Chemical Fingerprinting, Antioxidant, and Anti-Inflammatory Potential of Hydroethanolic Extract of Trigonella foenum-graecum.

In the current study, the antioxidant and anti-inflammatory potential of hydroethanolic extract of T. foenum-graecum seeds was evaluated. Phenolic profiling of T. foenum-graecum was conducted through high-performance liquid chromatography-photodiode array (HPLC-PDA) as well as through the mass spectrometry technique to characterize compounds responsible for bioactivity, which confirmed almost 18 compounds, 13 of which were quantified through a chromatographic assay. In vitro antioxidant analysis of the extract exhibited substantial antioxidant activities with the lowest IC50 value of both DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid) inhibition assays. The extract was found to be non-toxic against human RBCs and murine macrophage RAW 264.7 cells. Moreover, the extract significantly (p < 0.001) reduced the lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-α), intrlukin-6 (IL-6), prostaglandin E2 (PGE2), and nitric oxide (NO) in RAW 264.7 cells in a concentration-dependent manner. The hydroethanolic extract of T. foenum-graecum exhibited considerable anti-inflammatory potential by decreasing the cellular infiltration to the inflammatory site in both carrageenan-induced peritonitis and an air pouch model of inflammation. Pretreatment with T. foenum-graecum extract caused significant improvement in antioxidants such as superoxide dismutase (SOD), CAT (catalase), malondialdehyde (MDA), and myeloperoxidase (MPO) against oxidative stress induced by carrageenan. Based on our results of in vivo and in vitro experimentation, we concluded that hydroethanolic extract of T. foenum-graecum is a potential source of phenolic compounds with antioxidant and anti-inflammatory potential.

Utilization of Monitored Beds for Children Admitted With Unintentional Poisonings.

OBJECTIVES: Children with unintentional poisonings (UPs) are frequently admitted to monitored beds (MBs), though most require minimal interventions. We aimed to (1) describe clinical factors and outcomes for children admitted for UPs and (2) identify clinical factors associated with MB placement. METHODS: In this single-center retrospective cohort study, we studied patients younger than 6 years admitted from the emergency department (ED) for UPs over a 5-year period to a quaternary-care children's hospital. Primary outcome was disposition (MB vs non-MB). Secondary outcomes included length of stay, escalation of inpatient care, 7-day readmission, and death. Covariates included age, certainty of ingestion, altered mental status, and ED provider training level. Subanalysis of drug class effect on disposition was also studied. Associations of clinical factors with MB placement were tested with multivariable logistic regression. RESULTS: Of 401 patients screened, 345 subjects met inclusion criteria. Most subjects (308 of 345 [89%]) were admitted to MBs. Children with high certainty of ingestion (adjusted odds ratio [aOR], 4.2; 95% confidence interval [CI], 1.52-11.58), altered mental status (aOR, 5.82; 95% CI, 2.45-13.79), and a fellow (vs faculty) ED provider (aOR, 2.34; 95% CI, 1.04-5.24) were more likely to be admitted to MBs. No escalations of care, readmissions, or deaths occurred. Exposures to cardiac drugs had increased MB placement (aOR, 6.74; 95% CI, 1.93-23.59). CONCLUSIONS: The majority of children admitted for UPs were placed in MBs. Regardless of inpatient placement, no adverse events were observed, suggesting opportunities for optimized resource utilization. Future research may focus on direct costs, inpatient interventions, or prospective outcomes to validate these findings.

Digestive Enzyme Activity and Protein Degradation in Plasma of Heart Failure Patients.

INTRODUCTION: Heart failure is associated with degradation of cell functions and extracellular matrix proteins, but the trigger mechanisms are uncertain. Our recent evidence shows that active digestive enzymes can leak out of the small intestine into the systemic circulation and cause cell dysfunctions and organ failure. METHODS: Accordingly, we investigated in morning fasting plasma of heart failure (HF) patients the presence of pancreatic trypsin, a major enzyme responsible for digestion. RESULTS: Western analysis shows that trypsin in plasma is significantly elevated in HF compared to matched controls and their concentrations correlate with the cardiac dysfunction biomarker BNP and inflammatory biomarkers CRP and TNF-α. The plasma trypsin levels in HF are accompanied by elevated pancreatic lipase concentrations. The trypsin has a significantly elevated activity as determined by substrate cleavage. Mass spectrometry shows that the number of plasma proteins in the HF patients is similar to controls while the number of peptides was increased about 20% in HF patients. The peptides are derived from extracellular and intracellular protein sources and exhibit cleavage sites by trypsin as well as other degrading proteases (data are available via ProteomeXchange with identifier PXD026332).ConnclusionsThese results provide the first evidence that active digestive enzymes leak into the systemic circulation and may participate in myocardial cell dysfunctions and tissue destruction in HF patients. CONCLUSIONS: These results provide the first evidence that active digestive enzymes leak into the systemic circulation and may participate in myocardial cell dysfunctions and tissue destruction in HF patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12195-021-00693-w.

Elevated Resting and Postprandial Digestive Proteolytic Activity in Peripheral Blood of Individuals With Type-2 Diabetes Mellitus, With Uncontrolled Cleavage of Insulin Receptors.

Objective: To examine resting and postprandial peripheral protease activity in healthy controls and individuals with type 2 diabetes mellitus (T2DM) and pre-T2DM. Methods: Individuals with T2DM or pre-T2DM and healthy controls (mean age 55.8 years) were studied before and for a span of 300 minutes following a single high-calorie McDonald's breakfast. Metalloproteases-2/-9 (MMP-2/-9), elastase, and trypsin activities were assessed in whole blood before and following the meal using a novel high-precision electrophoretic platform. Also assessed were circulating levels of inflammatory biomarkers and insulin receptor density on peripheral blood mononuclear cells (PBMCs) in relationship to protease activity. Results: Premeal MMP-2/-9 and elastase activity levels in T2DM and in pre-T2DM participants were significantly elevated as compared to controls. The T2DM group showed a significant increase in elastase activity 15 minutes after the meal; elastase activity continued to increase to the 30-minute time point (p < 0.01). In control participants, MMP-2/-9, elastase, and trypsin were significantly increased at 15 minutes after the meal (p < 0.05) and returned to premeal values within a period of approximately 30 to 60 minutes post meal. PBMCs incubated for 1 hour with plasma from T2DM and pre-T2DM participants had significantly lower levels of insulin receptor density compared to those incubated with plasma from control participants (p < 0.001). Conclusions: The results of this study suggest that individuals with T2DM and pre-T2DM have higher resting systemic protease activity than nonsymptomatic controls. A single high-calorie/high-carbohydrate meal results in further elevations of protease activity in the systemic circulation of T2DM and pre-T2DM, as well as in healthy controls. The protease activity in turn can lead to a downregulation of insulin receptor density, potentially supporting a state of insulin resistance.