Adolescent stress accelerates postpartum novelty recognition impairment in 5xFAD mice.

Pregnancy and the postpartum period induce physiological changes that can influence women's cognitive functions. Alzheimer's disease (AD) has a higher prevalence in women and is exacerbated by early life stress. In the present study, we found that late adolescent social isolation combined with the experience of pregnancy and delivery accelerates the onset of cognitive deficits in 5xFAD dams, particularly affecting their ability to recognize novelty. These cognitive deficits manifested as early as 16 weeks, earlier than the usual timeline for these mice, and were closely associated with increased levels of corticosterone, suggesting dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Notably, the presence of ß-amyloid plaques in brain regions associated with novelty recognition did not significantly contribute to these deficits. This highlights the potential role of stress and HPA axis dysregulation in the development of cognitive impairments related to AD, and underscores the need for further investigation.

Nanoparticles fabricated from the bioactive tilapia scale collagen for wound healing: Experimental approach.

The creation of innovative wound-healing nanomaterials based on natural compounds emerges as a top research goal. This research aimed to create a gel containing collagen nanoparticles and evaluate its therapeutic potential for skin lesions. Collagen nanoparticles were produced from fish scales using desolvation techniques. Using SDS PAGE electrophoresis, Fourier transform infrared spectroscopy (FTIR) as well as the structure of the isolated collagen and its similarities to collagen type 1 were identified. The surface morphology of the isolated collagen and its reformulation into nanoparticles were examined using transmission and scanning electron microscopy. A Zeta sizer was used to examine the size, zeta potential, and distribution of the synthesized collagen nanoparticles. The cytotoxicity of the nanomaterials was investigated and an experimental model was used to evaluate the wound healing capability. The overall collagen output from Tilapia fish scales was 42%. Electrophoretic patterns revealed that the isolated collagen included a unique protein with chain bands of 126-132 kDa and an elevated beta band of 255 kDa. When compared to the isolated collagen, the collagen nanoparticles' FTIR results revealed a significant drop in the amide II (42% decrease) and amide III (32% decrease) band intensities. According to SEM analysis, the generated collagen nanoparticles ranged in size from 100 to 350 nm, with an average diameter of 182 nm determined by the zeta sizer. The produced collagen nanoparticles were polydispersed in nature and had an equivalent average zeta potential of -17.7 mV. Cytotoxicity study showed that, when treating fibroblast cells with collagen nanoparticle concentrations, very mild morphological alterations were detected after human skin fibroblasts were treated with collagen nanoparticles 32 µg/ml for 24 hours, as higher concentrations of collagen nanoparticles caused cell detachment. Macroscopical and histological investigations proved that the fabricated fish scale collagen nanoparticles promoted the healing process in comparison to the saline group.

Brain-targeted delivery of Valsartan using solid lipid nanoparticles labeled with Rhodamine B; a promising technique for mitigating the negative effects of stroke.

The brain is a vital organ that is protected from the general circulation and is distinguished by the presence of a relatively impermeable blood brain barrier (BBB). Blood brain barrier prevents the entry of foreign molecules. The current research aims to transport valsartan (Val) across BBB utilizing solid lipid nanoparticles (SLNs) approach to mitigate the adverse effects of stroke. Using a 32-factorial design, we could investigate and optimize the effect of several variables in order to improve brain permeability of valsartan in a target-specific and sustained-release manner, which led to alleviation of ischemia-induced brain damage. The impact of each of the following independent variables was investigated: lipid concentration (% w/v), surfactant concentration (% w/v), and homogenization speed (RPM) on particle size, zeta potential (ZP), entrapment efficiency (EE) %, and cumulative drug release percentage (CDR) %. TEM images revealed a spherical form of the optimized nanoparticles, with particle size (215.76 ± 7.63 nm), PDI (0.311 ± 0.02), ZP (-15.26 ± 0.58 mV), EE (59.45 ± 0.88%), and CDR (87.59 ± 1.67%) for 72 hours. SLNs formulations showed sustained drug release, which could effectively reduce the dose frequency and improve patient compliance. DSC and X-ray emphasize that Val was encapsulated in the amorphous form. The in-vivo results revealed that the optimized formula successfully delivered Val to the brain through intranasal rout as compared to a pure Val solution and evidenced by the photon imaging and florescence intensity quantification. In a conclusion, the optimized SLN formula (F9) could be a promising therapy for delivering Val to brain, alleviating the negative consequences associated with stroke.

Isoflavones derived from plant raw materials: bioavailability, anti-cancer, anti-aging potentials, and microbiome modulation.

Isoflavones are secondary metabolites that represent the most abundant category of plant polyphenols. Dietary soy, kudzu, and red clover contain primarily genistein, daidzein, glycitein, puerarin, formononetin, and biochanin A. The structural similarity of these compounds to ß-estradiol has demonstrated protection against age-related and hormone-dependent diseases in both genders. Demonstrative shreds of evidence confirmed the fundamental health benefits of the consumption of these isoflavones. These relevant activities are complex and largely driven by the source, active ingredients, dose, and administration period of the bioactive compounds. However, the preclinical and clinical studies of these compounds are greatly variable, controversial, and still with no consensus due to the non-standardized research protocols. In addition, absorption, distribution, metabolism, and excretion studies, and the safety profile of isoflavones have been far limited. This highlights a major gap in understanding the potentially critical role of these isoflavones as prospective replacement therapy. Our general review exclusively focuses attention on the crucial role of isoflavones derived from these plant materials and critically highlights their bioavailability, possible anticancer, antiaging potentials, and microbiome modulation. Despite their fundamental health benefits, plant isoflavones reveal prospective therapeutic effects that worth further standardized analysis.

Nanoparticles of ZnO/Berberine complex contract COVID-19 and respiratory co-bacterial infection in addition to elimination of hydroxychloroquine toxicity.

Purpose: A novel coronavirus (COVID-19) that has not been previously identified in humans and has no specific treatment has recently spread. Treatment trials using antiviral and immune-modulating drugs such as hydroxychloroquine (HCQ) were used to control this viral outbreak however several side effects have emerged. Berberine (BER) is an alkaloid that has been reported to reveal some pharmacological properties including antioxidant and antimicrobial activities. Additionally, Zinc oxide nanoparticles (ZnO-NPs) possess potent antioxidant and anti-inflammatory properties. Therefore, this study was undertaken to estimate the efficiency of both BER and synthetic ZnO/BER complex as an anti-COVID-19 therapy. Methods: First, the ZnO/BER complex was prepared by the facile mixing method. Then in vitro studies on the two compounds were conducted including VeroE6 toxicity, anti-COVID-19 activity, determination of inhibitory activity towards papain-like proteinase (PL pro) and spike protein- and receptor- binding domain (RBD) as well as assessment of drug toxicity on RBCs. Results: The results showed that ZnO/BER complex acts as an anti-COVID-19 by inhibiting spike protein binding with angiotensin-converting enzyme II (ACE II), PL pro activity, spike protein and E protein levels, and expression of both E-gene and RNA dependent RNA polymerase (RdRp) at a concentration lower than that of BER or ZnO-NPs alone. Furthermore, ZnO/BER complex had antioxidant and antimicrobial properties where it prevents the auto oxidation of 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and the culture of lower respiratory system bacteria that affected Covid 19 patients. The ZnO/BER complex prevented as well the HCQ cytotoxic effect on both RBC and WBC (in vitro) and hepatotoxicity, nephrotoxicity and anemia that occurred after HCQ long administration in vivo. Conclusion: The ZnO/BER complex can be accounted as promising anti-COVID 19 candidate because it inhibited the virus entry, replication, and assembly. Furthermore, it could be used to treat a second bacterial infection that took place in hospitalized COVID 19 patients. Moreover, ZnO/BER complex was found to eliminate the toxicity of long-term administration of HCQ in vivo.

Potential therapeutic and pharmacological strategies for SARS-CoV2.

BACKGROUND: At the end of 2019, the new Coronavirus disease 2019 (COVID-19) strain causing severe acute respiratory syndrome swept the world. From November 2019 till February 2021, this virus infected nearly 104 million, with more than two million deaths and about 25 million active cases. This has prompted scientists to discover effective drugs to combat this pandemic. AREA COVERED: Drug repurposing is the magic bullet for treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). Therefore, several drugs have been investigated in silico, in vitro, as well as through human trials such as anti-SARS-CoV2 agents, or to prevent the complications resulting from the virus. In this review, the mechanisms of action of different therapeutic strategies are summarized. According to the WHO, different classes of drugs can be used, including anti-malarial, antiviral, anti-inflammatory, and anti-coagulant drugs, as well as angiotensin-converting enzyme inhibitors, antibiotics, vitamins, zinc, neutralizing antibodies, and convalescent plasma therapy. Recently, there are some vaccines which are approved against SARS-CoV2. EXPERT OPINION: A complete understanding of the structure and function of all viral proteins that play a fundamental role in viral infection, which contribute to the therapeutic intervention and the development of vaccine in order to reduce the mortality rate. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40005-021-00520-4.

Assessment of Pregabalin-Induced Cardiotoxicity in Rats: Mechanistic Role of Angiotensin 1-7.

Pregabalin (PRG) possesses great therapeutic benefits in the treatment of epilepsy, neuropathic pain, and fibromyalgia. However, clinical data have reported incidence or exacerbation of heart failure following PRG administration. Experimental data exploring cardiac alterations and its underlying mechanisms are quite scarce. The aim of the present work was to investigate the effect of PRG on morphometric, echocardiographic, neurohumoral, and histopathological parameters in rats. It was hypothesized that alterations in cardiac renin angiotensin system (RAS) might be involved in PRG-induced cardiotoxicity. To further emphasize the role of RAS in the mechanism of PRG-induced cardiotoxicity, the protective potential of diminazene aceturate (DIZE), an ACE2 activator, was investigated. Results showed 44% decrease in ejection fraction and sevenfold increase in plasma N-terminal pro-brain natriuretic peptide. Histopathological examination also showed prominent vacuolar changes and edema in cardiomyocytes. In addition, PRG significantly increased angiotensin II (Ang II), angiotensin converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) levels, while decreased angiotensin 1-7 (Ang 1-7), angiotensin converting enzyme 2 (ACE2), and Mas receptor (MasR) cardiac levels. DIZE co-administration showed prominent protection against PRG-induced echocardiographic, neurohumoral, and histopathological alterations in rats. In addition, downregulation of ACE/Ang II/AT1R and upregulation of ACE2/Ang 1-7/MasR axes were noted in DIZE co-treated rats. These findings showed, for the first time, the detailed cardiac deleterious effects of PRG in rats. The underlying pathophysiological mechanism is probably mediated via altered balance between the RAS axes in favor to the ACE/Ang II/AT1R pathway. Accordingly, ACE2 activators might represent promising therapeutic agents for PRG-induced cardiotoxicity.