BACKGROUND
Pulmonary arterial hypertension (PAH) is a severe progressive disease with systemic metabolic dysregulation. Monocrotaline (MCT)-induced and hypoxia-induced pulmonary hypertension (PH) rodent models are the most widely used preclinical models, however, whether or not these preclinical models recapitulate metabolomic profiles of PAH patients remain unclear.
METHODS
In this study, a targeted metabolomics panel of 126 small molecule metabolites was conducted. We applied it to the plasma of the 2 preclinical rodent models of PH and 30 idiopathic pulmonary arterial hypertension (IPAH) patients as well as 30 healthy controls to comparatively assess the metabolomic profiles of PAH patients and rodent models.
RESULTS
Significantly different metabolomics profiling and pathways were shown among the 2 classical rodent models and IPAH patients. Pathway analysis demonstrated that methionine metabolism and urea cycle metabolism were the most significant pathway involved in the pathogenesis of hypoxia-induced PH model and MCT-induced model, respectively, and both of them were also observed in the dysregulated pathways in IPAH patients.
CONCLUSIONS
These 2 models may develop PAH through different metabolomic pathways and each of the 2 classical PH model resembles IPAH patients in certain aspects.
Background
‘
Bianliang ziyu
’, a famous chrysanthemum variety commonly planted in Kaifeng, China, is often consumed by local residents. However, the hepatoprotective effects of
Bianliang ziyu
and their underlying mechanisms are not clear.
Objective
In this study, we investigated the hepatoprotective and antioxidative effects of
Bianliang ziyu
extract (BZE) on liver injury and explored its molecular mechanisms.
Design
Sprague-Dawley rats were administered BZE by intragastric administration for 8–9 days, and then alcohol or carbon tetrachloride (CCl
4
) was administered by gavage to induce acute liver injury. The activities of serum alanine aminotransferase, aspartate aminotransferase, superoxide dismutase, and malondialdehyde in the rats were measured, and the liver of each rat was examined for histopathological changes.
In vitro
, HL-7702 cells were pretreated with BZE for 24 h and then exposed to 30 mmol•L
−1
acetaminophen (APAP) for 12 h. The survival rate of the cells and the alanine aminotransferase and aspartate aminotransferase activities were determined. Then, we investigated the effects of BZE on oxidative stress, apoptosis, and the activation of nuclear factor erythroid-2-related factor 2 (Nrf2) signaling in HL-7702 cells induced by APAP.
Results
The results showed that BZE prevented alcohol-, CCl
4
-, and APAP-induced liver injury and suppressed hepatic oxidative stress
in vitro
and
in vivo
. BZE was also observed to significantly inhibit the reduction of mitochondrial membrane potential and regulate the expression of Bcl-2, Bax and Caspase-3 in APAP-induced HL-7702 cells. In addition, BZE significantly promoted nuclear translocation and the expression of Nrf2 as well as its downstream gene hemeoxygenase-1 (HO-1)
in vitro
. Furthermore, the findings showed that Nrf2 siRNA reversed the effects of BZE on cell survival and apoptosis-related protein expression in APAP-induced HL-7702 cells.
Conclusions
BZE plays an important role in preventing hepatotoxicity by inhibiting oxidative stress and apoptosis through activation of Nrf2 signaling. BZE could be developed as an effective functional food for protecting the liver.
Apolipoprotein E4
(ApoE4) is the main genetic risk factor for Alzheimer’s
disease (AD), but the exact way in which it causes AD remains unclear.
Curcumin is considered to have good therapeutic potential for AD,
but its mechanism has not been clarified. This study aims to observe
the effect of curcumin on ApoE4 transgenic mice and explore its possible
molecular mechanism. Eight-month-old ApoE4 transgenic mice were intraperitoneally
injected with curcumin for 3 weeks, and the Morris water maze test
was used to evaluate the cognitive ability of the mice. Immunofluorescence
staining, immunohistochemistry, western blotting, and enzyme-linked
immunosorbent assay (ELISA) were used to examine the brain tissues
of the mice. Curcumin reduced the high expression of ApoE4 and the
excessive release of inflammatory factors in ApoE4 mice. In particular,
the expression of marker proteins of endoplasmic reticulum (ER) stress
was significantly increased in ApoE4 mice, while curcumin significantly
reduced the increase in the expression of these proteins. Collectively,
curcumin alleviates neuroinflammation in the brains of ApoE4 mice
by inhibiting ER stress, thus improving the learning and cognitive
ability of transgenic mice.
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