APS exhibited in vitro and in vivo anti-tumor activity targeted macrophages and host immune system via immunoregulation.
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•APS was non-cytotoxic against 4T1 cells.•APS mediated ...macrophages inhibited the growth of 4T1 cells.•APS mediated macrophages induced cell apoptosis by mitochondrial pathway.•APS exhibited in vivo anti-tumor activity by immunoregulation.•APS alleviated immunosuppression of 5-FU on immune system.
Astragalus polysaccharide (APS) has attracted growing interests in the field of anti-cancer by direct killing effect and improving immune function. In this study, the structure and composition of APS was determined, following the evaluation of in vitro and in vivo anti-tumor activity of APS targeted macrophages and host immune system based on immunoregulated strategy. The results indicated that APS had no direct cytotoxicity against 4T1 cells, but APS mediated macrophages could significantly inhibit the growth of 4T1 cells by the induction of cell cycle arrest (G2 phase) and cell apoptosis. APS mediated macrophages promoted the apoptosis of 4T1 cells mainly through the mitochondrial apoptosis pathway. The in vivo findings demonstrated that APS could markedly improve the thymus index and spleen index, and restore the structure of the damaged thymus and spleen tissue. APS could significantly enhance the proliferation of spleen lymphocytes and increase phagocytosis of peritoneal macrophages in mice. Furthermore, APS was capable of up-regulating the expression of IL-2, TNF-α and IFN-γ in peripheral blood. APS combined with 5-FU could improve the anti-tumor effect accompanied by the immunosuppressive alleviation of 5-FU on immune system, which may be suitable as an immune adjuvant for chemotherapy.
Phytosterols and Dementia Shuang, Rong; Rui, Xu; Wenfang, Li
Plant foods for human nutrition (Dordrecht),
12/2016, Letnik:
71, Številka:
4
Journal Article
Recenzirano
As the aging of the world’s population is becoming increasingly serious, dementia-related diseases have become a hot topic in public health research. In recent years, human epidemiological studies ...have focused on lipid metabolism disorders and dementia. The efficacy of phytosterol intake as a cholesterol-lowering agent has been demonstrated. Phytosterols directly serve as ligands of the nuclear receptors, peroxisome proliferator-activated receptors (PPARs), activating Sirtuin 1 (SIRT-1), which are involved in the regulation of lipid metabolism and the
pathogenesis
of dementia. Moreover, phytosterols mediate cell and membrane cholesterol efflux or beta amyloid (Aβ) metabolism, which have preventative and therapeutic effects on dementia. Additionally, incorporation of plant sterols in lipid rafts can effectively reduce dietary fat and alter the dietary composition of fiber, fat and cholesterol to regulate appetite and calories. Overall, the objectives of this review are to explore whether phytosterols are a potentially effective target for the prevention of dementia and to discuss a possible molecular mechanism by which phytosterols play a role in the pathogenesis of dementia via the PPARs-SIRT-1 pathway.
Inserting modification layers at the diamond/Al interface is an effective technique in improving the interfacial thermal conductance (ITC) of the composite. However, few study reports the effect of ...interfacial structure on the thermal conductivity (TC) of diamond/Al composites at room temperature. Herein, the scattering-mediated acoustic mismatch model, suitable for evaluating the ITC at room temperature, is utilized to predict the TC performance of the diamond/Al composite. According to the practical microstructure of the composites, the reaction products at diamond/Al interface on the TC performance are concerned. Results indicate that the TC of the diamond/Al composite is dominantly affected by the thickness, the Debye temperature and the TC of the interfacial phase, meeting with multiple documented results. This work provides a method to assess the interfacial structure on the TC performance of metal matrix composite at room temperature.
Neurogenic differentiation factor 1 (NeuroD1) is a transcription factor critical for promoting neuronal differentiation and maturation. NeuroD1 is involved in neuroblastoma and medulloblastoma; ...however, its molecular mechanism in promoting tumorigenesis remains unclear. Furthermore, the role of NeuroD1 in non–neural malignancies has not been widely characterized. Here, we found that NeuroD1 is highly expressed in colorectal cancer. NeuroD1‐silencing induces the expression of p21, a master regulator of the cell cycle, leading to G2‐M phase arrest and suppression of colorectal cancer cell proliferation as well as colony formation potential. Moreover, NeuroD1‐mediated regulation of p21 expression occurs in a p53‐dependent manner. Through chromatin immunoprecipitation and point mutation analysis in the predicted NeuroD1 binding site of the p53 promoter, we found that NeuroD1 directly binds to the p53 promoter and suppresses its transcription, resulting in increased p53 expression in NeuroD1‐silenced colorectal cancer cells. Finally, xenograft experiments demonstrated that NeuroD1‐silencing suppresses colorectal cancer cell tumorigenesis potential by modulating p53 expression. These findings reveal NeuroD1 as a novel regulator of the p53/p21 axis, underscoring its importance in promoting non–neural malignancies. Furthermore, this study provides insight into the transcriptional regulation of p53.
In this study, we found that NeuroD1 is a novel negative regulator of tumor suppressor p53 and is highly expressed in colorectal cancer. NeuroD1 binds to p53 promoter and suppresses its transcriptional activity, leading to the inhibition of the p53/p21 axis. NeuroD1‐silencing increases p53 and p21 levels, resulting in an inhibition of colorectal cancer cell proliferation and tumorigenesis potential.
Abstract
Background
Circular RNAs (circRNAs) play a vital role in cancer progression. However, there are still numerous circRNAs that have not been functionally explored. Our study aimed to disclose ...the role of circ-CSNK1G1 in triple-negative breast cancer (TNBC).
Methods
The expression of circ-CSNK1G1, miR-28-5p and lactate dehydrogenase A (LDHA) mRNA was measured by quantitative real-time polymerase chain reaction (qPCR), and the expression of LDHA protein was measured by western blot. Cell proliferation was assessed using MTT assay and colony formation assay. Cell apoptosis was monitored using flow cytometry assay. Cell migration and cell invasion were investigated using transwell assay. Glycolysis progression was assessed according to glucose consumption, lactate production and ATP/ADP ratio. Tumor formation assay in nude mice was conducted to verify the role of circ-CSNK1G1 in vivo. The interplays between miR-28-5p and circ-CSNK1G1 or LDHA were confirmed by dual-luciferase reporter assay.
Results
Circ-CSNK1G1 was upregulated in TNBC tissues and cells. Circ-CSNK1G1 knockdown suppressed cancer cell proliferation, migration, invasion and glycolysis energy metabolism, promoted cell apoptosis in vitro, and blocked tumor growth in vivo. Mechanism analysis showed that circ-CSNK1G1 positively regulated LDHA expression by suppressing miR-28-5p. Rescue experiments presented that circ-CSNK1G1 played functions by targeting miR-28-5p, and miR-28-5p participated in TNBC progression by degrading LDHA.
Conclusion
Circ-CSNK1G1 promotes cell proliferation, migration, invasion and glycolysis metabolism during TNBC development by regulating the miR-28-5p/LDHA pathway.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Astragalus polysaccharide (APS) has been frequently used as an adjuvant agent responsible for its immunoregulatory activity to enhance efficacy and reduce toxicity of chemotherapy used in the ...management of breast cancer. However, the other synergism mechanism of APS remains unclear. This study was performed to evaluate the potential targets and possible mechanism behind APS in vivo direct anti-tumor activity on breast cancer. Multiple biological detections were conducted to investigate the protein and mRNA expression levels of key targets. In total, 116 down-regulated and 73 up-regulated differential expressed genes (DEGs) were examined from 7 gene expression datasets. Top ten hub genes were obtained in four typical protein–protein interaction (PPI) network of DEGs involved in each specific biological process (BP, cell cycle, cell proliferation, cell apoptosis and death) that was related to inhibitory activity of APS in vitro against breast cancer cell lines. Four common DEGs (EGFR, ANXA1, KIF14 and IGF1) were further identified in the above four BP-PPI networks, among which EGFR and ANXA1 were the hub genes that were potentially linked to the progression of breast cancer. The results of biological detections indicated that the expression of EGFR in breast cancer cells was down-regulated, while the expression of ANXA1 was markedly increased in response to APS. In conclusion, the present study may provide potential molecular therapeutic targets and a new insight into the mechanism of APS against breast cancer.
Graphic abstract
The skin plays an important role in protecting the human body, and wound healing must be set in motion immediately following injury or trauma to restore the normal structure and function of skin. The ...extracellular matrix component of the skin mainly consists of collagen, glycosaminoglycan (GAG), elastin and hyaluronic acid (HA). Recently, natural collagen, polysaccharide and their derivatives such as collagen, gelatin, alginate, chitosan and pectin have been selected as the matrix materials of bioink to construct a functional artificial skin due to their biocompatible and biodegradable properties by 3D bioprinting, which is a revolutionary technology with the potential to transform both research and medical therapeutics. In this review, we outline the current skin bioprinting technologies and the bioink components for skin bioprinting. We also summarize the bioink products practiced in research recently and current challenges to guide future research to develop in a promising direction. While there are challenges regarding currently available skin bioprinting, addressing these issues will facilitate the rapid advancement of 3D skin bioprinting and its ability to mimic the native anatomy and physiology of skin and surrounding tissues in the future.
Phyllodes tumors (PTs), which account for less than 1% of mammary gland tumors, composed of both epithelial and stromal components. If a malignant heterologous component is encountered, PT is ...considered malignant. Malignant phyllodes tumors (MPTs) only account for 8% to 20% of PTs. We report a case of MPT with osteosarcoma and chondrosarcoma differentiation and review the literature to discuss the differential diagnosis and therapy.
A 59-year-old Chinese woman come to our hospital because of a palpable mass she had had for 1 months in the left breast. Preoperative core needle biopsy (CNB) was performed on the left breast mass on January 11, 2023. Pathological diagnosis was malignant tumor, the specific type was not clear. Mastectomy and sentinel lymph node biopsy of the left breast was performed. No metastasis was found in 3 sentinel lymph nodes identified by carbon nanoparticles and methylene blue double staining. Heterologous osteosarcoma and chondrosarcomatous differentiation of phyllodes tumor were observed. Immunohistochemistry: spindle tumor cells ER(-), PR(-), HER-2(-), CK-pan(-), CK7(-), CK8(-), SOX10(-), S100(-), and MDM2(-), CK5/6(-), P63(-), P40(-) were all negative. CD34:(+), SATB2(+), P53(90% strong), CD68 (+), Ki-67(LI: about 60%). No ductal carcinoma
was found in the breast. Fluorescence
hybridization (FISH) indicated USP6 was negatively expressed on formalin-fixed, paraffin-embedded (FFPE) tissue sections.
MPTs are rare, and heterologous differentiation in MPTs is exceedingly rare. It could be diagnosed by pathology when metaplastic carcinoma, primary osteosarcoma, or myositis ossificans were excluded. This case could help clinicians to improve the prognosis and treatment of this disease.
In addition to its surface glycoprotein (GP(1,2)), Ebola virus (EBOV) directs the production of large quantities of a truncated glycoprotein isoform (sGP) that is secreted into the extracellular ...space. The generation of secreted antigens has been studied in several viruses and suggested as a mechanism of host immune evasion through absorption of antibodies and interference with antibody-mediated clearance. However such a role has not been conclusively determined for the Ebola virus sGP. In this study, we immunized mice with DNA constructs expressing GP(1,2) and/or sGP, and demonstrate that sGP can efficiently compete for anti-GP(12) antibodies, but only from mice that have been immunized by sGP. We term this phenomenon "antigenic subversion", and propose a model whereby sGP redirects the host antibody response to focus on epitopes which it shares with membrane-bound GP(1,2), thereby allowing it to absorb anti-GP(1,2) antibodies. Unexpectedly, we found that sGP can also subvert a previously immunized host's anti-GP(1,2) response resulting in strong cross-reactivity with sGP. This finding is particularly relevant to EBOV vaccinology since it underscores the importance of eliciting robust immunity that is sufficient to rapidly clear an infection before antigenic subversion can occur. Antigenic subversion represents a novel virus escape strategy that likely helps EBOV evade host immunity, and may represent an important obstacle to EBOV vaccine design.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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