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Tannins are polyphenols that are present in various plants, and potentially contain antioxidant properties that promote reproduction in animals. This study investigated how tannic acid (TA) affects the reproductive parameters of male Brandt’s voles,Lasiopodomys brandtii(Radde, 1861). Specifically, the anti-oxidative level of serum, autophagy in the testis, and reproductive physiology were assessed in males treated with TA from the pubertal stage. Compared to the control, low dose TA enhanced relative testis and epididymis weight and sperm concentration in the epididymis, and significantly increased the level of serum superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). mRNA levels of autophagy related genes LC3 and Beclin1 decreased significantly with low dose TA compared to the control. However, compared to the control, high dose TA sharply reduced the levels of serum SOD, GSH-Px, CAT, serum testosterone (T), and mRNA level in steroidogenic acute regulatory protein (StAR) in the testis. Both sperm abnormality and mortality increased with high dose TA compared to the control and low dose TA. Collectively, this study demonstrated that TA treatment during puberty had a dose-dependent effect on the reproductive responses of male Brandt’s voles. TA might mediate autophagy in the testis, through both indirect and direct processes. TA mainly affected the reproductive function of male Brandt’s voles by regulating anti-oxidative levels. This study advances our understanding of the mechanisms by which tannins influence reproduction in herbivores.

Background High expression of monoamine oxidase A (MAOA) in non‐small cell lung cancer (NSCLC) is related to epithelial‐mesenchymal transition (EMT) and the development of clinicopathological features of NSCLC. Nevertheless, the role of MAOA in drug resistance still remains unclear. Hence, the aim of this article was to evaluate a previously synthesized MAOA inhibitor (G11) on inhibiting paclitaxel‐resistant NSCLC metastasis and growth. Methods First, MAOA expression level was evaluated in several NSCLC cell lines. An MTT assay was used to validate the inhibitory effect of G11 on NSCLC cells in vitro. Second, gene expression in G11‐treated H460/PTX cells was analyzed by microarray gene expression. Third, transwell assay was performed to assess the invasion and metastasis of G11‐treated A549/PTX and H460/PTX cells and western blot assay used to analyze vital protein expression level in G11‐treated H460/PTX cells. Finally, the antimetastatic effect of G11 was tested in an NSCLC in vivo model. Results Our data revealed that G11 significantly inhibited the viability of paclitaxel (PTX)‐resistant NSCLC cell lines (A549/PTX and H460/PTX). G11 dramatically reduced the expression of MAOA in A549/PTX and H460/PTX cells, which exhibited relatively high MAOA expression levels. Additionally, G11 was found to hinder A549/PTX and H460/PTX cell migration and invasion. Furthermore, the in vivo study indicated that the coadministration of G11 and paclitaxel significantly suppressed tumor metastasis in H460/PTX lung metastasis models. Conclusions These findings indicated G11 showed a moderate inhibitory effect on paclitaxel‐resistant NSCLC metastasis and growth, and support further investigation on MAOA potentially as a promising therapeutic target for paclitaxel‐resistant NSCLC treatment. Key points Significant findings of the study Inhibition of MAOA might contribute to the suppression of metastasis and growth in PTX‐resistant NSCLC cells. What this study adds This study explored the potential function of MAOA in drug‐resistant NSCLC and might consider MAOA as a promising target for the treatment of drug‐resistant NSCLC., In our article, a previously synthesized conjugate (G11) of cyanine dye and nonselective MAOA inhibitor was applied for evaluating the function of MAOA in paclitaxel (PTX)‐resistant NSCLC cells (H460/PTX). The results showed the antitumor efficacy of G11 against paclitaxel‐resistant NSCLC was closely correlated with MAOA inhibition.

Magnetic mesoporous silica nanospheres (MMSN) were prepared and the surface was modified with cancer cell-specific ligand folic acid. Calcium carbonate was then employed as acid-activated gatekeepers to cap the mesopores of the MMSN, namely, MMSN-FA-CaCO3. The formation of the MMSN-FA-CaCO3 was proved by several characterization techniques, viz. transmission electron microscopy, zeta potential measurement, Fourier transform infrared spectroscopy, BET surface area measurement, and UV–Vis spectroscopy. Daunomycin was successfully loaded in the MMSN-FA-CaCO3 and the system exhibited sensitive pH stimuli-responsive release characteristics under blood or tumor microenvironment. Cellular uptake by folate receptor (FR)-overexpressing HeLa cells of the MMSN-FA-CaCO3 was higher than that by non-folated-conjugated ones. Intracellular-uptake studies revealed preferential uptake of these nanoparticles into FR-positive [FR(+)] HeLa than FR-negative [FR(-)]A549 cell lines. DAPI stain experiment showed high apoptotic rate of MMSN-FA-DNM-CaCO3 to HeLa cells. The present data suggest that the CaCO3 coating and folic acid modification of MMSN are able to create a targeted, pH-sensitive template for drug delivery system with application in cancer therapy.

DNA polymorphism exerts a fascination on a large scientific community. Without crystallographic structural data, clarification of the binding modes between G-quadruplex (G4) and ligand (complex) is a challenging job. In the present work, three porphyrin compounds with different flexible carbon chains (arms) were designed, synthesized and characterized. Their binding, folding and stabilizing abilities to human telomeric G4 DNA structures were comparatively researched. Positive charges at the end of the flexible carbon chains seem to be favorable for the DNA-porphyrin interactions, which were evidenced by the spectral results and further confirmed by the molecular docking calculations. Biological function analysis demonstrated that these porphyrins show no substantial inhibition to Hela, A549 and BEL 7402 cancer cell lines under dark while exhibit broad inhibition under visible light. This significantly enhanced photocytotoxicity relative to the dark control is an essential property of photochemotherapeutic agents. The feature of the flexible arms emerges as critical influencing factors in the cell photocytotoxicity. Moreover, an ROS-mediated mitochondrial dysfunction pathway was suggested for the cell apoptosis induced by these flexible-armed porphyrins. It is found that the porphyrins with positive charges located at the end of the flexible arms represent an exciting opportunity for photochemotherapeutic anti-cancer drug design.

Tumor plasticity refers to tumor cell's inherent property of transforming one type of cell to different types of cells. Tumor plasticity is the main cause of tumor relapse, metastasis and drug resistance. Cancer stem cell (CSC) model embodies the trait of tumor plasticity. During carcinoma progression, epithelial-mesenchymal transition (EMT) plays crucial role in the formation of CSCs and vasculogenic mimicry (VM) based on epithelial-mesenchymal plasticity. And the unique tumor microenvironment (TME) not only provides suitable niche for CSCs but promotes the building of CSCs and VM that nourishes tumor tissue together with neoplasm metabolism by affecting tumor plasticity. Therapeutic strategies targeting tumor plasticity are promising ways to treat malignant tumor. In this article, we discuss the recent developments of potential drug targets related to CSCs, EMT, TME, VM, and metabolic pathways and summarize drugs that target these areas in clinical trials.

Monoamine oxidase A (MAOA) is an important mitochondria-bound enzyme that catalyzes the oxidative deamination of monoamine neurotransmitters. Accumulating evidence suggests a significant association of increased MAOA expression and advanced high-grade prostate cancer (PCa) progression and metastasis. Herein, a series of novel conjugates combining the MAOA inhibitor isoniazid (INH) and tumor-targeting near-infrared (NIR) heptamethine cyanine dyes were designed and synthesized. The synthesized compounds G1–G13 were evaluated in vitro for their cytotoxicity against PC-3 cells using the MTT assay, and molecular docking studies were performed. Results showed that most tested compounds exhibited improved antitumor efficacy compared with INH. Moreover, conjugates G10 and G11 showed potent anticancer activity with IC50 values (0.85 and 0.4 μM respectively) comparable to that of doxorubicin (DOX). This may be attributable to the preferential accumulation of these conjugates in tumor cells. G10, G11, and G12 also demonstrated moderate MAOA inhibitory activities. This result and the results of molecular docking studies were consistent with their cytotoxicity activities. Taken together, these data suggest that a combination of the MAOA inhibitor INH with tumor-targeting heptamethine cyanine dyes may prove to be a highly promising tool for the treatment of advanced prostate cancer.