11/14/2024


omolar range on purified human enzyme and highly selective with respect to other kinases. Current study demonstrates that the compound has efficacy both in the chronic mild stress paradigm of depression (mimicking the down phase of bipolar disorder) and on mice aggressiveness in the resident intruder model (mimicking the up phase). These findings underline the importance of aberrant GSK-3β activity in the development/ maintenance of mood oscillation in this peculiar pathological condition. Moreover, the present work also suggests a therapeutic potential for selective GSK-3 β inhibitors in the management of bipolar disorders patients.Piperlongumine (PL), a herbal drug extracted from long pepper (Piper longum L), is known for its anti-inflammatory and anti-cancer properties. Although, its anti-cancer potential has been evaluated in cancer models like breast, pancreatic, gastric, hepatocellular and lung carcinoma, there is no report on its bio-activity evaluation in intestinal cancers. Here, we report the anti-neoplastic potential of PL against human intestinal carcinoma in-vitro and its possible mechanisms of action. Cytotoxicity studies demonstrate that PL inhibits cell proliferation of INT-407 and HCT-116 cells in a concentration and time-dependent manner. Also, PL elevated the levels of intracellular reactive oxygen species, which may lead to lethal oxidative stress, mitochondrial dysfunction, and nuclear fragmentation. Remarkably, P53, P21, BAX, and SMAD4 were significantly upregulated after PL treatment whereas; BCL2 and SURVIVIN were down-regulated. Moreover, the combination study also shows the synergistic effect of PL with the current chemotherapeutic drug paclitaxel. These findings suggest that PL possesses anti-neoplastic properties in intestinal cancer cells.With the development of biomedicine, exosomes are rapidly developing as a new therapy for tumors. As biological carriers, exosomes possess biological activity and can transport their contents between cells. The contents are natural or artificially loaded with biomolecules or chemical drugs. https://www.selleckchem.com/products/pamapimod-r-1503-ro4402257.html Exosomes deliver biomolecules or chemical drugs into the pathological sites of recipient, which can effectively inhibit the progression of tumors. However, the treatments of tumors through the delivery of exosomes are not sufficiently accurate or efficient, and various challenges need to be overcome. Exosomes from different cell sources possess different characteristics, as well as different specificity for various cells. In the future, for the promotion and application of exosomes, it is of great significance to understand how to select appropriate exosomes loaded with biomolecules or chemical drugs for different tumors types, and how to deliver exosomes to recipient cells accurately and efficiently. This review introduces the application and challenges of exosomes as delivery carriers in tumors.The digestive tract is an important target organ for microplastics (MPs). However, little is known about the effects of digestive treatment on the intestinal toxicity of MPs. In this study, an in vitro digestive process was applied to transform 100 nm and 5 μm polystyrene microplastics (PS-MPs). Intestinal toxicities of original PS-MPs and transformed PS-MPs (t-PS-MPs) were determined using an in vitro Caco-2 monolayer model. Results showed that the digestive process did not alter the chemical constitution of PS-MPs, but formed a corona on the surface of PS-MPs. The 100 nm PS-MPs showed higher intestinal toxicity than 5 μm PS-MPs. Digestive treatment relieved cytotoxicity and transport function disorder of the Caco-2 monolayer induced by the original PS-MPs. Moreover, the combined toxicities of PS-MPs and arsenic were also decreased by digestive treatment. However, the in vitro digestive process increased the proinflammatory effects of PS-MPs. The formation of a corona on the PS-MP surface, which lead to a change in size, Zeta potential, and adsorbed compounds, might induce the above influence of digestive treatment. Our study suggests that direct cytotoxicity assays of PS-MPs might misestimate their intestinal effects, which provide new lights to the toxicity evaluation of PS-MPs by oral exposure.Microplastic pollution, one of the major global challenges, is a severe threaten to aquatic organisms. The purpose of this study was to investigate the abundance, distribution and characteristics of microplastics in coastal surface waters from eastern Guangdong, south China. We chose pelagic Konosirus punctatus and demersal Mugil cephalus from different sampling sites as candidate monitoring species for the ingestion of marine microplastics, and talked about the relationship between water samples and fish samples. We tried to find out the regulation about microplastics characteristics in fish samples and fish own traits. The mean abundance of microplastics in surface water was 8895 items/m3, small white fragments were dominating character. We need to increase the amount of fish data to further explore. This study would not only provide a detailed reference for a better understanding of microplastic pollution in Guangdong coastal areas, but also shed an insight in prospect of using fish as biomonitoring of microplastic wastes.Nanoplastic exposure could cause toxicity to Caenorhabditis elegans at various aspects. Nevertheless, the effects of chronic exposure to nanoplastics remain largely unclear in nematodes. In this study, we employed C. elegans as an animal model to determine the effects of nanopolystyrene (30 nm) exposure from adult day-1 for 8-day. After the exposure, only 1000 μg/L nanopolystyrene reduced the lifespan. In contrast, nanopolystyrene ≥1 μg/L decreased locomotion behavior and activated oxidative stress. Meanwhile, in 10 μg/L nanopolystyrene exposed nematodes, both expression of SOD-3, a Mn-SOD, and autophagy induction as indicated by LGG-1GFP expression were significantly increased. RNAi knockdown of daf-2 encoding an insulin receptor enhanced the autophagy induction, and RNAi knockdown of daf-16 encoding a FOXO transcriptional factor in insulin signaling pathway suppressed the autophagy induction in 10 μg/L nanopolystyrene exposed nematodes. Moreover, DAF-16 acted upstream of LGG-1, an ortholog of Atg8/LC3, to regulate the toxicity of nanopolystyrene toxicity in inducing ROS production and in decreasing locomotion behavior at adult day-9.