Purpose: We aimed to investigate the effects of adiponectin on liver cancer growth and metastasis and explore the underlying mechanisms.
Experimental Design: An orthotopic liver tumor nude mice model ...with distant metastatic potential was applied. Either Ad-adiponectin (1 × 10 8 ; treatment group) or Ad-luciferase (control group) was injected via portal vein after tumor implantation. Tumor growth and
metastasis were monitored by Xenogen In vivo Imaging System. Hepatic stellate cell activation by α-smooth muscle actin staining, microvessel density by CD34 staining,
macrophage infiltration in tumor tissue, and cell signaling leading to invasion, migration Rho kinase (ROCK), IFN-inducible
protein 10 (IP10), and matrix metalloproteinase 9, and angiogenesis vascular endothelial growth factor (VEGF) and angiopoietin
1 were also compared. Tumor-nontumor margin was examined under electron microscopy. Direct effects of adiponectin on liver
cancer cells and endothelial cells were further investigated by a series of functional studies.
Results: Tumor growth was significantly inhibited by adiponectin treatment, accompanied by a lower incidence of lung metastasis. Hepatic
stellate cell activation and macrophage infiltration in the liver tumors were suppressed by adiponectin treatment, along with
decreased microvessel density. The treatment group had less Ki-67–positive tumor cells and downregulated protein expression
of ROCK1, proline-rich tyrosine kinase 2, and VEGF. Tumor vascular endothelial cell damage was found in the treatment group
under electron microscopy. In vitro functional study showed that adiponectin not only downregulated the ROCK/IP10/VEGF signaling pathway but also inhibited the
formation of lamellipodia, which contribute to cell migration.
Conclusion: Adiponectin treatment significantly inhibited liver tumor growth and metastasis by suppression of tumor angiogenesis and
downregulation of the ROCK/IP10/matrix metalloproteinase 9 pathway. Clin Cancer Res; 16(3); 967–77
Due to the wide variety of morphology, size, and dynamics, selecting an optimal valve size and location poses great difficulty in percutaneous pulmonary valve implantation (PPVI). This study aimed to ...report our experience with in vitro bench testing using patient-specific three-dimensional (3D)-printed models for planning PPVI with the Venus P-valve.
Patient-specific 3D soft models were generated using PolyJet printing with a compliant synthetic material in 15 patients scheduled to undergo PPVI between July 2018 and July 2020 in Central China Fuwai Hospital of Zhengzhou University.
3D model bench testing altered treatment strategy in all patients (100%). One patient was referred for surgery because testing revealed that even the largest Venus P-valve would not anchor properly. In the remaining 14 patients, valve size and/or implantation location was altered to avoid valve migration and/or compression coronary artery. In four patients, it was decided to change the point anchoring because of inverted cone-shaped right ventricular outflow tract (RVOT) ( n = 2) or risk of compression coronary artery ( n = 2). Concerning sizing, we found that an oversize of 2-5 mm suffices. Anchoring of the valve was dictated by the flaring of the in- and outflow portion in the pulmonary artery. PPVI was successful in all 14 patients (absence of valve migration, no coronary compression, and none-to-mild residual pulmonary regurgitation PR). The diameter of the Venus P-valve in the 3D simulation group was significantly smaller than that of the conventional planning group (36 2 vs. 32 4, Z = -3.77, P <0.001).
In vitro testing indicated no need to oversize the Venus P-valve to the degree recommended by the balloon-sizing technique, as 2-5 mm sufficed.
This study was conducted to investigate the effects of Lonicera flos and Cnicus japonicus extracts (LCE) on the laying performance, egg quality, morphology, antioxidant status, inflammatory-related ...cytokines, and shell matrix protein expression of oviduct in laying hens. A total of 1,728 Roman Pink laying hens aged 73-wk-old were randomly assigned into 4 groups (18 replicates/group, 24 layers/replicate) fed basal diets supplemented with 0, 300, 500, and 1,000 mg of LCE per kg of diet, respectively. The trial lasted for 11 wk, including 2-wk adjustment period and 9-wk testing period. The results indicated that laying hens fed diets supplemented with LCE linearly increased egg weight, yolk color and shell thickness at wk 78 and albumen height, Haugh unit and shell thickness at wk 83 (P < 0.05). At wk 78, LCE groups linearly affected the hydrogen peroxide content in magnum (P < 0.05) and 300 mg/kg LCE groups had the highest catalase activity in isthmus (P < 0.05). At wk 83, LCE groups linearly reduced (P < 0.05) hydrogen peroxide content in the magnum and isthmus and malondialdehyde content in the uterus whereas increased catalase activity in isthmus (P < 0.05). Furthermore, LCE levels quadratically affected glutathione peroxidase activity in isthmus at wk 83 (P < 0.05). At wk 78, the mRNA expressions of inducible nitric oxide synthase and interferon-γ in isthmus and ovalbumin and ovocleidin-116 in uterus had linear effects in response to LCE levels (P < 0.05) and 1,000 mg/kg LCE group had the lowest mRNA expression of interleukin-6 in magnum (P < 0.05). At wk 83, LCE supplementation linearly decreased the mRNA expression of interleukin-1β, interferon-γ and tumor necrosis factor-α in magnum and tumor necrosis factor-α and inducible nitric oxide synthase in uterus (P < 0.05). It is concluded that LCE improved egg quality partly by modulating antioxidant status, inflammatory-related cytokines and shell matrix protein expression of oviduct in laying hens.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We investigated the mutational landscape of mammalian target of rapamycin (mTOR) signalling cascade in hepatocellular carcinomas (HCCs) with chronic HBV background, aiming to evaluate and delineate ...mutation-dependent mechanism of mTOR hyperactivation in hepatocarcinogenesis.
We performed next-generation sequencing on human HCC samples and cell line panel. Systematic mutational screening of mTOR pathway-related genes was undertaken and mutant genes were evaluated based on their recurrence. Protein expressions of tuberous sclerosis complex (TSC)1, TSC2 and pRPS6 were assessed by immunohistochemistry in human HCC samples. Rapamycin sensitivity was estimated by colony-formation assay in HCC cell lines and the treatment was further tested using our patient-derived tumour xenograft (PDTX) models.
We identified and confirmed multiple mTOR components as recurrently mutated in HBV-associated HCCs. Of significance, we detected frequent (16.2%, n=18/111) mutations of
and
genes in the HCC samples. The spectrum of
mutations likely disrupts the endogenous gene functions in suppressing the downstream mTOR activity through different mechanisms and leads to more aggressive tumour behaviour. Mutational disruption of
and
was also observed in HCC cell lines and our PDTX models.
-mutant cells exhibited reduced colony-forming ability on rapamycin treatment. With the use of biologically relevant
-mutant PDTXs, we demonstrated the therapeutic benefits of the hypersensitivity towards rapamycin treatment.
Taken together, our findings suggest the significance of previously undocumented mutation-dependent mTOR hyperactivation and frequent
mutations in HBV-associated HCCs. They define a molecular subset of HCC having genetic aberrations in mTOR signalling, with potential significance of effective specific drug therapy.
This review focuses on the fabrication and mechanical characterization of fibrous composites for engineering applications. Fibrous composites are materials composed of two or more distinct phases, ...with fibers embedded in a matrix. The properties of these materials depend on the properties of both the fibers and the matrix, as well as the way they are combined and fabricated. The various fabrication methods, along with the process parameters, used to manufacture synthetic and natural fibrous composites for engineering applications, including hand lay-up, compression molding, resin transfer molding, additive manufacturing, etc., are discussed. The mechanical characterization of fibrous composites, including their strength, stiffness, and toughness of both synthetic and natural fibrous composites are discussed. The advantages and disadvantages of fiber reinforcement are discussed, along with their influence on the resulting mechanical characteristics of the composites. It can be observed that the mechanical properties of fibrous composites can be tailored by controlling various factors, such as the fiber orientation, fiber volume fraction, and matrix type. Although fibrous composites offer significant advantages, several challenges hinder their widespread use in engineering applications. These challenges include high manufacturing costs, limited design guidelines, and difficulties in predicting their mechanical behavior under various loading conditions. Therefore, despite their unique properties, these challenges must be overcome for fibrous composites to realize their full potential as high-performance materials.
Long interspersed element-1 (L1) is an autonomous retroelement that is active in the human genome. The proposed mechanism of insertion for L1 suggests that cleavage of both strands of genomic DNA is ...required. We demonstrate that L1 expression leads to a high level of double-strand break (DSB) formation in DNA using immunolocalization of γ-H2AX foci and the COMET assay. Similar to its role in mediating DSB repair in response to radiation, ATM is required for L1-induced γ-H2AX foci and for L1 retrotransposition. This is the first characterization of a DNA repair response from expression of a non-long terminal repeat (non-LTR) retrotransposon in mammalian cells as well as the first demonstration that a host DNA repair gene is required for successful integration. Notably, the number of L1-induced DSBs is greater than the predicted numbers of successful insertions, suggesting a significant degree of inefficiency during the integration process. This result suggests that the endonuclease activity of endogenously expressed L1 elements could contribute to DSB formation in germ-line and somatic tissues.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Gold nanoshell’s high light scattering and absorption at its resonance wavelength have found applications in biomedical imaging and photothermal therapy. However, at nanoscale, metallic material’s ...dielectric function is affected by nanoparticle’s size, mainly via a mechanism called surface scattering of conduction electrons. In this work, the effect of surface scattering of electrons on the ratios of optical absorption and scattering to extinction (which is the sum of the absorption and scattering) of gold nanoshell is investigated. Simulation results for several shell thicknesses are compared. It is found that the electrons’ surface scattering increases the optical absorption ratio, and the thinner the shell thickness, the larger the increase in the difference of the absorption ratio between the situations with and without the surface scattering considered. The increase of absorption ratio is then verified by comparing simulation results to experimental measurements for three nanoshells. The parameters of the simulations to fit the experimental measurements show that the damping of conduction electrons in metallic shell geometry is larger than that predicted by the billiard scattering model.
Mica, a commonly occurring mineral, has significant potential for various applications due to its unique structure and properties. However, due to its non-Van Der Waals bonded structure, it is ...difficult to exfoliate mica into ultrathin nanosheets. In this work, we report a rapid solvothermal microwave synthesis of 2D mica with short reaction time and energy conservation. The resulting exfoliated 2D mica nanosheets (eMica nanosheets) were characterized by various techniques, and their ability to capture CO2 was tested by thermogravimetric analysis (TGA). Our results showed an 87% increase in CO2 adsorption capacity with eMica nanosheets compared to conventional mica. Further characterization by Fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS), as well as first-principles calculations, showed that the high specific surface area and deposited K2CO3 layer contribute to the increased CO2 adsorption on the mica nanosheets. These results speak to the potential of high-quality eMica nanosheets and efficient synthesis processes to open new avenues for new physical properties of 2D materials and the development of CO2 capture technologies.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
This study was conducted to simulate salpingitis of laying hens by observing the morphology and expression of inflammatory genes in the oviduct. A total of one hundred twenty 81-wk-old Roman Pink ...laying hens in good physical condition without the oviduct disease with an average egg production rate of 76% were fed a basal diet for 2 wks and then randomly allocated into 4 groups (6 replicates/group, 5 birds/replicate). The experimental treatments were as follows: 1) Control group (treated with PBS); 2) Organic chemical reagent (OCR) group; 3) Lipopolysaccharide (LPS) group; 4) LPS + OCR group. First, the chickens were kept upside down to make ectropion and exposure of the apertura uterinae; then prepared reagents were poured into the uterine part of the fallopian tube by using the chicken vas deferens (1 mL/layer); finally, the chickens were kept in the inverted position for 5 to 10 min. The fallopian tube samples (the magnum, isthmus, and uterus) were collected after 48 h of treatment. Compared with the control, treatment with LPS+OCR decreased (P < 0.05) the secondary villus length and primary villus area in magnum and villus length in isthmus (P < 0.05). An increase (P < 0.05) of the intervillous space of uterus was observed in LPS + OCR group compared with the control. The expressions of interleukin-6 mRNA of magnum and interferon-γ (IFN-γ) of isthmus in the LPS and LPS+OCR treatments were higher (P < 0.05) than that in control. Compared with the control, treatment with LPS+OCR increased (P < 0.05) the expressions of IFN-γ mRNA of magnum and IFN-γ, tumor necrosis factor-α and inducible nitric oxide synthase mRNA of uterus in laying hens. In conclusion, the results of morphological damage of fallopian tube tissue and increased expression of inflammatory factors in LPS + OCR treatment group suggested that LPS+OCR treatment can provide data basis to establish salpingitis model in laying hens for studying the pathogenesis of it.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Recent studies raised questions about the severity of cognitive impairment associated with dementia with Lewy bodies (DLB). However, there have been few analyses of large, multicenter data registries ...for clinical-pathologic correlation.
We evaluated data from the National Alzheimer's Coordinating Center registry (n = 5,813 cases meeting initial inclusion criteria) and the University of Kentucky Alzheimer's Disease Center autopsy series (n = 527) to compare quantitatively the severity of cognitive impairment associated with DLB pathology vs Alzheimer disease (AD) and AD+DLB pathologies.
Mini-Mental State Examination (MMSE) scores showed that persons with pure DLB had cognitive impairment of relatively moderate severity (final MMSE score 15.6 +/- 8.7) compared to patients with pure AD and AD+DLB (final MMSE score 10.7 +/- 8.6 and 10.6 +/- 8.6). Persons with pure DLB pathology from both data sets had more years of formal education and were more likely to be male. Differences in final MMSE scores were significant (p < 0.01) between pure DLB and both AD+DLB and pure AD even after correction for education level, gender, and MMSE-death interval. Even in cases with extensive neocortical LBs, the degree of cognitive impairment was most strongly related to the amount of concomitant AD-type neurofibrillary pathology.
Dementia with Lewy bodies can constitute a debilitating disease with associated psychiatric, motoric, and autonomic dysfunction. However, neocortical Lewy bodies are not a substrate for severe global cognitive impairment as assessed by the Mini-Mental State Examination. Instead, neocortical Lewy bodies appear to constitute or reflect an additive disease process, requiring Alzheimer disease or other concomitant brain diseases to induce severe global cognitive deterioration.
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