Gardenia jasminoides J. Ellis extract attenuates memory impairment in rats with Alzheimer's disease by suppressing NLRP3 inflammasome.

Alzheimer's disease (AD) is characterized by degeneration of the central nervous system. Recently, many studies have emphasized the beneficial role of Gardenia jasminoides J. Ellis extract (GJ-4) in neuroprotection, which is considered a potential drug for treating AD. However, the mechanism underlying its neuroprotective effects is obscure. This research intended to analyze the effectiveness of GJ-4 to induce neuronal protective role on a rat model of neurotoxicity and probe the potential mechanism. An AD model was established by intraperitoneal injection of aluminum chloride (AlCl3). Then, AlCl3-induced rats were administered 25 mg/kg and 50 mg/kg of GJ-4 orally. This study indicated that GJ-4 (25 and 50 mg/kg) mitigated AD-like behaviors, as evidenced by enhanced ambulation frequency, rearing frequency, and time spent in the target quadrant and decreased grooming frequency, defecation frequency, and escape latency in AlCl3-challenged rats. Also, GJ-4 at 25 and 50 mg/kg exerted an anti-apoptosis effect in the hippocampus of AlCl3-treated rats. Furthermore, GJ-4 (25 and 50 mg/kg) exhibited an anti-inflammatory effect in the hippocampus by repressing the activation of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, further inhibiting the activation of Caspase 1, ASC, IL-1ß, and IL-18 in AD hippocampus. Altogether, GJ-4 mitigated AlCl3-triggered impairment of learning and memory in AD rats via repressing NLRP3 inflammasome.

Baicalein promotes the microglia M2 polarization and suppresses apoptosis by targeting HMOX1/PDE4D to alleviate Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder that has quickly becoming one of the most expensive, lethal, and burdening diseases of this century. In the past twenty years, hundreds of drugs have been tested while only several have been authorized by FDA for AD treatment, hence, searching for candidate agent with therapeutic potential for AD is imminent. Controlling polarization direction of microglia is crucial in AD therapy. Recent research suggests that baicalein has potential to reduce neuroinflammation and prevent neurodegenerative diseases by affecting microglia, while the specific molecular mechanism of baicalein in regulating microglia in the treatment of AD is still unclear. In this study, we investigated how baicalein affected microglial polarization in AD and potential biological mechanisms. In cell experiments, it was verified that baicalein significantly shifted the BV-2 microglia phenotype from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype, inhibited the microglial apoptosis and pro-inflammatory factors, promoted the microglial Aß uptake and anti-inflammatory factors after LPS stimulated. In APP/PS1 mice, it was found that baicalein decreased the Aß plaque deposition in brain, attenuated NLRP3 inflammasome activation and neuronal apoptosis in APP/PS1 mice. Furthermore, bioinformatics analysis and experiment validated that HMOX1 is a target of baicalein, and we elucidated that baicalein modulated the microglial polarization to inhibit neuroinflammation and neural injury through targeting on the HMOX1/PDE4D axis in AD. In conclusion, our findings indicate the therapeutic effect of baicalein for AD, and baicalein might serve a potential agent for AD treatment.

Scedosporium apiospermum and Lichtheimia corymbifera Co-Infection Due to Inhalation of Biogas in Immunocompetent Patients: A Case Series.

This is the first report describing co-infection of Scedosporium apiospermum and Lichtheimia corymbifera caused by biogas inhalation in two people without underlying medical conditions. Two patients fell into the same pig manure pit at the same time while rescuing another patient (this person died in a few hours) and inhaled biogas. Both patients were diagnosed with pulmonary fungal disease and developed acute liver failure around Day 52. Their results were negative for the 1,3-ß-d-glucan test and weakly positive for the galactomannan test. They were treated with amphotericin B and/or posaconazole without surgery. The patient in case 2 required amphotericin B deoxycholate aerosol inhalation to complete the treatment. Both patients recovered completely. For patients with mucormycosis confined to the lungs who cannot tolerate intravenous drip amphotericin B, increasing the dose of nebulised administration maybe a salvage regimen.

Effects of continuous nursing on rehabilitation compliance, living quality and daily living ability of patients with acute ischemic stroke.

OBJECTIVES: To investigate the effect of continuous nursing on rehabilitation of patients with acute ischemic stroke (AIS). METHODS: In this prospective study, 150 patients were treated for AIS at our hospital from January 2017 to December 2019. The patients were separated into two groups: the conventional group (n = 75) that received conventional nursing and the continuous nursing group (n = 75) were treated with continuous nursing intervention. Patients were followed up for compliance, negative mood, living quality, nursing satisfaction, and daily living abilities. RESULTS: The compliance rate of the continuous nursing group (93.33%) was obviously higher than that of the conventional nursing group (85.33%, P<0.05). There was no obvious difference in the negative mood scores between the two groups before intervention (P>0.05); however, the negative mood scores of the two groups decreased after intervention. In particular, the scores in continuous nursing group were obviously lower than that in the conventional nursing group (P<0.05). After intervention, the living quality scores in the continuous nursing group were obviously higher than that in the conventional nursing group (P<0.05). The satisfaction of nurses in the continuous nursing (96.00%) was obviously higher than that in the conventional nursing group (70.00%, P<0.05). The Barthel index (BI) scores in the continuous nursing group were obviously higher than those in the conventional nursing at 1 d, 7 d, and 30 d after intervention (P<0.05). CONCLUSIONS: The results demonstrated that continuous nursing can enhance the rehabilitation compliance of patients with AIS, alleviate the negative mood of patients, enhance the living quality and daily living ability of patients.

Circular RNA circVMA21 ameliorates lipopolysaccharide (LPS)-induced acute kidney injury by targeting the miR-199a-5p/NRP1 axis in sepsis.

BACKGROUND: Sepsis is a serious and elusive syndrome caused by infection, with high mortality worldwide. Circular RNAs vacuolar ATPase assembly factor (circVMA21) has been reported to be related to the inflammatory damages in sepsis. This study is designed to explore the role and mechanism of circVMA21 in the lipopolysaccharide (LPS)-induced cell injury in sepsis. METHODS: Cell viability and apoptosis were detected by CCK-8, and flow cytometry assays. CircVMA21, microRNA-199a-5p (miR-199a-5p), and Neuropilin-1 (NRP1) level were determined by RT-qPCR. Protein levels of Bcl-2, Bax, cleaved-caspase 3, and NRP1 were examined by Western blot assay. IL-1ß, IL-6, and TNF-α were detected using ELISA. Superoxide Dismutase (SOD) and glutathione (GSH) were measured by the special kits. The binding relationship between miR-199a-5p and circVMA21 or NRP1 was predicted by Starbase 3.0 and then verified by a dual-luciferase reporter and RIP assays. RESULTS: CircVMA21 and NRP1 were decreased, and miR-199a-5p was increased in LPS-induced THP-1 cells. Moreover, circVMA21 overexpression could repress LPS-mediated cell viability, apoptosis, inflammation, and oxidative stress in THP-1 cells. The mechanical analysis suggested that circVMA21 regulated NRP1 expression through sponging miR-199a-5p. CONCLUSION: CircVMA21 upregulation could attenuate LPS-triggered THP-1 cell injury through modulating the miR-199a-5p/NRP1 axis, hinting an underlying therapeutic strategy for sepsis patients.

DL-3-n-butylphthalide attenuates lipopolysaccharide-induced acute lung injury via SIRT1-dependent and -independent regulation of Nrf2.

The acute respiratory distress syndrome (ARDS), a devastating clinical syndrome, is one of the most severe complications of acute lung injury (ALI). Despite of decades of clinical trials and supportive ventilation strategies, the incidence and mortality of ALI/ARDS remain high. DL-3-n-butylphthalide (NBP) is a synthesized raceme of L-3-n-butylphthalide which has been approved to possess various activities. In the current study, we aimed to investigate the effect of NBP on ALI in lipopolysaccharide (LPS)-treated mice. We found that 10 mg/kg and 50 mg/kg NBP significantly prevented LPS-induced increase of W/D ratio of lung, histological injury of lung, infiltration of inflammatory cells, release of pro-inflammatory cytokines and chemokines, and oxidative damage. Sirtuin 1 (SIRT1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression was increased by NBP in lung of LPS-treated mice. Knockout of SIRT1 significantly aggravated LPS-induced ALI. Moreover, the absence of SIRT1 notably inhibited NBP-induced protective effects against LPS-induced increase of W/D ratio of lung, histological injury of lung, infiltration of inflammatory cells, release of pro-inflammatory cytokines and chemokines, and oxidative damage. However, knockout of SIRT1 did not completely inhibit NBP-induced upregulation of Nrf2 and attenuation of ALI. The results demonstrated that NBP could activate Nrf2 antioxidant signaling in a SIRT1-dependent and SIRT1-independent manner, resulting in the amelioration of oxidative stress, inflammation and pulmonary edema. The data highlights the importance of SIRT1/Nrf2 signaling in the protective effects of NBP.