Non-Einstein Viscosity Phenomenon of Acrylonitrile–Butadiene–Styrene Composites Containing Lignin–Polycaprolactone Particulates Highly Dispersed by High-Shear Stress

Lignin powder was modified via ring-opening polymerization of caprolactone to form a lignin–polycaprolactone (LPCL) particulate. The LPCL particulates were mixed with an acrylonitrile–butadiene–styrene (ABS) matrix at an extremely high rotational speed of up to 3000 rpm, which was achieved by a closed-loop screw mixer and in-line melt extruder. Using this high-shear extruding mixer, the LPCL particulate size was controlled in the range of 3395 nm (conventional twin-screw extrusion) down to 638 nm (high-shear mixer of 3000 rpm) by altering the mixing speed and time. The resulting LPCL/ABS composites clearly showed non-Einstein viscosity phenomena, exhibiting reduced viscosity (2130 Pa·s) compared to the general extruded composite one (4270 Pa·s) at 1 s–1 and 210 °C. This is due to the conformational rearrangement and the increased free volume of ABS molecular chains in the vicinity of LPCL particulates. This was supported by the decreased glass transition temperature (Tg, 83.7 °C) of the LPCL/ABS composite specimens, for example, giving a 21.8% decrement compared to that (107 °C) of the neat ABS by the incorporation of 10 wt % LPCL particulates in ABS. The LPCL particulate morphology, damping characteristics, and light transmittance of the developed composites were thoroughly investigated at various levels of applied shear rates and mixing conditions. The non-Einstein rheological phenomena stemming from the incorporation of LPCL particulates suggest an interesting plasticization methodology: to improve the processability of high-loading filler/polymer composites and ultra-high molecular weight polymers that are difficult to process because of their high viscosity

Generation of subspecies level-specific microbial diagnostic microarrays using genes amplified from subtractive suppression hybridization as microarray probes

The generation of microarray probes with specificity below the species level is an ongoing challenge, not least because the high-throughput detection of microorganisms would be an efficient means of identifying environmentally relevant microbes. Here, we describe how suppression subtractive hybridization (SSH) can be applied to the production of microarray probes that are useful for microbial differentiation at the subspecies level. SSH was used to initially isolate unique genomic sequences of nine Salmonella strains, and these were validated in quadruplicate by microarray analysis. The results obtained indicate that a large group of genes subtracted by SSH could serve together, as one probe, for detecting a microbial subspecies. Similarly, the whole microbial genome (not subjected to SSH) can be used as a species-specific probe. The detailed methods described herein could be used and adapted for the estimation of any cultivable bacteria from different environments

Therapeutic Co-targeting of WEE1 and ATM Downregulates PD-L1 Expression in Pancreatic Cancer

Purpose Pancreatic cancer (PC) is one of the most lethal cancers worldwide, but there are currently no effective treatments. The DNA damage response (DDR) is under investigation for the development of novel anti-cancer drugs. Since DNA repair pathway alterations have been found frequently in PC, the purpose of this study was to test the DDR-targeting strategy in PC using WEE1 and ATM inhibitors. Materials and Methods We performed in vitro experiments using a total of ten human PC cell lines to evaluate antitumor effect of AZD1775 (WEE1 inhibitor) alone or combination with AZD0156 (ATM inhibitor). We established Capan-1-mouse model for in vivo experiments to confirm our findings. Results In our research, we found that WEE1 inhibitor (AZD1775) as single agent showed anti-tumor effects in PC cells, however, targeting WEE1 upregulated p-ATM level. Here, we observed that co-targeting of WEE1 and ATM acted synergistically to reduce cell proliferation and migration, and to induce DNA damage in vitro. Notably, inhibition of WEE1 or WEE1/ATM downregulated programmed cell death ligand 1 expression by blocking glycogen synthase kinase-3 beta serine 9 phosphorylation and decrease of CMTM6 expression. In Capan-1 mouse xenograft model, AZD1775 plus AZD0156 (ATM inhibitor) treatment reduced tumor growth and downregulated tumor expression of programmed cell death ligand 1, CMTM6, CD163, and CXCR2, all of which contribute to tumor immune evasion. Conclusion Dual blockade of WEE1 and ATM might be a potential therapeutic strategy for PC. Taken together, our results support further clinical development of DDR-targeting strategies for PC.

Anti-proliferative effects of Bifidobacterium adolescentis SPM0212 extract on human colon cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Lactic acid bacteria (LAB) are beneficial probiotic organisms that contribute to improved nutrition, microbial balance, and immuno-enhancement of the intestinal tract, as well as anti-tumor activity. The aim of the present work was to study the growth inhibition of tumor cells by butanol extract of <it>Bifidobacterium adolescentis </it>isolated from healthy young Koreans.</p> <p>Methods</p> <p>The anti-proliferative activity of <it>B. adolescentis </it>isolates was assessed by XTT assays on three human colon cancer cell lines (Caco-2, HT-29, and SW480). The effects of <it>B. adolescentis </it>SPM0212 butanol extract on tumor necrosis factor-α (TNF-α) and nitric oxide (NO) production were tested using the murine macrophage RAW 264.7 cell line.</p> <p>Results</p> <p>The butanol extract of <it>B. adolescentis </it>SPM0212 dose-dependently inhibited the growth of Caco-2, HT-29, and SW480 cells by 70%, 30%, and 40%, respectively, at 200 μg/mL. Additionally, the butanol extract of <it>B. adolescentis </it>SPM0212 induced macrophage activation and significantly increased the production of TNF-α and NO, which regulate immune modulation and are cytotoxic to tumor cells.</p> <p>Conclusion</p> <p>The butanol extract of <it>B. adolescentis </it>SPM0212 increased activity of the host immune system and may improve human health by helping to prevent colon cancer as a biological response modifier.</p

Inhibition of ATR Increases the Sensitivity to WEE1 Inhibitor in Biliary Tract Cancer

Purpose Currently, the DNA damage response (DDR) pathway represents a key target for new cancer drug development. Advanced biliary tract cancer (BTC) has a poor prognosis because of the lack of efficacious treatment options. Although DNA repair pathway alterations have been reported in many patients with BTC, little is known regarding the effects of DDR-targeted agents against BTC. Materials and Methods In this study, nine BTC cell lines were exposed to the WEE1 inhibitor (AZD1775). In vitro, MTT assay, colony-forming assay, cell cycle analysis, phospho-histone H3 staining assay, Transwell migration assay, and western blot were performed. Then, to enhance the antitumor effect of AZD1775, the combination treatment of WEE1 inhibitor and ataxia telangiectasia mutated and Rad3 related (ATR) inhibitor (AZD6738) was conducted using MTT assay and comet assay. Finally, HuCCT-1 and SNU2670 xenograft models were established to confirm the anti-tumor effect of AZD1775 alone. Furthermore, the combination treatment was also evaluated in SNU2670 xenograft models. Results AZD1775 blocked the phosphorylation of CDC2 and CDC25C in all cell lines, but significantly increased apoptosis and S phase arrest in sensitive cells. However, increased p-ATR and phosphorylated ataxia telangiectasia mutated levels were observed in less sensitive cells. In addition, in vitro and in vivo data illustrated that AZD1775 combined with AZD6738 exerted more potent anti-tumor effects than either drug alone. Although WEE1 inhibition has promising anti-tumor effects in some BTC cells, the addition of ATR inhibitors could enhance its efficacy. Conclusion Taken together, this study supports further clinical development of DDR-targeted strategies as monotherapy or combination regimens for BTC.

Management of Proximal Iliac Artery Injury during Lumbar Discectomy with Stent Graft

Iatrogenic vascular injuries during lumbar disc surgery may occur rarely but they are serious complications, which can be fatal without appropriate management. Prompt diagnosis and management of these complications are imperative to prevent a desperate outcome. A 72-year-old female with proximal left common iliac artery iatrogenic injury during lumbar discectomy was successfully treated by percutaneous deployment of a stent graft in an emergency setting. Postprocedural angiogram demonstrated complete exclusion of the iliac artery laceration. The patient became hemodynamically stable. Two weeks later she complained of vascular claudication. Follow-up angiography revealed decreased arterial flow in the opposite common iliac artery. An additional kissing stent was inserted into the right common iliac artery and the symptoms of vascular claudication disappeared. Endovascular stenting offers a safe and effective method for the treatment of an iatrogenic arterial laceration, particularly in a critical condition. But, the contralateral iliac arterial flow should be kept intact in case of proximal iliac artery injury. Otherwise, additional treatments may be needed

Lactic acid bacteria affect serum cholesterol levels, harmful fecal enzyme activity, and fecal water content

<p>Abstract</p> <p>Background</p> <p>Lactic acid bacteria (LAB) are beneficial probiotic organisms that contribute to improved nutrition, microbial balance, and immuno-enhancement of the intestinal tract, as well as lower cholesterol. Although present in many foods, most trials have been in spreads or dairy products. Here we tested whether <it>Bifidobacteria </it>isolates could lower cholesterol, inhibit harmful enzyme activities, and control fecal water content.</p> <p>Methods</p> <p><it>In vitro </it>culture experiments were performed to evaluate the ability of <it>Bifidobacterium </it>spp. isolated from healthy Koreans (20~30 years old) to reduce cholesterol-levels in MRS broth containing polyoxyethanylcholesterol sebacate. Animal experiments were performed to investigate the effects on lowering cholesterol, inhibiting harmful enzyme activities, and controlling fecal water content. For animal studies, 0.2 ml of the selected strain cultures (10⁸~10⁹CFU/ml) were orally administered to SD rats (fed a high-cholesterol diet) every day for 2 weeks.</p> <p>Results</p> <p><it>B. longum </it>SPM1207 reduced serum total cholesterol and LDL levels significantly (<it>p </it>< 0.05), and slightly increased serum HDL. <it>B. longum </it>SPM1207 also increased fecal LAB levels and fecal water content, and reduced body weight and harmful intestinal enzyme activities.</p> <p>Conclusion</p> <p>Daily consumption of <it>B. longum </it>SPM1207 can help in managing mild to moderate hypercholesterolemia, with potential to improve human health by helping to prevent colon cancer and constipation.</p

Curative Effects of Thiacremonone against Acetaminophen-Induced Acute Hepatic Failure via Inhibition of Proinflammatory Cytokines Production and Infiltration of Cytotoxic Immune Cells and Kupffer Cells

High doses of acetaminophen (APAP; N-acetyl-p-aminophenol) cause severe hepatotoxicity after metabolic activation by cytochrome P450 2E1. This study was undertaken to examine the preventive effects of thiacremonone, a compound extracted from garlic, on APAP-induced acute hepatic failure in male C57BL/6J. Mice received with 500 mg/kg APAP after a 7-day pretreatment with thiacremonone (10–50 mg/kg). Thiacremonone inhibited the APAP-induced serum ALT and AST levels in a dose-dependent manner, and markedly reduced the restricted area of necrosis and inflammation by administration of APAP. Thiacremonone also inhibited the APAP-induced depletion of intracellular GSH, induction of nitric oxide, and lipid peroxidation as well as expression of P450 2E1. After APAP injection, the numbers of Kupffer cells, natural killer cells, and cytotoxic T cells were elevated, but the elevated cell numbers in the liver were reduced in thiacremonone pretreated mice. The expression levels of I-309, M-CSF, MIG, MIP-1α, MIP-1β, IL-7, and IL-17 were increased by APAP treatment, which were inhibited in thiacremonone pretreated mice. These data indicate that thiacremonone could be a useful agent for the treatment of drug-induced hepatic failure and that the reduction of cytotoxic immune cells as well as proinflammatory cytokine production may be critical for the prevention of APAP-induced acute liver toxicity

Chylous Leakage: A Rare Complication after Axillary Lymph Node Dissection in Breast Cancer and Surgical Management

Chylous leakage is an extremely rare complication of surgery for breast cancer. We experienced a case of chylous leakage after axillary lymph node dissection. A 38-year-old woman with invasive ductal carcinoma in the left breast underwent a modified radical mastectomy after four cycles of neoadjuvant chemotherapy. The postoperative serosanguinous drainage fluid became "milky" on the fourth postoperative day. After trying conservative management, we re-explored the axilla and ligated the lymphatic trunk. Although the success of many cases supports conservative management, timely surgical intervention represents an alternative in cases where leakage persists or where the output is high

Trans-Differentiation of Neural Stem Cells: A Therapeutic Mechanism Against the Radiation Induced Brain Damage

Radiation therapy is an indispensable therapeutic modality for various brain diseases. Though endogenous neural stem cells (NSCs) would provide regenerative potential, many patients nevertheless suffer from radiation-induced brain damage. Accordingly, we tested beneficial effects of exogenous NSC supplementation using in vivo mouse models that received whole brain irradiation. Systemic supplementation of primarily cultured mouse fetal NSCs inhibited radiation-induced brain atrophy and thereby preserved brain functions such as short-term memory. Transplanted NSCs migrated to the irradiated brain and differentiated into neurons, astrocytes, or oligodendrocytes. In addition, neurotrophic factors such as NGF were significantly increased in the brain by NSCs, indicating that both paracrine and replacement effects could be the therapeutic mechanisms of NSCs. Interestingly, NSCs also differentiated into brain endothelial cells, which was accompanied by the restoration the cerebral blood flow that was reduced from the irradiation. Inhibition of the VEGF signaling reduced the migration and trans-differentiation of NSCs. Therefore, trans-differentiation of NSCs into brain endothelial cells by the VEGF signaling and the consequential restoration of the cerebral blood flow would also be one of the therapeutic mechanisms of NSCs. In summary, our data demonstrate that exogenous NSC supplementation could prevent radiation-induced functional loss of the brain. Therefore, successful combination of brain radiation therapy and NSC supplementation would provide a highly promising therapeutic option for patients with various brain diseases