Licochalcone A Suppresses Renal Cancer Cell Proliferation and Metastasis by Engagement of Sp1-Mediated LC3 Expression.

Licochalcone A (LicA) is a strong anti-inflammatory, antioxidant, and anticarcinogenic substance that is useful against a variety of human malignancies. However, its precise mechanism in mediating the development of renal cell carcinoma (RCC) is not entirely understood. In this work, LicA was discovered to limit cell growth and survival, induce cell cycle arrest, promote autophagy and LC3B expression, and inhibit the migration and invasion of RCC cells. In addition, the proliferation, migration, and invasion inhibited by LicA were restored by the transfection of siRNA-LC3. The effects of LC3B on the metastatic phenotype of ACHN cells was enhanced with the overexpression of Sp1 or suppressed by inhibiting the phosphorylation of FAK and Src. Finally, LicA showed antitumor properties against RCC in an in vivo xenograft model. In conclusion, our study demonstrated the chemotherapeutic potential of LicA on proliferation, migration, invasion, and autophagy through the activation of LC3B expression, ultimately modulating FAK/Src signaling pathway-mediated Sp1 expression. These findings illustrate the novel role and molecular mechanisms of LicA against RCC cells.

Mass defect filter technique combined with stable isotope tracing for drug metabolite identification using high-resolution mass spectrometry.

Metabolism studies are one of the important steps in pharmaceutical research. LC-MS combined with metabolomics data-processing approaches have been developed for rapid screening of drug metabolites. Mass defect filter (MDF) is one of the LC/MS-based metabolomics data processing approaches and has been applied to screen drug metabolites. Although MDF can remove most interference ions from an incubation sample, the true positive rate of the retaining ions is relatively low (approximately 10%). To improve the efficacy of MDF, we developed a two-stage data-processing approach by combining MDF and stable isotope tracing (SIT) for metabolite identification. Pioglitazone (PIO), which is an antidiabetic drug used to treat type 2 diabetes mellitus, was taken as an example drug. Our results demonstrated that this new approach could substantially increase the validated rate from about 10% to 74%. Most of these validated metabolite signals (13/14) could be verified as PIO structure-related metabolites. In addition, we applied this approach to identify uncommon metabolite signals (a mass change beyond the window of 50 Da around its parent drug, MDF1). SIT could remove most interference ions (approximately 98%) identified by MDF1, and four out of five validated metabolite signals could be verified as PIO structure-related metabolites. Interestingly, a lot of the verified metabolites (10/17) were novel PIO metabolites. Among these novel metabolites, nine were thiazolidinedione ring-opening signals that might be related to the toxicity of PIO. Our developed approach could significantly improve the efficacy in drug metabolite identification compared with that of MDF.

Serum soluble programmed death-1 levels predict the spontaneous HBeAg seroclearance in chronic hepatitis B.

BACKGROUND AND AIMS: In chronic hepatitis B virus (HBV) infection, earlier seroclearance of hepatitis B e antigen (HBeAg) is associated with more favorable outcomes. Soluble programmed cell death 1 (sPD-1) has been implicated in higher viral load and hepatocellular carcinoma. We investigated the association between sPD-1 levels and spontaneous HBeAg seroclearance. METHODS: Baseline serum samples from 488 HBeAg-seropositive patients in the REVEAL-HBV cohort were tested for sPD-1 levels. Among them, 329 with available follow-up serum samples were further assayed. Multivariate Cox regression analysis was used to estimate the adjusted rate ratio (aRR) and 95% confidence interval (CI) with adjustment of host and viral factors. The 66th percentile and an annual reduction of ≥ 10% were used as the cut-off point for baseline sPD-1 levels (high/low) and sPD-1 trajectory (decline/no decline), respectively. RESULTS: Lower baseline sPD-1 levels [aRR (95% CI): 2.19 (1.47-3.27)] and long-term decline in sPD-1 levels [aRR (95% CI): 4.08 (2.79-5.97)] were both independent predictors for HBeAg seroclearance. However, further stratification analysis by HBV genotype showed that lower baseline sPD-1 levels were significantly associated with HBeAg seroclearance only in genotype C infection [aRR (95% CI): 4.47 (2.38-8.37)] but not in genotype B infection. On the other hand, long-term decline in sPD-1 levels was predictive for HBeAg seroclearance regardless of HBV genotype with aRR (95% CI) of 4.62 (2.71-7.88) and 2.95 (1.68-5.17), respectively, for genotypes B and C. CONCLUSION: Serum sPD-1 levels may serve as a novel immunological predictor for spontaneous HBeAg seroclearance in patients with chronic hepatitis B.

Cefepime Induced Neurotoxicity Mimicking Clinical Presentation of Left Middle Cerebral Artery Infarction: A Case Report and Review of Literature.

PURPOSE: Cefepime is a widely used antibiotic which was known to have neurotoxicity resulted from its ability to cross the blood-brain barrier and a wide variety of symptoms had been documented. Here we reported a case of Cefepime induced neurotoxicity with rare presentation. The aim of this study was to improve the knowledge of this condition. CASE REPORT: A 89-year-old female with a history of ESRD (end stage renal disease) and superimposed acute cholecystitis was treated with Cefepime. She developed the symptoms of global aphasia, right hemiplegia, leftward eye deviation and abnormal plantar reflex at right foot, which resembled acute ischemic stroke at left MCA (middle cerebral artery), on the fourth day of Cefepime treatment. There was no evidence of acute infarction in MRI (magnetic resonance imaging) of brain and EEG (electroencephalography) revealed NCSE (nonconvulsive status epilepticus). NCSE was suspected to be attributed to Cefepime-induced neurotoxicity. The patient's main risk factors were decreased renal clearance and incorrect dosing. Conslusion: Cefepime-induced neurotoxicity should be suspected in patients who developed neurologic symptoms after the administration of Cefepime. Emergent image study for excluding more commonly seen or critical etiologies and further evaluation with EEG were necessary. For those patients who have risk factors for Cefepime neurotoxicity, such as ESRD, TDM (therapeutic drug monitoring) may be useful in providing close monitoring and preventing adverse effects associated with Cefepime treatment. Keyword: Cefepime, acute ischemic stroke, aphaia, nonconvulsive status epilepticus.

Serum soluble programmed cell death 1 levels predict spontaneous functional cure in inactive carriers with chronic hepatitis B.

BACKGROUND: Hepatitis B surface antigen (HBsAg) seroclearance is the most important milestone indicating favourable clinical outcomes in patients with chronic hepatitis B (CHB). However, it is difficult to achieve due to the impaired HBV-specific immunity, such as programmed cell death 1 (PD-1)-associated T cell exhaustion. We assessed soluble PD-1 (sPD-1) as a novel seromarker for predicting spontaneous HBsAg loss. METHODS: Serial serum levels of sPD-1 were evaluated in 1046 untreated hepatitis B e antigen (HBeAg)-seronegative individuals who had achieved undetectable serum HBV DNA. Multiple regression analyses were applied to assess associations among baseline and subsequent sPD-1 levels, HBsAg decline during follow-up, and spontaneous HBsAg seroclearance. RESULTS: A total of 390 individuals achieved spontaneous HBsAg seroclearance during 6464.4 person-years of follow-up. Baseline sPD-1 levels were inversely associated with baseline HBsAg levels (qHBsAg) as well as a greater decline in qHBsAg during follow-up. Incidence rates of HBsAg seroclearance were 11.5, 61.7, 96.7 and 151.0 per 1000 person-years for sPD-1 levels of ≥4000, 536-3999, 125-535 and <125 pg/mL, respectively (Ptrend  < 0.0001). Compared with baseline sPD-1 levels ≥4000 pg/mL, the rate ratio (95% CI) of HBsAg seroclearance was 2.1 (1.1-3.9), 3.0 (1.6-5.5) and 5.1 (2.8-9.5), for baseline sPD-1 levels of 536-3999, 125-535 and <125 pg/mL, respectively, after adjustment for sex, age and serum alanine aminotransferase and HBsAg levels. CONCLUSION: sPD-1 level is a novel marker which independently predicts spontaneous HBsAg seroclearance of HBeAg-negative inactive CHB patients with undetectable HBV DNA. (word count: 234, <250).

The impact of antiseizure medications on polysomnographic parameters: a systematic review and meta-analysis.

BACKGROUND: Oral antiseizure medications (ASMs) are first-line treatments for patients with epilepsy. However, ASMs may alter sleep architecture, adversely affecting patient outcomes. The meta-analysis aimed to elucidate the effect of ASMs on sleep architecture. METHODS: PubMed, Embase, and Cochrane Central database (up to Febrary 2021) were searched for randomized control trials (RCT) with effects of ASMs on polysomnography parameters. A meta-analysis using a random-effects model was performed. We did not set limitation to the participants with underlying diagnosis of epilepsy. RESULTS: Eighteen randomized-controlled trials fulfilled the eligibility criteria. The effects of five main groups of ASMs (sodium channel blockers, calcium channel blockers, GABA enhancers, synaptic vesicle glycoprotein 2A [SV2A] ligand, and broad-spetrum ASMs) on slow-wave sleep (SWS), rapid eye movement (REM) sleep, and sleep efficiency (SE) were analyzed. Compared with placebo, calcium channel blockers and GABA enhancers significantly increased SWS. GABA enhancers also decreased REM sleep percentage, whereas calcium channel blockers significantly increased SE. Sodium channel blockers, SV2A ligand and broad-spectrum ASMs did not affect SWS, REM sleep, or SE. The subgroup analysis revealed that gabapentin, pregabalin, and tiagabine increased the percentage of SWS. Tiagabine also decreased REM sleep, whereas pregabalin increased SE. Finally, levetiracetam did not affect SWS, REM sleep, and SE. CONCLUSIONS: This meta-analysis indicated that ASMs can have a statistically significant effect on sleep parameters; the effect differs between ASMs.

A Glycomarker for Short-term Prediction of Hepatocellular Carcinoma: A Longitudinal Study With Serial Measurements.

OBJECTIVES: Wisteria floribunda agglutinin-positive human Mac-2-binding protein (WFA+-M2BP) is a glycomarker. The present community-based long-term follow-up study repeatedly determined the serum WFA+-M2BP level and examined its short- and long-term associations with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). METHODS: A total of 921 participants with antibodies against HCV seropositive, but seronegative for hepatitis B surface antigen were enrolled from seven townships in Taiwan during 1991-1992. The participants were regularly followed and their serum WFA+-M2BP levels were measured at baseline and follow-up. HCC was ascertained through active follow-up and computerized data linkage with the National Cancer Registration System until December 31, 2013. Cox proportional hazards and logistic regression models were applied to estimate the magnitude of associations between serum WFA+-M2BP levels and HCC. RESULTS: During a median follow-up of 21.7 years, 122 new-onset HCC cases were identified. Elevated serum WFA+-M2BP levels were associated with an increased risk of HCC (p < 0.001). Patients with increasing changes in serum WFA+-M2BP levels, relative to their baseline levels, had a 4.36-fold risk of HCC. The areas under receiver operating curves (AUROCs) of WFA+-M2BP for predicting HCC showed that the prediction efficacy was significantly higher while closer to HCC diagnosis (p = 0.024). The AUROC was 0.91 for predicting HCC within 1 year by including the predictors of age, sex, alanine aminotransferase, alpha-fetoprotein (AFP) and WFA+-M2BP. CONCLUSIONS: Serum WFA+-M2BP level may elevate before HCC onset and is a short-term predictor of HCC among patients infected with HCV.

Association of body mass index and urine pH in patients with urolithiasis.

Increase in body size increases the risk of renal stone formation. The mechanism explaining this relationship remains unclear. Urine pH is one of the important factors for urinary stone formation. The purpose of this study was to determine whether there is an association between urine pH and body mass index (BMI) in patients with urolithiasis. Medical charts review that included 342 urinary stone formers (248 men and 94 women). Data obtained included patient sex, age, BMI, urine pH at diagnosis, and stone composition. The patients were classified as normal weight (18.5 or= 27). The mean urine pH of the normal body weight, overweight, and obese groups was 6.25, 6.14, and 6.00, respectively (P < 0.05). Urine pH is inversely related to BMI among patients with urolithiasis. Among patients with urolithiasis, higher BMI will have lower urine pH. This may explain why obesity is associated with an increased risk of nephrolithiasis. Weight loss should be explored as a potential treatment to prevent kidney stone formation. The prevention of urinary stone disease gives clinicians an additional reason to encourage weight reduction through diet.

Successful treatment of bilateral emphysematous pyelonephritis in a uremic patient without nephrectomy.

Emphysematous pyelonephritis (EPN) is a severe and complicated renal infection characterized by gas formation within the infected kidney and its surrounding tissues. Early diagnosis with a high index of suspicion and aggressive treatment are important for improving outcome. Bilateral involvement is rare, and surgical intervention is usually required because of its high mortality rate. A literature review found that EPN has rarely been noted in chronic dialysis patients, and those who show bilateral EPN have demonstrated no survival at all until now. Herein, we presented a 51-year-old diabetic uremic woman who developed right emphysematous pyelitis initially and then progressed to bilateral EPN when hospitalized. Percutaneous drainage (PCD) with simultaneous antibiotic therapy successfully eradicated her renal infection. In this study, all reported cases of EPN in chronic dialysis patients were also reviewed.

Clinical study of uric acid urolithiasis.

Uric acid urolithiasis develops from various causes. To investigate the clinical and biochemical presentation of patients with uric acid urolithiasis, a retrospective study was designed. A total of 46 cases were enrolled between January 2004 and December 2005. The compositions of the stones were analyzed by infrared spectrophotometry. There were 39 males (84.8%) and seven females (15.2%), with a mean age of 61.5 +/- 10.6 years and mean body mass index (BMI) of 26.7 +/- 3.1 kg/m2. The stone location was kidney in 10 (21.7%), ureter in 22 (41.8%), and bladder in 14 (30.5%). Multiple stones were diagnosed in 36 patients (78.3%). Pre-existing comorbidities included diabetes mellitus in 11 patients (23.9%), hypertension in 23 (50%), gout in 13 (28.2%), and benign prostatic hyperplasia in 14 (30.4%). Mean serum creatinine and uric acid was 1.6 +/- 0.6 mg/dL and 7.6 +/- 1.8 mg/dL, respectively. There were 27 patients (58%) with creatinine > 1.4 mg/dL. The mean urinary pH was 5.42 +/- 0.46. Patients with uric acid urolithiasis were predominantly male, older, with higher BMI, multiple stone presentation, with lower urinary pH, and hyperuricemia. Exacerbation of the renal function should also be of concern because of the high proportion of patients with renal insufficiency diagnosed in this study.