Hesperidin Attenuates Hypothyroidism-Induced Lung Damage in Adult Albino Rats by Modulating Oxidative Stress, Nuclear Factor Kappa-B Pathway, Proliferating Cell Nuclear Antigen and Inflammatory Cytokines.

The occurrence of worsening pulmonary function has been connected to hypothyroidism (HPO). Hesperidin (HES) was suggested to have antioxidant, anti-proliferative, and anti-inflammatory potential. Our study's objective was to determine whether HES could reduce carbimazole (CBZ)-induced lung injury more effectively than Eltroxin (ELT) in adult male albino rats or not. At random, 32 rats were distributed into four groups: Group I: normal control, to induce HPO, the remaining three groups were given CBZ (20 mg/kg/day) dissolved in distilled water for 1 week. They were then split up into three groups. Group II: orally administered CBZ (20 mg/kg b.w in water/day), Group III: HES (200 mg/kg/day) dissolved in 1% carboxymethyl-cellulose + CBZ treated, and Group IV: ELT (0.045 mg/kg/day) dissolved in distilled water + CBZ treated. All treatments were delivered for 12 weeks. Blood was collected to assess thyroid-stimulating hormone (TSH) and thyroid hormones (THs). Lung injury was evaluated based on the pulmonary content of interleukin (IL)-35, IL-6, and tumor necrosis factor-alpha (TNF-α), along with the estimation of lipid peroxidation, catalase, glutathione levels, superoxide dismutase, heme oxygenase-1 (HO-1), and nuclear factor erythroid 2-related factor 2 (Nrf2). The histological, ultrastructural, and immunohistochemical study of nuclear factor Kappa-B (NF-κB) and inducible nitric oxide synthase (iNOS), together with estimating the proliferation of cells using Antigen Ki-67 in lung tissue were performed. HES and ELT primarily suppressed variable lung damage mechanisms by suppressing TSH, the NF-κB/TNF-α pathway, iNOS, lipid peroxidation, Ki-67, and inflammatory mediators. On the other hand, they improved THs, antioxidant parameters, and the Nrf2/HO-1 pathway. HES and ELT exhibited an ameliorative effect that was reflected in the histopathological, immunohistochemical, and ultrastructural results. These results indicate that HES is a pneumoprotective agent that could be a promising treatment for oxidative stress, inflammation, and proliferation.

A Gadolinium-Based Magnetic Ionic Liquid for Dispersive Liquid-Liquid Microextraction of Ivermectin from Environmental Water.

The recently introduced gadolinium-based magnetic ionic liquid (Gd-MIL) has been exploited as an extractant in dispersive liquid-liquid microextraction (DLLME) for preconcentration of ivermectin (IVR) from water samples followed by analysis using reversed-phase HPLC with UV detection at 245 nm. The utilized Gd-MIL extractant is hydrophobic with markedly high magnetic susceptibility. These features result in an efficient extraction of the lipophilic analyte and facilitate the phase separation under the influence of a strong magnetic field, thus promoting the method sensitivity and increasing the potential for automation. To maximize the IVR enrichment by DLLME, the procedure was optimized for extractant mass, dispersive solvent type/volume, salt addition and diluent pH. At optimized conditions, an enrichment factor approaching 70 was obtained with 4.0-mL sample sizes. The method was validated in terms of accuracy, precision, specificity and limit of quantitation. The method was successfully applied to the determination of IVR in river water samples with a mean relative recovery of 97.3% at a spiked concentration of 400 ng/mL. Compared with other reported methods, this approach used a simpler procedure with improved precision, lower amounts of safer solvents and a short analysis time.

A gadolinium-based magnetic ionic liquid for supramolecular dispersive liquid-liquid microextraction followed by HPLC/UV for the determination of favipiravir in human plasma.

Favipiravir is a potential antiviral medication that has been recently licensed for Covid-19 treatment. In this work, a gadolinium-based magnetic ionic liquid was prepared and used as an extractant in dispersive liquid-liquid microextraction (DLLME) of favipiravir in human plasma. The high enriching ability of DLLME allowed the determination of favipiravir in real samples using HPLC/UV with sufficient sensitivity. The effects of several variables on extraction efficiency were investigated, including type of extractant, amount of extractant, type of disperser and disperser volume. The maximum enrichment was attained using 50 mg of the Gd-magnetic ionic liquid (MIL) and 150 µl of tetrahydrofuran. The Gd-based MIL could form a supramolecular assembly in the presence of tetrahydrofuran, which enhanced the extraction efficiency of favipiravir. The developed method was validated according to US Food and Drug Administration bioanalytical method validation guidelines. The coefficient of determination was 0.9999, for a linear concentration range of 25 to 1.0 × 105  ng/ml. The percentage recovery (accuracy) varied from 99.83 to 104.2%, with RSD values (precision) ranging from 4.07 to 11.84%. The total extraction time was about 12 min and the HPLC analysis time was 5 min. The method was simple, selective and sensitive for the determination of favipiravir in real human plasma.

Prevention of Hepatorenal Insufficiency Associated with Lead Exposure by Hibiscus sabdariffa L. Beverages Using In Vivo Assay.

Lead pollution is a major environmental challenge worldwide. Therefore, dietary interventions that are aimed at preventing lead's deleterious effects on body organs are needed. The study's goal was to study and compare the protective effect of cold and hot beverages of Roselle (Hibiscus sabdariffa L.) red calyces (CRB and HRB, respectively) on liver and kidney insufficiency associated with lead exposure in male rats. Adult albino rats (32 males) were divided into four groups of equal number, including a normal control (group 1), while groups from 2 to 4 received lead acetate (20 mg/kg body weight/day) and were kept untreated (group 2). The 3rd and the 4th groups received CRB and HRB (0.5 ml/100 g body weight/day), respectively, for 6 weeks. The gain in the body and relative weights of the liver and kidneys were calculated. Liver and kidney functions were determined in serum, while lead, delta-aminolevulinic acid dehydratase, and oxidative stress markers were established in tissues. Specimens from the liver and kidney of sacrificed rats were histopathologically examined. The total activity of antioxidants and total content of anthocyanin of both beverages were determined. Lead exposure resulted in its accumulation in tissues, leading to overweight and liver and kidney insufficiency along with oxidative stress, which was further confirmed by histological staining. CRB was more efficient than HRB in preventing the deleterious effects of lead intoxication. Due to their antioxidant properties, the present study proved that Roselle red calyx beverages, particularly the cold ones, are protective agents against lead-associated disorders in a rat model.

Multi-Spectroscopic, thermodynamic and molecular dynamic simulation studies for investigation of interaction of dapagliflozin with bovine serum albumin.

Dapagliflozin (DAPA) is a selective sodium-glucose cotransporter-2 inhibitor that reduces renal glucose reabsorption. The drug has recently become a crucial milestone in the management of diabetes and heart failure. In this study, the interaction of DAPA with bovine serum albumin (BSA) was investigated for the first time using various fluorescence spectroscopic techniques, UV-absorption spectroscopy, molecular docking, and molecular dynamic (MD) simulation. The fluorescence spectroscopic titration study performed at different temperatures showed that DAPA quenched the fluorescence of BSA through a combination of dynamic and static mechanisms, which was confirmed by UV absorption, fluorescence-resonance energy transfer measurements, and MD simulation. The binding thermodynamic parameters demonstrated that the binding stoichiometry between BSA and DAPA was 1:1. Competitive binding experiments using site-specific markers as well as molecular docking studies showed that DAPA binds to site I on BSA. The positive values of enthalpy change (ΔH) and entropy change (ΔS) revealed that hydrophobic forces played a predominant role in the binding of DAPA to BSA, whereas the negative value of Gibbs free energy change (ΔG) indicated the spontaneity of the interaction. Moreover, the synchronous fluorescence spectroscopy has shown that DAPA binding to the protein molecule occurs in the vicinity of the tryptophan residue. These findings were confirmed by the molecular docking and MD simulation studies.

In silico identification of potential inhibitors against main protease of SARS-CoV-2 6LU7 from Andrographis panniculata via molecular docking, binding energy calculations and molecular dynamics simulation studies.

BACKGROUND: The ongoing global outbreak of new corona virus (SARS-CoV-2) has been recognized as global public health concern since it causes high morbidity and mortality every day. Due to the rapid spreading and re-emerging, we need to find a potent drug against SARS-CoV-2. Synthetic drugs, such as hydroxychloroquine, remdisivir have paid more attention and the effects of these drugs are still under investigation, due to their severe side effects. Therefore, the aim of the present study was performed to identify the potential inhibitor against main protease SARS-CoV-2 6LU7. OBJECTIVE: In this study, RO5, ADME properties, molecular dynamic simulations and free binding energy prediction were mainly investigated. RESULTS: The molecular docking study findings revealed that andrographolide had higher binding affinity among the selected natural diterpenoids compared to co-crystal native ligand inhibitor N3. The persistent inhibition of Ki for diterpenoids was analogous. Furthermore, the simulations of molecular dynamics and free binding energy findings have shown that andrographolide possesses a large amount of dynamic properties such as stability, flexibility and binding energy. CONCLUSION: In conclusion, findings of the current study suggest that selected diterpenoids were predicted to be the significant phytonutrient-based inhibitor against SARS-CoV-2 6LU7 (Mpro). However, preclinical and clinical trials are needed for the further scientific validation before use.

Feasibility and Safety of Goel-Harms Posterior C1-C2 Fusion in the Management of Pediatric Reducible Atlantoaxial Instability.

BACKGROUND: Pediatric atlantoaxial instability (AAI) is not common and could be a serious clinical condition. The Goel-Harms technique is one of the most used techniques in adults and needs more evaluation in pediatric populations. This study reports the feasibility and safety of the Goel-Harms technique in the treatment of pediatric reducible AAI. METHODS: In this retrospective cohort study we reported all pediatric patients who underwent Goel-Harms technique for AAI with a minimum 1-year follow up. Patients were clinically assessed using the Japanese Orthopedic Association (JOA) score and radiologically with plain radiographs, computed tomography scan, and magnetic resonance imaging of the craniocervical region. Postoperatively, patients were followed up according to our clinical and radiographic imaging protocol. The following parameters were recorded: JOA score, construct stability, fusion, and abnormal events. RESULTS: A total of 25 patients have completed a 1-year follow-up and fulfilled our criteria. The mean age was 10.68 ± 4.47 (range, 3-17) years. Fifteen patients were male and 10 were female. The final diagnosis included Down syndrome (DS) in 8, type II dens fracture in 7, os odontoideum in 3, and atlantoaxial rotatory fixation in 7. The mean follow-up was 21.76 ± 8.22 months. The preoperative JOA score improved from 15.96 ± 1.46 to 16.76 ± 1.92 at the last follow-up. Sound bone fusion was reported in 92% of patients. CONCLUSIONS: Our data suggest that the Goel-Harms technique is a safe, feasible, and effective procedure in managing pediatric reducible AAI. Special perioperative care should be offered to young AAI patients with DS.

Ameliorative property of Sesbania grandiflora on carbohydrate metabolic enzymes in the liver and kidney of streptozotocin-induced diabetic rats.

In diabetic condition, endogenous glucose synthesis will be elevated due to defect in the action of vital enzymes involved in carbohydrate metabolism, which is the main cause for hyperglycemia. The current study was designed to explore the anti-hyperglycemic efficacy of Sesbania grandiflora flower (SGF) extract by evaluating the concentration of C-peptide, insulin, glucose, glycosylated hemoglobin (HbA1C), hemoglobin (Hb), glycogen and carbohydrate metabolic enzymes activities in diabetic rats. The study found to lower the level of glucose, HbA1C and simultaneously ameliorated concentrations of C-peptide, insulin, hemoglobin (Hb), glycogen and carbohydrate metabolic enzymes activities in SGF treated (250 mg/kg body weight for 45 days) diabetic rats. Moreover, SGF administered diabetic rats showed diminished consumption of food and water at the same time improved body weight. The results obtained from the present study were compared with glibenclamide treated (600 µg/kg body weight) diabetic rats. SGF were supplemented to normal rats to rule out toxic effect of SGF, to explore any significant alteration in the above parameters. Hence, the results depict that SGF modulated the carbohydrate metabolic enzymes activities through ameliorating the secretion of insulin and diminishing the level of glucose concentration in STZ-induced diabetic rats by its bioactive compounds.

A Low-Fat Diet Combined with Moderate-Intensity Aerobic Exercise is More Effective than a Low-Fat Diet or Aerobic Exercise Alone on Dyslipidemia and Depression Status in Obese Patients: A Randomized Controlled Trial.

BACKGROUND & OBJECTIVE: Exercise and dietary interventions are used to control dyslipidemia and depression in obese individuals, whilst rare investigations have examined the concurrent effects of a low-fat diet and moderate-intensity aerobic exercise training (MIAET) on dyslipidemia and depression in obese patients. Hence, we assessed the potential influences of a low-fat diet combined with MIAET on blood lipids and depression in those individuals. METHODS: Forty-two obese patients aged 30-50 years have been enrolled in this randomized controlled trial. They have been randomized equally into MIAET group (n=14, 60-70% of the maximum heart rate (Max HR), three sessions a week), a low-fat diet group (n=14, fat, 30% Kcal/day), and a low-fat diet plus MIAET (n=14) for 10 consecutive weeks. Body mass index (BMI), lipid profile, and Hamilton depression rating scale (HDRS) have been assessed on two occasions, pre and post- 10 weeks. RESULTS: It was demonstrated that a low-fat diet group showed an improvement in total cholesterol (T-Ch), p=0.046, with no changes in triglycerides (TGs), p=0.343, low-density lipoproteins (LDLs), p=0.187, and high-density lipoproteins (HDLs), p=0.224; however, MIAET group showed an improvement in TGs, p=0.042, HDLs, p=0.038 with no changes in T-Ch, p=0.126, and LDLs, p=0.368. Regarding the low-fat diet plus MIAET group, significant improvements were identified in TGs, p=0.003, T-Ch, p<0.001, LDLs, p=0.004, and HDLs, p<0.001. For the depression status, all groups showed a significant improvement in HDRS, p<0.001, with a low-fat diet plus MIAET group showing greater advantages, p<0.05. CONCLUSION: The results of the current trial suggest an important implication for promoting improvement in blood lipids and a reduction in depression status in obese patients with dyslipidemia following 10-week of a concurrent low-fat diet and moderate-intensity aerobic exercise more than low-fat diet or MIAET alone.

Short-Term Psychological and Hormonal Effects of Virtual Reality Training on Chronic Low Back Pain in Soccer Players.

OBJECTIVE: To find the short-term psychological and hormonal effects of virtual reality training on chronic low back pain in American soccer players. DESIGN, SETTING, PARTICIPANTS: The 3-block random sampling method was used on 54 university American soccer players with chronic low back pain, and they were allocated into 3 groups: virtual reality training (VRT; n = 18), combined physical rehabilitation (n = 18), and control (n = 18) groups at University Hospital. They underwent different balance training exercises for 4 weeks. The participants and the therapist who is assessing the outcomes were blinded. Psychological (pain intensity and kinesiophobia) and hormonal (glucose, insulin, Homeostatic Model Assessment of Insulin Resistance, growth hormone, prolactin, adrenocorticotropic hormone, and cortisol) values were measured at baseline, after 4 weeks, and after 6 months. RESULTS: The baseline demographic, psychological, and hormonal data between the VRT, combined physical rehabilitation, and control groups show no statistical difference (P ≥ .05). Four weeks following training, the VRT group shows more significant changes in pain intensity and kinesiophobia than the combined physical rehabilitation and control groups (P < .001), and the improvement was noted in the 6-month follow-up. All the hormonal variables (glucose, insulin, growth hormone, prolactin, adrenocorticotropic hormone, and cortisol) show significant changes at 4-week training (P < .001), except for the Homeostatic Model Assessment of Insulin Resistance (P = .075) between the 3 groups. At 6-month follow-up glucose, prolactin, adrenocorticotropic hormone, and cortisol show more significant difference in the VRT group than the other 2 groups (P < .001). At the same time, insulin (P = .694), Homeostatic Model Assessment of Insulin Resistance (P = .272), and growth hormone (P = .145) failed to show significant changes between the groups. CONCLUSION: Training through virtual reality is an effective treatment program when compared with conventional exercise training programs from a psychological and hormonal analysis perspective in American soccer players with chronic low back pain.

A gadolinium-based magnetic ionic liquid for dispersive liquid-liquid microextraction.

A hydrophobic gadolinium-based magnetic ionic liquid (MIL) was investigated for the first time as an extraction solvent in dispersive liquid-liquid microextraction (DLLME). The tested MIL was composed of trihexyl(tetradecyl)phosphonium cations and paramagnetic gadolinium chloride anions. The prepared MIL showed low water miscibility, reasonable viscosity, markedly high magnetic susceptibility, adequate chemical stability, low UV background, and compatibility with reversed-phase HPLC solvents. These features resulted in a more efficient extraction than the corresponding iron or manganese analogues. Accordingly, the overall method sensitivity and reproducibility were improved, and the analysis time was reduced. The applicability of the proposed MIL was examined through the microextraction of four sartan antihypertensive drugs from aqueous samples followed by reversed-phase HPLC with UV detection at 240 nm. The DLLME procedures were optimized for disperser solvent type, MIL mass, disperser solvent volume, as well as acid, base, and salt addition. The limits of quantitation (LOQs) obtained with the analysis of 1.2-mL samples after DLLME and HPLC were 80, 30, 40, and 160 ng/mL for azilsartan medoxomil, irbesartan, telmisartan, and valsartan, respectively. Correlation coefficients were greater than 0.9988 and RSD values were in the range of 2.48-4.07%. Under the optimized microextraction conditions and using a 5-mL sample volume, enrichment factors were raised from about 40 for all sartans using a 1.2-mL sample to 175, 176, 169, and 103 for azilsartan medoxomil, irbesartan, valsartan, and telmisartan, respectively. The relative extraction recoveries for the studied sartans in river water varied from 82.5 to 101.48% at a spiked concentration of 0.5 µg/mL for telmisartan and irbesartan and 1 µg/mL for azilsartan medoxomil and valsartan. Graphical abstract.

Association between endoglin/transforming growth factor beta receptors 1, 2 gene polymorphisms and the level of soluble endoglin with preeclampsia in Egyptian women.

INTRODUCTION: Preeclampsia (PE) is a pregnancy-specific hypertensive disease whose etiopathogenesis remains unclear. OBJECTIVES: This study was designed to assess association between PE and 3 single nucleotide polymorphisms (SNPs): ENG(G/A) rs11792480, TGFßR1(A/C) rs10739778 and TGFßR2(G/A) rs6550005, beside circulating soluble endoglin (sENG), oxidative stress biomarkers and nitric oxide (NO) in Egyptian women. METHODS: The study included 75 preeclamptic women stratified into 4 clinical subgroups and 50 normotensive pregnant women. Genotyping was performed by real time polymerase chain reaction-Taqman allelic discrimination. RESULTS: Preeclamptic women showed significantly increased sENG and malondialdehyde (MDA), decreased total antioxidant capacity (TAC), endothelial nitric oxide synthase (eNOS) and NO, without change in transforming growth factor beta 1 (TGFß1) versus controls. Moreover, sENG was significantly higher in severe and early than mild and late PE. Higher MDA and lower TAC and NO were observed in severe than mild PE. ENG(G/A) and TGFßR2(G/A) showed no association with PE. However, CC genotype of TGFßR1(A/C) was more frequent in controls than either PE, early-onset or severe revealing a reduced PE risk in CC genotype versus AA or AA + AC. Importantly, patients carrying AA genotype had higher SBP and MDA with lower TAC, gestational age at delivery (GA) and birth weight than those carrying CC genotype. CONCLUSIONS: Excessive sENG release with decreased eNOS/NO may be involved in PE pathogenesis. Women who carry C allele or CC genotype of TGFßR1(A/C) may be less prone to develop PE.

Ligand exchange method for determination of mole ratios of relatively weak metal complexes: a comparative study.

Ligand exchange method is introduced as an alternative to Job's and mole ratio methods for studying the stoichiometry of relatively weak metal complexes in solutions. The method involves adding varying amounts of a ligand (L) to an excess constant amount of a colored complex (MX) with appropriate stability and molar absorptivity. The absorbance of each solution is measured at the λmax of the initial complex, MX, and plotted against the concentration of the studied ligand, L. If the newly formed complex ML does not absorb at the λmax of the initial complex, then attenuation of the absorbance of the initial complex on adding varying quantities of the investigational ligand gives an inverse calibration line that intersects with the calibration curve of initial complex at a given point. If a line parallel to the ordinate is drawn from this point to the x-axis, the ratio of the two parts of the x-axis to the left and to the right (α/ß) gives the metal to ligand molar ratio in the complex formed, ML. The new method has been applied to the study of the composition of iron (III) complexes with three bisphosphonate drugs: alendronate, etidronate, and ibandronate. The mole ratio was found to be 1:1 with the three investigated bisphosphonates and results were further confirmed by Job's and mole ratio methods. The ligand exchange method is simpler, quicker, easier to perform and more accurate than Job's and mole ratio methods for studying weak and relatively weak complexes.

Prepuce preserving versus conventional Mathieu urethroplasty for distal hypospadias - a prospective randomized study.

OBJECTIVES: To evaluate the impact of prepuce preservation during Mathieu repair for distal hypospadias. METHODS: This prospective randomized comparative study, carried out in Assiut University Hospital, between 2006 and 2009, included 200 patients with distal penile or coronal hypospadias. They underwent either Mathieu repair with prepuce preservation (group I, n = 100) or traditional Mathieu repair with circumcision (group II, n = 100). Follow up was at 2 weeks, and 1 and 3 months postoperatively, which only 153 patients completed (I: n = 86 and II: n = 67). RESULTS: The mean operative time was 64.5 min in group I and 121.7 min in group II (p < 0.001). All patients in group I developed postoperative preputial edema. Patients from group I who had a successful operation underwent circumcision at least 3 months later. Urethrocutaneous fistulae developed in 7 and 6 patients in group I and II respectively (p = 0.967). Fistula closure was done at least 3 months postoperatively, and there was no significant difference in success between the two groups. Two cases of glanular dehiscence were detected (one in each group); the patient from group I had a successful onlay island flap repair. CONCLUSIONS: Preputial preservation during Mathieu repair is a time-saving procedure with similar complication rate to traditional repair. Valuable local tissue is preserved to deal with complications that may occur.