Triple‐negative breast cancer (TNBC) is the most aggressive and lethal clinical subtype and lacks effective targeted therapies at present. Isobavachalcone (IBC), the main active component of Psoralea ...corylifolia L., has potential anticancer effects. Herein, we identified IBC as a natural sirtuin 2 (SIRT2) inhibitor and characterized the potential mechanisms underlying the inhibition of TNBC. Molecular dynamics analysis, enzyme activity assay, and cellular thermal shift assay were performed to evaluate the combination of IBC and SIRT2. The therapeutic effects, mechanism, and safety of IBC were analyzed in vitro and in vivo using cellular and xenograft models. IBC effectively inhibited SIRT2 enzyme activity with an IC50 value of 0.84 ± 0.22 μM by forming hydrogen bonds with VAL233 and ALA135 within its catalytic domain. In the cellular environment, IBC bound to and stabilized SIRT2, consequently inhibiting cellular proliferation and migration, and inducing apoptosis and cell cycle arrest by disrupting the SIRT2/α‐tubulin interaction and inhibiting the downstream Snail/MMP and STAT3/c‐Myc pathways. In the in vivo model, 30 mg/kg IBC markedly inhibited tumor growth by targeting the SIRT2/α‐tubulin interaction. Furthermore, IBC exerted its effects by inducing apoptosis in tumor tissues and was well‐tolerated. IBC alleviated TNBC by targeting SIRT2 and triggering the reactive oxygen species ROS/β‐catenin/CDK2 axis. It is a promising natural lead compound for future development of SIRT2‐targeting drugs.
Tumor microenvironment consists of tumor cells, stromal cells, extracellular matrix and a plethora of soluble components. The complex array of interactions between tumor cells and their surrounding ...tumor microenvironments contribute to the determination of the fate of tumor cells during tumorigenesis and metastasis. Matricellular protein periostin is generally absent in most adult tissues but is highly expressed in tumor microenvironments. Current evidence reveals that periostin plays a critical role in establishing and remodeling tumor microenvironments such as the metastatic niche, cancer stem cell niche, perivascular niche, pre-metastatic niche, fibrotic microenvironment and bone marrow microenvironment. Here, we summarize the current knowledge of the multifaceted role of periostin in the tumor microenvironments.
The MSSM is extended to the
U
(
1
)
X
SSM, whose local gauge group is
S
U
(
3
)
C
×
S
U
(
2
)
L
×
U
(
1
)
Y
×
U
(
1
)
X
. To obtain the
U
(
1
)
X
SSM, we add the new superfields to the MSSM, namely: ...three Higgs singlets
η
^
,
η
¯
^
,
S
^
and right-handed neutrinos
ν
^
i
. It can give light neutrino tiny mass at the tree level through the seesaw mechanism. The study of the contribution of the two-loop diagrams to the MDM of muon under
U
(
1
)
X
SSM provides the possibility for us to search for new physics. In the analytical calculation of the loop diagrams (one-loop and two-loop diagrams), the effective Lagrangian method is used to derive muon MDM. Here, the considered two-loop diagrams include Barr-Zee type diagrams and rainbow type two-loop diagrams, especially
Z
–
Z
rainbow two-loop diagram is taken into account. The obtained numerical results can reach
7.4
×
10
-
10
, which can remedy the deviation between SM prediction and experimental data to some extent.
Background
We recently encountered a Rhnull phenotype proband within one family in the Chinese population. Rhnull is a rare autosomal recessive disorder characterized by the absence of the Rh ...antigens on the erythrocyte membrane, resulting in chronic hemolytic anemia. This study described the serological and molecular analysis of a Chinese Rhnull proband and his immediate family.
Methods
Red blood cells antigen phenotyping and antibody screening/identification were conducted. RHD, RHCE, and RHAG were analyzed using genomic DNA by polymerase chain reaction and sequence analysis.
Results
Serologic tests showed a D–C–E–c–e– phenotype in the proband associated with the suspicion of anti‐Rh29 (titer 16). Molecular analyses showed a new mutation (c.406dupA) in exon 3 of RHAG. This duplication introduced a reading frameshift (p.Thr136AsnfsTer21). The RHAG mutation was found in the homozygous state for the proband and heterozygous state for his parents.
Conclusion
We identified a novel RHAG mutation resulting in the Rhnull phenotype of the regulator type. Inheritance of the novel allele was shown by family study.
Abstract
Background
The Chinese government implemented the first round of National Centralized Drug Procurement (NCDP) pilot (so-called “4 + 7” policy) in mainland China in 2019. This study aims to ...examine the impact of “4 + 7” policy on the price of policy-related drugs.
Methods
This study used drug purchasing order data from the Centralized Drug Procurement Survey in Shenzhen 2019, covering 24 months from January 2018 to December 2019. “4 + 7” policy-related drugs were selected as study samples, including 25 drugs in the “4 + 7” procurement list and 57 alternative drugs that have an alternative relationship with “4 + 7” List drugs in clinical use. “4 + 7” List drugs were then divided into bid-winning and bid-non-winning products according to the bidding results. Single-group Interruption Time Series (ITS) analysis was adopted to examine the change of Drug Price Index (DPI) for policy-related drugs.
Results
The ITS analysis showed that the DPI of winning (− 0.183 per month,
p
< 0.0001) and non-winning (− 0.034 per month,
p
= 0.046) products significantly decreased after the implementation of “4 + 7” policy. No significant difference was found for the immediate change of DPI for alternative drugs (
p
= 0.537), while a significant decrease in change trend was detected in the post-“4 + 7” policy period (− 0.003 per month,
p
= 0.014). The DPI of the overall policy-related drugs significantly decreased (− 0.261 per month,
p
< 0.0001) after “4 + 7” policy.
Conclusions
These findings indicate that the price behavior of pharmaceutical enterprises changed under NCDP policy, while the price linkage effect is still limited. It is necessary to further expand the scope of centralized purchased drugs and strengthen the monitoring of related drugs regarding price change and consumption structure.
The huge prognostic difference between early and late stage hepatocellular carcinoma (HCC) is a challenging diagnostic problem. Alpha-fetoprotein is the mostly widely used biomarker for HCC used in ...the clinic, however it's sensitivity and specificity of is not optimal. The development and application of multiple biotechnologies, including next generation sequencing, multiple "omics" data, that include genomics, epigenomics, transcriptomics, proteomics, metabolomics, metagenomics has been used for HCC diagnostic biomarker screening. Effective biomarkers/panels/models have been identified and validated at different clinical levels. A large proportion of these have a good diagnostic performance for HCC, especially for early HCC. In this article, we reviewed the various HCC biomarkers derived from "omics" data and discussed the advantages and disadvantages for diagnosis HCC.
As a type of zero-determinant strategies, the extortion strategy was found to be an evolutionarily stable strategy in structural groups. However, instead of complex networks structure, this paper ...focus on a multi-group game in hypernetworks, using the framework of a gift giving game driven by replicator-like dynamics. We find that the extortion is evolutionarily stable in the hypernetwork structure. The extortion game in hypernetworks can promote the emergence of the cooperative behavior compared to the traditional dual-strategy game and the extortion game in complex networks. The results show that the cooperation behavior attracts most of the groups for the smaller benefit value. With the increase of benefit value, cooperators turn into defectors and extortioners, but cooperation behavior still survives in hypernetworks under extreme conditions. Moreover, small-scale groups are more conducive to cooperation.
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