Wiley最新文献

Background

Depression is a complex psychiatric disorder with limited therapeutic options and various side effects. Calycosin, a bioactive compound derived from Astragalus membranaceus, possesses multiple pharmacological properties. This study aimed to investigate the antidepressant effects of calycosin in chronic mild stress (CMS) animal models of depression and to elucidate its underlying mechanisms.

Methods

The antidepressant effects of calycosin were assessed in vivo using CMS animal models of depression, including the grooming frequency test, sucrose intake test, tail suspension test, and open field test. Neurogenic effects were evaluated by measuring the levels of BDNF, GDNF, and NGF in isolated hippocampus tissues. The hepatoprotective effects were assessed by measuring liver enzyme levels. The molecular mechanisms underlying calycosin's antidepressant effects were explored in vitro using PC12 cells.

Results

Calycosin exhibited potent antidepressant-like activities in CMS animal models of depression. Treatment with calycosin significantly alleviated depressive symptoms and improved neurogenic effects. Additionally, calycosin displayed hepatoprotective effects by modulating liver enzymes in vitro. The antidepressant effects of calycosin are mediated by the stimulation of the TrkB–MEK–Erk1/2–CREB signaling pathway.

Conclusion

In conclusion, calycosin shows promise as a novel therapeutic agent for depression due to its potent antidepressant-like activities and diverse pharmacological properties. Further studies are warranted to elucidate the exact molecular targets of calycosin and to assess its efficacy and safety in clinical settings.

Aims

The study aimed to determine the correlation between the maximum lactate on the first postoperative day and the incidence of postoperative delirium (POD) in patients after cardiac surgery.

Methods

The data of cardiac surgery patients were extracted from the Medical Information Mart for Intensive Care IV database. The cut-off value for the first postoperative day maximum lactate was determined, and all patients were categorized into two groups according to the cut-off value. Propensity score matching (PSM) was applied between the two groups, and the difference in the incidence of POD was analyzed. Then, we employed univariate logistic regression, multivariate logistic regression, PSM, and inverse probability of treatment weighting (IPTW) models to examine the relationship between the first postoperative day lactate levels and POD.

Results

Among the 4856 patients enrolled, there was a significant difference in lactate-max on the first postoperative day between patients without POD and patients with POD (median 2.5 vs. 3.1, p < 0.001). The cut-off value of lactate-max was 2.85 mmol/L. For the two groups after PSM, the incidence of POD in the lactate-max ≥ 2.85 mmol/L group was significantly elevated (19.2% vs. 15.9%, p = 0.029). The elevated lactate-max on the first postoperative day was substantially associated with an increased risk of POD in univariate and multivariate logistic regression analyses, PSM, and IPTW models.

Conclusions

The results demonstrated that the first postoperative day lactate-max was correlated with the risk of POD in patients undergoing cardiac surgery, with the POD risk increasing significantly in patients with a lactate-max ≥ 2.85 mmol/L on the first postoperative day.

Main Problem

The mechanism behind Parkinson's disease (PD) is still unclear, and a cure to stop its progression is yet to be found. This is mainly due to the lack of effective human PD models. To address this, we generated an in vitro PD model using Wharton's jelly-derived mesenchymal stem cells (WJMSCs).

Methods

WJMSCs were isolated from the umbilical cord using an enzymatic method. MSCs were characterized by RT-PCR, immunofluorescence, and trilineage differentiation. MSCs were differentiated into dopaminergic neuron-like cells (DAN) and further degenerated by treating them with either MPP+ iodide or the A53T mutated α-synuclein variant. Gene expression analysis by qRT-PCR and protein analysis by immunofluorescence, flow cytometry, and ELISA were performed. Assays to measure LDH, ROS, NO, GSH, and mitochondrial membrane potential were also performed after degeneration.

Results

WJMSCs were positive for MSC markers and were able to differentiate into adipocytes, chondrocytes, and osteocytes. DAN obtained after the differentiation of WJMSCs for 48 h expressed neuronal markers such as synapsin 1, neuropilin, neurofilament, and MAPT along with dopaminergic markers such as Nurr1, DAT, TH, DDC, and KCNJ6 and were functionally active. Upon degeneration of DAN by MPP+ or A53T, elevated levels of SNCA and downregulation of TH, Nurr1, DAT, and KCNJ6 were observed. Furthermore, increased expression of α-SYN was detected at the protein level as well. Finally, reduction in mitochondrial membrane potential and GSH levels along with an increase in intracellular ROS, nitrite production, and LDH levels confirmed that the in vitro PD-like model exhibited the molecular characteristics of PD.

Conclusion

This model is rapid, cost-efficient, and effective for understanding the molecular mechanisms of the disease and can also be used for screening of emerging therapeutics for PD.

The ability of carcass vascular rinsing supplemented with bacteriophage (BP) and peracetic acid (PAA) to reduce Salmonella in lymph nodes (LNs) from experimentally infected goats was determined. Cull dairy goats (n = 60) were randomly assigned to a control (CN, nonrinsed) and two vascular rinse treatments: BP and PAA. Goats were inoculated intradermally with Salmonella Enteritidis and slaughtered after a 7-day incubation. Vascular rinsing was performed postexsanguination via a catheter in the heart. Carcasses were skinned, eviscerated, sprayed with 5% lactic acid, and chilled (2°C) overnight. The superficial cervical, popliteal, medial iliac, and subiliac LNs were collected aseptically for Salmonella enumeration and phage titer determination. The longissimus dorsi (LD) and semimembranosus muscles were also excised, and stored for 1, 4, and 7 days for meat surface color measurements. PAA-treated carcasses showed lower (p < 0.05) temperatures and pH values within 8 h postmortem compared to CN and BP. The average counts of Salmonella in the LNs associated with PAA (3.4 ± 1.3 log CFU/g) were significantly lower compared to CN (3.8 ± 1.1 log CFU/g), with the lowest load observed in medial iliac LNs (2.7 ± 1.5 log CFU/g). Substantial phage titers were detected in LNs from BP-treated carcasses (7.0 ± 0.91 log PFU/g), and no differences were observed in Salmonella counts in BP compared to CN. The meat samples obtained from PAA-treated carcasses exhibited lower redness (a* values) and deoxymyoglobin in the LD (p < 0.05) but showed no differences in lightness or oxymyoglobin compared to BP and CN. Vascular rinsing has the potential to suppress Salmonella in the LNs with other antimicrobials and chemicals with different combinations and concentrations.

Practical Application

This study investigates a method to control Salmonella in goat meat by rinsing carcasses with peracetic acid (PAA) or bacteriophages through the bloodstream after slaughter. The findings suggest that PAA can mitigate Salmonella levels in lymph nodes, potentially improving meat safety. While bacteriophage treatment did not significantly affect the bacterial count to observe differences with the control group, vascular rinsing could still be promising with different antimicrobial combinations. This research would help meat processors enhance food safety measures, reducing the risk of Salmonella contamination in meat products.