Effects of down-regulated carbonic anhydrase 8 on cell survival and glucose metabolism in human colorectal cancer cell lines.

Carbonic anhydrase 8 (CA8) is a member of the α-carbonic anhydrase family but does not catalyze the reversible hydration of carbon dioxide. In the present study, we examined the effects of CA8 on two human colon cancer cell lines, SW480 and SW620, by suppressing CA8 expression through shRNA knockdown. Our results showed that knockdown of CA8 decreased cell growth and cell mobility in SW620 cells, but not in SW480 cells. In addition, downregulated CA8 resulted in a significant decrease of glucose uptake in both SW480 and SW620 cells. Interestingly, stable downregulation of CA8 decreased phosphofructokinase-1 expression but increased glucose transporter 3 (GLUT3) levels in SW620 cells. However, transient downregulation of CA8 fails to up-regulate GLUT3 expression, indicating that the increased GLUT3 observed in SW620-shCA8 cells is a compensatory effect. In addition, the interaction between CA8 and GLUT3 was evidenced by pull-down and IP assays. On the other hand, we showed that metformin, a first-line drug for type II diabetes patients, significantly inhibited cell migration of SW620 cells, depending on the expressions of CA8 and focal adhesion kinase. Taken together, our data demonstrate that when compared to primary colon cancer SW480 cells, metastatic colon cancer SW620 cells respond differently to downregulated CA8, indicating that CA8 in more aggressive cancer cells may play a more important role in controlling cell survival and metformin response. CA8 may affect glucose metabolism- and cell invasion-related molecules in colon cancer, suggesting that CA8 may be a potential target in future cancer therapy.

TNFα modulates PANX1 activation to promote ATP release and enhance P2RX7-mediated antitumor immune responses after chemotherapy in colorectal cancer.

ATP and its receptor P2RX7 exert a pivotal effect on antitumor immunity during chemotherapy-induced immunogenic cell death (ICD). Here, we demonstrated that TNFα-mediated PANX1 cleavage was essential for ATP release in response to chemotherapy in colorectal cancer (CRC). TNFα promoted PANX1 cleavage via a caspase 8/3-dependent pathway to enhance cancer cell immunogenicity, leading to dendritic cell maturation and T-cell activation. Blockade of the ATP receptor P2RX7 by the systemic administration of small molecules significantly attenuated the therapeutic efficacy of chemotherapy and decreased the infiltration of immune cells. In contrast, administration of an ATP mimic markedly increased the therapeutic efficacy of chemotherapy and enhanced the infiltration of immune cells in vivo. High PANX1 expression was positively correlated with the recruitment of DCs and T cells within the tumor microenvironment and was associated with favorable survival outcomes in CRC patients who received adjuvant chemotherapy. Furthermore, a loss-of-function P2RX7 mutation was associated with reduced infiltration of CD8+ immune cells and poor survival outcomes in patients. Taken together, these results reveal that TNFα-mediated PANX1 cleavage promotes ATP-P2RX7 signaling and is a key determinant of chemotherapy-induced antitumor immunity.

2D Nanomaterials and Their Drug Conjugates for Phototherapy and Magnetic Hyperthermia Therapy of Cancer and Infections.

Photothermal therapy (PTT) and magnetic hyperthermia therapy (MHT) using 2D nanomaterials (2DnMat) have recently emerged as promising alternative treatments for cancer and bacterial infections, both important global health challenges. The present review intends to provide not only a comprehensive overview, but also an integrative approach of the state-of-the-art knowledge on 2DnMat for PTT and MHT of cancer and infections. High surface area, high extinction coefficient in near-infra-red (NIR) region, responsiveness to external stimuli like magnetic fields, and the endless possibilities of surface functionalization, make 2DnMat ideal platforms for PTT and MHT. Most of these materials are biocompatible with mammalian cells, presenting some cytotoxicity against bacteria. However, each material must be comprehensively characterized physiochemically and biologically, since small variations can have significant biological impact. Highly efficient and selective in vitro and in vivo PTTs for the treatment of cancer and infections are reported, using a wide range of 2DnMat concentrations and incubation times. MHT is described to be more effective against bacterial infections than against cancer therapy. Despite the promising results attained, some challenges remain, such as improving 2DnMat conjugation with drugs, understanding their in vivo biodegradation, and refining the evaluation criteria to measure PTT or MHT effects.

Phytochemical-rich vegetable and fruit juice alleviates oral mucositis during concurrent chemoradiotherapy in patients with locally advanced head and neck cancer.

Background: Concurrent chemoradiotherapy (CCRT)-induced oral mucositis (OM) causes oral pain, malnutrition, and impaired quality of life in patients with head and neck cancer (HNC). Phytochemicals play a potential role in eliminating cancer therapy toxicity. Objective: To evaluate the effect of phytochemical-rich vegetable and fruit juice (VFJ) consumption in preventing CCRT-induced OM among patients with locally advanced HNC. Methods: Forty-nine patients with HNC undergoing CCRT were enrolled. All patients received nutritional counseling before CCRT and weekly follow-up. The VFJ group (25 patients) received 600 mL/day VFJ, 5 days/week for two weeks preceding CCRT and during CCRT, and the control group (24 patients) did not. The contents of total polyphenols and carotenoids in the VFJ were determined. Changes in anthropometric, dietary, and laboratory profiles were compared. Assessment of OM was based on the World Health Organization (WHO) scoring system. Results: Total polyphenols content was 64.6 mg gallic acid equivalents per 100 mL of the VFJ, and the main carotenoids were ß-carotene and lycopene. The mean daily consumption of the VFJ was 538 mL for VFJ group. Changes in body weight, albumin, and energy intake were not significantly different between the two groups. The incidence of ulcerative OM was significantly lower in VFJ (64.0%) than in control (95.8%) subjects at week 6 of CCRT. Multiple logistic regressions revealed that VFJ consumption correlated significantly with lower risks of ulcerative OM. Conclusion: Consumption of VFJ rich in phytochemicals including total polyphenols and carotenoids effectively alleviates the severity of CCRT-induced OM among patients with locally advanced HNC. Section: Preventive Medicine; Dietary Therapy/Nutrition Supplements. Taxonomy: (classification by EVISE)Preventive medicine, dietary therapy, nutrition supplements.

Estradiol-mediated inhibition of DNMT1 decreases p53 expression to induce M2-macrophage polarization in lung cancer progression.

Previous studies indicate that estrogen positively regulates lung cancer progression. Understanding the reasons will be beneficial for treating women with lung cancer in the future. In this study, we found that tumor formation was more significant in female EGFRL858R mice than in male mice. P53 expression levels were downregulated in the estradiol (E2)-treated lung cancer cells, female mice with EGFRL858R-induced lung cancer mice, and premenopausal women with lung cancer. E2 increased DNA methyltransferase 1 (DNMT1) expression to enhance methylation in the TP53 promoter, which led to the downregulation of p53. Overexpression of GFP-p53 decreased DNMT1 expression in lung cancer cells. TP53 knockout in mice with EGFRL858R-induced lung cancer not only changed gene expression in cancer cells but also increased the polarization of M2 macrophages by increasing C-C motif chemokine ligand 5 (CCL5) expression and decreasing growth differentiation factor 15 (GDF15) expression. The TP53 mutation rate was increased in females with late-stage but not early-stage lung cancer compared to males with lung cancer. In conclusion, E2-induced DNMT1 and p53 expression were negatively regulated each other in females with lung cancer, which not only affected cancer cells but also modulated the tumor-associated microenvironment, ultimately leading to a poor prognosis.

Estradiol-mediated inhibition of Sp1 decreases miR-3194-5p expression to enhance CD44 expression during lung cancer progression.

BACKGROUND: Sp1, an important transcription factor, is involved in the progression of various cancers. Our previous studies have indicated that Sp1 levels are increased in the early stage of lung cancer progression but decrease during the late stage, leading to poor prognosis. In addition, estrogen has been shown to be involved in lung cancer progression. According to previous studies, Sp1 can interact with the estrogen receptor (ER) to coregulate gene expression. The role of interaction between Sp1 and ER in lung cancer progression is still unknown and will be clarified in this study. METHODS: The clinical relevance between Sp1 levels and survival rates in young women with lung cancer was studied by immunohistochemistry. We validated the sex dependence of lung cancer progression in EGFRL858R-induced lung cancer mice. Wound healing assays, chamber assays and sphere formation assays in A549 cells, Taxol-induced drug-resistant A549 (A549-T24) and estradiol (E2)-treated A549 (E2-A549) cells were performed to investigate the roles of Taxol and E2 in lung cancer progression. Luciferase reporter assays, immunoblot and q-PCR were performed to evaluate the interaction between Sp1, microRNAs and CD44. Tail vein-injected xenograft experiments were performed to study lung metastasis. Samples obtained from lung cancer patients were used to study the mRNA level of CD44 by q-PCR and the protein levels of Sp1 and CD44 by immunoblot and immunohistochemistry. RESULTS: In this study, we found that Sp1 expression was decreased in premenopausal women with late-stage lung cancer, resulting in a poor prognosis. Tumor formation was more substantial in female EGFRL858R mice than in male mice and ovariectomized female mice, indicating that E2 might be involved in the poor prognosis of lung cancer. We herein report that Sp1 negatively regulates metastasis and cancer stemness in E2-A549 and A549-T24 cells. Furthermore, E2 increases the mRNA and protein levels of RING finger protein 4 (RNF4), which is the E3-ligase of Sp1, and thereby decreases Sp1 levels by promoting Sp1 degradation. Sp1 can be recruited to the promoter of miR-3194-5p, and positively regulate its expression. Furthermore, there was a strong inverse correlation between Sp1 and CD44 levels in clinical lung cancer specimens. Sp1 inhibited CD44 expression by increasing the expression of miR-3194-5p, miR-218-5p, miR-193-5p, miR-182-5p and miR-135-5p, ultimately resulting in lung cancer malignancy. CONCLUSION: Premenopausal women with lung cancer and decreased Sp1 levels have a poor prognosis. E2 increases RNF4 expression to repress Sp1 levels in premenopausal women with lung cancer, thus decreasing the expression of several miRNAs that can target CD44 and ultimately leading to cancer malignancy.

Establishing a protocol for the compatibilities of closed-system transfer devices with multiple chemotherapy drugs under simulated clinical conditions.

Closed-system drug transfer devices (CSTDs) are used to prevent occupational exposure to hazardous drugs in health care providers. They are considered Class II medical devices by the US FDA and are cleared but not approved before marketing. While compatibility tests are conducted by CSTD manufacturers, the procuring institution needs to consider performing its own studies before buying these devices. Herein we tested the compatibility of the components of the Needleless® DualGuard CSTD system (vial access clips, vial access spikes, and administration adaptors) with 10 antineoplastic drugs, under simulated clinical conditions, including compounding and administration, and examined drug potency maintenance, plasticizer migration, and device functionality. All drugs maintained potency within 5%. Diisononyl phthalate leakage was observed from the administration adaptors for paclitaxel and concentrated etoposide solution. In addition, white particles were discovered in CSTDs storing busulfan solution and small cracks were observed on devices which stored melphalan. Thus, it was concluded that even in simulated clinical conditions, instead of extreme conditions, there are still concerns regarding the efficacy and safety of CSTD components. The methodology may be used to implement and detect possible interactions between antineoplastic agents and CSTD components before procurement.

Correlation of grain orientations and the thickness of gradient MoS2 films.

In this study, we synthesized gradient MoS2 films with a home-made suspended mask and characterized them by transmission electron microscopy (TEM) and Raman spectroscopy. The advantage of using gradient films is to simultaneously produce numerous samples under the same growth condition but with different thicknesses. The cross-sectional TEM images and their Fourier transform spectra revealed the thickness dependency of the grain orientations for synthetic MoS2 films. Combining the TEM results and the data of Raman A1g and E1 2g peaks, we found the correlation between the grain orientation and the A1g/E1 2g peak area ratio. We demonstrated the potential of using the non-polarized Raman Spectroscopy to characterize the grain structures of synthetic MoS2 films.

Characterizing carrier transport in nanostructured materials by force-resolved microprobing.

The advent of novel nanostructured materials has enabled wearable and 3D electronics. Unfortunately, their characterization represents new challenges that are not encountered in conventional electronic materials, such as limited mechanical strength, complex morphology and variability of properties. We here demonstrate that force-resolved measurements can overcome these issues and open up routes for new applications. First, the contact resistance to 2D materials was found to be sensitively depending on the contact force and, by optimizing this parameter, reliable contacts could be repeatably formed without damage to the fragile material. Moreover, resistance of three-dimensional surfaces could be investigated with high accuracy in spatial position and signal through a force-feedback scheme. This force-feedback approach furthermore permitted large-scale statistical characterization of mobility and doping of 2D materials in a desktop-sized automatic probing system that fits into glove boxes and vacuum enclosures using easily available and low-cost components. Finally, force-sensitive measurements enable characterization of complex electronic properties with high lateral resolution. To illustrate this ability, the spatial variation of a surface's electrochemical response was investigated by scanning a single electrolyte drop across the sample.

Safety evaluation of water extract of Gastrodia elata Blume: Genotoxicity and 28-day oral toxicity studies.

Water extract of Gastrodia elata Blume (WGE) has great potential as an anti-depressant and could be developed as a functional food. This study aims to assess the safety of WGE using in vitro and in vivo genotoxicity assays and a 28-day oral toxicity study. Results from a bacterial reverse mutation assay (Ames test) using five Salmonella typhimurium strains (TA98, TA100, TA102, TA1535, and TA1537) with or without metabolic activation (S9 system) showed that WGE did not induce mutagenicity. Nor did it induce clastogenic effects in Chinese hamster ovary (CHO-K1) cells with or without S9 activation. Moreover, WGE did not affect the proportion of immature to total erythrocytes or the number of micronuclei in immature erythrocytes of ICR mice. Finally, a dose-dependent 28-day repeated dose toxicity assessment of WGE (2040, 4080, and 8065 mg/kg body weight, p.o.) in mice revealed no adverse effects on behavior, mortality, body weight, haematology, clinical biochemistry, or organ weight. No toxicopathologic lesions were detected following administration of high-dose WGE compared to controls. In conclusion, WGE has no significant mutagenic or toxic properties, and the no-observed-adverse-effect level (NOAEL) of WGE can be defined as at least 8065 mg/kg/day orally for 28 days for male and female mice.

Metformin reduces prostate cancer risk among men with benign prostatic hyperplasia: A nationwide population-based cohort study.

Benign Prostate Hyperplasia (BPH) has been associated with prostate cancer prevalent among men after 50 years of age, however, it is unclear whether the antidiabetic drug, metformin, can reduce prostate cancer for men with BPH. The insurance claims data of men aged 50 years or older, with both type 2 diabetes mellitus (T2DM) and BPH diagnosed from 1997 to 2007 were analyzed. Individuals were followed up for at least 5 years. We identified 2906 and 2906 patients as the metformin cohort and nonmetformin cohort, respectively. The Cox method analysis showed that the metformin cohort had an adjusted hazard ratio (aHR) of 0.69 (95% confidence interval [CI] = 0.49-0.96, P = 0.0298) for prostate cancer, compared to the nonmetformin cohort after controlling for age, traditional Chinese medicine (TCM) use, prostate specific antigen, and Charlson comorbidity index. Patients using TCM for BPH (per 6 months) also had an aHR of 0.41 (95% CI = 0.24-0.69; P = 0.0009). In conclusion, both metformin medication and TCM use could be associated with reduced risk of prostate cancer for men with BPH and diabetes.

Traditional Chinese medicine is associated with a decreased risk of heart failure in breast cancer patients receiving doxorubicin treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: Cardiovascular disease is the main concern of breast cancer survivors who received doxorubicin treatment. Traditional Chinese medicine (TCM) provides as a complementary therapy to patients with breast cancer and is an important component of health care in Taiwan. However, the TCM utilization patterns and it's efficacy in breast cancer patients is unknown. MATERIALS AND METHODS: From a sample of claims data collected over the period of 1997-2010 in Taiwan, we identified 24,457 breast cancer patients who received TCM treatments and 24,457 breast cancer patients who did not receive TCM treatments. All enrollment patients had received doxorubicin chemotherapy. These patients were paired by age; index day; and propensity score for selected comorbidities, Herceptin and tamoxifen. The incidence of cumulative congestive heart failure (CHF) was compared between cohorts. Fine and Gray regression hazard model was used to evaluate the risk of CHF. RESULTS: After adjusting for age, Herceptin, tamoxifen, diabetic drug, cardiovascular drug, statin and comorbidities, the stratified Fine and Gray model revealed that the TCM cohort had an adjusted subdistribution hazard ratio (sHR) of 0.68 (95% confidence interval (CI) = 0.62-0.76, p < 0.0001) for the development of CHF. In addition, the sub-cohort analysis revealed that the Baihuasheshecao cohort compared to the non-TCM cohort had an adjusted sHR of 0.29 (95% CI = 0.15-0.56, p = 0.0002) for the development of CHF. CONCLUSION: Using TCM significantly decreased the incidence of CHF in patients with breast cancer who received conventional chemotherapy with or without radiotherapy.

Effect of Chemotherapy on Dual-Energy X-ray Absorptiometry (DXA) Body Composition Precision Error in Head and Neck Cancer Patients.

BACKGROUND: Precision error in dual-energy X-ray absorptiometry (DXA) is defined as difference in results due to instrumental and technical factors given no biologic change. The aim of this study is to compare precision error in DXA body composition scans in head and neck cancer patients before and 2 months after chemotherapy. METHODOLOGY: A total of 34 male head and neck cancer patients with normal body mass index (BMI) were prospectively enrolled and all patients received 2 consecutive DXA scans both before and after 2 months of chemotherapy for a total of 4 scans. The precision error of 3 DXA body composition values (lean mass, fat mass, and bone mineral content) was calculated for total body and 5 body regions (arms, legs, trunk, android, and gynoid). Precision errors before and after treatment were compared using generalized estimating equation model. RESULTS: There was no significant change in precision error for the DXA total body composition values following chemotherapy; lean mass (0.33%-0.40%, p = 0.179), total fat mass (1.39%-1.70%, p = 0.259) and total bone mineral content (0.42%-0.56%, p = 0.243). However, there were significant changes in regional precision error; trunk lean mass (1.19%-1.77%, p = 0.014) and android fat mass (2.17%-3.72%, p = 0.046). CONCLUSIONS: For head and neck cancer patients, precision error of DXA total body composition values did not change significantly following chemotherapy; however, there were significant changes in fat mass in the android and lean mass in the trunk. Caution should be exercised when interpreting longitudinal DXA body composition data in those body parts.

Perceptions of Reducing Tube Feeding for Persons with Advanced Dementia among Various Professions in a Teaching Hospital.

BACKGROUND: Even though no evidence suggests tube feeding is beneficial for individuals with advanced dementia, many are still tube fed. OBJECTIVE: To assess perceptions of hospital staff regarding reducing tube feeding (RTF) of patients with advanced dementia. DESIGN: Cross-sectional survey. SETTING: A regional teaching hospital in Taipei, Taiwan. SUBJECTS: Hospital staff (n = 624), including physicians, nurses, dieticians, paramedical personnel, social workers, volunteers, attendants, and administrators. MEASUREMENTS: Anonymous questionnaires. RESULTS: The overall awareness of RTF for advanced dementia patients averaged 10.2 ± 3.74 points (maximum, 19 points) among all respondents. Among the different hospital professions, dieticians scored the highest, whereas nurses and attendants/volunteers had relatively low scores. Over half of respondents (57%) agreed tube feeding is the best choice for advanced dementia with dysphagia. Physicians of different specialties had significantly different responses toward RTF with regard to the belief that tube feeding reduces the risk of aspiration pneumonia, referring patients who refuse tube feeding to other health care team members, and the belief that family members would be able to accept the patient's death along with insufficient food/fluid intake. Only 35.1% of respondents believed they were able to implement comfort feeding. CONCLUSIONS: The present survey shows a persistent knowledge gap among various health care professions regarding tube feeding of patients with advanced dementia. Also, there is insufficient awareness about this subject, indicating that promotion of comfort feeding by enhanced training and communication within medical teams is essential to achieving better person-centered care and preventing unnecessary suffering.

Evaluation of nephroprotection of silymarin on contrast-induced nephropathy in liver cirrhosis patients: A population-based cohort study.

Recent findings from an animal experiment suggest a modest association between silymarin and decreased risk of contrast-induced nephropathy. However, the relationship between silymarin and contrast-induced nephropathy in patients with liver cirrhosis remains unclear.From 1997 to 2007, we identified 3019 patients with liver cirrhosis who were administered silymarin and matched them with 3019 patients with liver cirrhosis who were not administered silymarin. Each patient was followed up for a minimum of 4 years. After adjusting for age, gender, hepatitis B, hepatitis C, alcoholic hepatitis, and Charlson comorbidity index, we considered death occurrence and used the Fine and Gray regression models to calculate subdistribution hazard ratios (sHRs) for contrast-induced nephropathy. Sensitivity analyses were also performed using the same model on the subgroups classified by comorbidity.Using the Fine and Gray regression models and with death as the competing risk, we observed that sHR for contrast-induced nephropathy was 0.94-fold higher in the silymarin cohort than in the nonsilymarin cohort (95% confidence interval = 0.61-1.47, P = .791). On the basis of sensitivity analyses results classified by comorbidity, a nonsignificant decrease in risk of contrast-induced nephropathy was found.Silymarin shows no nephron-protective positive effects on contrast-induced nephropathy. Silymarin did not play a nephron-protective role according to Longitudinal Health Insurance Database of Taiwan. Clinical trials are necessary to further assess the nephron-protective effects of silymarin of contrast-induced nephropathy.

Long-term physical health consequences of abortion in Taiwan, 2000 to 2013: A nationwide retrospective cohort study.

The aim of this study was to quantitatively estimate the long-term risk of abortion-related consequences and comorbidities.We identified 36,375 patients with at least 2 diagnosed abortions from 2000 to 2013 and included them in the abortion group. This group was further subdivided into 4 subgroups: spontaneous abortion, induced abortion, nonspecific abortion, and mixed-type abortion groups. For comparison, another 36,375 pregnant women from the National Health Insurance Research Database of Taiwan were included in the nonabortion group. For the puerperal cohort, the index year was defined as the year with the occurrence of at least 1 pregnancy. The puerperal cohort was then matched to the abortion cohort by age; comorbidities of diabetes mellitus, hypertension, and hyperlipidemia; and index year at a 1:1 ratio. The data of these cohorts were used to examine the risk of abortion-related consequences and comorbidities in pregnant women after a mean follow-up period of 7.60 person-years.The spontaneous abortion group exhibited significantly elevated adjusted hazard ratios (HRs) of 1.493 for pelvic inflammatory disease (P < .001), 1.680 for urinary tract infection (P < .001), 3.771 for ectopic pregnancy (P < .001), and 1.938 for infertility with no subsequent conception (P < .001). However, this group exhibited statistically insignificant HRs of 1.709 for placenta previa (P = .260), 2.982 for placenta abruption (P = .344), 1.499 for incompetent cervix (P = .658), and 0.854 for early onset of labor (P = .624). The induced abortion group showed a statistically significant elevated adjusted HR of 1.291 for urinary tract infection (P = .008) but statistically insignificant HRs of 1.031 for pelvic inflammatory disease, 1.637 for ectopic pregnancy, 5.114 for placenta previa, 65.434 for placenta abruption, 0.998 for incompetent cervix, 0.285 for early onset of labor, and 1.019 for subsequent infertility with no subsequent conception.Clinicians encountering patients in a predicament such as spontaneous or induced abortion should unprejudicely and objectively inform the patients of the effects or influence of abortion on their physical health, including statistically significant and insignificant risks. Induced abortion may not be an independent risk factor for subsequent infertility.

Cytotoxicity and in Vitro Degradation Kinetics of Foundry-Compatible Semiconductor Nanomembranes and Electronic Microcomponents.

Foundry-compatible materials and processing approaches serve as the foundations for advanced, active implantable microsystems that can dissolve in biofluids into biocompatible reaction products, with broad potential applications in biomedicine. The results reported here include in vitro studies of the dissolution kinetics and nanoscale bioresorption behaviors of device-grade thin films of Si, SiN x, SiO2, and W in the presence of dynamic cell cultures via atomic force microscopy and X-ray photoemission spectroscopy. In situ investigations of cell-extracellular mechanotransduction induced by cellular traction provide insights into the cytotoxicity of these same materials and of microcomponents formed with them using foundry-compatible processes, indicating potential cytotoxicity elicited by W at concentrations greater than 6 mM. The findings are of central relevance to the biocompatibility of modern Si-based electronics technologies as active, bioresorbable microsystems that interface with living tissues.

Avian influenza viruses (AIVs) H9N2 are in the course of reassorting into novel AIVs.

In 2013, two episodes of influenza emerged in China and caused worldwide concern. A new H7N9 avian influenza virus (AIV) first appeared in China on February 19, 2013. By August 31, 2013, the virus had spread to ten provinces and two metropolitan cities. Of 134 patients with H7N9 influenza, 45 died. From then on, epidemics emerged sporadically in China and resulted in several victims. On November 30, 2013, a 73-year-old woman presented with an influenza-like illness. She developed multiple organ failure and died 9 d after the onset of disease. A novel reassortant AIV, H10N8, was isolated from a tracheal aspirate specimen that was obtained from the patient 7 d after onset. This case was the first human case of influenza A subtype H10N8. On 4 February, 2014, another death due to H10N8 avian influenza was reported in Jiangxi Province, China.

Pterostilbene modulates the suppression of multidrug resistance protein 1 and triggers autophagic and apoptotic mechanisms in cisplatin-resistant human oral cancer CAR cells via AKT signaling.

Pterostilbene is a natural polyphenolic compound that is primarily found in fruits, such as blueberries and has a similar structure to resveratrol. Pterostilbene exhibits antioxidant, anti-inflammatory and antitumor activity but the effects of pterostilbene on drug-resistant oral cancer cells and its underlying mechanisms of action have not yet been explored. Therefore, the present study was performed to clarify the anticancer effects of pterostilbene on cisplatin-resistant human oral cancer CAR cells. The results demonstrated that CAR cells exhibited marked shrinkage, cell membrane breakage and autophagic vacuole formation following treatment with pterostilbene. Pterostilbene also effectively inhibited cell viability and suppressed cell confluence in a time- and concentration-dependent manner. Probing with acridine orange, monodansylcadaverine and LysoTracker Red demonstrated that the number of acidic vesicular organelles was increased, indicating increased autophagy. Furthermore, Heochst 33342 staining determined that DNA condensation, a characteristic of apoptosis, was enhanced following treatment with pterostilbene. Furthermore, pterostilbene upregulated mRNA levels of LC3-II and Atg12, as well as the expression of Atgs/Beclin-1/LC3-associated signaling, suggesting that it enhances autophagy. The autophagy inhibitors 3-methyladenine and chloroquine were used to confirm that pterostilbene induces autophagy. It was also determined that pterostilbene triggered caspase-dependent apoptosis by directly testing DNA breakage and using the pan-caspase inhibitor carbobenzoxyvalyl-alanyl-aspartyl fluoromethyl ketone. The results demonstrated that pterostilbene mediates the apoptosis of CAR cells via the intrinsic apoptotic cascade. In addition, pterostilbene inhibited MDR1 expression and the phosphorylation of AKT on the Ser473 site in CAR cells. Therefore, pterostilbene may elicit an oral anticancer response in drug-resistant cells and may be used as a chemotherapeutic adjuvant to treat patients with oral cancer.

Biodegradable Electronic Systems in 3D, Heterogeneously Integrated Formats.

Biodegradable electronic systems represent an emerging class of technology with unique application possibilities, from temporary biomedical implants to "green" consumer gadgets. This paper introduces materials and processing methods for 3D, heterogeneously integrated devices of this type, with various functional examples in sophisticated forms of silicon-based electronics. Specifically, techniques for performing multilayer assembly by transfer printing and for fabricating layer-to-layer vias and interconnects by lithographic procedures serve as routes to biodegradable, 3D integrated circuits composed of functional building blocks formed using specialized approaches or sourced from commercial semiconductor foundries. Demonstration examples range from logic gates and analog circuits that undergo functional transformation by transience to systems that integrate multilayer resistive sensors for in situ, continuous electrical monitoring of the processes of transience. The results significantly expand the scope of engineering options for biodegradable electronics and other types of transient microsystem technologies.