular drugs and depression

Objective:Cardiovascular diseases are associated with an increased risk of depression,but it remains unclear whether treatment with cardiovascular agents decreases or increases this risk.The effects of drugs on individual usage are also often unknown.This review aimed to examine the correlation between depression and common cardiovascular drugs,develop more potent interventions for depression in cardiovascular patients,and further research on the bio-behavioural mechanisms linking cardiovascular drugs to depression.Data sources:The data in this review were obtained from articles included in PubMed,EMBASE,and Web of Science.Study selection:Clinical trials,observational studies,review literature,and guidelines about depression and cardiovascular drugs were selected for the article.Results:We systematically investigated whether the seven most used cardiovascular drugs were associated with altered risk of incident depression in this literature review.Statins have been proven to have antidepressant effects.Some studies believe angiotensin-converting enzyme inhibitors(ACEIs)/angiotensin receptor blocker(ARB)can exert an antidepressant influence by acting on the renin-angiotensin system,but further clinical trials are needed to confirm this.Beta-blockers have previously been associated with depression,but the current study found no significant association between beta blockers and the risk of depression.Aspirin may have antidepressant effects by suppressing the immune response,but its role as an antidepressant remains controversial.calcium channel blockers(CCBs)can regulate nerve signal transduction by adjusting calcium channels,but whether this effect is beneficial or harmful to depression remains unclear.Finally,some cases have reported that nitrates and diuretics are associated with depression,but the current clinical evidence is insufficient.Conclusions:Statins have been proven to have antidepressant effect,and the antidepressant effects of ACEIs/ARB and aspirin are still controversial.CCBs are associated with depression,but it is unclear whether it is beneficial or harmful.No association has been found with b-blockers,diuretics,and nitrates.

Repurposing non-oncology small-molecule drugs to improve cancer therapy: Current situation and future directions

Drug repurposing or repositioning has been well-known to refer to the therapeutic applications of a drug for another indication other than it was originally approved for.Repurposing non-oncology small-molecule drugs has been increasingly becoming an attractive approach to improve cancer therapy,with potentially lower overall costs and shorter timelines.Several non-oncology drugs approved by FDA have been recently reported to treat different types of human cancers,with the aid of some new emerging technologies,such as omics sequencing and artificial intelligence to overcome the bottleneck of drug repurposing.Therefore,in this review,we focus on summarizing the therapeutic potential of non-oncology drugs,including cardiovascular drugs,microbiological drugs,small-molecule antibiotics,anti-viral drugs,anti-inflammatory drugs,antineurodegenerative drugs,antipsychotic drugs,antidepressants,and other drugs in human cancers.We also discuss their novel potential targets and relevant signaling pathways of these old non-oncology drugs in cancer therapies.Taken together,these inspiring findings will shed new light on repurposing more non-oncology small-molecule drugs with their intricate molecular mechanisms for future cancer drug discovery.