Objective To investigate diabetes‐associated changes in urinary bladder expression of cannabinoid receptors 1 and 2 ( CB1 and CB2 ) and the functional role of CB agonists and antagonists in mediating phasic contractions of isolated bladder strips using a streptozotocin‐induced diabetic rat model. Materials and Methods The bladder and dorsal root ganglion ( DRG ) were removed from diabetic rats and age‐matched controls 8–10 weeks after diabetes induction. Expression of CB1 and CB2 m RNA was studied using quantitative real‐time PCR and protein levels were determined by W estern blot analysis. The effect of increasing concentrations (0.1–100 μM) of the mixed CB1/CB2 agonist R (+)‐ WIN 55,212–2 ( WIN ), selective CB 1 antagonist ( AM 251) and selective CB 2 antagonist ( AM 630) on carbachol‐evoked contraction of bladder strips from control and diabetic rats was investigated. WIN ‐induced alterations of bladder strip contraction were then studied after pre‐incubation with AM 251 and AM 630. Results Diabetes induced decreased CB 1 protein and m RNA expression in both the bladder and DRG ( P < 0.05), while decreased CB 2 expression was observed in the bladder ( P < 0.05). WIN decreased the amplitude, but not frequency, of carbachol‐induced phasic contractions of bladder strips in a concentration‐dependent manner and this effect was diminished in the diabetic state. AM 630 and AM 251 had no effect on isolated detrusor muscle function. Moreover, pre‐incubation with AM 251 partially counteracted the effect of WIN on detrusor muscle contraction. Conclusion The results indicate that CB 1 and CB 2 are responsible for the pathogenesis of bladder dysfunction in diabetes mellitus and represent a viable target for pharmacological treatment of bladder cystopathy.
Introduction: Inflammatory pain is a significant global clinical challenge that involves both unpleasant sensory and emotional experiences. The treatment of pain is imminent, and we are committed to seeking new analgesics for pain relief. Transcrocetin meglumine salt (TCMS), a saffron metabolite derived from the crocin apocarotenoids, has exhibited the ability to cross the blood-brain barrier and exert neuroprotective effects. In this study, we aimed to investigate whether TCMS could ameliorate complete Freund’s adjuvant (CFA)-induced inflammatory pain in mice and elucidate its underlying mechanisms. Methods: Here, we established an inflammatory pain model in mice by injecting CFA into the left hind paw. Three days later, we administered intraperitoneal injections of TCMS (10mg/kg) or saline to the animals. We examined mechanical allodynia, thermal hypersensitivity, and anxiety behavior. Furthermore, the activation of glial cells and proinflammatory cytokines in the spinal cord were detected. Results: Our results showed that TCMS significantly reversed the mechanical allodynia and thermal hypersensitivity in the CFA-injected mice. Furthermore, TCMS administration effectively inhibited the activation of microglia and astrocytes in the spinal cord induced by CFA. Additionally, TCMS suppressed the production and release of spinal proinflammatory cytokines, including TNF-α, IL-1β, and IL-6, in CFA-injected mice. Conclusion: Taken together, our findings demonstrate that TCMS holds promise as an innovative analgesic due to its ability to ameliorate inflammatory reactions.
The rapid spread of antibiotic resistance and lack of effective drugs for treating infections caused by multi-drug resistant bacteria in animal and human medicine have forced us to find new antibacterial strategies. Natural products have served as powerful therapeutics against bacterial infection and are still an important source for the discovery of novel antibacterial drugs. Curcumin, an important constituent of turmeric, is considered safe for oral consumption to treat bacterial infections. Many studies showed that curcumin exhibited antibacterial activities against Gram-negative and Gram-positive bacteria. The antibacterial action of curcumin involves the disruption of the bacterial membrane, inhibition of the production of bacterial virulence factors and biofilm formation, and the induction of oxidative stress. These characteristics also contribute to explain how curcumin acts a broad-spectrum antibacterial adjuvant, which was evidenced by the markedly additive or synergistical effects with various types of conventional antibiotics or non-antibiotic compounds. In this review, we summarize the antibacterial properties, underlying molecular mechanism of curcumin, and discuss its combination use, nano-formulations, safety, and current challenges towards development as an antibacterial agent. We hope that this review provides valuable insight, stimulates broader discussions, and spurs further developments around this promising natural product.
Salmonella is one of the most important foodborne pathogens, which causes a huge economic burden worldwide. To detect Salmonella rapidly is very meaningful in preventing salmonellosis and decreasing economic losses. Currently, isolation of Salmonella is confirmed by biochemical and serobased serotyping methods, which are time consuming, labor intensive, and complicated. To solve this problem, a hexa-plex polymerase chain reaction (PCR) method was developed using comparative genomics analysis and multiplex PCR technology to detect Salmonella and Salmonella Typhimurium, Salmonella Enteritidis, Salmonella Agona, Salmonella Choleraesuis, and Salmonella Pullorum simultaneously. The accuracy of this method was tested by a collection of 142 Salmonella. Furthermore, the strategy described in this article to mine serovar-specific fragments for Salmonella could be used to find specific fragments for other Salmonella serotypes and bacteria. The combination of this strategy and multiplex PCR is promising in the rapid identification of foodborne pathogens.
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