MARK3 kinase: Regulation and physiologic roles.

Microtubule affinity-regulating kinase 3 (MARK3), a member of the MARK family, regulates several essential pathways, including the cell cycle, ciliated cell differentiation, and osteoclast differentiation. It is important to understand the control of their activities as MARK3 contains an N-terminal serine/threonine kinase domain, ubiquitin-associated domain, and C-terminal kinase-associated domain, which perform multiple regulatory functions. These functions include post-translational modification (e.g., phosphorylation) and interaction with scaffolding and other proteins. Differences in the amino acid sequence and domain position result in different three-dimensional protein structures and affect the function of MARK3, which distinguish it from the other MARK family members. Recent data indicate a potential role of MARK3 in several pathological conditions, including congenital blepharophimosis syndrome, osteoporosis, and tumorigenesis. The present review focuses on the physiological and pathological role of MARK3, its regulation, and recent developments in the small molecule inhibitors of the MARK3 signalling cascade.

Inhibiting ALK-TOPK signaling pathway promotes cell apoptosis of ALK-positive NSCLC.

T-LAK cell-oriented protein kinase (TOPK) is a potential therapeutic target in tumors. However, its role in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) has not been reported. Here, we found that TOPK was highly expressed in ALK-positive NSCLC. Additionally, ALK was identified as another upstream kinase of TOPK by in vitro kinase assay screening. Then, it was proven that ALK phosphorylated TOPK at Y74 in vitro and ex vivo, and the pathways downstream of ALK-TOPK were explored by phosphoproteomic analysis. Subsequently, we demonstrated that inhibiting TOPK enhanced tumor sensitivity to alectinib (an ALK inhibitor). The combination of alectinib and HI-032 (a TOPK inhibitor) suppressed the growth and promoted the apoptosis of ALK-positive NSCLC cells ex vivo and in vivo. Our findings reveal a novel ALK-TOPK signaling pathway in ALK-positive NSCLC. The combination of alectinib and HI-032 might be a promising therapeutic strategy for improving the sensitivity of ALK-positive NSCLC to targeted therapy.

The role of T-LAK cell-originated protein kinase in targeted cancer therapy.

Targeted therapy has gradually become the first-line clinical tumor therapy due to its high specificity and low rate of side effects. TOPK (T-LAK cell-originated protein kinase), a MAP kinase, is highly expressed in various tumor tissues, while it is rarely expressed in normal tissues, with the exceptions of testicular germ cells and some fetal tissues. It can promote cancer cell proliferation and migration and is also related to drug resistance. Therefore, TOPK is considered a good therapeutic target. Moreover, a number of studies have shown that targeting TOPK can inhibit the proliferation of cancer cells and promote their apoptosis. Here, we discussed the biological functions of TOPK in cancer and summarized its tumor-related signaling network and known TOPK inhibitors. Finally, the role of TOPK in targeted cancer therapy was concluded, and future research directions for TOPK were assessed.

Analysis of volatile compounds causing undesirable odors in a polypropylene - high-density polyethylene recycled plastic resin with solid-phase microextraction.

Although recycled plastics provide a low-cost and environmentally friendly alternative for many applications, their desirability is significantly limited by the presence of unpleasant odors from volatile organic compounds (VOCs). In this work, a headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography-mass spectrometry (GC-MS) method was optimized to analyze volatile compounds from an odorous recycled plastic resin which was roughly composed of 85-90% polypropylene (PP) and 15-10% high-density polyethylene (HDPE). A large variety of aliphatic hydrocarbons and 13 additive residues were detected. Statistical tools were employed to screen the VOCs and successfully identified three components, i.e., 2,4-dimethyl-heptane, 4-methyl-octane and octamethylcyclotetrasiloxane (D4), which were significantly related to the odor intensity of the recycled plastic resin (p-values < 0.05). 2,4-Dimethyl-heptane has a strong, pungent plastic smell, which is very similar to the odor of the recycled resin. It is identified as a major source of the odor. Past relevant research has not been able to establish a direct link between an odorous compound and the undesirable odor of recycled plastic until now. 4-Methyl-octane was highly corelated to 2,4-dimethyl-heptane and somewhat contributed to the odor. D4 does not have an odor, but it may serve as an indicator of some odorous residues from personal care products.

Analysis of the Causes on Poor Clinical Efficacy of Kyphoplasty Performed in Unilateral Transpedicular Puncture for the Treatment of Senile Osteoporotic Vertebral Compression Fractures.

This study intends to analyze the causes on poor clinical efficacy of kyphoplasty performed in unilateral transpedicular puncture for the treatment of senile osteoporotic vertebral compression fractures. A retrospective study was conducted on a consecutive series of 70 patients who had underwent kyphoplasty performed in unilateral transpedicular puncture for the treatment of senile osteoporotic vertebral compression fractures between March 2016 to March 2017. These patients were compared for clinical data to investigate the causes on poor clinical efficacy of kyphoplasty performed in unilateral transpedicular puncture for the treatment of senile osteoporotic vertebral compression fractures. Comparison result of the indices between these patients showed that the differences in body weight, fracture type and bone cement dispersion were statistically significant. Logistic multivariate regression analysis showed body weight (OR = 0.892, p = 0.042), fracture type 2 (OR = 0.089, p = 0.020) and bone cement dispersion (OR = 4.773, p = 0.025) are risk factors for poor clinical efficacy. The results of corresponding analysis on VAS (Visual Analogue Scale), vertebral height and Cobb angle in patients with poor clinical efficacy showed that there is a correlation between them. We believe that patients' weight, dispersion degree of bone cement and fracture type of injured vertebra are the risk factors of kyphoplasty with poor clinical efficacy.

Adherent and non-adherent dendritic cells are equivalently qualified in GM-CSF, IL-4 and TNF-α culture system.

We compared the purities, phenotype, capabilities of antigen uptake and T lymphocytes stimulation abilities of adherent and non-adherent cells of human monocyte-derived dendritic cells (mono-DCs) in GM-CSF, IL-4 and TNF-α culture system. The results show that both the purities and the capabilities of antigen uptake of the adherent DCs are significantly higher than those of non-adherent ones. As for the expression levels of surface markers and the abilities of stimulating lymphocytes proliferation, our results also show that those of adherent DCs are a bit higher than those of non-adherent ones, although the differences are not significant.

[Comparison of phenotype and functions of dendritic cells in culture medium supplemented with different serum or plasma].

AIM: To find a safe and effective method of culturing dendritic cells (DCs) for clinical application by comparing the phenotype and functions of DCs in different culture mediums which are supplemented with 100 mL/L fetal bovine serum (FBS), 20 mL/L human AB serum and 10 mL/L autologous plasma. METHODS: Peripheral blood mononuclear cells (PBMCs) were induced to DCs in 100 mL/L FBS, 20 mL/L human AB serum, and 10 mL/L autologous plasma, respectively. On day 8, the purity, phenotype and antigen uptake capability of DCs were examined by flow cytometry. The mixed lymphocyte reaction (MLR) was detected by MTT assay. RESULTS: Focused on DC aggregates, DC yield, DC purity, antigen uptake capability and ability of stimulating lymphocyte proliferation, the experiments showed that those of 100 mL/L FBS culture group were better than those of 20 mL/L human AB serum and 10 mL/L autologous plasma culture groups. There was no significant difference among these three culture groups (P>0.05) except DC yield (P<0.05). CONCLUSION: Autologous plasma is the best choice for DC cultivation among these three culture ways. It is a safe and efficient way for culturing DCs for clinical purpose.