Metabolic syndrome and C-reactive protein concentration as independent correlates of chronic kidney disease.

Inflammation is a common phenotype for cardiometabolic disorders. In this study, we attempted to investigate inter-relationships between metabolic syndrome (MetS), C-reactive protein (an inflammatory biomarker) and chronic kidney disease (CKD). We performed a cross-sectional analysis of data from a representative sample of 4425 Chinese adults in Taiwan. The MetS was defined by a unified criteria set by several major organizations. A CKD event was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min per 1.73 m(2). Additionly, a CRP cutpoint of 3 mg/L was used to differentiate high and low CRP levels. Overall, 1000 participants had MetS, resulting in a prevalence rate of 22.6%. High CRP level was noted in 782 (17.6%) subjects. In addition, a total of 508 (11.5%) persons qualified as having CKD. Subjects with the MetS had 1.55-fold [95% confidence interval (CI), 1.03-2.32] increased odds of CKD compared with their counterparts without the MetS after multiple adjustments. In addition, there was a significantly graded relationship between increasing levels of serum CRP and prevalent CKD (p for trend = 0.001). Participants in the highest category of serum CRP had a significantly elevated odds of CKD as compared with those in the lowest category [odds ratio (OR), 1.60; 95% CI, 1.21-2.12]. However, there was no interaction in excess of additive scale between the presence of MetS and high CRP level (p = 0.83). These findings suggest that MetS and high CRP were independently associated with increased prevalence of CKD in Chinese adults.

Hyperglycemia exacerbates intracerebral hemorrhage via the downregulation of aquaporin-4: temporal assessment with magnetic resonance imaging.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is associated with high mortality and neurological deficits, and concurrent hyperglycemia usually worsens clinical outcomes. Aquaporin-4 (AQP-4) is important in cerebral water movement. Our aim was to investigate the role of AQP-4 in hyperglycemic ICH. METHODS: Hyperglycemia was induced by intraperitoneal injection of streptozotocin (STZ; 60 mg/kg) in adult Sprague-Dawley male rats. ICH was induced by stereotaxic infusion of collagenase/heparin into the right striatum. One set of rats was repeatedly monitored by MRI at 1, 4, and 7 days after ICH induction so as to acquire information on the formation of hematoma and edema. Another set of rats was killed and brains were examined for differences in the degree of hemorrhage and edema, water content, blood-brain barrier destruction, and AQP-4 expression. RESULTS: Hyperglycemia ICH rats exhibited increased brain water content, more severe blood-brain barrier destruction, and greater vasogenic edema as seen on diffusion-weighted MRI. Significant downregulation of AQP-4 was observed in STZ-treated rats after ICH as compared with non-STZ-treated rats. Apoptosis was greater on day 1 after ICH in STZ-treated rats. CONCLUSIONS: The expression of AQP-4 in the brain is downregulated in hyperglycemic rats as compared with normoglycemic rats after ICH. This change is accompanied by increased vasogenic brain edema and more severe blood-brain barrier destruction.

The Risk of Breast Cancer between Western and Mediterranean Dietary Patterns.

Breast cancer is a significant public health problem globally and prevention strategies have become of great interest as its incidence rises. Exploring the connection between dietary patterns and the reduction of breast cancer risk is considered a promising approach. High levels of fiber, phytochemicals, a good antioxidant profile, and a composition of advantageous fatty acids are characteristics of healthy dietary programs such as the Mediterranean diet. This review summarized and discussed the active compounds that are considered important in preventing breast cancer, including dietary components from recent related reports. These include polyunsaturated fatty acids, fiber, phytochemicals, and alcohol. Although the exact mechanism for preventing breast cancer using these dietary factors is not well understood, the combination of all the elements in a healthy diet plays a role in reducing breast cancer risk. Considering the elevated probability of breast cancer relapse and mortality, it is crucial to investigate the correlation between a nutritious dietary pattern and breast cancer, while identifying bioactive components that have the potential to mitigate the risk of breast cancer incidence.

Investigation of the effect of hyperglycemia on intracerebral hemorrhage by proteomic approaches.

Intracerebral hemorrhage (ICH) is associated with high mortality and disability, and hyperglycemia worsens the clinical and neurological outcomes of patients with ICH. In this study, we utilized proteomic approaches to investigate the role of hyperglycemia in ICH. Hyperglycemia was induced by intraperitoneal injection of streptozotocin (STZ) in adult Sprague-Dawley male rats; ICH was induced by stereotaxic infusion of collagenase/heparin into the right striatum. It was observed that the size of induced hemorrhage was significantly larger in the hyperglycemic group (n=6 in each group). On the first day after ICH, an apparent decrease in the bilateral grasp was also observed for the lesioned hyperglycemic rats compared with normoglycemic ones. When employing 2-DE and MS to examine the proteomes of perihematomal and control regions in individual hyperglycemic and normoglycemic rats, eight differentially expressed protein targets were identified. Most noteworthy, in response to ICH significant increase of albumin was ubiquitously observed in the brains of normoglycemic rats but not in the brains of hyperglycemic rats. Coincidentally, more significant neuronal apoptosis were found in the perihematomal regions of hyperglycemic rats. These observations described suggest the protection role of albumin in acute stage of ICH, which may be dependent on different blood sugar levels.

Impact of metabolic syndrome on the incidence of chronic kidney disease: a Chinese cohort study.

AIM: Metabolic syndrome (MetS) is a major culprit in cardiovascular disease and chronic kidney disease (CKD) in Western populations. We studied the longitudinal association between MetS and incident CKD in Chinese adults. METHODS: A cohort study was conducted in a nationally representative sample of 4248 Chinese adults in Taiwan. The MetS was defined according to a unified criteria set by several major organizations and CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min per 1.73 m(2). Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) adjusted for sex, age, body mass index (BMI) and serum levels of total cholesterol. RESULTS: The prevalence of MetS among participants at baseline recruitment was 15.0% (637/4248). During a median follow-up period of 5.40 years, 208 subjects (4.9%) developed CKD. The multivariate-adjusted HR of CKD in participants with MetS compared with those without was 1.42 (95% CI = 1.03, 1.73). Additionally, there was a significantly graded relationship between the number of the MetS components and risk of CKD. Further, the relation between MetS and incident CKD was more robust in subjects with BMI >27.5 kg/m(2) than in those with lower BMI. CONCLUSION: The results suggest that the presence of MetS was significantly associated with increased risk of incident CKD in a Chinese population. These findings warrant future studies to test the impact of preventing and treating MetS on the reduction of the occurrence of CKD.

The impact of frailty on breast cancer outcomes: evidence from analysis of the Nationwide Inpatient Sample, 2005-2018.

The aims of the present study were to examine whether and how frailty impacts the outcomes of breast cancer. Data of women with breast cancer hospitalized during 2005 and 2018 were extracted from the US Nationwide Inpatient Sample (NIS) database. Frailty was identified using a novel algorithm, Hospital Frailty Risk Score (HFRS). Propensity-score (PS) matching was utilized to balance the baseline characteristics between frail and non-frail groups. In-hospital mortality, unfavorable discharge, prolonged length of stay (LOS), and total hospital cost were compared using univariate and multivariable logistic regression analyses. A total of 19,522 patients with metastatic (frailty n = 9,906; no frailty n = 9,716) and 135,200 with non-metastatic breast cancer (frailty n = 30,235; no frailty n = 104,965) were included. After adjustment, frailty was significantly and independently associated with higher risk for in-hospital mortality, unfavorable discharge, prolonged LOS, and greater hospital cost in both metastatic and non-metastatic diseases, in which the impacts of frailty was greater in women with non-metastatic disease. In stratified analysis, frailty had the greatest impact on in-hospital mortality among women had had non-metastatic disease and aged <50 years (aOR = 3.88; 95% CI: 1.95-7.73). In conclusion, frailty is associated with worse outcomes in women with breast cancer, and the effects are greater in non-metastatic disease and younger patients.

Joint effect of peroxisome proliferator-activated receptor γ genetic polymorphisms and estrogen-related risk factors on breast cancer risk: results from a case-control study in Taiwan.

Peroxisome proliferator-activated receptor γ (PPARγ) has been linked with possible antineoplastic effects in colorectal carcinogenesis. However, data for the possible link between PPARγ and breast cancer risk are sparse. We assessed the association of three polymorphisms in PPARγ (rs10865710 [C-681T], rs1805192 [Pro12Ala], and rs3856806 [C1431T]) with the risk of breast cancer in an ethnic Chinese female population in Taiwan. In addition, interactions with estrogen exposures were also explored. Genotypes for the PPARγ polymorphisms were determined on 291 incident breast cancer cases and 589 matched controls by fluorogenic 5'-nuclease assay. The at-risk haplotypes were defined according to the three polymorphisms in the following order: C-681T, Pro12Ala, and C1431T, which include CCT, GGT, and GGC. In addition, a critical period of estrogen exposure was estimated by the interval between age at menarche and age at first full-term pregnancy. Overall, there was no evidence of a significant impact of individual polymorphisms of PPARγ on breast cancer risk. However, the haplotype analysis revealed that women harboring at-risk haplotypes showed a significant 67% increase in breast cancer risk [adjusted odds ratio (OR) 1.67; 95% confidence interval (CI) 1.11-2.52]. Furthermore, there was a significant joint effect of estrogen exposure-related factors and at-risk haplotypes of PPARγ on breast cancer risk (adjusted OR 4.04; 95% CI 1.89-8.65), particularly in premenopausal women. The present study implicates a role for PPARγ in breast cancer risk. Mechanistic studies to fully elucidate the mechanisms underlying PPARγ's effects should be pursued in future investigations.

Dietary intake of vitamin B(6) and risk of breast cancer in Taiwanese women.

BACKGROUND: B vitamins, including vitamin B(6), are coenzymes that are important for DNA integrity and stability. Deficiencies in B vitamins may promote tumor carcinogenesis. METHODS: We examined the association of dietary vitamin B(6) intake with overall breast cancer risk and breast cancers stratified by hormone receptor status. This case-control study included 391 breast cancer cases and 782 control subjects enrolled at the Tri-Service General Hospital in Taipei, Taiwan. Energy-adjusted intake of vitamin B(6) was derived from a food frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression. RESULTS: As compared with women in the lowest tertile, the multivariate-adjusted ORs for breast cancer among women in the second and highest tertiles of vitamin B(6) intake were 0.78 (95% CI, 0.64-2.52) and 0.64 (0.26-0.92), respectively. In addition, higher vitamin B(6) intake was associated with a significantly lower risk of developing ER-negative breast tumors. CONCLUSIONS: Our findings suggest that higher intake of vitamin B(6) is associated with a reduction in breast cancer risk, particularly ER-negative tumors.

Use of a totally implantable access port through the external jugular vein when the cephalic vein approach is not feasible.

BACKGROUND: We report our experience of using a totally implantable access port (TIAP) through the external jugular vein (EJV) when the cephalic vein (CV) approach is not feasible. METHODS: We reviewed 197 cases involving TIAP implantation through the EJV in a single medical center between January 1995 and January 2009. All the ports were implanted after the CV approach was found unfeasible. Patient characteristics, operating time, and early and late complications were recorded. RESULTS: The mean patient age was 50 years (range: 33-75). The mean operating time was 54.5 ± 7.5 minutes. Early complications within the first 30 postoperative days included port hematoma (2%) and catheter migration (2%). The late postoperative complications included catheter occlusion (2.5%), venous thrombosis (2%), and port infection (1.5%). There were no complications associated with TIAP disconnection. CONCLUSIONS: The EJV approach is an easy and safe alternative method for TIAP implantation when the CV approach is not feasible. This method can avoid conversion to percutaneous puncture of the subclavian vein, which could result in life-threatening complications such as pneumothorax and hemothorax. In patients with breast cancer or those who are contraindicated for TIAP implantation on the opposite side, the EJV cutdown approach provides an alternative route with comfortable and satisfactory results as complications with this approach are rare.

Survival outcomes in elderly Taiwanese women according to breast cancer subtype and lymph node status: A single-center retrospective study.

This study aimed to determine the rates of overall survival and recurrence-free survival among elderly Taiwanese women (>65 years old) according to breast cancer subtype and lymph node status. We identified 554 eligible patients who were >65 years old and had been treated based on international recommendations at our center between June 2005 and June 2015. Patients with the luminal A subtype had the highest rates of overall survival (90.6%) and recurrence-free survival (97.0%), while the lowest overall survival rate was observed in those with the triple-negative subtype (81.3%) and the lowest recurrence-free survival rate was observed in those with the luminal B subtype (84.0%). Multivariate Cox proportional hazard analysis, using the luminal A subtype as the reference, revealed significant differences in recurrence-free survival among luminal B patients according to lymph node status. Among elderly Taiwanese women with breast cancer, the breast cancer subtype might help predict survival outcomes. The luminal B subtype was associated with poor recurrence-free survival, and lymph node status was useful for predicting recurrence-free survival in this subset of patients.

A proteomics-based translational approach reveals an antifolate resistance inherent in human plasma derived from blood donation.

The inhibition of dihydrofolate reductase (DHFR) by antifolates is a common practice both in cell culture and in chemotherapy. Surprisingly, antifolate resistance was also observed in cultured murine myeloma cells (SP2/0) in the presence of human plasma (HP); thus, we used a proteomic approach to identify novel plasma biomarker(s) for this condition. In contrast to the in vitro antifolate response, metabolic enzymes and translation machinery proteins were found to be up-regulated in the presence of HP. The antifolate resistance inherent in HP may be explained by a simultaneous promotion of cell proliferation and the maintenance of DNA integrity. Furthermore, the factor(s) was found to be extrinsic, heat stable and very small in size. Adenine, a supplemented additive in erythrocyte preservation, was subsequently identified as the contributing factor and exogenous addition in cultures reversed the cytotoxicity induced by antifolates. Importantly, adenine-containing blood components, which may provide enhanced survival to otherwise sensitive antifolate-targeted cells, showed a dose-dependent adverse effect in transfusion recipients receiving antifolate (methotrexate) medications. These findings not only highlight a previously unnoticed role of adenine, but also emphasize a novel mechanistic link between transfusion and subsequently reduced survival in patients taking methotrexate.

Relationships between critical period of estrogen exposure and circulating levels of insulin-like growth factor-I (IGF-I) in breast cancer: evidence from a case-control study.

Epidemiological observations suggest that insulin-like growth factor-I (IGF-I), a potent mitogenic and anti-apoptotic peptide, plays a role in the etiology of breast cancer. Estrogen, which is crucial in breast carcinogenesis, both regulates and is influenced by IGF-I family. A case-control study was conducted to assess the role of IGF-I as a biomarker for breast cancer and to evaluate the potential joint effect of circulating IGF-I and critical period of estrogen exposure, as estimated by the interval between age at menarche and age at first full-term pregnancy on the risk of breast cancer. Questionnaire information and blood samples were taken before treatment from 297 incident cases with breast cancer and 593 controls admitted for health examination at the Tri-Service General Hospital, Taipei between 2004 and 2006. Plasma levels of IGF-I and IGFBP-3 were measured by immunoradiometric assay. Conditional logistic regression was used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs). Our case-control data indicate that breast cancer risk related to IGF-I differs according to menopausal status. High circulating levels of IGF-I increased risk of pre- but not postmenopausal breast cancer (top vs. bottom tertile, adjusted OR, 1.86; 95% CI, 1.01-3.44). Furthermore, elevated IGF-I concentrations in conjunction with prolonged interval of critical period of estrogen exposure were associated with significantly increased risk of breast cancer, particularly among estrogen-positive cases (adjusted OR, 2.42, 95% CI, 1.33-4.38). These results suggest that the joint effect of IGF-I and estrogens may provide novel methods of breast cancer risk reduction among women.

Adipocytokine resistin and breast cancer risk.

Adipocytokine resistin is a member of the newly discovered family of cysteine-rich protein. Recent data suggest that macrophages are a major source of human resistin. Given the obesity-breast cancer link and convergence of adipocyte and macrophage function, resistin may provide unique insight into links between obesity, inflammation, and breast cancer risk in humans. We conducted a hospital-based case-control study to evaluate whether plasma resistin levels were associated with breast cancer risk in women. We also examined the modification effect of estrogen exposures on the resistin-breast cancer link. Questionnaire information, anthropometric measures, and blood samples were taken before treatment from 380 incident cases with breast cancer and 760 controls admitted for health examination at the Tri-Service General Hospital, Taipei between 2004 and 2008. Plasma levels of resistin were measured by enzyme immunoassay. Cumulative exposure to estrogens were estimated according to the age at menarche and age at enrollment for premenopausal women and age at menarche and age at menopause for postmenopausal women. Cases with breast cancer had significantly elevated resistin concentrations as compared with control subjects. Compared with those in the lowest quartile, the adjusted odds ratios of breast cancer for women in the second, third, and highest quartiles were 1.48 [95% confidence interval (CI) = 0.65-3.38], 1.76 (95% CI = 1.00-4.73), and 2.08 (95% CI = 1.04-3.85), respectively. Furthermore, the biological gradient of breast cancer risk by plasma resistin levels remained after adjustment for measures of adiposity. The dose-dependent relationship of resistin levels with breast cancer risk was notably pronounced among women with excess exposure to estrogens. Adipocytokine resistin may have an adiposity-independent role in breast carcinogenesis. Mechanistic studies to fully elucidate the mechanisms underlying resistin's effects should be pursued in future investigations.

The effectiveness of benzydamine hydrochloride spraying on the endotracheal tube cuff or oral mucosa for postoperative sore throat.

BACKGROUND: The etiology of postoperative sore throat (POST) is considered to be the result of laryngoscopy, intubation damage, or inflated cuff compression of the tracheal mucosa. In this study, we compared the effectiveness in alleviating POST using different approaches to benzydamine hydrochloride (BH) administration by spraying the endotracheal tube (ET) cuff or the oropharyngeal cavity, or both. METHODS: Three hundred eighty patients were included in this prospective and double-blind study, which was randomized into 4 groups: group A, oropharyngeal cavity spray of BH, and distilled water on the ET cuff; group B, both the oropharyngeal cavity and the ET cuff received BH spray; group C, the ET cuff received BH spray, and the oropharyngeal cavity received distilled water; and group D, distilled water sprayed on both the ET tube and into the oropharyngeal cavity. The patients were examined for sore throat (none, mild, moderate, severe) at 0, 2, 4, and 24 hours postextubation. RESULTS: The incidence of POST was 23.2%, 13.8%, 14.7%, and 40.4% in groups A, B, C, and D, respectively. POST occurred significantly less frequently in groups B and C compared with group D (odds ratio: 0.36; 95% confidence interval: 0.21-0.60; P < 0.05). However, there was no significant difference between groups A and D (odds ratio: 0.62; 95% confidence interval: 0.38-1.01). Moreover, there was no significant interaction between spraying BH over the oropharyngeal cavity and the ET cuff on the incidence of POST (P = 0.088). The severity of POST was significantly more intense in group D compared with groups B and C (P < 0.001). Group B had a significantly higher incidence of local numbness, burning, and/or stinging sensation compared with patients in group D (P < 0.05). CONCLUSIONS: This study indicates that spraying BH on the ET cuff decreases the incidence and severity of POST without increased BH-related adverse effects.

Clonal dissemination of the multi-drug resistant Salmonella enterica serovar Braenderup, but not the serovar Bareilly, of prevalent serogroup C1 Salmonella from Taiwan.

BACKGROUND: Nontyphoidal Salmonella is the main cause of human salmonellosis. In order to study the prevalent serogroups and serovars of clinical isolates in Taiwan, 8931 Salmonellae isolates were collected from 19 medical centers and district hospitals throughout the country from 2004 to 2007. The pulsed-field eletrophoresis types (PFGE) and antibiotic resistance profiles of Salmonella enterica serovars Bareilly (S. Bareilly) and Braenderup (S. Braenderup) were compared, and multi-drug resistance (MDR) plasmids were characterized. RESULTS: Over 95% of human salmonellosis in Taiwan was caused by five Salmonella serogroups: B, C1, C2-C3, D1, and E1. S. Typhymurium, S. Enteritidis, S. Stanley and S. Newport were the four most prevalent serovars, accounting for about 64% of isolates. While only one or two major serovars from four of the most prevalent serogroups were represented, four predominant serovars were found in serogroup C1 Salmonellae. The prevalence was decreasing for S. Choleraeuis and S. Braenderup, and S. Virchow and increasing for S. Bareilly. S. Braenderup mainly caused gastroenteritis in children; in contrast, S. Bareiley infected children and elderly people. Both serovars differed by XbaI-PFGE patterns. Almost all S. Bareilly isolates were susceptible to antibiotics of interest, while all lacked plasmids and belonged to one clone. Two distinct major clones in S. Braenderup were cluster A, mainly including MDR isolates with large MDR plasmid from North Taiwan, and cluster B, mainly containing susceptible isolates without R plasmid from South Taiwan. In cluster A, there were two types of conjugative R plasmids with sizes ranging from 75 to 130 kb. Type 1 plasmids consisted of replicons F1A/F1B, blaTEM, IS26, and a class 1 integron with the genes dfrA12-orfF-aadA2-qacEDelta1-sulI. Type 2 plasmids belonged to incompatibility group IncI, contained tnpA-blaCMY-2-blc-sugE genetic structures and lacked both IS26 and class 1 integrons. Although type 2 plasmids showed higher conjugation capability, type 1 plasmids were the predominant plasmid. CONCLUSIONS: Serogroups B, C1, C2-C3, D1, and E1 of Salmonella caused over 95% of human salmonellosis. Two prevalent serovars within serogroup C1, S. Bareilly and cluster B of S. Braenderup, were clonal and drug-susceptible. However, cluster A of S. Braenderup was MDR and probably derived from susceptible isolates by acquiring one of two distinct conjugative R plasmids.

Evolution of genes on the Salmonella Virulence plasmid phylogeny revealed from sequencing of the virulence plasmids of S. enterica serotype Dublin and comparative analysis.

Salmonella enterica serotype Dublin harbors an approximately 80-kb virulence plasmid (pSDV), which mediates systemic infection in cattle. There are two types of pSDV: one is pSDVu (pOU1113) in strain OU7025 and the other pSDVr (pOU1115) in OU7409 (SD Lane) and many clinical isolates. Sequence analysis showed that pSDVr was a recombinant plasmid (co-integrate) of pSDVu and a plasmid similar to a 35-kb indigenous plasmid (pOU1114) of S. Dublin. Most of the F-transfer region in pSDVu was replaced by a DNA segment from the pOU1114-like plasmid containing an extra replicon and a pilX operon encoding for a type IV secretion system to form pSDVr. We reconstructed the particular evolutionary history of the seven virulence plasmids of Salmonella by comparative sequence analysis. The whole evolutionary process might begin with two different F-like plasmids (IncFI and IncFII), which then incorporated the spv operon and fimbriae operon from the chromosome to form the primitive virulence plasmids. Subsequently, these plasmids descended by deletion from a relatively large plasmid to smaller ones, with some recombination events occurring over time. Our results suggest that the phylogeny of virulence plasmids as a result of frequent recombination provides the opportunity for rapid evolution of Salmonella in response to the environmental cues.

Integrated omics-based pathway analyses uncover CYP epoxygenase-associated networks as theranostic targets for metastatic triple negative breast cancer.

BACKGROUND: Current prognostic tools and targeted therapeutic approaches have limited value for metastatic triple negative breast cancer (TNBC). Building upon current knowledge, we hypothesized that epoxyeicosatrienoic acids (EETs) and related CYP450 epoxygenases may have differential roles in breast cancer signaling, and better understanding of which may uncover potential directions for molecular stratification and personalized therapy for TNBC patients. METHODS: We analyzed the oxylipin metabolome of paired tumors and adjacent normal mammary tissues from patients with pathologically confirmed breast cancer (N = 62). We used multivariate statistical analysis to identify important metabolite contributors and to determine the predictive power of tumor tissue metabolite clustering. In vitro functional assays using a panel of breast cancer cell lines were carried out to further confirm the crucial roles of endogenous and exogenous EETs in the metastasis transformation of TNBC cells. Deregulation of associated downstream signaling networks associated with EETs/CYPs was established using transcriptomics datasets from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). Comparative TNBC proteomics using the same tissue specimens subjected to oxylipin metabolomics analysis was used as validation set. RESULTS: Metabolite-by-metabolite comparison, tumor immunoreactivity, and gene expression analyses showed that CYP epoxygenases and arachidonic acid-epoxygenation products, EET metabolites, are strongly associated with TNBC metastasis. Notably, all the 4 EET isomers (5,6-, 8,9-, 11,12-, and 14,15-EET) was observed to profoundly drive the metastasis transformation of mesenchymal-like TNBC cells among the TNBC (basal- and mesenchymal-like), HER2-overexpressing and luminal breast cancer cell lines examined. Our pathway analysis revealed that, in hormone-positive breast cancer subtype, CYP epoxygenase overexpression is more related to immune cell-associated signaling, while EET-mediated Myc, Ras, MAPK, EGFR, HIF-1α, and NOD1/2 signaling are the molecular vulnerabilities of metastatic CYP epoxygenase-overexpressing TNBC tumors. CONCLUSIONS: This study suggests that categorizing breast tumors according to their EET metabolite ratio classifiers and CYP epoxygenase profiles may be useful for prognostic and therapeutic assessment. Modulation of CYP epoxygenase and EET-mediated signaling networks may offer an effective approach for personalized treatment of breast cancer, and may be an effective intervention option for metastatic TNBC patients.

Genetic manipulation of islet cells in autoimmune diabetes: from bench to bedside.

Type 1 diabetes (T1D) develops via spontaneous autoimmune destruction of pancreatic beta cells. The immunoprogression and effectors of T1D have been determined using non-obese diabetic (NOD) mouse mode. Transgenic mice overexpressing a variety of transgenes driven by insulin promoter demonstrate that both apoptosis and necrosis lead to islet cells death; furthermore, various immune cells and cytokine effectors are involved in the immunoprogression of T1D. Efficiently halting immune attack in the islet milieu by an effector-specific manner apparently provides the preventive and therapeutic strategies in T1D. Islet transplantation has been reported as an appropriate treatment to accomplish insulin independence and long-term homeostasis of glucose in T1D. However, it is difficult to protect the islet grafts from subsequent immune attack and prolong their survival. In this review, we highlight the transgenic mice that express transgenes restricted in islet cells to depict the complicated interactions of immune cells in inflammatory islets, to investigate the protective efficacy of some immunomodulatory genes, and to develop genetically-modified islets tolerant to immune attack that might be used in future clinical application.

Prevalence and characterization of multidrug-resistant (type ACSSuT) Salmonella enterica serovar Typhimurium strains in isolates from four gosling farms and a hatchery farm.

Salmonella enterica serovar Typhimurium strains of phage types DT104 and U302 are often resistant to ampicillin, chloramphenicol, streptomycin, sulfonamides, and tetracycline (the ACSSuT resistance type) and are major zoonotic pathogens. Increased consumption of goose meat may enhance the risk of transferring S. enterica serovar Typhimurium and other enteric pathogens from geese to human due to the consumption of meats from infected geese or improper preparation of meats. Therefore, we characterized S. enterica serovar Typhimurium strains isolated from four goose farms (farms A, B, C, and D) and one hatchery farm (farm E) to determine the epidemic and genetic differences among them. Antibiotic susceptibility tests and multiplex PCR confirmed that 77.6% (52/67) of strains were ACSSuT strains isolated from farms A, C, and E. Antibiotic-susceptible strains were isolated mostly from farm B, and no strain was observed in farm D. All ACSSuT strains harbored a 94.7-kb virulence plasmid and contained one 1.1-kb conserved segment identical to that of Salmonella genomic island 1. Four genotypes were determined among these S. enterica serovar Typhimurium isolates by pulsed-field gel electrophoresis analysis of XbaI-digested DNA fragments. Most isolates (85.29%; 29/34) of major genotype Ib were ACSSuT strains isolated mainly from goslings of farm C and egg membranes of farm E, a hatchery farm, suggesting that S. enterica serovar Typhimurium strains in isolates from goslings might originate from its hatchery, from the egg membranes to the gosling fluff after hatching. Multiple phage types, types 8, 12, U283, DT104, and U302, were identified. In conclusion, geese were a reservoir of diverse multidrug-resistant (type ACSSuT) S. enterica serovar Typhimurium strains, and each farm was colonized with genetically closely related S. enterica serovar Typhimurium strains.

Matriptase and survivin expression associated with tumor progression and malignant potential in breast cancer of Chinese women: tissue microarray analysis of immunostaining scores with clinicopathological parameters.

OBJECTIVE: The aim of this study was to examine the expression of matriptase and survivin in breast carcinoma and correlate with clinicopathological parameters. METHODS: Immunohistochemical analysis of matriptase and survivin were performed in tissue microarray slides of 290 cases, including 11 normal breast tissue; 27 fibrocystic disease; 17 fibroadenoma; 6 atypical ductal hyperplasia; 39 ductal carcinoma in situ, low grade (DCIS, low grade); 39 ductal carcinoma in situ, high grade (DCIS, high grade); 27 invasive ductal carcinoma, grade I (IDC, grade I); 78 invasive ductal carcinoma, grade II (IDC, grade II); and 46 invasive ductal carcinoma, grade III (IDC, grade III). RESULTS: The average immunostaining scores of matriptase were 44.1 in normal breast tissue, 52.7 in fibrocystic disease, 76.5 in fibroadenoma, 81.7 in atypical ductal hyperplasia, 133.7 in low-grade DCIS, and 155.8 in high-grade DCIS. Among 151 breast IDC cases, the average immunostaining scores of matriptase were 172.7 in grade I, 211.7 in grade II, and 221.2 in grade III. Additionally, the average immunostaining scores of surviving also correlate with tumor grades and stages. CONCLUSIONS: Higher expressions of matriptase and survivin correlate significantly with clinicopathological parameters in breast cancer and the malignant potential in premalignant lesions. In addition, higher survivin expression had poorer prognosis of breast IDC cases.