Alzheimer's Disease and Aging Association: Identification and Validation of Related Genes.

BACKGROUND: Aging is considered a key risk factor for Alzheimer's disease (AD). This study aimed to identify and validate potential aging-related genes associated with AD using bioinformatics analysis. METHODS: Datasets GSE36980 and GSE5281 were selected to screen differentially expressed genes (DEGs), and the immune cell correlation analysis and GSEA analysis of DEGs were performed. The intersection with senescence genes was taken as differentially expressed senescence-related genes (DESRGs), and the GSE44770 dataset was used for further validation. The potential biological functions and signaling pathways were determined by GO and KEGG, and the hub genes were identified by 12 algorithms in Cytohubba. The expression of 10 hub genes in different brain regions was determined and single-cell sequencing analysis was performed, and diagnostic genes were further screened by gene expression and receiver operating characteristic (ROC) curve. Finally, a miRNA-gene network of diagnostic genes was constructed and targeted drug prediction was performed. RESULTS: A total of 2137 DEGs were screened from the GSE36980 and GSE5281 datasets, and 278 SRGs were identified from the CellAge database. The overlapping DEGs and SRGs constituted 29 DESRGs, including 14 senescence suppressor genes and 15 senescence inducible genes. The top 10 hub genes, including MDH1, CKB, PSMD14, SMARCA4, PEBP1, DDB2, ITPKB, ATF7IP, YAP1, and EWSR1 were screened. Furthermore, four diagnostic genes were identified: PMSD14, PEBP1, ITPKB, and ATF7IP. The ROC analysis showed that the respective area under the curves (AUCs) of PMSD14, PEBP1, ITPKB, and ATF7IP were 0.732, 0.701, 0.747, and 0.703 in the GSE36980 dataset and 0.870, 0.817, 0.902, and 0.834 in the GSE5281 dataset. In the GSE44770 dataset, PMSD14 (AUC, 0.838) and ITPKB (AUC, 0.952) had very high diagnostic values in the early stage of AD. Finally, based on these diagnostic genes, we found that the drug Abemaciclib is a targeted drug for the treatment of age-related AD. Flutamide can aggravate aging-related AD. CONCLUSION: The results of this study suggest that cellular SRGs might play an important role in AD. PMSD14, PEBP1, ITPKB, and ATF7IP have the potential as specific biomarkers for the early diagnosis of AD.

Scenario tree modelling to inform surveillance design for maintaining freedom from Coxiella burnetii infection in Australian commercial dairy goat herds.

We used scenario tree methods to determine how different disease detection methods might be used to provide quantitative evidence that Australian dairy goat herds are free of coxiellosis. The aim of our proposed C. burnetii surveillance programme is to find evidence of the absence of antigen as well as evidence of an absence of an immune response to C. burnetii infection in individual dairy goat herds. We defined a C. burnetii infected dairy goat herd as a herd in which at least one doe was showing evidence of either active infection or past C. burnetii exposure using four candidate surveillance system components (SSCs): (1) testing of individual doe whole blood using the C. burnetii com1 PCR; (2) testing of individual doe whole blood using the C. burnetii ELISA; (3) testing bulk tank milk (BTM) using the com1 PCR and the C. burnetii ELISA; and (4) investigations of abortions and stillborn kids submitted to a diagnostic laboratory for testing. Of eight candidate surveillance strategies (combinations of the SSCs listed above) individual doe ELISAs every six months combined with monthly BTM PCR and ELISA testing returned the highest surveillance system sensitivity of 0.963 (95% probability interval [PI] 0.911-0.982) for the lowest cost, at AUD 28.94 (95% PI 28.38-30.59) over a 12-month period, for every one percent increase in surveillance system sensitivity. Assuming a probability of disease freedom of 0.10 at the start of the surveillance program and a probability of C. burnetii introduction per month of 0.01 we estimate that 95% confidence that C. burnetii was absent from a herd could be achieved after a single round of individual doe ELISAs followed by period of 6 consecutive monthly BTM PCR and ELISA tests. The results of this study show that selection of the most efficient combination of surveillance system components requires a good understanding of initial herd C. burnetii status and the probability of introduction of infection and how this may change over time. Scenario tree analyses results have provided insight into the key determinants of C. burnetii detection ability.

Effect of polyethylene Glycol Loxenatide (long-acting GLP-1RA) on lipid, glucose levels and weight in type 2 diabetes mellitus patients with obesity.

OBJECTIVE: To explore the effect of polyethylene glycol loxenatide (long-acting GLP-1R agonist) on the lipid, glucose levels, and weight in type 2 diabetes mellitus patients with obesity. PATIENTS AND METHODS: A total of 40 obese patients with type 2 diabetes mellitus in our hospital from July 2019 to June 2020 were randomly divided into a control group and a study group. The study group was treated with metformin and polyethylene glycol loxenatide injection, while the control group was treated with metformin. RESULTS: Before treatment, there was no significant difference in FPG (Fasting Blood Glucose) and PPG (Post Prandial Glycaemia) levels between the study group and the control group (p>0.05). After a treatment period, the FPG and PPG levels in the study group were significantly lower than those in the control group (p<0.05). With the longer treatment time, the patient's weight and BMI were lower (p<0.05). The weight and BMI of patients changed the least after one month of treatment, and the weight and BMI changed the most after more than seven months of treatment. After a period of treatment, the levels of FPG and PPG in the blood of male patients in the study group were significantly lower than those of female patients (p<0.05). After treatment, the TG level of the study group was significantly lower than that of the control group (p<0.05). In comparison, the HDL-C level was significantly higher than that of the control group (p<0.05). CONCLUSIONS: Lipid and glucose levels of type 2 diabetes mellitus patients with obesity have decreased after 12 weeks of polyethylene glycol loxanatide use. The weight of type 2 diabetes mellitus patients with obesity has changed after using polyethylene glycol loxenatide for a period of treatment. Among them, there is a certain relationship between body weight and treatment time, gender, and original body weight, which is worthy of further research and promotion in clinical practice.

Bariatric surgery in a public hospital: a 10-year experience.

INTRODUCTION: Obesity is common and adversely impacts quality-of-life and healthcare cost. In Australia, less than 10% of bariatric surgeries are performed in the public sector. This study reports our 10-year experience from a high volume public bariatric service which delivers multi-disciplinary care for primary and revisional procedures with mid- to long-term follow-up. METHODS: A prospectively maintained database of all patients who underwent bariatric surgery from January 2010 to January 2020 at a tertiary metropolitan hospital was analysed. We analysed patient demographics, comorbidities, perioperative outcomes, 2- and 5-year weight loss as well as comorbidities reduction. RESULTS: A total of 995 patients underwent 1086 (674 primary and 412 revisional) bariatric procedures with mean age of 46.9 years, mean BMI of 49.6 ± 9.1 kg/m2 and 92% patients with ≥1 obesity-related co-morbidity. Length-of-stay was longer for revisional than primary surgery (5.6 vs. 3.5 days). Major complication rate was 4.2%. Overall, % Total body weight loss (%TBWL) for primary surgeries at 2 years was 26.2%, and for revision surgery was 17.4%. At 2 years follow-up, treatment was ceased or reduced in 65% of diabetics, 29% of hypertensive patients and 69% of sleep apnoea patients. CONCLUSION: This study confirms that bariatric surgery in Australia can be delivered effectively in resource constrained public health system with outcomes similar to private sector.

A cross-sectional survey of risk factors for the presence of Coxiella burnetii in Australian commercial dairy goat farms.

The largest Australian farm-based outbreak of Q fever originated from a dairy goat herd. We surveyed commercial dairy goat farms across Australia by testing bulk tank milk (BTM) samples using a commercial indirect enzyme-linked immunosorbent assay and two quantitative polymerase chain reactions (PCRs). Of the 66 commercial dairy goat herds on record, managers from 61 herds were contacted and 49 provided BTM samples. Five of the surveyed herds were positive on at least one of the diagnostic tests, thus herd-level apparent prevalence was 10% (95% confidence interval [CI] 4 to 22). True prevalence was estimated to be 3% (95% credible interval: 0 to 18). Herd managers completed a questionnaire on herd management, biosecurity and hygiene practices and risk factors were investigated using multivariable logistic regression. Herds with >900 milking does (the upper quartile) were more likely to be Coxiella burnetii positive (odds ratio = 6.75; 95% CI 1.65 to 27.7) compared with farms with ≤900 milking does. The odds of BTM positivity increased by a factor of 2.53 (95% CI 1.51 to 4.22) for each order of magnitude increase in the number of goats per acre. C. burnetii was not detected in samples from the majority of the Australian dairy goat herds suggesting there is an opportunity to protect the industry and contain this disease with strengthened biosecurity practices. Intensification appeared associated with an increased risk of positivity. Further investigation is required to discriminate the practices associated with an increased risk of introduction to disease-free herds, from practices associated with maintenance of C. burnetii infection in infected dairy goat herds.

Analysis of pharmacoeconomic value of sitagliptin in the treatment of diabetes mellitus.

OBJECTIVE: Diabetes mellitus is a chronic metabolic disease which has an adverse impact on the quality of patient's life, so patients often need to receive treatment for a long time. Selection of medications with high therapeutics effects and low cost is very important for patients to take medicine for a longer period of time. Sitagliptin is a drug which is widely used in clinics and can effectively control blood glucose level. This article explores the pharmacoeconomic value of Sitagliptin in the treatment of diabetes mellitus. PATIENTS AND METHODS: A total of 100 patients with diabetes mellitus treated were recruited in this study. The patients were randomly divided into 4 groups with 25 cases in each group. Patients in group A were treated with pioglitazone, group B with Sitagliptin, group C with metformin and group D with glimepiride. The cost of the drugs, the treatment results and adverse effects were compared. RESULTS: Compared with group A, C and D, the cost-effectiveness ratio of group B was low (p<0.05), and the therapeutic effect was high (p<0.05). In addition, the incidence of adverse reactions in group B was lower than that in group A, C and D (p<0.05). There was no significant difference in the levels of FPG, 2hPG and HbAlc in patients among the four groups before treatment (p>0.05). After treatment, the levels of FPG, 2hPG and HbAlc in group B were significantly lower than those in groups A, C and D (p<0.05). Finally, there was no significant difference in waist circumference and BMI among the four groups before treatment (p>0.05). After treatment, the waist circumference and BMI in group B were lower than those in groups A, C and D (p<0.05). CONCLUSIONS: The application of Sitagliptin in the treatment of diabetic patients can effectively enhance the therapeutic effect. The cost effectiveness is satisfactory, and the blood glucose level can be maintained at a stable state.

LncRNA INHBA-AS1 promotes colorectal cancer cell proliferation by sponging miR-422a to increase AKT1 axis.

OBJECTIVE: In recent years, long non-coding RNAs (lncRNAs) have emerged for regulating the development, as well as progression in colorectal cancer (CRC), which assists in finding new targets for CRC treatment. A previous study indicated that INHBA-AS1 promotes oral squamous cell progression by sponging miR-143-3p. However, the exact function possessed by lncRNA INHBA-AS1 in CRC development remains unclear. PATIENTS AND METHODS: The expression level of INHBA-AS1 in CRC tissues and cell lines was determined by qRT-PCR. The functional role of INHBA-AS1 in CRC was investigated by a series of in vitro assays. RNA immunoprecipitation (RIP), bioinformatics analysis was utilized to explore the potential mechanisms of INHBA-AS1. RESULTS: The present study identified INHBA-AS1 as a kind of lncRNA with high expression in CRC tissues and cells. Functionally, NHBA-AS1 downregulation in CRC cells suppressed CRC cell proliferation as well as colony formability. Mechanistically, INHBA-AS1/miR-422a/AKT1 established the ceRNA network to regulate MMP-2, -7, -9 expressions that participated the modulation of CRC progression. CONCLUSIONS: In summary, LncRNA INHBA-AS1 contributes to CRC progression through AKT1 pathway, and provides a new mechanism to regulate CRC development, as well as a potential target for treating CRC.

Testing the performance of sensors for ozone pollution monitoring in a citizen science approach.

Tropospheric ozone (O3) is an environmental pollutant of growing concern, especially in suburban and rural areas where the density of air quality monitoring stations is not high. In this type of areas citizen science strategies can be useful tools for awareness raising, but sensor technologies must be validated before sensor data are communicated to the public. In this work, the performance under field conditions of two custom-made types of ozone sensing devices, based on metal-oxide and electrochemical sensors, was tested. A large array of 132 metal-oxide (Sensortech MICS 2614) and 11 electrochemical (Alphasense) ozone sensors, built into 44 sensing devices, was co-located at reference stations in Italy (4 stations) and Spain (5). Mean R2 between sensor and reference data was 0.88 (0.78-0.96) and 0.89 (0.73-0.96) for Captor (metal-oxide) and Raptor (electrochemical) nodes. The metal-oxide sensors showed an upper limit (approximately 170 µg/m3) implying that these sensors may be useful to communicate mean ozone concentrations but not peak episodes. The uncertainty of the nodes was 10% between 100 and 150 µg/m3 and 20% between 150 and 200 µg/m3, for Captors, and 10% for >100 µg/m3 for Raptors. Operating both types of nodes up to 5 months did not evidence any clear influence of drifts. The use of these sensors in citizen science can be a useful tool for awareness raising. However, significant data processing efforts are required to ensure high data quality, and thus machine learning strategies are advisable. Relative uncertainties should always be reported when communicating ozone concentration data from sensing nodes.

Sirtuin 6 attenuates periapical lesion propagation by modulating hypoxia-induced chemokine (C-C motif) ligand 2 production in osteoblasts.

AIM: To investigate the attenuating effect of sirtuin 6 (SIRT6) on hypoxia-induced production of chemokine (C-C motif) ligand 2 (CCL2) by osteoblasts and the relevance of this action on the pathogenesis of periapical lesions. METHODOLOGY: Sirtuin 6 was overexpressed in MC3T3-E1 murine osteoblasts by lentivirus-mediated gene transfer. The relationship between the antiglycolytic/antioxidative activities of SIRT6 and its effect on hypoxia-induced CCL2 production were examined. Pathogenetic relevance of the actions of SIRT6 was assessed in a rat model of induced apical periodontitis. The data were analysed statistically using Student's t-test or one-way analysis of variance (anova) and then a Tukey's multiple comparison test. RESULTS: In cultured murine osteoblasts, 24-h hypoxic treatment significantly enhanced the generation of reactive oxygen species (P = 0.003), expression of lactate dehydrogenase A (LDHA) and production of lactate (P = 0.007). A reciprocal effect between hypoxia-induced redox imbalance and hypoxia-enhanced glycolysis was noted which in turn augmented the secretion of CCL2. Through its antiglycolytic and antioxidative effects, SIRT6 blocked the vicious cycle to suppress CCL2 production. In normal periapical tissues of rats, strong expression of SIRT6 and low levels of LDHA and 8-OHdG (a marker of oxidative DNA damage) were found in osteoblasts. In induced apical periodontitis, osteoblastic expression of SIRT6 was significantly suppressed (P = 0.001) which was associated with significantly elevated levels of LDHA (P = 0.003) and 8-OHdG (P = 0.004) and significantly enhanced recruitment of macrophages (P = 0.004). CONCLUSIONS: Sirtuin 6 has a therapeutic effect on periapical lesions through suppression of CCL2 synthesis. The anti-inflammatory action of SIRT6 is closely related to its regulatory activities in cellular metabolism and redox homoeostasis.

Delayed Gastric Emptying Following Laparoscopic Repair of Very Large Hiatus Hernias Impairs Quality of Life.

BACKGROUND: Delayed gastric emptying (DGE) following hiatus hernia surgery may affect a substantial number of patients with adverse clinical consequences. Here, we aim to evaluate the impact of DGE following laparoscopic repair of very large hiatus hernias on patients' quality of life, gastrointestinal symptomatology, and daily function. METHODS: Analysis of data collected from a multicenter prospective randomised trial of patients who underwent laparoscopic mesh versus sutured repair of very large hiatus hernias (>50% of stomach in chest). DGE was defined as gastric food retention visualised at endoscopy after 6 h of fasting at 6 months post-surgery. Quality of life (QOL), gastrointestinal symptomatology, and daily function were assessed with the SF-36 questionnaire, Visick scoring and structured surveys administered prior to surgery and at 1, 3, 6 and 12 months after surgery. RESULTS: Nineteen of 102 (18.6%) patients had DGE 6 months after surgery. QOL questionnaires were completed in at least 80% of patients across all time points. Compared with controls, the DGE group demonstrated significantly lower SF-36 physical component scores, delayed improvement in health transition, more adverse gastrointestinal symptoms, higher Visick scores and a slower rate of return to normal daily activities. These differences were still present 12 months after surgery. CONCLUSIONS: DGE following large hiatus hernia repair is associated with a negative impact on quality of life at follow-up to 12 months after surgery.

Exosomes promote cetuximab resistance via the PTEN/Akt pathway in colon cancer cells

Cetuximab is widely used in patients with metastatic colon cancer expressing wildtype KRAS. However, acquired drug resistance limits its clinical efficacy. Exosomes are nanosized vesicles secreted by various cell types. Tumor cell-derived exosomes participate in many biological processes, including tumor invasion, metastasis, and drug resistance. In this study, exosomes derived from cetuximab-resistant RKO colon cancer cells induced cetuximab resistance in cetuximab-sensitive Caco-2 cells. Meanwhile, exosomes from RKO and Caco-2 cells showed different levels of phosphatase and tensin homolog (PTEN) and phosphor-Akt. Furthermore, reduced PTEN and increased phosphorylated Akt levels were found in Caco-2 cells after exposure to RKO cell-derived exosomes. Moreover, an Akt inhibitor prevented RKO cell-derived exosome-induced drug resistance in Caco-2 cells. These findings provide novel evidence that exosomes derived from cetuximab-resistant cells could induce cetuximab resistance in cetuximab-sensitive cells, by downregulating PTEN and increasing phosphorylated Akt levels.

Exosomes promote cetuximab resistance via the PTEN/Akt pathway in colon cancer cells.

Cetuximab is widely used in patients with metastatic colon cancer expressing wildtype KRAS. However, acquired drug resistance limits its clinical efficacy. Exosomes are nanosized vesicles secreted by various cell types. Tumor cell-derived exosomes participate in many biological processes, including tumor invasion, metastasis, and drug resistance. In this study, exosomes derived from cetuximab-resistant RKO colon cancer cells induced cetuximab resistance in cetuximab-sensitive Caco-2 cells. Meanwhile, exosomes from RKO and Caco-2 cells showed different levels of phosphatase and tensin homolog (PTEN) and phosphor-Akt. Furthermore, reduced PTEN and increased phosphorylated Akt levels were found in Caco-2 cells after exposure to RKO cell-derived exosomes. Moreover, an Akt inhibitor prevented RKO cell-derived exosome-induced drug resistance in Caco-2 cells. These findings provide novel evidence that exosomes derived from cetuximab-resistant cells could induce cetuximab resistance in cetuximab-sensitive cells, by downregulating PTEN and increasing phosphorylated Akt levels.

The E3 ubiquitin ligase Cbl-b inhibits tumor growth in multidrug-resistant gastric and breast cancer cells.

Most receptor tyrosine kinases (RTKs) contribute to tumor growth, and their ubiquitination and degradation is related to the inhibition of tumor growth. Our previous study showed that the ubiquitin ligase Cbl-b was expressed at low levels in multidrug-resistant (MDR) gastric cancer cells compared with their parental cells. However, whether enhancement of Cbl-b expression in MDR cancer cells could prevent tumor proliferation via ubiquitination and degradation of RTK remains unclear. In the present study, Cbl-b overexpression reduced cell proliferation in MDR gastric and breast cancer cells, and effectively inhibited tumor growth in vivo. Additionally, Cbl-b overexpression reduced the total protein level of insulin-like growth factor 1 (IGF-1R), an important member of the RTK family. Moreover, Cbl-b overexpression promoted interaction of Cbl-b with IGF-1R, and induced ubiquitination and degradation of IGF-1R and inactivation of the IGF-1R pathway. These results suggest that the ubiquitin ligase Cbl-b inhibited tumor growth via ubiquitination and degradation of IGF-1R in MDR gastric and breast cancer cells.

[Influence of hypothyroidism on pregnancy outcome and fetus during pregnancy].

OBJECTIVE: To investigate the influence of hypothyroidism on pregnancy outcome and fetus in pregnant women. METHODS: A total of 4 286 pregnant women, who received prenatal examination in our hospital from January 2013 to October 2015, were selected as study subjects. The incidence of hypothyroidism and the influence on pregnancy outcomes and fetus were investigated. RESULTS: In 4 286 pregnant women surveyed, 209 hypothyroidism cases were detected(4.9%), including 85 clinical hypothyroidism cases and 124 subclinical hypothyroidism cases. In health group, the premature delivery rate was 1.0%, significantly lower than that in clinical hypothyroidism group(10.6%)and in subclinical hypothyroidism group(6.5%), the differences were significant(χ(2)= 38.884, P<0.001; χ(2)=17.722, P<0.001). In healthy group, the incidence of anemia was 3.8%, significantly lower than that in clinical hypothyroidism group(18.8%)and in subclinical hypothyroidism group(9.7%), the differences were significant(χ(2)=30.949, P<0.001; χ(2)=23.275, P<0.001). In health group, the incidence of low birth weight was 1.1%, significantly lower than that in clinical hypothyroidism group(14.1%)and in subclinical hypothyroidism group(4.8%), the differences were significant(χ(2)=50.593, P<0.001; χ(2)=15.637, P<0.001). In health group, the fetal distress incidence was 1.9%, significantly lower than that in clinical hypothyroidism group(10.6%)and in subclinical hypothyroidism group(5.6%), the differences were significant(χ(2)=19.257, P< 0.001; χ(2)=12.357, P<0.001). In health group, the fetal Apgar score(9.69 ± 0.32)was significantly higher than those in clinical hypothyroidism group(9.25 ± 0.45)and in subclinical hypothyroidism group(9.28 ± 0.44), the differences were significant(t=8.823, P<0.001; t=15.175, P<0.001). CONCLUSION: Hypothyroidism during pregnancy has adverse influences on pregnancy outcome and fetus, and it is necessary to strengthen the hypothyroidism detection in pregnant women for the early treatment.

[Analysis of the diagnosis and treatment of cerebrospinal fluid otorrhea].

Objective:To analyze the etiology and clinical symptoms and to investigate the therapeutic strategies of cerebrospinal fluid otorrhea. Method:A retrospective analysis of 37 cases of patients with cerebrospinal fluid otorrhea.The clinical symptoms, auxiliary examination, intraoperative findings, surgical methods and postoperative follow-up were analyzed. Result:In 37 cases, 35 patients underwent the plugging surgery once and cured, 1 patient with inner ear malformation underwent another operation and cured, 1 patient didn't have the operation. No cerebrospinal fluid leakage or meningitis recurrence was reported by the followed up from 1 months to 7 years after operation. Conclusion:Surgical repair is an effective method to treat the cerebrospinal fluid otorrhea. It is significant to take appropriate surgical approach to expose and to find the leak, according to the etiological factor and imaging examination.

A piecewise geometric analysis method for real-time ambulatory ECG detection.

BACKGROUND: As one of the pervasive healthcare services, Ubiquitous cardiac care (UCC) systems should have at least two significant characteristics: real-time detection capability for cardiac arrhythmia events and a small resource requirement for its computation and storage. PURPOSE: Due to the strict-constrained system support and ambulatory signal quality in the out-of-hospital pervasive healthcare applications, a dedicated real-time AED (Ambulatory Electrocardiograph Detection) algorithm has been implemented. METHODOLOGY: By adopting the piecewise geometric analysis method, this algorithm can provide a real-time continuous detection capability for QRS complexes, which consists of three main functional modules: the Data preparation; the R-wave vertex discovery; and the QRS complex recognition. Currently, this algorithm has been applied on an on-line UCC application system at the hospital for more than 30 patients. RESULT: The performance evaluation has been made not only on the standard MIT-BIH cardiac arrhythmia database but also on the clinical testing. The experiential results explore this algorithm has in average sensitivity of 99.37% and specificity of 99.72%. CONCLUSION: This AED algorithm has minimal beat detection latency and a less computation consumption, which make it meet the requirements of ubiquitous cardiac care applications.

Devolopmental and growth temperature regulation of omega-3 fatty acid desaturase genes in safflower (Carthamus tinctorius L.).

Three ω-3 fatty acid desaturase genes (CtFAD3, CtFAD7, and CtFAD8) were isolated from safflower (Carthamus tinctorius L.). Transcript analysis showed that the highest transcript levels were detected for CtFAD3 and the low transcript levels were detected for CtFAD7 and CtFAD8 in flowers. This result indicates that CtFAD3 enzyme activity is important for fatty acid desaturation in flowers. The low transcript level of CtFAD3 in developing seeds was consistent with the recorded high level of linoleic acid (18:2) and lack of linolenic acid (18:3) in safflower seed oil. At low temperatures, the induced transcription levels of ω-3 fatty acid desaturase genes in the stems and petioles were consistent with increased polyunsaturated fatty acids (PUFAs). In the roots, ω-3 fatty acid desaturase noticeably increased at low temperatures, whereas PUFA levels decreased. Interestingly, C18:3(Δ9,12,15) alcohol was specifically found in safflower roots, and showed a significant increase, indicating a flux in the acid to alcohol ratio of this compound in safflower roots.

Wireless and batteryless biomedical microsystem for neural recording and epilepsy suppression based on brain focal cooling.

This work presents a biomedical microsystem with a wireless radiofrequency (RF)-powered electronics and versatile sensors/actuators for use in nanomedicinal diagnosis and therapy. The cooling of brain tissue has the potential to reduce the frequency and severity of epilepsy. Miniaturised spiral coils as a wireless power module with low-dropout linear regulator circuit convert RF signals into a DC voltage, can be implanted without a battery in monitoring free behaviour. A thermoelectric (TE) cooler is an actuator that is employed to cool down brain tissue to suppress epilepsy. Electroencephalogram (EEG) electrodes and TE coolers are integrated to form module that is placed inside the head of a rat and fastened with a bio-compatible material. EEG signals are used to identify waveforms associated with epilepsy and are measured using readout circuits. The wireless part of the presented design achieves a low quiescent current and line/load regulation and high antenna/current efficiency with thermal protection to avoid damage to the implanted tissue. Epilepsy is suppressed by reducing the temperature to reduce the duration of this epileptic episode. Related characterisations demonstrate that the proposed design can be adopted in an effective nanomedicine microsystem.

Overexpression of HMGA2 in bladder cancer and its association with clinicopathologic features and prognosis HMGA2 as a prognostic marker of bladder cancer.

PURPOSE: To examine HMGA2 expression and investigate its clinical and prognostic significance in human urothelial bladder cancer (BUC). METHODS: We detected HMGA2 mRNA and protein expression by quantitative reverse-transcription polymerase chain reaction and western blotting, respectively in 44 frozen bladder cancer tissues and 18 adjacent normal bladder tissues. HMGA2 protein expression was assessed by immunohistochemical analysis of 148 paraffin-embedded specimens of human BUC and 30 specimens of adjacent normal bladder tissue. Correlations between HMGA2 and clinicopathologic features and prognosis were tested by statistical analyses. RESULTS: HMGA2 mRNA and protein levels in bladder cancer samples were significantly increased compared with adjacent normal bladder tissues (P < 0.001). mRNA overexpression correlated with high stage and grade of the bladder cancer (P < 0.001 and P = 0.002 respectively). HMGA2 protein expression was negative in all normal urothelial tissue samples, but positive in 52% (77/148) of bladder cancers (P < 0.001). HMGA2 expression correlated with tumor grade and stage (P < 0.001 and P = 0.003 respectively), Overexpression of HMGA2 protein in non-muscle-invasive bladder cancer was significantly associated with shorter recurrence-free survival (P < 0.001), and progression-free survival (P = 0.0004). Multivariate analysis showed that HMGA2 expression was an independent prognostic factor for both tumor recurrence (P < 0.001) and tumor progression (P = 0.006). CONCLUSIONS: HMGA2 is up-regulated in bladder cancer at both the transcriptional and translational levels compared with normal bladder tissue, HMGA2 protein is thus a potential prognostic marker for predicting tumor recurrence and progression.

Gastric cancer exosomes promote tumour cell proliferation through PI3K/Akt and MAPK/ERK activation.

BACKGROUND: Exosomes are nanometer-sized vesicles that are released by normal and neoplastic cells. Previous studies have focused on the interaction between tumour-derived exosomes and the immune system, as a consequence of immune suppression or enhancement. However, the effects of tumour-derived exosomes on tumour cells themselves have not been well studied. AIMS: To investigate the effects of gastric cancer exosomes on tumour cell proliferation and the possible mechanisms. METHODS: By serial centrifugation and sucrose gradient ultracentrifugation, we isolated and purified the exosomes from gastric cancer SGC7901 cells, then viewed them by electron microscopy. Cell proliferation was measured by 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide assay. Protein expression was assayed by Western blotting. RESULTS: SGC7901-cell-derived exosomes promoted the proliferation of SGC7901 and BGC823 cells. The increase in proliferation induced by exosomes was accompanied by activation of Akt and extracellular-regulated protein kinase, and phosphoinositide 3-kinase or extracellular-regulated protein kinase inhibitor partially reversed the proliferative effect of exosomes. Moreover, the exosome-induced increase in activity of Akt and extracellular-regulated protein kinase coincided with decreased expression of the Casitas B-lineage lymphoma family of ubiquitin ligases. CONCLUSION: Gastric cancer exosomes promoted tumour cell proliferation, at least in part, by activation of PI3K/Akt and mitogen-activated protein kinase/extracellular-regulated protein kinase pathways. The decreased expression of Casitas B-lineage lymphoma proteins might have contributed to the activation of Akt and extracellular-regulated protein kinase.