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An efficient stereoselective synthesis of 10-hydroxy-10-(1H-indol-3-yl)-9-(10H)-phenanthrene derivatives was realized through an organocatalyzed Friedel–Crafts reaction of phenanthrenequinones and indoles using a (S,S)-dimethylaminocyclohexyl-squaramide as the catalyst. Under the optimized conditions, the desired chiral products were obtained in good yields (73–90%) with moderate to high ee values (up to 97% ee). Two pairs of synthesized enantiomers were subjected to evaluation of their antiproliferative activities on four types of human cancer cell lines and one human umbilical vein endothelial cell line using the CCK-8 assay. The results indicated that stereoselectivity had obvious impacts on biological activity. (S)-4g was found to have optimal cytotoxicity against the A549 cell line and a good safety profile for human normal cells, which was better than the inhibitory activity of the positive control drug (doxorubicin).

Gastric cancer (GC) is the fifth most prevalent cancer worldwide and the fourth leading cause of cancer-related mortality. MAM Domain Containing 2 (MAMDC2) has been involved in many cancers. However, the impact of MAMDC2 on gastric cancer was unclear. This study aimed to investigate the role and mechanism of MAMDC2 in gastric cancer. Differential genes in gastric cancer are analyzed by GEO, TCGA, MSigDB database, R-packet limma, and Wilcoxon test. Survival analysis is performed through the R package survival. Construct a PPI network through the STRING database. Enrichment analysis is performed by Metascape. The infiltration level of gastric cancer immune cells is calculated by CIBERSORT. In addition, the expression of MAMDC2 was analyzed by immunohistochemistry and quantitative real-time polymerase chain reaction (RT-qPCR). siMAMDC2 was used to knock down the specific gene. Cell counting kit-8 (CCK-8) assay, colony formation assay, and cell migration were applied to evaluate the function of MAMDC2 in gastric cancer cells. In the present study, we revealed a significant upregulation of MAMDC2 in gastric cancer tissues and cells. Knocking down MAMDC2 inhibited the proliferation and migration of gastric cancer cells, while overexpression of MAMDC2 produced the opposite results. Furthermore, MAMDC2 may be an independent factor in poor prognosis in gastric cancer patients. These results illustrated that MAMDC2 promoted the proliferation and migration of gastric cancer cells. The newly identified MAMDC2 provides novel insight into the pathogenesis of gastric cancer.

ObjectivesTooth-colored composites have emerged as a standard restorative material in caries therapy and have largely replaced materials such as silver amalgam or glass ionomer cements. In addition to their superior esthetics and desirable mechanical properties, composites also comprise negative characteristics, such as wear, shrinkage, and an adverse biocompatibility. Modifications of classic resin-based dental composites have been developed to overcome these shortcomings. For example, ormocers are innovative inorganic-organic hybrid polymers that form a siloxane network modified by the incorporation of organic groups. Recently, a new ormocer, Admira Fusion (VOCO), was introduced to composite technology. The absence of cytotoxic matrix monomers leads to the hypothesis that ormocers have improved biocompatibility compared to resin-based dental restorative materials.Materials and methodsThe aim of this study was to compare the cytotoxic effects of Admira Fusion to a nanohybrid composite (GrandioSO, VOCO) and a nanofiller composite (Filtek Supreme XTE, 3M Espe) on the standard dermal mouse fibroblasts (L929) and human gingival fibroblasts (GF-1) via a Cell Counting Kit-8 (CCK-8) assay.ResultsAdmira Fusion was significantly less cytotoxic than GrandioSO and Filtek Supreme XTE to both the standard mouse dermal fibroblasts (L929) and human gingival fibroblasts.ConclusionsCompared to other resin-based dental restorative materials, the ormocer (Admira Fusion) possesses a superior biocompatibility in vitro. Future research studies are needed to confirm our results.Clinical significanceClinically, dental practitioners and their patients might benefit from Admira Fusion in terms of reduced adverse biologic reactions compared to resin-based dental restorative materials.

The first total synthesis of marine natural product, (−)-majusculoic acid (1) and its seven analogs (9–15), was accomplished in three to ten steps with a yield of 3% to 28%. The strategy featured the application of the conformational controlled establishment of the trans-cyclopropane and stereochemical controlled bromo-olefination or olefination by Horner–Wadsworth–Emmons (HWE) reaction. The potential anti-inflammatory activity of the eight compounds (1 and 9–15) was evaluated by determining the nitric oxide (NO) production in the lipopolysaccharide (LPS)-induced mouse macrophages RAW264.7. (−)-Majusculoic acid (1), methyl majusculoate (9), and (1R,2R)-2-((3E,5Z)-6-bromonona-3,5-dien-1-yl)cyclopropane-1-carboxylic acid (12) showed significant effect with inhibition rates of 33.68%, 35.75%, and 43.01%, respectively. Moreover, they did not show cytotoxicity against RAW264.7 cells, indicating that they might be potential anti-inflammatory agents.

Cirrhosis and portal hypertension are associated with an increased risk of developing liver cancer. However, it is unknown how changes in the cellular mechanical microenvironment induced by portal hypertension affect the occurrence and development of liver cancer. The aim of this study was to determine the effect of tensile strain on the proliferation of a human liver cancer cell line (HepG2 cells) using methods such as flow cytometry, Cell Counting Kit-8 and 5-bromodeoxyuridine assays, and to examine the changes in microRNA (miRNA/miR) expression using microarray, reverse transcription-quantitative (RT-q)PCR and bioinformatics analyses. It was demonstrated that cyclic tensile force promoted the proliferation of HepG2 cells. The most suitable research conditions were as follows: Tensile strain force loading amplitude 15%; frequency 1 Hz; and time 24 h. After loading the HepG2 cells under such conditions, the differentially expressed miRNAs were screened out using an Agilent Human miRNA Microarray, identifying seven miRNAs with significant differences (expression difference >2 times and P<0.05). A total of five were upregulated, including hsa-miR-296-5p, hsa-miR-6752-5p, hsa-miR-6794-5p, hsa-miR-6889-5p and hsa-miR-7845-5p; and two were downregulated, hsa-miR-4428 and hsa-miR-503-5p. The results of RT-qPCR also further confirmed the expression changes of these miRNAs. Gene Ontology and pathway analyses showed the involvement of these miRNAs in numerous important physiological processes. These findings may provide novel miRNA-based information, thus enhancing the understanding of the pathophysiological processes leading to liver cancer.

Malignant melanoma (MM) is a highly aggressive skin tumour. To investigate whether miR-22 is involved in the proliferation, invasion, and migration of melanoma cells (MCs) by negatively regulating NOD-like receptor protein 3 (NLRP3) gene. Human MCs (WM239a) and human epidermal melanocytes (HEM) were used as study material. The expression levels of miR-22 and NLRP3 were detected by qRT-PCR. The expression of NLRP3 protein was determined by Western blot (WB) analysis. The effects of miR-22 and NLRP3 on the proliferation, invasion, and migration of MCs were evaluated by cell counting kit-8 (CCK-8), Transwell cell invasion assay, and scratch assay. The expression of miR-22 was clearly lower in WM239a than in HEM. Up-regulation of miR-22 expression in WM239a clearly raised the expression of miR-22, Caspase-1, and E-cadherin and the apoptotic rate of WM239a; however, the levels of interleukin-1β (IL-1β) and NLRP3, cell proliferation activity, invasion and migration ability were clearly decreased. The negative regulation of NLRP3 by miR-22 may play a major role in activities of MM. Further studies will help to reveal the molecular details of this regulatory mechanism and provide new therapeutic strategies.

Background/Objectives: Addressing the risk of malnutrition at an early stage is crucial to preventing its development, which can have a detrimental impact on physical and mental health status. This study investigates the potential role of biochemical biomarkers such as sirtuin 1 (SIRT-1), melatonin, cholecystokinin-8 (CCK-8), and total antioxidant capacity (TAC) in identifying the risk of malnutrition. Methods: This cross-sectional study assessed malnutrition risk in 153 community-dwelling older adults using the Mini Nutritional Assessment (MNA). Serum levels of SIRT-1, melatonin, and CCK-8 were analyzed with enzyme-linked immunosorbent assay (ELISA), and total antioxidant capacity (TAC) was measured using the ferric reducing ability of plasma (FRAP) method. Results: Serum levels of TAC and CCK-8 were significantly positively correlated with grip strength and visceral adipose tissue, with TAC levels also showing associations with appendicular skeletal muscle mass index (ASMI), total body water, total energy expenditure, fat-free mass index, and fat mass index (p < 0.001). CCK-8 emerged as a strong predictor of malnutrition risk (AUC = 0.58 in females, AUC = 0.64 in males), whereas SIRT-1 (AUC = 0.57 for both sexes), melatonin (AUC = 0.46 for females, AUC = 0.51 for males), and TAC (AUC = 0.42 for females, AUC = 0.54 for males) exhibited weaker predictive abilities. A multivariate model incorporating CCK-8 demonstrated excellent predictive accuracy (AUC = 0.84, 95% CI: 0.77–0.90) and indicated a potential association between elevated CCK-8 levels and a higher risk of malnutrition. Conclusions: In conclusion, this study highlights the effectiveness of a multi-parameter model incorporating CCK-8 as a reliable approach for assessing malnutrition risk in older adults, offering a comprehensive evaluation of the condition. However, further research is needed to confirm its applicability and accuracy in diverse elderly populations and clinical settings.

The p21-activated kinases (PAKs) are a conserved family of serine/threonine protein kinases, which are effectors for the Rho family GTPases, namely, Rac/Cdc42. PAKs are divided into two groups: group I (PAK1–3) and group II (PAK4–6). Both groups of PAKs have been well studied in apoptosis, protein synthesis, glucose homeostasis, growth (proliferation and survival) and cytoskeletal regulation, as well as in cell motility, proliferation and cycle control. However, little is known about the role of PAKs in the secretory tissues, including in exocrine tissue, such as the exocrine pancreas (except for islet function and pancreatic cancer growth). Recent studies have provided insights supporting the importance of PAKs in exocrine pancreas. This review summarizes the recent insights into the importance of PAKs in the exocrine pancreas by reviewing their presence and activation; the ability of GI hormones/neurotransmitters/GFs/post-receptor activators to activate them; the kinetics of their activation; the participation of exocrine-tissue PAKs in activating the main growth-signaling cascade; their roles in the stimulation of enzyme secretion; finally, their roles in pancreatitis. These insights suggest that PAKs could be more important in exocrine/secretory tissues than currently appreciated and that their roles should be explored in more detail in the future.

We prepared a visual Rhodamine B- nido -carborane fluorescent marker by one-pot method for tumor cell imaging. Firstly, the fat-soluble carborane was treated with potassium hydroxide to obtain nido -carborane potassium salt. Secondly, it was combined with Rhodamine B to remove a molecule of potassium chloride, and finally a fluorescent marker of Rhodamine B- nido -carborane was obtained. In order to further understand its structural characteristics, it was observed that the nido -carborane and Rhodamine B are firmly bound together by ionic properties by X-ray single crystal diffraction. Such a design strategy is conducive to combining the advantages of the two, and can better promote its application in the biological field through the synergistic action of complementarity and mutual assistance. The addition rate and inhibition rate of Rhodamine B- nido -carborane in Hera cells were measured by CCK-8, and their maximum values were 71.76% and 28.24%, respectively. In fluorescence imaging, HeLa cells were selected to test their biocompatibility in different channels, and it was found that Rhodamine B- nido -carborane had a good labeling effect on tumor cells. Graphical abstract

Two new Ag(I) coordination polymers, namely [Ag(bpp)]·0.5 n(1,5-NDSA)·n(H 2 O) (1) and [Ag 2 (bpp) 2 ] n ·n(2,7-NDSA)·2 n(H 2 O)·n(CH 3 CN) (2) (Na 2 (1,5-NDSA) = sodium 1,5-naphthalenedisulfonate dibasic, Na 2 (2,7-NDSA) = sodium 1,5-naphthalenedisulfonate dibasic, bpp is 1,3-bis(4-pyridyl)propane), were generated via the solution evaporation method under room temperature. Moreover, the solids of these two compounds display strong luminescence emission at RT. And the application values of the compounds against the glioblastoma treatment were determined, and the corresponding mechanism was simultaneously tested. The analysis of CCK-8 was first implemented and the glioblastoma viability was measured. The real-time RT-PCR was next performed, and the signaling pathway activation of VEGF in glioblastoma cells was tested after treating by the above compound.