Sex comparison of oxidative stress, mitochondrial dysfunction, and apoptosis triggers induced by single-dose Abamectin in albino rats.

Abamectin (AB) is widely used in agriculture and has been employed as an insecticide, nematicide, and livestock pest control agent. However, it may also pose a serious threat to mammals. The primary purpose of this research was to compare the sex variations between male and female rats during exposure and to assess the risk of toxicity of abamectin, which are still largely unknown. The twenty albino rats were divided randomly into four groups (n = 5): 1) the male control group; 2) the male treatment group treated with AB (1 mg/kg B.W.); 3) the female control group; and 4) the female treatment group treated with AB (1 mg/kg B.W.). AB administration caused a drop in body weight in females more than males with showing oxidative stress in both sexes of animals, as characterized by an increase in MDA content and a decrease in glutathione (GSH) content and superoxide dismutase (SOD) activity. Reported sex-specific effects suggested that females are more susceptible from males in brain tissues for alteration of antioxidant markers while females' liver and kidney tissues showed more level of lipid peroxidation than males. In addition, mitochondrial dysfunction was associated with a significant decrease in NADH dehydrogenase (Complex I) and a significant decrease in mitochondrial ATPase, which led to apoptosis and histopathological alterations in the targeted tissues, indicating that females are higher sensitive than males to these biological events. In brief, the results of this study led to female rats are generally more sensitive than male rats to neurobehavioral and hepatic complications associated with abamectin treatment. Further evaluation should be performed to determine the adverse outcome pathways involved and to determine the effects of sex on improving the risk assessment of abamectin in both sexes.

Neuroprotective effect of Withania somnifera leaves extract nanoemulsion against penconazole-induced neurotoxicity in albino rats via modulating TGF-ß1/Smad2 signaling pathway.

Penconazole (PEN) is a systemic triazole fungicide used to control various fungal diseases on grapes, stone fruits, cucurbits, and strawberries. Still, it leaves residues on treated crops after collection with many hazardous effects on population including neurotoxicity. Withania somnifera leaves extract (WSLE) is known for its memory and brain function enhancing ability. To evoke such action efficiently, WSLE bioactive metabolites are needed to cross the blood-brain barrier, that could limit the availability of such compounds to be localized within the brain. Therefore, in the present study, the association between PEN exposure and neurotoxicity was evaluated, and formulated WSLE nanoemulsion was investigated for improving the permeability of the plant extract across the blood-brain barrier. The rats were divided into five groups (n = 6). The control group was administered distilled water, group II was treated with W. somnifera leaves extract nanoemulsion (WSLE NE), group III received PEN, group IV received PEN and WSLE, and group V received PEN and WSLE NE. All rats were gavaged daily for 6 weeks. Characterization of compounds in WSLE using LC-MS/MS analysis was estimated. Neurobehavioral disorders were evaluated in all groups. Oxidative stress biomarkers, antioxidant enzyme activities, and inflammatory cytokines were measured in brain tissue. Furthermore, the gene expression patterns of GFAP, APP, vimentin, TGF-ß1, Smad2 and Bax were measured. Histopathological changes and immunohistochemical expression in the peripheral sciatic nerve and cerebral cortex were evaluated. A total of 91 compounds of different chemo-types were detected and identified in WSLE in both ionization modes. Our data showed behavioral impairment in the PEN-treated group, with significant elevation of oxidative stress biomarkers, proinflammatory cytokines, neuronal damage, and apoptosis. In contrast, the PEN-treated group with WSLE NE showed marked improvement in behavioral performance and histopathological alteration with a significant increase in antioxidant enzyme activity and anti-inflammatory cytokines compared to the group administered WSLE alone. The PEN-treated group with WSLE NE in turn significantly downregulated the expression levels of GFAP, APP, vimentin, TGF-ß1, Smad2 and Bax in brain tissue. In conclusion, WSLE NE markedly enhanced the permeability of plant extract constituents through the blood brain barrier to boost its neuroprotective effect against PEN-induced neurotoxicity.

Influence of extracellular matrix scaffolds on histological outcomes of regenerative endodontics in experimental animal models: a systematic review.

BACKGROUND: Decellularized extracellular matrix (dECM) from several tissue sources has been proposed as a promising alternative to conventional scaffolds used in regenerative endodontic procedures (REPs). This systematic review aimed to evaluate the histological outcomes of studies utilizing dECM-derived scaffolds for REPs and to analyse the contributing factors that might influence the nature of regenerated tissues. METHODS: The PRISMA 2020 guidelines were used. A search of articles published until April 2024 was conducted in Google Scholar, Scopus, PubMed and Web of Science databases. Additional records were manually searched in major endodontic journals. Original articles including histological results of dECM in REPs and in-vivo studies were included while reviews, in-vitro studies and clinical trials were excluded. The quality assessment of the included studies was analysed using the ARRIVE guidelines. Risk of Bias assessment was done using the (SYRCLE) risk of bias tool. RESULTS: Out of the 387 studies obtained, 17 studies were included for analysis. In most studies, when used as scaffolds with or without exogenous cells, dECM showed the potential to enhance angiogenesis, dentinogenesis and to regenerate pulp-like and dentin-like tissues. However, the included studies showed heterogeneity of decellularization methods, animal models, scaffold source, form and delivery, as well as high risk of bias and average quality of evidence. DISCUSSION: Decellularized ECM-derived scaffolds could offer a potential off-the-shelf scaffold for dentin-pulp regeneration in REPs. However, due to the methodological heterogeneity and the average quality of the studies included in this review, the overall effectiveness of decellularized ECM-derived scaffolds is still unclear. More standardized preclinical research is needed as well as well-constructed clinical trials to prove the efficacy of these scaffolds for clinical translation. OTHER: The protocol was registered in PROSPERO database #CRD42023433026. This review was funded by the Science, Technology and Innovation Funding Authority (STDF) under grant number (44426).

Correlation between pulp sensibility and magnetic resonance signal intensity following regenerative endodontic procedures in mature necrotic teeth- a retrospective cohort study.

BACKGROUND: With increasing studies being published on regenerative endodontic procedures (REPs) as a treatment modality for mature necrotic teeth, the assessment of outcomes following regenerative endodontic procedures has become more challenging and the demand for a better understanding of the regenerated tissues following this treatment is rising. The study aimed to correlate cold, electric pulp testing (EPT), and magnetic resonance imaging (MRI) signal intensity (SI) in mature necrotic teeth treated with regenerative endodontic procedures. METHODOLOGY: This retrospective cohort study included eighteen adult patients who experienced tooth necrosis in mature maxillary anterior teeth recruited from the outpatient clinic, Conservative Dentistry Department, Faculty of Dentistry, Alexandria University, Alexandria, Egypt from July 2017 until December 2018 with 12 months of follow-up. regenerative endodontic procedures via blood clot were performed. The canals were instrumented by ProTaper Next (PTN) files until final sizes X3 or X5. Biodentine was used as cervical plug material. Pre and post-operative clinical follow-up was done where the patients' responses to cold and electric pulp testing were given a scoring system and were compared to the normal contralateral tooth. Pre and post-operative magnetic resonance imaging signal intensity of both the involved tooth and its contralateral at the middle and the apical thirds of the root canals were assessed after 3, 6, and 12 months. Data was analyzed using the ANOVA, Friedman and Bonferroni tests. Significance was set at a p-value < 0.05. RESULTS: All 18 teeth scored a baseline score of "2" for cold and electric pulp testing. There was a significant difference between scores of the cold test at baseline and 12-month follow-up (p < 0.001). There was a significant difference between scores of the electric pulp testing of baseline and 12-month follow-up (p < 0.001). There was a moderately significant indirect (inverse) correlation between magnetic resonance imaging signal intensity and cold test in both the middle and apical thirds at 12 months. No significant correlations were detected between magnetic resonance imaging signal intensity and electric pulp testingat any of the time intervals (p > 0.05). CONCLUSION: Magnetic resonance imaging is a successful non-invasive method to assess outcomes of regenerative endodontic procedures and correlating it with another reliable method of assessing pulpal responses, cold test, could validate these outcomes. CLINICAL TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov (ID: NCT03804450).

Optimizing cyclosporine A dose post allogeneic hematopoietic stem cell transplantation in paediatric cancer patients.

BACKGROUND/OBJECTIVES: Cyclosporine A (CSA) dosing has been complicated by considerable intra-patient and inter-patient variability in pharmacokinetics, which is affected by different factors. We aimed to assess the various factors that might affect the CSA dose and its plasma level. PATIENTS AND METHODS: This retrospective study included paediatric cancer patients who underwent allogeneic hematopoietic stem cell transplant at the Children's Cancer Hospital Egypt 57357 from matched related donors with CSA as graft versus host disease prophylaxis. The CSA initial dose was 1.5 mg/kg IV Q12H. Then, it was titrated according to the level and drug toxicity. Cyclosporine A trough levels were assessed two to three times per week using the Emit 2000 cyclosporine-specific assay. Moreover, factors that may affect cyclosporine levels, such as age, sex, weight and the antifungal used, were analyzed to determine their effect on CSA plasma levels. RESULTS: There were 119 patients included in the study. The median age was 10 years; and 43% of them used voriconazole as a prophylactic antifungal. The multivariate analysis revealed that female patients, those >9 years or on voriconazole reached the target level at low initial CSA doses. A higher probability (93%) of reaching the desired plasma level with doses 1.5 mg/kg IV Q12H was observed among patients >9 years, and on voriconazole. While those who were ≤9 years and not on voriconazole required doses >1.5 mg/kg IV Q12H, with an 89% probability of reaching the desired level. CONCLUSION: This study suggests that the initial CSA dose should consider the patient's age and the antifungal used. Patients >9 years and/or on voriconazole may require lower initial CSA doses and could start with 1.5 mg/kg IV Q12H.

Neuroprotective effect of piracetam-loaded magnetic chitosan nanoparticles against thiacloprid-induced neurotoxicity in albino rats.

Thiacloprid (TH) is a neurotoxic agricultural insecticide and potential food contaminant. The purpose of this study was to investigate the relationship between TH exposure and memory dysfunction in rats, as well as the potential protective effect of piracetam and piracetam-loaded magnetic chitosan nanoparticles (PMC NPs). Rats were divided into five equal groups (six rats/group). The control group received saline. Group II was treated with PMC NPs at a dose level of 200 mg/kg body weight (Bwt); Group III was treated with 1/10 LD50 of TH (65 mg/kg Bwt); Group IV was treated with TH (65 mg/kg Bwt) and piracetam (200 mg/kg Bwt); Group V was co-treated with TH (65 mg/kg Bwt) and PMC NPs (200 mg/kg Bwt). All animal groups were dosed daily for 6 weeks by oral gavage. Footprint analysis, hanging wire test, open field test, and Y-maze test were employed to assess behavioral deficits. Animals were euthanized, and brain tissues were analyzed for oxidative stress biomarkers, proinflammatory cytokines, and gene expression levels of glial fibrillary acidic protein (GFAP), amyloid-beta precursor protein (APP), B-cell lymphoma 2 (Bcl-2), and caspase-3. Brain and sciatic nerve tissues were used for the evaluation of histopathological changes and immunohistochemical expression of tau protein and nuclear factor kappa B (NF-κB), respectively. The results revealed that TH-treated rats suffered from oxidative damage and inflammatory effect on the central and peripheral nerves. The administration of PMC NPs considerably protected against TH-induced neuronal damage, increased antioxidant enzyme activity, decreased inflammatory markers, and improved behavioral performance than the group treated with piracetam. The neuroprotective effect of PMC NPs was mediated through the inhibition of GFAP, APP, caspase-3, Tau, and NF-κB gene expression with induction of Bcl-2 expression. In conclusion, TH could induce oxidative stress, inflammatory and neurobehavior impairment in rats. However, PMC NPs administration markedly mitigated TH-induced brain toxicity, possibly via oxidative and inflammatory modulation rather than using piracetam alone.

SumStatsRehab: an efficient algorithm for GWAS summary statistics assessment and restoration.

BACKGROUND: Generating polygenic risk scores for diseases and complex traits requires high quality GWAS summary statistic files. Often, these files can be difficult to acquire either as a result of unshared or incomplete data. To date, bioinformatics tools which focus on restoring missing columns containing identification and association data are limited, which has the potential to increase the number of usable GWAS summary statistics files. RESULTS: SumStatsRehab was able to restore rsID, effect/other alleles, chromosome, base pair position, effect allele frequencies, beta, standard error, and p-values to a better extent than any other currently available tool, with minimal loss. CONCLUSIONS: SumStatsRehab offers a unique tool utilizing both functional programming and pipeline-like architecture, allowing users to generate accurate data restorations for incomplete summary statistics files. This in turn, increases the number of usable GWAS summary statistics files, which may be invaluable for less researched health traits.

Outcomes of allogenic hematopoietic cell transplantation for childhood chronic myeloid leukemia: Single-center experience.

BACKGROUND/OBJECTIVES: Despite the apparent efficacy and favorable toxicity profile of TKIs, allogeneic SCT remains the only curative treatment for CML especially in younger patients, but TRM should be considered. We evaluated the clinical outcomes of pediatric CML patients who had SCT in our center. METHODS: This retrospective study included children with CML, who received an allogeneic SCT at Children Cancer Hospital Egypt, 57357, from 2007 to 2017. All patients received myeloablative conditioning chemotherapy containing busulfan/cyclophosphamide followed by stem cell infusion from MRD. RESULTS: From 121 patients diagnosed with CML, 43 had available MRD and subjected to HSCT while 78 patients continued TKI therapy. The median time to transplant from diagnosis was 13 months. At initial diagnosis, there were 39 patients in CP and 4 had blastic crises. Bone marrow harvest was the stem cell source in 32 patients, while 11 cases received mobilized peripheral blood stem cells with average stem cell dose of 4.45 × 106 /kg. The probabilities of overall survival and event-free survival at 5 years were 97.4% and 79.8%, respectively. TRM at 100 days and TRM at 1-year post-transplant were 0%. The incidence of chronic GVHD was significantly higher in peripheral blood than bone marrow stem cell source (P = .004). CONCLUSION: Considering the excellent survival rates and very low TRM, HSCT is still a valid option for pediatric patients with newly diagnosed CML with best using marrow stem cell source to avoid a significant risk of cGVHD and its related complications.

Low-level laser therapy affects dentinogenesis and angiogenesis of in vitro 3D cultures of dentin-pulp complex.

To investigate the effects of gallium-aluminum-arsenide (GaAlAs) diode laser low-level laser therapy (LLLT) on angiogenesis and dentinogenesis of the dentin-pulp complex in a human tooth slice-based in vitro model. Forty tooth slices were prepared from 31 human third molars. Slices were cultured at 37 °C, 5% CO2, and 95% humidity and randomly assigned to one of the following groups: group I: no laser treatment, group II: 660-nm diode laser; energy density = 1 J/cm2, group III: 660-nm diode laser; energy density = 3 J/cm2, group IV: 810-nm diode laser; energy density = 1 J/cm2 and group V: 810-nm diode laser; energy density = 3 J/cm2. LLLT was applied on the third and fifth days of culture. After 7 days, tissues were retrieved for real-time RT-PCR analysis to investigate the expression of VEGF, VEGFR2, DSPP, DMP-1, and BSP in respect to controls. Lower energy density (1 J/cm2) with the 660 nm wavelength showed a statistically significant up-regulation of both angiogenic (VEGF: 15.3-folds and VEGFR2: 3.8-folds) and odontogenic genes (DSPP: 6.1-folds, DMP-1: 3-fold, and BSP: 6.7-folds). While the higher energy density (3 J/cm2) with the 810 nm wavelength resulted in statistically significant up-regulation of odontogenic genes (DSPP: 2.5-folds, DMP-1: 17.7-folds, and BSP: 7.1-folds), however, the angiogenic genes had variable results where VEGF was up-regulated while VEGFR2 was down-regulated. Low-level laser therapy could be a useful tool to promote angiogenesis and dentinogenesis of the dentin-pulp complex when parameters are optimized.

Non-traumatic Simultaneous Bilateral Femur Neck Fracture in a Young Female Unraveling End-Stage Renal Disease: A Case Report and Literature Review.

Introduction: Spontaneous femur neck fracture is rare, especially when they occur bilaterally. Renal osteodystrophy is among the causes of these fractures that should be kept in mind. We report a case of a young female who presented with bilateral hip pain and was found to have bilateral femur neck fracture due to renal osteodystrophy. This was the first presentation of an undiagnosed end-stage kidney disease. This case report aims to highlight the importance of investigating the cause of these rare fractures in young patients and discuss available surgical options. Case Report: A 19-year-old female presented complaining of bilateral hip pain. On physical examination, there was tenderness on palpation of both thighs. Her workup was significant for anemia, a high level of creatinine, hypocalcemia, elevated alkaline phosphatase, and parathyroid hormone. A pelvis radiograph showed bilateral femur neck fracture. Considering her very young age, the metabolic derangements she had and to avoid exposing her to a major surgery, we treated her fractures by fixation using three cannulated screws on each side. We aimed to report this case as it is an unusual presentation of a previously undetected stage 5 chronic kidney disease (CKD) in a very young patient. Conclusion: Renal osteodystrophy due to CKD can present with spontaneous bilateral femur neck fracture. Physicians should have a high index of suspicion for this condition not to miss a chronic disease with multiple sequelae. Furthermore, these fractures carry a high risk of complications and mortality, so they should be addressed promptly.

SUBACUTE COMBINED DEGENERATION OF THE SPINAL CORD SECONDARY TO NITROUS OXIDE-INDUCED B12 DEFICIENCY.

A previously healthy adolescent male was admitted with paraesthesia of his arms and legs. He admitted to daily recreational nitrous oxide use for the previous 3-4 months. He was found to have severe vitamin B12 deficiency, while magnetic resonance imaging of his spine showed T2 hyperintensity within the dorsal columns. This was suggestive of subacute combined degeneration of the spinal cord. He was treated with intramuscular injections of hydroxocobalamin and showed moderate improvement 1 month post-discharge. LEARNING POINTS: It is important to take a full history of illicit drug use, especially in young patients presenting with unusual symptoms.In cases of suspected nitrous oxide-induced neurological dysfunction with normal vitamin B12 levels, serum levels of methylmalonic acid and homocysteine can be measured to aid diagnosis.Prompt treatment of nitrous oxide-induced subacute combined degeneration of the spinal cord with B12 injections and discontinuation of nitrous oxide use allow for a gradual recovery, although in some cases patients may be left with residual symptoms.

Protective action of polysaccharides from Laurencia papillose (Rhodophyta) against imidacloprid induced genotoxicity and oxidative stress in male albino rats.

Imidacloprid (IMI), the main component of neonicotinoid insecticides, promotes oxidative stress and genotoxicity in mammals. The aim of this experiment is to assess oxidative stress in liver cells and genotoxicity of erythrocytes for rats exposed to sub-lethal doses of IMI and the protective effects for Rhodophyta as antioxidant material versus imidacloprid. A total of 30 adult male albino rats (average body weight, 190-200 g) were divided into six groups (n=5) as follows: group 1 served as the control, group 2 received 200 mg/kg red algae, group 3 received 45 mg/kg IMI (high-dose group), group 4 received 22.5 mg/kg IMI (low-dose group), group 5 received 200 mg/kg red algae +45 mg/kg IMI, and group 6 received 200 mg/kg red algae +22.5 mg/kg IMI. After 28 d of treatment, the antioxidant activity of the crude extract of red algae was assessed in terms of free radical scavenging activity and found to be higher in TCA (75.57%) followed by DPPH (50.08%) at concentration 100 µg extract and a significant increase in lipid peroxidation and reductions in glutathione were observed in liver cells were intoxicated with high and low doses of IMI. Moreover decreases in catalase and glutathione peroxidase parameters in same previous groups which indicated oxidative stress. In addition significant increases in micronucleus frequency (MN) in the bone marrow of the rats as a genotoxicity marker which indicated DNA damage in erythrocytes cells with alterations in the histopathology of liver cells were also noted such as necrosis, inflammatory cells, infiltration, and necrobiotic changes. Whereas Rhodophyta succeeded in alleviation the oxidative damage and genotoxicity induced by the insecticide. In conclusion, IMI demonstrates hazardous effects, such as alterations in antioxidant status and mutagenicity of erythrocytes and polysaccharides from Rhodophyta has good antioxidant activity in vivo model systems against imidacloprid.

The Reproductive Injury and Oxidative Testicular Toxicity Induced by Chlorpyrifos Can Be Restored by Zinc in Male Rats.

The current study aimed to evaluate the harmful effect of chlorpyrifos (CPF) on the reproductive functions and fertility in male rats and to assess the protective role of zinc (Zn) in improving the adverse effects of CPF on male fertility. Sixty mature male rats were divided into four groups: Group 1: The control group was orally administered with the corresponding dose of corn oil. Group 2 animals received chlorpyrifos (1 mg/kg, oral). Group 3 rats received oral zinc (25 mg/kg) daily. Group 4 animals received oral zinc treatment (25 mg/kg). CPF caused a significant decrease in the body and reproductive organs' weights, sperm count, sperm motility percent, serum testosterone, FSH, and LH. The CPF-treated group showed a significant increase in dead sperm percent and sperm abnormalities. CPF induced a significant internucleosomal DNA fragmentation and marked histological alterations in the testes of treated male rats. Conversely, co-treatment with Zn improved the reproductive organs weights, sperm characteristics, internucleosomal DNA fragmentation, and histological alterations of the testes. In conclusion, CPF triggered significant detrimental effects on male reproductive organs and functions and the co-treatment with zinc partly alleviate the injurious effects of CPF on male fertility.

Ameliorative effects of the phytochemicals in dates (Phoenix dactylifera) against the toxicological changes induced by fipronil in male albino rats.

Scientific evidence has shown that fipronil induces oxidative stress and genotoxicity. Our study aimed to evaluate the potential oxidation in redox parameters and DNA, as well as determine the protective effect of date extract of increasing resistance to cellular damage. 30 Male albino rats were divided into six groups ( n = 5): 1) control group; 2) treatment group with date extract (1 g/kg B.W.); 3) treatment group with 1/20 LD50 of fipronil; 4) treatment group with 1/40 LD50 of fipronil; 5) treatment group with 1/20 LD50 of fipronil + 1 g/kg date extract; and 6) treatment group with 1/40 LD50 of fipronil + 1 g/kg dates extract. Date extract showed a high content of phenolic compounds and antioxidant properties. Fipronil increased 8-hydroxy-2-deoxyguanosine levels and lipid peroxidation by malondialdehyde but decreased the total antioxidant capacity in plasma. Moreover, glutathione, catalase, and superoxide dismutase levels in the liver and kidney decreased, along with histopathological abnormalities. Additionally, tail moment parameters of liver DNA and micronucleus frequencies in the bone marrow increased. This study showed that fipronil-induced various health hazards in vivo, whereas date extract alleviated the said toxicological effects. However, date extract failed to reduce genotoxicity.

A comparative analysis of current phasing and imputation software.

Whole-genome data has become significantly more accessible over the last two decades. This can largely be attributed to both reduced sequencing costs and imputation models which make it possible to obtain nearly whole-genome data from less expensive genotyping methods, such as microarray chips. Although there are many different approaches to imputation, the Hidden Markov Model (HMM) remains the most widely used. In this study, we compared the latest versions of the most popular HMM-based tools for phasing and imputation: Beagle5.4, Eagle2.4.1, Shapeit4, Impute5 and Minimac4. We benchmarked them on four input datasets with three levels of chip density. We assessed each imputation software on the basis of accuracy, speed and memory usage, and showed how the choice of imputation accuracy metric can result in different interpretations. The highest average concordance rate was achieved by Beagle5.4, followed by Impute5 and Minimac4, using a reference-based approach during phasing and the highest density chip. IQS and R2 metrics revealed that Impute5 and Minimac4 obtained better results for low frequency markers, while Beagle5.4 remained more accurate for common markers (MAF>5%). Computational load as measured by run time was lower for Beagle5.4 than Minimac4 and Impute5, while Minimac4 utilized the least memory of the imputation tools we compared. ShapeIT4, used the least memory of the phasing tools examined with genotype chip data, while Eagle2.4.1 used the least memory phasing WGS data. Finally, we determined the combination of phasing software, imputation software, and reference panel, best suited for different situations and analysis needs and created an automated pipeline that provides a way for users to create customized chips designed to optimize their imputation results.

Effect of different irrigation protocols for applications in regenerative endodontics on mechanical properties of root dentin.

The objective of this study was to evaluate the effect of different concentrations of NaOCl with and without passive ultrasonic irrigation (PUI) on mechanical properties of human dentin for applications in regenerative endodontics (RE). Sixty single-rooted teeth were sectioned into 2 halves (n = 120). Dentin bars were produced from one half for flexural strength and the other half was used for microhardness. Specimens were randomly assigned into 10 groups: G1 and G2 (control): distilled water for 30 and 60 min, respectively; G3: 1.5%NaOCl for 30 min; G4:1.5%NaOCl for 60 min; G5: 1.5%NaOCl + PUI for 30 min; G6: 1.5%NaOCl + PUI for 60 min; G7: 5.25%NaOCl for 30 min; G8: 5.25%NaOCl for 60 min; G9: 5.25%NaOCl + PUI for 30 min; G10: 5.25%NaOCl + PUI for 60 min. An increase in NaOCl concentration showed highly significant reduction in mechanical properties. There was no significant difference between 1.5% NaOCl and control group except for specimens treated with PUI for 60 min. NaOCl in concentrations recommended for RE did not have a significant effect on mechanical properties of dentin. However, PUI with increased irrigation time might have an effect even with low NaOCl concentration.

The protective effects of Terminalia laxiflora extract on hepato-nephrotoxicity induced by fipronil in male rats.

The present study was led to investigate the defensive role of Terminalia laxiflora extract (TLE) on fipronil (FPN) induced hepatotoxicity and nephrotoxicity in male rats. Rats were administered with TLE (100 mg/kg) against the renal toxicity and hepatotoxicity induced by administration of FPN (10.5 mg/kg) for 30 days. At the end of the experimental period, the serum, liver, and kidneys were harvested and assessed for subsequent analysis. FPN administration to rats resulted in a significant elevation of serum transaminases, urea, and creatinine. Also, FPN-treated groups exhibited a marked reduction in total protein and albumin levels. Compared with the control group, the level of malondialdehyde (MDA) was elevated in groups treated with FPN, whereas superoxide dismutase (SOD), catalase (CAT) activities, and glutathione levels were distinctly reduced in this group. Significant increases in genomic DNA fragmentation and the expression level of the caspase-3 gene were also recorded. The biochemical result was supported by histopathological findings. Co-administration of TLE along with FPN significantly diminished the liver and kidney function tests decreased the level of lipid peroxidation, and enhanced all the antioxidant enzymes, while also diminishing the expression of caspase-3 and DNA laddering, indicating amelioration of DNA damage. These results indicate that TLE plays a vital role in diminishing FPN-induced hepatotoxicity and nephrotoxicity.

Calculation of Thermodynamic Properties of Bound Water Molecules.

Water molecules in the binding site of a protein significantly influence protein structure and function, for example, by mediating protein-ligand interactions or in form of desolvation as driving force for ligand binding. The knowledge about location and thermodynamic properties of water molecules in the binding site is crucial to the understanding of protein function. This chapter describes the method of calculating the location and thermodynamic properties of bound water molecules from molecular dynamics (MD) simulation trajectories. Thermodynamic profiles of water molecules can be calculated either with or without the presence of a bound ligand based on the scientific problem. The location and thermodynamic profile of hydration sites mediating the protein-ligand interactions is important for understanding protein-ligand binding. The protein desolvation free energy can be estimated for any ligand by summation of the hydration site free energies of the displaced hydration sites. The WATsite program with an easy-to-use graphical user interface (GUI) based on PyMOL was developed for those calculations and is discussed in this chapter. The WATsite program and its PyMOL plugin are available free of charge from http://people.pharmacy.purdue.edu/~mlill/software/watsite/version3.shtml .