Search

Immobilizing of attapulgite into phthalocyanine not only enhanced the catalytic efficiency of metal phthalocyanine compound materials but also prevented the aggregation of phthalocyanines. Therefore, a novel isoamoxyphthalocyanine-attapulgite (ZnPc(3-iso-PeO)4-ATP) composites were fabricated by the ultrasonic impregnation menthod. The as-prepared ZnPc(3-iso-PeO)4-ATP composites were characterized by powder X-ray diffraction, Fourier transform infrared spectra, scanning electron microscopy (SEM), transmission electron microscopy, thermogravimetric analysis and UV–Vis diffuse reflectance spectroscopy spectra. The photocatalytic activities of as-obtained photocatalysts were measured by the degradation of malachite green (MG) under visible-light irradiation. The optimal conditions for the degradation of MG were determined with changing kind of catalysts and the ratio of phthalocyanine to attapulgite. In the ZnPc(3-iso-PeO)4-ATP system, it was demonstrated that preventing the aggregation of phthalocyanines was helpful to enhance the photocatalytic property. It was found that the degradation efficiency of MG reached 70% after 50 min when the ratio of ZnPc(3-iso-PeO)4 to ATP was up to 2:1. Furthermore, the possible visible-light photocatalytic mechanism of ZnPc(3-iso-PeO)4-ATP composites for the photodegradation of MG was also discussed. The excellent activity is mainly attributed to its more effective separation of electron–hole pairs. [ABSTRACT FROM AUTHOR]

etylcholinesterase inhibitors played significant roles in treatment of Alzheimer's disease. Based on the research foundation of our previous work and molecular modeling, twelve 3,6-diaryl-7 H-thiazolo[3,2- b][1,2,4]triazin-7-one derivatives were synthesized and characterized by mass spectra, infrared spectra, NMR and elemental analyses. The study of AChE inhibitory activity was carried out using the Ellman colorimetric assay with huperzine-A as the positive control. All target compounds exhibited more than 40% inhibition at 10 μM. Some target compounds showed good inhibition against AChE. The preliminary structure-activity relationships were the halogen atoms at the phenyl ring at the C6 position, the hydroxy groups and the long side chains at the phenyl ring at the C3 position of the parent nucleus played significant roles in the AChE inhibitory activity of the target compounds. [ABSTRACT FROM AUTHOR]

Abstract MiR-155-3p, which is derived from the same pre-miRNA as miR-155-5p, the latter has been reported to be dysregulated in multiple tumor tissues and associated with clinicopathologic markers, tumor subtypes, and poor survival rates. However, the biological effects of miR-155-3p are rarely explored. In this study, we find that miR-155-3p was down-regulated in breast cancer and MYD88 was validated as the target for miR-155-3p. Moreover, miR-155-3p showed a negative effect on apoptosis, invasion and metastasis, reverses paclitaxel resistance by suppression of the corresponding target gene MYD88 in vitro and in vivo experiments. Taking together, our studies suggest that miR-155-3p, which serve as a negative regulatory mechanism for breast cancer development. The mechanism further complicates the regulatory network in human breast cancer. Highlights • miR-155-3p was a novel tumor-suppressor by targeting MYD88. • miR-155-3p showed a negative effect on apoptosis, invasion and metastasis by suppression of the corresponding target gene MYD88 in vitro and vivo. • miR-155-3p/MYD88 has important roles in cancer cell resistance to chemotherapy drugs. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs/miRs) are small, non-coding RNAs that are reported to serve numerous important regulatory functions; however, the role of miRNAs in regulating breast cancer cell biology remains poorly understood. Accumulating evidence has demonstrated that miRNAs orchestrate multiple cellular functions and serve crucial roles in cell differentiation and cancer development, either by acting as tumor suppressors or oncogenes. In particular, miR-155-5p expression levels have been found to be upregulated and serve as a prognostic marker in numerous types of solid cancer, including human breast cancer. More than half of patients with breast cancer benefit from treatment with adjuvant paclitaxel chemotherapy following the early postoperative period. Despite the initial response to intensive combination chemotherapy, the majority of most patients will eventually acquire resistance to the drug and succumb to their disease. Therefore, further investigations into the association between miRNAs and the mechanism of paclitaxel resistance are required. The results of the present study revealed a strong positive association between miR-155-5p expression levels and the paclitaxel resistance, as the expression levels of miR-155-5p were upregulated in resistant cells. MiR‐155-5p was further validated to regulate paclitaxel resistance using gain- and loss‐of‐function experiments. TP53INP1 was identified as a direct target gene of miR-155-5p by combining the results from the prediction algorithm based on free energy minimization and reverse transcription-quantitative PCR (qRT-PCR) analysis. Also, miR-155-5p was suggested to be a key regulator of paclitaxel resistance in tumor cells, as it increased cell viability and motility, and promoted resistance to paclitaxel‐induced apoptosis. The transfection with miR-155-5p inhibitors re-sensitized the paclitaxel-resistant breast cancer cells, while the overexpression of miR-155-5p led to an increase in the resistance to paclitaxel. Furthermore, the overexpression of the target gene, TP53INP1, contributed to the re-sensitivity of drug-resistant cells to paclitaxel. The subsequent combination of the knockdown of miR-155-5p and the overexpression of TP53INP1 conferred paclitaxel sensitivity in resistant cells. These results may enhance the understanding of the molecular mechanisms underlying breast cancer progression and resistance to chemotherapy, and suggested that miR-155-5p or TP53INP1 may serve as novel therapeutic approaches to combat resistance to therapy, as well as the proliferation and evasion of apoptosis in breast cancer. [ABSTRACT FROM AUTHOR]

2'-O-methylation is one of the most prevalent RNA modifications found in different RNA types. However, the identities of enzymes participating in the transfer of methyl groups are not well defined. To date, fibrillarin (FBL) is the only known small nucleolar ribonucleoprotein (snoRNP) 2'-O-methyltransferase. Whether other snoRNP 2'-O-methyltransferases exist and their functions in targeting RNAs to determine cell differentiation and function need to be elucidated. Here, we identify FBL-like protein 1 (FBLL1) as a 2'-O-methyltransferase and find its function in promoting neuronal differentiation. We show that FBLL1 is a key snoRNP complex enzyme that transfers methyl groups to substrate RNAs both in vitro and in vivo. Moreover, FBLL1 exhibits different 2'-O-methyltransferase site selectivity from FBL and tissue-specific distribution. FBLL1 is preferentially expressed in the brain, especially in human neuron cells, and promotes neuronal differentiation through 2'-O-methylation of GAP43 messenger RNA (mRNA). Knockdown of FBLL1, but not FBL, reduced 2'-O-methylation levels in GAP43 mRNA, decreased expression of GAP43 proteins, and eventually repressed neuronal differentiation. Our finding of neuron-specific FBLL1 adds insights into RNA modification in neurobiology and provides clues for understanding 2'-O-methylation in health and disease., Competing Interests: Competing interests statement:The authors declare no competing interest.

Cancer is one of the most difficult diseases to be treated in the world. Immunotherapy has made great strides in cancer treatment in recent years, and several tumor immunotherapy drugs have been approved by the U.S. Food and Drug Administration. Currently, immunotherapy faces many challenges, such as lacking specificity, cytotoxicity, drug resistance, etc. Nanoparticles have the characteristics of small particle size and stable surface function, playing a miraculous effect in anti-tumor treatment. Nanocarriers such as polymeric micelles, liposomes, nanoemulsions, dendrimers, and inorganic nanoparticles have been widely used to overcome deficits in cancer treatments including toxicity, insufficient specificity, and low bioavailability. Although nanomedicine research is extensive, only a few nanomedicines are approved to be used. Either Bottlenecks or solutions of nanomedicine in immunotherapy need to be further explored to cope with challenges. In this review, a brief overview of several types of cancer immunotherapy approaches and their advantages and disadvantages will be provided. Then, the types of nanomedicines, drug delivery strategies, and the progress of applications are introduced. Finally, the application and prospect of nanomedicines in immunotherapy and Chimeric antigen receptor T-cell therapy (CAR-T) are highlighted and summarized to address the problems of immunotherapy the overall goal of this article is to provide insights into the potential use of nanomedicines and to improve the efficacy and safety of immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a shared parent affiliation with the author HX at the time of review., (Copyright © 2022 Wang, Xu, Weng, Sun, Jin and Xiao.)

The matrix protein of many enveloped RNA viruses regulates multiple stages of viral life cycle and has the characteristics of nucleocytoplasmic shuttling. We have previously demonstrated that matrix protein 1 (M1) of an RNA virus, influenza virus, blocks host cell cycle progression by interacting with SLD5, a member of the GINS complex, which is required for normal cell cycle progression. In this study, we found that M protein of several other RNA viruses, including VSV, SeV and HIV, interacted with SLD5. Furthermore, VSV/SeV infection and M protein of VSV/SeV/HIV induced cell cycle arrest at G0/G1 phase. Importantly, overexpression of SLD5 partially rescued the cell cycle arrest by VSV/SeV infection and VSV M protein. In addition, SLD5 suppressed VSV replication in vitro and in vivo , and enhanced type Ⅰ interferon signalling. Taken together, our results suggest that targeting SLD5 by M protein might be a common strategy used by multiple enveloped RNA viruses to block host cell cycle. Our findings provide new mechanistic insights for virus to manipulate cell cycle progression by hijacking host replication factor SLD5 during infection.

Curcumin (Cur) has been widely used in medicine, due to its antibacterial, anti-inflammatory, antioxidant, and antitumor effects. However, its clinic application is limited by its instability and poor solubility. In the present wok, curcumin was loaded into solid lipid nanoparticles (SLNs), in order to improve the therapeutic efficacy for breast cancer. The results measured using transmission electron microscopy (TEM) indicated that Cur-SLNs have a well-defined spherical shape; the size was about 40 nm with a negative surface charge. The drug loading and encapsulation efficiency in SLNs reached 23.38% and 72.47%, respectively. The Cur-SLNs showed a stronger cytotoxicity against SKBR3 cells. In vitro cellular uptake study demonstrated a high uptake efficiency of the Cur-SLNs by SKBR3 cells. Moreover, Cur-SLNs induced higher apoptosis in SKBR3 cells, compared to cells treated by free drug. In addition, Western blot analysis revealed that Cur-SLNs could promote the ratio of Bax/Bcl-2 , but decreased the expression of cyclin D1 and CDK4 . These results suggested that Cur-SLNs could be a potential useful chemotherapeutic formulation for breast cancer therapy.

Background: Osteoporosis (OP) is a common bone disease, most often diagnosed in post-menopausal women. The majority of OP treatments are focused on manipulation of the patient's hormone levels, therefore, they are associated with significant adverse effects., Objective: The study aimed to design, synthesize and evaluate the β-catenin translocation capability and the alkaline phosphatase (ALP) activation activity of 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives., Method: The styrene derivatives were synthesized as raw materials, followed by oxidation and condensation reactions, in which 6-aryl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H)-one derivatives (1) were obtained. The 3,6-diaryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-ones (2) were obtained by a condensation reaction of compound 1 with substituted phenacyl chlorides in acetic acid. The target compounds 3,6-diaryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-ones (3a-3c) were prepared by compound 2 with substituted alkyl chloride by Williamson reaction. As to 6-benzyl-3-aryl-7H-thiazolo[3,2- b]-1,2,4-triazin-7-one derivatives as the target compounds, the benzaldehyde and acetylglycine used as raw materials, followed by Erlenmeyer-Plochl reaction, condensation reaction, hydrolysis reaction, condensation reaction, 6-benzyl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H)-one derivatives were obtained, and were converted to the target compounds 6-benzyl-3-(hydroxylaryl)-7Hthiazolo[ 3,2-b]-1,2,4-triazin-7-one derivatives (5a-5d) using reaction with substituted α-phenacyl chlorides. Finally, Williamson reaction were used to yield 6-benzyl-3-aryl-7H-thiazolo[3,2-b]- 1,2,4-triazin-7-ones as target compounds (6a-6e). The β-catenin translocation capability and the ALP activation activity were tested, and the glycogen synthase kinase-3 (GSK-3) inhibition was simulated by molecular docking., Results: Fourteen 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives were synthesized and characterized by mass spectra, proton NMR and infrared spectra, the β-catenin translocation capability and the ALP activation activities of the target compounds were tested and calculated. The EC50 value of the ALP activation activity of 6-(4-chlorobenzyl)-3-{4-[(2-dimethylamino)-2- oxoethoxy]phenyl}-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one (6b) was 11.283 µM. The molecular docking results have showed that the target compounds would be GSK-3 inhibitors., Conclusion: Based on the results of the biological activity test, the target compounds have exhibited the β-catenin translocation capability and the ALP activation activity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)