2'-Hydroxychalcone Induces Autophagy and Apoptosis in Breast Cancer Cells via the Inhibition of the NF-κB Signaling Pathway: In Vitro and In Vivo Studies.

2'-Hydroxychalcone is a hydroxyl derivative of chalcones, which are biosynthetic precursors of flavonoids and rich in the human diet. The anticancer activity of 2'-hydroxychalcone has been reported in several cancers but remains to be investigated in breast cancer. In the current study, 2'-hydroxychalcone showed significant cytotoxicity against breast cancer cell lines MCF-7 and CMT-1211. It could inhibit breast cancer cell proliferation, migration, and invasion in vitro and suppress tumor growth and metastasis in vivo. Mechanistic investigation revealed that the NF-κB pathway was significantly inhibited by 2'-hydroxychalcone treatment accompanied by an excessive intracellular accumulation of reactive oxygen species, induction of endoplasmic reticulum stress, and activation of JNK/MAPK. In addition, 2'-hydroxychalcone elevated the autophagic levels in breast cancer cells equipped with increasing numbers of autophagy vesicles and complete autophagic flux. Finally, autophagy-dependent apoptosis was observed in 2'-hydroxychalcone-induced cell death. In conclusion, 2'-hydroxychalcone enhances the autophagic levels and induces apoptosis in breast cancer cells, which could be contributed to the inhibition of the pro-survival NF-κB signaling, indicating a promising potential for 2'-hydroxychalcone in future anticancer drug development.

A selenium-based NIR-II photosensitizer for a highly effective and safe phototherapy plan.

High efficiency, stability, long emission wavelength (NIR-II), and good biocompatibility are crucial for photosensitizers in phototherapy. However, current Food and Drug Administration (FDA)-approved organic fluorophores exhibit poor chemical stability and photostability as well as short emission wavelength, limiting their clinical usage. To address this, we developed Se-IR1100, a novel organic photosensitizer with a photostable and thermostable benzobisthiadiazole (BBTD) backbone. By incorporating selenium as a heavy atom and constructing a D-A-D structure, Se-IR1100 exhibits a maximum fluorescence emission wavelength of 1100 nm. Compared with FDA-approved indocyanine green (ICG), DSPE-PEGylated Se-IR1100 nanoparticles exhibit prominent photostability and long-lasting photothermal effects. Upon 808 nm laser irradiation, Se-IR1100 NPs efficiently convert light energy into heat and reactive oxygen species (ROS), inducing cancer cell death in cellular studies and living organisms while maintaining biocompatibility. With salient photostability and a photothermal conversion rate of 55.37%, Se-IR1100 NPs hold promise as a superior photosensitizer for diagnostic and therapeutic agents in oncology. Overall, we have designed and optimized a multifunctional photosensitizer Se-IR1100 with good biocompatibility that performs NIR-II fluorescence imaging and phototherapy. This dual-strategy method may offer novel approaches for the development of multifunctional probes using dual-strategy or even multi-strategy methods in bioimaging, disease diagnosis, and therapy.

MicroRNAs in equine Endometritis: A review of pathophysiology and molecular insights for diagnostic and therapeutic strategies.

Endometritis plays an important role in mare infertility. Certain infectious agents interfere with the innate immune system of endometrium, causing a systemic inflammatory response that lasts for a long time and circulates via the blood or cellular degeneration, leading to endometritis due to bacterial endotoxins. Different small, non-coding RNA molecules are involved in many biological functions. For instance, microRNAs (miRNAs) are involved in the post-transcriptional regulation of gene expression. These miRNAs are important regulators of gene expression, primarily via inhibiting transcription and translation processes. This manuscript reviews: (1) pathomorphological findings in equine endometritis, (2) the expression and effects of eca-miR-17, eca-miR-223, eca-miR-200a, eca-miR-155, and eca-miR-205 in endometritis and (3) the therapeutic role of miRNA in equine endometritis. The miRNAs have a vital regulatory role in a wide range of inflammatory diseases by regulating the molecular mechanism of cytokines that cause inflammation through signal pathways. This review emphasizes the demand for cutting-edge genetic technologies and the development of novel pharmaceutical preparations to improve our understanding of the genes encoding by these miRNAs. It also focuses on the efficacy of miRNAs for control, early diagnosis, and prevention of endometritis.

6-Gingerol via overexpression of miR-322-5p impede lipopolysaccharide-caused inflammatory response in RAW264.7 cells.

Acute lung injury (ALI) and sepsis are complicated syndromes that are often left untreated in critically ill patients. 6-Gingerol is a phenolic phytochemical compound that is found in fresh ginger, has pharmacological effects against inflammation. This study explored the roles of 6-gingerol in a mouse model of acute lung injury caused by lipopolysaccharide (LPS) and RAW-264.7 cells inflammation. The LPS-induced animal model underwent histopathological examinations, and RAW-264.7 cells viability was determined by Cell counting Kit-8 (CCk-8) assay. Additionally, qRT-PCR, Immunofluorescence, Western blot, and ELISA were used in vivo and in vitro to identify inflammatory factors and proteins associated with NF-κB and MAPK signaling pathways. In a histological examination 6-gingerol exhibited protective effects. Moreover, 6-gingerol elevated cell viability and downregulated inflammatory factors Interlukin-1ß (IL-1ß), Interlukin-6 (IL-6) and Tumor necrosis factor-α (TNF-α) in LPS-treated RAW-264.7 cells. Furthermore, 6-gingerol decreased phosphorylation of P65, P38 and the level of JNK in NF-κB and MAPK pathways. Importantly, 6-gingerol increased transcript abundance of miR-322-5p which suppressed by LPS and miR-322-5p downregulation negated the protective functions of 6-gingerol. The protective activity of 6-gingerol was mediated by miR-322-5p up-regulation.

Sodium New Houttuyfonate Induces Apoptosis of Breast Cancer Cells via ROS/PDK1/AKT/GSK3ß Axis.

BACKGROUND: Sodium new houttuyfonate (SNH) has been reported to have anti-inflammatory, anti-fungal, and anti-cancer effects. However, few studies have investigated the effect of SNH on breast cancer. The aim of this study was to investigate whether SNH has therapeutic potential for targeting breast cancer. METHODS: Immunohistochemistry and Western blot analysis were used to examine the expression of proteins, flow cytometry was used to detect cell apoptosis and ROS levels, and transmission electron microscopy was used to observe mitochondria. RESULTS: Differentially expressed genes (DEGs) between breast cancer-related gene expression profiles (GSE139038 and GSE109169) from GEO DataSets were mainly involved in the immune signaling pathway and the apoptotic signaling pathway. According to in vitro experiments, SNH significantly inhibited the proliferation, migration, and invasiveness of MCF-7 (human cells) and CMT-1211 (canine cells) and promoted apoptosis. To explore the reason for the above cellular changes, it was found that SNH induced the excessive production of ROS, resulting in mitochondrial impairment, and then promoted apoptosis by inhibiting the activation of the PDK1-AKT-GSK3ß pathway. Tumor growth, as well as lung and liver metastases, were suppressed under SNH treatment in a mouse breast tumor model. CONCLUSIONS: SNH significantly inhibited the proliferation and invasiveness of breast cancer cells and may have significant therapeutic potential in breast cancer.

Establishment of a new cell line of canine inflammatory mammary cancer: IMC-118.

Canine inflammatory mammary cancer (IMC) has long been regarded as an attractive animal model for research into human inflammatory breast cancer (IBC), Although some canine mammary tumour cell lines corresponding to human mammary cancer cell lines have been established, there is still a need to supplement the canine mammary tumour cell bank. The goal of this study was to create a new type of IMC cell line. The primary tumour, IMC-118, was identified as IMC by pathology examination. Immunohistochemistry analysis revealed negative immunoreactivity to oestrogen receptor (ER), but positive immunoreactivity to progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2). Immunofluorescence (IF) analysis revealed that the IMC-118 cell line from this primary tumour was negative for ER but positive for PR and HER-2, and was also positive for epithelial and mesenchymal cell markers. This cell line was cultured stably for more than 50 passages and grew well after cryopreservation. In vivo, tumour masses and metastases in the lungs were discovered after inoculating the IMC-118 cells into the nude mice model. As a result, a novel canine IMC cell line, IMC-118, was effectively established, and could be employed as a promising model for immunotherapy and epithelial-mesenchymal transition mechanism of IMC research in both dogs and humans.

Curcumin regulates insulin pathways and glucose metabolism in the brains of APPswe/PS1dE9 mice.

Recent studies have shown the therapeutic potential of curcumin in Alzheimer's disease (AD). In 2014, our lab found that curcumin reduced Aß40, Aß42 and Aß-derived diffusible ligands in the mouse hippocampus, and improved learning and memory. However, the mechanisms underlying this biological effect are only partially known. There is considerable evidence in brain metabolism studies indicating that AD might be a brain-specific type of diabetes with progressive impairment of glucose utilisation and insulin signalling. We hypothesised that curcumin might target both the glucose metabolism and insulin signalling pathways. In this study, we monitored brain glucose metabolism in living APPswe/PS1dE9 double transgenic mice using a micro-positron emission tomography (PET) technique. The study showed an improvement in cerebral glucose uptake in AD mice. For a more in-depth study, we used immunohistochemical (IHC) staining and western blot techniques to examine key factors in both glucose metabolism and brain insulin signalling pathways. The results showed that curcumin ameliorated the defective insulin signalling pathway by upregulating insulin-like growth factor (IGF)-1R, IRS-2, PI3K, p-PI3K, Akt and p-Akt protein expression while downregulating IR and IRS-1. Our study found that curcumin improved spatial learning and memory, at least in part, by increasing glucose metabolism and ameliorating the impaired insulin signalling pathways in the brain.