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Background: The aim of this study is to investigate whether vitamin D, calcium, ferritin, and uric acids play a beneficial biomarker role in the prevention of colorectal cancer (CRC) risk., Methods: The case-control design was employed, including 650 CRC cases and 650 controls aged 35 to 70 years, comprising both men and women. The study encompasses sociodemographic data, clinical information, radiological diagnoses, and biochemical measurements., Results: Statistically significant differences were observed between CRC and controls in terms of age, diagnostic radiology, tomography, positron emission tomography/computed tomography (PET/CT), colonoscopy, CRC awareness, risk factors, age, genetics, exposure to chemicals, inadequate nutrition, smoking, hookah and alcohol use. Significant differences were also identified in intestinal inflammations, obesity, processed foods (P < 0.001), abdominal pain and cramps, diarrhea, constipation, blood in stool, bloating (gas), irritable bowel, nausea/vomiting, anemia, stress, fatigue, weakness, and weight loss. Regarding biochemical parameters, statistically significant differences were found between CRC and controls in terms of hemoglobin, glycated hemoglobin (HbA1c), fasting blood glucose (FBG), vitamin D, neutrophil level, red blood cell (RBC), white blood cell (WBC), platelet level, platelet count, hematocrit, potassium, sodium (Na), calcium, creatinine, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), bilirubin, uric acid, iron (Fe), ferritin, C-reactive protein (CRP), total protein, systolic blood pressure (SBP), and diastolic blood pressure (DBP) parameters (P < 0.001). Multivariate stepwise regression analysis was performed to find the best risk factors for the diagnosis of CRC as the dependent variable. As a result of the analysis, intestinal inflammation (P < 0.001), nausea/vomiting (P < 0.001), stomach pain (P = 0.003), hookah-smoking (P = 0.034), uric acid (P < 0.001), bilirubin (P < 0.001), cigarette smoke exposure (P = 0.033), processed food consumption (P = 0.002), calcium levels (P = 0.029), vitamin D deficiency (P < 0.001), and ferritin (P < 0.001) levels were identified as significant determinants for CRC., Conclusions: The current study demonstrated that vitamin D, calcium, ferritin, and uric acids play a beneficial biomarker role in reducing the risk of CRC prevention. The increase in CRC rates may be associated with lifestyle, environmental and hereditary factors, nutrition, alcohol consumption, hookah use, and cigarette smoking., Competing Interests: The author(s) declared no potential conflict of interest with respect to the research, authorship, and/or publication of this article., (Copyright 2024, Bener et al.)

A one-pot direct synthesis of xanthine and uric acid derivates is reported. This simple yet efficient methodology illustrates concurrent formation of two C–N bonds using CuBr2 as catalyst and one of those C–N bonds is formed by uracil C6–H bond activation. [ABSTRACT FROM AUTHOR]

Alterations in microbiota are known to affect kidney disease conditions. We have previously shown that germ-free conditions exacerbated adenine-induced kidney damage in mice; however, the mechanism by which this occurs has not been elucidated. To explore this mechanism, we examined the influence of germ-free conditions on purine metabolism and renal immune responses involved in the kidney damage. Germ-free mice showed higher expression levels of purine-metabolizing enzymes such as xanthine dehydrogenase, which converts adenine to a nephrotoxic byproduct 2,8-dihydroxyadenine (2,8-DHA). The germ-free mice also showed increased urinary excretion of allantoin, indicating enhanced purine metabolism. Metabolome analysis demonstrated marked differences in the purine metabolite levels in the feces of germ-free mice and mice with microbiota. Furthermore, unlike the germ-free condition, antibiotic treatment did not increase the expression of purine-metabolizing enzymes or exacerbate adenine-induced kidney damage. Considering renal immune responses, the germ-free mice displayed an absence of renal IL-17A expression. However, the adenine-induced kidney damage in wild-type mice was comparable to that in IL-17A-deficient mice, suggesting that IL-17A does not play a major role in the disease condition. Our results suggest that the enhanced host purine metabolism in the germ-free mice potentially promotes the conversion of the administered adenine into 2,8-DHA, resulting in exacerbated kidney damage. This further suggests a role of the microbiota in regulating host purine metabolism.

Background: Eosinophils recognize various stimuli, such as cytokines, chemokines, immunoglobulins, complement, and external pathogens, resulting in their accumulation in mucosal tissues and the progression of inflammation. Eosinophils are also involved in innate Th2-type immune responses mediated through endogenous danger signals, including IL-33, uric acid (UA), or ATP, in non-sensitized mice exposed to environmental allergens. However, the mechanism involved in eosinophil responses to these danger signals remains insufficiently understood. Methods: We examined migration, adhesion, superoxide production and degranulation of human eosinophils. Isolated eosinophils were incubated with monosodium urate (MSU) crystals and ATPγS, a non-hydrolysable ATP analogue. To determine the involvement of P2 or P2Y2 receptors in eosinophil responses to UA and ATP, eosinophils were preincubated with a pan-P2 receptor inhibitor, oxidized ATP (oATP), or anti-P2Y2 antibody before incubation with MSU crystals or ATPγS. Results: MSU crystals induced adhesion of eosinophils to recombinant human (rh)-ICAM-1 and induced production of superoxide. oATP abolished eosinophil responses to MSU crystals, suggesting involvement of endogenous ATP and its receptors. Furthermore, exogenous ATP, as ATPγS, induced migration of eosinophils through a model basement membrane, adhesion to rh-ICAM-1, superoxide generation, and degranulation of eosinophil-derived neurotoxin (EDN). oATP and anti-P2Y2 significantly reduced these eosinophil responses. Conclusions: ATP serves as an essential mediator of functional responses in human eosinophils. Eosinophil responses to ATP may be implicated in airway inflammation in patients with asthma.

The search for crystalluria and morphologic analysis of urinary crystals is of interest in the diagnostic evaluation and assessment of efficacy of therapeutic strategies in stone formers. In common calcium oxalate (CaOx) nephrolithiasis, identification of the monohydrate or dihydrate form of CaOx orients toward hyperoxaluria or hypercalciuria as the main lithogenic mechanism, respectively. An unusual high abundance of crystals exclusively made of CaOx monohydrate is highly suggestive of primary hyperoxaluria, the most severe of all types of renal stone diseases. The identification of crystal species such as struvite, cystine, 2,8-dihydroxyadenine, which are not found in normal urine, is indicative of specific pathological conditions, namely, infection stones and hereditary diseases such as cystinuria and dihydroxyadeninuria. Such diseases expose to progressive loss of renal function unless they are prevented by specific therapeutic measures. The presence of crystals made of drugs may entail the risk of kidney dysfunction because of crystallization of the drug or its metabolites. Serial determination of crystalluria, which reflects the activity of stone disease and its response to therapeutic measures, is of major interest in the follow-up of patients suffering from nephrolithiasis. It should be more largely used in clinical practice in most stone formers, still more for the surveillance of patients affected by severe, hereditary renal stone diseases such as primary hyperoxaluria, cystinuria, and dihydroxyadeninuria, where determination of the global crystal volume allows assessing the efficacy of therapeutic measures and optimizing the medical management of the patients. [ABSTRACT FROM AUTHOR]

Abstract: A novel nanocomposites film of conducting polymers including single-walled carbon nanotubes (SWCNTs), polypyrrole (PPy) and gold nanoparticles (AuNPs) modified electrode has been applied in voltammetric sensors to detect epinephrine (EP) sensitively when ascorbic acids (AA) and uric acids (UA) exist. The nanocomposites film of conducting polymers which show an excellent electrocatalystic activity for the oxidation of EP and UA was characterized by scanning electron microscopy (SEM) and electrochemical methods. The catalytic peak currents obtained from differential pulse voltammetry (DPV) increased linearly with increasing EP concentrations in the range of 4.0×10−9–1.0×10−7 M with a detection limit of 2.0×10−9 M (S/N=3), respectively. The results showed that the nanocomposites of conducting polymers can selectively determine EP in the coexistence of a large amount of UA and AA. In addition, the sensor exhibited excellent sensitivity, selectivity and stability. The PPy/AuNPs/SWCNTs nanocomposites film can also be satisfactorily used for detecting EP in epinephrine hydrochloride injection when contain AA and UA, which also shows good recovery for determination of EP in some biological fluids. [Copyright &y& Elsevier]

Fasting during Ramadan is mandatory for all healthy Muslim adults. During the fasting month, many physiological and biochemical changes occur that may be due to alterations in eating and sleeping patterns. A concern for Muslim multiple sclerosis (MS) patients is whether prolonged fasting might have an unfavorable impact on the course of their disease. The aim of this prospective study was to determine the effects of prolonged intermittent fasting on the course of MS in a cohort of patients who reside in Isfahan, Iran. The cohort consisted of 40 adult MS patients who fasted during Ramadan and 40 MS patients who did not fast. Only patients with mild disability (expanded disability status scale (EDSS) score ≤3) were included. All patients were followed for 6 months after Ramadan to assess their EDSS score changes and to record the number of clinical relapses. At the end of the study, no significant changes in EDSS or the frequency of clinical relapses were detected between the 2 groups (p > 0.05). Fasting had no short-term unfavorable effects on the disease course in MS patients with mild disability. However, larger multi-center prospective studies of longer duration are needed to validate the results of this study. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Alterations in microbiota are known to affect kidney disease conditions. We have previously shown that germ-free conditions exacerbated adenine-induced kidney damage in mice; however, the mechanism by which this occurs has not been elucidated. To explore this mechanism, we examined the influence of germ-free conditions on purine metabolism and renal immune responses involved in the kidney damage. Germ-free mice showed higher expression levels of purine-metabolizing enzymes such as xanthine dehydrogenase, which converts adenine to a nephrotoxic byproduct 2,8-dihydroxyadenine (2,8-DHA). The germ-free mice also showed increased urinary excretion of allantoin, indicating enhanced purine metabolism. Metabolome analysis demonstrated marked differences in the purine metabolite levels in the feces of germ-free mice and mice with microbiota. Furthermore, unlike the germ-free condition, antibiotic treatment did not increase the expression of purine-metabolizing enzymes or exacerbate adenine-induced kidney damage. Considering renal immune responses, the germ-free mice displayed an absence of renal IL-17A expression. However, the adenine-induced kidney damage in wild-type mice was comparable to that in IL-17A-deficient mice, suggesting that IL-17A does not play a major role in the disease condition. Our results suggest that the enhanced host purine metabolism in the germ-free mice potentially promotes the conversion of the administered adenine into 2,8-DHA, resulting in exacerbated kidney damage. This further suggests a role of the microbiota in regulating host purine metabolism. [ABSTRACT FROM AUTHOR]

Background Eosinophils recognize various stimuli, such as cytokines, chemokines, immunoglobulins, complement, and external pathogens, resulting in their accumulation in mucosal tissues and the progression of inflammation. Eosinophils are also involved in innate Th2-type immune responses mediated through endogenous danger signals, including IL-33, uric acid (UA), or ATP, in non-sensitized mice exposed to environmental allergens. However, the mechanism involved in eosinophil responses to these danger signals remains insufficiently understood. Methods We examined migration, adhesion, superoxide production and degranulation of human eosinophils. Isolated eosinophils were incubated with monosodium urate (MSU) crystals and ATPγS, a non-hydrolysable ATP analogue. To determine the involvement of P2 or P2Y 2 receptors in eosinophil responses to UA and ATP, eosinophils were preincubated with a pan-P2 receptor inhibitor, oxidized ATP (oATP), or anti-P2Y 2 antibody before incubation with MSU crystals or ATPγS. Results MSU crystals induced adhesion of eosinophils to recombinant human (rh)-ICAM-1 and induced production of superoxide. oATP abolished eosinophil responses to MSU crystals, suggesting involvement of endogenous ATP and its receptors. Furthermore, exogenous ATP, as ATPγS, induced migration of eosinophils through a model basement membrane, adhesion to rh-ICAM-1, superoxide generation, and degranulation of eosinophil-derived neurotoxin (EDN). oATP and anti-P2Y 2 significantly reduced these eosinophil responses. Conclusions ATP serves as an essential mediator of functional responses in human eosinophils. Eosinophil responses to ATP may be implicated in airway inflammation in patients with asthma. [ABSTRACT FROM AUTHOR]