Notes

The surroundings from the post-pandemic situation: keeping size increases.
Cardiovascular diseases (CVD) remain a major cause of death worldwide. Evidence suggests that the risk for CVD can increase at fetal stages due to maternal metabolic diseases such as gestational diabetes mellitus (GDM) and maternal supraphysiological hypercholesterolemia (MSPH). GDM is a hyperglycemic, inflammatory and insulin-resistant state that increases plasma levels of free fatty acids and triglycerides, impairs endothelial vascular tone regulation and, due to increased nutrient transport, exposes the fetus to the altered metabolic conditions of the mother. MSPH involves increased levels of cholesterol (mainly as low-density lipoprotein cholesterol) which also causes endothelial dysfunction and alters nutrient transport to the fetus. Despite that an association has already been established between MSPH and increased CVD risk, little is known about the cellular processes underlying this relationship. Our knowledge is further obscured when simultaneous presentation of MSPH and GDM takes place. In this context, GDM and MSPH may substantially increase fetal CVD risk due to synergistic impairment of placental nutrient transport and endothelial dysfunction. More studies on the separate and/or cumulative role of both processes are warranted to suggest specific treatment options.
Fenofibrate (FNB) is a commonly used hypolipidemic agent. However, the oral bioavailability of FNB is limited by slow dissolution due to its low solubility. Thus, investigations on novel FNB formulations are necessary for their use.

To enhance the oral bioavailability of FNB using optimized Nanostructured Lipid Carrier (NLC) formulations.

Hot homogenization followed by ultrasonication was used to prepare FNB-NLCs. These formulations were optimized using a Box-Behnken design, where the amount of FNB (X1), a ratio of solid lipid/liquid lipid (X2), and the percentage of emulsifier (X3), were set as independent variables, while the particle size (Y1), and Entrapment Efficiency (EE%) (Y2), were used as dependent factors. An in vitro dissolution test was then performed using a paddle method, while an in vivo pharmacokinetic study of FNB-NLC formulation was performed in rats.

FNB-NLCs were successfully prepared and optimized using a Box-Behnken design. The particle size and EE% of the FNB-NLC had less than 5% difference from predicted values. The in vitro dissolution and oral bioavailability of the FNB-NLC were both higher than those of raw FNB.

A Box-Behnken design was successfully applied to optimize FNB-NLC formulation for the enhancement of the dissolution and bioavailability of FNB, a poorly water-soluble drug.
A Box-Behnken design was successfully applied to optimize FNB-NLC formulation for the enhancement of the dissolution and bioavailability of FNB, a poorly water-soluble drug.Cyclodextrin based nanosponges are the designed nanocarriers for projected delivery of complex drugs. They are multifunctional hypercrosslinked cyclodextrin polymers connected in a three dimensional, mesh like network. Their functional characteristics can be fabricated by using different crosslinkers or their different rations with polymer. They can encapsulate various hydrophilic, lipophilic, small sized or large sized drug molecules. They offer formulation flexibility and are primarily used for solubility, bioavailability and stability enhancement purposes. This system is also pliable for co-delivery of pharmaceutical entities, improving therapeutic efficacy and patient compliance. If the surface of nanosponge is coupled with an appropriate ligand, even a target specific drug delivery can be achieved. It has a variety of applications in the field of pharmacy for the delivery of tricky drug molecules, proteins, enzymes, natural moieties and gaseous compounds. The list of its applications further widens with the development of nanodiagnostics, nanosensors, biomimetics and scaffolds based on nanosponges. The sudden explosion of research in this working area signifies cyclodextrin nanosponge based product in the market soon.DNA damage usually happens in all cell types, which may originate from endogenous sources, (i.e., DNA replication errors) or be emanated from radiations or chemicals. These damages range from changes in few nucleotides to large structural abnormalities on chromosomes and, if not repaired, could disturb the cellular homeostasis or cause cell death. DNA repair, as the most significant response to DNA damage, provides biological pathways by which DNA damages are corrected and returned into their natural circumstance. However, aberration in the DNA repair mechanisms may result in genomic and chromosomal instability and the accumulation of mutations. The activation of oncogenes and/or inactivation of tumor suppressor genes are serious consequence of genomic and chromosomal instability and may bring the cells into a cancerous phenotype. Therefore, genomic and chromosomal instability is usually considered as a crucial factor in the carcinogenesis and an important hallmark of various human malignancies. In the present study, we review our current understanding of the most updated mechanisms underlying genomic instability in cancer and discuss about the potential promises of these mechanisms in finding new targets for the treatment of cancer.Cardiovascular diseases (CVD), primarily inflammatory cardiomyopathy, are characterized by the infiltration of inflammatory cells into the myocardium. It has a relatively high risk of deteriorating heart function and has heterogeneous etiologies. Inflammatory cardiomyopathy is mainly mediated by viral infections but can also be mediated by protozoa, fungal or bacterial infections. Besides that, there are a wide variety of drugs, toxic substances, and systemic immune-mediated diseases that result in the development of cardiovascular diseases (CVDs). Despite broad research, inflammatory cardiomyopathy has a poor prognosis. The roles of the pathogens, host genomic counterparts and environmental triggers in the progression of disease are still under consideration, including the role of some viruses as active inducers and others as bystanders. In this review article, we review the available evidence on the types, pathogenesis and treatment of myocarditis, inflammatory cardiomyopathy, and atherosclerosis with a particular focus on virus-associated cardiac diseases.
In this review we discuss the emerging evidence for the effectiveness of cannabinoids in the treatment of cancer and inflammation. The remarkable effects complete the traditional evidence for their successful application in the treatment of pain and cancer-related side effects.

we searched Pub Med (132 articles) and Google scholar (9 articles) databases and gathered the clinical (4 articles), preclinical (28 articles) studies, reports on cell culture models (30 articles) and other original and review articles (78 articles) related to inflammation, cancer and cannabinoids.

Cannabinoids are described in three different forms, comprising endo- phyto- and synthetic compounds that exert biological effects. The molecular and cellular pathways of endogenous cannabinoids in the maintenance of homeostasis are well documented. In addition to classical cannabinoid receptors type 1 and 2, Vanilloid receptors and G protein-coupled receptor 55 were identified as common receptors. Subsequently, the effectiveness of phrent review provides and overview the role of endocannabinoid system in the mediation of physiological functions, the type and expression of cannabinoids receptors under physiological and pathological conditions. In additions, the molecular pathways involved in the effects of cannabinoids and the effectiveness of cannabinoids in the treatment of inflammations and cancers are highlighted.This review provides comprehensive information about the advances in gene therapy in the anterior segment of the eye including cornea, conjunctiva, lacrimal gland, and trabecular meshwork. We discuss gene delivery systems including viral and non-viral vectors as well as gene editing techniques, mainly CRISPR-Cas9, and epigenetic treatments including antisense and siRNA therapeutics. We also provide a detailed analysis of various anterior segment diseases where gene therapy has been tested with corresponding outcomes. Disease conditions include corneal and conjunctival fibrosis and scarring, corneal epithelial wound healing, corneal graft survival, corneal neovascularization, genetic corneal dystrophies, herpetic keratitis, glaucoma, dry eye disease, and other ocular surface diseases. Although most of the analyzed results on the use and validity of gene therapy at the ocular surface have been obtained in vitro or using animal models, we also discuss the available human studies. Gene therapy approaches are currently considered very promising as emerging future treatments of various diseases, and this field is rapidly expanding.
Cannabis and synthetic cannabinoids (SC) are related to several neuropsychiatric symptoms and disorders, especially psychotic symptoms and disorders. Interestingly, catatonia-like symptoms associated with cannabis and SC have been generally neglected in research and scarcely described despite the clinical repercussions. Hence, this review aims to analyze current clinical publications on catatonia induced by cannabis or SC in a systematized way.
A search using PRISMA guidelines was performed on three databases based on a specific inclusion and exclusion criteria.
11 publications describing 14 patients (10 males; mean age 22.50 ± 6.67 years old) with catatonia apparently precipitated by the use of cannabis (
 = 6) or SC (
 = 8) were found. Clinical features and treatment are described and discussed.
From a clinical perspective, cannabis and SC use may be related to catatonia-like symptoms and catatonia syndrome in the same way these substances (cannabis and SC) are related to induced-psychotic episbis (n = 6) or SC (n = 8) were found. Clinical features and treatment are described and discussed. Conclusion From a clinical perspective, cannabis and SC use may be related to catatonia-like symptoms and catatonia syndrome in the same way these substances (cannabis and SC) are related to induced-psychotic episodes. However, further research will be required to understand the exact nature of that relationship. Selleck Onvansertib Additionally, investigations focused on the clinical significance (i.e., prognosis, evolution, and outcomes) of catatonia-like symptoms induced by cannabis and SC use in patients are also needed.Pupurpose of the study Oxidative stress has been reported to be an important mechanism for brain damage following ischemic stroke. Recently, the involvement of cytosolic receptors capable of forming protein complexes called inflammasomes has been demonstrated to perpetuate oxidative stress. Herein, we report the effect of NLRP3 inhibition with MCC950 on brain oxidative stress in an animal model of transient global cerebral ischemia.Materials and methods Male Wistar rats received an intracerebroventricularly (icv) injection of MCC950 (140 ng/kg) or saline and were subjected to sham procedure or ischemia/reperfusion (I/R). Twenty-four hours after I/R, myeloperoxidase (MPO) activity, nitrite/nitrate (N/N) concentration, lipid peroxidation, protein carbonyls formation, superoxide dismutase (SOD) and catalase (CAT) activity were determined in the prefrontal cortex, hippocampus, cortex, cerebellum and striatum. Results After I/R, MPO activity increased in the prefrontal cortex, hippocampus, cortex and cerebellum and N/N concentration elevated in the prefrontal cortex, hippocampus and cortex, while MCC950 decreased this level except in hippocampus.
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