Accurate diagnosis and staging are crucial for selecting treatment for patients with pancreatic ductal adenocarcinoma (PDAC). The desmoplastic responses associated with PDAC are often characterized ...by hypometabolism. Here, we investigated
F-fibroblast activation protein inhibitor (FAPI)-04 PET/CT in evaluation of PDAC and compared the findings with those obtained using
F-FDG.
Sixty-two PDAC patients underwent
F-FAPI-04 PET/CT and
F-FDG PET/CT. Identification of primary lesions, lymph node (LN) metastasis, and distant metastasis (DM) by these methods was evaluated, and TNM staging was performed. Correlation between SUV
of the primary lesion and treatment response was explored in patients who received systemic therapy.
F-FAPI-04 PET/CT identified all patients with PDAC;
F-FDG PET/CT missed 1 patient. Tracer uptake was higher in
F-FAPI-04 PET/CT than in
F-FDG PET/CT in primary tumors (10.63 vs. 2.87,
< 0.0001), LN metastasis (2.90 vs. 1.43,
< 0.0001), and DM (liver, 6.11 vs. 3.10,
= 0.002; peritoneal, 4.70 vs. 2.08,
= 0.015). The methods showed no significant difference in the T staging category, but the N and M values were significantly higher for
F-FAPI-04 PET/CT than for
F-FDG PET/CT (
= 0.002 and 0.008, respectively). Thus, 14 patients were upgraded, and only 1 patient was downgraded, by
F-FAPI-04 PET/CT compared with
F-FDG PET/CT. A high SUV
of the primary tumor did not correlate with treatment response for either
F-FAPI-04 or
F-FDG.
F-FAPI-04 PET/CT performed better than
F-FDG PET/CT in identification of primary tumors, LN metastasis, and DM and in TNM staging of PDAC.
MiR-21 is known to play an important role in the development and progression, including migration and invasion, of many malignancies including breast cancer. Accumulating evidence suggest that the ...induction of epithelial–mesenchymal transition (EMT) phenotype and acquisition of cancer stem cell (CSC) characteristics are highly interrelated, and contribute to tumorigenesis, tumor progression, metastasis, and relapse. The molecular mechanisms underlying EMT and CSC characteristics during miR-21 contributes to cell migration and invasion of breast cancer are poorly understood. Therefore, we established miR-21 re-expressing breast cancer MCF-7 (MCF-7/miR-21) cells, which showed increasing cell growth, migration and invasion, self-renewal and clonogenicity. Our data showed that re-expression of miR-21 induced the acquisition of EMT phenotype by activation of mesenchymal cell markers (N-cadherin, Vimentin, α-SMA) and inhibition of epithelial cell marker (E-cadherin) in MCF-7/miR-21 cells, which consistent with increased cell subpopulation expressing CSC surface markers (ALDH1
+
and CD44
+
/CD24
−/low
) and the capacity of sphereforming (mammospheres). Our results demonstrated that re-expression of miR-21 is responsible for migration and invasion by activating the EMT process and enhancing the characteristics of CSCs in MCF-7 cells.
Triple-negative breast cancer (TNBC) is an aggressive breast cancer with a generally poor prognosis. Due to lack of specific targets for its treatment, an efficient therapy is needed. G ...protein-coupled estrogen receptor (GPER), a novel estrogen receptor, has been reported to be expressed in TNBC tissues. In this study, we investigated the effects of blocking non-genomic signaling mediated by the estrogen/GPER pathway on cell viability and motility in the TNBC cells. GPER was strongly expressed in the TNBC cell lines MDA-MB-468 and MDA-MB-436, and the estrogen-mediated non-genomic ERK signaling activated by GPER was involved in cell viability and motility of TNBC cells. Treatment with 17β-estradiol (E2), the GPER-specific agonist G-1 and tamoxifen (TAM) led to rapid activation of p-ERK1/2, but not p-Akt. Moreover, estrogen/GPER/ERK signaling was involved in increasing cell growth, survival, and migration/invasion by upregulating expression of cyclinA, cyclinD1, Bcl-2, and c-fos associated with the cell cycle, proliferation, and apoptosis. Immunohistochemical analysis of TNBC specimens showed a significantly different staining of p-ERK1/2 between GPER-positive tissues (58/66, 87.9%) and GPER-negative tissues (13/30, 43.3%). The positivity of GPER and p-ERK1/2 displayed a strong association with large tumor size and poor clinical stage, indicating that GPER/ERK signaling might also contribute to tumor progression in TNBC patients which corresponded with in vitro experimental data. Our findings suggest that inhibition of estrogen/GPER/ERK signaling represents a novel targeted therapy in TNBC.
A novel pH-sensitive and macroporous NaAlg-based hydrogels were prepared, the monomers of which were
N
-methylolacrylamide (NMAAm) and acrylic acid, using
N
,
N
-methylene-bis-acrylamide (MBA) as a ...cross-linker, 2,2-dimethoxy-2-phenylacetophenone as a photoinitiator via ultraviolet irradiation. The morphology, thermal property and structure of hydrogel were characterized by Fourier transform infrared spectroscopy, scanning electron microscope, X-ray diffractometer and thermogravimetric analysis. The swelling ratios (SRs) of hydrogel were investigated in water, salt and pH solutions. The SR of hydrogel in water increased from 8.1 to 19.4 g/g with increase in weight of NaAlg from 0.2 to 1.0. The result indicated that hydrogel displayed favorable pH- and salt-sensitive. 5-fluorouracil (5-FU) as a model drug was loaded on hydrogel, the drug encapsulation efficiency of products reached to 85.2%, and the cumulative release rate of drug was 78.4 and 37% in the intestinal and gastric fluid, respectively. In addition, the dynamic data of drug release were evaluated by different mathematical models, and the experimental results revealed that it was more fitted to Ritger–Peppas and Higuchi equation models, correlation coefficients (
R
2
) of which were up to 0.99.
The aim of this study was to evaluate the association of p73 G4C14-A4T14 polymorphisms with susceptibility to breast cancer in Chongqing women of Han Nationality in China. In a case–control study, ...single-nucleotide polymorphisms of p73 G4C14-A4T14 at exon 2 were genotyped by Sequenom MassArray
®
iPLEX GOLD System in 170 patients with breast cancer and 178 healthy controls. Data were analyzed via
t
test, Chi-square test, and logistic regression analysis. The distribution of p73 genotypes and allelotypes had no significant difference between patients with breast cancer and healthy controls (χ
2
= 2.750,
P
= 0.253; χ
2
= 2.195,
P
= 0.138). More risk of developing triple negative breast cancer (TNBC) was found in the individuals who carried with GC/GC genotype than individuals carried with GC/AT and AT/AT genotypes (OR = 2.99; 95 % CI, 1.30–6.89;
P
= 0.010). p73 G4C14-A4T14 polymorphisms are closely associated with the increased risk for TNBC in Chongqing women of Han Nationality in China; GC/GC genotype is susceptible genotype for TNBC in Chongqing women of Han Nationality in China. The patients with breast cancer who carried with GC/GC genotype may have bad prognosis. Additional larger studies are required to confirm these findings.
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•ACPs are absent in vertebrates and most arthropods.•ACPs are undergoing rapid turnover and diversification, hence no orthologs between phyla.•ApeC is a promiscuous domain, and domain ...pairs like ApeC-ApeC and MACPF-ApeC are prevalent, suggesting conserved functions.•ApeC-like domains were found in bacteria, suggesting the origin of the domain.•ACPs seems most prevalent in invertebrates from aquatic or moist environments.
Apextrin C-terminal (ApeC) is a novel protein domain with unknown functions, although early studies suggest that some ApeC-containing proteins (ACPs) bind to carbohydrates and have a role in development and immunity. Here we investigated the taxonomic distribution, sequence diversification and origin of ACPs in Metazoa.
Most ACPs are present in invertebrates from aquatic or moist environments, including cnidarians, mollusks, echinoderms, cephalochordates, flatworms, water bears, nematodes and annelids. However, ACPs are absent in vertebrates and in most arthropod lineages (e.g. insects and crustaceans) except arachnids. ACPs apparently undergo rapid turnover and diversification, hence no orthologs could be found between (sub)phyla. ApeC can function either as a standalone domain or as a partner domain. It has been found to pair up with over ten different domain types in different ACPs. The partner domains are related to immunity, extracellular matrix, protein-protein and protein-carbohydrate interactions. Notably, the domain pair with the widest taxonomic distribution is MACPF/perforin-ApeC, which represent a classic group of ACPs called apextrins. ApeC also frequently pairs up with itself to form dual-ApeC modules in different phyla. Notably, in parasite flatworms, dual-ApeCs are present in 70% of ACPs and all inherited from a common ancestor. The broad distribution of MACPF-ApeC and dual-ApeC suggest their conserved yet unknown functions. We also discovered distant ApeC homologs in bacteria, hence tracing the origin of ApeC back to prokaryotes.
Our findings show that ApeC has an ancient origin and is able to function alone or in complex domain architectures, though it is less prevalent than other versatile domains such as immunoglobulin domains and C-type lectin domains. This work provides a foundation for further functional study of this novel domain type.
In this manuscript, the novel sodium alginate-
g
-poly acrylic acid–
N
-(3-dimethylaminopropyl) methyl acrylamide NaAlg-
g
-P(AA-
co
-DMAPMA) hydrogel was prepared using free radical polymerization. ...Fourier transform infrared spectroscopy (FT-IR), thermogravimetry (TG), point zero charge and scanning electron microscopy were used to investigate the structure, thermal stability, surface charge and microstructure of the hydrogel. The factors that affected the swelling ratio of the hydrogel were investigated in detail, such as pH and ionic strength; the results showed that the hydrogel has a favorable pH-sensitive property. To investigate drug loading and sustained release of NaAlg-
g
-P(AA-
co
-DMAPMA), rhodamine B as a model drug was loaded on NaAlg-
g
-P(AA-
co
-DMAPMA). The in vitro drug release study conducted at pH 1.86 and 6.86 shows that NaAlg-
g
-P(AA-
co
-DMAPMA) was suitable for colon-specific drug delivery systems.
The chitin‐based peritrophic matrix (PM) is a structure critical for both gut immunity and digestion in invertebrates. PM was traditionally considered lost in all vertebrates, but a PM‐like chitinous ...membrane (CM) has recently been discovered in fishes, which may increase the knowledge on vertebrate gut physiology and structural evolution. Here, we show that in zebrafish, the CM affects ingestion behavior, microbial homeostasis, epithelial renewal, digestion, growth, and longevity. Young mutant fish without CM appear healthy and are able to complete their life cycle normally, but with increasing age they develop gut inflammation, resulting in gut atrophy. Unlike mammals, zebrafish have no visible gel‐forming mucin layers to protect their gut epithelia, but at least in young fish, the CM is not a prerequisite for the antibacterial gut immunity. These findings provide new insights into the role of the CM in fish prosperity and its eventual loss in tetrapods. These findings may also help to improve fish health and conservation, as well as to advance the understanding of vertebrate gut physiology and human intestinal diseases.
Synopsis
The chitinous membrane (CM) is an essential gut structure in invertebrates that was considered lost in vertebrates, but was recently discovered in fish. This study shows that it has differential roles in zebrafish digestion and gut immunity.
The presence of the CM affects ingestive behavior, gut homeostasis, microbiota, digestion, growth, and longevity.
The CM is not a prerequisite for fish survival, reproduction, and gut immunity against bacteria.
CM absence results in age‐dependent gut inflammation and atrophy.
The CM has an important role in fish health, conservation, prosperity, and diversity.
The chitinous membrane (CM) is an essential gut structure in invertebrates that was considered lost in vertebrates, but was recently discovered in fish. This study shows that it has differential roles in zebrafish digestion and gut immunity.
Excessive use of chemical fertilizers and their loss have resulted in low utilization efficiency of nutrient and the heavy metal pollution of soil. To solve these problems, the multifunctional ...fertilizer (nZVI@MOF-g-DCUF) was prepared and characterized, using nanoscale zero-valent iron-doped MOF(Mg)-74 (nZVI@MOF) as the core and a dialdehyde carboxymethylcellulose urea-formaldehyde (DCUF) as the coating. The addition of nZVI@MOF-g-DCUF improved the water retention capacity of the soil. The cumulative release ratios (Cr%) of nZVI@MOF-g-DCUF2.0, nZVI@MOF-g-DCUF1.0, nZVI@MOF-g-DCUF0.5, and nZVI@MOF-g-DCUF0.25 in soil were respectively 96.72 %, 93.68 %, 90.67 %, and 82.75 % at the 35th day, which confirmed the long-term release of nZVI@MOF-g-DCUF. In subsequent pot experiments, nZVI@MOF-g-DCUF exhibited a positive effect on the growth of Chinese cabbage. The results of soil remediation showed that the Cr(VI) removal ratio of soil with adding 1 % (wt%) of nZVI@MOF-g-DCUF2.0 and nZVI@MOF-g-DCUF1.0 were 84.40 % and 76.83 %, respectively, indicating a significant remediation effect on Cr-polluted soil. The mechanism of soil remediation indicated that the Cr(VI) immobilization on nZVI@MOF-g-DCUF via H-bonding, reduction, precipitation, and complexation. Therefore, the proposed materials are promising fertilizers for the long-term release of nutrients and immobilization of Cr(VI) in polluted soil.
A novel multifunctional fertilizer (nZVI@MOF-g-DCUF) was prepared using nZVI@MOF as core and DCMC-Urea formaldehyde(DCUF) as coating. It exhibited excellent long-time release for nutrient and Cr(VI) immobilization in soil.
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