Highlights SARS-CoV-2 mainly enter to CNS via direct (neuronal and hematologic route) and indirect route. SARS-CoV-2 can infect leukocytes within the bloodstream and then cross the blood-brain-barrier via diapedesis. SARS-CoV-2 can invade the vascular endothelium by binding to ACE-2, leading to increased permeability of blood-brain-barrier and then infecting glial cells in the CNS. Future research is desirable to confirm or disprove such hypothesis.

1 AbstractPurpose: To investigate the therapeutic potential of honey, Nigella sativa (N. sativa) and their combination in rat model of excisional wound healing. Methods: A circular excision wound was established in the back region of 50 Wistar rats. Subsequently, they were divided into 5 groups and daily topical administration of lanolin in the control group, honey in the honey group, cold-pressed N. sativa seed oil in the N. sativa groups, mix of 1:1 ratio of honey and N. sativa seed oil in the mix group, and phenytoin cream in the phenytoin group were used. Then, wound surface areas were evaluated using digital camera immediately after the injury and at post excision days 5, 10, 15 and 20. Results: Significant reduction in wound surface area was observed within and between the groups (P < 0.001). In the post excision days 5, 10, 15 and 20 the wound surface areas in the mix group were significantly lower than the other groups followed by the phenytoin, honey, N. sativa, and control groups. Conclusion:The wound healing may be improved and accelerated by using topical solutions of honey, N. sativa seed oil and especially their mixture.

Actinomycin D may be a better option than methotrexate as a first-line chemotherapy agent for patients with LR-GTN.

Purpose: To investigate the protective effect of preconditioning with non-toxic dose of hydrogenperoxide (H2O2) as a possible cell signaling molecule, against cell death induced by toxicconcentration of H2O2 or by serum deprivation in human Wharton’s jelly-derived mesenchymalstem cells (HWJ-MSCs) and underlying mechanisms.Methods: HWJ-MSCs were isolated and identified using flow cytometry. After finding non-toxicconcentration of H2O2, cells preconditioning was performed by H2O2 (20 μM) for 12 h and celltolerance against serum deprivation or toxic levels of H2O2 was assayed by MTT test. Effect ofpreconditioning on mRNA and protein expression of Akt-1, Bcl-2 and Bax were examined usingreverse transcription polymerase chain reaction (RT-PCR) and western blotting respectively. Roleof hypoxia-inducible factor (HIF)-1α was explored in presence HIF-1α inhibitor.Results: Preconditioning with 20 μM H2O2 for 12 h was non-toxic and decreased cell deathinduced by oxidative stress and serum deprivation in MSC cultures. However, the increasedtolerance reversed in the presence of inhibitor of HIF-1α. By regards to RT-PCR and westernblotting data, although expression of Akt-1, Bcl-2 and Bax was not change considerably butphosphorylated Akt-1 (pAkt-1) was up regulated after treatment with 20 μM H2O2 compared tocontrol group. Moreover after exposure to 100 μM H2O2, western blotting analysis showed thatcell pretreatment with 20 μM H2O2, decremented Bax/Bcl2 ratio and up-regulated HIF-1α andpAkt-1 compared to the control group.Conclusion: Increased tolerance of H2O2-pretreated cells led to the suggestion that transplantationof H2O2 preconditioned MSCs may improve therapeutic potential of stem cells in cell therapyprocedures.

Lead exposure continues to be a significant public health problem. Osteoporosis, inhibition of fracture healing, and cartilage functional impairment have been reported from lead exposure. Mesenchymal stem cells (MSCs) are a bone marrow population of cells with the ability to differentiate into various cell types, particularly osteocytes and chondrocytes. Despite intensive investigation on the effect of lead poisoning on various cell types, there is very little if any report on the effect of lead on MSCs. The aim of this study, therefore, was to investigate the effect of lead acetate on rat bone marrow derived MSCs toxicity and its mechanism by examining the role of pro- and anti-apoptotic proteins in this process. It was revealed that lead acetate could induce cell death in a dose-dependent manner using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium (MTT) assay. Compared to controls, the significant over-expression of pro-apoptotic proteins, including Bax, caspases-9, -3, and p53, with no significant change in anti-apoptotic Bcl(2) protein were obtained in lead-treated cells using western blotting analysis. There was a significant increase in DNA fragmentation in treated MSCs compared to controls using flow-cytometry. Finally, it might be concluded that lead acetate could induce cell toxicity and apoptosis in MSCs, causing instability in mitochondria and in turn activation of the intrinsic pathway including over-expression of Bax, caspase 9 and caspase 3, leading to DNA damage and activation of P53.