Topical gel formulations as potential dermal delivery carriers for green-synthesized zinc oxide nanoparticles.

This study aimed to incorporate green-synthesized zinc oxide nanoparticles (ZnO NPs), functionalized with polyethylene glycol (PEG) and linked to doxorubicin (DOX), into various topical gel formulations (hydrogel, oleogel, and bigel) to enhance their dermal delivery. The ZnO NPs were produced using the aqueous extract of the root hair of Phoenix dactylifera. The optimized green-synthesized ZnO NPs, PEGylated and conjugated to DOX, demonstrated a particle size below 100 nm, low polydispersity index, and zeta potential between - 11 and - 19 mV. The UV-Vis spectroscopy analysis confirmed characteristic absorption peaks at 351 and 545 nm for ZnO and DOX, respectively. The transmission electron microscope (TEM) images revealed well-dispersed spherical nanoparticles without aggregation. Additionally, ZnO NPs-loaded gels exhibited uniformity, cohesion, no phase separation, pseudoplastic flow, and viscoelastic properties. The in vitro release studies showed that DOX-PEG-ZnO NPs hydrogel released 99.5% of DOX after 5 h of starting the release. Moreover, the penetration of DOX-PEG-ZnO NPs through excised rat skin was visualized by TEM. In conclusion, the hydrogel formulation containing green-synthesized DOX-PEG-ZnO NPs holds great promise for dermal administration in skin cancer treatment. Furthermore, the release rate and skin penetration of DOX from gels were varied based on the type of gel matrix and corroborated with their corresponding rheological properties.

Melatonin mitigates cisplatin-induced cognitive impairment in rats and improves hippocampal dendritic spine density.

Cisplatin-induced cognitive impairment (chemobrain) affects a considerable percentage of cancer patients and has no established pharmacological treatment. Chemobrain can be associated with neuroinflammation and oxidative stress. Melatonin, a pineal hormone, is known to have antioxidant, anti-inflammatory and neuroprotective potential. In this study, we investigated cisplatin-induced cognitive impairment in rats and whether melatonin can improve or reverse this impairment. Behavioral testing involved measuring working memory using the novel location recognition test (NLRT) under conditions of cisplatin or cisplatin + melatonin treatment, followed by the collection of rats' brains. The brains were subsequently stained with Golgi-Cox stain and then the hippocampus area CA3 of each one was examined, and dendritic spine density was calculated. Treatment with cisplatin resulted in deficits in the rats' performance in the NLRT (P < 0.05). These deficits were prevented by the coadministration of melatonin (P < 0.05). Cisplatin also reduced the density of dendritic spines in the hippocampus (P < 0.0001), specifically CA3 area, while the coadministration of melatonin significantly reversed this reduction (P < 0.001). This study showed that melatonin can ameliorate cisplatin-induced spatial memory deficits and dendritic spines density abnormalities in rats. Given that melatonin is a safe and wildly used supplement, it is feasible to explore its use as a palliative intervention in cancer treatment.

PD-L1 expression in breast invasive ductal carcinoma with incomplete pathological response to neoadjuvant chemotherapy.

OBJECTIVES: To investigate the expression of programmed death-ligand 1 (PD-L1) in breast cancer in association with incomplete pathological response (PR) to neoadjuvant chemotherapy (NAC). METHODS: PD-L1 expression was evaluated using immunohistochemistry in post-operative, post-NAC samples of 60 patients (n = 60) diagnosed with breast invasive ductal carcinoma with incomplete PR to NAC, including 31 matched pre-NAC and post-NAC samples (n = 31). PD-L1 protein expression was assessed using three scoring approaches, including the tumor proportion score (TPS), the immune cell score (ICS), and the combined tumor and immune cell score (combined positive score, CPS) with a 1% cut-off. RESULTS: In the post-operative, post-NAC samples (n = 60), positive expression rate of PD-L1 was observed in 18.3% (11/60) of cases by TPS, 31.7% (19/60) by ICS, and 25% (15/60) by CPS. In matched samples, positive expression rate of PD-L1 was observed in 19.3% (6/31) of patients by TPS, 51.6% (16/31) by ICS, and 19.3% (6/31) by CPS in pre-NAC specimens, while it was observed in 22.6% (7/31) of matched post-NAC samples by TPS, 22.6% (7/31) by ICS, and 19.3% (6/31) by CPS. In the matched samples, there was a significant decrease in PD-L1 immunoexpression using ICS in post-NAC specimens (McNemar's, p = 0.020), while no significant differences were found using TPS and CPS between pre- and post-NAC samples (p = 1.000, p = 0.617; respectively). PD-L1 immunoexpression determined by TPS or CPS was only significantly associated with ER status (p = 0.022, p = 0.021; respectively), but not with other clinicopathological variables. We could not establish a correlation between PD-L1 expression and the overall survival rate (p > 0.05). There were no significant differences in the tumor infiltrating lymphocytes count between the paired pre- and post-NAC samples (t = 0.581, p = 0.563 or Wilcoxon's Signed Rank test; z = -0.625, p = 0.529). CONCLUSION: Our findings indicate that PD-L1 protein expression in infiltrating immune cells was significantly reduced in breast tumors that developed incomplete PR following the exposure to NAC.

Anatomical and ultrastructural sex differences in mean diameter and thickness of myelinated axons in adult rat corpus callosum / Diferencias sexuales anatómicas y ultraestructurales del diámetro medio y grosor de los axones mielinizados en el cuerpo calloso de ratas adultas

Sexual dimorphism exists at all levels of the nervous system. These sex differences could underlie genderrelated differences in behavior and neuropsychological function, as well as the gender differences in the prevalence of various mental disorders such as autism, attention deficit disorders, and schizophrenia. Myelination, on the other hand, is a unique cellular process that can have a dramatic impact on the structure and physiology of an axon and its surrounding tissue. The corpus callosum (CC) is the largest of the brain commissures, which connects the cerebral cortices of the two hemispheres, and provides interhemispheric connectivity for information transfer and processing between cortical regions. Variation in the axonal properties of CC will alter the interhemispheric connectivity. The CC consists of myelinated and unmyelinated axons, glial cells and blood vessels. Several functional studies have reported that the function of CC is associated with its axons density and myelination properties. The sexual dimorphism in the axonal content of the CC has always been controversial; hence, the aim of this study was to analyze the differences in axons' diameter and myelin sheath thickness of the CC between male and female rats. For this purpose, five pairs of adult male and female rats were perfused and the CC were removed and sectioned. Four sections from different subregions of the corpus callosum that represent the genu, anterior body, posterior body, and splenium of the CC were stained and electron microscopic images were captured using stereological guidelines. Later, the axons diameter and myelin sheath thickness for each subregion were calculated and compared between males and females. Our preliminary findings of the present study indicated region specific differences in the myelinated axon thickness and diameter in the CC between male and female rats.

El dimorfismo sexual existe en todos los niveles del sistema nervioso. Estas diferencias de sexo podrían ser la base de las diferencias de comportamiento y función neuropsicológica relacionadas con el sexo, así como las diferencias en la prevalencia de diversos trastornos mentales, como el autismo, los trastornos por déficit de atención y la esquizofrenia. La mielinización, por otro lado, es un proceso celular único que puede tener un impacto dramático en la estructura y fisiología de un axón y su tejido circundante. El cuerpo calloso (CC) es la mayor comisura cerebral, que conecta las cortezas cerebrales de ambos hemisferios, y proporciona la conectividad interhemisférica para la transferencia y el procesamiento de información entre regiones corticales. La variación en las propiedades axonales de CC alterará la conectividad interhemisférica. El CC consiste en axones mielinizados y no mielinizados, células gliales y vasos sanguíneos. Varios estudios funcionales han informado que la función de CC está asociada con la densidad de axones y las propiedades de mielinización. El dimorfismo sexual en el contenido axonal del CC siempre ha sido controvertido; por lo tanto, el objetivo de este estudio fue analizar las diferencias en el diámetro de los axones y el grosor de la vaina de mielina del CC entre ratas macho y hembra. Para este propósito, se perfundieron cinco pares de ratas macho y hembra adultas y se extrajeron y seccionaron las CC. Se tiñeron cuatro secciones de diferentes subregiones del cuerpo calloso que representan el genu, el cuerpo anterior, el cuerpo posterior y el esplenio y se capturaron imágenes de microscopía electrónicas utilizando referencias estereológicas. Posteriormente se calculó el diámetro de los axones y el grosor de la vaina de mielina para cada subregión y se compararon entre machos y hembras. Nuestros hallazgos preliminares del presente estudio indicaron diferencias específicas en el grosor y diámetro del axón mielinizado en el CC entre ratas macho y hembra.

Gender differences in the rat corpus callosum: An ultrastructure study.

Sexual dimorphism exists at all levels of the nervous system, from genetic, anatomical and system levels. The sexual dimorphism in the axonal content of the corpus callosum (CC) has always been controversial; hence, the aim of this study was to analyse the differences in total, myelinated and unmyelinated axons density of various regions of the CC between male and female rats. To assess that, six pairs of adult male and female rats were perfused and the CC was removed and sectioned. Four sections from different subregions of the corpus callosum that represent the genu, anterior body, posterior body, and splenium, were stained, and electron microscopic images were captured using stereological guidelines. Later, the axons density for each subregion was calculated and compared between males and females. The findings of the present study indicated region-specific differences in the myelinated, unmyelinated or the ratio of myelinated/total axons in the CC between male and female rats.

Gold nanoparticles loaded into polymeric hydrogel for wound healing in rats: Effect of nanoparticles' shape and surface modification.

Nanotechnology-based platforms have gained a growing interest in skin wound healing. Herein, gold nanoparticles (AuNPs) of different shapes (rods and spheres) and surface modifications (neutral, cationic and anionic charged polymers) were synthesized, characterized and loaded into a thermosensitive hydrogel (poloxamer 407). AuNPs-hydrogels exhibited excellent colloidal stability and demonstrated slow and prolonged release behavior over a 48-h of exposure using in vitro model. Hydrogels of poly ethylene glycol (PEG)-gold nanorods (AuNRs) and cationic poly allyl amine hydrochloride (PAH)-AuNRs demonstrated remarkable wound healing properties upon topical application on wounds using an animal model. PEGylated and cationic charged-AuNRs hydrogels have enhanced skin re-epithelization and collagen deposition after 14 days of daily wound treatment compared to controls, and they affected the gene expression of several inflammatory and anti-inflammatory mediators. Hydrogels of PEG-AuNRs and PAH-AuNRs exhibited potent in vitro antibacterial activity against staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa). Furthermore, AuNPs of different shapes and surface modifications demonstrated low percentages of deposition into the main body organs after 21 days of daily wound treatment. Hydrogels of AuNRs could be a promising nano-platform for wound healing.

C1q nephropathy among children with nephrotic syndrome: Ten-year experience from a pediatric nephrology unit.

Abu-Shahin N, Al-Khader A, Qattan D, Akl K. C1q nephropathy among children with nephrotic syndrome: Ten-year experience from a pediatric nephrology unit. Turk J Pediatr 2018; 60: 14-21. C1q nephropathy (C1qN) is a rare glomerulopathy mostly seen in children, and presents with nephrotic syndrome (NS). Diagnosis depends on immunoflourescence or immunohistochemical C1q mesangial deposition, excluding other immune-mediated diseases. We retrospectively investigated C1qN incidence, clinicopathological features, and outcome among pediatric NS in our institution.Clinical data, microscopic slides and corresponding tissue blocks of pediatric renal biopsies were retrieved. According to diagnostic criteria for C1qN, 53 pediatric NS renal biopsies were selected for Anti-C1qA IHC stain microscopic examination. Clinicopathological features and follow up data were recorded. C1qN incidence was 9.4% among pediatric NS biopsies. Mesangial proliferation was the most common histopathological pattern. Steroid dependency with frequent relapses was the most frequent outcome, with a second line immunosuppressant added, yet without impact on progression. Small sample size hinders coherent conclusions; nevertheless, it indicates that C1qN is a rare cause of pediatric NS. C1qN may require second line immunosupressants more often than non-C1q NS.