Association of heavy metals and trace elements in carcinoma urinary bladder: A case-controlled study.

Introduction: Abnormal levels of heavy metals (HM) and trace elements (TE) affect body metabolism and can induce carcinogenesis. This study aims to evaluate the role of HM and TE in carcinoma urinary bladder (CAUB). Methods: Patients with biopsy-proven CAUB (n = 100) were taken as the study group, while age-and sex-matched healthy volunteers were taken as control (n = 100). Blood and urine samples were compared for Arsenic (As), Copper (Cu), Manganese (Mn), Selenium (Se), Cadmium (Cd), Lead (Pb), and Mercury (Hg) levels. Serum glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and lipid peroxidation (LPO) levels were assessed to know the redox status between the two groups. Results: A significantly higher blood level of As, Mn, and Pb was observed in CAUB cases as compared to controls. Blood Se level was significantly lower in CAUB patients. On comparing urinary levels, CAUB patients had a higher As, Mn, and Pb levels compared to controls. Further, 68% and 59% of patients had their blood and urinary HM and TE levels above the permitted level, respectively. CAUB cases also had a lower GSH-Px (113.5 ± 44.7 vs. 163.9 ± 120.5, P = 0.0002), lower SOD levels (11.35 ± 5.6 vs. 13.75 ± 3.9, P = 0.008), and a higher LPO levels (15.5 ± 14.7 vs. 11.18 ± 11.2, P = 0.02) in the serum. Conclusions: A significantly higher concentration of As, Mn, and Pb was noted in the blood and urine of CAUB patients compared to controls. CAUB cases also had lower serum GSH-Px and SOD levels with a concomitant increased serum LPO assay suggesting underlying oxidative stress.

Synergistic action of lactoferrin and its derived functional fragments as a promising therapeutic agent in combating mucormycosis.

Aim: Currently, we have limited armamentarium of antifungal agents against Mucorales. There is an urgent need to discover novel antifungal agents that are effective, safe and affordable. Materials & methods: In this study, the anti-Mucorale action of native lactoferrin (LF) and its functional fragments CLF, RR6 and LFcin against three common Mucorale species are reported. The synergistic action of LF with antifungal agents like amphotericin B, isavuconazole and posaconazole was analyzed using checkerboard technique. Results: All the three mucor species showed inhibition when treated with fragments. The checkerboard assay confirmed that native LF showed the best synergistic action against Mucorales in combination with Amphotericin B. Conclusion: These results highlight the potential therapeutic value of native LF against Mucorales.

Black fungus, or 'mucormycosis', is a dangerous fungal infection. Normally, it affects people with a weakened immune system. It is only treatable when diagnosed early. It spreads by breathing the fungus in, eating contaminated food or direct contact with an infected wound. There are not many medicines that can treat this type of fungus, so it is important to find new ones. In this study, we tested a natural protein called lactoferrin and some of its building blocks, called peptides, to see if they could stop the fungus from growing. Lactoferrin and its peptides could stop the fungus from growing, especially when used with a medicine called amphotericin B. This means that lactoferrin could potentially be a helpful treatment for this fungal infection.

Impact of heavy metals, oxidative stress, expression of VHL, and antioxidant genes in the pathogenesis of renal cell carcinoma.

INTRODUCTION: Heavy metals exposure is a known carcinogen in humans. The impact of heavy metals in the pathogenesis of renal cell carcinoma (RCC) is unclear with scant available literature. Though previous studies have evaluated the role of heavy metals in RCC, majority of those studies have evaluated either single or few heavy metals in urine. None of the prior studies have evaluated an extensive panel of heavy metals in blood, urine, and tissue in the same patient along with the serum oxidation status and gene expression to establish a cause-and-effect relationship. This study aims to evaluate the role of extensive panel of heavy metals, oxidative status, and gene expression in RCC. METHODOLOGY: This observational study recruited RCC patients who visited our tertiary care centre from 2019 to 2023. Age matched healthy volunteers were included as controls. Blood, urine, and tissue samples (tumor and adjacent normal tissue) were collected from RCC patients. Levels of arsenic, copper, manganese, selenium, cadmium, lead, and mercury were measured in each of the samples. Serum oxidative stress markers like glutathione peroxidase (GPX), lipid peroxidase (LPO), and superoxide dismutase (SOD) were measured. Genetic expression of Von Hippel-Lindau (VHL), catalase (CAT), superoxide dismutase (SOD1), and glutathione peroxidase (GPX1) genes were measured in the tumor tissue and adjacent normal parenchyma. RESULTS: 150 cases and 150 age matched controls were enrolled. RCC cases had elevated blood levels of arsenic (P = 0.02), copper (P = 0.01), manganese (P < 0.001), cadmium (P < 0.001), lead (P < 0.001), and mercury (P = 0.02) compared to controls. Urine levels of selenium (P = 0.02), mercury (P = 0.03), and lead (P = 0.04) were higher in cases. Reduced levels of serum GPx (P = 0.02) and higher levels of LPO (P = 0.04) were detected in cases. Elevated levels of copper (P = 0.03), manganese (P = 0.002), selenium (P < 0.001), and cadmium (P < 0.001) were found in the adjacent normal parenchyma compared to the tumor tissue. VHL (P = 0.03) and oxidative stress gene expressions were lower in the tumour tissue compared to the normal parenchyma. CONCLUSION: Elevated levels of heavy metals in the blood, urine, tissue, and imbalance in the serum oxidative status along with downregulated tumor suppressor VHL and oxidative stress genes in the tumor tissues likely explain the carcinogenic role of heavy metals in RCC. Environmental exposure is the main cause of heavy metal toxicity. Mitigating the environmental exposure of heavy metals and thereby their toxicity might play a role in cancer prevention.

Association of heavy metals and trace elements in renal cell carcinoma: A case-controlled study.

PURPOSE: Trace elements and/or heavy metals are important for various biological activities. However, excess amount of these elements is associated with a variety of diseases, including cancer. We aimed to analyse the alterations of trace elements levels in renal cell carcinoma (RCC) patients. MATERIALS AND METHODS: In this observational study, patients with biopsy proven RCC were taken as study group while age- and sex-matched healthy volunteers were taken as control. Blood and urine samples were compared for Arsenic (As), Copper (Cu), Manganese (Mn), Selenium (Se), Cadmium (Cd), Lead (Pb) and Mercury (Hg) levels measured by inductively coupled plasma mass-spectroscopy. Serum glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) antioxidant enzymes and lipid peroxidation (LPO) levels were assessed to know the redox status between 2 groups. RESULTS: A total of 76 RCC cases and 64 controls were recruited in the study. A significantly higher concentration of As, Cu, Mn, Cd, Pb and Hg were observed in the blood of RCC patients as compared to controls. However, blood Se level was significantly lower in RCC patients. In 33 (43.4%) patients, one or more heavy metals were higher in the blood above their permitted level as compared to 10 (15.6%) subjects in control group. RCC patients had a higher urinary Mn and Se levels compared to controls. A significantly lower GSH-Px (182.08 ± 132.91 vs. 236.95 ± 132.94, P = 0.04) and a higher LPO levels (26.02 ± 20.79 vs. 14.06 ± 8.44, P = 0.003) were noted in RCC patients than controls. SOD levels were comparable between two groups. CONCLUSIONS: A significantly altered heavy metals concentration is noted in the blood and urine in RCC patients as compared to healthy controls. An associated lower levels of GSH-Px antioxidant enzyme and increased LPO in RCC patients signifies an imbalance in the redox status.