In Vivo Wound Healing Potential and Molecular Pathways of Amniotic Fluid and Moringa Olifera-Loaded Nanoclay Films.

Cutaneous wounds pose a significant health burden, affecting millions of individuals annually and placing strain on healthcare systems and society. Nanofilm biomaterials have emerged as promising interfaces between materials and biology, offering potential for various biomedical applications. To explore this potential, our study aimed to assess the wound healing efficacy of amniotic fluid and Moringa olifera-loaded nanoclay films by using in vivo models. Additionally, we investigated the antioxidant and antibacterial properties of these films. Using a burn wound healing model on rabbits, both infected and non-infected wounds were treated with the nanoclay films for a duration of twenty-one days on by following protocols approved by the Animal Ethics Committee. We evaluated wound contraction, proinflammatory mediators, and growth factors levels by analyzing blood samples. Histopathological changes and skin integrity were assessed through H&E staining. Statistical analysis was performed using SPSS software (version 2; Chicago, IL, USA) with significance set at p < 0.05. Our findings demonstrated a significant dose-dependent increase in wound contraction in the 2%, 4%, and 8% AMF-Me.mo treatment groups throughout the study (p < 0.001). Moreover, macroscopic analysis revealed comparable effects (p > 0.05) between the 8% AMF-Me.mo treatment group and the standard treatment. Histopathological examination confirmed the preservation of skin architecture and complete epidermal closure in both infected and non-infected wounds treated with AMF-Me.mo-loaded nanofilms. RT-PCR analysis revealed elevated concentrations of matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF), along with decreased levels of tumor necrosis factor-alpha (TNF-α) in AMF-Me.mo-loaded nanofilm treatment groups. Additionally, the antimicrobial activity of AMF-Me.mo-loaded nanofilms contributed to the decontamination of the wound site, positioning them as potential candidates for effective wound healing. However, further extensive clinical trials-based studies are necessary to confirm these findings.

Rescue of synaptic and cognitive functions in polysialic acid-deficient mice and dementia models by short polysialic acid fragments.

Dysregulated cortical expression of the neural cell adhesion molecule (NCAM) and deficits of its associated polysialic acid (polySia) have been found in Alzheimer's disease and schizophrenia. However, the functional role of polySia in cortical synaptic plasticity remains poorly understood. Here, we show that acute enzymatic removal of polySia in medial prefrontal cortex (mPFC) slices leads to increased transmission mediated by the GluN1/GluN2B subtype of N-methyl-d-aspartate receptors (NMDARs), increased NMDAR-mediated extrasynaptic tonic currents, and impaired long-term potentiation (LTP). The latter could be fully rescued by pharmacological suppression of GluN1/GluN2B receptors, or by application of short soluble polySia fragments that inhibited opening of GluN1/GluN2B channels. These treatments and augmentation of synaptic NMDARs with the glycine transporter type 1 (GlyT1) inhibitor sarcosine also restored LTP in mice deficient in polysialyltransferase ST8SIA4. Furthermore, the impaired performance of polySia-deficient mice and two models of Alzheimer's disease in the mPFC-dependent cognitive tasks could be rescued by intranasal administration of polySia fragments. Our data demonstrate the essential role of polySia-NCAM in the balancing of signaling through synaptic/extrasynaptic NMDARs in mPFC and highlight the therapeutic potential of short polySia fragments to restrain GluN1/GluN2B-mediated signaling.

An assessment of the current practice of community pharmacists for the disposal of medication waste in the United Arab Emirates: A deep analysis at a glance.

Objective: The study aimed to identify the current practice carried out by community pharmacists to dispose of expired medications in their workplace and assess any practical steps utilized to reduce medication waste. Method: A cross-sectional study was conducted among community pharmacists in the United Arab Emirates (UAE). The participants were asked about their routine practice in disposing of different expired medications and the current actions taken to reduce the number of disposed medicines. Results: The study included (n = 418) community pharmacists. More than a third of expired liquid, solid, and semi-solid dosage forms were collected by licensed contractors. In addition, more than a third of the pharmacists disposed of different dosage forms via unauthorized methods (general garbage, sink and toilet). Most expired drugs were skin and hair products, antibiotics and analgesics. The majority of pharmacists (68.4 %, n = 286) agreed that expired pharmaceutical and non-pharmaceutical products, other than those disposed of via contractor, should be done through a specialized centre. This opinion was found to be strongly associated with years of practice as community pharmacists (P < 0.05). Conclusion: Part of the existing disposal practices for expired pharmaceutical products in the UAE is carried out by contractors licensed by health authorities. However, concern remains regarding some pharmaceutical and non-pharmaceutical products that have not been disposed of correctly. Additionally, there is a need for a specialized center for medication disposal (p < 0.05). A stock limitation is the best practice for managing medication quantities in stock (p < 0.05).

Knowledge, Attitudes, and Practices Concerning Breast Cancer and Self Examination Among Females in UAE.

Breast cancer (BC) is one of the most prevalent cancers and the leading cause of cancer related deaths among women worldwide with a steadily increasing global annual incidence. This study aims is to evaluate the knowledge, attitude, and practice of females in the UAE toward BC and Breast Self-Examination practice in the seven Emirates. This was a face-to-face questionnaire-based study using CAM (Breast Cancer Awareness Measure) conducted over 3 months (from March to June 2019) on a random sample of females across the UAE. Of the 400 females who filled the questionnaire, 112 (28%) did the CBE at least once, and 184 (46%) practice BSE. Only 33% of participants were aware of the incidence of the BC in the UAE and those females were more likely to practice BSE (P < 0.05). In contrast, the majority showed a high awareness level in identifying cancer as a curable (91.5%) and non-transmittable (87%) disease that can be diagnosed at its earlier stages (93%). Only 11% of the participants identified weight reduction as a way to prevent BC. Knowledge of breast cancer sign/symptoms were good, as 41-87% of respondents were able to identify at least a single sign/symptom. The lack of awareness of BC among females in the UAE is of concern as it leads to low practices of screening and early detection, which ultimately will result in increased morbidity, mortality, and treatment costs. Further initiatives should be taken to increase practice, knowledge and awareness on early detection and screening for BC in the UAE community.

Effectiveness of testosterone therapy in hypogonadal patients and its controversial adverse impact on the cardiovascular system.

Testosterone is the major male hormone produced by testicles which are directly associated with man's appearance and secondary sexual developments. Androgen deficiency starts when the male hormonal level falls from its normal range though, in youngsters, the deficiency occurs due to disruption of the normal functioning of pituitary, hypothalamus glands, and testes. Thus, testosterone replacement therapy was already known for the treatment of androgen deficiency with lesser risks of producing cardiovascular problems. Since from previous years, the treatment threshold in the form of testosterone replacement therapy has effectively increased to that extent that it was prescribed for those conditions which it was considered as inappropriate. However, there are some research studies and clinical trials available that proposed the higher risk of inducing cardiovascular disease with the use of testosterone replacement therapy. Thus under the light of these results, the FDA has published the report of the increased risk of cardiovascular disease with the increased use of testosterone replacement therapy. Nevertheless, there is not a single trial available or designed that could evaluate the risk of cardiovascular events with the use of testosterone replacement therapy. As a result, the use of testosterone still questioned the cardiovascular safety of this replacement therapy. Thus, this literature outlines the distribution pattern of disease by investigating the data and link between serum testosterone level and the cardiovascular disease, also the prescription data of testosterone replacement therapy patients and their tendency of inducing cardiovascular disease, meta-analysis and the trials regarding testosterone replacement therapy and its connection with the risks of causing cardiovascular disease and lastly, the possible effects of testosterone replacement therapy on the cardiovascular system. This study aims to evaluate the available evidence regarding the use of testosterone replacement therapy when choosing it as a treatment plan for their patients.

Potential therapy of vitamin B17 against Ehrlich solid tumor induced changes in Interferon gamma, Nuclear factor kappa B, DNA fragmentation, p53, Bcl2, survivin, VEGF and TNF-α Expressions in mice.

Breast cancer is the most common cancer in females, and the leading cause of cancer-related mortality in the world. Among the available treatment options for cancer, chemotherapy is the therapy for treating a variety of cancer patients. However, the therapeutic efficacy of current agents is minimal and these drugs do not retard the progression of disease pathology. Lack of appropriate therapy may increase the prevalence of disease in world. Hence, more effective strategies and novel therapies must be pursued for altering the progression of the disease acting through different mechanisms. There is a continuing need for new and improved therapy. Hence, Vitamin B17 is suggested a therapeutic potential for treating breast cancer. This study is to evaluate the potential therapy of vitamin B17 (Vit B17, amygdalin) against Ehrlish solid tumors, bearing mice (EST) induced DNA damage, NF-Kb, TNFα and apoptosis. Sixty female mice were randomly divided into four groups: (I, control group; II, VitB17 group; III, EST group; IV, EST+VitB17 group). EST induced group had elevated in the levels of serum ALT, AST, ALP, creatinine, urea, potassium ions, cholesterol, triglycerides, cytokine IFNγ, NF-kb, DNA damage, tumor TNF-α, VEGF expressions and had an associated reduction in serum albumin, total proteins, sodium ions, tumor NF-kb, Bcl2 and survivin expressions. Treatment of EST with vitamin B17 (EST+VitB17) modulates the changes in liver and kidney functions, electrolytes, cytokines, NF-kb and apoptosis in mice bearing EST. Hence, these findings suggest that vitamin B17 can be a reliable and novel therapy for breast cancer, further validate the neoplastic activity of Vitamin B17 as a potential therapy for other types of cancer is needed.

PPAR-δ Activation Ameliorates Diabetes-Induced Cognitive Dysfunction by Modulating Integrin-linked Kinase and AMPA Receptor Function.

An estimated 9% of the American population experiences type II diabetes mellitus (T2DM) due to diet or genetic predisposition. Recent reports indicate that patients with T2DM are at increased risk for cognitive dysfunctions, as observed in conditions like Alzheimer's disease (AD). In addition, AD is the leading cause of dementia, highlighting the urgency of developing novel therapeutic targets for T2DM-induced cognitive deficits. The peroxisome proliferator activated receptor-δ (PPAR-δ) is highly expressed in the brain and has been shown to play an important role in spatial memory and hippocampal neurogenesis. However, the effect of PPAR-δ agonists on T2DM-induced cognitive impairment has not been explored. In this study, the effects of GW0742 (a selective PPAR-δ agonist) on hippocampal synaptic transmission, plasticity, and spatial memory were investigated in the db/db mouse model of T2DM. Oral administration of GW0742 for 2 weeks significantly improved hippocampal long-term potentiation. In addition, GW0742 effectively prevented deficits in hippocampal dependent spatial memory in db/db mice. PPAR-δ-mediated improvements in synaptic plasticity and behavior were accompanied by a significant recovery in hippocampal α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated synaptic transmission. Our findings suggest that activation of PPAR-δ might ameliorate T2DM-induced impairments in hippocampal synaptic plasticity and memory.

Doxorubicin-induced neurotoxicity is associated with acute alterations in synaptic plasticity, apoptosis, and lipid peroxidation.

Cognitive deficits are commonly reported by patients following treatment with chemotherapeutic agents. Anthracycline-containing chemotherapy regimens are associated with cognitive impairment and reductions in neuronal connectivity in cancer survivors, and doxorubicin (Dox) is a commonly used anthracycline. Although it has been reported that Dox distribution to the central nervous system (CNS) is limited, considerable Dox concentrations are observed in the brain with co-administration of certain medications. Additionally, pro-inflammatory cytokines, which are overproduced in cancer or in response to chemotherapy, can reduce the integrity of the blood-brain barrier (BBB). Therefore, the aim of this study was to evaluate the acute neurotoxic effects of Dox on hippocampal neurons. In this study, we utilized a hippocampal cell line (H19-7/IGF-IR) along with rodent hippocampal slices to evaluate the acute neurotoxic effects of Dox. Hippocampal slices were used to measure long-term potentiation (LTP), and expression of proteins was determined by immunoblotting. Cellular assays for mitochondrial complex activity and lipid peroxidation were also utilized. We observed reduction in LTP in hippocampal slices with Dox. In addition, lipid peroxidation was increased as measured by thiobarbituric acid reactive substances content indicating oxidative stress. Caspase-3 expression was increased indicating an increased propensity for cell death. Finally, the phosphorylation of signaling molecules which modulate LTP including extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase, and Akt were increased. This data indicates that acute Dox exposure dose-dependently impairs synaptic processes associated with hippocampal neurotransmission, induces apoptosis, and increases lipid peroxidation leading to neurotoxicity.

The therapeutic and antineoplastic effects of vitamin B17 against the growth of solid-form Ehrlich tumours and the associated changes in oxidative stress, DNA damage, apoptosis and proliferation in mice.

Many cancer therapies indirectly activate apoptosis by chemical or physical damage of DNA. This study was performed to evaluate protective potential of vitamin B17 (VitB17) against Ehrlich solid tumor (EST) induced changes in the oxidative stress, DNA damage, apoptosis and proliferation in mice. In the experiment, 60 female CD1 mice were randomly and allocated to the following four equal-sized groups [G1, negative control; G2, positive control (VitB17); G3, untreated EST; G4, EST treated with VitB17 (EST+VitB17)]. The untreated EST group displayed major increases in tumor volume, significant increase in the levels of MDA, H2O2, NO, PCNA, TNF-α, AFP and dsDNA and notable reductions in the catalase, GSH, P53 and SOD activities. By contrast, reduced levels of TNF-α, AFP, MDA, H2O2, NO, PCNA and dsDNA, along with enhanced levels of P53 and the antioxidant indicators catalase, GSH and SOD were observed in the EST+VitB17 group. These results indicate the antineoplastic and antioxidant properties of vitamin B17 with the potential to decrease the oxidative stress associated with ESTs by augmenting the antioxidant defence system.

Altered AMPA receptor expression plays an important role in inducing bidirectional synaptic plasticity during contextual fear memory reconsolidation.

Retrieval of a memory appears to render it unstable until the memory is once again re-stabilized or reconsolidated. Although the occurrence and consequences of reconsolidation have received much attention in recent years, the specific mechanisms that underlie the process of reconsolidation have not been fully described. Here, we present the first electrophysiological model of the synaptic plasticity changes underlying the different stages of reconsolidation of a conditioned fear memory. In this model, retrieval of a fear memory results in immediate but transient alterations in synaptic plasticity, mediated by modified expression of the glutamate receptor subunits GluA1 and GluA2 in the hippocampus of rodents. Retrieval of a memory results in an immediate impairment in LTP, which is enhanced 6h following memory retrieval. Conversely, memory retrieval results in an immediate enhancement of LTD, which decreases with time. These changes in plasticity are accompanied by decreased expression of GluA2 receptor subunits. Recovery of LTP and LTD correlates with progressive overexpression of GluA2 receptor subunits. The contribution of the GluA2 receptor was confirmed by interfering with receptor expression at the postsynaptic sites. Blocking GluA2 endocytosis restored LTP and attenuated LTD during the initial portion of the reconsolidation period. These findings suggest that altered GluA2 receptor expression is one of the mechanisms that controls different forms of synaptic plasticity during reconsolidation.

Involvement of Nrf2-PPAR-γ signaling in Coenzyme Q10 protecting effect against methotrexate-induced testicular oxidative damage.

Studies have identified Coenzyme Q10 (CoQ10) as a promising agent in improving idiopathic male infertility; however, its role in chemically or environmentally induced testicular dysfunction is not well-established. We investigated the potential of CoQ10 to attenuate methotrexate (MTX)-induced testicular damage and to identify molecular targets of CoQ10 effects. Wistar rats received a single intraperitoneal dose of 20 mg/kg MTX on the fifth day of the 10-day experimental protocol. 100 mg/kg CoQ10 was given orally daily for ten days, alone or combined with MTX. The testes of MTX-treated animals showed thickened tunica albuginea, distortion of seminiferous tubules with a marked reduction of germinal lining, a few primary spermatocytes with no spermatozoa, apoptotic cells, congested sub-capsular and interstitial blood vessels, and interstitial edema. Reduction of reproductive hormones and increased oxidative, inflammatory, and apoptotic biomarkers levels were also seen in the MTX-treated rats. CoQ10 + MTX-treated rats were protected against MTX-induced testicular histological changes and showed improvement in testosterone, luteinizing-, and follicle-stimulating hormone serum levels compared to the MTX group. The testes of the CoQ10 + MTX-treated rats showed reduced malondialdehyde, myloperoxidase, tumor necrosis factor -α, interleukin-6 and -1ß and Bax: Bcl2 ratio and enhanced glutathione, and catalase compared to MTX alone. CoQ10 enhanced MTX-induced downregulation of Nrf2 and PPAR-γ signaling and modulated its downstream targets, the inducible nitric oxide synthase, NF-κB, Bax, and Bcl2. In conclusion, CoQ10 targeted the Nrf2-PPAR-γ signaling loop and its downstream pathways, mitigating MTX-induced oxidative stress-related damages and alleviating the testicular dysfunction MTX caused. Our data suggest Nrf2-PPAR-γ signaling as a potential therapeutic target in testicular toxicity, where oxidative stress, inflammation, and apoptosis trigger damage.

Long term alterations in synaptic physiology, expression of ß2 nicotinic receptors and ERK1/2 signaling in the hippocampus of rats with prenatal nicotine exposure.

Smoking during pregnancy is associated with long lasting, hippocampus dependent, cognitive deficits in children. The current study was performed to investigate the effect of prenatal nicotine exposure on excitatory synaptic physiology and cellular signaling in the hippocampus using a rodent model. Excitatory synaptic physiology was analyzed using electrophysiological methods to detect changes in synaptic plasticity, excitatory synaptic transmission and synaptic currents mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in the hippocampus. Additionally, western blot experiments were performed to quantify alterations in protein expression levels in the hippocampus. Prenatal nicotine exposure resulted in a decrease in long term potentiation (LTP) and an increase in long term depression (LTD). Basal synaptic transmission was also reduced with a concomitant decline in AMPAR mediated synaptic currents at the cellular and single channel levels. Presynaptic pool of vesicles docked close to release sites were also diminished in nicotine exposed rats. Moreover, reduced levels of ß2 subunit containing nicotinic receptors and extracellular signal regulated kinase1/2 (ERK1/2) were observed in nicotine exposed rats. These results suggest that long lasting alterations in excitatory synaptic physiology, AMPAR synaptic currents and ERK1/2 signaling may serve as the molecular mechanisms for cognitive deficits associated with prenatal nicotine exposure.

Developmental nicotine exposure induced alterations in behavior and glutamate receptor function in hippocampus.

In the developing brain, nicotinic acetylcholine receptors (nAChRs) are involved in cell survival, targeting, formation of neural and sensory circuits, and development and maturation of other neurotransmitter systems. This regulatory role is disrupted when the developing brain is exposed to nicotine, which occurs with tobacco use during pregnancy. Prenatal nicotine exposure has been shown to be a strong risk factor for memory deficits and other behavioral aberrations in the offspring. The molecular mechanisms underlying these neurobehavioral outcomes are not clearly elucidated. We used a rodent model to assess behavioral, neurophysiological, and neurochemical consequences of prenatal nicotine exposure in rat offspring with specific emphasis on the hippocampal glutamatergic system. Pregnant dams were infused with nicotine (6 mg/kg/day) subcutaneously from the third day of pregnancy until birth. Results indicate that prenatal nicotine exposure leads to increased anxiety and depressive-like effects and impaired spatial memory. Synaptic plasticity in the form of long-term potentiation (LTP), basal synaptic transmission, and AMPA receptor-mediated synaptic currents were reduced. The deficit in synaptic plasticity was paralleled by declines in protein levels of vesicular glutamate transporter 1 (VGLUT1), synaptophysin, AMPA receptor subunit GluR1, phospho(Ser845) GluR1, and postsynaptic density 95 (PSD-95). These results suggest that prenatal nicotine exposure by maternal smoking could result in alterations in the glutamatergic system in the hippocampus contributing to the abnormal neurobehavioral outcomes.

Zinc's protective role against hydroxychloroquine-induced cardiac effects in adult male albino rats.

Background: Long exposure to Hydroxychloroquine (HCQ) has been complicated by some dangerous though infrequent cardiotoxicity. Methods: A total of 40 normal adult male albino rats dispersed into 4 groups were used. Group 1 (Control group), Group II (HCQ treated group), Group III (zinc [Zn]-treated group), and Group IV (HCQ and Zn treated group). Once the experimentation ended, rats were sacrificed and cardiac soft tissue sections were processed twenty-four hours at the end of the experiment for histological study. Results: Cardiac-stained sections revealed that HCQ induced widespread necrosis, dilatation, and vacuolar degeneration. However, the combination of HCQ with Zn ameliorated these damaging effects. Cardiac enzyme parameters were also studied in the 4 groups and revealed CK-MB and troponin were considerably elevated in groups II associated to the control group. Conclusion: It was concluded that Zn revealed a protective role against HCQ cardiomyopathy in adult male albino rats. This might signify an appreciated means for Zn-based treatment in the upcoming subsequent clinical records to adjust doses and guarantee patient safeguard.

Fabrication of solid lipid nanoparticles-based patches of paroxetine and their ex-vivo permeation behaviour.

Paroxetine is not suitable for oral administration due to its extensive first-pass metabolism, thus resulting in less bioavailability. This study aimed to prepare novel paroxetine-loaded solid lipid nanoparticles (SLNs) based sustained-release transdermal patches to overcome these problems by enhancing drug absorption and bioavailability. Nine formulations of paroxetine SLNs were prepared by the hot melt-homogenization method using different concentrations of glycerol monostearate (Kolliwax) and Tween 80. Then these prepared SLNs were incorporated in a matrix type transdermal patch having a matrix of ethyl cellulose and polyvinyl pyrrolidone in 3:2 with polyvinyl alcohol. The SLNs showed a particle size range of 113-230 nm and an entrapment efficiency of 85.14%. The SLNs showed sustained paroxetine release (77.86-95.63% release) up to 48 h. FTIR studies showed no interaction between drug and formulation components. Paroxetine is evenly distributed in an amorphous form in SLNs, as demonstrated by DSC as well as PXRD analysis. SLNs formulated patches showed higher drug permeation through the skin than drug-based transdermal patches., Draize patch test revealed no sign of erythema after applying paroxetine-loaded SLN patches (score 0) as observed with the marketed product. The developed SLNs based transdermal patches showed increased permeability and sustained release behaviour.

Deep learning in drug discovery: a futuristic modality to materialize the large datasets for cheminformatics.

Artificial intelligence (AI) development imitates the workings of the human brain to comprehend modern problems. The traditional approaches such as high throughput screening (HTS) and combinatorial chemistry are lengthy and expensive to the pharmaceutical industry as they can only handle a smaller dataset. Deep learning (DL) is a sophisticated AI method that uses a thorough comprehension of particular systems. The pharmaceutical industry is now adopting DL techniques to enhance the research and development process. Multi-oriented algorithms play a crucial role in the processing of QSAR analysis, de novo drug design, ADME evaluation, physicochemical analysis, preclinical development, followed by clinical trial data precision. In this study, we investigated the performance of several algorithms, including deep neural networks (DNN), convolutional neural networks (CNN) and multi-task learning (MTL), with the aim of generating high-quality, interpretable big and diverse databases for drug design and development. Studies have demonstrated that CNN, recurrent neural network and deep belief network are compatible, accurate and effective for the molecular description of pharmacodynamic properties. In Covid-19, existing pharmacological compounds has also been repurposed using DL models. In the absence of the Covid-19 vaccine, remdesivir and oseltamivir have been widely employed to treat severe SARS-CoV-2 infections. In conclusion, the results indicate the potential benefits of employing the DL strategies in the drug discovery process.Communicated by Ramaswamy H. Sarma.

Phenyl-2-aminoethyl selenide ameliorates hippocampal long-term potentiation and cognitive deficits following doxorubicin treatment.

Chemotherapy-induced memory loss ("chemobrain") can occur following treatment with the widely used chemotherapeutic agent doxorubicin (DOX). However, the mechanisms through which DOX induces cognitive dysfunction are not clear, and there are no commercially available therapies for its treatment or prevention. Therefore, the aim of this study was to determine the therapeutic potential of phenyl-2-aminoethyl selenide (PAESe), an antioxidant drug previously demonstrated to reduce cardiotoxicity associated with DOX treatment, against DOX-induced chemobrain. Four groups of male athymic NCr nude (nu/nu) mice received five weekly tail-vein injections of saline (Control group), 5 mg/kg of DOX (DOX group), 10 mg/kg PAESe (PAESe group), or 5 mg/kg DOX and 10 mg/kg PAESe (DOX+PAESe group). Spatial memory was evaluated using Y-maze and novel object location tasks, while synaptic plasticity was assessed through the measurement of field excitatory postsynaptic potentials from the Schaffer collateral circuit. Western blot analyses were performed to assess hippocampal protein and phosphorylation levels. In this model, DOX impaired synaptic plasticity and memory, and increased phosphorylation of protein kinase B (Akt) and extracellular-regulated kinase (ERK). Co-administration of PAESe reduced Akt and ERK phosphorylation and ameliorated the synaptic and memory deficits associated with DOX treatment.

Investigate the chronic neurotoxic effects of diquat.

Chronic exposure to agricultural chemicals (pesticides/herbicides) has been shown to induce neurotoxic effects or results in accumulation of various toxic metabolic by-products. These substances have the relevant ability to cause or increase the risk for neurodegeneration. Diquat is an herbicide that has been extensively used in the United States of America and other parts of the world. Diquat is constantly released into the environment during its use as a contact herbicide. Diquat structurally resembles 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) and paraquat. Rotenone, paraquat, maneb and MPTP reproduce features of movement disorders in experimental animal models. Based on the structural similarity to other neurotoxins, chronic exposure of diquat can induce behavioral and neurochemical alterations associated with dopaminergic neurotoxicity. However, in the present study, diquat unlike other neurotoxins (rotenone, 6-hydroxydopamine, MPTP, paraquat and maneb) did not induce dopamine depletion in the mouse striatum. Although, notable exacerbation in motor impairment (swimming score, akinesia and open field) were evident that may be due to the decreased dopamine turnover and mild nigrostriatal neurodegeneration. These data indicate that, despite the apparent structural similarity to other dopaminergic neurotoxins, diquat did not exert severe deleterious effects on dopamine neurons in a manner that is unique to rotenone and MPTP.

Anti-Inflammatory and Anti-Angiogenic Aattributes of Moringa olifera Lam. and its Nanoclay-Based Pectin-Sericin films.

Background: Inflammation is a strong reaction of the non-specific natural immune system that helps to start protective responses against encroaching pathogens and develop typical immunity against intruding factors. However, prolonged inflammation may lead to chronic autoimmune diseases. For thousands of years, medicinal plants have served as an excellent source of treatment for chronic pathologies such as metabolic diseases. Purpose: The present study aims to evaluate the anti-inflammatory and anti-angiogenic potential of Moringa olifera Lam. extract (MO) and Moringa-loaded nanoclay films. Methods: The extract preparation was done through the maceration technique using absolute methanol (99.7%) and labelled as Mo. Me. Mo. Me-loaded nanoclay-based films were prepared by using pectin and sericin (Table 1). The in vitro studies characterized the film thickness, moisture, and phytochemical contents. The in vivo anti-inflammatory tests involved using a cotton pellet-induced granuloma model assay. In addition, the chick chorioallantoic membrane (CAM) assay was employed for angiogenesis activity. Results: The phytochemical analysis of the extract confirmed the presence of alkaloids, glycosides, flavonoids and phytosterol. This extract contained quercetin in a large quantity. Cotton-pellet induced granuloma model study revealed a comparable (p > 0.05) effect of a high dose of Mo. Me (500 mg/kg) as compared with standard drug. Noteworthy, data obtained through the RT-PCR technique manifested the dose-dependent anti-oedematous effect of Moringa olifera via downregulation of TNF-α and interleukin-1ß. The findings of the CAM assay exhibited a remarkable anti-angiogenic activity of Mo. Me loaded nanoclay films, showing diffused vasculature network in the macroscopic snapshot. Conclusion: Moringa olifera and its nanocomposite films have therapeutic potential against inflammation.

The impact of oral ciprofloxacin on the structure and functions of rat gastric mucosa.

Ciprofloxacin (CPX), is a fluoroquinolone antibiotic used to treat a number of gram-negative and gram-positive bacterial infections. Ciprofloxacin can cause severe side effects, ranging from tendon problems, nerve damage, to serious mood or behavior changes. The purpose of this study was to investigate how ciprofloxacin affects gastric cell lines in rats with a distinctive emphasis on physiological, histopathological, and bacteriological changes. Male albino rats (n = 21) were distributed into three groups; control, CPX, and CPX-withdrawal groups. The treated rats were given CPX tablets (12.5 mg/kg) dissolved in carboxymethyl cellulose (CMC) 0.5% orally once daily via gavage for sixty consecutive days. Control rats received only the vehicle. The withdrawal group was treated for 60 days and the drug was withdrawn for another sixty days. After completion of the experiment, all rats were sacrificed and gastric tissues were treated for light, immunohistochemical, and scanning electron microscopic examination. Image J software was used to measure immune-labeled gastric epithelial cells. Blood samples were also collected for H. Pylori immunoglobulins IgM, IgA, and IgG. Results showed that treated rats acquired significantly strongly positive tumor necrosis factor (TNFα) and significant reduction of serum level of H. pylori IgM, IgA, and IgG in all the study groups. It could be concluded that prolonged oral CPX administration to albino rats changes the gastric mucosal architecture and bacteriology.