Vascular endothelial dysfunction induced by 3-bromofluoranthene via MAPK-mediated-NFκB pro-inflammatory pathway and intracellular ROS generation.

3-Bromofluoranthene (3-BrFlu) is the secondary metabolite of fluoranthene, which is classified as a polycyclic aromatic hydrocarbon, through bromination and exists in the fine particulate matter of air pollutants. Endothelial dysfunction plays a critical role in the pathogenesis of cardiovascular and vascular diseases. Little is known about the molecular mechanism of 3-BrFlu on endothelial dysfunction in vivo and in vitro assay. In the present study, 3-BrFlu included concentration-dependent changes in ectopic angiogenesis of the sub-intestinal vein and dilation of the dorsal aorta in zebrafish. Disruption of vascular endothelial integrity and up-regulation of vascular endothelial permeability were also induced by 3-BrFlu in a concentration-dependent manner through pro-inflammatory responses in vascular endothelial cells, namely, SVEC4-10 cells. Generation of pro-inflammatory mediator PGE2 was induced by 3-BrFlu through COX2 expression. Expression of COX2 and generation of pro-inflammatory cytokines, including TNFα and IL-6, were induced by 3-BrFlu through phosphorylation of NF-κB p65, which was mediated by phosphorylation of MAPK, including p38 MAPK, ERK and JNK. Furthermore, generation of intracellular ROS was induced by 3-BrFlu, which is associated with the down-regulated activities of the antioxidant enzyme (AOE), including SOD and catalase. We also found that 3-BrFlu up-regulated expression of the AOE and HO-1 induced by 3-BrFlu through Nrf-2 expression. However, the 3-BrFlu-induced upregulation of AOE and HO-1 expression could not be revised the responses of vascular endothelial dysfunction. In conclusion, 3-BrFlu is a hazardous substance that results in vascular endothelial dysfunction through the MAPK-mediated-NFκB pro-inflammatory pathway and intracellular ROS generation.

Symptomatic cholelithiasis patients have an increased risk of pancreatic cancer: A population-based study.

BACKGROUND AND AIM: Pancreatic cancer is a fatal disease; currently, the risk factor survey is not suitable for sporadic pancreatic cancer, which has neither family history nor the genetic analysis data. The aim of the present study was to evaluate the roles of cholelithiasis and cholelithiasis treatments on pancreatic cancer risk. METHODS: Symptomatic adult patients with an index admission of cholelithiasis were selected from one million random samples obtained between January 2005 and December 2009. The control group was matched with a 1:1 ratio for sex, age, chronic pancreatitis, and pancreatic cystic disease. Subsequent pancreatic cancer, which we defined as pancreatic cancer that occurred ≥ 6 months later, and total pancreatic cancer events were calculated in the cholelithiasis and control groups. The cholelithiasis group was further divided into endoscopic sphincterotomy/endoscopic papillary balloon dilatation, cholecystectomy, endoscopic sphincterotomy/endoscopic papillary balloon dilatation and cholecystectomy, and no-intervention groups for evaluation. RESULTS: The cholelithiasis group and the matched control group included 8265 adults. The cholelithiasis group contained 86 cases of diagnosed pancreatic cancer, and the control group contained 8 cases (P < 0.001). The incidence rate ratio (IRR) of subsequent pancreatic cancer was significantly higher in the cholelithiasis group than in the control group (IRR: 5.28, P < 0.001). The IRR of subsequent pancreatic cancer was higher in the no-intervention group comparing with cholecystectomy group (IRR = 3.21, P = 0.039) but was similar in other management subgroups. CONCLUSION: Symptomatic cholelithiasis is a risk factor for pancreatic cancer; the risk is similar regardless of the intervention chosen for cholelithiasis.

Oral treatment for diabetes using α-glucosidase inhibitors was a risk factor for chronic obstructive pulmonary disease: a cohort study.

Objectives: Currently, diabetes mellitus (DM) and chronic obstructive pulmonary disease (COPD) have proven to be risk factors for each other. This study aimed to determine the risk relationship between COPD and five common oral medications for DM among patients with DM. Methods: This population-based cohort study was conducted from 2008 to 2013. Patient data were retrieved from the Longitudinal Health Insurance Database (LHID) of the National Health Insurance Research Database (NHIRD). After pairing by gender, age, and index date, time-to-event analysis and multiple regression analysis were performed to determine the factors associated with COPD in patients taking oral medication for DM, including age, gender, income, and comorbidities. We identified 1,028 patients who took oral medication for DM and 1,028 controls who did not take oral medication for DM. Results: We observed that the use of α-glucosidase inhibitors was associated with a higher risk of COPD (hazard ratio [HR]: 1.964, 95% confidence interval [CI]: 1.207-2.380). Furthermore, compared with the control group, α-glucosidase inhibitor users had a higher risk of COPD (HR: 2.295, 95% CI: 1.304-4.038), and no significant difference was observed in other oral medications for DM. Conclusions: Based on present results, we could suggest that patients with DM who used α-glucosidase inhibitors are probably a higher risk of COPD. We recommend that in the future, treatment with α-glucosidase inhibitors upregulate the occurrence of COPD might through gastrointestinal side effects and malnutrition.

Association of urate-lowering drugs with the risk of future urolithiasis in patients with gout: A population-based nested case-control study.

BACKGROUND: Patients with gout have an increased risk of urolithiasis and usually need urate-lowering therapy (ULT) for the prevention of disease progression. However, there is a paucity of clinical data regarding the risk of future urolithiasis in ULT users. METHODS: This nested case-control study was performed using the Taiwan National Health Insurance Research Database. The aim of this study was to examine whether ULT (xanthine oxidase inhibitors [XOIs] or uricosuric agents) is associated with risk of future urolithiasis in patients with gout. Data were collected from January 2000 to December 2012. RESULTS: This study included 2307 case patients and 2307 matched controls. Case patients had gout that developed into urolithiasis, and control patients had gout but were not diagnosed with urolithiasis during the study period. Patients had a mean age of 56.3 years at diagnosis of gout, and 83.2% were male patients. No association was detected between use of XOIs or uricosuric agents and risk of future urolithiasis. Furthermore, there was no significant difference in the risk of future urolithiasis in patients exposed to various cumulative days of XOI or uricosuric prescriptions. CONCLUSION: The present study provides evidence that neither XOIs nor uricosuric agents are associated with risk of future urolithiasis in patients with gout. Before the availability of more clinical evidence, ensuring high fluid intake and prospective monitoring of urolithiasis development are still important for uricosuric agent users.

Genotoxic effects of 1-nitropyrene in macrophages are mediated through a p53-dependent pathway involving cytochrome c release, caspase activation, and PARP-1 cleavage.

Genotoxic stress from environmental pollutants plays a critical role in cytotoxicity. The most abundant nitro-polycyclic aromatic hydrocarbon in environmental pollutants, 1-nitropyrene (1-NP), is generated during fossil fuel, diesel, and biomass combustion under sunlight. Macrophages, the key regulators of the innate immune system, provide the first line of defense against pathogens. The toxic effects of 1-NP on macrophages remain unclear. Through a lactate dehydrogenase assay, we measured the cytotoxicity induced by 1-NP. Our results revealed that 1-NP induced genotoxicity also named DNA damage, including micronucleus formation and DNA strand breaks, in a concentration-dependent manner. Furthermore, 1-NP induced p53 phosphorylation and nuclear accumulation; mitochondrial cytochrome c release; caspase-3 and -9 activation and cleavage; and poly (ADP-ribose) polymerase-1 (PARP-1) cleavage in a concentration-dependent manner. Pretreatment with the PARP inhibitor, 3-aminobenzamide, significantly reduced cytotoxicity, genotoxicity, and PARP-1 cleavage induced by 1-NP. Pretreatment with the caspase-3 inhibitor, z-DEVD-fmk, significantly reduced cytotoxicity, genotoxicity, PARP-1 cleavage, and caspase 3 activation induced by 1-NP. Pretreatment with the p53 inhibitor, pifithrin-α, significantly reduced cytotoxicity, genotoxicity, PARP-1 cleavage, caspase 3 activation, and p53 phosphorylation induced by 1-NP. We propose that cytotoxicity and genotoxicity induced by 1-NP by PARP-1 cleavage via caspase-3 and -9 activation through cytochrome c release from mitochondria and its upstream p53-dependent pathway in macrophages.

Rutin-protected BisGMA-induced cytotoxicity, genotoxicity, and apoptosis in macrophages through the reduction of the mitochondrial apoptotic pathway and induction of antioxidant enzymes.

Bisphenol-A-glycidyldimethacrylate (BisGMA) is a resin monomer frequently used in dentin restorative treatments. The leakage of BisGMA monomer from BisGMA-based polymeric resins can lead to cytotoxicity in macrophages. Rutin has various beneficial bioeffects, including antioxidation and antiinflammation. In this study, we found that pretreatment of RAW264.7 macrophages with rutin-inhibited cytotoxicity induced by BisGMA in a concentration-dependent manner. BisGMA-induced apoptosis, which was detected by levels of phosphatidylserine from the internal to the external membrane and formation of sub-G1, and genotoxicity, which was detected by cytokinesis-blocked micronucleus and single-cell gel electrophoresis assays, were inhibited by rutin in a concentration-dependent manner. Rutin suppressed the BisGMA-induced activation of caspase-3 and -9 rather than caspase-8. Rutin inhibited the activation of the mitochondrial apoptotic pathway, including cytochrome C release and mitochondria disruption, after macrophages were treated with BisGMA. Finally, BisGMA-induced reactive oxygen species (ROS) generation and antioxidant enzyme (AOE) deactivation could be reversed by rutin. Parallel trends were observed in the elevation of AOE activation and inhibition of ROS generation, caspase-3 activity, mitochondrial apoptotic pathway activation, and genotoxicity. These results suggested that rutin suppressed BisGMA-induced cytotoxicity through genotoxicity, the mitochondrial apoptotic pathway, and relatively upstream factors, including reduction of ROS generation and induction of AOE.

Neochlorogenic Acid Attenuates Hepatic Lipid Accumulation and Inflammation via Regulating miR-34a In Vitro.

Neochlorogenic acid (5-Caffeoylquinic acid; 5-CQA), a major phenolic compound isolated from mulberry leaves, possesses anti-oxidative and anti-inflammatory effects. Although it modulates lipid metabolism, the molecular mechanism is unknown. Using an in-vitro model of nonalcoholic fatty liver disease (NAFLD) in which oleic acid (OA) induced lipid accumulation in HepG2 cells, we evaluated the alleviation effect of 5-CQA. We observed that 5-CQA improved OA-induced intracellular lipid accumulation by downregulating sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FASN) expression, which regulates the fatty acid synthesis, as well as SREBP2 and HMG-CoA reductases (HMG-CoR) expressions, which regulate cholesterol synthesis. Treatment with 5-CQA also increased the expression of fatty acid ß-oxidation enzymes. Remarkably, 5-CQA attenuated OA-induced miR-34a expression. A transfection assay with an miR-34a mimic or miR-34a inhibitor revealed that miR-34a suppressed Moreover, Sirtuin 1 (SIRT1) expression and inactivated 5' adenosine monophosphate-activated protein kinase (AMPK). Our results suggest that 5-CQA alleviates lipid accumulation by downregulating miR-34a, leading to activation of the SIRT1/AMPK pathway.

Analysis of microbial community, physiochemical indices, and volatile compounds of Chinese te-flavor baijiu daqu produced in different seasons.

BACKGROUND: Chinese te-flavor baijiu (CTF), the most famous Chinese baijiu in Jiangxi province, China, is made from a unique daqu. Its characteristic style is closely related to the daqu used for fermentation. However, current studies on the effects of different production seasons on microbial communities, physicochemical indices, and volatile compounds in CTF daqu are very rare. RESULTS: The relationships of microbial communities, physicochemical indices, and volatile compounds in CTF daqu produced in summer (July and August) and autumn (September and October) were studied. The results of Illumina MiSeq sequencing indicated that there was greater bacterial diversity in the CTF daqu-7 (produced in July) and CTF daqu-8 (produced in August) and greater fungal diversity in the CTF daqu-9 (produced in September) and CTF daqu-10 (produced in October). The physicochemical indices of CTF daqu produced in different seasons were significantly different. It was determined that CTF daqu-9 had the highest esterification and liquefaction abilities. A total of 44 volatile compounds, including alcohols, esters, aldehydes, and ketones were identified in CTF daqu produced during different seasons. Among them, CTF daqu-9 had the greatest alcohol content. CONCLUSION: September (early autumn) is the best production period for CTF daqu. The results of the study provide a theoretical basis for the standardized and uniform production of Chinese baijiu. © 2021 Society of Chemical Industry.

Evaluation of cytotoxicity, apoptosis, and genotoxicity induced by indium chloride in macrophages through mitochondrial dysfunction and reactive oxygen species generation.

Due to rapid advances in the era of electronic technologies, indium has played the important material for the production of liquid crystal display screens in the semiconductor and optoelectronic industries. The present study focuses on evaluating the toxic effects and related mechanisms of indium chloride (InCl3) on RAW264.7 macrophages. Cytotoxicity was induced by InCl3 in a concentration- and time-dependent manner. InCl3 had the ability to induce macrophage death through apoptosis rather than through necrosis. According to the cytokinesis-block micronucleus assay and alkaline single-cell gel electrophoresis assay, InCl3 induced DNA damage, also called genotoxicity, in a concentration-dependent manner. Cysteine-dependent aspartate-directed protease (caspase)-3, -8, and -9 were activated by InCl3 in a concentration-dependent manner. Mitochondria dysfunction and cytochrome c release from the mitochondria were induced by InCl3 in a concentration-dependent manner. Downregulation of BCL2 and upregulation of BAD were induced by InCl3 in a concentration-dependent manner. More, we proposed that InCl3 treatment generated reactive oxygen species (ROS) in a concentration-dependent manner. In conclusion, the current study revealed that InCl3 induced macrophage cytotoxicity, apoptosis, and genotoxicity via a mitochondria-dependent apoptotic pathway and ROS generation.

Kaempferol Inhibits the Invasion and Migration of Renal Cancer Cells through the Downregulation of AKT and FAK Pathways.

Kaempferol, which is isolated from several natural plants, is a polyphenol belonging to the subgroup of flavonoids. Kaempferol exhibits various pharmacological activities, including anti-inflammatory, antioxidant, antimicrobial, and anticancer activities. In this study, kaempferol can significantly inhibit the invasion and migration of 786-O renal cell carcinoma (RCC) without cytotoxicity. We examined the potential mechanisms underlying its anti-invasive activities on 786-O RCC cells. Western blot was performed, and the results showed that kaempferol attenuates the manifestation of metalloproteinase-2 (MMP-2) protein and activity. The inhibitive effect of kaempferol on MMP-2 may be attributed to the downregulation of phosphorylation of Akt and focal adhesion kinase (FAK). By examining the SCID mice model, we found that kaempferol can safely inhibit the metastasis of the 786-O RCC cells into the lungs by about 87.4% as compared to vehicle treated control animals. In addition, the lung tumor masses of mice pretreated with 2-10 mg/kg kaempferol were reduced about twofold to fourfold. These data suggested that kaempferol can play a promising role in tumor prevention and cancer metastasis inhibition.

Everolimus suppresses invasion and migration of renal cell carcinoma by inhibiting FAK activity and reversing epithelial to mesenchymal transition in vitro and in vivo.

Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults and the major cause of mortality in urological cancer. Most patients with RCC are asymptomatic until the disease is advanced and unresectable. In this situation, systemic therapy with immunotherapy or molecularly targeted therapy agents play an important role in therapeutic strategy. Everolimus (EVE), an m-TOR inhibitor, has the potential to inhibit tumor progression at multiple levels and is indicated for the treatment of advanced RCC in patients whose disease has metastasis. In this study, we provide molecular evidence associated with the antimetastatic effect of everolimus by demonstrating the suppression of lung metastasis of 786-O cells in mouse model. This effect was associated with reduced protein expressions of p-FAK (Tyr 925), p-Src (Tyr416), Vimentin, and RhoA and also with increased the E-cadherin protein expression. In summary, these findings provide new insights into the molecular mechanisms involved in the antimetastatic effect of everolimus and are thus valuable in the treatment of metastatic RCC.

Meta-analysis of defunctioning stoma in low anterior resection with total mesorectal excision for rectal cancer: evidence based on thirteen studies.

BACKGROUND: Recent studies have shown that a protective stoma can reduce morbidity in low anterior resection for rectal cancer; however, the necessity of it is still controversially discussed. METHODS: We performed this meta-analysis to provide a comprehensive evaluation of the role of defunctioning stoma in low anterior resection for rectal cancer on the rates of anastomotic leakage and reoperation related to leakage with or without defunctioning stoma by calculating the pooled risk ratio. RESULTS: Studies and relevant literature published between 2004 and 2014 regarding the construction of a protective stoma after low anterior resection were searched though PubMed and EMBASE databases. Finally, a total of 13 studies including 8,002 patients were included in this meta-analysis. The results indicated that protective stomas significantly reduced the rate of postoperative anastomotic leakage and reoperation after low anterior rectal resection. The pooled risk ratios were 0.47 (95% CI: 0.33-0.68, P <0.0001) and 0.36 (95% CI: 028-0.46, P <0.00001), respectively. CONCLUSIONS: The findings from this present meta-analysis suggest that a defunctioning stoma could effectively reduce the clinical consequences of anastomotic leakage and reoperation, it is recommended in patients undergoing low rectal anterior resection for rectal cancer.

The value of single-incision laparoscopic surgery for colorectal cancer: a systematic literature review.

BACKGROUND/AIMS: Recently, single-incision laparoscopic colectomy (SILC) for colorectal malignancy is rapidly becoming the central issue for explorers of minimally invasive surgery worldwide. The aim of this systematic review was to establish the safety and efficacy of SILC for colorectal malignancy when implemented by experienced surgeons. METHODOLOGY: PubMed, WHO international trial register and Embase were searched for publications concerning SILC and MLC from 2000 to 2013, with the last search on September 10, 2013. Only pure single-incision laparoscopic colonic surgery for malignant disease was included. Primary outcomes were the early postoperative complication profiles of SILC. Secondary outcomes were duration of operation time, blood loss, lymph node yields, conversion rate, distal margin of the resected tumor, and duration of hospital stay. RESULTS: Eight studies involving 547 patients met the inclusion criteria. Compared with multiport laparoscopic colectomy (MLC), SILC has less postoperative complication and bleeding. The conversion, the median lymph node retrieval, proximal margin of the resected tumor and distal margin of the resected tumor for malignant disease achieved with SILC was acceptable. There was no significant reduction in length of hospital stay with SILC. CONCLUSION: SILC is a technically reliable and realistic approach with short-term results similar to those obtained with the MLC procedure.

The prognostic value of HER-2/neu overexpression in colorectal cancer: evidence from 16 studies.

Human epidermal growth factor receptor (HER-2/neu) plays an important role in the progression of several types of cancer. Numerous studies examining the relationship between HER-2 overexpression and prognostic impact in patients with colorectal cancer have yielded inconclusive results. We therefore conducted a meta-analysis to provide a comprehensive evaluation of the prognostic value of HER-2 expression on the survival, which compared the positive and negative expressions of HER-2 in patients of the available studies. Hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CIs) were pooled in terms of disease-specific or overall survival. A detailed search was made in PubMed for relevant original articles published in English. Finally, a total of 18 studies with 16 colorectal cancer patients were involved. Overexpression of HER-2 was negatively related to survival in colorectal cancer patients with the pooled HR of 1.05 (95% CI 0.78-1.31, P = 0.000). In conclusion, the finding from this present meta-analysis suggested that HER-2 overexpression was not related to poor prognostic of colorectal cancer.

Chlorpyrifos-induced suppression of the antioxidative defense system leads to cytotoxicity and genotoxicity in macrophages.

Chlorpyrifos, widely used for pest control, is known to have various harmful effects, although its toxic effects in macrophages and the mechanisms underlying its toxicity remain unclear. The present study investigated the toxic effects of chlorypyrifos in a macrophage cell line. Here, we found that chlorpyrifos induced cytotoxicity and genotoxicity in RAW264.7 macrophages. Moreover, chlorpyrifos induced intracellular ROS production, subsequently leading to lipid peroxidation. Chlorpyrifos reduced the activation of antioxidative enzymes including superoxide dismutase, catalase, and glutathione peroxidase. Chlorpyrifos upregulated HO-1 expression and activated the Keap1-Nrf2 pathway, as indicated by enhanced Nrf2 phosphorylation and Keap1 degradation. Chlorpyrifos exerted effects on the following in a dose-dependent manner: cytotoxicity, genotoxicity, lipid peroxidation, intracellular ROS production, antioxidative enzyme activity reduction, HO-1 expression, Nrf2 phosphorylation, and Keap1 degradation. Notably, N-acetyl-L-cysteine successfully inhibited chlorpyrifos-induced intracellular ROS generation, cytotoxicity, and genotoxicity. Thus, chlorpyrifos may induce cytotoxicity and genotoxicity by promoting intracellular ROS production and suppressing the antioxidative defense system activation in macrophages.

Renal expression of hypoxia inducible factor-1α in patients with chronic kidney disease: a clinicopathologic study from nephrectomized kidneys.

BACKGROUND & OBJECTIVES: Hypoxia inducible factor-1α (HIF-1α) has been shown to play a role in the pathogenesis of renal interstitial fibrosis. However, the relationship of HIF-1α expression intensity in human renal tissue with the degree of renal function or renal fibrosis has not been investigated. We therefore, undertook this study to assess the relationship between HIF-1α expression and degree of renal impairment and renal fibrosis using renal tissue from nephrectomized kidneys from patients with chronic kidney disease. METHODS: This retrospective study was performed with 70 patients undergoing unilateral or bilateral nephrectomy because of renal cell carcinoma, urothelial cell carcinoma, or renal abscess. Immunohistochemical analysis of HIF-1α expression in non-tumourous or non-abscess renal parenchyma was performed. The patients were divided into two groups: group 1 (n=37) with low intensity HIF-1α expression and group 2 (n=33) with high intensity HIF-1α expression. RESULTS: The intensity of renal HIF-1α expression was significantly associated with serum creatinine level (P =0.005), estimated glomerular filtration rate (P=0.02), fibrosis score of the interstitium (P=0.004) and glomerular sclerosis (P=0.013). A high intensity of HIF-1α expression tended to be associated with lower serum creatinine, higher estimated glomerular filtration rate, low interstitial fibrosis score and low glomerular sclerosis. In addition, multivariate analysis by step-wise logistic regression demonstrated that interstitial fibrosis was the only independent factor associated with the intensity of renal HIF-1α expression (OR 4.107, CI 1.535-11.313, P=0.005). INTERPRETATION & CONCLUSIONS: This study demonstrated a correlation between intensity of HIF-1α expression and degree of renal interstitial fibrosis. The association demonstrated an elevated HIF-1α expression in less severe kidney disease. The intensity of HIF-1α renal expression plays a role in the pathogenesis of chronic kidney disease.

Retrospective analysis of protective stoma after low anterior resection for rectal cancer with total mesorectal excision: three-year follow-up results.

BACKGROUND/AIMS: Anastomotic leakage is a complication of low anterior resection (LAR) for rectal cancer with total mesorectal excision (TME). This study evaluated the need for a protective stoma by a three-year follow-up. METHODOLOGY: A retrospective study of 56 LAR patients was conducted. Thirty patients (53.6%) had a protective stoma. C-reactive protein (CRP), interleukin 6 (IL-6) and tumor necrosis factor (TNF) in peripheral blood on the first and third day after surgery were compared, in addition to short-term and later complications, long-term mortality and quality of life (QOL). RESULTS: There was significant difference between patients with and without a stoma in CRP, IL-6 on the third day after surgery (p<0.05). Anastomotic leakage occurred in two patients (6.7%) with a stoma and seven (26.9%) without (p=0.039). The incidence of leaks requiring re-operation was significantly lower with a stoma (p=0.012). After a mean follow-up of three years, there was no difference in long-term mortality, survival or scores on QOL questionnaires. CONCLUSIONS: A protective stoma can reduce the stress reaction, promote recovery of bowel function and reduce anastomotic leakage and re-operation rates in LAR for rectal cancer with TME. No significant difference was observed in long-term mortality or QOL.

Community-acquired urinary tract infection in kidney transplantation: risk factors for bacteremia and recurrent infection.

BACKGROUND/PURPOSE: Urinary tract infection (UTI) is the most common type of infectious complication among kidney transplant patients. However, the antibiotic susceptibility of causative microorganisms and risk factors for concomitant bacteremia and recurrent infection are rarely discussed. METHODS: This was a retrospective cohort review of kidney transplant recipients who had received follow-up in the past 10 years at the Chung-Shan Medical University (Taichung, Taiwan). Only community-acquired and symptomatic UTIs were included in this study. RESULTS: During the 53 ± 22 months of follow-up, 99 patients developed 167 episodes of UTI. Forty-two (25%) episodes had concomitant bacteremia. Escherichia coli was the most common causative microorganism, and strains with resistance to multiple commonly used empirical antibiotics began to emerge. The independent risk factors for UTI with concomitant bacteremia in multivariate analysis were immunosuppression with tacrolimus (adjusted odds ratio [AOR] 3.17; 95% confidence interval [CI] 1.29-7.75; P = 0.011) and baseline serum creatinine level >1.3 mg/dL before first UTI (AOR 2.55; 95% CI 1.02-6.36; P = 0.045). However, there were no factors that were significantly associated with recurrent infection. CONCLUSION: From this study, we found that E coli tends to have resistance to commonly used empirical antibiotics in this modern era and that patients who use the immunosuppressant tacrolimus and have baseline serum creatinine level >1.3 mg/dL before their first UTI have a tendency to suffer from concomitant bacteremia and even sepsis.

Dissecting aneurysm at the A1 segment of the anterior cerebral artery presenting as visual loss and visual field defect.

Intracranial dissecting aneurysms mainly occur in the territory of the vertebrobasilar system. Dissecting aneurysms confined to the anterior cerebral artery are rare, and the presentations are usually of either subarachnoid hemorrhage or cerebral infarction. Here, we report a unique case of a dissecting aneurysm of the anterior cerebral artery presenting as a visual field defect. After surgical decompression, visual symptoms recovered.

Y27632 attenuates the aristolochic acid-promoted invasion and migration of human urothelial cancer TSGH cells in vitro and inhibits the growth of xenografts in vivo.

BACKGROUND: Aristolochic acid I (AAI) has been implicated in urothelial cell carcinoma (UCC) in humans. However, whether AAI promotes invasion/migration of UCC has not been established. METHODS: A study of human UCC TSGH cells cultured with AAI was conducted. Cell viability, the effects of AAI on the activity of matrix metalloproteinase (MMP)-9, the abilities of invasion/migration and the migration-related proteins (Ras, RhoA, ROCK1, PI-3K, pAkt and nuclear factor-kappaB) of the TSGH cells were assessed. The TSGH cells were subcategorized to 1-day or 30-day AAI exposure. An in vivo study using a nude mice xenograft model was employed to test the antitumor effects of Rho kinase inhibitor or Y27632. RESULTS: A time- and dose-dependent increase in both activity and messenger RNA (mRNA) level of MMP-9 were demonstrated. The mRNA level of urokinase-type plasminogen activator was increased and tissue inhibitor of metalloproteinase-1 was decreased in the cells with 30-day but not 1-day AAI exposure. A dose-dependent enhancement in wound-healing rate and cell migration was demonstrated, especially in the 30-day AAI-exposed cells. Expressions of Ras/RhoA and other migration-related proteins were increased after AAI treatment, which could be inhibited by Y27632. The in vivo results demonstrated that Y27632 was able to attenuate the speed of growth of the inoculated tumors in nude mice. CONCLUSION: Clinically, the patients with prolonged AAI exposure are highly associated UCC, our results provided in vitro and in vivo evidence that prolonged AAI exposure enhances invasion and migration of human TSGH cells.