Current Issue : April-June
Volume : 2022
Issue Number : 2
Articles : 5 Articles
A series of coumarin derivatives and isosteres were synthesized from the reaction of triflic
intermediates with phenylboronic acids, terminal alkynes, and organozinc compounds through
palladium-catalyzed cross-coupling reactions. The in vitro cytotoxic effect of the compounds was
evaluated against two non-small cell lung carcinoma (NSCLC) cell lines (A-549 and H2170) and
a normal cell line (NIH-3T3) using cisplatin as a reference drug. Additionally, the effects of the most
promising coumarin derivative (9f) in reversing the epithelial-to-mesenchymal transition
The mitochondrial GTPase mitofusin-2 (MFN2Th gene can suppress the cell cycle and regulate cell proliferation in a number of cell
types. However, its function in hepatic fibrosis remains largely unexplored. We attempted to understand the mechanism of MFN2
in hepatic stellate cell (HSCTh proliferation and the development of hepatic fibrosis. Rat HSC-T6 HSC were cultured and
transfected by adenovirus- (Ad-Th Mfn2 or its negative control (NCTh vector (Ad-green fluorescent protein (GFPThTh; a rat liver
cirrhosis model was established via subcutaneous injection with carbon tetrachloride (CCl4Th. Seventy-two rats were randomly
divided into four groups: CCl4, Mfn2, GFP, and NC. Ad-Mfn2 or Ad-GFP was transfected into the circulation via intravenous
injection at day 1, 14, 28, 42, or 56 after the first injection of CCl4 in the Mfn2/GFP groups. Biomarkers related to HSC
proliferation and the development of hepatic fibrosis were detected using western blotting, hematoxylin-eosin and Masson
staining, and immunohistochemistry. In vitro, Mfn2 interfered specifically with platelet-derived growth factor- (PDGF-Th induced
signaling pathway (phosphatidylinositol 3-kinase- (PI3K-Th AKTTh, inhibiting HSC-T6 cell activation and proliferation. During the
process of hepatic fibrosis in vivo, extracellular collagen deposition and the expression of fibrosis-related proteins increased
progressively, while Mfn2 expression decreased gradually. Upregulating Mfn2 expression at the early stage of fibrosis impeded the
process, triggered the downregulation of type I collagen, and antagonized the formation of factors associated with liver fibrosis.
Mfn2 suppresses HSC proliferation and activation and exhibits antifibrotic potential in early-stage hepatic fibrosis. Therefore, it
may represent a significant therapeutic target for eradicating hepatic fibrosis....
The infection of coronavirus disease (COVID-19) seriously threatens human life. It is urgent to generate effective and safe specific
antibodies (Abs) against the pathogenic elements of COVID-19. Mice were immunized with SARS-CoV-2 spike protein antigens:
S ectodomain-1 (CoV, in short) mixed in Alum adjuvant for 2 times and boosted with CoV weekly for 6 times. A portion of mice
were treated with Maotai liquor (MTL, in short) or/and heat stress (HS) together with CoV boosting. We observed that the anti-
CoV Ab was successfully induced in mice that received the CoV/Alum immunization for 2 times. However, upon boosting with
CoV, the CoV Ab production diminished progressively; spleen CoV Ab-producing plasma cell counts reduced, in which
substantial CoV-specific Ab-producing plasma cells (sPC) were apoptotic. Apparent oxidative stress signs were observed in
sPCs; the results were reproduced by exposing sPCs to CoV in the culture. The presence of MTL or/and HS prevented the
CoV-induced oxidative stress in sPCs and promoted and stabilized the CoV Ab production in mice in re-exposure to CoV. In
summary, CoV/Alum immunization can successfully induce CoV Ab production in mice that declines upon reexposure to
CoV. Concurrent administration of MTL/HS stabilizes and promotes the CoV Ab production in mice....
Ursodeoxycholic acid (UDCA) is a first-line clinical drug for the treatment of liver diseases.
U12, a derivative of UDCA, showed effective anti-hepatoma activities in previous works.
However, the low polarity and large doses limited the druglikeness of U12. In this study, the structural
modification and optimization of U12 were further investigated and twelve U12 derivatives
were synthesized by substitution, esterification and amidation reactions. The evaluation of the cytotoxicity
of synthetic derivatives against hepatoma cell lines (HepG2) indicated that U12-I, U12a-d
and U12h showed more effective cytotoxic effects on the growth of HepG2 cells than U12, and the
preliminary structure–activity relationship was discussed. Among them, U12a exhibited the most
potent anti-hepatocellular carcinoma activity. Mechanism studies indicated that U12a inhibited
HepG2 cell proliferation by arresting the G0/G1 phase, and suppressed the activation of the
PI3K/AKT/mTOR pathway. Further studies showed that U12a induced HepG2 cells apoptosis
through activating the caspase signaling pathway. Furthermore, U12a evidently inhibits the growth
of HepG2-derived tumor xenografts in vivo without observable adverse effects. Thus, U12a might
be considered as a promising candidate for the treatment of hepatocellular carcinoma....
Four isobutyric acids (two nitro and two acetamido derivatives) were prepared in two
steps and characterized using spectral analysis. The mRNA concentrations of PPAR
(two proteins documented as key diabetes targets) were increased by 3T3-L1 adipocytes treated
with compounds 1–4, but an absence of in vitro expression of PPAR was observed. Docking and
molecular dynamics studies revealed the plausible interaction between the synthesized compounds
. In vivo studies established that compounds 1–4 have antihyperglycemic modes of action
associated with insulin sensitization. Nitrocompound 2 was the most promising of the series, being
orally active, and one of multiple modes of action could be selective PPAR
modulation due to its
extra anchoring with Gln-286. In conclusion, we demonstrated that nitrocompound 2 showed strong
in vitro and in vivo effects and can be considered as an experimental antidiabetic candidate....
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