Patients with COVID-19 who require ICU admission might have the cytokine storm. It is a state of out-of-control release of a variety of inflammatory cytokines. The molecular mechanism of the cytokine storm has not been explored extensively yet. The attachment of SARS-CoV-2 spike glycoprotein with angiotensin-converting enzyme 2 (ACE2), as its cellular receptor, triggers complex molecular events that leads to hyperinflammation. Four molecular axes that may be involved in SARS-CoV-2 driven inflammatory cytokine overproduction are addressed in this work. The virus-mediated down-regulation of ACE2 causes a burst of inflammatory cytokine release through dysregulation of the renin-angiotensin-aldosterone system (ACE/angiotensin II/AT1R axis), attenuation of Mas receptor (ACE2/MasR axis), increased activation of [des-Arg9]-bradykinin (ACE2/bradykinin B1R/DABK axis), and activation of the complement system including C5a and C5b-9 components. The molecular clarification of these axes will elucidate an array of therapeutic strategies to confront the cytokine storm in order to prevent and treat COVID-19 associated acute respiratory distress syndrome.

Background: Chronic kidney diseases and end stage renal disease are growing threats worldwide. Tissue engineering is a new hope to surpass the current limitations such as the shortage of donor. To do so, the rst step would be fabrication of an intact decellularized kidney scaffold. In the current study, an automatic decellularization device was developed to perfuse and decellularize male rats' kidneys using both sodium lauryl ether sulfate (SLES) and sodium dodecyl sulfate (SDS) and to compare their e cacy in kidney decellularization and post-transplantation angiogenesis.Methods: After anesthesia, kidneys were perfused with either 1% SDS solution for 4 h or 1% SLES solution for 6 h. The decellularized scaffolds were stained with hematoxylin and eosin, periodic acid Schiff, Masson's trichrome, and Alcian blue to determine cell removal and glycogen, collagen and glycosaminoglycan contents, respectively. Moreover, scanning electron microscopy was performed to evaluate the cell removal and preservation of microarchitecture of both SDS and SLES scaffolds. Additionally, DNA quanti cation assay was applied for all groups in order to measure residual DNA in the scaffolds and normal kidney. In order to demonstrate biocompatibility and bioactivity of the decellularized scaffolds two tests were done. The scaffolds were recellularized with the human umbilical cord mesenchymal stromal/stem cells (hUC-MSCs). In addition, the allotransplantation was performed in back muscle and angiogenesis was evaluated.Results: Complete cell removal in both SLES and SDS groups was observed in scanning electron microscopy and DNA quanti cation assays. Moreover, the extracellular matrix architecture of rat kidney in the SLES group was signi cantly preserved better than the SDS group. The hUC-MSCs were successfully migrated from the cell culture plate surface into the SDS and SLES decellularized scaffolds. The formation of blood capillaries and vessels were observed in the kidney allotransplantation in both SLES and SDS decellularized kidneys.Conclusions: We demonstrated that both SLES and SDS could be promising tools in kidney tissue engineering. The better preservation of extracellular matrix than SDS, introduces SLES as the solvent of choice for kidney decellularization.

Background Accumulating evidence indicates that vitamin D deficiency has been increased globally over the last two decades. However, the majority of these studies are concerned with cities and there is scant information regarding the prevalence of vitamin D in rural areas. The main aim of this study was to investigate the prevalence of vitamin D deficiency and its associated risk factors among the rural population in Bushehr province which shares the longest border with the Persian Gulf. Methods The rural inhabitants of more than 25 years old from three mountainous, plain, and seashore areas of Bushehr province were selected through a stratified multi-cluster random sampling method. After obtaining the participants’ demographic and anthropometric data and their past medical history, serum 25-hydroxyvitamin D [25(OH)D] was measured using ELISA. Results A total of 1806 (means ±SD, 46± 14years old) rural subjects (35 % males and 65 % females) participated in this study. The prevalence of vitamin D deficiency, insufficiency, and sufficiency were 28 %, 50 %, and 22 %, respectively. The deficiency of vitamin D in women was higher than in men (OR=1.27, 95 % CI: 1.05 to 1.54, P=0.04). There was a positive significant correlation between age and serum vitamin D levels. Men with vitamin D deficiency had higher BMI (P=0.008); this association was not observed among women (P=0.7). There was no significant difference between the food item’s consumption frequencies, and vitamin D status (P>0.05). The mountainous, and plain areas had the highest and lowest vitamin D levels, respectively. Conclusions Although, Bushehr province is located in a sunny part of Iran, the prevalence of vitamin D deficiency was high among its rural population. The shift of their lifestyle patterns and rapid industrialization in these rural areas may be responsible. Therefore, the enrichment of dietary sources with vitamin D and the use of vitamin D supplements are recommended to tackle the high prevalence of vitamin D deficiency in the rural population of the northern part of the Persian Gulf.

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Although SARS-CoV-2 entry to cells strictly depends on angiotensin-converting enzyme 2 (ACE2), the virus also needs transmembrane serine protease 2 (TMPRSS2) for its spike protein priming. It has been shown that the entrance of SARS-CoV-2 through ACE2 can be blocked by cellular TMPRSS2 blockers. The main aim of this study was to find potential inhibitor(s) of TMPRSS2 through virtual screening against a homology model of TMPRSS2 using the library of marine natural products (MNPs). The homology modeling technique for generating a three-dimensional structure of TMPRSS2 was applied. Molecular docking, MM-GBSA and absorption, distribution, metabolism, excretion (ADME) evaluations were performed to investigate the inhibitory activity of marine natural products (MNPs) against TMPRSS2 and their pharmacokinetic properties. Camostat and nafamostat mesylate were used as the standard inhibitory molecules. Seven MNPs were able to inhibit TMPRSS2 better than the standard compounds. MNP 10 with CAS number 107503-09-3, called Watasenia β-D- Preluciferyl glucopyrasoiuronic acid, was found to be the best inhibitor of TMPRSS2 with acceptable pharmacokinetic properties. Herein, for the first time, a new marine natural product was introduced with potent inhibitory effects against TMPRSS2. MNP 10 exhibited favorable drug-like pharmacokinetic properties and it promises a novel TMPRSS2 blocker to combat SARS-CoV-2.