The benefit of vegetarian diets for reducing blood pressure in Taiwan: a historically prospective cohort study.

OBJECTIVE: Past vegetarians research has often found that they have lower blood pressure (BP). Effects may include their lower BMI and higher intake levels of fruit and vegetables. Besides, the study pursues to extend this evidence in a diverse population containing vegans, lacto-ovo vegetarians and omnivores. DESIGN: The study analyzed data on five hundred vigorous individuals aged 20 years or older from a standard medical screening program and provided validated questionnaire. Criteria were established for vegan, lacto-ovo vegetarian, partial vegetarian and omnivorous dietary patterns. SETTING: Health screening programs were conducted at a standard medical screening program in Taiwan between 2006 and 2017. Dietary data were gathered by self-administered questionnaire. SUBJECTS: Five hundred Taiwanese subjects representing the cohort. RESULTS: Multiple regression analyses confirmed that the vegan vegetarians had lower systolic and diastolic BP (mmHg) than omnivorous Taiwanese (ß = - 6.8, p < 0.05 and ß = - 6.9, p < 0.001). Findings for lacto-ovo vegetarians (ß = - 9.1, p < 0.001 and ß = - 5.8, p < 0.001) were similar. The vegetarians were also less likely to be using antihypertensive medications. Defining hypertension as systolic BP > 139 mmHg or diastolic BP > 89 mmHg or routine of antihypertensive medications, the odds ratio of hypertension compared with omnivores was 0.37 (95% CI = 0.19-0.74), 0.57 (95% CI = 0.36-0.92) and 0.92 (95% CI = 0.50-1.70), respectively, for vegans, lacto-ovo vegetarians and partial vegetarians. Results were reduced after adjustment for BMI. CONCLUSIONS: The study concludes from this relatively large study that vegetarians, especially vegans, with otherwise diverse characteristics but stable diets, do have lower systolic and diastolic BP and less hypertension than omnivores.

Standardized rate of hospitalization for violent injuries among different generations in counties and cities in Taiwan from 2000 to 2015.

This study aimed to understand the distribution of the standardized rate of hospitalization for violent injuries in counties and cities in Taiwan. The ICD-9 diagnosis code N-codes 995.5 (abused child) and 995.8 (abused adult) or E-code E960-E969 (homicide and intentional injury by others) were defined as research cases. The study analyzed the standardized medical treatment rate of children and adolescents aged 0 to 17, adults aged 18 to 64, and older adults over 65 years old suffering from violence for the first time. During the 15-year period, the counties and cities with the highest rate of medical treatment for violent injuries among children (unit: per 105 people) were Pingtung County (33.1 males, 22.9 females), Lienchiang County (8.8 males, 9.8 females), and New Taipei City (8.2 males, 8.8 females). For adults, Pingtung County (73.2 males, 36.8 females), New Taipei City (26.0 males, 14.3 females), and Yunlin County (19.7 males, 7.7 females) registered the highest rates. For older adults, Pingtung County (33.6 persons), New Taipei City (12.5 persons), Yun Lin County (11.2 persons), and Taichung City (9.2 persons) registered the highest rates. The highest rates of older female adults receiving treatment were recorded in Pingtung County (15.1 persons), Yunlin County (9.0 persons), Taichung City (5.5 persons), and New Taipei City (5.1 persons). With the Poisson regression model, the relative risk ratio of seeking medical care owing to violence in Pingtung County (reference: Taipei City) was 25.1 times for children, 20.1 times for adults, and 11.7 times for older adults. The counties and cities with higher rates of violent medical treatment for adults and older adults during the 15-year period were Pingtung County, New Taipei City, and Yunlin County. For children and adolescents, Pingtung County, Lienchiang County, and New Taipei City recorded the highest rates. Pingtung County had the highest risk of sexual violence. These results may be related to the local industrial structure, demographic composition, and other characteristics explained in the text.

The Synergetic Impact of Physical Activity and Fruit and Vegetable Consumption on the Risk of Depression in Taiwanese Adults.

BACKGROUND: This research focused on the association between physical activity and fruit-vegetable intake and the risk of depression in middle aged and older Taiwanese adults. METHODS: Data were obtained from the 1999 to 2015 datasets of the Taiwan Longitudinal Survey on Aging (TLSA), and 4400 participants were included in 1999 (aged ≥53 years). Descriptive statistics provided all of the basic characteristic variables. A chi-square test analyzed the association between sex, age, years of education, marriage, hypertension, drinking, smoking, and the incidence of depression. Logistic regression analysis was used to determine significant associations between physical activity and fruit-vegetable intake, and the presence or absence of depression after 16 years. RESULTS: Combined high physical activity and fruit-vegetable intake reduced the risk of depression by 80% (OR = 0.20, 95% CI = 0.10-0.45, p = 0.001) compared to low physical activity and fruit-vegetable intake; high physical activity and moderate or low fruit-vegetable intake caused a 70% reduction (OR = 0.30, 95% CI = 0.15-0.63, p = 0.005). High fruit-vegetable intake and low physical activity caused a 65% reduction (OR = 0.35, 95% CI = 0.15-0.63, p = 0.005), compared to low physical activity and low fruit-vegetable intake. High physical activity alone caused a 40% reduction, which is the same as by high fruit-vegetable intake alone. CONCLUSIONS: Fruit-vegetable intake combined with physical activity was negatively correlated with the risk of depression. More fruit-vegetable intake and physical activity might reduce this risk. The results highlight the importance of physical activity and fruit-vegetable consumption for middle-aged and older adults to prevent depression.

A new test for autism spectrum disorder: Metabolic data from different cell types.

Experiments employing the Phenotype Mammalian Microarray (PM-M) technology were performed on lymphoblastoid cell lines (LCLs) from individuals with autism spectrum disorder (ASD) and age-matched controls. We used the custom-made PM-M plate designed to assess differential utilization of the amino acid tryptophan. Multiple parameters such as the sample size, incubation time, and cell concentration have been tested, leading to optimized protocols and minimized background noise by variable selection while controlling for false discoveries. The assay generated data based on the production of nicotinamide adenine dinucleotide (NADH) in the presence of different compounds containing tryptophan and showed clear differences between ASD and control samples.

Chemoreversal Agents from Taiwanofungus Genus and Their More Potent Methyl Derivatives Targeting Signal Transducer and Activator of Transcription 3 (STAT3) Phosphorylation.

Multidrug resistance (MDR), for which the mechanisms are not yet fully clear, is one of the major obstacles to cancer treatment. In recent years, signal transducer and activator of transcription 3 (STAT3) were found to be one of the important MDR mechanism pathways. Based on the previous research, zhankuic acid A, B, and C were found to have collateral sensitivity effects on MDR cancer cells, and MDR inhibitory activity of zhankuic acid methyl ester was found to be better than that of its acid. Therefore, we executed a systematic examination of the structure-activity relationship of zhankuic acid methyl ester derivatives to collateral sensitivity in MDR cancer cells. The results showed that compound 12 is the best in terms of chemoreversal activity, where the reversal fold was 692, and the IC50 value of paclitaxel combined with 10 µM compound 12 treatment was 1.69 nM in MDR KBvin cells. Among all the derivatives, methyl ester compounds were found to be better than their acids, and a detailed discussion of the structure-activity relationships of all of the derivatives is provided in this work. In addition, compounds 8, 12, and 26 were shown to influence the activation of STAT3 in KBvin cells, accounting for part of their chemoreversal effects. Our results may provide a new combined therapy with paclitaxel to treat multidrug-resistant cancers and provide a new therapy option for patients.

Bioactive naphthoquinones and triterpenoids from the fruiting bodies of Taiwanofungus salmoneus.

Drug resistance of cancer cells stands for the major problem of the treatment failure for chemotherapy or target therapy. Overexpression of efflux pumps leading to multidrug resistance (MDR) is still an important issue needed to be solved. In the present study, Taiwanofungus salmoneus was selected as the topic and eleven undescribed constituents including four naphthoquinones salmonones A-D (1-4) and seven triterpenoids salmoneatins A-G (5-11), along with one chromanone (12) and two benzenoids (13 and 14) reported from the natural sources for the first time, as well as twenty-one known compounds were characterized. The structures of undescribed compounds were established by the spectroscopic and spectrometric analyses. In addition, the plausible biosynthetic mechanism of purified naphthoquinones was proposed and these compounds may be the excellent chemotaxonomic markers. Moreover, the isolates were evaluated for their P-gp inhibitory effects and the results showed that most of the examined compounds were effective. Among the tested compounds, 5, 10, 2,3-dimethoxy-5-(2',5'-dimethoxy-3',4'-methylenedioxyphenyl)-7-methyl-[1,4]naphthoquinone, zhankuic acid A methyl ester, and camphoratin F can reverse the resistance of paclitaxel or vincristine with the reversal folds in the range of 51093.3 and 259.5. These experimental data would initiate the possible development of Taiwanofungus salmoneus for the cancer therapy in the future.

Abnormalities in the genes that encode Large Amino Acid Transporters increase the risk of Autism Spectrum Disorder.

BACKGROUND: Autism spectrum disorder (ASD) is a common neurodevelopmental disorder whose molecular mechanisms are largely unknown. Several studies have shown an association between ASD and abnormalities in the metabolism of amino acids, specifically tryptophan and branched-chain amino acids (BCAAs). METHODS: Ninety-seven patients with ASD were screened by Sanger sequencing the genes encoding the heavy (SLC3A2) and light subunits (SLC7A5 and SLC7A8) of the large amino acid transporters (LAT) 1 and 2. LAT1 and 2 are responsible for the transportation of tryptophan and BCAA across the blood-brain barrier and are expressed both in blood and brain. Functional studies were performed employing the Biolog Phenotype Microarray Mammalian (PM-M) technology to investigate the metabolic profiling in lymphoblastoid cell lines from 43 patients with ASD and 50 controls with particular focus on the amino acid substrates of LATs. RESULTS: We detected nine likely pathogenic variants in 11 of 97 patients (11.3%): three in SLC3A2, three in SLC7A5, and three in SLC7A8. Six variants of unknown significance were detected in eight patients, two of which also carrying a likely pathogenic variant. The functional studies showed a consistently reduced utilization of tryptophan, accompanied by evidence of reduced utilization of other large aromatic amino acids (LAAs), either alone or as part of a dipeptide. CONCLUSION: Coding variants in the LAT genes were detected in 17 of 97 patients with ASD (17.5%). Metabolic assays indicate that such abnormalities affect the utilization of certain amino acids, particularly tryptophan and other LAAs, with potential consequences on their transport across the blood barrier and their availability during brain development. Therefore, abnormalities in the LAT1 and two transporters are likely associated with an increased risk of developing ASD.

Constituents and Anti-Multidrug Resistance Activity of Taiwanofungus camphoratus on Human Cervical Cancer Cells.

Resistance to anti-cancer drugs is one of the main factors of treatment failure resulting in high morbidity. Among the reasons of resistance, overexpression of efflux pumps leading to multidrug resistance is an important issue that needs to be solved. Taiwanofungus camphoratus has been used as a nutritional supplement to treat various cancers. However, its effects on the resistance to chemotherapeutic agents are still unknown. In this study, we report four new chemical constituents of T. camphoratus isolated from an ether extract: camphoratins K (1) and N (2) and benzocamphorins G (3) and I (4). Furthermore, we evaluated zhankuic acids A-C for their P-glycoprotein (P-gp) inhibitory effects. The results showed that zhankuic acid A was the most potent P-gp inhibitor compound and (at 20 µM) could reverse drug resistance in human cancer cells, restoring an IC50 of 78.5 nM for doxorubicin, of 48.5 nM for paclitaxel, and of 321.5 nM for vincristine, indicating a reversal fold of 48, 38, and 45 times, respectively. This study provides support for the use of T. camphoratus in the further development of cancer therapy.

Thermo-responsive hydrogel as an anti-VEGF drug delivery system to inhibit retinal angiogenesis in Rex rabbits.

BACKGROUND: Wet age-related macular degeneration (Wet AMD) has been treated clinically by intravitreal injection of bevacizumab, which is a kind of the anti-VEGF antibody drug. Nevertheless, because of the short half-life and frequent injections, the use of this treatment is limited. OBJECTIVE: To confirm whether mPEG-PLGA-BOX can be considered as a VEGF drug delivery system to inhibit retinal angiogenesis. METHODS: A thermo-responsive hydrogel of methoxy-poly (ethylene glycol)-block-poly (lactic-co-glycolic acid) (mPEG-PLGA-BOX) was synthesized. The thermo-responsive hydrogel mPEG-PLGA-BOX was able to have sol-gel phase transition upon stimulation by the body temperature with improved biocompatibility and biodegradation. The bevacizumab released from mPEG-PLGA-BOX inhibited RF/6A cells according to a JC-1 assay, which indicated that the released bevacizumab was active to be able to suppress the growth of new blood vessels. In an animal study, retinal laser photocoagulation was performed to induce angiogenesis in the eyes of Rex rabbits using an 810-mm laser. RESULTS: The retina was penetrated when the laser power was more than 500 mW and the exposure time was more than 500 ms. New blood vessels were created at the 28th day after retinal laser photocoagulation. At this time, intravitreal 0.05-mL injections of mPEG-PLGA-BOX (bevacizumab) solution were administered. The bevacizumab released from mPEG-PLGA-BOX (bevacizumab) solution suppressed the angiogenesis. In an in vivo study, the histomorphology of the rabbit retina also indicated that mPEG-PLGA-BOX after intravitreal injection is not toxic to the rabbit retina. CONCLUSIONS: Bevacizumab released from mPEG-PLGA-BOX (bevacizumab) solution suppressed angiogenesis, and mPEG-PLGA-BOX can be considered as a novel thermo-responsive hydrogel with potential as a gelling carrier for extended bevacizumab drug release to treat intraocular neovascular diseases.

Hand stereotypies: Lessons from the Rett Syndrome Natural History Study.

OBJECTIVE: To characterize hand stereotypies (HS) in a large cohort of participants with Rett syndrome (RTT). METHODS: Data from 1,123 girls and women enrolled in the RTT Natural History Study were gathered. Standard tests for continuous and categorical variables were used at baseline. For longitudinal data, we used repeated-measures linear and logistic regression models and nonparametric tests. RESULTS: HS were reported in 922 participants with classic RTT (100%), 73 with atypical severe RTT (97.3%), 74 with atypical mild RTT (96.1%), and 17 females with MECP2 mutations without RTT (34.7%). Individuals with RTT who had classic presentation or severe MECP2 mutations had higher frequency and earlier onset of HS. Heterogeneity of HS types was confirmed, but variety decreased over time. At baseline, almost half of the participants with RTT had hand mouthing, which like clapping/tapping, decreased over time. These 2 HS types were more frequently reported than wringing/washing. Increased HS severity (prevalence and frequency) was associated with worsened measures of hand function. Number and type of HS were not related to hand function. Overall clinical severity was worse with decreased hand function but only weakly related to any HS characteristic. While hand function decreased over time, prevalence and frequency of HS remained relatively unchanged and high. CONCLUSIONS: Nearly all individuals with RTT have severe and multiple types of HS, with mouthing and clapping/tapping decreasing over time. Interaction between HS frequency and hand function is complex. Understanding the natural history of HS in RTT could assist in clinical care and evaluation of new interventions.

Correction: Evaluation of a novel biodegradable thermosensitive keto-hydrogel for improving postoperative pain in a rat model.

[This corrects the article DOI: 10.1371/journal.pone.0186784.].

Synergistic inhibitory effects of cetuximab and curcumin on human cisplatin-resistant oral cancer CAR cells through intrinsic apoptotic process.

Cetuximab, an epidermal growth factor receptor (EGFR)-targeting monoclonal antibody (mAb), is a novel targeted therapy for the treatment of patients with oral cancer. Cetuximab can be used in combination with chemotherapeutic agents to prolong the overall survival rates of patients with oral cancer. Curcumin is a traditional Chinese medicine, and it has been demonstrated to have growth-inhibiting effects on oral cancer cells. However, information regarding the combination of cetuximab and curcumin in drug-resistant oral cancer cells is lacking, and its underlying mechanism remains unclear. The purpose of the present study was to explore the oral anticancer effects of cetuximab combined with curcumin on cisplatin-resistant oral cancer CAR cell apoptosis in vitro. The results demonstrated that combination treatment synergistically potentiated the effect of cetuximab and curcumin on the suppression of cell viability and induction of apoptosis in CAR cells. Cetuximab and curcumin combination induced apoptosis and dramatically increased caspase-3 and caspase-9 activities compared with singular treatment. Combination treatment also markedly suppressed the protein expression levels of EGFR and mitogen-activated protein kinases (MAPKs) signaling (phosphorylation of ERK, JNK and p38). The results demonstrated that co-treatment with cetuximab and curcumin exerts synergistic oral anticancer effects on CAR cells through the suppression of the EGFR signaling by regulation of the MAPK pathway.

Ursolic acid elicits intrinsic apoptotic machinery by downregulating the phosphorylation of AKT/BAD signaling in human cisplatin­resistant oral cancer CAR cells.

Oral squamous cell carcinoma (OSCC) is a type of cancer with high morbidity and mortality rates worldwide; it also demonstrates chemotherapeutic resistance. Triterpenoid ursolic acid has been shown to exhibit various biological activities and anticancer effects in several preclinical studies. In our previous study, human cisplatin­resistant oral cancer CAR cells were established, and the present study aimed to further examine the effects of ursolic acid on CAR cells. The results revealed that ursolic acid inhibited CAR cell viability, as determined using a 3­(4,5­dimethylthiazol­2­yl)­2,5­diphenyltetrazolium bromide assay. Ursolic acid­induced cell death was mediated through a caspase­dependent pathway, determined with the pan­caspase inhibitor, z­VAD­fmk. Ursolic acid also increased the activities of caspase­3 and caspase­9 in CAR cells, determined by a colorimetric assay. Specifically, the production of reactive oxygen species and loss of mitochondrial membrane potential, detected by flow cytometry, were observed in the ursolic acid­treated CAR cells. The apoptosis­associated signaling showed that ursolic acid decreased the phosphorylation of AKT (Ser473) and B­cell lymphoma 2 (Bcl­2)­associated agonist of cell death (BAD; Ser136), and the protein levels of Bcl­2 and Bcl­extra large (Bcl­xL), and increased the expression of BAD and Bcl­2­associated X (Bax) protein in CAR cells. In summary, the results supported the potential application of ursolic acid against drug­resistant oral carcinoma and to improve oral anticancer efficacy in the near future.

Evaluation of a novel biodegradable thermosensitive keto-hydrogel for improving postoperative pain in a rat model.

This study evaluates the sustained analgesic effect of ketorolac-eluting thermosensitive biodegradable hydrogel in the plantar incisional pain model of the rat hind-paw. A ketorolac-embedded 2, 2'-Bis (2-oxazolin) (BOX) linking methoxy-poly(ethylene glycol) and poly(lactide-co-glycolide) (mPEG-PLGA) diblock copolymer (BOX copolymer) was synthesized as keto-hydrogel based on optimal sol-gel phase transition and in vitro drug release profile. The effect of keto-hydrogel on postoperative pain (POP) was assessed using the established plantar incisional pain model in hind-paw of rats and compared to that of ketorolac solution. Pain and sensory threshold, as well as pain scoring, were evaluated with behavioral tests by means of anesthesiometer and incapacitance apparatus, respectively. Pro-inflammatory cytokine levels (TNF-α, IL-6, VEGF, and IL-1ß) around incisional wounds were measured by ELISA. Tissue histology was assessed using hematoxylin and eosin and Masson's trichrome staining. Ten mg/mL (25 wt%) keto-hydrogel showed a sol-gel transition at 26.4°C with a 10-day sustained drug release profile in vitro. Compared to ketorolac solution group, the concentration of ketorolac in tissue fluid was higher in the keto-hydrogel group during the first 18 h of application. Keto-hydrogel elevated pain and sensory threshold, increased weight-bearing capacity, and significantly reduced the levels of TNF-α, IL-6, and IL-1ß while enhanced VEGF in tissue fluid. Histologic analysis reveals greater epithelialization and collagen deposition around wound treated with keto-hydrogel. In conclusion, our study suggests that keto-hydrogel is an ideal compound to treat POP with a secondary gain of improved incisional wound healing.

High Thermal Dissipation of Al Heat Sink When Inserting Ceramic Powders by Ultrasonic Mechanical Coating and Armoring.

Aluminum alloys, which serve as heat sink in light-emitting diode (LED) lighting, are often inherent with a high thermal conductivity, but poor thermal total emissivity. Thus, high emissive coatings on the Al substrate can enhance the thermal dissipation efficiency of radiation. In this study, the ultrasonic mechanical coating and armoring (UMCA) technique was used to insert various ceramic combinations, such as Al2O3, SiO2, or graphite, to enhance thermal dissipation. Analytic models have been established to couple the thermal radiation and convection on the sample surface through heat flow equations. A promising match has been reached between the theoretical predictions and experimental measurements. With the adequate insertion of ceramic powders, the temperature of the Al heat sinks can be lowered by 5-11 °C, which is highly favorable for applications requiring cooling components.

Treatment of critically sized femoral defects with recombinant BMP-2 delivered by a modified mPEG-PLGA biodegradable thermosensitive hydrogel.

BACKGROUND: Reconstruction of a segmental fracture with massive bone loss is still a challenge for orthopaedic surgeons. The aim of our study was to develop a suitable biodegradable thermosensitive hydrogel system as a carrier for bone morphogenetic protein (BMP)-2 delivery in the treatment of critical-sized femoral defects. METHODS: A block copolymer composed of monomethoxypoly(ethylene glycol) (mPEG), poly(lactic-co-glycolic acid) (PLGA) and 2, 2'-Bis (2-oxazolin) (Box) was synthesized by ring opening polymerization. The synthesized block copolymer was characterized by (1)H-NMR spectroscopy and gel permeation chromatography (GPC). Different biophysical and biochemical properties of the synthesized copolymer, including temperature-induced structure changes, degradation rate, pH changes during hydrolytic degradation, cell toxicity, and the release profile of BMP-2, were also evaluated and/or were compared with those of a well-characterized mPEG-PLGA copolymer. In animal testing, rabbits (n = 36) that received critically sized (10 mm) femoral defects were divided into 6 groups. These experimental groups included an untreated group, autograft, and groups treated with the synthesized copolymer carrying different concentrations of BMP-2 (0, 5, 10, and 20 µg/ml). Bone repair was evaluated using X-ray radiography, histological staining, micro-computed tomography (µCT), biomarker examination and biomechanical testing in a 12-week treatment period. RESULTS: A new thermosensitive mPEG-PLGA/Box/mPEG-PLGA block copolymer, or named as BOX copolymer, was successfully prepared. Compared to the reported mPEG-PLGA in vitro, the prepared BOX copolymer at the same weight percent concentrations exhibited wider temperature ranges of gelation, slower degradation rates, higher the pH values, as well as less cytotoxicity. Furthermore, the BMP-2 release from BOX hydrogel exhibited a near-linear release profile in vitro. In animal experiments, treatment of critical-sized bony defects with 25 wt% BOX hydrogel carrying BMP-2 effectively promoted fracture healing during the 12-week trial period and higher concentrations of BMP-2 treatment correlated with better bone quality. Most importantly, clinical outcome and bone healing in the BOX-hydrogel group with 20 µg/ml BMP-2 were nearly equivalent to those in the autograft group in a 12-week treatment course. CONCLUSION: These data support that the use of BOX hydrogel (25 wt%) as a drug delivery system is a promising method in the treatment of large bone defects.

A healthy lifestyle index is associated with reduced risk of colorectal adenomatous polyps among non-users of non-steroidal anti-inflammatory drugs.

In a Columbia, South Carolina-based case-control study, we developed a healthy lifestyle index from five modifiable lifestyle factors (smoking, alcohol intake, physical activity, diet, and body mass index), and examined the association between this lifestyle index and the risk of colorectal adenomatous polyps (adenoma). Participants were recruited from a local endoscopy center and completed questionnaires related to lifestyle behaviors prior to colonoscopy. We scored responses on each of five lifestyle factors as unhealthy (0 point) or healthy (1 point) based on current evidence and recommendations. We added the five scores to produce a combined lifestyle index for each participant ranging from 0 (least healthy) to 5 (healthiest), which was dichotomized into unhealthy (0-2) and healthy (3-5) lifestyle scores. We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) for adenoma with adjustment for multiple covariates. We identified 47 adenoma cases and 91 controls. In the main analyses, there was a statistically nonsignificant inverse association between the dichotomous (OR 0.54; 95% CI 0.22, 1.29) and continuous (OR 0.75; 95% CI 0.51, 1.10) lifestyle index and adenoma. Odds of adenoma were significantly modified by the use of non-steroidal anti-inflammatory drugs (NSAIDs) (p(interaction) = 0.04). For participants who reported no use of NSAIDs, those in the healthy lifestyle category had a 72% lower odds of adenoma as compared to those in the unhealthy category (OR 0.28; 95% CI 0.08, 0.98), whereas a one-unit increase in the index significantly reduced odds of adenoma by 53% (OR 0.47; 95% CI 0.26, 0.88). Although these findings should be interpreted cautiously given our small sample size, our results suggest that higher scores from this index are associated with reduced odds of adenomas, especially in non-users of NSAIDs. Lifestyle interventions are required to test this approach as a strategy to prevent colorectal adenomatous polyps.

Case-control study of the PERIOD3 clock gene length polymorphism and colorectal adenoma formation.

Clock genes are expressed in a self-perpetuating, circadian pattern in virtually every tissue including the human gastrointestinal tract. They coordinate cellular processes critical for tumor development, including cell proliferation, DNA damage response and apoptosis. Circadian rhythm disturbances have been associated with an increased risk for colon cancer and other cancers. This mechanism has not been elucidated, yet may involve dysregulation of the 'period' (PER) clock genes, which have tumor suppressor properties. A variable number tandem repeat (VNTR) in the PERIOD3 (PER3) gene has been associated with sleep disorders, differences in diurnal hormone secretion, and increased premenopausal breast cancer risk. Susceptibility related to PER3 has not been examined in conjunction with adenomatous polyps. This exploratory case-control study was the first to test the hypothesis that the 5-repeat PER3 VNTR sequence is associated with increased odds of adenoma formation. Information on demographics, medical history, occupation and lifestyle was collected prior to colonoscopy. Cases (n=49) were individuals with at least one histopathologically confirmed adenoma. Controls (n=97) included patients with normal findings or hyperplastic polyps not requiring enhanced surveillance. Unconditional multiple logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs), after adjusting for potential confounding. Adenomas were detected in 34% of participants. Cases were more likely to possess the 5-repeat PER3 genotype relative to controls (4/5 OR, 2.1; 95% CI, 0.9-4.8; 5/5 OR, 5.1; 95% CI, 1.4-18.1; 4/5+5/5 OR, 2.5; 95% CI, 1.7-5.4). Examination of the Oncomine microarray database indicated lower PERIOD gene expression in adenomas relative to adjacent normal tissue. Results suggest a need for follow-up in a larger sample.

Controlled release bevacizumab in thermoresponsive hydrogel found to inhibit angiogenesis.

Age-related macular degeneration (ARMD) and intraocular neovascular diseases have been treated clinically by anti-VEGF antibody drug bevacizumab. However, the use of bevacizumab in the treatment of retinal neovascular diseases has been limited due to the short half-life and frequent injections. In this research, novel amphiphilic hydrophilic-hydrophobic block copolymers of methoxy-poly (ethylene glycol)-block-poly (lactic-co-glycolic acid) were synthesized with ring-opening polymerization, and cross-linked with 2,2-bis (2-oxazoline) (BOX). The aqueous solution of the block copolymers can reverse the sol-gel-sol phase transition. After 1 month of intravitreal injection, the histomorphology of a rabbit's retina was preserved, which indicated the mPEG-PLGA-BOX hydrogel had no cytotoxicity in vivo. Released bevacizumab from the mPEG-PLGA-BOX hydrogel inhibited the RF/6A (Maraca mulatta retina epithelial cell) and HUVEC cell growth, and anti-angiogenesis in 3-D cultures, which showed the bioactivity of the anti-VEGF agent, were maintained in the hydrogel within the release process. In conclusion, the mPEG-PLGA-BOX hydrogel had a sol-gel behavior phase transition, and its intraocular biocompatibility and the characteristics of biodegradability and bioactivity appear to be a promising intravitreal injection carrier for bevacizumab delivery.

MICO: A meta-tool for prediction of the effects of non-synonymous mutations.

UNLABELLED: The Next Generation Sequencing (NGS) is a state-of-the-art technology that produces high throughput data with high resolution mutation information in the genome. Numerous methods with different efficiencies have been developed to predict mutational effects in the genome. The challenge is to present the results in a balanced manner for better biological insights and interpretation. Hence, we describe a meta-tool named Mutation Information Collector (MICO) for automatically querying and collecting related information from multiple biology/bioinformatics enabled web servers with prediction capabilities. The predicted mutational results for the proteins of interest are returned and presented as an easy-to-read summary table in this service. MICO also allows for navigating the result from each website for further analysis. AVAILABILITY: http: //mico.ggc.org /MICO.