Preparation of Thifluzamide Polylactic Acid Glycolic Acid Copolymer Microspheres and Its Effect on the Growth of Cucumber Seedlings.

The polylactic acid-glycolic acid copolymer (PLGA) has been proven to be applicable in medicine, but there is limited research on its application and safety in the agricultural field. In this paper, thifluzamide PLGA microspheres were prepared via phacoemulsification and solvent volatilization, using the PLGA copolymer as the carrier and thifluzamide as the active component. It was found that the microspheres had good slow-release performance and fungicidal activity against Rhizoctonia solani. A comparative study was conducted to show the effect of thifluzamide PLGA microspheres on cucumber seedlings. Physiological and biochemical indexes of cucumber seedlings, including dry weight, root length, chlorophyll, protein, flavonoids, and total phenol content, indicated that the negative effect of thifluzamide on plant growth could be mitigated when it was wrapped in PLGA microspheres. This work explores the feasibility of PLGA as carriers in fungicide applications.

C6 ceramide motivates the anticancer sensibility induced by PKC412 in preclinical head and neck squamous cell carcinoma models.

The purpose of this study was to evaluate the anti-head and neck squamous cell carcinoma (anti-HNSCC) cell activity by C6 ceramide and multikinase inhibitor PKC412. Experiments were performed on HNSCC cell lines (SQ20B and SCC-9) and primary human oral carcinoma cells. Results showed that PKC412 inhibited HNSCC cell proliferation without provoking apoptosis activation. Cotreatment of C6 ceramide significantly augmented PKC412-induced lethality in HNSCC cells. PKC412 decreased Akt-mammalian target of rapamycin (mTOR) activation in HNSCC cells, facilitated with cotreatment of C6 ceramide. In contrast, exogenous expression of a constitutively active Akt restored Akt-mTOR activation and attenuated lethality by the cotreatment. We propose that Mcl-1 is a primary resistance factor of PKC412. The cytotoxicity of PKC412 in HNSCC cells was potentiated with Mcl-1 short hairpin RNA knockdown, but was attenuated with Mcl-1 overexpression. Intriguingly, C6 ceramide downregulated Mcl-1 in HNSCC cells. In vivo, PKC412 oral administration inhibited SQ20B xenograft tumor growth in severe combined immunodeficient mice. The antitumor activity of PKC412 was further sensitized with coadministration of liposomal C6 ceramide. Together, we suggest that PKC412 could be further studied as a promising anti-HNSCC strategy, alone or in combination with C6 ceramide.

Delivery of LINC00589 via mesoporous silica nanoparticles inhibits peritoneal metastasis in gastric cancer.

Peritoneal metastasis is one of the common forms of metastasis in gastric cancer (GC). In this study, we identified the expression pattern of LINC00589 in GC patients and investigate the biological function in GC cells. RNA-pulldown assay was performed to explore the underlying molecular mechanism. Further, we utilize polyethyleneimine-modified mesoporous silica nanoparticles (PMSNs) as the nanocarriers for delivery of LINC00589 encoding plasmid and tested its therapeutic potential for GC with peritoneal dissemination. We revealed that LINC00589 was downregulated in GC tissues and suppressed the metastatic ability of GC cells. Mechanistically, LINC00589 exerted tumor suppressive function by promoting hnRNPA1 protein ubiquitination and proteasomal degradation, thus blocking alternative splicing of PKM to PKM2. Furthermore, LINC00589 delivered by PMSNs could suppress the peritoneal metastasis of GC in vivo and in vitro. This work may provide a new treatment option in GC peritoneal metastasis.