A novel amphiphilic squalene-based compound with open-chain polyethers reduces malignant melanoma metastasis in-vitro and in-vivo.

Squalene (SQ) is a well-known antioxidant and anti-inflammatory agent that provides promising anti-aging and UV-protective roles on human skin. However, its strong hydrophobic nature, accompanied by issues such as poor solubility and limited tissue permeation, has created challenges for scientists to investigate its untapped potential in more complex conditions, including cancer progression. The present study assessed the potent anti-metastatic properties of a newly synthesized amphiphilic ethylene glycol SQ derivative (SQ-diEG) in melanoma, the most fatal skin cancer. In vitro and in vivo experiments have discovered that SQ-diEG may exert its potential on melanoma malignancy through the mitochondria-mediated caspase activation apoptotic signaling pathway. The potent anti-metastatic effect of SQ-diEG was observed in vitro using highly proliferative and aggressive melanoma cells. Administration of SQ-diEG (25 mg/kg) significantly decreased the tumor burden on the lung and inhibited the metastasis-associated proteins and gene markers in B16F10 lung colonization mice model. Furthermore, global gene profiling also revealed a promising role of SQ-diEG in tumor microenvironment. We anticipated that the amphiphilic nature of the SQ compound bearing ethylene glycol oligomers could potentially augment its ability to reach the pathology site, thus enhancing its therapeutic potential in melanoma.

A comparative transcriptomics analysis reveals ethylene glycol derivatives of squalene ameliorate excessive lipogenesis and inflammatory response in 3T3-L1 preadipocytes.

Squalene (SQ) is a natural compound with anti-inflammatory, anti-cancer, and anti-oxidant effects, but due to its low solubility, its biological properties have been greatly underestimated. This study aims to explore the differences in gene expression patterns of four newly synthesized amphipathic ethylene glycol (EG) derivatives of SQ by whole-genome transcriptomics analysis using DNA microarray to examine the mRNA expression profile of adipocytes differentiated from 3T3-L1 cells treated with SQ and its EG derivatives. Enrichment analyses of the transcriptional data showed that compared with SQ, its EG derivatives exerted different, in most cases desirable, biological responses. EG derivatives showed increased enrichment of mitochondrial functions, lipid and glucose metabolism, and inflammatory response. Mono-, di-, and tetra-SQ showed higher enrichment of the cellular component-ribosome. Histological staining showed EG derivatives prevented excessive lipid accumulation. Additionally, mitochondrial transcription factors showed upregulation in tetra-SQ-treated cells. Notably, EG derivatives showed better anti-inflammatory effects. Further, gene-disease association analysis predicted substantial improvement in the bioactivities of SQ derivatives in metabolic diseases. Cluster analyses revealed di- and tetra-SQ had more functional similarities than others, reflected in their scanning electron microscopy images; both di- and tetra-SQ self-organized into similar sizes and shapes of vesicles, subsequently improving their cation binding activities. Protein-protein interaction networks further revealed that cation binding activity might explain a major part, if not all, of the differences observed in functional analyses. Altogether, the addition of EG derivatives may improve the biological responses of SQ and thus may enhance its health-promoting potential.

A Two-Flap Combination for Auricular Elevation in Microtia Reconstruction.

BACKGROUND: The aims of this study were to describe and evaluate the effectiveness of combined flaps, a modification of the Nagata technique, for providing a reasonable projection for reconstructed auricles. METHODS: The authors modified the Nagata method for covering the cartilage block by introducing a new combined flap technique, including the temporoparietal skin flap and retroauricular flap. The authors compared the shape, size, and position of the reconstructed ear to the opposite ear, and we evaluated postoperative complications and patient satisfaction levels. They verified the effectiveness of the combined flap by assessing flap necrosis, skin color, thickness, hair in the auricular area, and scars. RESULTS: A total of 38 consecutive patients (39 ears) with microtia, aged 6 to 34 years, underwent reconstruction using the modified method and were followed up for 33.6 months on average. The reconstructed auricle's shape was well defined, with 41.0% having good and 15.4% having excellent results. Most cases achieved good and acceptable levels in size, position, medial longitudinal axis angle, and auriculocephalic angles, and 79.9% of patients/their families were satisfied. The authors observed no cases of flap necrosis or hypertrophic scarring, and there were low rates of flap complications, such as unmatched skin color (7.7%), unacceptable thickness (5.1%), or hair and stretch marks (10.3%). CONCLUSIONS: The modified method's reconstructed ear achieved stable projection, symmetric appearance, and obvious anatomical landmarks with high patient satisfaction. The combined flap method showed certain advantages: high survival rate, less skin contrast, no hypertrophic scars, and fewer complications. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Microalgae extract induces antidepressant-like activity via neuroinflammation regulation and enhances the neurotransmitter system.

The increasing prevalence of mental disorders, such as depression, is currently a serious public health concern. Microalgae are a diverse group of organisms that contain many bioactive compounds such as polyunsaturated fatty acids and polyphenols. These compounds can exhibit many health benefits such as antioxidative, anti-inflammatory, anticancer, and anti-obesity effects. In the present study, we focused on microalgal (Botryococcus terribilis) extract (ME) rich in Me-meijicoccene (MM), a novel compound. Our results showed that pretreatment of SH-SY5Y cells with ME and MM ameliorated dexamethasone (depression-causing substance)-induced cytotoxicity. The results of the tail suspension test (TST) indicated that ME (50 mg/kg) induced antidepressant-like activity in TST-stressed mice. Our microarray analysis revealed that ME upregulated neurotransmitter-related gene (neurotransmitter secretion) expression and downregulated neuroinflammatory-related gene (chemokine-mediated signaling) expression in the cerebral cortex. ME also induced an increase in neurotransmitter and brain-derived neurotrophic factor levels, and a decrease in corticosterone and pro-inflammatory cytokine levels in the serum, cerebral cortex, and hypothalamus. Altogether, our study is the first to report that 50 mg/kg ME (not 100 mg/kg) exerts antidepressant-like effects via regulating neuroinflammation and modulating neurotransmitter systems in the mouse brain, highlighting the prospects of ME in the treatment of depressive disorders of a psychosocial nature.

Elucidation of the Potential Hair Growth-Promoting Effect of Botryococcus terribilis, Its Novel Compound Methylated-Meijicoccene, and C32 Botryococcene on Cultured Hair Follicle Dermal Papilla Cells Using DNA Microarray Gene Expression Analysis.

A person's quality of life can be adversely affected by hair loss. Microalgae are widely recognized for their abundance and rich functional components. Here, we evaluated the hair growth effect of a green alga, Botryococcus terribilis (B. terribilis), in vitro using hair follicle dermal papilla cells (HFDPCs). We isolated two types of cells from B. terribilis-green and orange cells, obtained from two different culture conditions. Microarray and real time-PCR results revealed that both cell types stimulated the expression of several pathways and genes associated with different aspect of the hair follicle cycle. Additionally, we demonstrated B. terribilis' effect on collagen and keratin synthesis and inflammation reduction. We successfully isolated a novel compound, methylated-meijicoccene (me-meijicoccene), and C32 botryococcene from B. terribilis to validate their promising effects. Our study revealed that treatment with the two compounds had no cytotoxic effect on HFDPCs and significantly enhanced the gene expression levels of hair growth markers at low concentrations. Our study provides the first evidence of the underlying hair growth promoting effect of B. terribilis and its novel compound, me-meijicoccene, and C32 botryococcene.

Release kinetics of esterified p-coumaric acid and ferulic acid from rice straw in mild alkaline solution.

The release kinetics of esterified p-coumaric acid (PCA) and ferulic acid (FA) from rice straw under a mild alkaline condition were investigated to collect fundamental data for the design of a recovery process. The results showed that the straw size, NaOH concentration, and temperature were the key parameters governing release kinetics. The analysis demonstrated that FA is released considerably faster than PCA. The close relationship between lignin and the PCA dissolution indicates a reciprocal and/or simultaneous release. Moreover, PCA is broadly distributed in the lignin network but tends to be located more densely in the lignin fraction which is not easily solubilized by alkaline treatment. In contrast, the release of FA is strongly affected by removal of lignin fraction which is easily solubilized. These results suggest that the release kinetics are controlled by the accessibility of NaOH to their ester sites in the lignin/hemicellulose network, and by their localization.