Targeting cAMP in D1-MSNs in the nucleus accumbens, a new rapid antidepressant strategy

Studies have suggested that the nucleus accumbens(NAc)is implicated in the pathophysiology of major depression;however,the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated.Here,we identified a specific reduction of cyclic adenosine monophosphate(cAMP)in the subset of dopamine D1 receptor medium spiny neurons(D1-MSNs)in the NAc that promoted stress susceptibility,while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors.Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons(D2-MSNs)of depressed mice,however,the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs.We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration,but not a lower dose.The fast onset property of crocin was verified through multicenter studies.Moreover,crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN.These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc,and provide a potential rapid antidepressant drug candidate,crocin.

Intestinal Barrier Function in the Pathogenesis of Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide.The mechanisms involved in NAFLD onset are complicated and multifactorial.Recent literature has indicated that altered intestinal barrier function is related to the occurrence and progression of liver disease.The intestinal barrier is important for absorbing nutrients and electrolytes and for defending against toxins and antigens in the enteric environment.Major mechanisms by which the intestinal barrier influences the development of NAFLD involve the altered epithelial layer,decreased intracellular junction integrity,and increased intestinal barrier permeability.Increased intestinal permeability leads to luminal dysbiosis and allows the translocation of pathogenic bacteria and metabolites into the liver,inducing inflammation,immune response,and hepatocyte injury in NAFLD.Although research has been directed to NAFLD in recent decades,the pathophysiological changes in NAFLD initiation and progression are still not completely understood,and the therapeutic targets remain limited.A deeper understanding on the correlation between NAFLD pathogenesis and intestinal barrier regulation must be attained.Therefore,in this review,the components of the intestinal barrier and their respective functions and disruptions during the progression of NAFLD are discussed.

The antimicrobial interventions of cilantro(Coriandrum sativum)in mitigating cross-contamination of foodborne pathogens during the retail soaking process

The efficacy of commercially available antimicrobials for fresh produce—electrolyzed water(EW;around 60 mg/L of free chlorine),a combination of lactic acid and phosphoric acid-based(LPA)and citric acid-based(CA)—was compared with tap water(TW)in preventing cross-contamination during the soaking step of crisping at a retail setting.A bunch of cilantro((103.7±14.9)g/bunch)was inoculated with a three-strain cocktail of nalidixic acid-resistant Salmonella enterica(S.enterica)and Escherichia coli(E.coli)O157:H7,S.enterica and Listeria monocytogenes(L.monocytogenes),or E.coli O157:H7 and L.monocytogenes(around 5.0 log CFU/g).One inoculated and seven non-inoculated cilantro bunches were soaked in 76 L of TW,EW,LPA,and CA for 5 min.Two additional soakings,each with eight bunches of non-inoculated cilantro,were performed in the same soaking water.To determine the cross-contamination of inoculated foodborne pathogens via soaking water,the cilantro samples and soaking water following each soaking step were subjected to microbiological analyses using selective media supplemented with nalidixic acid(100μg/mL).During the first soaking,significantly greater reductions in Salmonella((2.9±0.5)log CFU/g),E.coli O157:H7((3.0±0.1)log CFU/g),and L.monocytogenes((2.7±0.3)log CFU/g)on cilantro were achieved with EW compared to soaking with TW,LPA,and CA(P<0.05).Cross-contamination of foodborne pathogens from inoculated cilantro to non-inoculated cilantro was completely mitigated by EW during three subsequent soaking events.With the exception of TW soaking water,no inoculated foodborne pathogens were detected in the 100 mL soaking water of EW,CA,and LPA collected.Including an appropriate concentration of chemical antimicrobial in water during the soaking step of crisping aids in mitigating cross-contamination of foodborne pathogen(s)in cilantro bunches.