Natural STAT3 inhibitors for cancer treatment: A Comprehensive Literature Review.

Cancer is one of the leading causes of mortality and morbidity worldwide, affecting millions of people physically and financially every year. Over time, many anticancer treatments have been proposed and studied, including synthetic compound consumption, surgical procedures, or grueling chemotherapy. Although these treatments have improved the daily life quality of patients and increased their survival rate and life expectancy, they have also shown significant drawbacks, including staggering costs, multiple side effects, and difficulty in compliance and adherence to treatment. Therefore, natural compounds have been considered a possible key to overcoming these problems in recent years, and thorough research has been done to assess their effectiveness. In these studies, scientists have discovered a meaningful interaction between several natural materials and signal transducer and activator of transcription 3 molecules. STAT3 is a transcriptional protein that is vital for cell growth and survival. Mechanistic studies have established that activated STAT3 can increase cancer cell proliferation and invasion while reducing anticancer immunity. Thus, inhibiting STAT3 signaling by natural compounds has become one of the favorite research topics and an attractive target for developing novel cancer treatments. In the present article, we intend to comprehensively review the latest knowledge about the effects of various organic compounds on inhibiting the STAT3 signaling pathway to cure different cancer diseases.

Comparing the Effect of Immediate versus Delayed Initiation of Tacrolimus on Delayed Graft Function in Kidney Transplant Recipients: A Randomized Open-label Clinical Trial.

OBJECTIVE: Delayed graft function (DGF) is an early complication after kidney transplantation with negative impact on allograft outcomes. This study assessed the effect of delayed initiation of tacrolimus as a nephrotoxic drug, on DGF occurrence and allograft function. METHODS: This randomized, open-label clinical trial was conducted on kidney transplant recipients with the age of at least 14 years who underwent the first kidney transplantation from deceased or living donor. Patients were randomly allocated to immediate (n = 26) or delayed tacrolimus (n = 27) groups. All patients received thymoglobulin as induction therapy and similar maintenance immunosuppression including tacrolimus, mycophenolate, and prednisolone with the difference in the time of initiation of tacrolimus either on the day of transplantation (immediate tacrolimus group) or day 3 after transplant (delayed tacrolimus group). FINDINGS: DGF incidence (46.15% vs. 37.04%; P = 0.501) and duration (9.75 ± 6.41 vs. 8.6 ± 6.16 days; P = 0.675) were not different between the immediate and delayed tacrolimus groups. Estimated creatinine clearance using Cockcroft-Gault equation (63.14 ± 18.81 vs. 58.19 ± 19.42 mL/min in immediate and delayed tacrolimus groups respectively; P = 0.373) and estimated acute rejection-free survival were also comparable between the groups over the 3 months of follow-up. Compared with the immediate group, the delayed tacrolimus group showed higher estimated 3-month grafts' survival (100% vs. 84.27%; P = 0.072). CONCLUSION: Delayed initiation of tacrolimus after kidney transplantation under the umbrella of thymoglobulin induction did not result in either lower incidence or duration of DGF or improved the level of graft function in kidney transplant recipients but non-statistically significant increased 3-month grafts' survival.

Isfahan MISP Dataset.

An online depository was introduced to share clinical ground truth with the public and provide open access for researchers to evaluate their computer-aided algorithms. PHP was used for web programming and MySQL for database managing. The website was entitled "biosigdata.com." It was a fast, secure, and easy-to-use online database for medical signals and images. Freely registered users could download the datasets and could also share their own supplementary materials while maintaining their privacies (citation and fee). Commenting was also available for all datasets, and automatic sitemap and semi-automatic SEO indexing have been set for the site. A comprehensive list of available websites for medical datasets is also presented as a Supplementary (http://journalonweb.com/tempaccess/4800.584.JMSS_55_16I3253.pdf).

Antibiotic resistance patterns of microorganisms isolated from nephrology and kidney transplant wards of a referral academic hospital.

OBJECTIVE: Antibiotic use pattern and emergence of resistant bacteria are major concerns in clinical settings. This study aimed to detect common bacteria and their antibiotic sensitivity patterns in nephrology and kidney transplant wards. METHODS: This 1-year, observational study was performed in the nephrology and kidney transplant wards of Imam Khomeini Hospital Complex, Tehran, Iran. All patients treated with antimicrobial agents for confirmed or suspected infections were included. Their demographic, clinical, and laboratory data (including biological media used for microbial culture, growth organisms, and antibiograms) were collected. Adherence of antimicrobial regimen to standard guidelines was also assessed. FINDINGS: About half of the patients received antibiotic. The most common infecting bacteria were Escherichia coli followed by Enterococcus sp. and Staphylococcus aureus. E. coli showed high rate of sensitivity to carbapenems and nitrofurantoin and high rate of resistance to co-trimoxazole and ciprofloxacin. Enterococcus sp. in both wards had high rate of resistance to ampicillin and were all sensitive to linezolid. Unlike to the nephrology ward, more than 50% of Enterococcus sp. from kidney transplant ward was resistant to vancomycin. The most common type of S. aureus in this nephrology ward was methicillin-resistant S. aureus (MRSA). Most commonly-prescribed antibiotics were carbapenems followed by vancomycin, ciprofloxacin, and ceftriaxone. Antibiotic regimens were 75% and 83%, 85% and 91%, and 80% and 87% compatible with international guidelines in antibiotic types, dosages, and treatment durations, respectively, in nephrology and kidney transplant wards, respectively. CONCLUSION: MRSA, fluoroquinolone-resistant E. coli, and vancomycin resistant Enterococcus species are major threats in nephrology and kidney transplant wards. Most commonly-prescribed antibiotics were carbapenems that necessitate providing internal guidelines by the teamwork of clinical pharmacist, infectious disease specialists, and nephrologists to avoid the widespread use of broad-spectrum antibiotics.

Prevention of hemodialysis catheter-related blood stream infections using a cotrimoxazole-lock technique.

BACKGROUND & AIM: This trial assessed the efficacy of cotrimoxazole lock solution in reducing catheter-related blood stream infections (CRBSIs) among hemodialysis (HD) patients who were dialyzed using tunneled catheters. METHOD: Patients randomly received either heparin (2500 U/ml) (control group) or a mixture of 10 mg/ml cotrimoxazole (based on trimethoprim) and 2500 U/ml heparin (antibiotic group) as catheters lock solution. RESULTS: Compared with the control group, CRBSIs rates per 1000 catheter-days was significantly lower (0.58 vs 4.4 events; p = 0.002) and cumulative infection-free catheter survival was significantly higher (log rank statistic 5.88; p = 0.015) in the antibiotic group. There were no statistical differences regarding incidences of catheter removal (8.7% in the antibiotic group vs 22% in the control group; p = 0.116) or thrombosis (2.2% in the antibiotic group vs 9.8% in the control group; p = 0.129) between the two groups. CONCLUSION: cotrimoxazole containing catheter lock solution is effective in reducing CRBSIs incidence and prolonging dialysis catheter survival in HD patients.

Waste load allocation in rivers under uncertainty: application of social choice procedures.

In this paper, a waste load allocation model is developed which can incorporate uncertainties due to randomness as well as vagueness regarding some variables and parameters. A probabilistic water quality index is also presented and used in the waste load allocation model. For any discharger of the system, different wastewater treatment scenarios are defined. All possible combinations of these scenarios make different wastewater treatment alternatives for the system. An optimization model having the objectives of minimizing total treatment cost as well as water quality violation risk is also developed for finding the optimum treatment alternatives. The uncertainty related to the upstream river flow is addressed through considering probability distribution functions with fuzzy parameters. To deal with fuzzy and random inputs, the fuzzy transformation technique and Monte Carlo analysis are respectively used, and for each alternative, fuzzy membership function of the violation risk is obtained. The optimization model only takes into account the economic and environmental objectives and does not specifically consider the stakeholders satisfaction. To consider this and help the decision maker choose a final alternative among non-dominated solutions, three different social choice procedures which focus on stakeholders priorities are employed. The applicability and effectiveness of the methodology are evaluated by applying it to the Zarjub River in Iran facing serious water quality issues. The results indicate that the presented methodology can effectively take account of priorities of various decision makers as well as economic and environmental considerations, while incorporating multiple forms of uncertainties.

Comparing the frequency of hypertension determined by peri-dialysis measurement and ABPM in hemodialysis patients.

Controlling blood pressure in hemodialysis patients is crucial but not always easy. The most common blood pressure measurement method is peri-dialysis measurement, but due to interdialytic blood pressure fluctuations, we are unsure if it is the proper way for evaluating blood pressure. Some studies have shown the superiority of 24-h ambulatory blood pressure monitoring over peri-dialysis blood pressure measurement. We aimed to compare the consistency of these methods in determining hypertension among hemodialysis patients. We studied 50 patients (mean age: 55.8 years) on regular hemodialysis in Imam Khomeini University Hospital, Tehran, Iran. Peri-dialysis blood pressure and interdialytic 24-h ambulatory blood pressure monitoring were recorded for each patient. Patients' demographic data and peri-dialysis weight were recorded too. All data were analyzed using the PASW Statistics 18.0, SPSS Inc. (Chicago, IL). There was a significant difference between pre-dialysis mean systolic blood pressure (146.1 ± 23.3 mmHg) and mean systolic blood pressure recorded by ambulatory blood pressure monitoring (135.3 ± 19.3 mmHg) (p = 0.001). There was also a significant difference between pre-dialysis mean diastolic blood pressure (83 ± 14 mmHg) and mean diastolic blood pressure recorded by ambulatory blood pressure monitoring (77.3 ± 10 mmHg) (p = 0.003). But the frequencies of hypertension measured with both methods were significantly consistent and the Kappa agreement coefficient was 0.525 (p = 0.001). Considering ambulatory blood pressure monitoring as the gold standard for blood pressure measurement, our recommendation for the best cutoff point to diagnose hypertension, with the highest sensitivity and specificity would be 135/80 mmHg for pre-dialysis blood pressure and 115/70 mmHg for post-dialysis blood pressure.

Cardiac troponins in patients with chronic kidney disease and kidney transplant recipients without acute cardiac symptoms.

INTRODUCTION: Cardiovascular diseases are the most common causes of death in chronic kidney disease (CKD) and kidney transplant patients. This study aimed to evaluate cardiac troponins in transplant recipients and CKD patients without cardiac symptoms. MATERIALS AND METHODS: Two groups of patients (CKD and kidney transplant recipients) were evaluated for troponins T and I levels. These values were associated with renal replacement therapy and demographic and clinical characteristics of the patients. RESULTS: Eighty CKD patients and 80 kidney transplant recipients were studied. There was a significant difference in Troponins T and I levels were significantly higher in the CKD group than in the transplant recipients. In the CKD group, 14 patients (17.5%) had an elevated troponin T level and 8 (10.0%) had an elevated troponin I, all of whom were in stage 4 of CKD. None of the kidney transplant patients had a positive troponin. Among CKD patients, decreased glomerular filtration rate was associated with elevated troponin I level. Elevated troponin T level was significantly associated with age and decreased glomerular filtration rate. In multivariable analysis, significant associations were found between troponin T level and age, serum creatinine, and glomerular filtration rate. A significant relationship was also found between troponin I and cholesterol and glomerular filtration rate. CONCLUSIONS: The assessment of troponin T and I in CKD and kidney transplant patients shows that in patients with CKD and without any symptoms of acute coronary syndrome, serum level of cardiac troponins increase and it is linked to serum creatinine and GFR.

Uremic pruritus and serum phosphorus level.

Pruritus is a common and bothersome problem among uremic patients which negatively affects life quality and prognosis of the patient. Various factors are known to be involved in the development of pruritus. The aim of this study was to assess the frequency and the factors which may have relationship with uremic pruritus, especially bone mineral metabolism indicators. Current cross-sectional study was done on 99 hemodialysis patients. Having pruritus, its duration, severity and correlation with patient's laboratory data was evaluated. For each patient a questionnaire was filled. The mean age of patients was 55.9±15.4 (23-87) years and 35.7% were female. They were on hemodialysis for 74.79±75.04 months. Frequency of pruritus was 58.6% (58 patients). Considering the severity, 16.2% suffered from severe pruritus, measured by visual analogue scale (VAS). Pruritus was more common in those on dialysis for more than 2 years (0.014). 82.8% of those with VAS of less than 3, in comparison with 37.5% of those with VAS of greater than 7, had no complaint of awakening due to pruritus. The frequency of pruritus and its severity was more in patients with higher serum phosphorus level (P=0.048). It seems that phosphate control which is not mainly attributed to dialysis adequacy and efficiency, needs more attention not only by medical team but also by patient. Decreasing the phosphate content of regimen may be cheap and helpful modality in pruritus management.

Effect of add-on pentoxifylline on proteinuria in membranous glomerulonephritis: a 6-month placebo-controlled trial.

BACKGROUND: Membranous glomerulonephritis (MGN) may cause proteinuria as the main complication and is a strong risk factor for end-stage renal disease. Current therapeutic regimens provide only partial renoprotection. Data derived from both animal and human studies provide a scientific basis for the use of pentoxifylline as an antiproteinuric agent. OBJECTIVE: This study was designed to evaluate the antiproteinuric effect of add-on pentoxifylline therapy in non-diabetic patients with MGN. STUDY DESIGN: This was a double-blind, placebo-controlled trial. SETTING: Non-diabetic patients with histologically proven MGN and urinary protein excretion (UPE) > 500 mg/24 h, entered a 6-month study period. Enrolled patients were selected from a university and three private clinics. INTERVENTION: Patients were assigned to one of the two treatment groups: pentoxifylline 400 mg two or three times a day, or matching placebo. MAIN OUTCOME MEASURES: Baseline and follow-up assessments included estimated glomerular filtration rate (eGFR) and UPE. Differences in the changes in variables within the placebo and pentoxifylline treatment groups during the study period were assessed using Friedman's test. RESULTS: Treatment with pentoxifylline for 6 months resulted in a significant reduction of mean UPE (p < 0.001) along with a slight, non-significant increase of eGFR, in comparison to the mean UPE and eGFR increase in the placebo group. CONCLUSION: This study showed that add-on therapy of pentoxifylline in MGN was beneficial, and could be considered as a potential new therapeutic indication for the drug in such kidney diseases.

The role of clinical pharmacy services in achieving treatment targets in Iranian haemodialysis patients.

INTRODUCTION: The number of patients suffering from chronic kidney disease (CKD) is increasing worldwide. Hyperphosphataemia and high serum calcium (Ca) and phosphorus (P) product contribute to the substantial increase in cardiovascular events in CKD patients. Although reports of CKD complications in Iranian haemodialysis (HD) patients are comparable to data from other developed countries, management of these complications has failed to meet generally accepted targets. This study evaluated the impact of clinical pharmacy services in the management of complications in HD patients. METHODS: During a six-month prospective study, clinical pharmacists conducted medical visits in the HD ward and adjusted the patients' medications according to their laboratory findings. RESULTS: Serum Ca concentration was increased in hypocalcaemia patients and decreased in hypercalcaemia patients until it reached the optimal range in both groups. A decline in serum P level was noted in hyperphosphataemia patients, although it did not reach the target range. The Ca × P product decreased in patients with Ca × P > 55 mg2/dL2. Although it did not reach the goal, there was an increase and decrease in serum intact parathyroid hormone (iPTH) concentration in suboptimal and supraoptimal range patients, respectively. Serum Ca, P and iPTH levels did not change in patients with optimal values at the initiation of the study. Haemoglobin concentration increased in anaemic patients and serum ferritin reached target values in all patients. Total cholesterol, low-density lipoprotein cholesterol and triglycerides decreased to near-optimal values in dyslipidaemia patients. CONCLUSION: This study showed that clinical pharmacy services at the HD centre can improve the management of complications in CKD patients.

Efficacy of HBV vaccination in various stages of chronic kidney disease: is earlier better?

BACKGROUND: Despite improvement in hepatitis B infection prevention through national vaccination programs, implementation of compulsory and thorough blood donor screening, and reduction of transfusion numbers due to erythropoietin administration,hepatitis B remains a major concern in hemodialysis (HD) centers [1]. Compared to aresponse rate of over 90% in the normal population, only 50 to 60% of those with endstage renal disease (ESRD) achieve protective antibody levels following immunization against hepatitis B [2][3]. Various strategies have been developed to overcome the low seroconversion rate in ESRD patients, including co-administering zinc, gamma-interferon,thymopentin, interleukin-2, and levamisole as immunostimulants or adjuvants [3][4],changing the injection mode (intradermal versus intramuscular), or doubling the vaccine dose [5]. OBJECTIVES: Previous studies demonstrated that renal failure patients benefit from HBV vaccination; however, not all studies have demonstrated this. Therefore, we compared the rates of seroconversion (hepatitis B surface antibody [HBsAb] titer > 10 IU/mL) in patients at various stages of chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2) who received HBV vaccination. PATIENTS AND METHODS: A total of 167 patients in 3 different stages of CKD were vaccinated against HBV. Each patient received the vaccine according to a standardized vaccination schedule consisting of 40 µg of the recombinant vaccine "Engerix" at 0, 1, and 6 months.Eight to 12 weeks after the last dose of vaccination, anti-HBsAb levels were measured. RESULTS: Mean age and eGFR were 57.4 ± 16.5 years and 26.7 ± 14.7 mL/min/1.73 m2, respectively.The overall seroconversion rate was 78%. Although a significant correlation between HBsAb titer and eGFR (r = 0.265, P = 0.001) was observed, in the multivariate analysis using age, CKD stage, diabetes mellitus, and gender as independent variables,the degree of renal function did not significantly contribute to seroconversion. In contrast,higher age (> 60 years) showed a significant negative correlation to seroconversion (odds ratio = 0.22; P = 0.004). CONCLOUSIONS: CKD patients of advanced age should be vaccinated against HBV. Although higher eGFR was not associated with improved seroconversion, the persistence of seroconversion was not evaluated; future studies should be conducted to develop recommendations for earlier or later vaccination.

Tribulus terrestris-induced severe nephrotoxicity in a young healthy male.

Herbal medications are being progressively utilized all over the world. Nevertheless, herbal remedies are not without hazards and several cases of adverse reactions have been described. Tribulus terrestris is traditionally used because of its aphrodisiac and antiurolithiatic activities with almost complete inhibition of stone formation. We report a case of T. terrestris-induced hepatotoxicity, nephrotoxicity and neurotoxicity in an Iranian male patient who used the plant's extract to prevent kidney stone formation. He presented with seizure and very high serum aminotransferases and creatinine after consuming herbal water for 2 days. Discontinuation of the herbal remedy resulted in improvement in symptoms and normalization of his liver enzymes.

Effect of antibiotic therapy on asymptomatic bacteriuria in kidney transplant recipients.

PURPOSE: Asymptomatic bacteriuria is a very common complication after kidney transplantation and the need for antibiotic therapy is controversial. The aim of this study was to evaluate the effect of antibiotic therapy on the clinical course of asymptomatic bacteriuria in renal transplant recipients. MATERIALS AND METHODS: In the present study, 88 kidney transplant recipients with asymptomatic bacteriuria were divided into two groups of cases and controls. The patients had been selected from among those with at least 1 year follow-up. In the case group, asymptomatic bacteriuric episodes were treated with antibiotics, and in control group, they were followed without antibiotic therapy. The follow-up period was 9 to 12 months. Bacteriuric episodes, symptomatic urinary tract infection (UTI) episodes, and changes in plasma creatinine level were recorded and compared between the two groups. RESULTS: The rate of bacteriuric episodes and symptomatic UTIs were not significantly different between the two groups (P >0.05). In addition, level of plasma creatinine did not increase significantly in neither of the groups during the study (P >0.05). CONCLUSION: It seems that treatment of asymptomatic bacteriuria in kidney recipients does not decrease the rate of UTI episodes afterwards. Asymptomatic bacteriuria does not affect renal function in short term. Thus, we can abandon antibiotic therapy, subject to careful follow-up.