Enhancing Effector Jurkat Cell Activity and Increasing Cytotoxicity against A549 Cells Using Nivolumab as an Anti-PD-1 Agent Loaded on Gelatin Nanoparticles.

The current research investigated the use of gelatin nanoparticles (GNPs) for enhancing the cytotoxic effects of nivolumab, an immune checkpoint inhibitor. The unique feature of GNPs is their biocompatibility and functionalization potential, improving the delivery and the efficacy of immunotherapeutic drugs with fewer side effects compared to traditional treatments. This exploration of GNPs represents an innovative direction in the advancement of nanomedicine in oncology. Nivolumab-loaded GNPs were prepared and characterized. The optimum formulation had a particle size of 191.9 ± 0.67 nm, a polydispersity index of 0.027 ± 0.02, and drug entrapment of 54.67 ± 3.51%. A co-culture experiment involving A549 target cells and effector Jurkat cells treated with free nivolumab solution, and nivolumab-loaded GNPs, demonstrated that the latter had significant improvements in inhibition rate by scoring 87.88 ± 2.47% for drug-loaded GNPs against 60.53 ± 3.96% for the free nivolumab solution. The nivolumab-loaded GNPs had a lower IC50 value, of 0.41 ± 0.01 µM, compared to free nivolumab solution (1.22 ± 0.37 µM) at 72 h. The results indicate that administering nivolumab-loaded GNPs augmented the cytotoxicity against A549 cells by enhancing effector Jurkat cell activity compared to nivolumab solution treatment.

Preclinical evaluation of novel synthesised nanoparticles based on tyrosine poly(ester amide) for improved targeted pulmonary delivery.

Fixed dose combinations (FDCs) incorporating two or three medicines in a single inhaler have been created to enhance patient compliance and hence clinical outcomes. However, the development of dry powder inhalers (DPIs), particularly for FDCs, faces challenges pertinent to formulation uniformity and reproducibility. Therefore, this project aimed to employ nanotechnology to develop a FDC of DPIs for market-leading medicines-fluticasone propionate (FP) and salmeterol xinafoate (SAL)-for asthma management. Nanoaggregates were prepared using a novel biocompatible and biodegradable poly(ester amide) based on the amino acid tyrosine, utilising a one-step interfacial polymerisation process. The produced tyrosine poly (ester amide) drug-loaded nanoparticles were evaluated for content uniformity, PSA, FTIR, TEM, DSC, XRD and aerodynamic performance (in vitro and in vivo). The optimised formulation demonstrated high entrapment efficiency- > 90%. The aerodynamic performance in terms of the emitted dose, fine particle fraction and respirable dose was superior to the carrier-based marketed product. In-vivo studies showed that FP (above the marketed formulation) and SAL reached the lungs of mice in a reproducible manner. These results highlight the superiority of novel FDC FP/SAL nanoparticles prepared via a one-step process, which can be used as a cost-effective and efficient method to alleviate the burden of asthma.

Apigenin and Rutaecarpine reduce the burden of cellular senescence in bone marrow stromal stem cells.

Introduction: Osteoporosis is a systemic age-related disease characterized by reduced bone mass and microstructure deterioration, leading to increased risk of bone fragility fractures. Osteoporosis is a worldwide major health care problem and there is a need for preventive approaches. Methods and results: Apigenin and Rutaecarpine are plant-derived antioxidants identified through functional screen of a natural product library (143 compounds) as enhancers of osteoblastic differentiation of human bone marrow stromal stem cells (hBMSCs). Global gene expression profiling and Western blot analysis revealed activation of several intra-cellular signaling pathways including focal adhesion kinase (FAK) and TGFß. Pharmacological inhibition of FAK using PF-573228 (5 µM) and TGFß using SB505124 (1µM), diminished Apigenin- and Rutaecarpine-induced osteoblast differentiation. In vitro treatment with Apigenin and Rutaecarpine, of primary hBMSCs obtained from elderly female patients enhanced osteoblast differentiation compared with primary hBMSCs obtained from young female donors. Ex-vivo treatment with Apigenin and Rutaecarpine of organotypic embryonic chick-femur culture significantly increased bone volume and cortical thickness compared to control as estimated by µCT-scanning. Discussion: Our data revealed that Apigenin and Rutaecarpine enhance osteoblastic differentiation, bone formation, and reduce the age-related effects of hBMSCs. Therefore, Apigenin and Rutaecarpine cellular treatment represent a potential strategy for maintaining hBMSCs health during aging and osteoporosis.

Development and Characterization of Transdermal Patches Using Novel Thymoquinone-L-Arginine-Based Polyamide Nanocapsules for Potential Use in the Management of Psoriasis.

Thymoquinone (TQ) is a phytochemical compound present in Nigella sativa and has potential benefits for treating dermatological conditions such as psoriasis. However, its clinical use is limited due to its restricted bioavailability, caused mainly by its low solubility and permeability. To overcome this, a new transdermal drug delivery system is required. Nanoparticles are known to enhance material solubility and permeability, and hence, this study aimed to synthesize TQ-loaded L-arginine-based polyamide (TQ/Arg PA) nanocapsules incorporated into transdermal patches for prolonged delivery of TQ. To achieve this, Eudragit E polymer, plasticizers, and aloe vera as penetration enhancer were used to develop the transdermal patch. Furthermore, novel TQ/Arg-PA was synthesized via interfacial polymerization, and the resultant nanocapsules (NCs) were incorporated into the matrix transdermal patch. The Arg-PA NCs' structure was confirmed via NMR and FTIR, and optimal TQ/Arg-PA NCs containing formulation showed high entrapment efficiency of TQ (99.60%). Molecular and thermal profiling of TQ/Arg-PA and the transdermal patch revealed the effective development of spherical NCs with an average particle size of 129.23 ± 18.22 nm. Using Franz diffusion cells and synthetic membrane (STRAT M®), the in vitro permeation profile of the prepared patches demonstrated an extended release of TQ over 24 h, with enhanced permeation by 42.64% when aloe vera was employed. In conclusion, the produced formulation has a potential substitute for corticosteroids and other drugs commonly used to treat psoriasis due to its effectiveness, safety, and lack of the side effects typically associated with other drugs.

Optimum phosphate ion removal from aqueous solutions using roller kiln industrial solid waste.

Water scarcity is the most imperative predicament that concerns the population. In this research, a roller kiln (RK) industrial solid waste was used in the adsorption of phosphate ions from aqueous solutions thus converting a waste to wealth through aiding in serving as a water treatment application. The RK waste was produced from an Egyptian factory with a flow rate of million tons/day. Surface characterization for this solid waste was performed including transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray fluorescence (XRF), Fourier transform infra-red (FTIR), zeta potential (ZP), and particle size distribution (PSD). Based on the kinetics and isotherm studies, the pseudo first order (PFO) kinetic model and Freundlich isotherm model were the best-fitted models with the experimental data as well as the Dubinin-Radushkevich isotherm model indicated that the adsorption type was physical. The attained experimental results were then optimized to attain the experimental conditions at which the optimum adsorption percentage was achieved using response surface methodology (RSM). The optimum percentage removal of phosphate ions 99.5 (%) was achieved at the following experimental conditions; pH 8, temperature = 25 °C, contact time = 9 min, initial phosphate ion concentration = 10 mg/L and adsorbent dose 0.5 = g/L.

Kinetics and Isotherm Studies for Adsorption of Gentian Violet Dye from Aqueous Solutions Using Synthesized Hydroxyapatite.

Water is the most important resource for life, but it has been greatly exhausted over the past century as a result of the human population and environmentally harmful activities. The excessive quantity of dyes exists in the wastewater produced from the textile industries which is the main reason for serious human health and environmental problems. There are many dye removal techniques, and the most promising one is the adsorption technique. The novelty of this research is using unmodified synthesized hydroxyapatite (HAp) as an adsorbent for the removal of gentian violet (GV) dye from aqueous solutions as there are no sufficient data in the literature about using it in the adsorption of GV dye from aqueous solutions. Unmodified HAp was synthesized by a combined precipitation microwave method. The prepared adsorbent was characterized by scanning electron microscopy (SEM), energy dispersive X-ray (EDX), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and zeta potential analyses. The kinetic study showed that the pseudo-second-order (PSO) model was the best fitted model with the experimental data. Analysis of adsorption isotherms using different models showed that this adsorption system was better described by the Halsey isotherm with a maximum adsorption capacity (qmax) of 1.035 mg/g. The effects of experimental factors such as initial solution pH, initial dye concentration, adsorbent dose, and contact time were studied during the investigation of GV dye removal efficiency. The experimental results indicated that the maximum adsorption efficiency (99.32%) of the GV dye using HAp adsorbent was achieved at the following conditions: contact time = 90 min, pH = 12, initial GV dye concentration = 3 mg/L, and adsorbent dose = 1 g/L. The adsorption mechanism of the GV dye using HAp might be explained by the electrostatic interaction between the negatively charged surface of the HAp and the positively charged group of the GV dye. Thermodynamics study was performed on the adsorption process of GV dye from aqueous solutions using the synthesized HAp which revealed that this process was endothermic and spontaneous due to positive values of ΔH and ΔS and negative values of ΔG.

Empagliflozin Protects against Haloperidol Experimentally-Induced Ovarian Toxicity.

The present experiment aimed to identify the potential protective role of empagliflozin (EMPA) on haloperidol (HAL)-induced ovarian damage in female rats because of its anti-inflammatory, antioxidant, and antiapoptotic effects. EMPA was administered in the presence and absence of HAL. Thirty-two adult female albino rats were divided into four groups. Control group, EMPA group: received EMPA (10 mg/kg/day) p.o., HAL group: received HAL (2 mg/kg/day) p.o., HAL + EMPA group: HAL (2 mg/kg/day) combined with EMPA for 28 days. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-mullerian hormone (AMH) levels were measured. Ovarian oxidative stress parameters, besides inflammatory and apoptotic biomarkers, and ovarian Sirtuin-1 (Sirt-1) were evaluated. Ovarian histopathological examination and heat shock protein 70 (Hsp70) immunohistochemical study were performed. HAL significantly increased serum levels of FSH, LH, and ovarian inflammatory, apoptotic, and oxidative stress biomarkers and decreased serum AMH levels and Sirt-1 expression. Histopathological findings of ovarian damage and high Hsp70 immunoexpression were detected. EMPA significantly normalized the distributed hormonal levels, oxidative stress, inflammatory, and apoptotic biomarkers with a prompt improvement in the histopathological picture and a decrease in Hsp70 immunoexpression. Accordingly, EMPA protected against HAL-induced ovarian toxicity by modulating the Sirt-1/Hsp70/TNF-α/caspase-3 signaling pathway.

Diacerein modulates TLR4/ NF-κB/IL-1ß and TRPC1/CHOP signalling pathways in gentamicin-induced parotid toxicity in rats.

The present study aimed to identify the possible protective effect of diacerein (DIA) on gentamicin (GNT)-induced parotid toxicity in rats. DIA was administered in the presence and absence of GNT. Thirty-two Wistar adult male rats were randomly arranged into four groups: control, DIA (50 mg/kg/day), GNT (100 mg/kg) and GNT+DIA groups for 8 days. Parotid oxidative stress parameters, besides inflammatory and apoptotic biomarkers, were evaluated. Salivary flow rate, transient receptor potential canonical 1 (TRCP1), and C/EBP homologous protein (CHOP) in parotid tissue were measured. A parotid histopathological examination and an interleukin-1 beta (IL-1ß) immunohistochemical study were also performed. GNT significantly increased parotid oxidative stress, inflammatory, apoptotic and CHOP biomarkers with decreased salivary flow rate and TRCP1 level. A histopathological picture of parotid damage and high IL-1ß immunoexpression were detected. DIA significantly normalized the distributed oxidative, inflammatory and apoptotic indicators, CHOP and TRCP1, with a prompt improvement in the histopathological picture and a decrease in IL-1ß immunoexpression. These results reported that DIA protects against GNT-induced parotid toxicity via modulation of TLR4/NF-κB/IL-1ß and TRPC1/CHOP signalling pathways.

HR LC-MS/MS metabolomic profiling of Yucca aloifolia fruit and the potential neuroprotective effect on rotenone-induced Parkinson's disease in rats.

Yucca aloifolia L. fruit (Yucca or Spanish bayonet, family Asparagaceae) is recognized for its purplish red color reflecting its anthocyanin content, which has a powerful antioxidant activity. This study aimed to investigate yucca (YA) fruit extract's protective effect on Parkinson's disease (PD). In vitro study, the anti-inflammatory activity of yucca fruit extracts was explored by measuring tumor necrosis factor receptor 2 (TNF-R2) and nuclear factor kappa B (NF-KB) to choose the most effective extract. Afterward, a detailed in vivo investigation of the protective effect of the most active extract on rotenone-induced PD was performed on male albino Wister rats. First, the safety of the extract in two different doses (50 and 100 mg/kg in 0.9% saline orally) was confirmed by a toxicological study. The rats were divided into four groups: 1) normal control (NC); 2) rotenone group; and third and fourth groups received 50 and 100 mg/kg yucca extract, respectively. The neurobehavioral and locomotor activities of the rats were tested by rotarod, open field, and forced swim tests. Striatal dopamine, renal and liver functions, and oxidative stress markers were assessed. Western blot analysis of brain tissue samples was performed for p-AMPK, Wnt3a, and ß-catenin. Histopathological examination of striatal tissue samples was performed by light and electron microscopy (EM). The metabolites of the active extract were characterized using high-resolution LC-MS/MS, and the results showed the prevalence of anthocyanins, saponins, phenolics, and choline. Biochemical and histopathological tests revealed a dose-dependent improvement with oral Yucca extract. The current study suggests a possible neuroprotective effect of the acidified 50% ethanol extract (YA-C) of the edible Yucca fruit, making it a promising therapeutic target for PD.

In silico and in vitro anti-inflammatory study of phenolic compounds isolated from Eucalyptus maculata resin.

Plant resins are rich in bioactive compounds with high medicinal values. However, the chemistry and anti-inflammatory activity of the resins produced by trees of the genus Eucalyptus were scarcely investigated. The inflammatory targets cyclooxygenase-1 (COX-1), COX-2, TNF-, NF-B, and NO were significantly inhibited by the methanolic extract of Eucalyptus maculata kino resin (EME) and its CH2Cl2 soluble fraction (MCF). Sakuranetin (C1), (E)-cinnamic acid (C2), kaempferol 7- methyl ether (C3), 7-O-methyl aromadendrin (C4), and 1,6- dicinnamoyl-O-α-D-glucopyranoside (C5) were isolated from MCF. Three compounds (C1, C2, and C4) showed potent in vitro COX-1 inhibition, while C5 inhibited COX-2, TNF-α, NF-κB, and NO significantly. An in-silico study revealed that C5 had the highest binding affinity to the active site in COX-2 with binding energy score (S) of -14.85 kcal/mol, better than celecoxib (COX-2 inhibitor). In conclusion, 1,6-dicinnamoyl-O-α-D-glucopyranoside (C5) could be investigated further in the search for anti-inflammatory agents.

Taste Masking of Promethazine Hydrochloride Using l-Arginine Polyamide-Based Nanocapsules.

Promethazine hydrochloride (PMZ), a potent H1-histamine blocker widely used to prevent motion sickness, dizziness, nausea, and vomiting, has a bitter taste. In the present study, taste masked PMZ nanocapsules (NCs) were prepared using an interfacial polycondensation technique. A one-step approach was used to expedite the synthesis of NCs made from a biocompatible and biodegradable polyamide based on l-arginine. The produced NCs had an average particle size of 193.63 ± 39.1 nm and a zeta potential of −31.7 ± 1.25 mV, indicating their stability. The NCs were characterized using differential scanning calorimetric analysis and X-ray diffraction, as well as transmission electron microscopy that demonstrated the formation of the NCs and the incorporation of PMZ within the polymer. The in vitro release study of the PMZ-loaded NCs displayed a 0.91 ± 0.02% release of PMZ after 10 min using artificial saliva as the dissolution media, indicating excellent taste masked particles. The in vivo study using mice revealed that the amount of fluid consumed by the PMZ-NCs group was significantly higher than that consumed by the free PMZ group (p < 0.05). This study confirmed that NCs using polyamides based on l-arginine and interfacial polycondensation can serve as a good platform for the effective taste masking of bitter actives.

Management challenges and choices in patients with bipolar disorder: An Egyptian observational study.

BACKGROUND: Patients with bipolar disorder (BD) had contributed immensely to high health service utilization. Variation in clinical practices that miss to follow the standard guidelines all with the disorder complexity, deepened the management gap. This study aimed to provide an Egyptian epidemiological database of the ongoing clinical practices that framed different diagnostic and management choices in a sample of patients with bipolar disorder. Highlighting challenges and the need for optimized clinical practices. METHODS: Over 4 months in 2014, 20 clinicians filled in a designed sheet of their routine healthcare practice with information about; caseload /month, management guidelines knowledge background. Out of 301 patients in acute episode BD, 300 patients aged 20 to 60 years from both sexes, completed their assessment using; (1) a semi-structured interview sheet, (2) Structured Clinical Interview for DSM-IV Axis I (SCID I) for psychiatric diagnoses, (3) Global Assessment of Functioning scale for illness impact. RESULTS: Psychiatrists received 49.5 ± 37.0 (mean ± SD) patient /month. 95% of them reported positive knowledge background on BD diagnostic guidelines and treatment recommendations (G/R), 89.6% of patients had different initial diagnosis than BD.The most commonly given initial diagnosis was major depressive disorder (33%) followed by brief psychotic disorder(20.7%) and others. The median of time taken from the initial to bipolar diagnosis was 12.3 months. Majority of patients had evident functional impairment. Atypical antipsychotics were mostly used. Drug abuse and obesity were high comorbidities. CONCLUSION: The evident gap in practice and BD complexity have negative impact on clinical outcomes. Physician's continuous medical education programs and individually tailored standard medical care are recommended for optimized practices.

Opposites Attract: Electrostatically Driven Loading of Antimicrobial Peptides into Phytoglycogen Nanocarriers.

Antimicrobial peptides, such as GL13K, have a high binding selectivity toward bacterial membranes, while not affecting healthy mammalian cells at therapeutic concentrations. However, delivery of these peptides is challenging since they are susceptible to proteolytic hydrolysis and exhibit poor cellular uptake. A protective nanocarrier is thus proposed to overcome these obstacles. We investigate the potential to employ biodegradable phytoglycogen nanoparticles as carriers for GL13K using a simple loading protocol based on electrostatic association rather than chemical conjugation, eliminating the need for control of chemical cleavage for release of the peptide in situ. Both the native (quasi-neutral) and carboxymethylated (anionic) phytoglycogen were evaluated for their colloidal stability, loading capacity, and release characteristics. We show that the anionic nanophytoglycogen carries a greater cationic GL13K load and exhibits slower release kinetics than native nanophytoglycogen. Isotope exchange measurements demonstrate that the antimicrobial peptide is entrapped in the pores of the dendritic-like macromolecule, which should provide the necessary protection for delivery. Importantly, the nanoformulations are active against a Pseudomonas aeruginosa clinical isolate at concentrations comparable to those of the free peptide and representative, small molecule antibiotics. The colloidal nanocarrier preserves peptide stability and antimicrobial activity, even after long periods of storage (at least 8 months).

Gastroprotective and anti-Helicobacter pylori potentials of essential oils from the oleoresins of Araucaria bidwillii and Araucaria heterophylla.

Plant resins or oleoresins comprise a chemically complex mixture of different classes of compounds. Oleoresin of the genus Araucaria combines essential oil (EO) and resin. It possesses gastroprotective, cytotoxic, and timicrobial, antipyretic, and anti-inflammatory activities. The study aimed to investigate the EOs from the oleoresins of two Araucaria species, A. bidwillii and A. heterophylla, chemically and biologically for their gastroprotective, anti-inflammatory, antioxidant, and anti-Helicobacter pylori potentials. The chemical composition of both species cultivated in Egypt was analyzed with GC-MS and compared with those cultivated abroad using principal component analysis (PCA). There were 37 and 17 secondary metabolites identified in A. heterophylla and A. bidwillii, respectively. The EOs of both species showed a pronounced inhibitory effect on Helicobacter pylori activity in vitro. The gastroprotective effect was assessed in vivo using ethanol-induced gastric ulcer model in rats. Inflammatory cytokines, oxidative stress, and the nuclear factor-kappa B (NF-κB) biomarkers were assessed in the stomach tissues. The ulcer index and percentage of ulcer protection were determined. Stomach sections were examined histopathologically by staining with (H/E) and periodic acid Schiff (PAS). Moreover, the proliferative index was determined using the Ki-67 immunostaining. The treatment of rats with EOs (50, 100, and 200 mg/kg, orally) 1 hour prior to ethanol administration showed promising gastroprotective, anti-inflammatory, and antioxidant potentials. These findings declared the gastroprotective role played by both EOs with the superiority of A. bidwillii over A. heterophylla via modulation of oxidative stress/NF-κB/inflammatory cytokines. Their use can be recommended to protect against the recurrence of peptic ulcers.

High-fat diet-induced obesity augments the deleterious effects of estrogen deficiency on bone: Evidence from ovariectomized mice.

Several epidemiological studies have suggested that obesity complicated with insulin resistance and type 2 diabetes exerts deleterious effects on the skeleton. While obesity coexists with estrogen deficiency in postmenopausal women, their combined effects on the skeleton are poorly studied. Thus, we investigated the impact of high-fat diet (HFD) on bone and metabolism of ovariectomized (OVX) female mice (C57BL/6J). OVX or sham operated mice were fed either HFD (60%fat) or normal diet (10%fat) for 12 weeks. HFD-OVX group exhibited pronounced increase in body weight (~86% in HFD and ~122% in HFD-OVX, p < 0.0005) and impaired glucose tolerance. Bone microCT-scanning revealed a pronounced decrease in trabecular bone volume/total volume (BV/TV) (-15.6 ± 0.48% in HFD and -37.5 ± 0.235% in HFD-OVX, p < 0.005) and expansion of bone marrow adipose tissue (BMAT; +60.7 ± 9.9% in HFD vs. +79.5 ± 5.86% in HFD-OVX, p < 0.005). Mechanistically, HFD-OVX treatment led to upregulation of genes markers of senescence, bone resorption, adipogenesis, inflammation, downregulation of gene markers of bone formation and bone development. Similarly, HFD-OVX treatment resulted in significant changes in bone tissue levels of purine/pyrimidine and Glutamate metabolisms, known to play a regulatory role in bone metabolism. Obesity and estrogen deficiency exert combined deleterious effects on bone resulting in accelerated cellular senescence, expansion of BMAT and impaired bone formation leading to decreased bone mass. Our results suggest that obesity may increase bone fragility in postmenopausal women.

The pathophysiology of osteoporosis in obesity and type 2 diabetes in aging women and men: The mechanisms and roles of increased bone marrow adiposity.

Osteoporosis is defined as a systemic skeletal disease characterized by decreased bone mass and micro-architectural deterioration leading to increased fracture risk. Osteoporosis incidence increases with age in both post-menopausal women and aging men. Among other important contributing factors to bone fragility observed in osteoporosis, that also affect the elderly population, are metabolic disturbances observed in obesity and Type 2 Diabetes (T2D). These metabolic complications are associated with impaired bone homeostasis and a higher fracture risk. Expansion of the Bone Marrow Adipose Tissue (BMAT), at the expense of decreased bone formation, is thought to be one of the key pathogenic mechanisms underlying osteoporosis and bone fragility in obesity and T2D. Our review provides a summary of mechanisms behind increased Bone Marrow Adiposity (BMA) during aging and highlights the pre-clinical and clinical studies connecting obesity and T2D, to BMA and bone fragility in aging osteoporotic women and men.

Drowning versus postmortem submersion: Biochemical and histopathological examination and estimation of postmortem intervals (an experimental study).

Estimation of the postmortem interval (PMI) is a very essential task for forensic experts especially in criminal cases. drowning is still the most difficult tasks for forensic pathologists to be diagnosed and differentiated from a body disposed of in water following death especially after long post-mortem period. The objective of this study was to estimate the PMI in drowning in comparison to postmortem submersion using mRNA expression of AQP1 in addition to histological and immunohistochemical examination of caspase-3 in the adrenal and thyroid glands of adult albino rats. Adult albino rats were divided into 2 groups; group A (drowning) and group B (post-mortem submersion). Thyroid and adrenal glands were examined at different PMI. The results revealed significant differences at AQP1 levels between drowning and postmortem submersion at different PMI. Histological changes and caspase-3 expression immunologically in both glands were helpful.

Synthesis and Characterization of Chelating Hyperbranched Polyester Nanoparticles for Cd(II) Ion Removal from Water.

Chelating hyperbranched polyester (CHPE) nanoparticles have become an attractive new material family for developing high-capacity nanoscale chelating agents with highly branched structures and many functional groups in the main chains and end groups that can be used to remove heavy metals from water. In this study, a hyperbranched polyester with a particle size of 180-643 nm was synthesized with A2+B3 interfacial polymerization, using dimethylmalonyl chloride as the difunctional monomer (A2) and 1,1,1-tris(4-hydroxyphenyl)ethane (THPE) as the trifunctional monomer (B3). FTIR and NMR were used to characterize the CHPE and confirm the structure. The CHPE nanoparticles were generally considered hydrophilic, with an observed swelling capacity of 160.70%. The thermal properties of the CHPE nanoparticles were studied by thermal gravimetric analysis (TGA) with 1% mass loss at temperatures above 185 °C. The XRD of the CHPE nanoparticles showed a semi-crystalline pattern, as evident from the presence of peaks at positions ~18° and 20°. The nature of the surface of the CHPE was examined using SEM. Batch equilibrium was used to investigate the removal properties of the CHPE nanoparticles towards Cd(II) ions as a function of temperature, contact time, and Cd(II) concentration. The Cd(II) ion thermodynamics, kinetics, and desorption data on the CHPE nanoparticles were also studied.

Synthesis and In-Vivo Evaluation of Benzoxazole Derivatives as Promising Anti-Psoriatic Drugs for Clinical Use.

2-(4-Chlorophenyl)-5-benzoxazoleacetic acid (CBA) and its ester, methyl-2-(4-chloro-phenyl)-5-benzoxazoleacetate (MCBA), were synthesized, and their structures were confirmed by 1HNMR, IR, and mass spectrophotometry. The anti-psoriatic activities of CBA and MCBA were tested using an imiquimod (IMQ)-induced psoriatic mouse model, in which mice were treated both topically (1% w/w) and orally (125 mg/kg) for 14 days. The erythema intensity, thickness, and desquamation of psoriasis were scored by calculating the psoriasis area severity index (PASI). The study also included the determination of histopathological alterations in the skin tissues of treated mice. Topical and oral administration of CBA and MCBA led to a reduction in erythema intensity, thickness, and desquamation, which was demonstrated by a significant decrease in the PASI value. In addition, skin tissues of mice treated with CBA and MCBA showed less evidence of psoriatic alterations, such as hyperkeratosis, parakeratosis, scale crust, edema, psoriasiform, and hyperplasia. After administration of either topical or oral dosing, the anti-psoriatic effects were found to be stronger in MCBA-treated than in CBA-treated mice. These effects were comparable to those produced by Clobetasol propionate, the reference drug. This drug discovery could be translated into a potential new drug for future clinical use in psoriasis treatment.

Impaired Bone Fracture Healing in Type 2 Diabetes Is Caused by Defective Functions of Skeletal Progenitor Cells.

The mechanisms of obesity and type 2 diabetes (T2D)-associated impaired fracture healing are poorly studied. In a murine model of T2D reflecting both hyperinsulinemia induced by high-fat diet and insulinopenia induced by treatment with streptozotocin, we examined bone healing in a tibia cortical bone defect. A delayed bone healing was observed during hyperinsulinemia as newly formed bone was reduced by -28.4 ± 7.7% and was associated with accumulation of marrow adipocytes at the defect site +124.06 ± 38.71%, and increased density of SCA1+ (+74.99 ± 29.19%) but not Runx2+ osteoprogenitor cells. We also observed increased in reactive oxygen species production (+101.82 ± 33.05%), senescence gene signature (≈106.66 ± 34.03%), and LAMIN B1- senescent cell density (+225.18 ± 43.15%), suggesting accelerated senescence phenotype. During insulinopenia, a more pronounced delayed bone healing was observed with decreased newly formed bone to -34.9 ± 6.2% which was inversely correlated with glucose levels (R2 = 0.48, P < .004) and callus adipose tissue area (R2 = .3711, P < .01). Finally, to investigate the relevance to human physiology, we observed that sera from obese and T2D subjects had disease state-specific inhibitory effects on osteoblast-related gene signatures in human bone marrow stromal cells which resulted in inhibition of osteoblast and enhanced adipocyte differentiation. Our data demonstrate that T2D exerts negative effects on bone healing through inhibition of osteoblast differentiation of skeletal stem cells and induction of accelerated bone senescence and that the hyperglycemia per se and not just insulin levels is detrimental for bone healing.