Endoplasmic reticulum stress (ERS)-induced inflammation participates in the occurrence of pulmonary arterial hypertension (PAH) by promoting pulmonary vascular remodeling, which involved in the activation of PERK/eIF2α/NF-κB signaling pathway. 18β-Glycyrrhetinic acid (18β-GA) has been found efficacious for attenuating PAH through its anti-remodeling effects in our previous research and it remains unclear whether 18β-GA has an effect on the remodeling caused by ERS-induced inflammation. In this study, we made observations in monocrotaline-induced PAH rats and found improvement of hemodynamic and histopathological parameters, decreases in the right ventricular hypertrophy index, and alleviation of pulmonary vascular remodeling after 18β-GA administration in vivo. Moreover, 18β-GA could significantly inhibit the proliferation and DNA synthesis of human pulmonary arterial smooth muscle cells (HPASMCs) induced by platelet-derived growth factor BB. At the cellular and molecular levels, we found that 18β-GA could significantly reduce the accumulation of misfolded protein in rat lung tissue, inhibit ERS activation, reduce the expression of GRP78, p-PERK, p-eIF2α, and p-NF-κB p65, and increase IκB protein expression. 18β-GA could inhibit the migration of NF-κB into the nucleus, reduce the contents of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and monocyte chemoattractant protein-1 (MCP-1) in the culture supernatant of HPASMCs, and reduce GRP78, p-PERK, p-eIF2α, p-NF-κB p65, TNF-α, IL-6, and MCP-1 protein expression, increase IκB protein expression in HPASMCs. According to what we observed, this study indicated that 18β-GA could treat PAH, which is related to the inhibition of PERK/eIF2α/NF-κB signaling pathway.

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Bilateral nucleus tractus solitarii (NTS) lesions, possibly caused by enterovirus 71 infection, cause severe neurogenic hypertension, leading to acute heart failure (HF), pulmonary edema, and death within hours. Alpha-adrenergic blockers attenuate blood pressure and ameliorate HF and pulmonary edema, thereby prolonging survival time. However, the molecular mechanisms of these blockers are not clear. In this study, we investigated these mechanisms in a rat model of 6-hydroxydopamine (6-OHDA)-induced HF. Sprague–Dawley rats were treated with prazosin 10 min after the microinjection of 6-OHDA into the NTS. Immunohistochemistry and dihydroethidium (DHE) staining were used for analysis. In the cardiac tissue of 6-OHDA-induced HF, in situ expression of tumor necrosis factor-alpha (TNF-α), fibroblast growth factor-23 (FGF23), and FGF receptor 1 (FGFR1) increased, but in situ expression of Vitamin D receptor (VDR) decreased. DHE staining revealed several heart cells with high reactive oxygen species production. Prazosin treatment decreased TNF-α, FGF23, and FGFR1 expression in the heart of rats with 6-OHDA-induced HF. It also prevented cardiomyopathy caused by 6-OHDA-induced bilateral NTS lesions by inhibiting the FGF23-FGFR1 pathway and downregulating TNF-α expression. In situ, FGF23, FGFR1, VDR, superoxide, and TNF-α in the heart were found to be involved in acute HF in our rat model of 6-OHDA-induced bilateral NTS lesions. These findings are potentially useful for treating fatal enterovirus 71 infection-induced NTS lesions and HF.

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Antrodia salmonea (AS) is a fungus, which belongs to a fungal family of Taiwanofungus salmoneus with the features of anti-oxidant, anti-inflammatory, and anticancer. Recent studies have shown that AS has anti-cancer functions in ovarian and breast cancer. However, the effects of AS on prostate cancer (PCa) proliferation remain unknown. Therefore, we investigated the role of AS in PCa proliferation through apoptosis, and cell cycle regulation in PCa cell lines. Our results showed that Antrodia salmonea extract (ASE) inhibited PCa cells growth with a dose-dependent manner. In addition, ASE decreased the anchorage-independent growth formation ability in PC3 cells. Moreover, ASE-induced cell growth inhibition in PCa cells (DU145, PC3) was correlated to decreased cell cycle-related proteins such as cyclin A/B and cyclin-dependent kinase CDK1/2/4, and increased cell cycle inhibitor proteins p21. Besides, ASE decreased the total protein level of epidermal growth factor receptor and its downstream signaling pathways Akt and Erk in both PCa cells. We found that apoptotic markers such as cleaved-PARP protein levels increased significantly in DU145 cells indicating ASE might induce apoptosis. In conclusion, our results suggest that ASE may have the ability to induce PCa cell death through regulating cell cycle arrest and apoptosis pathways.

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As a noninvasive behavioral intervention, the retrieval-extinction (R-E) procedure has drawn much research attention for its capacity to target the reconsolidation of maladaptive memories. However, later research findings suggest that the cause and consequence of R-E may be more complicated than previously suggested. For example, the R-E procedure could increase an animal's motivation for drug-seeking under certain circumstances, and the reversed extinction-retrieval (E-R) procedure could also suppress the drug memory. Two possible mechanisms underlying the R-E procedure have been proposed: the reconsolidation-update and extinction-facilitation hypotheses. To elucidate the paradoxical prior findings and examine these two hypotheses, we systematically examined the efficacy of the extinction (E), R-E, and E-R procedures in mice's low-dose versus high-dose cocaine-induced conditioned place preference (CPP) memory. We showed that the dose of cocaine is a crucial determinant of the efficacy of the three behavioral interventions. The E procedure exerted a long-lasting suppression of the low-dose cocaine CPP memory, while the R-E procedure induced more memory defects than the E and E-R procedures in its long-term suppression of the high-dose cocaine CPP memory. It warrants further investigation of whether the R-E procedure's underlying neurochemical and molecular mechanisms differ from the E and E-R procedures.

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Taurine is a free amino acid that prevents reactive oxygen species (ROS) formation. ROS production is associated with oxidative stress, cell proliferation, apoptosis, inflammation, and DNA alterations in benzo[α]pyrene (BaP)-induced lung cells. Here, we assessed the effect of adding of 25 mM taurine on human pulmonary alveolar epithelial A549 cells treated with different concentrations of BaP. After culturing for 24 h, the cells were tested for biomarkers including cell viability, cellular morphology, Annexin V-FITC/propidium iodide, cell cycle regulation, ROS accumulation, mitochondrial membrane potential (MMP), and expression of related signaling genes and proteins. BaP induced cell cycle arrest and decreased cell viability in a dose-dependent manner. In addition, 50 μM BaP induced a 52.2% increase in ROS levels and inhibited MMP by up to 80%; however, taurine decreased BaP-induced ROS production by 19.5% and restored MMP. The expression of nuclear factor-kappa B (NF-κB), B-cell lymphoma-2 (BCL-2) homologous antagonist killer (Bak), BCL-2-associated X protein (Bax), and cytochrome c at both the mRNA and protein levels were increased, and the expression of BCL-2 and BCL-x1 was decreased by BaP treatment. Furthermore, BaP activated caspase-3/7 expression by up to 25%. However, taurine decreased the expression of NF-κB, Bak, Bax and cytochrome c levels, reduced caspase-3/7 activities, and increased the expression of BCL-2 and BCL-x1. Hence, taurine attenuates BaP-induced oxidative stress and mitochondrial dysfunction by inhibiting the NF-κB-mediated intrinsic apoptosis pathway in A549 cells. Taurine can be considered as a preventive molecule to prevent lung damage.

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Spectral analysis of heart rate (HR) and blood pressure (BP) variabilities (BPV and HRV) is widely available and utilized in understanding the dynamic cardiovascular autonomic regulation in a variety of pathophysiological conditions. In conscious cold-stressed (CS) rats, we examined the effect of a 7-day regimen administration of losartan, a selective nonpeptide angiotensin AT1 receptor blockade, on BPV and HRV at three frequency components: very-low frequency (VLF), low frequency (LF), and high frequency (HF). Key findings in changes of systolic BP (SBP), HR, and spectral power densities for cardiopulmonary oscillations (HF), sympathetic oscillations (LF), cardiovascular myogenic oscillations (VLF), and overall autonomic activity total power (TP) showed: (I) In the resting PreCS trial, compared with the saline, losartan increased HFBPV, TPHRV, all three HRV frequency powers, and the occurrence of the dicrotic notch (DN). However, it decreased SBP, HR, and the LFBPV frequency power. (II) In the CS trial, losartan significantly decreased SBP and DN occurrence and HR and LF/HFHRV but significantly increased HFHRV, TPBPV, and all three BPV frequency powers. In addition, similar to the saline, losartan showed positively correlated LFBPV and VLFBPV. Conversely, losartan converted the original inverse correlations between LFHRV and LFBPV of CS to a positive correlation. (III) Compared with saline in PreCS and CS trials, losartan detached the corresponding sympathetic oscillations between LFBPV and LFHRV. The overall result indicates that endogenous angiotensin II, through stimulation of the AT1 receptor, augments sympathetic tone but attenuates sympathetic oscillations in rats, particularly under the stressful cooling impacts.

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