Caffeic acid phenethyl ester suppresses EGFR/FAK/Akt signaling, migration, and tumor growth of prostate cancer cells.

BACKGROUND: Epidermal growth factor receptor (EGFR) is upregulated in prostate cancer (PCa). However, suppression of EGFR did not improve the patient outcome, possibly due to the activation of PI3K/Akt signaling in PCa. Compounds able to suppress both PI3K/Akt and EGFR signaling may be effective for treating advanced PCa. PURPOSE: We examined if caffeic acid phenethyl ester (CAPE) simultaneously suppresses the EGFR and Akt signaling, migration and tumor growth in PCa cells. METHODS: Wound healing assay, transwell migration assay and xenograft mice model were used to determine the effects of CAPE on migration and proliferation of PCa cells. Western blot, immunoprecipitation, and immunohistochemistry staining were performed to determine the effects of CAPE on EGFR and Akt signaling. RESULTS: CAPE treatment decreased the gene expression of HRAS, RAF1, AKT2, GSK3A, and EGF and the protein expression of phospho-EGFR (Y845, Y1069, Y1148, Y1173), phospho-FAK, Akt, and ERK1/2 in PCa cells. CAPE treatment inhibited the EGF-induced migration of PCa cells. Combined treatment of CAPE with EGFR inhibitor gefitinib showed additive inhibition on migration and proliferation of PCa cells. Injection of CAPE (15 mg/kg/3 days) for 14 days suppressed the tumor growth of prostate xenografts in nude mice as well as suppressed the levels of Ki67, phospho-EGFR Y845, MMP-9, phospho-Akt S473, phospho-Akt T308, Ras, and Raf-1 in prostate xenografts. CONCLUSIONS: Our study suggested that CAPE can simultaneously suppress the EGFR and Akt signaling in PCa cells and is a potential therapeutic agent for advanced PCa.

The Role of Vitamin D in SARS-CoV-2 Infection and Acute Kidney Injury.

Vitamin D has been described as an essential nutrient and hormone, which can cause nuclear, non-genomic, and mitochondrial effects. Vitamin D not only controls the transcription of thousands of genes, directly or indirectly through the modulation of calcium fluxes, but it also influences the cell metabolism and maintenance specific nuclear programs. Given its broad spectrum of activity and multiple molecular targets, a deficiency of vitamin D can be involved in many pathologies. Vitamin D deficiency also influences mortality and multiple outcomes in chronic kidney disease (CKD). Active and native vitamin D serum levels are also decreased in critically ill patients and are associated with acute kidney injury (AKI) and in-hospital mortality. In addition to regulating calcium and phosphate homeostasis, vitamin D-related mechanisms regulate adaptive and innate immunity. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have a role in excessive proinflammatory cell recruitment and cytokine release, which contribute to alveolar and full-body endothelial damage. AKI is one of the most common extrapulmonary manifestations of severe coronavirus disease 2019 (COVID-19). There are also some correlations between the vitamin D level and COVID-19 severity via several pathways. Proper vitamin D supplementation may be an attractive therapeutic strategy for AKI and has the benefits of low cost and low risk of toxicity and side effects.

Vitamin D for Recovery of COVID-19 in Patients With Chronic Kidney Disease.

The severity of coronavirus disease 2019 (COVID-19) is determined not only by viral damage to cells but also by the immune reaction in the host. In addition to therapeutic interventions that target the viral infection, immunoregulation may be helpful in the management of COVID-19. Vitamin D exerts effects on both innate and adaptive immunity and subsequently modulates immune responses to bacteria and viruses. Patients with chronic kidney disease (CKD) frequently have vitamin D deficiency and increased susceptibility to infection, suggesting a potential role of vitamin D in this vulnerable population. In this paper, we review the alterations of the immune system, the risk of COVID-19 infections and mechanisms of vitamin D action in the pathogenesis of COVID-19 in CKD patients. Previous studies have shown that vitamin D deficiency can affect the outcomes of COVID-19. Supplementing vitamin D during treatment may be protective against COVID-19. Future studies, including randomized control trials, are warranted to determine the effect of vitamin D supplementation on the recovery from COVID-19 in CKD patients.

Antiproteinuria Effect of Calcitriol in Patients With Chronic Kidney Disease and Vitamin D Deficiency: A Randomized Controlled Study.

OBJECTIVE: Vitamin D has been demonstrated to lessen proteinuria severity in chronic kidney disease (CKD). Compared with healthy populations, patients with CKD may have lower serum levels of 1,25-dihydroxy vitamin D (1,25-(OH)2 D) and 25-hydroxy vitamin D (25-(OH) D). We investigated the effect of  oral low-dose active vitamin D (calcitriol at 0.25 µg, 3 times weekly) on urinary protein excretion. DESIGN AND METHODS: We conducted a nonblinded and non-placebo-controlled study. In total, 60 patients with CKD (average estimated glomerular filtration rate of >15 mL/min) who received a stable dose of angiotensin receptor blocker (ARB) or angiotensin-converting enzyme inhibitor (ACEI) were enrolled in this 24-week study. We randomly assigned these patients to the vitamin D group (oral calcitriol at 0.25 µg 3 times weekly with an ACEI or ARB) or the control group (ACEI or ARB). Change in the urine protein/creatinine ratio (uPCR) was the primary endpoint in this study. RESULTS: The mean baseline uPCRs of the 2 groups were comparable (1.84 ± 0.83 g/g vs. 2.02 ± 0.97 g/g, control vs. vitamin D group; P = .46). After the 24-week treatment, the uPCRs were significantly lower than the baseline values in the vitamin D group (1.35 ± 0.64 g/g; P < .05) but not in the control group. The values of uPCR decreased significantly at 8, 16, and 24 weeks (P < .05 vs. baseline) in the vitamin D group. The values of uPCRs were significantly lower in the vitamin D group than in the control group at 8, 16, and 24 weeks (P < .05). A positive correlation was discovered between reduction in uPCRs at 24-week and baseline 25-(OH) D serum level in the vitamin D group (r = 0.738, P < .001). CONCLUSION: Supplementary low-dose active vitamin D could reduce proteinuria in CKD patients with low serum 25-(OH) D levels.

Etiologies of community-onset urinary tract infections requiring hospitalization and antimicrobial susceptibilities of causative microorganisms.

BACKGROUND: Community-onset urinary tract infections (CoUTIs) are the most common bacterial infections, and a decline in antibiotic susceptibility causes many clinical challenges. Adequate empiric antibiotic treatment can decrease unnecessary hospital stays and complications, while reducing the antimicrobial resistance progression. METHODS: From October 2014 to April 2015, we retrospectively enrolled patients who were at least 18 years old and required hospitalization for CoUTIs. Demographic variables of these patients, and uropathogens and their antimicrobial susceptibilities were evaluated. RESULTS: In total, 457 patients were enrolled in this study. Their mean age was 71.9 years, and 35.2% of the patients were male. Escherichia coli (54.5%) was the most common uropathogen, followed by Klebsiella pneumoniae (13.1%), Enterococcus spp. (7.1%), Pseudomonas aeruginosa (4.6%), and Proteus mirabilis (3.5%). Bacteremia was present in 25.2% of patients. Diabetes mellitus and acute kidney injury at admission were risk factors for CoUTIs with concomitant bacteremia. Among the UTI-associated bloodstream strains, E. coli (53.1%) was also the most predominant pathogen, followed by K. pneumoniae (11.3%), Staphylococcus aureus (6.1%), and P. mirabilis (4.3%). The overall susceptibility of cefazolin was 62.8%, ceftriaxone 71.4%, ceftazidime 82.8%, flomoxef 82%, cefepime 94.5%, ampicillin-sulbactam 41.6%, piperacillin-tazobactam 85%, levofloxacin 65.2%, trimethoprim-sulfamethoxazole 61.5%, imipenem 92.3%, gentamicin 76.1%, and amikacin 97.5%. Cefazolin-susceptible isolates could be found more frequently among patients who are less than 65 years of age and without diabetes mellitus, had no UTI episode in the past year, and have no bacteremia risk. Patients with nasogastric tube retention more commonly experienced antimicrobial resistance to all the third-generation cephalosporins. CONCLUSION: Third-generation cephalosporins effectively treated CoUTIs. However, patients with nasogastric tube retention more commonly experienced cephalosporin resistance. Cefepime, imipenem, and amikacin may be used in patients with higher antimicrobial resistance. In selected patients, cefazolin may still be an adequate drug of choice for CoUTIs.

Comparison of short-term efficacy of iron sucrose with those of ferric chloride in hemodialysis patients: An open-label study.

BACKGROUND: It is intriguing and imperative that the comparison of the iron preparations in hemodialysis (HD) patients. This study aimed to observe the short-term efficacy of parenteral iron sucrose and ferric chloride in HD patients. MATERIALS AND METHODS: This was a consecutive 10-week single-blind study in Taiwan. An intravenous iron supplement of 100 mg/week was administered as an infusion in 100 ml of normal saline, until a total dose of 1000 mg was achieved. The primary outcome was evaluated by the changes in serum hematocrit (Hct) levels. The changes in serum Hct and iron indices were evaluated every 2 weeks for 10 weeks. The results were collected from 21 April to 4 July 2013. RESULTS: A total of 56 HD patients completed the study. Subjects were randomized into an iron sucrose group (26 patients) and a ferric chloride group (30 patients). Between the two treatment groups, there were no statistically significant differences in the change in serum Hct, ferritin, iron, or total iron binding capacity (P > 0.05). In the iron sucrose group, the increase in Hct levels was statistically significant at weeks 4, 8, and 10. In the ferric chloride group, the increase in Hct levels was statistically significant at week 8. No obvious major side effects were observed in both groups. CONCLUSION: In the study subjects, parenteral iron sucrose was as effective and safe as ferric chloride for treating anemia in HD patients.

Use of traditional Chinese medicine (Ren Shen Yang Rong Tang) against microinflammation in hemodialysis patients: An open-label trial.

BACKGROUND: Complementary and alternative medicine such as traditional Chinese medicine (TCM) is now frequently used combined with Western medicine for treatment in chronic kidney disease (CKD). OBJECTIVE: We designed an open-label trial to investigate the safety and potential therapeutic effects of Ren Shen Yang Rong Tang (R-S-Y-R-T) in hemodialysis (HD) patients. METHODS: The experimental group was treated with additional R-S-Y-R-T combined with routine western medicine, while the control group was treated only with routine western medicine. The duration of study was 6 months. Primary outcomes were to evaluate the changes in serum hematocrit and albumin levels. Secondary outcomes including blood inflammatory markers (c-reactive protein [CRP], interleukin-6 [IL-6], and tumor necrosis factor-α [TNF-α]) were checked. Finally we also followed up the change of quality of life (QOL) in our subjects. RESULTS: Sixty nine respondents were enrolled in this trial. Finally a total of 59 patients (27 R-S-Y-R-T group, 32 control group) completed the 6-month follow-up. Primary outcomes showed no significant statistical change of hematocrit in either 2 group (P>0.05). But the R-S-Y-R-T group had a statistical increase in serum albumin (P<0.05). Secondary outcomes were that both TNF-α (P=0.003) and IL-6 (P=0.001) showed evident decrease in the R-S-Y-R-T group. CRP was identified without statistical difference in both groups (P=0.226). The R-S-Y-R-T group also had a significant improvement in QOL (P<0.05). CONCLUSIONS: Our study suggests that R-S-Y-R-T could decrease chronic inflammation and increase the life quality in HD patients. Further larger clinical trial of long-term treatment with R-S-Y-R-T is necessary for evaluating treatment use.

Body mass index and age are predictors for symptom improvement after high-power laser vaporization for benign prostatic hyperplasia.

BACKGROUND/PURPOSE: To evaluate the effectiveness and safety of high-power 120W Greenlight HPS laser (HPS) and compare the results to transurethral resection of the prostate (TURP), and define a subgroup of patients who had better symptom score improvement after HPS. METHODS: One hundred and twenty-five patients who underwent surgery for benign prostatic hyperplasia (BPH) (61 HPS and 64 TURP) were retrospectively followed. Improvements of International Prostate Symptom Score (IPSS), quality of life score (QoL), maximum flow rate (Qmax) and post-void residual (PVR) were assessed at 4 weeks after the procedures. Potential covariates including age, body mass index (BMI), prostate volume (PV) and serum prostate-specific antigen (PSA) were defined and further subgroup analyses were utilized. RESULTS: The HPS group had a significantly higher education level, annual household income and larger prostate size. Compared with TURP, HPS resulted in comparable IPSS, QoL, Qmax and PVR improvements, but shorter hospitalization duration, serum hemoglobin loss and blood transfusion rate. Subgroup analyses showed that men in the HPS group were younger (age<76 years), had higher BMI (≥24kg/m(2)) and greater adjusted IPSS and QoL improvements than men in the TURP group. CONCLUSION: HPS offered adequate effectiveness for symptomatic BPH versus TURP and was advantageous with regard to operative safety. Patients who are younger and have higher BMI may achieve better improvements with HPS than with TURP. Further long-term follow-up study is warranted.