Evaluation of sub-chronic toxicity of melamine via systematic or oral delivery in adult zebrafish based on behavioral endpoints.

Melamine-tainted products have been found in the market and raised issues about food safety. Recent studies done in rodents and humans demonstrated the toxicities of melamine, especially in causing kidney damage and bladder stone formation. However, very few studies assessed its behavior toxicity in organisms, including fish. Therefore, in this study, the researchers aim to determine whether sub-chronic exposure to melamine via oral and systematic administration could induce behavioral abnormality in zebrafish. After 14 days of systematic exposure to melamine at doses of 0.1 and 10 ppm levels, zebrafish were subjected to multiple behavioral assays. Results from both exposure routes showed that melamine indeed slightly increased fish locomotion and altered their exploratory behaviors in the novel tank assay. Furthermore, tightened shoaling formation was also displayed by the treated fish in the waterborne exposure group. However, melamine exposure did not cause any obvious alterations in fish behaviors during other behavioral tests. In addition, in comparison with previously published data on the behavior toxicities of several solvents in zebrafish, our phenomic analysis suggests the relatively low behavior toxicities of melamine via either systematic exposure or oral administration to zebrafish compared to those solvents. Nevertheless, our data indicate that the potential neurotoxicity of chronic low-dose melamine should not be ignored.

Taurine Rescues Cancer-induced Atrophy in Human Skeletal Muscle Cells via Ameliorating the Inflammatory Tumor Microenvironment.

BACKGROUND/AIM: Cancer cachexia is a wasting syndrome that has a devastating impact on the prognosis of patients with cancer. It is well-documented that pro-inflammatory cytokines are involved in the progression of this disorder. Therefore, this study was conducted to investigate the protective effect of taurine, an essential nonprotein amino acid with great anti-inflammatory properties, in attenuating muscle atrophy induced by cancer. MATERIALS AND METHODS: Conditioned media (CM) derived from T24 human bladder carcinoma cells with or without 5 mM taurine were incubated with human skeletal muscle cells (HSkMCs) and their differentiation was examined. The intracellular reactive oxygen species (ROS), morphology, and the catabolic pathway were monitored. RESULTS: T24-derived CM with high levels of TNF-α and IL-6 caused aberrant ROS accumulation and formation of atrophic myotubes by HSkMCs. In T24 cancer cells, taurine significantly inhibited the production of TNF-α and IL-6. In HSkMCs, taurine increased ROS clearance during differentiation and preserved the myotube differentiation ability impaired by the inflammatory tumor microenvironment. In addition, taurine ameliorated myotube atrophy by regulating the Akt/FoxO1/MuRF1 and MAFbx signaling pathways. CONCLUSION: Taurine rescues cancer-induced atrophy in human skeletal muscle cells by ameliorating the inflammatory tumor microenvironment. Taurine supplementation may be a promising approach for intervening with the progression of cancer cachexia.

Evaluation of Tacrolimus' Adverse Effects on Zebrafish in Larval and Adult Stages by Using Multiple Physiological and Behavioral Endpoints.

Tacrolimus (FK506) is a common immunosuppressant that is used in organ transplantation. However, despite its importance in medical applications, it is prone to adverse side effects. While some studies have demonstrated its toxicities to humans and various animal models, very few studies have addressed this issue in aquatic organisms, especially zebrafish. Here, we assessed the adverse effects of acute and chronic exposure to tacrolimus in relatively low doses in zebrafish in both larval and adult stages, respectively. Based on the results, although tacrolimus did not cause any cardiotoxicity and respiratory toxicity toward zebrafish larvae, it affected their locomotor activity performance in light-dark locomotion tests. Meanwhile, tacrolimus was also found to slightly affect the behavior performance, shoaling formation, circadian rhythm locomotor activity, and color preference of adult zebrafish in a dose-dependent manner. In addition, alterations in the cognitive performance of the fish were also displayed by the treated fish, indicated by a loss of short-term memory. To help elucidate the toxicity mechanism of tacrolimus, molecular docking was conducted to calculate the strength of the binding interaction between tacrolimus to human FKBP12. The results showed a relatively normal binding affinity, indicating that this interaction might only partly contribute to the observed alterations. Nevertheless, the current research could help clinicians and researchers to further understand the toxicology of tacrolimus, especially to zebrafish, thus highlighting the importance of considering the toxicity of tacrolimus prior to its usage.

Characterization of young infants with fecal carriage of multidrug-resistant Escherichia coli in Southern Taiwan.

BACKGROUND: The accelerating prevalence of extended-spectrum ß-lactamase (ESBL)-producing and multidrug-resistance (MDR) Escherichia coli(E. coli) become a public health challenge worldwide. This study aimed to discuss the prevalence of drug-resistant E. coli colonization and analyze its risk factors and clinical characteristics among young infants in Southern Taiwan. METHODS: Stool samples were collected from young infants, aged less than three months, within three days of their hospitalization from September to December 2019 in a tertiary hospital. A questionnaire was designed for parents to complete. E. coli colonies were selected and analyzed for antimicrobial susceptibility. PCR-based multilocus sequence typing was to detect the presence of sequence type ST131 and blaCTX-M genes. RESULTS: Among 100 enrolled infants, 36% had fecal carriage of E. coli isolates, of which twenty nine (80.5%) were MDR, thirteen (36.1%) were ESBL-producing isolates and five (13.8%) and ten (27.7%) were ST131 and strains carrying CTX-M-14 gene, respectively. Compared to non-ST131 and non-CTX-M-14 gene carrier, isolates of ST131 and CTX-M-14 gene carrier showed a significantly higher resistance rate to cefixime, ceftriaxone, and gentamycin, with p value all <0.05. CONCLUSION: The prevalence of ESBL-producing and MDR E. coli fecal carriage were both high in young infants. The most common sequence type is ST131, of which all are strains carrying CTX-M-14. Further surveillance and investigation to control for the high prevalence of antimicrobial-resistant E. coli fecal carriage among infants in Taiwan are warranted.

Using crayfish behavior assay as a simple and sensitive model to evaluate potential adverse effects of water pollution: Emphasis on antidepressants.

The freshwater crayfish, Procambarus clarkii is an excellent aquatic animal model that is highly adaptable and tolerant. P. clarkii is widely used as a toxicity model to study various pharmaceutical exposure. This animal model has complex behavioral traits and is considered sensitive to environmental changes, making it an excellent candidate to study psychoactive drugs based on a behavioral approach. However, up to now, most behavioral studies on crayfish use manual observation and scoring that require panelists. In this study, we aim to develop an automation pipeline to analyze crayfish behavior automatically. We use a deep-learning approach to label body parts in multiple crayfish, and based on the trajectory results, the intra- or inter-individual crayfish were calculated. Reliable and fast results of several behavior endpoints in multiple crayfish were retrieved. We then validated the detection performance of numerous crayfish in specific gender groups (male-male and female-female). Based on the result, the male crayfish displayed significantly higher aggression than females. We also tested the antidepressant exposure on this animal model to evaluate the psychoactive effects of this drug. As male crayfish display more distinct agonistic behavior than females, we exposed them to sertraline (SRT) 1 ppb for 7 and 14 days. It was revealed that sertraline was able to alter several behavioral endpoints in crayfish. Significant increases in extend claw ratio, total distance moved, average speed, and rapid movement were displayed in sertraline-exposed crayfish but decreased interaction time and longest interaction time. In addition, SRT 14 days exposure could atler the aggressiveness and bold behavior In the present method, DeepLabCut (DLC) has been utilized to analyze the locomotion behavior of multiple crayfish. This established method provides rapid and accurate ecotoxicity measurements using freshwater crayfish, which beneficient and applicable for environmental research.

Using DeepLabCut for markerless cardiac physiology and toxicity estimation in water fleas (Daphnia magna).

Daphnia magna is one species of water flea that has been used for a long time for ecotoxicity studies. In addition, Daphnia has a myogenic heart that is very useful for cardiotoxicity studies. Previous attempts to calculate the cardiac parameter endpoints in Daphnia suffer from the drawback of tedious operation and high variation due to manual counting errors. Even the previous method that utilized deep learning to help the process suffer from either overestimation of parameters or the need for specialized equipment to perform the analysis. In this study, we utilized DeepLabCut software previously used for animal pose tracking and demonstrated that ResNet_152 was the best fit for training the network. The trained network also showed comparable results with ImageJ and Kymograph, which was mostly done manually. In addition to that, several macro scripts in either Excel or Python format were developed to help summarize the data for faster analysis. The trained network was then challenged to analyze the potential cardiotoxicity of imidacloprid and pendimethalin in D. magna, and it showed that both pesticides cause alteration in their cardiac performance. Overall, this method provides a simple and automatic method to analyze the cardiac performance of Daphnia by utilizing DeepLabCut. The method proposed in this paper can contribute greatly to scientists conducting fast and accurate cardiotoxicity measurements when using Daphnia as a model.

Deep Learning-Based Automatic Duckweed Counting Using StarDist and Its Application on Measuring Growth Inhibition Potential of Rare Earth Elements as Contaminants of Emerging Concerns.

In recent years, there have been efforts to utilize surface water as a power source, material, and food. However, these efforts are impeded due to the vast amounts of contaminants and emerging contaminants introduced by anthropogenic activities. Herbicides such as Glyphosate and Glufosinate are commonly known to contaminate surface water through agricultural industries. In contrast, some emerging contaminants, such as rare earth elements, have started to enter the surface water from the production and waste of electronic products. Duckweeds are angiosperms from the Lemnaceae family and have been used for toxicity tests in aquatic environments, mainly those from the genus Lemna, and have been approved by OECD. In this study, we used duckweed from the genus Wolffia, which is smaller and considered a good indicator of metal pollutants in the aquatic environment. The growth rate of duckweed is the most common endpoint in observing pollutant toxicity. In order to observe and mark the fronds automatically, we used StarDist, a machine learning-based tool. StarDist is available as a plugin in ImageJ, simplifying and assisting the counting process. Python also helps arrange, manage, and calculate the inhibition percentage after duckweeds are exposed to contaminants. The toxicity test results showed Dysprosium to be the most toxic, with an IC50 value of 14.6 ppm, and Samarium as the least toxic, with an IC50 value of 279.4 ppm. In summary, we can provide a workflow for automatic frond counting using StarDist integrated with ImageJ and Python to simplify the detection, counting, data management, and calculation process.

Geographic distribution of the major clone of extended-spectrum beta-lactamase-producing Escherichia coli infection in a pediatric community in southern Taiwan.

BACKGROUND: The geographic distribution of the major clone of sequence type 131 (ST131) in extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli) infections is not known. We analyzed the clinical features, resistance mechanisms, and geographic distribution of ESBL-producing E. coli clones in 120 children. METHODS: We studied the 120 ESBL-producing E. coli strains from children younger than 18 years. A VITEK 2 automated system was used to determine bacterial identification and ESBL production. Sequence type was determined by multi-locus sequence typing (MLST). The genetic relationship of the ESBL-producing strains was studied using pulsed-field gel electrophoresis (PFGE). Phylogenetic group and blaCTX-M group was performed using polymerase chain reaction (PCR). Multiplex PCR for detecting the common group 9 variant, CTX-M-14, and group 1 variant, CTX-M-15, was also performed. The addresses of the 120 children were collected, and plotted on the Taiwan map. RESULTS: The groups in the center of Kaohsiung City lived mainly in urban areas with a population density of over 10,000 people per square kilometer, and the majority of the Kaohsiung groups on the outskirts of the city center lived in suburban areas with a population density of under 6000 people per square kilometer. There was no statistically significant difference between the city center and outskirt groups in terms of clinical presentation, laboratory, and imaging data. However, more ST131 clones, major pulsotype groups, and phylogenetic group B2 strains were found in the center of Kaohsiung than on the outskirts. CONCLUSION: ESBL-producing E. coli clones may be more challenging to treat clinically. Most infections were community-acquired, and there appeared to be major pulsotype clones, mainly in urban areas. This reinforces the necessity of environmental surveillance and sanitary procedures for ESBL-producing E. coli.

Impact of Gut Dysbiosis on the Risk of Non-Small-Cell Lung Cancer.

Background: The imbalance of gut microbiota, dysbiosis, is associated with various malignant diseases. This study aimed to identify the characteristics of gut microbiota in age-matched treatment-naïve non-small-cell lung cancer (NSCLC) patients and healthy individuals to investigate possible gut-microbe-related pathways involved in the development of NSCLC. Methods: We enrolled 34 age-matched NSCLC patients and 268 healthy individuals. Hypervariable V3−V4 amplicons of 16S rRNA in freshly collected fecal samples were sequenced. Diversity, microbial composition, functional pathways, smoking history, and gut-microbe-related comorbidities were analyzed to assess the factors associated with the risk of NSCLC. Results: Microbial alpha diversity was decreased in the patients with NSCLC, and beta diversity was significantly different between the patients and controls (p < 0.001). After adjustments for sex, smoking history, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, and 11 abundant microbes with significant differences between the patients and controls, the enrichment of Anaerotruncus spp. and Bacteroides caccae was associated with an increased risk of NSCLC (p = 0.003 and 0.007, respectively). The areas under receiver operating characteristic curves were 71.4% and 66.9% for Anaerotruncus spp. and Bacteroides caccae, respectively (both p < 0.001). Furthermore, the abundance of Bacteroides caccae was positively correlated with steroid hormone biosynthesis (p < 0.001), N-glycan biosynthesis (p = 0.023), glycosaminoglycan degradation (p < 0.001), lipoic acid metabolism (p = 0.039), peroxisome (p < 0.001), and apoptosis (p < 0.001), but inversely related to glycerolipid metabolism (p < 0.001). Anaerotruncus spp. was positively associated with decreased biosynthesis of ansamycin only (p = 0.001). No overlapping signaling pathways were modulated by Bacteroides caccae or Anaerotruncus spp. Conclusions: Our results revealed that fecal Anaerotruncus spp. and Bacteroides caccae were abundant and may be associated with the risk of NSCLC regardless of sex, smoking history, and gut-microbe-related comorbidities. Further investigations on the mechanism underlying the potential association between gut dysbiosis and the development of NSCLC are warranted.

Distribution and Genomic Characterization of Third-Generation Cephalosporin-Resistant Escherichia coli Isolated from a Single Family and Home Environment: A 2-Year Longitudinal Study.

Third-generation cephalosporin-resistant Escherichia coli (CREC), particularly strains producing extended-spectrum ß-lactamases (ESBLs), are a global concern. Our study aims to longitudinally assemble the genomic characteristics of CREC isolates from fecal samples from an index patient with recurrent CREC-related urinary tract infections and his family and swabs from his home environment 12 times between 2019 and 2021 to investigate the distribution of antibiotic resistance genes. CREC identified using the VITEK 2 were subjected to nanopore whole-genome sequencing (WGS). The WGS of 27 CREC isolates discovered in 137 specimens (1 urine, 123 feces, and 13 environmental) revealed the predominance of ST101 and ST131. Among these sequence types, blaCTX-M (44.4%, n = 12) was the predominant ESBL gene family, with blaCTX-M-14 (n = 6) being the most common. The remaining 15 (55.6%) isolates harbored blaCMY-2 genes and were clonally diverse. All E. coli isolated from the index patient's initial urine and fecal samples belonged to O25b:H4-B2-ST131 and carried blaCTX-M-14. The results of sequence analysis indicate plasmid-mediated household transmission of blaCMY-2 or blaCTX-M-55. A strong genomic similarity was discovered between fecal ESBL-producing E. coli and uropathogenic strains. Furthermore, blaCMY-2 genes were widely distributed among the CREC isolated from family members and their home environment.

Toxicity Assessment of an Anti-Cancer Drug of p-Toluene Sulfonamide in Zebrafish Larvae Based on Cardiovascular and Locomotion Activities.

p-Toluene sulfonamide (p-TSA), a small molecular drug with antineoplastic activity is widely gaining interest from researchers because of its pharmacological activities. In this study, we explored the potential cardio and neural toxicity of p-TSA in sublethal concentrations by using zebrafish as an in vivo animal model. Based on the acute toxicity assay, the 96hr LC50 was estimated as 204.3 ppm, suggesting the overall toxicity of p-TSA is relatively low in zebrafish larvae. For the cardiotoxicity test, we found that p-TSA caused only a minor alteration in treated larvae after no overall significant alterations were observed in cardiac rhythm and cardiac physiology parameters, as supported by the results from expression level measurements of several cardiac development marker genes. On the other hand, we found that acute p-TSA exposure significantly increased the larval locomotion activity during the photomotor test while prolonged exposure (4 days) reduced the locomotor startle reflex activities in zebrafish. In addition, a higher respiratory rate and blood flow velocity was also observed in the acutely treated fish groups compared to the untreated group. Finally, by molecular docking, we found that p-TSA has a moderate binding affinity to skeletal muscle myosin II subfragment 1 (S1), ATPase activity, actin- and Ca2+-stimulated myosin S1 ATPase, and v-type proton ATPase. These binding interactions between p-TSA and proteins offer insights into the potential molecular mechanism of action of p-TSA on observed altered responses toward photo and vibration stimuli and minor altered vascular performance in the zebrafish larvae.

Nuclear Respiratory Factor 1 Overexpression Inhibits Proliferation and Migration of PC3 Prostate Cancer Cells.

BACKGROUND/AIM: The role of nuclear respiratory factor 1 (NRF1) on the prostate cancer progression is controversial. We aimed to investigate the effect of NRF1 overexpression on the metastasis potential of PC3 prostate cancer cells and the associated molecular mechanisms. MATERIALS AND METHODS: Cell survival, migration capacity, mitochondrial biogenesis, the expression of TGF-ß signaling and EMT markers were examined after overexpression and silencing of NRF1 in PC3 cells. RESULTS: We found that NRF1-overexpressing cells exhibited a decreased cell viability and proliferation ability as well as a reduced migration capacity compared to control cells. Moreover, ectopic expression of NRF1 increased the mitochondrial biogenesis and inhibited the EMT characteristics, including a decrease in the mesenchymal marker, α-SMA and an increase in the epithelial cell marker, E-cadherin. We also demonstrated that overexpression of NRF1 suppressed the expression of TGF-ß signaling in PC3 cells. As expected, silencing of NRF1 reversed the abovementioned effects. CONCLUSION: This study demonstrated that upregulation of NRF1 holds the potential to inhibit the metastasis of prostate cancer, possibly through an elevation of mitochondrial biogenesis and the subsequent repression of TGF-ß-associated EMT. Therapeutic avenues that increase NRF1 expression may serve as an adjunct to conventional treatments of prostate cancer.

Prevalence and household risk factors for fecal carriage of ESBL-producing, sequence type 131, and extraintestinal pathogenic Escherichia coli among children in southern Taiwan.

BACKGROUND: The rapidly increasing prevalence of antimicrobial-resistant Escherichia coli (E. coli) is a global concern. This study determined the prevalence and risk factors for the fecal carriage of drug-resistant E. coli and extraintestinal pathogenic E. coli (ExPEC) among children. MATERIALS AND METHODS: In this prospective study, stool samples from children aged 0-18 years were obtained within three days of hospitalization between April 2016 and March 2019. E. coli were selected and tested for extended-spectrum ß-lactamase (ESBL)-production and antimicrobial susceptibility. Multilocus sequence typing, blaCTX-M gene groups and ExPEC were determined using polymerase chain reactions. Questionnaires were recorded for risk factor analysis. RESULTS: Among 179 E. coli isolates, 44.1% were multi-drug resistant, 20.7% produced ESBL, and 50.3% were ExPEC. Children carrying ESBL-producing E. coli were younger than those carrying non-ESBL strains. Several anthropogenic factors, including drinking water process, pork consumption, pets and household density might be associated with ESBL-producing E. coli, sequence type (ST) 131 E. coli, or ExPEC fecal carriage. Compared with families who live in less crowded houses, participants with pets had a similar trend of higher risks of ESBL-producing E. coli, ST131 E. coli, and ExPEC fecal carriage among those living in houses accommodating relatively more people. CONCLUSIONS: Children accounted for a large proportion of instances of feces carrying ESBL E. coli. In addition to antimicrobial control for people and livestocks, avenues of exposure, such as drinking water, food, pets, household density, and socioeconomic deprivation might present potentially novel opportunities to reduce the burden of nonsusceptible E. coli and ExPEC.

Syphilis and ischemic stroke: Old question revisited by a nationwide cohort study.

BACKGROUND AND PURPOSE: In the era of easily available antibiotic use, this study provides epidemiological evidence for a re-examination of the relationship between syphilis and ischemic stroke (IS). METHODS: Patients aged 18 years and older with newly diagnosed syphilis were included (n = 1585) from 2000 to 2012, and participants without syphilis in the control group (n = 6340) were matched by propensity score (age, sex, index year, insured amount, urbanization, seasons, and comorbidities). The Cox proportional hazard model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of IS. Five different Cox regression models, sensitivity analyses, and negative control were conducted to test our findings. RESULTS: In all, 1585 patients (1055 (66.56%) men; mean (SD) age, 49.59 (20.32) years) had syphilis, and 3.8% had new-onset IS. The syphilis group had a higher risk of IS than the controls (adjusted HR, 1.35; 95% CI, 1.01-1.80; p value < 0.05) after full adjustment. Serial sensitivity analyses yielded consistent results. CONCLUSION: Syphilis patients have higher risk of IS, and our data raise the question of implementation of prophylactic treatment for IS.

Risk Factors and Prevalence of mcr-1-Positive Escherichia coli in Fecal Carriages Among Community Children in Southern Taiwan.

Colistin is the last resort antimicrobial for treating multidrug-resistant gram-negative bacterial infections. The plasmid-mediated colistin resistance gene, mcr-1, crucially influences colistin's resistance transmission. Human fecal carriages of mcr-1-positive Escherichia coli (E. coli) were detected in many regions worldwide; however, only a few studies have focused on children. Therefore, we identified the prevalence and risk factors of mcr-1-positive E. coli in fecal carriages among community children in Southern Taiwan. In this study, 510 stool samples were collected from April 2016 to August 2019 from the pediatric department at a medical center in Southern Taiwan. These samples were collected within 3 days after admission and were all screened for the presence of the mcr-1 gene. Diet habits, travel history, pet contact, and medical history were also obtained from participants to analyze the risk factors of their fecal carriages to mcr-1-positive E. coli. Antimicrobial susceptibility testing was determined using the VITEK 2 system and the broth microdilution test. Twelve mcr-1-positive E. coli. were isolated from 2.4% of the fecal samples. Through multivariate analysis, frequent chicken consumption (at least 3 times per week) had a significantly positive association with the presence of mcr-1-positive E. coli in fecal carriages (adjust odds ratio 6.60, 95% confidence interval1.58- 27.62, p = 0.033). Additionally, multidrug resistance was more common in mcr-1-positive E. coli. (75.0% vs. 39.5%, p = 0.031) than in non-mcr-1-positive Escherichia coli. Furthermore, the percentage of extraintestinal pathogenic E. coli in mcr-1-positive isolates was 83.3%. Some multi-locus sequence types in our mcr-1-positive E. coli were also similar to those isolated from food animals in the literature. The prevalence of fecal carriages of mcr-1-positive E. coli was low among community children in Southern Taiwan. Our data shows that chicken consumption with a higher frequency increases the risk of mcr-1-positive E. coli. in fecal carriages.

Therapeutic Efficacy of Sesquiterpene Farnesol in Treatment of Cutibacterium acnes-Induced Dermal Disorders.

Acne vulgaris is a highly prevalent skin disorder requiring treatment and management by dermatologists. Antibiotics such as clindamycin are commonly used to treat acne vulgaris. However, from both medical and public health perspectives, the development of alternative remedies has become essential due to the increase in antibiotic resistance. Topical therapy is useful as a single or combined treatment for mild and moderate acne and is often employed as maintenance therapy. Thus, the current study investigated the anti-inflammatory, antibacterial, and restorative effects of sesquiterpene farnesol on acne vulgaris induced by Cutibacterium acnes (C. acnes) in vitro and in a rat model. The minimum inhibitory concentration (MIC) of farnesol against C. acnes was 0.14 mM, and the IC50 of 24 h exposure to farnesol in HaCaT keratinocytes was approximately 1.4 mM. Moreover, 0.8 mM farnesol exhibited the strongest effects in terms of the alleviation of inflammatory responses and abscesses and necrotic tissue repair in C.acnes-induced acne lesions; 0.4 mM farnesol and clindamycin gel also exerted similar actions after a two-time treatment. By contrast, nearly doubling the tissue repair scores, 0.4 mM farnesol displayed great anti-inflammatory and the strongest reparative actions after a four-time treatment, followed by 0.8 mM farnesol and a commercial gel. Approximately 2-10-fold decreases in interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α, found by Western blot analysis, were predominantly consistent with the histopathological findings and tissue repair scores. The basal hydroxypropyl methylcellulose (HPMC) gel did not exert anti-inflammatory or reparative effects on rat acne lesions. Our results suggest that the topical application of a gel containing farnesol is a promising alternative remedy for acne vulgaris.

Temporal Trend of ST131 Clone among Urinary Escherichia coli Isolates in the Community: A Taiwan National Surveillance from 2002 to 2016.

Sequence type (ST) 131 is a multidrug-resistant pandemic lineage of E. coli responsible for extraintestinal infections. Few surveillance data of ST131 included all antimicrobial-susceptible and -resistant isolates or focused on community-acquired urinary tract infection (UTI). From a population-based surveillance pool of 2997 outpatient urine E. coli isolates, 542 were selected for detection of ST131 based on ciprofloxacin and/or cefotaxime resistance. Pulsed-field gel electrophoresis (PFGE) was performed on all ST131 isolates to further determine their relatedness. The estimated overall ST131 prevalence in this community UTI cohort increased from 11.2% (in 2002-2004), 12.2% (in 2006-2008), 13.6% (in 2010-2012), to 17.4% in 2014-2016 (p < 0.01). In the ciprofloxacin-resistant/cefotaxime-resistant group, ST131 increased from 33.3% in 2002-2004 to 72.1% in 2014-2016 (p < 0.01). In the ciprofloxacin-resistant/cefotaxime-susceptible group, ST131 was found in 24.3% overall without significant increase in its prevalence over time. PFGE showed emergence of a cluster of ciprofloxacin-resistant/cefotaxime-resistant ST131 carrying Gr. 1 CTX-M ESBL in 2014-2016, especially 2016. Multivariate analysis revealed that age (≥65 y.o) and ciprofloxacin resistance were independent factors associated with ST131. This longitudinal surveillance showed that ciprofloxacin-resistant/cefotaxime-susceptible ST131 has been circulating in the community since 2002 but ciprofloxacin-resistant/cefotaxime-resistant ST131 increased rapidly in the later years.

Appendectomy and Non-Typhoidal Salmonella Infection: A Population-Based Matched Cohort Study.

The potential association between appendectomy and non-typhoidal Salmonella (NTS) infection has not been elucidated. We hypothesized that appendectomy may be associated with gut vulnerability to NTS. The data were retrospectively collected from the Taiwan National Health Insurance Research Database to describe the incidence rates of NTS infection requiring hospital admission among patients with and without an appendectomy. A total of 208,585 individuals aged ≥18 years with an appendectomy were enrolled from January 2000 to December 2012, and compared with a control group of 208,585 individuals who had never received an appendectomy matched by propensity score (1:1) by index year, age, sex, occupation, and comorbidities. An appendectomy was defined by the International Classification of Diseases, Ninth Revision, Clinical Modification Procedure Codes. The main outcome was patients who were hospitalized for NTS. Cox proportional hazards models were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Two sensitivity analyses were conducted for cross-validation. Of the 417,170 participants (215,221 (51.6%) male), 208,585 individuals (50.0%) had an appendectomy, and 112 individuals developed NTS infection requiring hospitalization. In the fully adjusted multivariable Cox proportional hazards regression model, the appendectomy group had an increased risk of NTS infection (adjusted HR (aHR), 1.61; 95% CI, 1.20-2.17). Females and individuals aged 18 to 30 years with a history of appendectomy had a statistically higher risk of NTS than the control group (aHR, 1.92; 95% CI, 1.26-2.93 and aHR, 2.67; 95% CI, 1.41-5.07). In this study, appendectomy was positively associated with subsequent hospitalization for NTS. The mechanism behind this association remains uncertain and needs further studies to clarify the interactions between appendectomy and NTS.

Verbascoside inhibits the epithelial-mesenchymal transition of prostate cancer cells through high-mobility group box 1/receptor for advanced glycation end-products/TGF-ß pathway.

INTRODUCTION: Prostate cancer has significant mortality and metastasis rate in the male. Unfortunately, effective treatment for patients with advanced prostate cancer is still lacking. Verbascoside, a phenylethanoid glycoside, displays various pharmacological properties, such as the anti-cancer activities. The present study aimed to evaluate the effects of purified verbascoside on human prostate cancer and the associated molecular mechanisms. MATERIALS AND METHODS: The human prostate cancer cell lines, Du-145 and PC-3, were treated with various concentrations of verbascoside (0.1, 1, 10 µM) for 24 h followed by the examination of cell viability using MTT and trypan blue exclusion assays. Cell migration and invasion capacities were assessed by wound healing assay and transwell system. Western blot and immunofluorescence staining were used to detect the expression of epithelial-mesenchymal transition (EMT)-associated factors, components of transforming growth factor (TGF-ß)/Smad signaling, and high-mobility group box (HMGB)/receptor for advanced glycation end-products (RAGE) axis. RESULTS: Verbascoside treatment significantly inhibited cell proliferation, migration, and invasion abilities of Du-145 and PC-3 cells. We showed that verbascoside decreased the expression of EMT promotors, Snail and Slug, and increased the expression of E-cadherin. Moreover, the expression level of alpha-smooth muscle actin was downregulated by verbascoside as well. Besides, we found that the TGF-ß pathway was suppressed, which was demonstrated by the diminished expression of type I and II TGF-ß receptors and phosphorylated Smad2/3 along with the upregulated Smad7. Our data suggested that this downregulation of TGF-ß signaling was mediated by repression of HMGB 1 (HMGB1)/RAGE axis. CONCLUSION: Verbascoside mitigated the cell proliferation and aggressiveness of prostate cancer via downregulation of TGF-ß-associated EMT progression through HMGB1/RAGE suppression. Collectively, our findings revealed that verbascoside may be a beneficial dietary supplement for prostate cancer patients.

Bloodstream Infections Caused by Extended-Spectrum Beta-Lactamase-Producing Escherichia coli in Patients with Liver Cirrhosis.

BACKGROUND: This study aimed to investigate the frequency of sequence type (ST) 131 strains and outcome of cirrhotic patients with bloodstream infections (BSIs) caused by extended-spectrum beta-lactamase-producing Escherichia coli (ESBLEC) and non-extended-spectrum beta-lactamase-producing Escherichia coli (NESBLEC). METHODS: The incidence of ST 131 strains, hospital stay, and 30-day re-admission/mortality were compared between 51 ESBLEC and 51 NESBLEC bacteremic patients with cirrhosis. RESULTS: ST 131 strains were found in 35.3% of the ESBLEC group and 0% of the NESBLEC group (p < 0.001). Mean hospital stay was 26.5 days in the ESBLEC group and 17.1 days in the NESBLEC group (p = 0.006). Thirty-day re-admission rates were 11.8% in the ESBLEC group and 5.9% in the NESBLEC group (p = 0.5). ST 131 strains were associated with 30-day re-admission (odds ratio: 4.5, 95% confidence interval: 1.1-18.9). Thirty-day mortality rate was 31.4% in the ESBLEC group and 23.5% in the NESBLEC group (p = 0.4). CONCLUSION: In patients with cirrhosis, the ESBLEC BSIs group had a higher frequency of ST 131 strains and longer hospital stay than the NESBLEC BSIs group with similar 30-day re-admission/mortality. ST 131 strains were associated with 30-day re-admission.