Histological Studies Research Articles

A Comparative Study Between Cold Static Storage and Normothermic Ex-Situ Donor Heart Preservation in a Rat Model of Heterotopic Heart Transplantation.

Cold static storage (CSS) and normothermic ex-situ preservation are the most widely used donor heart preservation techniques worldwide. The current study compares both CSS and normothermic ex-situ preservation methods in terms of graft performance, morphologic changes, and acute immune response in an experimental model. Twenty rats underwent heterotopic abdominal heart transplantation after 2h of CSS (group 1; n=10) or normothermic ex-situ perfusion (group 2; n=10). Blood samples were obtained from recipients just before and after 4h of transplantation to analyze surface markers of immune cells and cytokines. Electrocardiography and echocardiography were performed before donor heart harvesting and after heterotopic transplantation. After 4h of transplantation, donor hearts were extracted for further histologic studies. All recipient animals in both groups successfully survived after heterotopic transplantation. The mean ischemic time of the donor heart was 163±8.34mins in group 1 and 43.8±6.97mins in group 2 (P<0.01). Ejection fraction significantly decreased after transplantation in both groups but were less significant in group 2 (the mean difference group 1: -34.3±3.54, P<0.01; group 2: -14.3±15.47, P=0.01). The percentage of granulocyte significantly increased in both group 1 and group 2, but the significance was more pronounced in group 1 (the mean difference group 1: 48.7±5.36, P<0.01; group 2: 39.7±13.1, P<0.01). Normothermic ex-situ perfusion is associated with well-preserved donor hearts but a similar recipient acute immune response in comparison with CSS in the rat model.

Ameliorative Effect of Combined Placenta-Derived Mesenchymal Stem Cells plus Platelet-rich Plasma on Polycystic Ovarian Model in Rats: A Biochemical and Histological Study.

Polycystic ovary syndrome (PCOS) is a common cause of infertility in women, characterized by metabolic and hormonal irregularities. We investigated the effects of placenta-derived mesenchymal stem cells (PDMSCs) and platelet-rich plasma (PRP), as well as their combination on follicular development, hormonal profile, inflammatory parameters, and insulin resistance in a model of PCOS. In this study, 25 female Wistar rats were randomly allocated into five groups: Sham (given a dose of 1 mL of a 0.5% carboxymethylcellulose (CMC) solution), PCOS (administered 1mg/kg of letrozole (LTZ) dissolved in CMC for 21 days), PDMSC (treated with a single intraovarian dose of PDMSCs), PRP (treated with a single intraovarian dose of PRP), and a combined PDMSC and PRP-treated group. After two weeks, serum and ovarian samples were collected for biochemical and histological analyses. Our results demonstrated that the simultaneous administration of PDMSCs and PRP had a synergistic effect compared to monotherapy, leading to an increase in estradiol (E2) and follicle-stimulating hormone (FSH) serum levels, a decrease in luteinizing hormone (LH) and testosterone levels, as well as inflammatory factors. Moreover, the combined therapy was associated with significantly lower levels of the homeostatic model of insulin resistance (HOMA-IR), fasting insulin (FINS), and blood glucose (FBG) compared to monotherapy. The combined treatment also caused a significant reduction in cystic follicles and an elevated number of corpus luteum, primordial, primary, secondary, and antral follicles. In conclusion, the combination of PRP and PDMSCs may have an ameliorative effect on modifying metabolic abnormalities and accelerating ovarian regeneration in PCOS.

First insights into the life history of the early Miocene deer Procervulus ginsburgi from Spain.

The small-sized cervid Procervulus is considered as the most basal member of the Cervidae and one of the earliest ruminants bearing antler-like appendages. The Iberian Miocene record of this stem-cervid is extensively documented and largely overlaps with the Miocene Climatic Optimum (MCO), a transient period of global warming of particular interest when comparing present and near future conditions. Despite receiving a substantial amount of attention, histological studies on Procervulus are very scarce and only limited to postcranial remains of Procervulus praelucidus from Germany (MN3). Here we focus for the first time on the dental histology of Procervulus ginsburgi from the Early Miocene Iberian site of Artesilla (MN4, 16.49 Ma), and examine its daily enamel secretion rate (DSR), enamel extension rate (EER) and crown formation time (CFT). Results reveal a brief CTF and high DSR and EER for P. ginsburgi and suggest a fast development at least early in its ontogeny. In addition, the pronounced growth rate of P. ginsburgi emerges as higher than that of the roe deer C. capreolus-documented as an r-strategist and here examined as a possible extant analog. Overall, our findings point toward a fast life history strategy for P. ginsburgi, which unexpectedly contrasts with that of the 2 million-year-older P. praelucidus from Wintershof-West, with a marked slower growth and maturation. When these results are analyzed together with other evidence, the somewhat drier and more open conditions of Artesilla as a result of the effects of the MCO seem to be the explanation for the different life history and ecology between these Procervulus species. More generally, this study illustrates that life histories within a single genus evolve in response not only to internal constraints but also to the environments, as predicted by the Life History Theory.

A Therapeutic Approach of Chitosan-loaded p-Coumaric Acid Nanoparticles to Alleviate Diabetic Nephropathy in Wister Rats.

This study evaluated the renoprotective effects of p-Coumaric acid nanoparticles (PCNPs) in nephropathic rats. Six groups of male Albino Wistar rats were randomly assigned. Group 1 was the control, while Group 2 received 45 mg/kg of streptozotocin (STZ) to induce diabetic nephropathy. Groups 3, 4, and 5 received STZ (45 mg/kg) along with PCNPs at doses of 20, 40, and 80 mg/kg, respectively. Group 6 received 80 mg/kg of PCNPs without STZ. Body weight, blood glucose, insulin, hemoglobin (Hb), and glycosylated hemoglobin (HbA1c) levels were measured. Blood urea, serum creatinine, kidney antioxidant enzymes, and lipid peroxidation levels were also analyzed. Histological and immunohistochemical studies of kidney tissues were performed. PCNPs (80 mg/kg) significantly reduced serum glucose, creatinine, and urea levels while increasing insulin levels and antioxidant activity in the kidneys. Histological analysis revealed that nephropathic rats exhibited cellular damage, including shrinkage of Bowman's capsule and lesions in the kidneys, along with degeneration in the Islets of Langerhans in the pancreas. PCNPs treatment restored these morphological alterations in the pancreas, liver, and kidneys to near-normal. Furthermore, nephropathic rats had elevated IL-6 and TNF-α expression in the renal tubules and glomeruli, which was reduced following PCNPs treatment. The findings suggest that PCNPs exhibit antihyperglycemic, antioxidant, antiglycation, and renoprotective effects in STZ-induced diabetic nephropathy.

Analysis of the therapeutic role of stem cells versus selenium nanoparticles in lipopolysaccharide-induced acute lung injury in adult male albino rat: A histological, immunohistochemical and histochemical study

Pharmacological research using Lipopolysaccharide (LPS) is a reliable model of acute lung injury. This study aims to compare the therapeutic efficacy of selenium nanoparticles (SeNPs) and bone-marrow-derived mesenchymal stem cells (BMSCs) against lung damage generated by lipopolysaccharides. Fifty adult male albino rats were employed and divided into 5 groups (control group, shame control group, LPS-treated group, SeNPs-treated group, and BMSCs-treated group). Histological and immunohistochemical staining for tumor necrosis factor-alpha (TNFα), Interleukin 6 (IL-6), and Caspase 3 were carried out and followed by histomorphometric analysis. Histochemical measurements of the oxidative-antioxidative markers, superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) were performed in addition to western blotting analysis to detect the antioxidative activity of Nrf2. LPS-treated group showed distorted pulmonary architecture with the upsurge in the caspase-3, TNF-α, IL-6, and MDA along with a significant decrease in GPx, SOD, and Nrf2 in the lung homogenates. These findings were relatively improved after adding SeNPs and stem cells. On comparing BMSCs and SeNPs treated group, there was a significant decrease in caspase-3, TNF-α, and IL-6 with BMSCs treatment relative to SeNPs. Treatment with selenium nanoparticles and BMSCs has improved pulmonary changes through their antioxidant and anti-inflammatory role. The level of pulmonary regeneration exerted by BMSCs is better than selenium nanoparticles so the BMSCs may be given preference for a particular course of treatment.

Zirconia Barriers in Bone Regeneration Procedures: A Scoping Review.

To identify the current status and development of zirconia barriers in bone augmentation procedures in the maxillofacial area of adult human patients. Two independent reviewers conducted an electronic literature search in PubMed/MEDLINE, Web of Science, Scopus, EBSCO, the Cochrane Library, and LILACS databases, as well as a manual search to identify eligible clinical studies up to April 15, 2024. The protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. The initial electronic search resulted in 240 studies. The systematic application of inclusion and exclusion criteria resulted in 6 articles that met the purpose of the study. The included articles were 5 clinical case series and 1 case report, published between 2016 and 2023. Only 4 articles reported histological studies. A total of 40 sites regenerated with zirconium barriers were reported in 30 patients. Results were obtained with variability in bone gain values, between 0.9-8.0 mm horizontally and 1.4-12.0 mm vertically, in addition to a 30% complication rate. Although the results obtained in the studies included in this scoping review are favorable with respect to the amount of bone formation and the reduced surgical time required, the number of complications is considered high. Moreover, due to a limited number of patients included in the case series and the short duration of follow-up, additional studies including a control group are required.

In-vitro and in-vivo studies of Tridax procumbens leaf extract incorporated bilayer polycaprolactone/polyvinyl alcohol-chitosan electrospun nanofiber for wound dressing application.

This study was an attempt to fabricate an antibacterial wound dressing, which was a bilayered polycaprolactone / polyvinyl alcohol-chitosan (PCL/PVA-CS) nanofibrous membrane. Entrapping ethanolic leaf extract of Tridax procumbens L. (PCL/PVA-CS/Tp). The membrane was prepared using the electrospinning technique to obtain beadless uniform nanofibers. The extract was then infused into the membrane by spraying and exposing to high temperature. in vitro antibacterial activity and cell viability of the membranes were performed. An optimized concentration of 800μg. mL-1 of Tp extract in PCL/PVA-CS/Tp evinced better antibacterial effect on E. coli than S. aureus and also showed rapid wound closure with a positive impact on the viability of L929 cell line. The tissue regeneration efficacy of PCL/PVA-CS/Tp was validated by the experiments on mice models with subcutaneous wounds created using biopsy punch and laser radiation causing burns. Furthermore, in vivo assessments illustrated that the biopsy punch wounds healed more rapidly than laser burn though healing was significant in both. The healing processes such as anti-inflammation and re-epithelialization were observed through histological study. The upregulation of proteins namely VEGF and CD31 along with a decrease in protein levels of Wnt and TGF-β indicated significant wound healing. In conclusion, the bilayered membrane infused with plant extract could be considered a potential material for wound dressing.

The expression of transcription factors in the human fetal subthalamic nucleus suggests its origin from the first hypothalamic prosomere.

In this study, we analyzed the spatio-temporal pattern of expression of specific transcription factors (PITX2, FOXA1, BARHL1, FOXP1, FOXP2) in the human fetal subthalamic nucleus and its neighboring structures from 11 postconceptional weeks (PCW) to 3 postnatal months. We found that all analyzed transcription factors are expressed already during the early fetal period (at 11 PCW). Both FOXP1- and FOXP2-immunoreactive cells were found in the subthalamic nucleus as well as in the striatum, thalamus, reticular nucleus, but not in the zona incerta. FOXP2-ir cells were also found in the lateral hypothalamic-supramamillary area (LHA-SMA) and internal pallidal segment.On the other hand, PITX2, FOXA1 and BARHL1 were expressed exclusively in the subthalamic nucleus and LHA-SMA, from 11 PCW until the birth, the only exception being gradual loss of BARHL1 expression in the LHA-SMA during the late fetal period.Our findings present the first evidence in the human fetal brain that neurons of the subthalamic nucleus do not originate in the diencephalon, as was proposed by classical histological studies, but instead share a common hypothalamic (hp1 prosomere) origin with neurons of the LHA-SMA group, as proposed by the prosomeric model of brain development.

Quercetin: An anthelmintic potential against zoonotic tapeworm Hymenolepis diminuta (Rudolphi, 1819).

Quercetin, a vital flavonoid found in many medicinal plants, has shown anti-inflammatory, anti-cancerous, anti-aging, anti-tumour, anti-viral, anti-fungal, anti-bacterial, anti-obesity, anti-diabetic, and anti-protozoal activity. However, very little is known of its anthelmintic activity; there is no literature against tapeworm infection so far. The present study was performed to expose its cestocidal role by using the zoonotic tapeworm Hymenolepis diminuta as a parasite model. The parasite was exposed to different concentrations of 0.125, 0.25, 0.5, 1, 2.5, 5, 10, 20, and 40 mg/mL Quercetin prepared in RPMI 1640, with 1% Tween 20. Another set of parasites was treated with a standard dose of Praziquantel (0.001 mg/ml), and another set of parasites was kept as control. All experiments were maintained at 37°C ± 1°C in the incubator. Quercetin activity was assessed through viability test, and time of motility was observed through paralysis. After the experiment, worms were processed for light and electron microscopic analysis to observe the post-treatment effect on their tegument. Dose-dependent efficacy was observed in all the treatments. Time of paralysis and time of mortality for 20 mg/mL Quercetin dose was 1.40±0.03h and 2.35±0.03h, respectively, which is at par with the drug Praziquantel. Histological study showed constrictions in the tegument, while extensive damage in suckers and neck region with deformed and shrunken proglottids, sloughed-off microtriches and undistinguished nucleus with loss of envelope architecture were observed in treated parasites under electron microscopic studies, which indicates the negative activity of Quercetin on the parasite thus suggesting its cestocidal activity.

Enhanced multiscale human brain imaging by semi-supervised digital staining and serial sectioning optical coherence tomography

A major challenge in neuroscience is visualizing the structure of the human brain at different scales. Traditional histology reveals micro- and meso-scale brain features but suffers from staining variability, tissue damage, and distortion, which impedes accurate 3D reconstructions. The emerging label-free serial sectioning optical coherence tomography (S-OCT) technique offers uniform 3D imaging capability across samples but has poor histological interpretability despite its sensitivity to cortical features. Here, we present a novel 3D imaging framework that combines S-OCT with a deep-learning digital staining (DS) model. This enhanced imaging modality integrates high-throughput 3D imaging, low sample variability and high interpretability, making it suitable for 3D histology studies. We develop a novel semi-supervised learning technique to facilitate DS model training on weakly paired images for translating S-OCT to Gallyas silver staining. We demonstrate DS on various human cerebral cortex samples, achieving consistent staining quality and enhancing contrast across cortical layer boundaries. Additionally, we show that DS preserves geometry in 3D on cubic-centimeter tissue blocks, allowing for visualization of meso-scale vessel networks in the white matter. We believe that our technique has the potential for high-throughput, multiscale imaging of brain tissues and may facilitate studies of brain structures.

Investigation of the Effects of Light, Darkness, and Dim Light on Rat Brain Tissue: A Biochemical and Histological Study.

This study evaluates acetylcholinesterase (AChE) enzyme activity levels, oxidative stress parameters, histopathological findings, and serum melatonin levels in rat brain tissue. 32 male Wistar Albino rats were randomly divided into four groups: Control, Light, Dark, Dim light (n = 8 each group). After a 30 day experiment, brain tissues were collected to measure AChE, glutathione S-transferase (GST), glutathione (GSH), and malondialdehyde (MDA) levels and conduct histopathological analyses. Serum melatonin levels were also measured. In this study, we observed a significant increase in MDA levels in dim light, dark, and light groups. AChE and α-GST enzyme activity levels were significantly decreased in the dark group compared with the other groups. Additionally, there was a statistical difference in melatonin levels between the light and dark groups. In the light microscope examination of the sections stained with hematoxylin-eosin from the dark group brain tissue, mild perineuronal edema was observed in all areas. Our study is the first to compare the effects of three groups on the brain: continuous light, continuous darkness, and dim light at night. Additionally, it is the only study to examine the effects of light exposure differences on the brain AChE levels.

Peri-Implant Soft Tissue in Contact with Zirconium/Titanium Abutments from Histological and Biological Perspectives: A Concise Review.

Dental implants are crucial in contemporary oral rehabilitation, necessitating optimal integration with the surrounding soft tissues for durable success. The attachment between the implant surface and peri-implant mucosa should establish a secure seal to prevent bacterial infiltration and subsequent tissue inflammation. This concise review examines the histological and biological perspectives of peri-implant soft tissue reactions to zirconium and titanium abutments, shedding light on their respective advantages and limitations. While titanium has been the gold standard, zirconia has gained attention due to its biocompatibility and aesthetic appeal. Histological studies show comparable soft tissue attachment and inflammatory responses between the two materials. Further research is needed to explore surface treatments and optimize outcomes in dental implant rehabilitation.

Noninvasive Vagus Nerve Stimulation Protects Neurons in the Perihematomal Region and Improves the Outcomes in a Rat Model of Intracerebral Hemorrhage.

Intracranial hemorrhage (ICH) is a devastating stroke subtype with a high rate of mortality and disability. Therapeutic options available are primarily limited to supportive care and blood pressure control, whereas the surgical approach remains controversial. In this study, we explored the effects of noninvasive vagus nerve stimulation (nVNS) on hematoma volume and outcome in a rat model of collagenase-induced ICH. Adult male Wistar rats were randomized into two study groups: (1) ICH-treated (rats treated with five 2-min nVNS) and (2) ICH-control (ICH with sham nVNS). Each group received either a 0.1-U or a 0.2-U collagenase dose. After assessing neurological function, rats were euthanized at 24 h for spectrophotometric hemoglobin assay, hematoma volume measurements, and histological studies. The ICH-treated group that received the 0.1-U collagenase dose demonstrated significantly smaller hematoma volume and improved motor function compared with the ICH-control with the same dose. Furthermore, the pooled data for the ICH-treated groups (both 0.1 U and 0.2 U of collagenase) revealed a reduction in neuronal loss in the perihematomal region in the histopathological studies. This effect was not significant for the group that received a 0.2-Ucollagenase dose. nVNS therapy in acute settings may provide a neuroprotective effect and limit hematoma expansion in smaller volumes, improving neurological function post-ICH.

Characterization and interactions between piperine and ezetimibe in their Anti-hyperlipidemic efficacy using Biopharmaceutics and Pharmacokinetics

BackgroundPiperine, a secondary metabolite, affects the antihyperlipidemic effect of Ezetimibe (EZ). Hyperlipidemia is one of the independent risk factors for cardiovascular disorders such as atherosclerosis. Antihyperlipidemic drugs are essential for reducing cardiovascular events and patient mortality. Our study aimed to improve the solubility of EZ, a lipid-lowering drug that belongs to BCS II and has low solubility. Piperine, a bioenhancer, can increase the bioavailability of other pharmaceuticals without modifying their fundamental characteristics or enhancing their efficacy. The objective of this study was to increase the bioavailability of EZ while also improving its potency and reducing its toxicity by using piperine as a bioenhancer. Therefore, rats were given piperine combined with EZ, and their antihyperlipidemic activity was assessed while fed a high-fat diet.MethodThe in vivo antihyperlipidemic effect of EZ with piperine was assessed at doses of 10 and 5–20 mg/kg b.w. The evaluation was conducted using propylthiouracil-induced and triton X-100-induced hyperlipidemia in rats. Give 400 mg/kg body weight of propylthiouracil along with piperine. Serum levels of total cholesterol (TC) (p < 0.01), triglycerides (TG) (p < 0.01), low-density lipoprotein (LDL) (p < 0.01), and very low-density lipoprotein (VLDL) (p < 0.01) all went up significantly. Additionally, it led to the induction of high-density lipoprotein (HDL) (p < 0.01). Administration of Triton X-100 via intraperitoneal injection at a single dose resulted in an elevation of lipid levels.ResultsLower levels of high-density lipoprotein (LDL), total cholesterol (TC), triglycerides (TG), and very low-density lipoprotein (VLDL) were significantly reduced by EZ at 10 mg/kg b.w. and piperine at 20 mg/kg b.w., respectively (p < 0.01 and p < 0.05). Liver histology studies provided further evidence supporting the present findings. Areas of concentrated periportal lymphocytes and hepatocytes formed a cord pattern in rats with hyperlipidaemia. It seemed like the hepatocytes, periportal area, and centrilobular part of the liver were all normal in the group who had the treatment. An analysis of the EZ plasma drug concentration with time was carried out in a research. The medication’s most effective concentration (Cmax) was determined to be within 4 h after delivery, and The quantified concentration of the active medication was detectable in the bloodstream for 24 h.ConclusionIn combination with piperine, EZ has demonstrated significant antioxidant and antihyperlipidemic effects. This indicates that EZ could be further utilised for treating hyperlipidemia and atherosclerosis due to its potential to boost the bioavailability and oral absorption of the drug.

Osteoporosis' effects on dental implants osseointegration and survival rate: a systematic review of clinical studies.

The goal of this systematic review was to critically appraise the existing evidence evaluating osteoporosis' effects on dental implant osseointegration and survival rate. A search was conducted in two databases, PubMed/MEDLINE and Scopus, until October 2024, using the keywords 'osteoporosis,' 'osteopenia,' 'osseointegration,' and 'dental implants'. The inclusion criteria were clinical studies that evaluated the implant placement, complications, and osseointegration results in patients with osteoporosis; literature reviews and clinical studies addressing the outcome were considered; and articles written in English and published since 2000. Descriptive data analysis included author, year of publication, study design, number of patients, osteoporosis assessment, follow-up, and main findings. JBI quality assessment was performed. 24 articles were included with a total of 2,102 patients; 5954 dental implants were considered and evaluated. Most studies evaluated bone density for osteoporosis by dual-energy x-ray technology. The follow-up ranged from 1 month to 25 years. Four studies evaluated implants with over 10 years of follow-up. All studies' survival rate was higher than 90%, even for osteoporotic patients. Most studies indicated no differences between osteoporotic and healthy patients regarding marginal bone loss (MBL), bone-to-implant contact, cytokine levels, and mineral bone density. A prospective cohort study found a small MBL (-0.34 mm) in osteoporotic female patients, but there was insufficient evidence to prove any causal relationship between MBL and osteoporosis. Another study showed no clinical differences between implants placed in osteoporotic and healthy individuals. In contrast, other studies showed lower stability scores for implants placed in osteoporotic sites and a higher risk of failure for implant placement. Osteoporosis status was not a risk factor for dental implant failure, which was also confirmed by histological studies. Three studies had a medium risk of bias and 21 a low risk. Osteoporosis is not a contraindication for dental implant placement. Osseointegration in patients with osteoporosis is feasible; however, planning must be cautious and personalized for the installation of dental implants.

Neuroprotective Effect of Melatonin Loaded in Human Serum Albumin Nanoparticles Applied Subconjunctivally in a Retinal Degeneration Animal Model.

Neurodegenerative ocular diseases, such as age-related macular degeneration (AMD) and glaucoma, represent growing public health concerns. Oxidative stress plays a key role in their development, damaging retinal cells and accelerating disease progression. Melatonin (Mel) is a potent antioxidant with neuroprotective properties; however, it faces limitations such as low solubility. This study proposes the use of human serum albumin nanoparticles (Np-HSA) to enhance the delivery of Mel to the posterior segment of the eye and evaluates its neuroprotective and anti-apoptotic effects on the retina. A model of retinal degeneration was induced in New Zealand albino rabbits using cytotoxic and oxidative agents. Np-HSA-Mel nanoparticles were administered subconjunctivally, and cellular viability and retinal functionality were assessed using flow cytometry and pupillary light reflex (PLR). Histological and immunohistochemical studies, including the TUNEL assay, were performed to analyse cell survival and apoptotic index. Np-HSA-Mel significantly preserved pupillary function and cell viability, demonstrating lower apoptosis compared to Mel solution and Np-HSA alone. Histologically, eyes treated with Np-HSA-Mel exhibited fewer structural alterations and greater cellular organisation. The TUNEL assay confirmed a significant reduction in the apoptotic index of retinal ganglion cells (RGCs) treated with Np-HSA-Mel. Np-HSA-Mel effectively overcame ocular barriers, achieving greater neuroprotective efficacy at the retinal level. These findings highlight the synergistic potential of albumin and Mel in treating neurodegenerative ocular diseases, opening new perspectives for future therapies.

Chemotherapy-induced diminished murine ovarian reserve model and impact of low-dose chemotherapy on fertility.

To establish a murine model of chemotherapy-induced diminished ovarian reserve (DOR) and investigate residual fertility after chemotherapy exposure. Two different chemotherapy protocols were tested to establish a valid DOR model by comparing follicle densities in mice given either protocol versus physiological solution. An ovarian stimulation protocol was then selected from among different gonadotropins by counting the number of day-2 embryos obtained from normal mice. Finally, DOR mice were stimulated 5 and 8 weeks after chemotherapy with the chosen gonadotropin protocols and day-2 embryos were recovered after mating, as was ovarian tissue for further immunohistological analyses. Seventy-two Naval Medical Research Institute (NMRI) mice. To compare day-2 embryo counts in both normal and chemotherapy-induced DOR mice. Ovarian histology and morphology were also investigated by follicle counting and classification, as was immunostaining for apoptosis (cleaved caspase-3), activation (phospho-Akt) and proliferation (Ki67). A dose of 12 mg/kg busulfan (Bu) + 120 mg/kg cyclophosphamide (Cy) was chosen to establish the DOR model, as it significantly reduced the ovarian reserve compared to both control mice (physiological solution) and the 1.2 mg/kg Bu + 12 mg/kg Cy protocol, without depleting it completely. When stimulated with 3.75 IU Menopur, normal mice produced significantly more embryos than DOR mice given 12 mg/kg Bu + 120 mg/kg Cy (41.40 ± 14.74 versus 23.67 ± 15.55 day-2 embryos). While the follicle count was statistically diminished after single-dose chemotherapy administration, the remaining follicles did not display any difference in terms of apoptosis, activation or proliferation rates. We successfully established a chemotherapy-induced DOR model using 12 mg/kg Bu + 120 mg/kg Cy, as evidenced by lower, but not completely depleted, follicle numbers and fewer retrieved embryos. Histological study of ovarian tissue exposed to DOR-inducing chemotherapy revealed that surviving follicles were of the same quality as tissue not exposed to chemotherapy.

Protective effects of polydatin amphiphilic chitosan nanocarriers against an aluminum chloride-induced model of Alzheimer's disease in rats: relevance to its anti-inflammatory and antioxidant effects.

Alzheimer's disease (AD) is the most frequent cause of dementia. Since there are complex pathophysiological mechanisms behind AD, and there is no effective treatment strategy, it is necessary to introduce novel multi-targeting agents with fewer side effects and higher efficacy. Polydatin (PD) is a naturally occurring resveratrol glucoside employing multiple mechanisms toward neuroprotection. In the current study, the anti-AD mechanisms of a novel amphiphilic chitosan nanocarrier formulation (ACN) of PD (NPD) were studied. After preparing the amphiphilic chitosan nanoformulation (i.e., NPD), physicochemical properties were assessed, including particle size, zeta potential, drug loading, drug release, MTT, Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM). For in vivo analysis, aluminum chloride (AlCl3) was injected intraperitoneally for 14 days to induce AD in male Albino Wistar rats. To examine the anti-AD mechanisms of NPD, a total of 36 rats were divided into six groups of six. Behavioral tests, including open field, Y-maze, elevated plus maze, and shuttle box were done on days 7, 8, 14, and 15. Additionally, zymography, biochemical analysis, and histological studies were done. NPD, as a newly synthesized formulation for PD, potentially improved memory and cognitive behavioral parameters and reduced the activity ofinflammatory matrix metalloproteinase 9 (MMP9) and serum nitrite levels, while increasing anti-inflammatory MMP2, antioxidant catalase, and glutathione. NPD also prevented morphological changes and increased neuronal survival in the CA2, CA4, and DG regions of the rat hippocampus. In conclusion,NPD is a novel formulation against AD through anti-inflammatory, antioxidant, and neuroprotective mechanisms.

Gastroprotective effect of selenium nanoparticles in indomethacin-induced chronic gastritis in adult male albino rats: a histological, immumohistochemical and biochemical study

Gastroprotective effect of selenium nanoparticles in indomethacin-induced chronic gastritis in adult male albino rats: a histological, immumohistochemical and biochemical study

Olive oil and castor oil-based self-nanoemulsifying drug delivery system of flurbiprofen can relieve peripheral pain and inflammation through reduction of oxidative stress and inflammatory biomarkers: a comprehensive formulation and pharmacological insights.

Flurbiprofen (FBP) is poorly water-soluble BCS class II drug with anti-inflammatory and analgesic effects, used to treat arthritis and degenerative joint diseases. This study was aimed to develop SNEDDS loaded with FBP. Six SNEDDS using two oils olive oil (F1OLV, F2OLV, F3OLV) and castor oil (F4CAS, F5CAS, F6CAS) with three different Smix ratios consisting of Tween 20 and PEG 400 (1:1, 1:2, 2:1) were prepared and characterized. Compatibility between FBP and polymers was investigated using FTIR. SNEDDS were characterized for physicochemical attributes. Two optimized formulations were investigated at 10mg/kg dose given orally in Wistar rats for analgesic activity by hot plate and tail flick methods, and anti-inflammatory activity by carrageenan induced paw edema method. Anti-inflammatory activity was further explored by motor coordination and motility by Rota rod and cage activity tests. Following anesthesia blood samples were collected before dissection to measure inflammatory mediators and oxidative stress markers. Sciatica nerves and hind paws of rats were also removed for histopathological evaluation.FTIR studies revealed compatibility of FBP with other components. Droplet size of F1OLV, F2OLV, F3OLV was 128.5 ± 0.7 nm, 202.5 ± 1.3 nm, and 541.5 ± 1.7 nm, whereas it was 142.5 ± 1.1 nm, 215.4 ± 1.2 nm and 349.9 ± 1.8 nm for F4CAS, F5CAS, F6CAS. %EE of F1OLV, F2OLV, F3OLV was found 85 ± 4.89%-91 ± 4.67%, whereas the %EE F4CAS, F5CAS, F6CAS was 84 ± 4.15%-90 ± 4.21%. DSC curves of F1OLVand F4CASrevealed amorphous nature of the FBP. SEM showed spherical shape of globules. % of drug released in the pH medium 1.2 for plain FBP, F1OLVand F4CASwas 25%, 59% and 57%. % drug released in the pH 6.8 for plain FBP, F1OLVand F4CASwas 59%, 85% and 83%. Oral administration of FBP-loaded SNEDDS (F1OLV and F4CAS) significantly decreased paw diameter and enhanced motor coordination in rats when compared to the disease control group. This was linked to the ability of FBP to reduce inflammation and oxidative stress, with histological studies indicating decreased tissue damage in SNEDDS treated groups, implying the possibility of tissue recovery. Administration of both formulations started to demonstrate analgesic and anti-inflammatory effects after one hour of administration. In addition to anti-inflammatory effect, both formulations improved motor coordination, motility, and reduced infiltration of inflammatory cells in the inflamed paws. The anti-inflammatory and analgesic activities were attributed to decreased serum levels of IL-6 and TNF-α, increased activity of SOD and reduced nitrite content in sciatic nerves. Histopathological evaluation revealed reduced vascularity, inflammation and synovial hyperplasia. The overall findings suggest that the FBP loaded SNEDDS can be used as carriers for improved delivery of FBP which can effectively be used to cure pain and inflammation.