Juglone triggers apoptosis of non-small cell lung cancer through the reactive oxygen species -mediated PI3K/Akt pathway.

Non-small cell lung cancer (NSCLC) is one of the most common malignancies worldwide, and oxidative stress plays a crucial role in its development. Juglone, a naturally occurring naphthoquinone in J. mandshurica, exhibits significant cytotoxic activity against various cancer cell lines. However, whether the anticancer activity of juglone is associated with oxidative stress remains unexplored. In this study, mouse Lewis lung cancer (LLC) and human non-small cell lung cancer A549 cells were used to explore the anticancer mechanisms of juglone. Juglone inhibited LLC and A549 cells viability, with IC50 values of 10.78 µM and 9.47 µM, respectively, for 24 h, and substantially suppressed the migration and invasion of these two lung cancer cells. Additionally, juglone arrested the cell cycle, induced apoptosis, increased the cleavage of caspase 3 and the protein expression of Bax and Cyt c, and decreased the protein expression of Bcl-2 and caspase-3. Furthermore, juglone treatment considerably increased intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels, but suppressed glutathione peroxidase 4 (GPX4) and superoxide dismutase (SOD) activities. It also inhibited the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, which was attenuated by 1,3-diCQA (an activator of PI3K/Akt). Moreover, N-acetylcysteine (a ROS scavenger) partially reversed the positive effects of juglone in terms of migration, invasion, ROS production, apoptosis, and PI3K/Akt pathway-associated protein expression. Finally, in tumor-bearing nude mouse models, juglone inhibited tumor growth without any apparent toxicity and significantly induced apoptosis in NSCLC cells. Collectively, our findings suggest that juglone triggers apoptosis via the ROS-mediated PI3K/Akt pathway. Therefore, juglone may serve as a potential therapeutic agent for the treatment of NSCLC.

Ginsenoside Rg1 Induces Autophagy in Colorectal Cancer through Inhibition of the Akt/mTOR/p70S6K Pathway.

This study aimed to elucidate the anti-colon cancer mechanism of ginsenoside Rg1 in vitro and in vivo. Cell viability rate was detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tetrazolium assay. The inhibitory effect of ginsenoside Rg1 against CT26 cell proliferation gradually increased with increasing concentration. The in vivo experiments also demonstrated an antitumor effect. The monodansylcadaverine (MDC), transmission electron microscopy (TEM), and expression of autophagy marker proteins confirmed that ginsenoside Rg1 induced autophagy in vitro. Ginsenoside Rg1 induced autophagy death of CT26 cells, but this effect could be diminished by autophagy inhibitor (3-methyladenine, 3-MA). Additionally, in a xenograft model, immunohistochemical analysis of tumor tissues showed that the LC3 and Beclin-1 proteins were highly expressed in the tumors from the ginsenoside Rg1-treated nude mice, confirming that ginsenoside Rg1 also induced autophagy in vivo. Furthermoer, both in vivo and in vitro, the protein expressions of p-Akt, p-mTOR, and p-p70S6K were inhibited by ginsenoside Rg1, which was verified by Akt inhibitors. These results indicated that the mechanism of ginsenoside Rg1 against colon cancer was associated with autophagy through inhibition of the Akt/mTOR/p70S6K signaling pathway.

Fenchone Ameliorates Constipation-Predominant Irritable Bowel Syndrome via Modulation of SCF/c-Kit Pathway and Gut Microbiota.

In this study we sought to elucidate the therapeutic effects of fenchone on constipation-predominant irritable bowel syndrome (IBS-C) and the underlying mechanisms. An IBS-C model was established in rats by administration of ice water by gavage for 14 days. Fenchone increased the reduced body weight, number of fecal pellets, fecal moisture, and intestinal transit rate, and decreased the enhanced visceral hypersensitivity in the rat model of IBS-C. In addition, fenchone increased the serum content of excitatory neurotransmitters and decreased the serum content of inhibitory neurotransmitters in the IBS-C rat model. Meanwhile, western blot and immunofluorescence experiments indicated that fenchone increased the expressions of SCF and c-Kit. Furthermore, compared with the IBS-C model group, fenchone increased the relative abundance of Lactobacillus, Blautia, Allobaculum, Subdoligranulum, and Ruminococcaceae_UCG-008, and reduced the relative abundance of Bacteroides, Enterococcus, Alistipes, and Escherichia-Shigella on the genus level. Overall, fenchone ameliorates IBS-C via modulation of the SCF/c-Kit pathway and gut microbiota, and could therefore serve as a novel drug candidate against IBS-C.

Combination of fenchone and sodium hyaluronate ameliorated constipation-predominant irritable bowel syndrome and underlying mechanisms.

We sought to explore the protective effect of the combination of fenchone (FE) and sodium hyaluronate (SH) on ice water-induced IBS-C rats and the potential mechanism. The neurotransmitter levels, including substance P (SP), motilin (MTL), 5-hydroxytryptamine (5-HT), and vasoactive intestinal peptide (VIP), were determined by ELISA methods. The stem cell factors (SCF)/c-Kit signaling pathway-related protein and mRNA levels were determined by western blot and reverse transcription quantitative polymerase chain reaction (RT-qPCR) analyses, respectively. The expressions of tight ZO-1, Occludin, and Claudin-1 were also measured by western blot assay and immunofluorescence staining. The 16S rRNA gene sequence was used to measure the composition of gut microbiota. The co-administration of FE and SH improved the body weight, number of fecal pellets, fecal moisture, abdominal with drawal reflex score, and gastrointestinal transit rate in IBS-C rats. The unique efficacy of combination depended on the regulation of balance between excitatory and inhibitory neurotransmitters, enhancement of intestinal barrier function, and activation of SCF/c-Kit pathway. The gut microbiota structure was also restored. The ability of FE combined with SH to regulate SCF/c-Kit signaling pathway, enhance intestinal barrier function, and modulate gut microbiota contributes to their efficacy in managing IBS-C in rats.

Potential effects of sodium hyaluronate on constipation-predominant irritable bowel syndrome.

Treatment strategies for constipation-predominant irritable bowel syndrome (IBS-C) continue to improve. However, effective drugs are still lacking. Herein, we explored whether sodium hyaluronate (SH) could be used to treat IBS-C. The effects of SH with different molecular weights were compared in a rat model of IBS-C. Low-molecular-weight SH (LMW-SH, 5 âˆ¼ 10 kDa), medium-molecular-weight SH (MMW-SH, 200 âˆ¼ 400 kDa), and high-molecular-weight SH (HMW-SH, 1300 âˆ¼ 1500 kDa) were screened for efficacy in IBS-C using the following indicators: body weight, number of fecal pellets, fecal moisture, visceral hypersensitivity, and gastrointestinal transit rate. H-HMW-SH was the most effective in improving IBS-C symptoms. The ELISA kits indicated that H-HMW-SH reduced the levels of pro-inflammatory cytokines IL-1ß, IL-18, and TNF-α in IBS-C rats. In addition, both western blot and immunofluorescence analyses showed that H-HMW-SH increased the protein expressions of claudin-1, occludin and zonula occludens-1. Furthermore, H-HMW-SH restored the balance of intestinal flora in different intestinal contents (duodenum, jejunum, ileum, and colon) and feces of rats with IBS-C. Overall, our study illustrates the therapeutic potential of H-HMW-SH in the treatment of IBS-C.

Identification of alpha-linolenic acid as a broad-spectrum antiviral against zika, dengue, herpes simplex, influenza virus and SARS-CoV-2 infection.

Zika virus (ZIKV) has garnered global attention due to its association with severe congenital defects including microcephaly. However, there are no licensed vaccines or drugs against ZIKV infection. Pregnant women have the greatest need for treatment, making drug safety crucial. Alpha-linolenic acid (ALA), a polyunsaturated ω-3 fatty acid, has been used as a health-care product and dietary supplement due to its potential medicinal properties. Here, we demonstrated that ALA inhibits ZIKV infection in cells without loss of cell viability. Time-of-addition assay revealed that ALA interrupts the binding, adsorption, and entry stages of ZIKV replication cycle. The mechanism is probably that ALA disrupts membrane integrity of the virions to release ZIKV RNA, inhibiting viral infectivity. Further examination revealed that ALA inhibited DENV-2, HSV-1, influenza virus and SARS-CoV-2 infection dose-dependently. ALA is a promising broad-spectrum antiviral agent.

Synthesis of multiple longitudinal polarization vortex structures and its application in sorting chiral nanoparticles.

As the essential properties of organisms, detection and characterization of chirality are of supreme importance in physiology and pharmacology. In this work, we propose an optical technique to sort chiral materials by use of longitudinal polarization vortex (LPV) structures, which is generated with tightly focusing Pancharatnam-Berry tailored Laguerre-Gaussian beam. The nonparaxial propagation of the focusing field leads to the creation of multiple pairs of dual LPV structures with arbitrary topological charge and location, which can be independently controlled by the spatial phase modulation applied on the illumination. More importantly, the opposite spin angular momentums carried by each pair of dual foci lead to different energy flow directions, making it suitable to sort nanoparticles by their handedness. In addition, the LPV structures would also bring different dynamic behaviors to the enantiomers, providing a feasible route toward all-optical enantiopure chemical syntheses and enantiomer separations in pharmaceuticals.

Fast parallel molecular algorithms for DNA-based computation: solving the elliptic curve discrete logarithm problem over GF2.

Elliptic curve cryptographic algorithms convert input data to unrecognizable encryption and the unrecognizable data back again into its original decrypted form. The security of this form of encryption hinges on the enormous difficulty that is required to solve the elliptic curve discrete logarithm problem (ECDLP), especially over GF(2(n)), n in Z+. This paper describes an effective method to find solutions to the ECDLP by means of a molecular computer. We propose that this research accomplishment would represent a breakthrough for applied biological computation and this paper demonstrates that in principle this is possible. Three DNA-based algorithms: a parallel adder, a parallel multiplier, and a parallel inverse over GF(2(n)) are described. The biological operation time of all of these algorithms is polynomial with respect to n. Considering this analysis, cryptography using a public key might be less secure. In this respect, a principal contribution of this paper is to provide enhanced evidence of the potential of molecular computing to tackle such ambitious computations.