Evaluation of Plant-Based Silver Nanoparticles for Antioxidant Activity and Promising Wound-Healing Applications.

The current research focuses on the green synthesis of silver nanoparticles (AgNPs) using a polar extract of taro corms and the evaluation of its antioxidant properties and wound-healing applications. Taro corm extract (100 mL) was treated with a 5 mM AgNO3 solution (100 mL) at room temperature for the formation of AgNPs, and a color change was observed. The surface plasmon resonance (SPR) peaks in their UV-visible spectra appeared at a range of 438-445 nm. Fourier transform infrared, scanning electron microscopy, energy-dispersive X-ray, dynamic light scattering, and X-ray diffraction were used for the characterization of the taro corms extract-mediated AgNPs (TCE-AgNPs). The synthesized AgNPs were crystalline and spherical, with an average size of 244.9-272.2 nm with a polydispersity index of 0.530 and zeta potential of -18.8 mV, respectively. The antibacterial potential of TCE-AgNPs was tested, and the inhibition zones detected against Cronobacter sakazakii, Pseudomonas aeruginosa, Listeria monocytogenes, and Enterococcus faecalis were 28, 26, 18, and 13 mm, respectively. Furthermore, the antioxidant activity of TCE-AgNPs showed significant radical-scavenging activity compared to the standard used. Collagen content data collected from regenerated tissue and higher collagen content indicated rapid wound healing compared to others, which was seen in a group treated with TCE-AgNP film bandages.

Formulation and Characterization of Curcumin Niosomes: Antioxidant and Cytotoxicity Studies.

Curcumin's applications in the treatment of conditions including osteoarthritis, dementia, malignancies of the pancreas, and malignancies of the intestines have drawn increasing attention. It has several wonderful qualities, including being an anti-inflammatory agent, an anti-mutagenic agent, and an antioxidant, and has substantially reduced inherent cytotoxicity outcomes. Although curcumin possesses multiple known curative properties, due to its limited bioavailability, it is necessary to develop efficient strategies to overcome these hurdles. To establish an effective administration method, various niosomal formulations were optimized using the Box-Behnken design and assessed in the current investigation. To examine the curcumin niosomes, zeta sizer, zeta potential, entrapment efficiency, SEM, antioxidant potential, cytotoxicity, and release studies were performed. The optimized curcumin niosomes exhibited an average particle size of 169.4 nm, a low PDI of 0.189, and high entrapment efficiency of 85.4%. The release profile showed 79.39% curcumin after 24 h and had significantly higher antioxidant potential as compared with that of free curcumin. The cytotoxicity results of curcumin niosomes presented increased mortality in human ovarian cancer A2780.

Arsenic fractionation and speciation in different textured soils supplied with farmyard manure and accumulation by sunflower under alkaline calcareous conditions.

Arsenic (As) is a naturally occurring element that is found in soil, water, and rocks. However, it can also be released into the environment through human activities. Arsenic is considered an environmental hazard because it is toxic to humans and animals and can cause serious health problems. Additionally, As-contaminated soil can limit plant growth and reduce crop yields, leading to economic losses for farmers. So, decreasing metal/metalloid solubility in soil by synthetic and organic amendments leads to better crop productivity on contaminated soils. The current study aimed to evaluate farmyard manure (FYM)-mediated changes in soil arsenic (As) behavior, and subsequent effects on achene yield of sunflower. Treatment plan comprised of two As levels, i.e., As-60 (60 mg kg-1) and As-120 (120 mg kg-1), four FYM levels (0, 20, 35, and 50 g kg-1), three textural types (sandy, loamy and clayey), and replicated thrice. Seven As fractions including water soluble-As (WS-As), labile-As (L-As), calcium-bound As (Ca-As), aluminum-bound As (Al-As), iron-bound As (Fe-As), organic-matter-bound As (OM-As), and residual-As (R-As) were determined which differed significantly (P ≤ 0.05) with FYM and soil texture. FYM supplementation decreased WS-As, L-As, Ca-As, and Al-As while increased Fe-As, OM-As, and R-As. The immobilizing effect of FYM increased with increasing its rate of application, and maximum effect was found in clayey soil. As speciation in soil also significantly (P ≤ 0.05) affected by FYM and soil texture, with a reduction in arsenate while increase in arsenite, mono-methyl arsenate, and di-methyl arsenate with increasing the rate of FYM supplementation. Bioaccumulation factor reduced with FYM addition, and highest reduction of 38.65 and 42.13% in sandy, 34.24 and 36.26% in loamy while 29.16 and 35.10% in clayey soils at As-60 and As-120, respectively, by 50 g kg-1 FYM compared with respective As treatments without FYM. As accumulation in plant parts was significantly (P ≤ 0.05) reduced by FYM with the subsequent improvement in achene yield.

Mimosa pudica mucilage nanoparticles of losartan potassium: Characterization and pharmacodynamics evaluation.

The current research was to develop nanoparticles based on Mimosa pudica mucilage (MPM) that could encapsulate losartan potassium (LP). Nanoparticles (NPs) produced through ionic-gelation method; the polymerization of the mucilage carried out using calcium chloride as cross-linking agent. The MPMLP-NPs demonstrated vastly enhanced pharmaceutical characteristics, presented discrete surface with spherical shape of 198.4-264.6 nm with PDI ranging 0.326-0.461 and entrapment efficiency was in the range of 80.65 ± 0.82-90.79 ± 0.96%. FTIR and DSC indicated the stability of drug during the formulation of nanoparticles. An acute oral toxicity investigation found no significant alterations in behavior and histopathology criteria. The MPMLP-NPs formulation revealed the better rates and sustained effect as assessed with the commercial product. Moreover, low dose of MPMLP-NPs showed similar anti-hypertensive effect as assessed with the marketed tablet.

In Vitro/In Vivo Evaluation of Clomipramine Orodispersible Tablets for the Treatment of Depression and Obsessive-Compulsive Disorder.

The first and only antidepressant drug on the market with solid proof of clinically significant serotonin and noradrenaline reuptake inhibition is clomipramine (CLP). However, significant first-pass metabolism reduces its absorption to less than 62%. It is heavily protein-bound and broadly dispersed across the body (9-25 L/kg volume of distribution). The purpose of this research was to formulate CLP orodispersible tablets that immediately enable the drug to enter the bloodstream and bypass systemic portal circulation to improve its bioavailability. A factorial design was employed using varied amounts of Plantago ovata mucilage (POM) as a natural superdisintegrant, as well as croscarmellose sodium and crospovidone as synthetic disintegrants. Their physiochemical compatibility was evaluated by FTIR, DSC/TGA, and PXRD analysis. The blend of all formulations was assessed for pre- and post-compaction parameters. The study found that tablets comprising Plantago ovata mucilage as a superdisintegrant showed a rapid in vitro disintegration time, i.e., around 8.39 s, and had an excellent dissolution profile. The anti-depressant efficacy was evaluated by an open-field test (OFT) and the forced swimming test (FST) was applied to create hopelessness and despair behavior as a model of depression in animals (Albino rats). The in vivo study revealed that the efficiency of the optimized formulation (F9) in the treatment of depression is more than the marketed available clomfranil tablet, and may be linked to its rapid disintegration and bypassing of systemic portal circulation.

Evaluation of CSF kappa free light chains for the diagnosis of multiple sclerosis (MS): a comparison with oligoclonal bands (OCB) detection via isoelectric focusing (IEF) coupled with immunoblotting.

This study was done to evaluate the diagnostic accuracy of cerebrospinal fluid kappa free light chain (KFLC) for diagnosis of multiple sclerosis, against isoelectrofocusing (IEF) to detect oligoclonal bands (OCB) as gold standard. 64 cases were divided into positive and negative based on the OCB results. Diagnostic accuracy was calculated for the 1 mg/L cut-off. The 1 mg/L cut-off yielded a percent agreement of 86.1% and Cohen's kappa value of 0.8. Youden's index, yielded a cut-off of 0.92 mg/L as optimal (90.3% specificity and 90.9% sensitivity). The analytical time was 3 hours and 55 min for IEF and 25 min for KFLC. The cost of a single OCB test was PKR12 000 (US$68.17) compared with PKR4150 (US$23.58) for KFLC. KFLC proved to be an accurate, cheaper and time-saving alternative and can be performed prior to the contemporary testing.

Synthesis and evaluation of chitosan based controlled release nanoparticles for the delivery of ticagrelor.

The aim of this contemporary work was to formulate a controlled release mucoadhesive nanoparticle formulation for enhancing the oral bioavailability of Ticagrelor (TG), a BCS class IV drug, having low oral bioavailability of about 36%. The nanoparticles can act as efficient carriers for hydrophobic drugs, due to having high surface area and hence can improve their aqueous solubility due to their hydrophilic nature. The nanoparticles (NPs) of TG were formulated using chitosan (CH) as polymer and sodium tripolyphosphate (TPP) as cross-linker, by ionic gelation technique with varying concentrations of polymer with respect to TG and TPP. Characterization of prepared nanoparticles was carried out to assess zeta potential, size, shape, entrapment efficiency (EE) and loading capacity (LC), using zeta sizer, surface morphology and chemical compatibility analysis. Drug release was observed using UV-Spectrophotometer. By increasing concentration of CH the desired size of particles (106.9 nm), zeta potential (22.6 mv) and poly dispersity index (0.364) was achieved. In vitro profiles showed a controlled and prolonged release of TG in both lower pH-1.2 and neutral pH-7.4 mediums, with effective protection of entrapped TG in simulated gastric conditions. X-ray diffraction patterns (XRD) showed the crystalline nature of formed NPs. Hence, this effort showed that hydrophobic drugs can be effectively encapsulated in nanoparticulate systems to enhance their solubility and stability, ultimately improving their bioavailability and effectiveness with better patient compliance by reducing dosing frequencies as well.

Interactive effect of different salinity sources and their formulations on plant growth, ionic homeostasis and seed quality of maize.

Soil salinity is one of the most pernicious environmental hazards affecting crop growth and productivity in arid and semi-arid climates. In saline soils, the crop plants encounter nutrients deficient conditions mainly due to antagonistic affinity of sodium (Na+) and chloride (Cl-). The accumulation of salts in the rhizosphere restricts plant growth, the severity of which depends on the source and concentration of the salt. Therefore, we hypothesized that sodium containing salts could have toxic effects on maize plants either in a single or in combined form. To evaluate the interactive effect of sodium salts on plant growth, ionic homeostasis, and seed quality attributes, a pot study was performed using maize as a test plant at the research area of the College of Agriculture, University of Sargodha. Selected salts including, NaCl, Na2SO4 and their combination (NaCl + Na2SO4), were applied in equal ratio for different salinity levels (7, 10, 13 and 16 dS m-1) and the untreated control. The results show that all the measured growth, yield, biochemical and quality attributes of maize were negatively affected with increasing concentration of all the salt sources; however, severity of these effects were more intense when NaCl was applied at all salinity levels. It is concluded that all salts (NaCl, Na2SO4 and NaCl + Na2SO4) had negative effects on biochemical, qualitative, growth and yield characteristics of maize plant. Most importantly, NaCl was found to be more harmful compared to Na2SO4 and mixtures of both salts due to the dominance of Na+ and Cl-ions. Among all salinity levels, the more detrimental effects of NaCl occurred at salinity level of 16 dS m-1.

Fabrication, Characterization and Toxicity Evaluation of Chemically Cross linked Polymeric Network for Sustained Delivery of Metoprolol Tartrate.

Natural mucilages are auspicious biodegradable polymeric materials. The aim of the present research work was to elucidate the characteristics of quince mucilage-based polymeric network for sustained delivery of metprolol tartrate and its toxicity evaluation. Mucilage was extracted by hot water extraction, and characterization of quince mucilage was accomplished by using Fourier transform infrared (FTIR) spectroscopy. Different batches of quince mucilage polymeric network were prepared by free radical polymerization by utilizing varying ratios of quince mucilage, acrylamide and crosslinker. Degree of swelling depends on concentration of mucilage, monomer and also on crosslinking density of polymeric network. FTIR illustrates proficient grafting, and morphological (scanning electron microscopy) analysis signified porous design. Hence, quince mucilage-based design was encouraging for sustained delivery of metprolol tartrate and acute toxicity evaluation proved that mucilage-based network was safe for oral drug delivery system.

Formulation and Evaluation of Linum usitatissimum Mucilage-Based Nanoparticles for Effective Delivery of Ezetimibe.

INTRODUCTION: The aim of current study was to prepare Linum usitatissimum mucilage (LUM) based nanoparticles, capable of encapsulating hydrophobic drug ezetimibe as nanocarriers. METHODS: Solvent evaporation and nanoprecipitation techniques were used to develop nanoparticles by encapsulating ezetimibe in the articulated matrix of polysaccharide fractions. Developed nanoparticles were characterized to determine the particle size, zeta potential, polydispersibility index (PDI), and entrapment efficiency (EE). Morphology and physicochemical characterization were carried out through SEM, FTIR, PXRD and thermal analysis. Saturation solubility and in vitro release studies were also performed. Safety assessment of ezetimibe loaded nanoparticles was evaluated via oral acute toxicity study. RESULTS: The mean particle size, zeta potential, PDI and EE for emulsion solvent evaporation were 683.6 nm, -28.3 mV, 0.39, 63.7% and for nanoprecipitation were 637.7 nm, 0.07, -27.1 mV and 80%, respectively. Thermal analysis confirmed enhanced thermal stability, whereas PXRD confirmed amorphous nature of drug. Saturation solubility (p-value <0.05) demonstrated improved solubility of drug when enclosed in linseed nanoparticles. Nanoprecipitation surpasses emulsion solvent evaporation in dissolution test by possessing smaller size. Acute oral toxicity study indicated no significant changes in behavioral, clinical or histopathological parameters of control and experimental groups. CONCLUSION: The in vitro release of ezetimibe was augmented by enhancing aqueous solubility through devised nanoparticles. Thus, linseed mucilage could act as biopolymer in the fabrication of nanoparticle formulation. The acute oral toxicological investigations provided evidence that LUMNs were safe after oral administration.

Aloe vera and artemisia vulgaris hydrogels: exploring the toxic effects of structural transformation of the biocompatible materials.

OBJECTIVES: This study was aimed to evaluate the toxicity profile of hydrogels of plant-derived mucilage from Aloe vera and Artemisia vulgaris used for various drug delivery applications, yet no such toxicity study has been reported for the toxicity evaluation of 3 D structures. New Drug carriers should be harmless for drug delivery applications. METHODS: Acute and sub-acute (repeated dose) oral toxicity studies were conducted following OECD 407 and 425 guidelines. In vitro toxicity through hemolysis and MTT assay were checked against RBC's and human macrophages respectively. RESULTS: The hemolysis and MTT assay showed good compatibility of hydrogels with blood components. Mutagenicity testing showed no genotoxic effects of hydrogels. In vivo toxicity evaluation was done in female albino rats and rabbits. General behavior, adverse effects, clinical signs and symptoms, and mortality were recorded for 14 days post-treatment which showed no significant (p < 005) abnormality. Hematological and biochemical parameters including LFTs and RFTs appeared to be normal with slight variations in the treated groups. The normal architecture of kidney, liver, heart and intestine was evident upon histopathological analyses. CONCLUSION: Hence, the results suggested that the 3 D structure of Aloe vera and Artemisia vulgaris based hydrogels are safe upon ingestion and can be used for drug delivery science being cheap, natural and biocompatible.

Clinical Spectrum in a Cohort of Patients With High Fecal Calprotectin Levels.

INTRODUCTION: Distinguishing between inflammatory bowel disease (IBD) and functional gastrointestinal disorders is a diagnostic challenge. The need for non-invasive biomarker as a diagnostic tool in the assessment of gastrointestinal symptoms is required. The objectives of current study were to determine the spectrum of clinical features in patients tested for fecal calprotectin presenting with high levels and to compare calprotectin levels among already diagnosed patients known to have IBD as per biopsy findings and documented on patients' file with newly presenting patients who were being investigated and did not have a diagnosis. METHODS: This retrospective cross-sectional study was conducted in the Department of Pathology and Laboratory Medicine and Department of Medicine, Aga Khan University, Karachi, Pakistan from January 2017 to December 2019. Subjects tested for fecal calprotectin who had elevated fecal calprotectin levels (n = 150) were included in the current study. Each patient deposited a random stool sample in an airtight container for calprotectin analysis. Biochemical analysis of calprotectin was performed by enzyme-linked immunosorbent assay using epitope calprotectin test kit (Epitope Diagnostics, Italy) on ETI-Max 3000 immunoassay analyzer (DiaSorin, Italy). A structured history form was used for data collection.  Results: One hundred and fifty patients were available for inclusion in the final analysis. Majority of the patients (n = 117, 78%) were adults (>18 years of age), and 52.7% (n = 79) were females. Median fecal calprotectin (IQR) was 317.3 µg/g (549.10 - 239.2 µg/g) in children (n = 33) and 305 µg/g (609.9 - 201.6 µg/g) in adults; the difference was statistically non-significant (p value > 0.05). On categorization according to disease, fecal calprotectin levels were significantly elevated (p value = 0.033) in IBD patients compared to normal subjects, 644 µg/g (644 - 587.8 µg/g) vs 308.5 µg/g (505.4 - 233.8 µg/g), respectively. Diarrhea (n = 13, 38.4%), abdominal cramps (n = 12, 36.4%), and weight loss (n = 11, 33.3%) were the most common complaints noted in children with high fecal calprotectin levels, whereas in adults, abdominal cramps (n = 60, 51.3%), diarrhea (n = 59, 50.4%), and weight loss (n = 46, 39.3%) were the common complaints. The median fecal calprotectin levels in children already known to have IBD (n = 3) were higher than the levels noted in children with no diagnosis (n = 30); p value > 0.05. Similarly, median fecal calprotectin levels in adults with IBD (n = 28) were higher than the levels noted in patients with no specific diagnosis (n = 91), 400.7 µg/g (656.6 - 244.3 µg/g) vs 302.7 µg/g (564.6 - 206 µg/g); p value > 0.05. CONCLUSION: Current study affirms that the fecal calprotectin test can be used in identifying IBD patients in all age groups.

WDR62 is associated with the spindle pole and is mutated in human microcephaly.

Autosomal recessive primary microcephaly (MCPH) is a disorder of neurodevelopment resulting in a small brain. We identified WDR62 as the second most common cause of MCPH after finding homozygous missense and frame-shifting mutations in seven MCPH families. In human cell lines, we found that WDR62 is a spindle pole protein, as are ASPM and STIL, the MCPH7 and MCHP7 proteins. Mutant WDR62 proteins failed to localize to the mitotic spindle pole. In human and mouse embryonic brain, we found that WDR62 expression was restricted to neural precursors undergoing mitosis. These data lend support to the hypothesis that the exquisite control of the cleavage furrow orientation in mammalian neural precursor cell mitosis, controlled in great part by the centrosomes and spindle poles, is critical both in causing MCPH when perturbed and, when modulated, generating the evolutionarily enlarged human brain.