ABSTRACT
COVID-19-caused neurological problems are the important post-CoV-2 infection complications, which are recorded in ~ 40% of critically ill COVID-19 patients. Neurodegeneration (ND) is one of the most serious complications. It is necessary to understand its molecular mechanism(s), define research gaps to direct research to, hopefully, design new treatment modalities, for predictive diagnosis, patient stratification, targeted prevention, prognostic assessment, and personalized medical services for this type of complication. Individualized nano-bio-medicine combines nano-medicine (NM) with clinical and molecular biomarkers based on omics data to improve during- and post-illness management or post-infection prognosis, in addition to personalized dosage profiling and drug selection for maximum treatment efficacy, safety with least side-effects. This review will enumerate proteins, receptors, and enzymes involved in CoV-2 entrance into the central nervous system (CNS) via the blood-brain barrier (BBB), and list the repercussions after that entry, ranging from neuroinflammation to neurological symptoms disruption mechanism. Moreover, molecular mechanisms that mediate the host effect or viral detrimental effect on the host are discussed here, including autophagy, non-coding RNAs, inflammasome, and other molecular mechanisms of CoV-2 infection neuro-affection that are defined here as hallmarks of neuropathology related to COVID-19 infection. Thus, a couple of questions are raised; for example, "What are the hallmarks of neurodegeneration during COVID-19 infection?" and "Are epigenetics promising solution against post-COVID-19 neurodegeneration?" In addition, nano-formulas might be a better novel treatment for COVID-19 neurological complications, which raises one more question, "What are the challenges of nano-bio-based nanocarriers pre- or post-COVID-19 infection?" especially in the light of omics-based changes/challenges, research, and clinical practice in the framework of predictive preventive personalized medicine (PPPM / 3P medicine).
ABSTRACT
Numerous non-avian theropod dinosaur fossils have been reported from the Upper Cretaceous (Cenomanian) Bahariya Formation, Bahariya Oasis, Western Desert of Egypt, but unambiguous materials of Abelisauridae have yet to be documented. Here we report Mansoura University Vertebrate Paleontology Center (MUVP) specimen 477, an isolated, well-preserved tenth cervical vertebra of a medium-sized abelisaurid from the Bahariya Formation. The new vertebra shows affinities with those of other Upper Cretaceous abelisaurids from Madagascar and South America, such as Majungasaurus crenatissimus, Carnotaurus sastrei, Viavenator exxoni and a generically indeterminate Patagonian specimen (Museo Padre Molina specimen 99). Phylogenetic analysis recovers the Bahariya form within Abelisauridae, either in a polytomy of all included abelisaurids (strict consensus tree) or as an early branching member of the otherwise South American clade Brachyrostra (50% majority rule consensus tree). MUVP 477, therefore, represents the first confirmed abelisaurid fossil from the Bahariya Formation and the oldest definitive record of the clade from Egypt and northeastern Africa more generally. The new vertebra demonstrates the wide geographical distribution of Abelisauridae across North Africa during the middle Cretaceous and augments the already extraordinarily diverse large-bodied theropod assemblage of the Bahariya Formation, a record that also includes representatives of Spinosauridae, Carcharodontosauridae and Bahariasauridae.
ABSTRACT
AIMS: Cognitive decline is one of the most challenging issues for cancer survivors undergoing doxorubicin (DOX) based chemotherapy. Oxidative stress and inflammation primarily through tumor necrosis factor-alpha (TNF-α) are considered the key contributors to DOX-induced chemobrain. Berberine (BBR) has attracted much interest because of its anti-oxidative, anti-inflammatory and anti-apoptotic actions. This study aimed to evaluate the potential neuroprotective effect of BBR in DOX-induced neurodegeneration and cognitive deficits. MATERIALS AND METHODS: Chemobrain was induced by DOX i.p. injection at the dose of 2 mg/kg, once/week, for four consecutive weeks. Rats were treated with BBR (100 mg/kg, p.o.) for 5 days/week for four consecutive weeks. KEY FINDINGS: BBR significantly attenuated behavioral defects in DOX-induced cognitive impairment. Besides, BBR reversed histopathological abnormalities. Mechanistically, it reversed DOX-induced neuroinflammation by attenuating NF-κB gene and protein expression in addition to diminishing expression of pro-inflammatory mediators (TNF-α and IL-1ß), as well as apoptotic related factors (Bax, Bcl2 and Bax/Bcl2 ratio). Additionally, BBR activated the anti-oxidative defense via upregulating the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and manganese superoxide dismutase (MnSOD). BBR improved synaptic plasticity through cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF). These effects were related through the modulation of Sirtuin1 (SIRT1) expression. SIGNIFICANCE: BBR is highlighted to induce neuroprotection against DOX-induced cognitive decline through modulating brain growth factors and imposing an anti-inflammatory, anti-apoptotic and anti-oxidative effects.
