NIR triggered polydopamine coated cerium dioxide nanozyme for ameliorating acute lung injury via enhanced ROS scavenging.

Acute lung injury (ALI) is a life threatening disease in critically ill patients, and characterized by excessive reactive oxygen species (ROS) and inflammatory factors levels in the lung. Multiple evidences suggest that nanozyme with diversified catalytic capabilities plays a vital role in this fatal lung injury. At present, we developed a novel class of polydopamine (PDA) coated cerium dioxide (CeO2) nanozyme (Ce@P) that acts as the potent ROS scavenger for scavenging intracellular ROS and suppressing inflammatory responses against ALI. Herein, we aimed to identify that Ce@P combining with NIR irradiation could further strengthen its ROS scavenging capacity. Specifically, NIR triggered Ce@P exhibited the most potent antioxidant and anti-inflammatory behaviors in lipopolysaccharide (LPS) induced macrophages through decreasing the intracellular ROS levels, down-regulating the levels of TNF-α, IL-1ß and IL-6, up-regulating the level of antioxidant cytokine (SOD-2), inducing M2 directional polarization (CD206 up-regulation), and increasing the expression level of HSP70. Besides, we performed intravenous (IV) injection of Ce@P in LPS induced ALI rat model, and found that it significantly accumulated in the lung tissue for 6 h after injection. It was also observed that Ce@P + NIR presented the superior behaviors of decreasing lung inflammation, alleviating diffuse alveolar damage, as well as promoting lung tissue repair. All in all, it has developed the strategy of using Ce@P combining with NIR irradiation for the synergistic enhanced treatment of ALI, which can serve as a promising therapeutic strategy for the clinical treatment of ROS derived diseases as well.

Potential Dexamethasone-Direct Oral Anticoagulant Drug Interaction: Is This a Concern in COVID?

OBJECTIVE: To evaluate the literature on a potential dexamethasone-direct oral anticoagulant (DOAC) drug interaction and provide management considerations with COVID hypercoagulability. DATA SOURCES: A search of EMBASE, PubMed, and Google Scholar (January 1990 to May 2021), limited to the English language, using applicable search terms resulted in 137 articles, with 21 relevant articles included. Regulatory agency and clinical guidance documents were also reviewed. STUDY SELECTION AND DATA EXTRACTION: Included articles describe in vitro or in vivo animal or human data for dexamethasone induction of cytochrome P450 (CYP) 3A4 or P-glycoprotein (P-gp). DATA SYNTHESIS: Dexamethasone has the potential to interact with the DOACs via CYP3A4 and/or P-gp induction. Only apixaban and rivaroxaban have CYP3A4 metabolism. Dexamethasone can increase CYP3A4 activity by up to 70% and reduce the area under the concentration-time curve (AUC) of CYP3A4 substrates by >40%, which is consistent with criteria for a weak CYP inducer. In rodents, dexamethasone P-gp induction is associated with AUC reductions of 20% to 50%. Human data are lacking. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Severe COVID-19 infection is associated with hypercoagulability. Although heparins are the preferred anticoagulants for hospitalized COVID-19 patients, DOACs are being utilized. Dexamethasone is recommended for hospitalized COVID-19 patients requiring supplemental oxygen. The concurrent use of dexamethasone and apixaban or rivaroxaban in such patients carries the potential for reduced anticoagulant effect during a state of heightened thrombotic risk. CONCLUSIONS: Concurrent use of dexamethasone and apixaban or rivaroxaban in hospitalized COVID-19 patients with laboratory evidence of COVID coagulopathy should be avoided until higher-quality data are available.

Combinative effect of sardine peptides and quercetin alleviates hypertension through inhibition of angiotensin I converting enzyme activity and inflammation.

Hypertension had relation to angiotensin I converting enzyme (ACE) activity and inflammation. In our previous research, sardine peptides (SP) with ACE inhibitory activity were prepared. However, the combinative effect of SP and quercetin (QC) on hypertension alleviation was still unknown. In the present study, the antihypertensive effect of SP and QC was discovered and the optimal proportion of SP and QC (v/v=8:2, with 20.00mg/mL of SP and 12.99µg/mL of QC for their original concentrations) was screened on ACE activity inhibition in vitro. And the in vivo experiment supported it by indicating that the mixture reduced the systolic blood pressure, heart, left ventricular and kidney weight and their corresponding indices, serum ACE activity, angiotensin-II (ANG-II) and tumor necrosis factor-α (TNF-α) (in high dose) concentration in SHR rats. Besides, the mixture also lowers NO, TNF-α andinterleukin-6 (IL-6) concentration significantly in vitro. Hence, the combinative effect of SP and QC in optimal proportion had stronger inhibition on ACE activity than SP or QC alone, and could alleviate hypertension through inhibition of ACE activity and inflammation.

Angiotensin-I-Converting Enzyme Inhibitory Activities and In Vivo Antihypertensive Effects of Sardine Protein Hydrolysate.

In our previous study, an antihypertensive protein hydrolysate was prepared from sardine. This study aimed to investigate the composition of sardine protein hydrolysate (SPH) and it's in vivo antihypertensive effect. SPH was separated sequentially with ultrafiltration and size exclusion chromatography. Fractions with high angiotensin-I-converting enzyme (ACE) inhibitory activity were further analyzed with RP-HPLC and amino acids analysis. Then, SPH was individually oral administrated to spontaneously hypertensive rats (SHR) and normotensive wistar kyoto rats (WKY) for 4 wk. After treatment, the systolic blood pressure (SBP), organ index, oxidative status, serum ACE activity, and serum angiotensin-II (ANG-II) of all the rats were determined. According to the separation and analysis results, 3 main fractions with high ACE-inhibitory activity were obtained with different amino acids composition. The animal experiments results showed that SPH could significantly reduce SBP (P < 0.05 or P < 0.01) within 4 h after a single oral administration. After a chronic oral administration, a steady state of SBP in SHR rats was attained. The heart weight index and left ventricular weight index were significantly reduced (P < 0.05) in SPH-treated SHR rats. The malonyldialdehyde (MDA) levels in organs and serum, serum ACE activity, and serum ANG-II concentration in SPH-treated SHR rats were significantly lowered (P < 0.05 or P < 0.01) as compared to their controls. Meanwhile there was no significant effect (P > 0.05) on those parameters in WKY rats. These results indicate that SPH can decrease blood pressure in SHR rats and not in WKY rats.

Different Flavonoids Can Shape Unique Gut Microbiota Profile In Vitro.

The impact of flavonoids has been discussed on the relative viability of bacterial groups in human microbiota. This study was aimed to compare the modulation of various flavonoids, including quercetin, catechin and puerarin, on gut microbiota culture in vitro, and analyze the interactions between bacterial species using fructo-oligosaccharide (FOS) as carbon source under the stress of flavonoids. Three plant flavonoids, quercetin, catechin, and puerarin, were added into multispecies culture to ferment for 24 h, respectively. The bacterial 16S rDNA amplicons were sequenced, and the composition of microbiota community was analyzed. The results revealed that the tested flavonoids, quercetin, catechin, and puerarin, presented different activities of regulating gut microbiota; flavonoid aglycones, but not glycosides, may inhibit growth of certain species. Quercetin and catechin shaped unique biological webs. Bifidobacterium spp. was the center of the biological web constructed in this study.