Benchmarking the Humidity-Dependent Mechanical Response of (Nano)fibrillated Cellulose and Dissolved Polysaccharides as Sustainable Sand Amendments.

Soil quality is one of the main limiting factor in the development of the food sector in arid areas, mainly due to its poor mechanics and lack of water retention. Soil's organic carbon is nearly absent in arid soils, though it is important for water and nutrient transport, to soil mechanics, to prevent erosion, and as a long-term carbon sink. In this study, we evaluate the potential benefits that are brought to inert sand by the incorporation of a range of, mainly, cellulosic networks in their polymeric or structured (fiber) forms, analogously to those found in healthy soils. We explore the impact of a wide range of nonfood polysaccharide-based amendments, including pulp fibers, nanocellulose, cellulose derivatives, and other readily available polysaccharide structures derived from arthropods (chitosan) or fruit peels (pectin) residues. A practical methodology is presented to form sand-polymer composites, which are evaluated for their soil mechanics as a function of humidity and the dynamics of their response to water. The mechanics are correlated to the network of polymers formed within the pores of the sandy soil, as observed by electron microscopy. The response to water is correlated to both the features of the network and the individual polysaccharides' physicochemical features. We expect this work to provide a rapid and reproducible methodology to benchmark sustainable organic amendments for arid soils.

First derivative synchronous spectrofluorimetric method for the simultaneous determination of tramadol and celecoxib in their dosage forms and human plasma.

One of the most common features of many different clinical conditions is pain; hence, there is a crucial need for eliminating or reducing it to a tolerable level to retrieve physical, psychological and social functioning. A first derivative synchronous spectrofluorimetry technique is proposed for the simultaneous determination of celecoxib and tramadol HCl, a recent coformulation authorized for treating acute pain in adults. The method includes using synchronous spectrofluorimetry at ∆λ = 80 nm where tramadol HCl was determined using first derivative technique at λ = 230.2 nm, while celecoxib was determined at λ = 288.24 nm. The proposed method was successfully applied to their co-formulated dosage forms in addition to spiked human plasma and validated in agreement with the guidelines of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH). The linear ranges were found to be 0.50-5.0 and 0.15-0.50, the limits of detection to be 0.088 and 0.011 and the limits of quantification to be 0.266 and 0.032 µg/ml for celecoxib and tramadol, respectively. Statistical analysis revealed no significant difference when compared with previously reported methods as evidenced by the values of the variance ratio F-test and Student t-test. The proposed method was successfully applied to commercial dosage forms and spiked human samples. Moreover, the greenness of the proposed method was investigated based on the analytical eco-scale approach, with the results showing an excellent green scale with a score of 95.

Tyrosinase enzyme purification and immobilization from Pseudomonas sp. EG22 using cellulose coated magnetic nanoparticles: characterization and application in melanin production.

Melanin is a brown-black pigment with significant roles in various biological processes. The tyrosinase enzyme catalyzes the conversion of tyrosine to melanin and has promising uses in the pharmaceutical and biotechnology sectors. This research aims to purify and immobilize the tyrosinase enzyme from Pseudomonas sp. EG22 using cellulose-coated magnetic nanoparticles. Various techniques were utilized to examine the synthesized nanoparticles, which exhibited a spherical shape with an average diameter of 12 nm and a negative surface potential of - 55.7 mV with a polydispersity index (PDI) of 0.260. Comparing the immobilized magnetic tyrosinase enzyme with the free enzyme, the study's findings showed that the immobilized tyrosinase enzyme had optimal activity at a pH of 6 and a temperature of 35 °C, and its activity increased as the concentration of tyrosine increased. The study investigated the antibacterial and anticancer bioactivity of the enzyme's melanin product and found that it exhibited potential antibacterial activity against a multi-drug resistant strain including S. aureus and E. coli. The produced melanin also demonstrated the potential to decrease cell survival and induce apoptosis in initiation cells.

Predictive urinary RNA biomarkers of kidney injury after extracorporeal shock wave lithotripsy.

BACKGROUND: Extracorporeal shock wave lithotripsy (ESWL) is considered one of the best choices for the treatment of various kinds of urinary tract calculi, although it might cause acute kidney injury. OBJECTIVE: To measure the urinary long non-coding RNA-messenger RNA (LncRNA-mRNA) panel before and after ESWL to evaluate post-ESWL renal injury in a reliable and non-invasive method. PATIENTS AND METHODS: The study included 60 patients with renal stones treated with ESWL and 30 healthy volunteers. Voided urine samples were obtained before, 2 h, and 1 day after ESWL. We measured the urinary level of LncRNA (SBF2-AS1, FENDRR-19) and mRNA (GBP1, NLRP3) by real-time qPCR and compared the results with serum creatinine and eGFR. RESULTS: LncRNA (SBF2-AS1, FENDRR-19) and mRNA (GBP1, NLRP3) levels were higher in patients with renal stones when compared with healthy volunteers. They showed a statistically significant increase in the level of LncRNA-mRNA panel in baseline and after ESWL treatment. CONCLUSION: LncRNA (SBF2-AS1, FENDRR-19) and mRNA (GBP1, NLRP3) levels were significantly elevated following ESWL treatment, highlighting the usefulness of urinary biomarkers in identifying patients at higher risk of developing renal injury after ESWL treatment.

Enhancing pre-school teachers' competence in managing pediatric injuries in Pemba Island, Zanzibar.

BACKGROUND: Safe and healthy learning environment in pre-schools has received increased attention in promoting the well-being of pre-school children. However, pediatric injuries have remained one of the leading causes of childhood morbidity and mortality around the globe. Empowering pre-school teachers with first aid competencies have been identified as being of potential strategy against pediatric health burdens of problem. This study tested the effect of established pediatric first aid training on pre-school teachers' knowledge, attitude, and intention to practice first aid management to pre-school children in Zanzibar.  METHODS: Uncontrolled quasi-experimental design with a quantitative research approach was conducted in Teachers' Resource Centers among 120 preschool teachers at Pemba Island, Zanzibar. First aid training was facilitated based on the prescribed guidelines and standards of materials adapted from the American Academy of Pediatrics and implemented. The intervention was preceded by a baseline assessment using structured questionnaires adopted from previous studies that served as the main data collection tool. RESULTS: Participants' mean age was 32 years ± 6.2 with 84.2% of the sample being females. Given the training, post-test findings demonstrated a significant increase (p < 0.01) in participants' first aid management scores with mean differences of M = 15.08 ± 5.34 (Knowledge), M = 26.99 ± 6.587 (Attitude), and (M = 4.76 ± 0.648 (Intentional practice). CONCLUSION: The established pediatric first aid training can enhance the spectrum of managing pediatric injuries among preschool teachers in Zanzibar. Ongoing public health services opportunities should be structured within teachers' continuous learning against pediatric injuries in Zanzibar-Tanzania.

Gastroenterology manifestations and COVID-19 outcomes: A meta-analysis of 25,252 cohorts among the first and second waves.

A meta-analysis was performed to identify patients with coronavirus disease 2019 (COVID-19) presenting with gastrointestinal (GI) symptoms during the first and second pandemic waves and investigate their association with the disease outcomes. A systematic search in PubMed, Scopus, Web of Science, ScienceDirect, and EMBASE was performed up to July 25, 2020. The pooled prevalence of the GI presentations was estimated using the random-effects model. Pairwise comparison for the outcomes was performed according to the GI manifestations' presentation and the pandemic wave of infection. Data were reported as relative risk (RR), or odds ratio and 95% confidence interval. Of 125 articles with 25,252 patients, 20.3% presented with GI manifestations. Anorexia (19.9%), dysgeusia/ageusia (15.4%), diarrhea (13.2%), nausea (10.3%), and hematemesis (9.1%) were the most common. About 26.7% had confirmed positive fecal RNA, with persistent viral shedding for an average time of 19.2 days before being negative. Patients presenting with GI symptoms on admission showed a higher risk of complications, including acute respiratory distress syndrome (RR = 8.16), acute cardiac injury (RR = 5.36), and acute kidney injury (RR = 5.52), intensive care unit (ICU) admission (RR = 2.56), and mortality (RR = 2.01). Although not reach significant levels, subgroup-analysis revealed that affected cohorts in the first wave had a higher risk of being hospitalized, ventilated, ICU admitted, and expired. This meta-analysis suggests an association between GI symptoms in COVID-19 patients and unfavorable outcomes. The analysis also showed improved overall outcomes for COVID-19 patients during the second wave compared to the first wave of the outbreak.

Synchronous spectrofluorometric methods for simultaneous determination of diphenhydramine and ibuprofen or phenylephrine in combined pharmaceutical preparations.

Simple and rapid synchronous fluorometric methods were adopted and validated for the simultaneous analysis of a binary mixture of diphenhydramine (DIP) and ibuprofen (IBU) (Mix I) or DIP and phenylephrine (PHE) (Mix II) in their co-formulated pharmaceuticals without prior separation. Analysis of Mix I is based on the measurement of the peak amplitudes (D1 ) of synchronous fluorescence intensities at 265.1 nm for DIP and 260 nm for IBU. The relationship between the concentration and the amplitude of the first-derivative synchronous fluorescence spectra showed good linearity over the concentration ranges 0.50-10.00 µg ml-1 and 0.50-7.90 µg ml-1 for DIP and IBU, respectively. Analysis of Mix II was based on measurement of the peak amplitude (D1 ) synchronous fluorescence intensities at 230 nm for DIP and at 253.9 nm for PHE. Moreover, for Mix II, the peak amplitude (D2 ) synchronous fluorescence intensities were measured at 227.9 nm for DIP and at 264.9 nm for PHE. Calibration plots were rectilinear over the concentration range 0.30-3.50 µg ml-1 and 0.03-0.75 µg ml-1 for DIP and PHE, respectively. The proposed methods were successfully applied to determine the studied compounds in pure form and in pharmaceutical preparations.

Transseptal puncture and catheter ablation of atrial fibrillation in patients with atrial septal occluder: initial experience of a single centre.

Aims: Catheter ablation is underutilized in atrial septal defect (ASD) patients who have undergone implantation of an atrial septal occluder (ASO). This study evaluates the feasibility and safety of catheter ablation of atrial fibrillation (AF) in this subset of patients. Methods and results: Sixteen patients (age 56 ± 12 years, 10 men) with drug-refractory AF (10 paroxysmal and 6 persistent) and previously implanted ASO were enrolled. Balloon dilatation of the closure device was performed if the native septum passage could not be achieved. For paroxysmal AF, the ablation strategy was circumferential pulmonary vein isolation (CPVI), and for persistent AF, additional linear ablation was performed. Transseptal access was achieved through the native septum in 11 patients (Group A) and through the ASO using balloon dilatation in 5 patients (Group B). Circumferential pulmonary vein isolation was achieved in all 16 patients, and linear block was achieved in all persistent patients except for 1 patient who did not achieve mitral isthmus block. The transseptal, total fluoroscopy, and procedural durations were 5 ± 3 vs. 38 ± 8 min, 31 ± 11 vs. 54 ± 15 min, and 165 ± 35 vs. 224 ± 36 min, respectively, in Group A vs. Group B, respectively (all P < 0.05). No shunt at atrial level was detected by transthoracic echocardiography at 3-month follow-up. During a follow-up of 16 ± 6 months, sinus rhythm was maintained in 12 of 16 patients. No severe complications were observed. Conclusion: In ASD patients with ASO, catheter ablation of AF is feasible, safe, and effective. The balloon dilatation technique can facilitate transseptal access through the ASO.

Psychological Comfort of Paramedics with Field Death Pronouncement: A National Asian Study to Prepare Paramedics for Field Termination of Resuscitation.

OBJECTIVES: Paramedics' decision to terminate field resuscitation without a physician present may depend on personal and external factors. This study investigates factors associated with paramedic psychological comfort with termination of resuscitation (TOR) to inform future training. METHODS: We administered an anonymous survey to all practicing paramedics in a large urban Asian Emergency Medical Services system where formal TOR training had not yet been conducted and field TOR was not routinely applied. The survey assessed psychological comfort using the validated Psychological Comfort Total (PCT) scale (summed score of 28 items, with higher scores representing greater comfort). We examined scores associated with four personal (prior resolution of personal loss, knowledge of survival probability, religious affiliation and experience with death pronouncements) and two external (location of patient and perceived trust of family) factors. Data were entered into Excel and analyzed by t-tests and ANOVA. RESULTS: Response rate was 73.6% (254/345). Respondents were 30.3 years (mean, SD 7.1) with 7.2 years (mean, SD 5.54) of practice experience. Over 60% had been involved in 6 or more field death pronouncements in the prior 12 months. Higher PCT scores were associated with prior resolution of personal loss and knowledge of survival probability. Lower PCT scores were associated with patient location in a public place and perceived family lack of trust. PCT scores were not associated with paramedic religious affiliation or number of prior death pronouncements. CONCLUSIONS: Paramedic psychological comfort with field death pronouncement is associated with personal and external factors. Since paramedic comfort is important for protocol adoption, TOR education should target not only knowledge, but also public arena management, communication skills for engaging with families, and help paramedics resolve prior personal loss.

Prophylactic Atropine Administration Prevents Vasovagal Response Induced by Cryoballoon Ablation in Patients with Atrial Fibrillation.

BACKGROUND: Cryoballoon (CB) ablation of pulmonary vein ostia often induces a vagal response. This prospective study was designed to assess the effectiveness of prophylactic intravenous administration of atropine on hemodynamic impairment induced by CB ablation in patients with atrial fibrillation. METHODS: Twenty-five patients with paroxysmal atrial fibrillation undergoing CB ablation were prospectively enrolled and assigned to one of two groups. First 12 patients (trial group) were administered 1 mg of atropine before deflation of the CB, while the following 13 patients (control group) were given atropine only after the onset of the hemodynamic variation (decrease in heart rate and/or blood pressure). Treatment was considered effective when the hemodynamic variations were restored. RESULTS: In the trial group, three patients with transient hypotension did not require supportive care throughout the procedures, and one patient with hypotension required supportive care. In the control group, hypotension, bradycardia, and mixed bradycardia with hypotension requiring supportive care occurred in six, three, and three patients, respectively. Overall, the rate of marked vagal responses was significantly lower when prophylactic atropine was administrated (4/12 patients vs 12/13 patients, respectively; P < 0.01). CONCLUSIONS: Atropine is significantly effective in the prevention of all types of vasovagal responses induced by CB ablation in patients with atrial fibrillation.

QTc Interval Prolongation Predicts Arrhythmia Recurrence After Catheter Ablation of Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: In hypertrophic cardiomyopathy (HCM) patients complicated with atrial fibrillation (AF), catheter ablation has been recommended as a treatment option. Meanwhile, prolongation of QTc interval has been linked to an increased AF incidence in the general population and to poor outcomes in HCM patients. However, whether QTc prolongation predicts arrhythmia recurrence after AF ablation in the HCM population remains unknown. METHODS AND RESULTS: Thirty-nine HCM patients undergoing primary AF ablation were enrolled. The ablation strategy included bilateral pulmonary vein isolation (PVI) for paroxysmal AF (n=27) and PVI plus left atrial roof, mitral isthmus and tricuspid isthmus linear ablations for persistent AF (n=12). Pre-procedural QTc was corrected by using the Bazett's formula. At a 14.8-month follow up, 23 patients experienced atrial tachyarrhythmia recurrence. Recurrent patients had longer QTc than non-recurrent patients (461.0±28.8 ms vs. 434.3±18.2 ms, P=0.002). QTc and left atrial diameter (LAD) were independent predictors of recurrence. The cut-off value of QTc 448 ms predicted arrhythmia recurrence with a sensitivity of 73.9% and a specificity of 81.2%. A combination of LAD and QTc (global chi-squared=13.209) was better than LAD alone (global chi-squared=6.888) or QTc alone (global chi-squared=8.977) in predicting arrhythmia recurrence after AF ablation in HCM patients. CONCLUSIONS: QTc prolongation is an independent predictor of arrhythmia recurrence in HCM patients undergoing AF ablation, and might be useful for identifying those patients likely to have a better outcome following the procedure.

Electroanatomical mapping of the right atrium during atrial tachycardia originating from right superior pulmonary vein: additional insights on differential diagnosis.

BACKGROUND: Atrial tachycardia (AT) from the right superior pulmonary vein (RSPV) may mimic right atrial (RA)-AT due to its proximity to the superior vena cava (SVC) and the preferential connections between the left atrium and right atrium. OBJECTIVE: RA electroanatomical mapping was performed and analyzed during RSPV-AT to differentiate it from RA-AT. METHODS: Electroanatomical mapping of the RA was performed in 16 consecutive patients with RSPV-AT and eight consecutive patients with SVC-AT served as control group. RESULTS: RA mapping revealed single breakthrough in six patients and double breakthroughs in 10 patients in the RSPV-AT group. The initial 10-ms atrial depolarization area averaged 4.3 ± 1.5 cm(2). None of the SVC-ATs exhibited double breakthrough sites with an initial 10-ms atrial depolarization area of 2.0 ± 0.6 cm(2) (P = 0.001). A cutoff value of activation area of initial 10 ms > 3.15 cm(2) was able to predict RSPV-AT with a sensitivity of 87.5% and a specificity of 100%. Preceding far-field RSPV potentials could be documented in the RA in six patients during RSPV-AT. CONCLUSIONS: During RSPV-AT, diffused initial depolarization and one or two separated breakthrough sites consistent with the preferential connections as revealed by RA mapping could help rule out RA-AT and avoid unnecessary ablation at the RA.

Hydroxylated near-infrared BODIPY fluorophores as intracellular pH sensors.

In this study, a series of new, highly sensitive BF2-chelated tetraarylazadipyrromethane dyes are synthesized and analyzed to be suitable as on/off photo-induced electron transfer modulated fluorescent sensors for determination of intracellular pH. The ethanolic solutions of the new indicators feature absorption maxima in the range of 696-700 nm and a fluorescence emission maximum at 720 nm. Molar absorptivity and fluorescence quantum yield data were determined for the studied set of aza-BODIPY indicators. These indicators have high molar absorption coefficients of ∼80,000 M(-1) cm(-1) and quantum yields (up to 18%). Corresponding pKa values of indicators are determined from absorbance and fluorescence measurements and range from 9.1 to 10.8, depending on the selective positioning of electron-donating functionalities. The excellent photostability of the aza-BODIPY indicators makes them particularly suitable for long duration measurements. The in vitro cellular staining of living tissues in PC3 cells based on the isosbestic point at pH 7.8 and pH 9.3 has been employed which shows an increase in fluorescence intensity at 800 nm with increase in pH for certain compounds and fluorescence intensity decreases at 700 nm. Therefore, the new indicators are suitable for exploitation and adaptation in a diverse range of analytical applications.

Predictors of recurrence after a repeat ablation procedure for paroxysmal atrial fibrillation: role of left atrial enlargement.

AIMS: This study sought to explore the predictors of recurrence in patients with paroxysmal atrial fibrillation (AF) undergoing repeat catheter ablation, especially the impact of left atrial (LA) remodelling after the original procedure on the outcome of repeat procedure. METHODS AND RESULTS: Ninety-five patients undergoing repeat ablation were enrolled in this study. Repeat procedure endpoints were pulmonary vein isolation, linear block when linear ablation is performed, and non-inducibility of atrial tachyarrhythmia by burst pacing. Patients with LA enlargement between the pre-original procedure and pre-repeat procedure were categorized as Group 1 (35 patients), while individuals with no change or decrease of LA diameter were categorized as Group 2 (60 patients). The mean duration from the original procedure to the repeat procedure was 12 months (1-40 months). After 29.6 ± 20.5 (3-73) months follow-up from the repeat procedure, 33 patients experienced recurrence (34.7%). The recurrence rate was significantly higher in Group 1 than in Group 2 (51.4 VS. 25.0%, P = 0.017). In univariate analysis, LA remodelling was the only predictor of recurrence. In multivariate analysis, after adjustment for age and LA diameter, Group 1 had a greater risk of recurrence after the repeat procedure (hazard ratio = 2.22, 95% confidence interval: 1.02-4.81, P = 0.043). CONCLUSIONS: Left atrial enlargement after undergoing the original catheter ablation of paroxysmal AF was an independent risk factor of recurrence after repeat ablation.

Pacing or ablation: which is better for paroxysmal atrial fibrillation-related tachycardia-bradycardia syndrome?

BACKGROUND: Symptomatic prolonged sinus pauses on termination of atrial fibrillation (AF) are an accepted indication for pacemaker implantation. We evaluated the outcome of AF ablation in patients with paroxysmal AF-related tachycardia-bradycardia syndrome and compared the efficacy of catheter ablation with permanent pacing plus antiarrhythmic drugs (AADs). METHODS AND RESULTS: Patients with prolonged symptomatic sinus pauses on termination of AF were retrospectively analyzed. Forty-three consecutive patients who underwent catheter ablation (ABL group) were compared to 57 patients who underwent permanent pacing plus AADs (PM group). All 43 patients in the ABL group fulfilled Class I indication for pacemaker implantation at baseline but they actually underwent AF ablation. Reevaluation after 20.1 ± 9.6 months of follow-up showed that 41 patients (95.3%) did no longer need a pacemaker (Class III indication). Total cardiac-related rehospitalization was not significantly different between the two groups (P = 0.921). Tachycardia-related hospitalization was significantly higher in the PM group than the ABL group (14.0% and 0%, P = 0.029). More patients in the PM group were on AADs (PM 40.4%, ABL 4.7%, P < 0.001) while sinus rhythm maintenance was remarkably higher in the ABL group at the end of follow-up (83.7% vs 21.1% in PM group, P < 0.001). CONCLUSIONS: In patients with paroxysmal AF-related tachycardia-bradycardia syndrome, AF ablation seems to be superior to a strategy of pacing plus AAD. Pacemaker implantation can be waived in the majority of patients after a successful ablation.

Simultaneous determination of aliskiren hemifumarate, amlodipine besylate, and hydrochlorothiazide in their triple mixture dosage form by capillary zone electrophoresis.

A novel, specific, reliable, and accurate capillary zone electrophoretic method was developed and validated for the simultaneous determination of aliskiren hemifumarate, amlodipine besylate, and hydrochlorothiazide in their triple mixture dosage form. Separation was carried out in a fused-silica capillary (57.0 cm total length and 50.0 cm effective length, 75.6 µm internal diameter) by applying a potential of 17 kV and a running buffer consisting of 40 mM phosphate buffer at pH 6.0 with UV detection at 245 nm. The method was suitably validated with respect to specificity, linearity, LOD, and LOQ, accuracy, precision, and robustness. The method showed good linearity in the ranges 1-10, 2.5-25, and 30-300 µg/mL with LODs of 0.11, 0.33, and 5.83 µg/mL for amlodipine besylate, hydrochlorothiazide, and aliskiren hemifumarate, respectively. The proposed method was successfully applied for the analysis of the studied drugs in their coformulated tablets. The results of the proposed method were statistically compared with those obtained by the RP-HPLC reference method revealing no significant differences in the performance of the methods regarding accuracy and precision.

Process-structure-property relationships of cellulose nanocrystals derived from Juncus effusus stems on Ò¡-carrageenan-based bio-nanocomposite films.

This study investigates the potential of Juncus plant fibers as a renewable source for producing cellulose nanocrystals (CNs) to reinforce polymers. Cellulose microfibers (CMFs) were extracted with a 0.43 ± 0.2 µm diameter and 69 % crystallinity through alkaline and bleaching treatments, then subjected to sulfuric acid hydrolysis, yielding four CN types (CN10, CN15, CN20 and CN30) with distinct physico-chemical properties and aspect ratios (47, 55, 57, and 60). The study assessed the influence of cellulose nanocrystals (CNs), incorporated at different weight percentages (3 %, 5 %, and 8 %), on thermal, transparency, and mechanical properties in k-carrageenan (CA) biocomposite films. The results indicate significant enhancements in these characteristics, highlighting good compatibility between CNs and CA matrix. Particularly noteworthy is the observed substantial improvement in tensile strength at an 8 wt% loading, with values of 23.43 ± 0.83 MPa for neat CA, 33.53 ± 0.83 MPa for CA-CN10, 36.67 ± 0.71 MPa for CA-CN15, 37.65 ± 0.56 MPa for CA-CN20, and 39.89 ± 0.77 MPa for CA-CN30 composites. Furthermore, the research explores the connection between the duration of hydrolysis and the properties of cellulose nanocrystals (CNs), unveiling their influence on the characteristics of nanocomposite films. Prolonged hydrolysis enhances CN crystallinity (CrI), aspect ratio, and surface charge content, consequently enhancing mechanical features like strength and flexibility in these films. These findings demonstrate the potential of Juncus plant fibers as a natural and eco-friendly resource for producing CNs that effectively reinforce polymers, making them an attractive option for diverse applications in the field.

Study of the binding interaction of salmon sperm DNA with nintedanib, a tyrosine kinase inhibitor using multi-spectroscopic, thermodynamic, and in silico approaches.

The study of the intermolecular binding interaction of small molecules with DNA can guide the rational drug design with greater efficacy and improved or more selective activity. In the current study, nintedanib's binding interaction with salmon sperm DNA (ssDNA) was thoroughly investigated using UV-vis spectrophotometry, spectrofluorimetry, ionic strength measurements, viscosity measurements, thermodynamics, molecular docking, and molecular dynamic simulation techniques under physiologically simulated conditions (pH 7.4). The obtained experimental results showed that nintedanib and ssDNA had an apparent binding interaction. Nintedanib's binding constant (Kb) with ssDNA, as determined using the Benesi-Hildebrand plot, was 7.9 × 104 M-1 at 298 K, indicating a moderate binding affinity. The primary binding contact forces were hydrophobic and hydrogen bonding interactions, as verified by the enthalpy and entropy changes (ΔH0 and ΔS0), which were - 16.25 kJ.mol-1 and 39.30 J mol-1 K-1, respectively. According to the results of UV-vis spectrophotometry, viscosity assays, and competitive binding interactions with ethidium bromide or rhodamine B, the binding mode of nintedanib to ssDNA was minor groove. Molecular docking and molecular dynamic simulation studies showed that nintedanib fitted into the B-DNA minor groove's AT-rich region with high stability. This study can contribute to further understanding of nintedanib's molecular mechanisms and pharmacological effects.

Interrogating the estrogen-mediated regulation of adrenocortical Klotho expression using ovariectomized albino rat model exposed to repeated restraint stress.

Reproductive aging is associated with altered stress response and many other menopausal symptoms. Little is known about the adrenal expression of the anti-aging protein Klotho or how it is modulated by estrogen in ovariectomized stressed rats. Fifty-six Wistar female rats were assigned into seven equal groups. Sham-operated (Sham), sham stressed (Sham/STS), ovariectomized (OVR), ovariectomized stressed (OVR/STS), ovariectomized stressed rosiglitazone-treated (OVR/STS/R), ovariectomized stressed estrogen-treated (OVR/STS/E), and ovariectomized stressed estrogen/GW9662 co-treated (OVR/STS/E/GW) groups. All stressed rats were subjected daily to a one-hour restraint stress test for 19 days. At the end of the experiment, blood was collected for serum corticosterone (CORT) analysis. Adrenal tissues were obtained and prepared for polymerase chain reaction (PCR) assay, hematoxylin and eosin (H&E), immunohistochemistry-based identification of Klotho and PPAR-γ, and Oil Red O (ORO) staining. The rise in serum CORT was negligible in the OVR/STS group, in contrast to the Sham/STS group. The limited CORT response in the former group was restored by estrogen and rosiglitazone and blocked by estrogen/GW9226 co-administration. ORO-staining revealed a more evident reduction in the adrenal fat in the OVR/STS group, which was reversed by estrogen and counteracted by GW. Also, there was a comparable expression pattern of Klotho and PPAR-γ in the adrenals. The adrenal Klotho decreased in the OVR/STS group, but was reversed by estrogen treatment. GW9226/estrogen co-treatment interfered with the regulatory effect of estrogen on Klotho. The study suggested modulation of the adrenal Kotho expression by estrogen, in the ovariectomized rats subjected to a restraint stress test. This estrogen-provided adrenal protection might be mediated by PPAR-γ activation.

NOD2 deletion promotes cardiac hypertrophy and fibrosis induced by pressure overload.

Nucleotide-binding oligomerization domain-2 (NOD2, also designated CARD15), a member of the NOD-leucine-rich repeat (LRR) protein family (also called the CATERPILLAR family), is upregulated in atheroma lesions and has an important role in regulating the intracellular recognition of bacterial components by immune cells. However, the effect of NOD2 on cardiac hypertrophy induced by a pathological stimulus has not been determined. Here, we investigated the effects of NOD2 deficiency on cardiac hypertrophy induced by aortic banding (AB) in mice. Cardiac hypertrophy was evaluated by echocardiographic, hemodynamic, pathological, and molecular analyses. NOD2 expression was upregulated in cardiomyocytes after aortic banding surgery in wild-type (WT) mice. NOD2 deficiency promoted cardiac hypertrophy and fibrosis 4 weeks after AB. Further, the enhanced activation of TLR4 and the MAPKs, NF-κB and TGF-ß/Smad pathways were found in NOD2-knockout (KO) mice compared with WT mice. Our results suggest that NOD2 attenuates cardiac hypertrophy and fibrosis via regulation of multiple pathways.