Particulate Cell Wall Materials of Lactobacillus acidophilus as Vaccine Adjuvant.

We evaluated Lactobacillus acidophilus (LA) for adjuvant application in animal vaccines. LA particles (LAPs) are made by treating LA with purification processes and high-pressure homogenization (HPH). We found that LAPs treated with HPH with trehalose and emulsifiers had an average particle size of 179 nm, considerably smaller than LAPs without additives. First, we evaluated the adjuvanticity of LAPs using a murine model with ovalbumin antigens, revealing that LAPs, especially in a five-fold concentration, could induce a considerable antibody response compared with other current adjuvants. In poultry vaccination tests using inactivated Newcastle disease virus, LAPs alone could induce a similar antibody response compared to commercial water-in-oil (W/O) adjuvant ISA70, a commercial adjuvant, at weeks 4 and 6; however, they declined faster than ISA70 at weeks 8 and 10. LAPs added to conventional adjuvant materials, such as mineral oil-based O/W emulsions, showed similar adjuvanticity to ISA70. LA-H5-C, composed of carbomer, emulsifiers and trehalose showed no significant body weight change in acute toxicity compared to other adjuvants including ISA70, making formulated LAPs a potential candidate for use as a veterinary vaccine adjuvant.

Metabolic remodeling in tumor-associated macrophages contributing to antitumor activity of cryptotanshinone by regulating TRAF6-ASK1 axis.

Dampening tumor growth by converting tumor-associated macrophages (TAMs) from M2/repair-types to M1/kill-types is of high interest. Here, we show that cryptotanshinone (CPT) can function as an antitumor immune modulator that switches TAMs from an M2 to an M1 phenotype, leading to tumor regression. An orthotopic triple-negative breast cancer (TNBC) implantation model was used to determine the role and mechanism of CPT in suppressing M1-to-M2 repolarization of TAMs. Co-culturing TNBC cells with CPT-treated macrophages reduced TNBC proliferation and motility, while in TNBC orthotopic mouse models, CPT treatment inhibited breast tumor formation. Moreover, we identified that CPT inhibits mitochondrial oxidative phosphorylation and mitochondrial fusion via autophagy and transcriptional activation of the apoptosis signal-regulating kinase 1 (ASK1) pathway. Suppression of ASK1 downregulates autophagy and abolishes CPT-induced effects upon TAMs. In addition, CPT inhibits M2 macrophage differentiation and causes TRAF6 auto-ubiquitination-dependent activation of the ASK1, leading to M1 polarization. On the contrary, in M1 macrophage, CPT increases interaction of ASK1 and TRAF6 which induces ASK1 ubiquitination and degradation. Intriguingly, CPT plays opposite roles in the M1 and M2 phenotype. Our findings help to illuminate a previously unrecognized antitumor mechanism of CPT and suggest that this natural compound offers a macrophage-based approach for cancer immunotherapy.

Autophagy Upregulates miR-449a Expression to Suppress Progression of Colorectal Cancer.

Many studies reported that microRNAs (miRNAs) target autophagy-related genes to affect carcinogenesis, however, autophagy-deficiency-related miRNA dysfunction in cancer development remains poorly explored. During autophagic progression, we identified miR-449a as the most up-regulated miRNA. MiR-449a expression was low in the tumor parts of CRC patient specimens and inversely correlated with tumor stage and metastasis with the AUC (area under the curve) of 0.899 and 0.736 as well as poor overall survival rate, indicating that miR-449a has the potential to be a prognostic biomarker. In the same group of CRC specimens, low autophagic activity (low Beclin 1 expression and high p62 accumulation) was detected, which was significantly associated with miR-449a expression. Mechanistic studies disclosed that autophagy upregulates miR-449a expression through degradation of the coactivator p300 protein which acetylates the transcription factor Forkhead Box O1 (FoxO1). Unacetylated FoxO1 translocated to the nucleus and bound to the miR-449a promoter to drive gene expression. Either activation of autophagy by the inducer or overexpression of exogenous miR-449a decreases the expression of target gene LEF-1 and cyclin D1, which lead to decreased proliferation, colony formation, migration, and invasion of CRC cells. Autophagy-miR-449a-tartet genes mediated suppression of tumor formation was further confirmed in the xenograft mouse model. In conclusion, this study reveals a novel mechanism wherein autophagy utilizes miR-449a-LEF1-cyclin D1 axis to suppress CRC tumorigenesis. Our findings open a new avenue toward prognosis and treatment of CRC patients by manipulating autophagy-miR-449a axis.

Dual-acting antibacterial porous chitosan film embedded with a photosensitizer.

This study proposes to develop a dual-acting antibacterial film of porous chitosan (Cs) embedded with small molecular compound, which possesses photosensitive characteristics with bactericidal efficacy, to promote the accelerated recovery of infectious wounds. The Cs/small molecular compound (Cs-cpd.2) dressing was prepared using the freeze-drying method. Characterization of the synthesized Cs-cpd.2 indicated that it has high porosity and moisture absorption effect, hence enhancing the absorption of wound exudate. Experimental results showed that Cs-cpd.2 dressing has good bactericidal and bacteriostatic effects on Staphylococcus aureus under visible-light irradiation and has antibacterial effect in the dark. It was also found that the small molecular compound does not have cytotoxicity at a dose of 0-5 µM. Furthermore, Cs-cpd.2 that contained small molecular compound with a concentration of 0.3-1 µM has positive effect on both the cell viability rate and cell proliferation rate of human fibroblast CG1639. Cs-cpd.2 can significantly promote cell proliferation when the small molecular compound and the basic fibroblast growth factor bFGF were added together. Therefore, the proposed Cs-cpd.2 dressing is feasible for photodynamic therapy (PDT) and clinical wound dressing applications.

Higher NAFLD fibrosis score is associated with impaired eGFR.

BACKGROUND/PURPOSE: Chronic kidney disease (CKD) has become a worldwide health problem, leading to high morbidity and mortality, and non-alcoholic fatty liver disease (NAFLD) is considered a risk factor for CKD. The aim of this study was to explore the relationship between NAFLD fibrosis score (NFS) and the estimated glomerular filtration rate (eGFR), and identify possible risk factors related to the NFS among Taiwanese subjects. METHODS: Subjects were enrolled from the database of the Department of Preventive Medicine of Kaohsiung Municipal Hsiao-Kang Hospital. The eGFR was calculated according to the Taiwanese Modification of Diet in Renal Disease (TMDRD) equation, and the NFS was employed to evaluate the fibrotic level. RESULTS: In total, 11,376 subjects were enrolled in this study, with a mean age of 52.0 ± 6.81 years, including 4529 (39.8%) males. A fasting sugar level ≥100 mg/dL (OR = 1.70, 95% CI = 1.52-1.87) and an abnormal waist circumference (OR = 1.81, 95% CI = 1.65-1.99) were significant factors associated with NFS (p < 0.05). Trends of a decreasing TMDRD score and an increasing NFS with increasing age were noted (p < 0.05). The NFS was significantly negatively correlated with the TMDRD score (standard coefficients: -0.067, p < 0.001). CONCLUSION: A higher NFS is associated with an impaired eGFR in Taiwanese subjects. Controlling risk factors, especially fasting sugar level and waist circumference, may be useful in preventing NFS deterioration, which is negatively correlated with the eGFR.

Micropatterned topographies reveal measurable differences between cancer and benign cells.

During metastasis, cancer cells migrate away from the primary tumor-site, encountering different microenvironment topographies that may facilitate or inhibit cancer cell adherence and growth; those relate to sites of invasion and seeding. To evaluate topography effects, poly-lactic-poly-glycolic (PLGA) gels are generated as flat substrates, porous, or with rectangular microchannels of varying widths (5-100 µm) and depths (10/20 µm). The topography effect on time-dependent adherence, proliferation, morphology, alignment and long-term structural development of metastatic breast-cancer and benign cells are evaluated; adherence at short time-scales (3 h) is compared to developed morphologies and multicellular structures (>2 days) indicating function. At short time-scales, both cell types exhibit rounded morphologies, however, while the benign cells tend to cluster the cancer cells preferentially adhered as single cells at high-curvature substrate-sites (e.g. convex pore-edges or channel-edges). At long times, the benign cells develop extensive, tissue-like multicellular sheets spanning across several 10 µm deep channels or filling in single-file 20 µm-deep narrow channels (5-15 µm). Contrastingly, cancer cells mainly attach as single cells to high-curvature channel bottoms, in alignment with narrow channels. Thus, cell responses to topography, specifically their localization and growth in narrow microchannels, may provide a way to distinguish cancer from benign cells, by demonstrating their inherent function.

Muscle relaxation for individuals having tattoos removed through laser treatment: possible effects regarding anxiety and pain.

Effectively managing pain is vital for the well-being and satisfaction of patients undergoing dermatologic treatments involving lasers. This study investigates the potential outcome of using muscle relaxation techniques to reduce pain among people having their tattoos removed with laser treatment. This study consists of 56 participants (mean age 18.1 ± 2.1 years) that had tattoos removed using the principle of selective photothermolysis. These participants underwent muscle relaxation before receiving the laser treatment. Their peripheral skin temperatures (PST) were measured both at the beginning and the end of the muscle relaxation period. Then, the Beck Anxiety Inventory was applied to evaluate anxiety levels. Once the laser treatment was completed, pain levels were measured using a visual analogue scale. A total of 125 person-sessions of laser treatment and psychometric assessments were performed in this study. The muscle relaxation method significantly increased the PST of the participants while reducing the levels of anxiety and pain throughout the course of the laser treatment procedure. The PST, anxiety scores, and pain scores all showed significant correlations with one another. According to the results obtained, this study proposes that muscle relaxation techniques be considered possibly auxiliary treatment options for individuals having tattoos removed through laser treatment. Additional studies with a comparison group and a larger sample size are required in the future to confirm the effectiveness of such intervention.

Pulse shortening mode-locked fiber laser by thickness and concentration product of carbon nanotube based saturable absorber.

The dependence of thickness and concentration product (TCP) of single-wall carbon nanotubes saturable absorber (SWCNTs SA) on stabilizing and shortening pulsewidth in mode-locked fiber lasers (MLFLs) was investigated. We found that an optimized TCP for pulse energy and nonlinear self-phase modulation (SPM) enabled to determine the shorter pulsewidth and broader 3-dB spectral linewidth of the MLFLs. The shortest MLFL pulsewidth of 418 fs and broad spectral linewidth of 6 nm were obtained as the optimized TCP was 70.93 (µm•wt%), which was in good agreement with the area theorem prediction. This significant effect of TCP on pulse energy, SPM, pulsewidth, and spectral linewidth of MLFLs suggests that the TCP represents the total amount of SWCNTs in SA, which can be used as one of important and key parameters for characterizing the passive MLFL pulsewidth.

Revised Acute Physiology and Chronic Health Evaluation score as a predictor of neurosurgery intensive care unit readmission: a case-controlled study.

PURPOSE: Patients with neurologic system problems are among the most common patients readmitted to the intensive care unit (ICU). Readmission predictors for neurologic ICU patients have not been established. Previous research suggests that the Revised Acute Physiology and Chronic Health Evaluation (APACHE II) score is one indication of the critical status of ICU-admitted patients; however, the ability of the discharge APACHE II to predict readmission to the ICU requires further study. The purpose of this study was to investigate the ability of the APACHE II scoring system to predict ICU readmission of neurosurgical and ICU patients. MATERIALS AND METHODS: A retrospective case-controlled comparison study and a review of patient records for all patients admitted to 8 ICUs from January 2003 to June 2005 (N = 753) were conducted. Readmitted neurosurgery ICU patients were matched with 58 randomly selected nonreadmitted patients. RESULTS: Nine variables were significantly different between the readmission and case-controlled group. The APACHE II discharge score was the only significant predictor and was able to predict 18.6% of neurologic ICU readmissions. The risk of ICU readmission increased when the APACHE II score at the time of discharge exceeded 8.5 points. CONCLUSIONS: The risk of ICU readmission of neurologic ICU patients can be predicted by determining APACHE II score upon ICU discharge.