Lag Plot: A Novel Method to Determine Viable Bacterial Cell Number via a Single OD Measurement.

Bactericidal activity is a valuable parameter which is considered and measured for antimicrobial compounds. The available standard protocol to evaluate bactericidal activity is based on the direct colony count. Colony counting requires serial dilution, plating, overnight incubation, and direct counting, which is time-and labor-intensive. In regard to eliminate direct plate count, novel techniques were developed based on the real-time growth monitoring which can come with some limitations and drawbacks. These drawbacks encourage us to develop a novel technique with simple procedure to determine viable bacterial cell count. In this procedure, real-time growth monitoring is not required. In fact, after an incubation time, the number of viable bacteria can be determined with a single OD measurement and through an equation. In this regard, four standard bacterial strains, including Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), and Bacillus subtilis (ATCC 23857), were cultured with descending inoculum densities (1.5 × 107 to 15 CFU/mL) and growth curves were drawn. As expected, growth in the samples with lower inoculum densities recorded with longer lag phase. Also, a direct relation was observed between the recorded turbidities and initial cell counts. A logarithmic curve (lag plot) was obtained by plotting the OD, after 12-18 h incubation, against initial cell counts. In all examined strains, R2 was calculated in the range of 0.96-0.99 which is acceptable value for coefficient of determination. Equation corresponding to the lag plot was obtained and called lag equation. This equation is applicable to calculate the number of viable cells in unknown samples simply by inoculation, incubation, and single OD measurement. Developed technique can be introduced as a simple substitution for labor- and time-intensive direct colony counting.

Molecular signaling directing neural plate border formation.

During embryonic development, the vertebrate embryonic epiblast is divided into two parts including neural and superficial ectoderm. The neural plate border (NPB) is a narrow transitional area which locates between these parts and contains multipotent progenitor cells. Despite its small size, the cellular heterogeneity in this region produces specific differentiated cells. Signaling pathways, transcription factors, and the expression/repression of certain genes are directly involved in these differentiation processes. Different factors such as the Wnt signaling cascade, fibroblast growth factor (FGF), bone morphogenetic protein (BMP) signaling, and Notch, which are involved in various stages of the growth, proliferation, and differentiation of embryonic cells, are also involved in the determination and differentiation of neural plate border stem cells. Therefore, it is essential to consider the interactions and temporospatial coordination related to cells, tissues, and adjacent structures. This review examines our present knowledge of the formation of the neural plate border and emphasizes the requirement for interaction between different signaling pathways, including the BMP and Wnt cascades, the expression of its special target genes and their regulations, and the precise tissue crosstalk which defines the neural crest fate in the ectoderm at the early human embryonic stages.

Protective effects of limb remote ischemic per-conditioning on the heart injury induced by renal ischemic-reperfusion through the interaction of the apelin with the RAS/iNOS pathway.

Introduction: Remote ischemic conditioning upregulates endogenous protective pathways in response to ischemia-reperfusion injury. This study tested the hypothesis that limb remote ischemic per- conditioning (RIPerC) exerts cardioprotective effects via the renin-angiotensin system (RAS)/inducible nitric oxide synthase (iNOS)/apelin pathway. Methods: Renal ischemia-reperfusion injury (I/R) was induced by bilateral occlusion of the renal pedicles for 60 minutes, followed by 24 hours of reperfusion; sham-operated rats served as controls. RIPerC was induced by four cycles (5 minutes) of limb ischemia-reperfusion along with bilateral renal ischemia. The functional disturbance was evaluated by renal (BUN and creatinine) and cardiac (troponin I and lactate dehydrogenase) injury biomarkers. Results: Renal I/R injury increased renal and cardiac injury biomarkers that were reduced in the RIPerC group. Histopathological findings of the kidney and heart were also suggestive of amelioration injury-induced changes in the RIPerC group. Assessment of cardiac electrophysiology revealed that RIPerC ameliorated the decline in P wave duration without significantly affecting other cardiac electrophysiological changes. Further, renal I/R injury increased the plasma (322.40±34.01 IU/L), renal (8.27±1.10 mIU/mg of Protein), and cardiac (68.28±10.28 mIU/mg of protein) angiotensin-converting enzyme (ACE) activities in association with elevations in the plasma and urine nitrite (25.47±2.01 & 16.62±3.05 µmol/L) and nitrate (15.47±1.33 & 5.01±0.96 µmol/L) levels; these changes were reversed by RIPerC. Further, renal ischemia-reperfusion injury significantly (P=0.047) decreased the renal (but not cardiac) apelin mRNA expression, while renal and cardiac ACE2 (P<0.05) and iNOS (P=0.043) mRNA expressions were significantly increased compared to the sham group; these effects were largely reversed by RIPerC. Conclusion: Our results indicated that RIPerC protects the heart against renal ischemia- reperfusion injury, likely via interaction of the apelin with the RAS/iNOS pathway.

Effects of conditioned media derived from human Wharton's jelly mesenchymal stem cells on diabetic nephropathy and hepatopathy via modulating TGF-ß and apelin signaling pathways in male rats.

BACKGROUND: Diabetic nephropathy and hepatopathy are health problems described by specific renal and hepatic structure and function disturbances. The protective effects of the stem cell secretome have been shown in several kidney and liver diseases. The current study aims to evaluate the capability of conditioned media derived from human Wharton's jelly mesenchymal stem cells (hWJ-MSCs-CM) to alleviate diabetic complications. METHODS: Twenty Sprague Dawley rats were made diabetic through injection of STZ (60 mg/kg, i.p.). At week 8, diabetic rats were divided into two groups: treated [DM + hWJ-MSCs-CM (500 µl/rat for three weeks, i.p.)] and not treated (DM). At the 11th week, three groups (control, DM, and DM + hWJ-MSCs-CM) were kept in metabolic cages, and urine was collected for 24 h. The serum samples were maintained for measuring fasting blood glucose (FBG) and kidney and liver functional analysis. The left kidney and liver parts were kept at -80 °C to assess apelin and transforming growth factor-beta (TGF-ß) expression. The right kidney, pancreas, and liver parts were used for histopathologic evaluation. RESULTS: DM was detected by higher FBG, microalbuminuria, increased albumin/creatinine ratio, and pancreas, renal, and hepatic structural disturbances. Diabetic hepatopathy was determined by increasing liver enzymes and decreasing total bilirubin. The TGF-ß gene expression was significantly upregulated in the diabetic kidney and liver tissues. Apelin gene expression was significantly downregulated in the diabetic liver tissue but did not change in kidney tissue. Administration of hWJ-MSCs-CM improved renal and hepatic functional and structural disturbances. Moreover, CM therapy significantly decreased TGF-ß expression and enhanced apelin expression in the kidney and liver tissues. CONCLUSION: Human WJ-MSCs-CM may have protective effects on diabetic renal and hepatic complications. These effects may happen through the regulation of TGF-ß and apelin signaling pathways.

Association of Oxidative Stress with Kidney Injury in a Hyperandrogenemic Female Rat Model.

Background: Polycystic ovary syndrome (PCOS) is the most common reproductive dysfunction in premenopausal women. PCOS is associated with oxidative stress (OS), which is the main risk factor for renal diseases. This study aimed to investigate the mechanisms responsible for renal injury in a hyperandrogenemic female rat model. Methods: This study was conducted from December 2019 to September 2021 at Shiraz Nephro-Urology Research Centre, Shiraz University of Medical Sciences (Shiraz, Iran). Thirty female Sprague-Dawley rats were randomly divided into three groups (n=10), namely control, sham, and dehydroepiandrosterone (DHEA). Plasma total testosterone, plasma creatinine (Cr), and blood urea nitrogen (BUN) levels were measured. In addition, total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), and histopathological changes in the ovaries and kidneys were determined. Data were analyzed using the GraphPad Prism software, and P<0.05 was considered statistically significant. Results: Plasma total testosterone levels increased by nine-fold in DHEA-treated rats compared to controls (P=0.0001). Administration of DHEA increased Cr and BUN levels and caused severe renal tubular cell injury. In addition, plasma and tissue (kidney and ovary) TAC levels decreased significantly, but TOS levels and OSI values were significantly increased (P=0.019). Significant damage to both glomerular and tubular parts of the kidney and ovarian follicular structure was observed in the DHEA group. Conclusion: Hyperandrogenemia caused systemic abnormalities through OS-related mechanisms and damaged renal and ovarian tissues. DHEA treatment in rat models is recommended to study the mechanisms that mediate PCOS-associated renal injury.

Coronavirus Disease 2019 and Hypertension: How Anti-hypertensive Drugs Affect COVID-19 Medications and Vice Versa.

BACKGROUND: As a medical problem, hypertension is one of the most common disorders in cardiovascular disease. High blood pressure has been identified as one of the most familiar risk factors for the ongoing COVID-19 pandemic. We planned to explore the possible interactions between anti-hypertensive agents and drugs targeting SARS-CoV-2 with broad investigations of these medications' mechanism of action and adverse effects. METHODS: Two co-authors searched the electronic databases (PubMed, Scopus, and Google Scholar) to collect papers relevant to the subject. The keywords searched were angiotensin-converting enzyme inhibitors (ACEI), angiotensin-II receptor blockers (ARBs), sympatholytic drugs (alpha-1 blockers, beta-blockers), vasodilators (calcium channel blockers, nitrates, and hydralazine), diuretics, chloroquine, hydroxychloroquine, lopinavir/ritonavir, remdesivir, favipiravir, interferons, azithromycin, anti-cytokine agents, glucocorticoids, anticoagulant agents, nitric oxide, and epoprostenol. RESULTS: QT prolongation, arrhythmia, hypokalemia, hypertriglyceridemia are the most dangerous adverse effects in the patients on COVID-19 medications and anti-hypertensive drugs. CONCLUSION: This review emphasized the importance of the potential interaction between drugs used against COVID-19 and anti-hypertensive agents. Therefore, caution must be exercised when these medications are being used simultaneously.

Acute lung injury induced by acute uremia and renal ischemic-reperfusion injury: The role of toll-like receptors 2 and 4, and oxidative stress.

Objectives: Acute lung injury (ALI) is a common complication of distant organ dysfunction induced by acute kidney injury (AKI). Toll-like receptors (TLRs) have a critical role in progression of AKI. The main goal of this study was to determine whether lung gene expression of TLR2 and TLR4 change by ischemic (renal bilateral ischemic-reperfusion; BIR) and uremic (bilateral nephrectomy; BNX) AKI. Materials and Methods: Forty male rats were divided into five groups. Two kidneys were removed in BNX, and renal pedicles were clamped in BIR for 45 min. The kidney and lung tissue, and blood samples were collected and saved after 24 hr in all groups. The bone marrow mesenchymal stem cells were immediately injected (1×106,IV) into the treated groups. The expression of TLR2, TLR4, TNF-α, and VEGF was checked by RT-PCR in the tissue samples. MDA level, SOD, and CAT activity were evaluated in the tissue samples. Results: Structural disturbance of ALI was detected as alveolar hemorrhage and vascular congestion after BIR and BNX. Lung TLR2 and TLR4 but not TNF-α and VEGF up-regulated in these groups. Oxidative stress stabilized after the BIR and BNX in the tissue samples. BMSCs reduce the expression of TLR2 and TLR4 and oxidative stress in the treated groups. Conclusion: Acutely gathering systemic mediators after renal ischemic or uremic injury induce ALI through overexpression of TLR2 and TLR4 and oxidative stress. Therefore, the Lung protective effect of BMSCs may be related to modulation of TLR2 and TLR4 and oxidative stress in the kidney and lung tissue.

Assessment of the relationship between 25-hydroxyvitamin D and albuminuria in type 2 diabetes mellitus.

BACKGROUND: Diabetic nephropathy occurs in about one-third of diabetic patients. This health problem is characterized by increased urinary albumin excretion, leading to decreased glomerular filtration rate and renal failure. In this regard, previous investigations have revealed the possibility of a relationship between vitamin D deficiency and diabetic nephropathy. The present study assessed the relationship between vitamin D deficiency and albuminuria in patients with type 2 diabetes. METHODS: This study was conducted with 200 participants with type 2 diabetes mellitus from December 2019 to January 2021. The patients' 25-hydroxyvitamin D (25OHD) serum level and urinary albumin-to-creatinine ratio (UACR) were measured concurrently. Afterward, the subjects were divided into three groups based on their albuminuria level. Finally, 25OHD serum level and other clinical characteristics were compared among these albuminuria groups, and the relation between albuminuria level and 25OHD was analyzed. RESULTS: The prevalence of vitamin D deficiency in macroalbuminuric patients (UACR≥300 mg/g) was 61.8%, and in microalbuminuric (30 ≤ UACR< 300 mg/g) and normoalbuminuric groups (UACR< 30 mg/g) was 33.3% and 24%, respectively. Further analysis revealed a significant negative relationship between 25OHD and albuminuria(r = - 0.257, p-value< 0.001). According to ROC curve analysis, a 25OHD level ≤ 21 ng/ml was considered an optimal cut-off point value for having macroalbuminuria in diabetic patients. CONCLUSIONS: The current study evaluates the relation between vitamin D deficiency and the prevalence of albuminuria in the setting of diabetes. Overall, the prevalence of macroalbuminuria increased when the 25OHD serum level was less than 20 ng/ml.

The effect of influenza virus on the metabolism of peripheral blood mononuclear cells with a metabolomics approach.

Respiratory viruses have led to many deaths and hospitalizations per year in the world. The influenza virus is one of the most important respiratory viruses. Recently, metabolic studies in viral infections have been widely studied by scientists. Metabolomics states the metabolites present in a living organism under certain conditions. In this study, peripheral blood mononuclear cells were spinoculated using a virus produced by the Madin-Darby canine kidney cell culture system, and cells were harvested following spinoculation by the influenza virus. Isolation of peripheral blood mononuclear cells was performed by Ficoll-Paque density gradient centrifugation. Metabolites were extracted using organic and water approaches. Metabolic profiling was performed by a nontargeted  technique using liquid chromatography with tandem mass spectrometry. Multivariate analysis methods were used to determine the main variables. the metabolic pathways involved were determined using databases. Results of the present study showed changes in biosynthesis pathways such as lipids, polyamines, catecholamines, and vitamins. Findings also showed that it is possible to explain the process of inflammation caused by the influenza virus by studying the metabolism of immune cells.

Proposed Pathway Linking Respiratory Infections with Depression.

Depression is one of the most important causes of disability and loss of useful life of people around the world. Acute respiratory infection caused a large number of severe illnesses and deaths of the world and most of these due to viral infections, which is estimated more than 80% of respiratory infections. Detection of viruses by immune pathogen recognition receptors activates the intracellular signaling cascade and eventually cause produces interferons. Inflammatory process begins with secretion of interferons and the expression of interferon-stimulated genes. One of the most important of these genes is indoleamine-pyrrole 2,3-dioxygenase (IDO), which plays a major role in tryptophan catabolism. IDO is an intracellular monomeric enzyme that is also responsible for breaking down and consuming tryptophan in the Kynurenine pathway. Increased inflammation has been linked to decrease tryptophan concentrations and increase kynurenine levels. We tried to explain the role of inflammation by viral respiratory infections in causing depression.

Cultural Adaption and Psychometric Analysis of Family APGAR Scale in Iranian Older People.

BACKGROUND: Family function is a necessary factor that influences older people's health. The Family APGAR has been widely used to study family functions. However, there has been no Persian version of this instrument to assess family function in older people. The aim of this study was to determine the psychometric properties of the Persian version of the Family APGAR Scale to evaluate the perception of family functions. METHODS: The "forward-backward" procedure was applied to translate the scale from English into Persian. The translated version was checked in terms of validity and reliability, with a sample of 281 older people selected from retirement centers. The factor structure of the scale was also tested using a confirmatory factor analysis. To test reliability, internal consistency and test-retest analyses were performed. RESULTS: The results of the confirmatory factor analysis indicated a good structural model. Criterion-related validity was strongly supported by the pattern of association between the APGAR Scale and the social support survey. Cronbach's α of the scale was 0.88 and test-retest reliability ranged from 0.96 to 0.98, indicating a good range of reliability. CONCLUSION: The findings of this study suggest that the Iranian version of the Family APGAR is a valid and reliable scale to evaluate family functions in health intervention programs.

Guillain-Barré/Miller Fisher overlap syndrome in a patient after coronavirus disease-2019 infection: a case report.

BACKGROUND: Beyond the typical respiratory symptoms associated with novel coronavirus, increasing evidence has been reported of the neurological manifestations affecting both the central and peripheral nervous systems. CASE PRESENTATION: We observed a 30-year-old Persian woman developing acute motor sensory axonal neuropathy, a variant of Guillain-Barré syndrome that overlaps Miller Fisher syndrome, 30 days after confirmed coronavirus disease-2019 infection. Our case highlight the rare occurrence of Guillain-Barré syndrome overlapping with Miller Fisher during the coronavirus disease-2019 pandemic. These neurologic manifestations may occur because of an aberrant immune response to coronavirus disease-2019. CONCLUSIONS: The early recognition of Guillain-Barré syndrome symptoms is critical, given the associated severe motor disabilities that may seriously limit the quality of life of these patients. We may still have much to learn about the co-occurrence of Guillain-Barré syndrome and Miller Fisher to improve the quality of life of these patients requiring an accurate evaluation by neurologists.

SARS-CoV-2 in brief: from virus to prevention.

The recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ahighly transmissible virus with a likely animal origin, has posed major and unprecedentedchallenges to millions of lives across the affected nations of the world. This outbreak firstoccurred in China, and despite massive regional and global attempts shortly thereafter, itspread to other countries and caused millions of deaths worldwide. This review presents keyinformation about the characteristics of SARS-CoV-2 and its associated disease (namely,coronavirus disease 2019) and briefly discusses the origin of the virus. Herein, we also brieflysummarize the strategies used against viral spread and transmission.

Involvement of oxidative stress and toll-like receptor-4 signaling pathways in gentamicin-induced nephrotoxicity in male Sprague Dawley rats.

Gentamicin (GM) is an antibiotic belonging to an aminoglycoside family that might induce nephrotoxicity in human and animal models via oxidative stress. Toll-like receptors (TLRs) are part of innate immune systems that participate in inflammatory responses. In this regard, we investigated the effect of GM on kidney functional and structural parameters, enzymatic antioxidant levels, and mRNA expression of TLR4 and IL6 in the rat kidney. Adult male Sprague Dawley rats were randomly divided into two groups (n = 10): Control and Gentamicin (100 mg/kg, i.p.). After ten days of GM administration, a blood sample was taken, and the kidneys were removed. The serum levels of creatinine (Cr) and blood urea nitrogen (BUN) were measured. Furthermore, the right kidney was preserved in formalin 10% for hematoxylin and eosin (H&E) staining, and the left kidney was kept at -80 °C for molecular and oxidative indexes analysis. Administration of GM caused tubular damages and functional disturbance. So that, Cr and BUN values in the GM group were higher than Control group. Furthermore, molecular findings showed upregulation of TLR4 and IL-6 mRNA expression in renal tissue of the GM-received group. In this study, superoxide dismutase (SOD) activity was slightly increased as a compensatory mechanism in response to elevated malondialdehyde (MDA) levels in the GM-treated group. On the other hand, the activity of catalase (CAT) and glutathione peroxidase (GPx) were significantly declined. Our results demonstrated that oxidative stress and subsequent TLR4 upregulation signaling pathways are involved in GM-induced nephrotoxicity.

Therapeutic effects of bone marrow mesenchymal stem cells via modulation of TLR2 and TLR4 on renal ischemia-reperfusion injury in male Sprague-Dawley rats.

Introduction: Acute kidney injury (AKI) induced by renal ischemia-reperfusion (I/R) injury is a pro-inflammatory process that activates toll-like receptors (TLRs). Stem cell therapy holds a great promise for kidney repair. Therefore, we investigated the immunomodulatory role of bone marrow stromal cells (BMSCs) on TLR2 and TLR4 expression in AKI in male Sprague-Dawley rats. Methods: BMSCs were isolated from the bone marrow of male rats, cultured in DMEM, and characterized using appropriate markers before transplantation. Renal I/R was induced by 45 minutes bilateral ischemia followed by 24 hours of reperfusion. Rats received intraperitoneal injections of BMSCs (1.5 × 106 cells, i.p, per rat) immediately after termination of renal ischemia. Serum samples were collected pre-and post-stem cells injection for assessment of blood urea nitrogen (BUN) and creatinine (Cr) levels. The kidneys were harvested after 24 hours of reperfusion for structural and molecular analysis. Results: Renal I/R caused severe tissue injuries and increased the level of BUN (166.5 ± 12.9 vs. 18.25 ± 1.75) and Cr (3.7 ± 0.22 vs. 0.87 ± 0.06) compared to the sham group. In addition, mRNA expression of TLR2 and TLR4 elevated in the renal I/R group. Administration of BMSCs improved the functional and structural state of the kidney induced by I/R and down-regulated TLR2 and TLR4 gene expression. Conclusion: The results showed a highly significant renoprotection by BMSCs that indicates their therapeutic potential in I/R injures. These effects are most likely associated with the TLR2/4 signaling pathway via modulation of the inflammatory response cascades.

Potential Mechanisms of the SARS-CoV-2-induced AKI Progression to CKD: A Forward-Looking Perspective.

Coronavirus disease 2019 (COVID­19) was identified in December 2019 and is still expanding in most parts of the world. The wide variety of affected organs is likely based upon the shared expression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) important entry-receptor angiotensin-converting enzyme 2 (ACE2). For this reason, the broad distribution of ACE2 receptors in different tissues plays a crucial role in the multi-organ dysfunction and fatality due to COVID-19. Because of the high prevalence of acute kidney injury (AKI) in patients with COVID-19, we review the molecular understanding into viral infection mechanisms and implications for AKI. Furthermore, mechanisms of the AKI to chronic kidney disease (CKD) progression, such as the relative contribution of immune cell reaction, fibroblasts activation, endothelial dysfunction, and subsequent hypoxia may contribute to the association of AKI with worse outcomes during this virus pandemic. We highlight the state of the knowledge on SARS-CoV-2-dependent mechanisms for AKI and list the potential management choices for the prevention of AKI aggravation and the impending possibility of CKD. Finally, we intend to provide a much better understanding of why Coronavirus induces AKI and its subsequent progression to CKD in the coming years and further discuss the acute and long-term renal consequences.

Nanomicellar curcuminoids attenuates renal ischemia/reperfusion injury in rat through prevention of apoptosis and downregulation of MAPKs pathways.

Renal ischemia/reperfusion (I/R) injury is considered as a main problem in clinical practice. Curcuminoids, the active constituents of turmeric, seem to have potential renoprotective effects. However, the poor bioavailability of curcuminoids restricts their therapeutic effects. In the present study, the effect of nanomicellar curcuminoids (NC) treatment on renal function, histology, total antioxidant capacity (TAC), total oxidative stress (TOS), caspase-3 level as well as mitogen activated protein kinases (MAPKs: JNK, p38 and ERK) phosphorylation were evaluated following renal I/R. Adult male Sprague-Dawley rats were administered NC at the dose of 25 mg/kg 1 h before renal ischemia induction. The animals were subjected to bilateral renal ischemia for 60 min and reperfusion for 24 h. Subsequently, blood urea nitrogen (BUN), creatinine (Cr), renal histopathology, TAC, TOS, and oxidative stress index, cleaved caspase-3 level, Bax and MAPKs signaling were evaluated. The results indicated that NC pretreatment at the dose of 25 mg/kg significantly improved renal function as well as histolopatholgical damages. Moreover, NC reduced the level of renal oxidative stress, cleaved caspase-3 and Bax (as the proapoptotic proteins) and suppressed the activated Jun N-terminal Kinase (JNK), p38 and extracellular receptor kinase (ERK) signaling induced by renal I/R. The findings of the current study indicate that NC might prevent the injury induced by renal I/R through suppression of oxidative stress, apoptosis and MAPKs pathways.

A binuclear iron(III) complex of 5,5'-dimethyl-2,2'-bipyridine as cytotoxic agent.

The binuclear iron(III) complex (1), namely, {[Fe(5,5'-dmbpy)2(OH2)]2(µ-O)}(NO3)4 with a distorted octahedral coordination, formed by four nitrogen and two oxygen atoms, was previously reported by our team. In this study the DNA-binding and cytotoxicity evaluation for target complex were studied. The results indicated strong cytotoxicity activity against A549 cells comparable to cisplatin values. The binding interaction between complex 1 and FS-DNA was investigated by UV-Vis, fluorescence spectroscopy, and gel electrophoresis at physiological pH (7.2). The DNA binding investigation has shown groove binding interactions with complex 1, therefore the hydrogen binding plays an important role in the interaction of DNA with complex 1. The calculated thermodynamic parameters (ΔH°, ΔS° and ΔG°) show that hydrogen bonding and Vander-Waals forces have an important function in Fe(III) complex-DNA interaction. Moreover, DNA cleavage was studied using agarose gel electrophoresis. Viscosity measurements illustrated that relative viscosity of DNA was unchanged with the adding concentrations of Fe(III) complex. Molecular docking simulation results confirmed the spectroscopic and viscosity titration outcomes.

Role of vitamin D in oxidative stress modulation in end-stage renal disease patients: A double-blind randomized clinical trial.

INTRODUCTION: Oxidative stress is considered as important actor in uremia-associated morbidity and mortality in hemodialysis (HD) patients. We aimed to evaluate the role of vitamin D supplementation on oxidative stress parameters in this group. METHODS: This double-blind randomized clinical trial was conducted on HD patients who were randomly allocated into intervention (n = 40) or control groups (n = 38) for 10 weeks. Blood samples were taken before and at the end of the trial to measure serum 25-hydroxyvitamin D (25(OH)D), malondialdehyde (MDA), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD). Data were analyzed using SPSS, and P value <0.05 was considered to be statistically significant. FINDINGS: Out of the 78 patients with a mean age of 44.7 ± 13.0 years, 55.1% were men. At the commencement of the study, there was no difference with respect to serum 25(OH)D levels in our groups (P = 0.575), but during the study it was significantly elevated in the intervention group (18.1 ± 9.1 vs. 31.7 ± 12.9, P < 0.0001). Serum antioxidative enzymes activity (GPx, CAT, and SOD) had significantly increased after vitamin D supplementation in the intervention group (P < 0.05). Furthermore, MDA levels was significantly reduced only in the intervention group (31.7 ± 18.0 vs. 24.7 ± 7.7, P = 0.018). DISCUSSION: Regular consumption of vitamin D can increase the GPx, CAT, SOD, and reduce the MDA plasma levels in HD patients. Since no adverse effects of vitamin D supplementation was reported by the patients; hence, it can be prescribed for HD patients.

Toll-like receptor-2 mediates systemic inflammation in gentamicin-induced rat nephrotoxicity.

Gentamicin is an aminoglycoside antibiotic commonly administrated to patients with Gram-negative infections. Gentamicin induced nephrotoxicity by functional and structural impairment. Toll-like receptors (TLRs) as key mediators in the innate and adaptive immune system response involved in gentamicin-induced nephrotoxicity. The present study aimed to investigate the gene expression of TLR2 and pro-inflammatory cytokines in the renal tissues and buffy coat of the whole blood in gentamicin-treated rats. Twenty adult male Sprague Dawley rats weighing 180-200 were randomly divided into gentamicin (100 mg/kg, i.p) and control groups (n = 10). After 10 days, the serum creatinine (Cr) levels and blood urea nitrogen (BUN) were measured. The mRNA levels of TLR2, tumour necrosis factor (TNF)-α, interleukin (IL)-1ß, and monocyte chemoattractant peptide (MCP)-1 were investigated in the renal tissue and buffy coat by qRT-PCR. Kidney histological analysis performed by hematoxylin-eosin (H&E) staining. Functional disturbance is characterized by a significant increase in the serum levels of Cr and BUN in the gentamicin group. Renal tissue slides of the gentamicin group indicated severe glomerular and tubular damage including lobulation of the glomerular tuft, Bowman's space enlargement, acute tubular necrosis, and proximal tubular destruction. The mRNA levels of IL-1ß, TNF-α, MCP-1, and TLR2 increased in the buffy coat, but all of them except TLR2 decreased in the renal tissues in the gentamicin group compared with controls. Gentamicin administration induced relative systemic inflammation, which may be related to an increase in the mRNA levels of TLR2 results in gene expression of pro-inflammatory chemokines and cytokines including IL-1ß, TNF-α, and MCP-1 in immune cells.