Hepatic ischemia-reperfusion (IR) injury is a common clinical issue lacking effective therapy and validated pharmacological targets. Here, using integrative 'omics' analysis, we identified an arachidonate 12-lipoxygenase (ALOX12)-12-hydroxyeicosatetraenoic acid (12-HETE)-G-protein-coupled receptor 31 (GPR31) signaling axis as a key determinant of the hepatic IR process. We found that ALOX12 was markedly upregulated in hepatocytes during ischemia to promote 12-HETE accumulation and that 12-HETE then directly binds to GPR31, triggering an inflammatory response that exacerbates liver damage. Notably, blocking 12-HETE production inhibits IR-induced liver dysfunction, inflammation and cell death in mice and pigs. Furthermore, we established a nonhuman primate hepatic IR model that closely recapitulates clinical liver dysfunction following liver resection. Most strikingly, blocking 12-HETE accumulation effectively attenuated all pathologies of hepatic IR in this model. Collectively, this study has revealed previously uncharacterized metabolic reprogramming involving an ALOX12-12-HETE-GPR31 axis that functionally determines hepatic IR procession. We have also provided proof of concept that blocking 12-HETE production is a promising strategy for preventing and treating IR-induced liver damage.
The increasing numbers of infections caused by multidrug-resistant (MDR) pathogens highlight the urgent need for new alternatives to conventional antibiotics. Antimicrobial peptides have the potential to be promising alternatives to antibiotics because of their effective bactericidal activity and highly selective toxicity. The present study was conducted to investigate the antibacterial, antibiofilm, and anti-adhesion activities of different CTP peptides (CTP: the original hybrid peptide cathelicidin 2 (1-13)-thymopentin (TP5); CTP-NH2: C-terminal amidated derivative of cathelicidin 2 (1-13)-TP5; CTPQ: glutamine added at the C-terminus of cathelicidin 2 (1-13)-TP5) by determining the minimal inhibitory concentrations (MICs), minimal bactericidal concentrations (MBCs), propidium iodide uptake, and analysis by scanning electron microscopy, transmission electron microscopy, and confocal laser scanning microscopy). The results showed that CTPs had broad-spectrum antibacterial activity against different gram-positive and gram-negative bacteria, with MICs against the tested strains varying from 2 to 64 μg/mL. CTPs at the MBC (2 × MIC 64 μg/mL) showed strong bactericidal effects on a standard methicillin-resistant Staphylococcus aureus strain ATCC 43300 after co-incubation for 6 h through disruption of the bacterial membrane. In addition, CTPs at 2 × MIC also displayed effective inhibition activity of several S. aureus strains with a 40–90% decrease in biofilm formation by killing the bacteria embedded in the biofilms. CTPs had low cytotoxicity on the intestinal porcine epithelial cell line (IPEC-J2) and could significantly decrease the rate of adhesion of S. aureus ATCC 43300 on IPEC-J2 cells. The current study proved that CTPs have effective antibacterial, antibiofilm, and anti-adhesion activities. Overall, this study contributes to our understanding of the possible antibacterial and antibiofilm mechanisms of CTPs, which might be an effective anti-MDR drug candidate.
Objectives:China's 2009 national essential medicine system (NEMS) was designed to reduce prices through a zero-markup policy and a centralized bidding system. To analyze NEMS's short-term impact on drug prices, we estimated the retail and wholesale prices before and after the reform at health institutions in rural Jiangxi Province.Materials and Methods:We undertook two cross-sectional surveys of prices of 39 medicines in November 2008 and May 2010, calculated inflation adjusted prices, and used the Wilcoxon signed-rank and rank-sum tests to examine price changes at different health institutions.Results:Retail prices at pilot (P < 0.01) and nonpilot (P < 0.01) township health centers decreased significantly, whereas the declines at retail pharmacies (P = 0.57) and village clinics (P = 0.29) were insignificant. The decline at pilot township health centers was the largest, compared with other kinds of health institutions (P < 0.01). Retail prices of essential and non-essential medicines declined significantly at pilot facilities (P < 0.05); price drops for non-essential medicines occurred only at pilot facilities (P < 0.05). No significant decline of wholesale prices were found at pilot (P = 0.86) and nonpilot units (P = 0.18), retail pharmacies (P = 0.18), and village clinics (P = 0.20). The wholesale prices changes at pilot units before and after the reform were higher than at nonpilot public units (P < 0.05), retail pharmacies (P < 0.05), and village clinics (P < 0.05).Conclusion:While the NEMS zero-markup policy significantly reduced retail prices at pilot health institutions, the centralized bidding system was insufficient to lower wholesale prices. A drug price management system should be constructed to control medicine prices and a long-term price information system is needed to monitor price changes.
Objective To understand the present status of high blood pressure in Jiangxi adults including the prevalence rate, overall awareness, and hypertension treatment. Methods a total of 7,200 adult participants (over 18 years old) lived in Jiangxi were recruited using a stratified sampling method. Blood pressure was measured for all the participants and a questionnaire survey was conducted. A 24-hour urine sample was also collected to understand urine sodium and potassium levels. Results Our findings revealed that the measured systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 125.9 mmHg (95% CI, 124.85-126.95) and 79.2 mm Hg (95% CI, 78.15-80.25). The prevalence of hypertension among the enrolled adults was 27.43% (95% CI, 26.38%–28.48%). Among the affected participants, less than 30% of them (95% CI) were aware of their hypertension condition, and only 28.56% (95% CI) were under anti-hypertension medications. The mean salt intake converted from urinary sodium was 10.92±4.07 g and the mean±SD of 24-h urinary sodium and potassium excretion were 185.51±65.44 mmol and 25.98±9.16 mmol, respectively. The high-salt condiments was determined to be the main source of sodium in the region. Conclusion Findings from this study form the baseline information to understand the hypertension condition in the region and indicate a possible solution for hypertension prevention through avoiding high-salt condiments.
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