Multifunctional Covalent Organic Framework-Based Microneedle Patch for Melanoma Treatment.

Melanoma is resistant to conventional chemotherapy and radiotherapy. Therefore, it is essential to develop a targeted, low-toxic, and minimally invasive treatment. Here, DTIC/ICG-Fe3O4@TpBD BSP/HA microneedles (MNs) were designed and fabricated, which can enhance targeting to melanoma and perform photothermal therapy (PTT) and chemotherapy simultaneously to synergistically exert anticancer effects. The system consisted of magnetic nanoparticles (DTIC/ICG-Fe3O4@TpBD), dissoluble matrix (Bletilla polysaccharide (BSP)/hyaluronic acid (HA)), and a polyvinyl alcohol backing layer. Due to the good magnetic responsiveness of Fe3O4@TpBD, dacarbazine (DTIC) and indocyanine green (ICG) can be better targeted to the tumor tissue and improve the therapeutic effect. BSP and HA have good biocompatibility and transdermal ability, so that the MNs can completely penetrate the tumor tissue, be dissolved by the interstitial fluid, and release DTIC and ICG. Under near-infrared (NIR) light irradiation, ICG converts light energy into thermal energy and induces ablation of B16-OVA melanoma cells. In vivo results showed that DTIC/ICG-Fe3O4@TpBD BSP/HA MNs combined with chemotherapy and PTT could effectively inhibit the growth of melanoma without tumor recurrence or significant weight loss in mice. Therefore, DTIC/ICG-Fe3O4@TpBD BSP/HA MNs are expected to provide new ideas and therapeutic approaches for the clinical treatment of melanoma.

Short-term efficacy of music therapy combined with α binaural beat therapy in disorders of consciousness.

Objective: To investigate the short-term effect of music therapy combined with binaural frequency difference therapy on patients with consciousness disorder. Materials and methods: Ninety patients with definite diagnosis of disorders of consciousness (DOC) were selected. These patients were randomly divided into control group, experiment 1 group and experiment 2 group, with 30 patients in each group. The control group was treated with routine clinical treatment and rehabilitation. In experiment 1 group, music therapy was added to the control group. In experimental group 2, music therapy combined with binaural α frequency difference therapy was added to the control group. All patients were assessed before and after 30 treatments. The assessment items included Glasgow Coma Scale (GCS), Coma Recovery Scale revised (CRS-R), electroencephalogram (EEG), upper somatosensory evoked potential (USEP), and brainstem auditory evoked potential (BAEP). Results: Before treatment, there were no significant differences in GCS score, CRS-R score, USEP, BAEP, and EEG scores among the three groups (P > 0.05). After 30 times of treatment, GCS score, CRS-R score, USEP, BAEP, and EEG scores in 3 groups were significantly higher than those before treatment (P < 0.05), and experimental group 2 >experimental group 1 >control group (P < 0.05). And the consciousness rate of experimental group 2 was better than experimental group 1, experimental group 1 was better than the control group and the difference was statistically significant (P < 0.05). Conclusion: Music therapy combined with binaural α frequency difference therapy is more effective in stimulating DOC patients.

Alisol A 24-acetate stimulates lipolysis in 3 T3-L1 adipocytes.

BACKGROUND: Alisol A 24-acetate (AA-24-a), one of the main active triterpenes isolated from the well-known medicinal plant Alisma orientale (Sam.) Juz., exhibits multiple biological activities including hypolipidemic activity. However, its effect on lipid metabolism in adipocytes remains unclear. The present study aimed to clarify the effect of AA-24-a on adipocyte lipolysis and to determine its potential mechanism of action using 3 T3-L1 cells. METHODS: We assayed the release of glycerol into culture medium of 3 T3-L1 cells under treatment with AA-24-a. Protein and mRNA expression and phosphorylation levels of the main lipases and kinases involved in lipolysis regulation were determined by quantitative polymerase chain reaction and western blotting. Specific inhibitors of protein kinase A (PKA; H89) and extracellular signal-regulated kinase (ERK; PD98059), which are key enzymes in relevant signaling pathways, were used to examine their roles in AA-24-a-stimulated lipolysis. RESULTS: AA-24-a significantly stimulated neutral lipolysis in fully differentiated adipocytes. To determine the underlying mechanism, we assessed the changes in mRNA and protein levels of key lipolysis-related genes in the presence or absence of H89 and PD98059. Both inhibitors reduced AA-24-a-induced lipolysis. Moreover, pretreatment with H89 attenuated AA-24-a-induced phosphorylation of hormone-sensitive lipase at Ser660, while pretreatment with PD98059 attenuated AA-24-a-induced downregulation of peroxisome proliferator-activated receptor-γ and perilipin A. CONCLUSIONS: Our results indicate that AA-24-a promoted neutral lipolysis in 3 T3-L1 adipocytes by activating PKA-mediated phosphorylation of hormone-sensitive lipase and ERK- mediated downregulation of expression of perilipin A.

Association between microRNA 21 expression in serum and lung cancer: A protocol of systematic review and meta-analysis.

BACKGROUND: Previous studies have reported that microRNA 21 (mRNA 21) has involved in the procedure of lung cancer (LC). However, its conclusions are still unclear. Thus, this study will try to elaborate the association between mRNA 21 expression in serum and LC. METHODS: The electronic databases of Cochrane Library, PubMed, EMBASE, Allied and Complementary Medicine Database, WANGFANG database, and China National Knowledge Infrastructure will be retrieved from the inception to the present. All electronic databases will be searched without limitations of language and geographical location. Case-controlled studies reporting the association between mRNA 21 expression in serum and LC will be included. In addition, we will also identify other literature sources to avoid missing potential studies. All study selection, information collection, and study quality assessment will be performed by 2 independent authors. RevMan V.5.3 software and Stata V.12.0 software will be used for data synthesis and analysis. RESULTS: This study will summarize current evidence to investigate the association between mRNA 21 expression in serum and LC. CONCLUSION: The findings of this study will present comprehensive evidence to determine whether mRNA 21 expression in serum is relevant with LC or not. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040055.

Alisol A-24-acetate promotes glucose uptake via activation of AMPK in C2C12 myotubes.

BACKGROUND: Alisol A-24-acetate (AA-24-a) is one of the main active triterpenes isolated from the well-known medicinal plant Alisma orientale (Sam.) Juz., which possesses multiple biological activities, including a hypoglycemic effect. Whether AA-24-a is a hypoglycemic-active compound of A. orientale (Sam.) Juz. is unclear. The present study aimed to clarify the effect and potential mechanism of action of AA-24-a on glucose uptake in C2C12 myotubes. METHOD: Effects of AA-24-a on glucose uptake and GLUT4 translocation to the plasma membrane were evaluated. Glucose uptake was determined using a 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino)-2-deoxyglucose (2-NBDG) uptake assay. Cell membrane proteins were isolated and glucose transporter 4 (GLUT4) protein was detected by western blotting to examine the translocation of GLUT4 to the plasma membrane. To determine the underlying mechanism, the phosphorylation levels of proteins involved in the insulin and 5'-adenosine monophosphate-activated protein kinase (AMPK) pathways were examined using western blotting. Furthermore, specific inhibitors of key enzymes in AMPK signaling pathway were used to examine the role of these kinases in the AA-24-a-induced glucose uptake and GLUT4 translocation. RESULTS: We found that AA-24-a significantly promoted glucose uptake and GLUT4 translocation in C2C12 myotubes. AA-24-a increased the phosphorylation of AMPK, but had no effect on the insulin-dependent pathway involving insulin receptor substrate 1 (IRS1) and protein kinase B (PKB/AKT). In addition, the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and the AKT substrate of 160 kDa (AS160), two proteins that act downstream of AMPK, was upregulated. Compound C, an AMPK inhibitor, blocked AA-24-a-induced AMPK pathway activation and reversed AA-24-a-induced glucose uptake and GLUT4 translocation to the plasma membrane, indicating that AA-24-a promotes glucose metabolism via the AMPK pathway in vitro. STO-609, a calcium/calmodulin-dependent protein kinase kinase ß (CaMKKß) inhibitor, also attenuated AA-24-a-induced glucose uptake and GLUT4 translocation. Moreover, STO-609 weakened AA-24-a-induced phosphorylation of AMPK, p38 MAPK and AS160. CONCLUSIONS: These results indicate that AA-24-a isolated from A. orientale (Sam.) Juz. significantly enhances glucose uptake via the CaMKKß-AMPK-p38 MAPK/AS160 pathway.

The inulin-type oligosaccharides extract from morinda officinalis, a traditional Chinese herb, ameliorated behavioral deficits in an animal model of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a severe psychiatric condition. The allopregnanolone biosynthesis has been implicated as one of the possible contributors to PTSD. Inulin-type oligosaccharides of morinda officinalis (IOMO) had been shown to be effective in the therapy of depression. However, few studies concern the anti-PTSD-like effects of IOMO. To evaluate this, the single prolonged stress (SPS) model was used in the present study. It had been shown that the behavioral deficits of SPS-treated rats were reversed by IOMO (25.0 and 50.0 mg/kg, i.p.), which reversed the increased freezing time in contextual fear paradigm (CFP) and the decreased time and entries in open arms in the elevated plus maze (EPM) test without affecting the locomotor activity in the open field (OF) test. In addition, the decreased allopregnanolone in the prefrontal cortex, hippocampus, and amygdala was reversed by IOMO (25.0 and 50.0 mg/kg, i.p.), respectively. In summary, the present study indicated that the IOMO exert anti-PTSD-like behaviors, which maybe associated with the brain allopregnanolone biosynthesis.

Baicalein inhibits DMBA/TPA-induced skin tumorigenesis in mice by modulating proliferation, apoptosis, and inflammation.

Baicalein, one of the four major flavanoids extracted from the root of Scutellaria baicalensis, has been shown to exert chemopreventive effect against several cancers, including skin cancer. However, the precise mechanisms remain to be elucidated. In the present study, we investigated the chemopreventive activity of baicalein against 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-mediated skin tumorigenesis in C57BL/6 mice. We found that topical treatment with baicalein resulted in a significant inhibitory effect on DMBA/TPA-mediated tumor promotion. Furthermore, we observed that baicalein suppressed cell proliferation and promoted apoptosis in DMBA/TPA-mediated group. Additionally, pretreatment with baicalein inhibited the production of inflammatory cells in DMBA/TPA-induced skin/tumors. Further experiments showed that baicalein reduced TPA-induced skin hyperplasia as well as infiltration of polymorphonuclear leukocytes in the dermis. In conclusion, our data suggest that baicalein inhibits DMBA/TPA-induced skin tumorigenesis by suppressing proliferation and inflammation and promoting apoptosis.