Recent findings on the role of fungal products in the treatment of cancer.

In modern medicine, natural products have aided humans against their battles with cancer. Among these products, microorganisms, medicinal herbs and marine organisms are considered to be of great benefit. In recent decades, more than 30 fungal immunity proteins have been identified and proved to be extractable from a wide range of fungi, including mushrooms. Although chemotherapy is used to overcome cancer cells, the side effects of this method are of great concern in clinical practice. Fungal products and their derivatives constitute more than 50% of the clinical drugs currently being used globally. Approximately 60% of the clinically approved drugs for cancer treatment have natural roots. Anti-tumor immunotherapy is prospective with a rapidly growing market worldwide due to its high efficiency, immunity, and profit. Polysaccharide extracts from natural sources are being used in clinical and therapeutic trials on cancer patients. This review aims to present the latest findings in cancer treatment through isolated and extraction of fungal derivatives and other natural biomaterials.

Dietary pattern, colonic microbiota and immunometabolism interaction: new frontiers for diabetes mellitus and related disorders.

In this review, the numerous possible mechanisms that provide supportive evidence for how colonic dysbiosis denotes metabolic dysfunction, dysregulates glucose homeostasis and leads to diabetes mellitus and related metabolic disorders are defined. Information was gathered from articles identified by systematic reviews and searches using Google, PubMed and Scopus. The composition of the colonic microbiota plays an integral role in maintaining host homeostasis by affecting both metabolic activities and underlying functional gene transcription in individuals with diabetes and related metabolic disorders. Increased colonic microbiome-derived concentrations of lipopolysaccharides, also known as 'metabolic endotoxaemia', as well as alterations in bile acid metabolism, short-chain fatty acids, intestinal hormones and branched-chain amino acid secretion have been associated with the diverse production of pro-inflammatory cytokines and the recruitment of inflammatory cells. It has been shown that changes to intestinal bacterial composition are significant even in early childhood and are associated with the pathogenesis of both types of diabetes. We hope that an improved understanding of related mechanisms linking the colonic microbiome with glucose metabolism might provide for innovative therapeutic approaches that would bring the ideal intestinal ecosystem to a state of optimal health, thus preventing and treating diabetes and related metabolic disorders.

Risk of Renal Cell Carcinoma Among Kidney Transplant Recipients in the United States.

Renal cell carcinoma (RCC) is a common malignancy following kidney transplantation. We describe RCC risk and examine RCC risk factors among US kidney recipients (1987-2010). The Transplant Cancer Match Study links the US transplant registry with 15 cancer registries. Standardized incidence ratios (SIRs) were used to compare RCC risk (overall and for clear cell [ccRCC] and papillary subtypes) to the general population. Associations with risk factors were assessed using Cox models. We identified 683 RCCs among 116 208 kidney recipients. RCC risk was substantially elevated compared with the general population (SIR 5.68, 95% confidence interval 5.27-6.13), especially for papillary RCC (SIR 13.3 versus 3.98 for ccRCC). Among kidney recipients, RCC risk was significantly elevated for blacks compared to whites (hazard ratio [HR] 1.50) and lower in females than males (HR 0.56). RCC risk increased with prolonged dialysis preceding transplantation (p-trend < 0.0001). Risk was variably associated for RCC subtypes with some medical conditions that were indications for transplantation: ccRCC risk was reduced with polycystic kidney disease (HR 0.54), and papillary RCC was increased with hypertensive nephrosclerosis (HR 2.02) and vascular diseases (HR 1.86). In conclusion, kidney recipients experience substantially elevated risk of RCC, especially for papillary RCC, and multiple factors contribute to these cancers.

Pharmacokinetic Comparison of Omeprazole Granule and Suspension Forms in Children: A Randomized, Parallel Pilot Trial.

Although, omeprazole is widely used for treatment of gastric acid-mediated disorders. However, its pharmacokinetic and chemical instability does not allow simple aqueous dosage form formulation synthesis for therapy of, especially child, these patients. The aim of this study was at first preparation of suspension dosage form omeprazole and second to compare the blood levels of 2 oral formulations/dosage forms of suspension & granule by high performance liquid chromatography (HPLC). The omeprazole suspension was prepared; in this regard omeprazole powder was added to 8.4% sodium bicarbonate to make final concentration 2 mg/ml omeprazole. After that a randomized, parallel pilot trial study was performed in 34 pediatric patients with acid peptic disorder who considered usage omeprazole. Selected patients were received suspension and granule, respectively. After oral administration, blood samples were collected and analyzed for omeprazole levels using validated HPLC method. The mean omeprazole blood concentration before usage the next dose, (trough level) were 0.12±0.08 µg/ml and 0.18±0.15 µg/ml for granule and suspension groups, respectively and mean blood level after dosing (C2 peak level) were 0.68±0.61 µg/ml and 0.86±0.76 µg/ml for granule and suspension groups, respectively. No significant changes were observed in comparison 2 dosage forms 2 h before (P=0.52) and after (P=0.56) the last dose. These results demonstrate that omeprazole suspension is a suitable substitute for granule in pediatrics.

The rationale behind antibiotic resistance pattern in Klebsiella pneumoniae.

Presently, there is an increase in antibiotic resistance in bacteria, due to relax prescription of antibiotics, especially in Iran. Undoubtedly, in toxin antitoxin (TA) system, a toxin neutralized by antitoxin, which known as a potent antimicrobial target; but there is no extensive survey on the prevalence of TA loci in large scale of Klebsiella pneumoniae. Therefore, this study aims to determine the prevalence of different TA loci in clinical and environmental K. pneumoniae isolates. For this reason, 48 K. pneumoniae clinical isolates and 49 K. pneumoniae environmental isolates were subjected for evaluation of different TA loci. The results of current study indicated that there is no association between antibiotic resistances and presence of TA loci in clinical and environmental K. pneumoniae. The role of TA loci as a potent target in antibiotic resistant K. pneumoniae has been complicated. Therefore, more studies should be performed to explain why TA loci are presented in K. pneumoniae and what is the rationale behind antibiotic resistant K. pneumoniae?

The rationale behind antibiotic resistance pattern in Klebsiella pneumoniae

Presently, there is an increase in antibiotic resistance in bacteria, due to relax prescription of antibiotics, especially in Iran. Undoubtedly, in toxin antitoxin (TA) system, a toxin neutralized by antitoxin, which known as a potent antimicrobial target; but there is no extensive survey on the prevalence of TA loci in large scale of Klebsiella pneumoniae. Therefore, this study aims to determine the prevalence of different TA loci in clinical and environmental K. pneumoniae isolates. For this reason, 48 K. pneumoniae clinical isolates and 49 K. pneumoniae environmental isolates were subjected for evaluation of different TA loci. The results of current study indicated that there is no association between antibiotic resistances and presence of TA loci in clinical and environmental K. pneumoniae. The role of TA loci as a potent target in antibiotic resistant K. pneumoniae has been complicated. Therefore, more studies should be performed to explain why TA loci are presented in K. pneumoniae and what is the rationale behind antibiotic resistant K. pneumoniae?

Patulin in apple leather in Iran.

Apple leather is made by dehydration of cooked fruit into leathery sheets. Mould growth and patulin production can occur in damaged apples or when fallen fruit is collected for apple leather processing. A survey was conducted to determine levels and dietary intake of patulin from apple leather marketed in Iran. Patulin was detected in all samples at concentrations ranging from <10 to 2559 µg/kg. Mean patulin concentration was 620 µg/kg and 91.4% of the samples had levels higher than 50 µg/kg. Estimated daily intake (EDI) of patulin for adults and children considering the mean concentration of patulin obtained in this study (620 µg/kg) were higher than the provisional maximum tolerable daily intake (PMTDI) of 0.4 µg/kg bw/day for patulin that has been established by the Joint FAO/WHO Expert Committee on Food Additives. This indicated the need for stricter control and improvement in processing techniques to reduce the incidence of patulin in apple leather.

Evaluation of metal pollution in fish and water collected from Gorgan coast of the Caspian Sea, Iran.

In this study, concentrations of zinc, chromium, cadmium and lead were determined in water and three species of fish sampled from 10 selected stations along Gorgan coast using atomic absorption spectrophotometery, summer 2009. Mean lead levels in water and fish samples (119.50 ± 22.24 µg/L and 113.80 ± 33.11 µg/kg) were significantly higher than that of cadmium and chromium (p < 0.05). Cyprinus carpio had highest metals content than Mugila auratus and Rutilus frisikutum. The evaluated metals values in water collected from Gomishan wetland (Pb, Cd, Cr and Zn values are 145.31 ± 35.32, 120.46 ± 11.44, 96.47 ± 6.05 and 82.02 ± 34.37 µg/L, respectively) were higher than the other sampling sites. The result is consistent with the findings accessed by evaluation of the metals in fish specimens. The metals concentrations in the fish and water samples were below the recommended limits. But, elevating levels of metals in water and fish made a serious concern about ecosystem and food chain contamination.

Genomic copy number alterations in clear cell renal carcinoma: associations with case characteristics and mechanisms of VHL gene inactivation.

Array comparative genomic hybridization was used to identify copy number alterations in clear cell renal cell carcinoma (ccRCC) patient tumors to identify associations with patient/clinical characteristics. Of 763 ccRCC patients, 412 (54%) provided frozen biopsies. Clones were analyzed for significant copy number differences, adjusting for multiple comparisons and covariates in multivariate analyses. Frequent alterations included losses on: 3p (92.2%), 14q (46.8%), 8p (38.1%), 4q (35.4%), 9p (32.3%), 9q (31.8%), 6q (30.8%), 3q (29.4%), 10q (25.7%), 13q (24.5%), 1p (23.5%) and gains on 5q (60.2%), 7q (39.6%), 7p (30.6%), 5p (26.5%), 20q (25.5%), 12q (24.8%), 12p (22.8%). Stage and grade were associated with 1p, 9p, 9q, 13q and 14q loss and 12q gain. Males had more alterations compared with females, independent of stage and grade. Significant differences in the number/types of alterations were observed by family cancer history, age at diagnosis and smoking status. Von Hippel-Lindau (VHL) gene inactivation was associated with 3p loss (P

Occupational exposure to dusts and risk of renal cell carcinoma.

BACKGROUND: Occupational exposures to dusts have generally been examined in relation to cancers of the respiratory system and have rarely been examined in relation to other cancers, such as renal cell carcinoma (RCC). Although previous epidemiological studies, though few, have shown certain dusts, such as asbestos, to increase renal cancer risk, the potential for other occupational dust exposures to cause kidney damage and/or cancer may exist. We investigated whether asbestos, as well as 20 other occupational dust exposures, were associated with RCC risk in a large European, multi-center, hospital-based renal case-control study. METHODS: General occupational histories and job-specific questionnaires were reviewed by occupational hygienists for subject-specific information. Odds ratios (ORs) and 95% confidence intervals (95% CIs) between RCC risk and exposures were calculated using unconditional logistic regression. RESULTS: Among participants ever exposed to dusts, significant associations were observed for glass fibres (OR: 2.1; 95% CI: 1.1-3.9), mineral wool fibres (OR: 2.5; 95% CI: 1.2-5.1), and brick dust (OR: 1.5; 95% CI: 1.0-2.4). Significant trends were also observed with exposure duration and cumulative exposure. No association between RCC risk and asbestos exposure was observed. CONCLUSION: Results suggest that increased RCC risk may be associated with occupational exposure to specific types of dusts. Additional studies are needed to replicate and extend findings.

Family history of cancer and renal cell cancer risk in Caucasians and African Americans.

BACKGROUND: The association between renal cell carcinoma (RCC) risk and family history of cancer has not been examined with an adequate number of African Americans (AAs). METHODS: In a population-based case-control study, unconditional logistic regression was used to calculate the association between RCC risk and a family history of cancer among 1217 RCC cases and 1235 controls. RESULTS: Increased RCC risk was shown for subjects with at least one first-degree relative with kidney cancer (odds ratio=2.29; 95% confidence interval=1.31-4.00). No differences in risk were observed when analyses were stratified by race. For Caucasians, excess risk was observed among those reporting a sibling with kidney cancer, whereas for AAs, increased risk occurred among subjects reporting either a sibling or parent affected with the disease. A family history of non-renal cancers, and those related to smoking or to the von Hippel-Lindau syndrome, revealed no association with RCC risk. CONCLUSION: The RCC risk associated with a family history of kidney cancer is similar among Caucasians and AAs.

Vitamin d pathway genes, diet, and risk of renal cell carcinoma.

Mediated by binding to the high-affinity vitamin D receptor (VDR), vitamin D forms a heterodimer complex with the retinoid-X-receptor (RXR). Variation in both genes has been shown to modify renal cell carcinoma (RCC) risk. Therefore, we investigated whether VDR and RXRA polymorphisms modify associations between RCC risk and frequency of dietary intake of vitamin D and calcium rich foods, and occupational ultraviolet exposure among 777 RCC case and 1035 controls from Central and Eastern Europe. A positive association was observed in this population between increasing dietary intake frequency of yogurt, while an inverse association was observed with egg intake frequency. RXRA polymorphisms, located 3' of the coding sequence, modified associations between specific vitamin D rich foods and RCC risk, while RXRA polymorphisms, located in introns 1 and 4, modified associations with specific calcium rich foods. Results suggest that variants in the RXRA gene modified the associations observed between RCC risk and calcium and vitamin D intake.

Occupation and renal cell cancer in Central and Eastern Europe.

OBJECTIVE: Central and Eastern Europe has among the highest rates of renal cell cancer worldwide. Few studies have been conducted in these areas to investigate the possible role of occupational exposures in renal cell cancer aetiology. The purpose of this study was to examine the association of renal cell cancer with employment in specific occupations and industries. METHODS: From 1999 to 2003, we conducted a hospital-based case-control study in seven areas of the Czech Republic, Poland, Romania and Russia. A detailed occupational history was collected from renal cell cancer cases and controls, together with information on potential confounders. Odds ratios (ORs) and 95% CI of cancer risk were calculated for having ever been employed in selected jobs and industries, with follow-up analyses examining duration of employment. RESULTS: A total of 992 histologically confirmed incident renal cell cancer cases and 1459 controls were included in the analysis. An increased risk of renal cell cancer was observed for workers in agricultural labour and animal husbandry (OR 1.43; 95% CI 1.05 to 1.93), particularly among women employed as general farm workers (OR 2.73; 95% CI 1.05 to 7.13). Risk gradients for agricultural work increased with longer employment. An overall increased risk of renal cell cancer was seen among architects and engineers (OR 1.89; 95% CI 1.35 to 2.65), and mechanical engineers (OR 1.71; 95% CI 1.03 to 2.84). CONCLUSIONS: Our data suggest an association between renal cell cancer and agricultural work, particularly among female workers.

Toxic effects of cobalt chloride on hematological factors of common carp (Cyprinus carpio).

In this study, we investigate the toxic effects of cobalt chloride on some hematological factors of the carp Cyprinus carpio, such as white blood cell count, red blood cell count, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. At first, LC50 of cobalt in C. carpio was measured during 96 h after exposure. Also, physicochemical parameters of water including pH, dissolved oxygen, viscosity, temperature, and conductivity were monitored, continuously. The results showed that LC50 values of cobalt in C. carpio were 327 and 328 mg/L in two replicates, respectively. Then, the changes in some hematological factors in the five treatment groups placed under concentration of 100, 200, 300, 400, and 500 mg/L cobalt were compared with the control group. Based on hematological tests conducted in this research, exposure of carp to 500- and 300-mg/L concentrations of cobalt in 48 h showed significant difference (p<0.05) in white blood cell count. The concentration of 500 mg/L cobalt in 24 h showed a significant difference in the amount of hemoglobin, number of red blood cells, and hematocrit level as compared with the control group. The concentration of 100 mg/L cobalt in 48 h did not show a significant difference in comparison with the control group (p>0.05). Also, the concentration of 500 mg/L cobalt in 24 h showed a significant difference in the amount of mean corpuscular volume and mean corpuscular hemoglobin as compared with the control group and other treatments. Also, the percentage of mean corpuscular hemoglobin concentration in a concentration of 200 mg/L cobalt in 24 h showed a significant difference as compared with the control group and other treatments.

Renal cell carcinoma, occupational pesticide exposure and modification by glutathione S-transferase polymorphisms.

This study investigated associations between occupational pesticide exposure and renal cell carcinoma (RCC) risk. To follow-up on a previous report by Buzio et al., we also considered whether this association could be modified by glutathione S-transferase M1 and T1 (GSTM1 and GSTT1) genotypes. About 1097 RCC cases and 1476 controls from Central and Eastern Europe were interviewed to collect data on lifetime occupational histories. Occupational information for jobs held for at least 12 months duration was coded for pesticide exposures and assessed for frequency and intensity of exposure. GSTM1 and GSTT1 gene deletions were analyzed using TaqMan assays. A significant increase in RCC risk was observed among subjects ever exposed to pesticides [odds ratio (OR): 1.60; 95% confidence interval (CI): 1.00-2.55]. After stratification by genotypes, increased risk was observed among exposed subjects with at least one GSTM1 active allele (OR: 4.00; 95% CI: 1.55-10.33) but not among exposed subjects with two GSTM1 inactive alleles compared with unexposed subjects with two inactive alleles (P-interaction: 0.04). Risk was highest among exposed subjects with both GSTM1 and GSTT1 active genotypes (OR: 6.47; 95% CI: 1.82-23.00; P-interaction: 0.02) compared with unexposed subjects with at least one GSTM1 or T1 inactive genotype. In the largest RCC case-control study with genotype information conducted to date, we observed that risk associated with pesticide exposure was exclusive to individuals with active GSTM1/T1 genotypes. These findings further support the hypothesis that glutathione S-transferase polymorphisms can modify RCC risk associated with occupational pesticide exposure.

Vitamin D receptor polymorphisms and renal cancer risk in Central and Eastern Europe.

Previous studies investigated the role of vitamin D intake and cancer risk. The kidney is a major organ for vitamin D metabolism, activity, and calcium homeostasis; therefore, it was hypothesized that dietary vitamin D intake and polymorphisms in the vitamin D receptor (VDR) gene may modify renal cell carcinoma (RCC) risk. Three common VDR gene polymorphisms (BsmI, FokI, TaqI) were evaluated among 925 RCC cases and 1192 controls enrolled in a hospital-based case-control study conducted in Central and Eastern Europe. Overall associations with RCC risk were not observed; however, subgroup analyses revealed associations after stratification by median age of diagnosis and family history of cancer. Among subjects over 60 yr, reduced risks were observed among carriers of the f alleles in the FokI single-nucleotide polymorphism (SNP) (odds ratio [OR] = 0.61 for Ff and OR = 0.74 for ff genotypes) compared to subjects with the FF genotype (P trend = 0.04; P interaction = 0.004). Subjects with the BB BsmI genotype and a positive family history of cancer had lower risk compared to subjects with the bb allele (OR = 0.60; 95% CI: 0.33-1.1; P trend = 0.05). Genotype associations with these subgroups were not modified when dietary sources of vitamin D or calcium were considered. Additional studies of genetic variation in the VDR gene are warranted.

Glutathione S-transferase polymorphisms, cruciferous vegetable intake and cancer risk in the Central and Eastern European Kidney Cancer Study.

High consumption of cruciferous vegetables has been associated with reduced kidney cancer risk in many studies. Isothiocyanates, thought to be responsible for the chemopreventive properties of this food group, are conjugated to glutathione by glutathione S-transferases (GSTs) before urinary excretion. Modification of this relationship by host genetic factors is unknown. We investigated cruciferous vegetable intake in 1097 cases and 1555 controls enrolled in a multicentric case-control study from the Czech Republic, Poland, Romania and Russia. To assess possible gene-diet interactions, genotyped cases (N = 925) and controls (N = 1247) for selected functional or non-synonymous polymorphisms including the GSTM1 deletion, GSTM3 3 bp deletion (IVS6 + 22-AGG) and V224I G>A substitution, GSTT1 deletion and the GSTP1 I105V A>G substitution. The odds ratio (OR) for low (less than once per month) versus high (at least once per week) intake of cruciferous vegetables was 1.29 [95% confidence interval (CI): 1.02-1.62; P-trend = 0.03]. When low intake of cruciferous vegetables (less than once per month) was stratified by GST genotype, higher kidney cancer risks were observed among individuals with the GSTT1 null (OR = 1.86; 95% CI: 1.07-3.23; P-interaction = 0.05) or with both GSTM1/T1 null genotypes (OR = 2.49; 95% CI: 1.08-5.77; P-interaction = 0.05). These data provide additional evidence for the role of cruciferous vegetables in cancer prevention among individuals with common, functional genetic polymorphisms.