SARS-CoV-2 host diversity: An update of natural infections and experimental evidence

Coronavirus disease-19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is now a pandemic threat. This virus is supposed to be spread by human to human transmission. Cellular angiotensin-converting enzyme 2 (ACE2) is the receptor of SARS-CoV-2 which is identical or similar in different species of animals such as pigs, ferrets, cats, orangutans, monkeys, and humans. Moreover, a recent study predicted that dogs might be secondary hosts during the evolution of SARS-CoV-2 from bat to human. Therefore, there is a possibility of spreading SARS-CoV-2 through domestic pets. There are now many reports of SARS-CoV-2 positive cases in dogs, cats, tigers, lion, and minks. Experimental data showed ferrets and cats are highly susceptible to SARS-CoV-2 as infected by virus inoculation and can transmit the virus directly or indirectly by droplets or airborne routes. Based on these natural infection reports and experimental data, whether the pets are responsible for SARS-CoV-2 spread to humans; needs to be deeply investigated. Humans showing clinical symptoms of respiratory infections have been undergoing for the COVID-19 diagnostic test but many infected people and few pets confirmed with SARS-CoV-2 remained asymptomatic. In this review, we summarize the natural cases of SARS-CoV-2 in animals with the latest researches conducted in this field. This review will be helpful to think insights of SARS-CoV-2 transmissions, spread, and demand for seroprevalence studies, especially in companion animals.     

Association of total antioxidants level with glaucoma type and severity

Objectives:

To compare the mean total antioxidant status (TAS) among 3 glaucoma types, namely: pseudoexfoliation glaucoma (PEG), primary open angle glaucoma (POAG), and primary angle closure glaucoma (PACG), and study its potential association with various clinical glaucoma-parameters.

Methods:

In this case-control study, plasma samples were obtained between September 2013 and October 2014 from 340 glaucoma patients (PEG [n=54]; POAG [n=147]; PACG [n=139]), and 351 controls of matching age, gender, ethnicity, and 5 different systemic co-morbidities from King Abdulaziz University Hospital, Riyadh, Saudi Arabia. The TAS in all samples was determined by a colorimetric-based assay.

Results:

The mean±standard deviation of TAS was significantly lower among cases: 0.77±0.32 than controls: 1.1±0.22, p<0.0001. Moreover, the TAS levels were significantly different across the 3 types of glaucoma: 0.86±0.24 in PEG, 0.47±0.32 in POAG, and 0.98±0.41 in PACG (all p<0.0001). In addition, there was a significant correlation between TAS and age at onset (Pearson correlation coefficient [R] 0.17, p<0.0001), cup/disc ratio (R: -0.13, p=0.004), and number of anti-glaucoma medications (R: -0.16, p=0.001).

Conclusion:

Our findings provide evidence that plasma TAS levels are decreased in patients with glaucoma, more so in POAG and PEG than PACG, supporting the hypothesis that decreased antioxidative defense and/or increased oxidative stress may have a critical role in the pathogenesis of glaucoma.Glaucoma is a progressive optic neuropathy associated with optic nerve damage, and is one of the most leading cause of blindness worldwide.1 Elevated intraocular pressure (IOP) as a result of reduction in normal aqueous outflow is a major causal risk factor that is well supported by animal studies.2-4 Although IOP is considered a major risk factor for glaucoma,2,3 other concomitant factors affecting the pathophysiology of glaucomatous retinal ganglion cell (RGC) death include retinal ischemia,5 nutritional status,6 and oxidative stress.7 There is evidence of oxidative damage in ocular diseases, such as cataract and age-related macular degeneration.8 In addition, significant oxidative damage has been demonstrated in human trabecular meshwork (TM) cells of patients with glaucoma,7 causing elevated IOP and visual field damage.9 Furthermore, our previous studies have documented mitochondrial abnormalities10-12 (oxidative stress marker), and glutathione-S-transferase (antioxidant) gene (GST) polymorphisms to be associated with various types of glaucoma.13 It is clearly evident from the literature, and our own studies, that oxidative stress mechanisms play a critical role in the pathogenesis of glaucoma. Previous studies had demonstrated reduced total antioxidant capacity in aqueous humor and blood samples from patients with glaucoma.14-17 To evaluate the role of oxidative stress in different types of glaucoma we had previously investigated total antioxidants status (TAS) in the plasma of pseudoexfoliation glaucoma (PEG) patients,18 primary angle closure glaucoma (PACG) patients,19 and in the plasma of primary open angle glaucoma (POAG) patients.20 As an extension to these studies, here, we compare the mean TAS level among these 3 glaucoma types, and study the potential association between the TAS level and various clinical parameters important to each type of glaucoma.18-20     

Synthesis,acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities,and molecular docking studies of a novel compound based on combination of flurbiprofen and isoniazide

Synthesis of a compound with balanced bioactivities against a specific target is always a challenging task. In this study, a novel compound (1) has been synthesized by combination of flurbiprofen and isoniazide and shows ∼2.5 times enhanced acetylcholinesterase (AChE) inhibition activity and ∼1.7 times improved butyrylcholinesterase (BuChE) inhibition activity compared to flurbiprofen and a standard drug (i.e. physostigmine). A comparative AutoDock study has been performed, based on the optimized structure, by the DFT/B3LYP method, which confirmed that compound (1) is more active against AChE and BuChE, with calculated binding energies of −12.9 kcal mol⁻¹ and −9.8 kcal mol⁻¹ respectively as compared to flurbiprofen and an eserine (physostigmine) standard for which the binding energy was calculated to be −10.1 kcal mol⁻¹ and −8.9 kcal mol⁻¹, respectively. A mixed mode of inhibition of AChE and BuChE with compound 1 was confirmed by Lineweaver–Burk plots. AChE and BuChE inhibition activity alongside docking results suggests that compound (1) could be used for treatment of Alzheimer''s disease. Moreover, compound (1) also exhibit better α-chymotrypsin activity compared to flurbiprofen. Furthermore, in vitro and in vivo analysis confirmed that compound (1) exhibit more activity and less toxicity than the parent compounds.

A novel compound (1) shows ∼2.5 and ∼1.7 times enhanced AChE inhibition activity and BuChE inhibition activity respectively compared to flurbiprofen and standard drug (i.e. physostigmine). It has also been confirmed by comparative AutoDock studies.     

Increase in the effectiveness of somatodendritic 5-HT-1A receptors in a rat model of tardive dyskinesia

The present study concerns responsiveness of pre- and postsynaptic 5-hydroxytryptamine (5-HT)-1A receptors in a rat model of tardive dyskinesia (TD). Vacuous chewing movements (VCMs) in rats are widely accepted as an animal model of TD. Results show that haloperidol injected at a dose of 1 mg/kg twice a day for 5 weeks elicited VCMs, which increased in a time dependent manner following the drug administration for 3-5 weeks. Tolerance was produced in motor coordination during the potentiation of VCMs. Exploratory activity in an open field and in an activity box decreased in haloperidol treated animals. The effects of 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT; 0.5 mg/kg) were monitored 48-h after withdrawal from repeated administration of haloperidol. 8-OH-DPAT-induced locomotion was greater in haloperidol treated rats. 5-HT synthesis increased in haloperidol treated animals, while 8-OH-DPAT-induced decreases of 5-HT synthesis were greater in repeated haloperidol than repeated saline injected animals. The results suggest that an increase in the effectiveness of somatodendritic 5-HT-1A receptors may decrease the inhibitory influence of 5-HT on the activity of dopaminergic neurons to precipitate VCMs. The 5-HT-1A agonist may help to alleviate neuroleptic-induced TD.     

Effectiveness of School-Based Intervention Programs in Reducing Prevalence of Overweight

Objectives:

To assess the effectiveness of school-based interventions program in reducing the prevalence of overweight or obesity among schoolchildren.

Data source:

Ovid Medline (1950-December 2012), Embase (1980-2012), CINAHL (1982-2012), secondary references, review articles, and expert in the field.

Study selection:

All published clinical trials were eligible for study if were randomized, methodologically strong-based on a validity assessment, aimed to evaluate a school-based intervention for childhood overweight or obesity, and measured outcome in term of prevalence/incidence difference in overweight and obesity among both groups. Studies involved in cost-effective analysis of school-based intervention have been excluded. Data from eligible studies abstracted and pooled for relative risk.

Results:

Five trials with 3,904 schoolchildren were included. Mean age of the students (boys and girls) ranges 8.6-12.6 years. Meta-analysis showed a statistical significance beneficial effect of school-based intervention programs on obesity status of schoolchildren (risk ratio (RR) 0.58, 95% confidence interval (CI) 0.43-0.78) and suggested 42% reduction in prevalence of obesity among schoolchildren through school-based intervention programs. Individual studies also showed effectiveness of these school-based interventions.

Conclusion:

School-based intervention programs are effective in prevention of childhood overweight and obesity problem and our results quantitatively supported this argument.     

An advanced and efficient Co3O4/C nanocomposite for the oxygen evolution reaction in alkaline media

The design of efficient nonprecious catalysts for the hydrogen evolution reaction (HER) or the oxygen evolution reaction (OER) is a necessary, but very challenging task to uplift the water-based economy. In this study, we developed a facile approach to produce porous carbon from the dehydration of sucrose and use it for the preparation of nanocomposites with cobalt oxide (Co₃O₄). The nanocomposites were studied by the powder X-ray diffraction and scanning electron microscopy techniques, and they exhibited the cubic phase of cobalt oxide and porous structure of carbon. The nanocomposites showed significant OER activity in alkaline media, and the current densities of 10 and 20 mA cm⁻² could be obtained at 1.49 and 1.51 V versus reversible hydrogen electrode (RHE), respectively. The impedance study confirms favorable OER activity on the surface of the prepared nanocomposites. The nanocomposite is cost-effective and can be capitalized in various energy storage technologies.

The design of efficient nonprecious catalysts for the hydrogen evolution reaction (HER) or the oxygen evolution reaction (OER) is a necessary, but very challenging task to uplift the water-based economy.     

Apigenin as an anticancer agent

Apigenin is an edible plant‐derived flavonoid that has been reported as an anticancer agent in several experimental and biological studies. It exhibits cell growth arrest and apoptosis in different types of tumors such as breast, lung, liver, skin, blood, colon, prostate, pancreatic, cervical, oral, and stomach, by modulating several signaling pathways. Apigenin induces apoptosis by the activation of extrinsic caspase‐dependent pathway by upregulating the mRNA expressions of caspase‐3, caspase‐8, and TNF‐α. It induces intrinsic apoptosis pathway as evidenced by the induction of cytochrome c, Bax, and caspase‐3, while caspase‐8, TNF‐α, and B‐cell lymphoma 2 levels remained unchanged in human prostate cancer PC‐3 cells. Apigenin treatment leads to significant downregulation of matrix metallopeptidases‐2, ?9, Snail, and Slug, suppressing invasion. The expressions of NF‐κB p105/p50, PI3K, Akt, and the phosphorylation of p‐Akt decreases after treatment with apigenin. However, apigenin‐mediated treatment significantly reduces pluripotency marker Oct3/4 protein expression which might be associated with the downregulation of PI3K/Akt/NF‐κB signaling.