The role of IL-1 family of cytokines and receptors in pathogenesis of COVID-19.

A global pandemic has erupted as a result of the new brand coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pandemic has been consociated with widespread mortality worldwide. The antiviral immune response is an imperative factor in confronting the recent coronavirus disease 2019 (COVID-19) infections. Meantime, cytokines recognize as crucial components in guiding the appropriate immune pathways in the restraining and eradication of the virus. Moreover, SARS-CoV-2 can induce uncontrolled inflammatory responses characterized by hyper-inflammatory cytokine production, which causes cytokine storm and acute respiratory distress syndrome (ARDS). As excessive inflammatory responses are contributed to the severe stage of the COVID-19 disease, therefore, the pro-inflammatory cytokines are regarded as the Achilles heel during COVID-19 infection. Among these cytokines, interleukin (IL-) 1 family cytokines (IL-1, IL-18, IL-33, IL-36, IL-37, and IL-38) appear to have a strong inflammatory role in severe COVID-19. Hence, understanding the underlying inflammatory mechanism of these cytokines during infection is critical for reducing the symptoms and severity of the disease. Here, the possible mechanisms and pathways involved in inflammatory immune responses are discussed.

Sex-dependent effects of postweaning exposure to an enriched environment on novel objective recognition memory and anxiety-like behaviors: The role of hippocampal BDNF level.

Exposure to enriched environment (EE) has been indicated to enhance cognitive functions, hippocampal neural plasticity, neurogenesis, long-term potentiation, and levels of the brain-derived neurotrophic factor (BDNF) in laboratory animals. Also, studies on the sex-dependent effects of exposure to EE during adolescence on adult cognitive functions are less. This is important because the beneficial effects of EE may be predominant in the adolescence stage. Therefore, the present study was designed to compare the effects of EE during adolescence (PND21-PND60) on novel objective recognition memory (NORM), anxiety-like behaviors, and hippocampal BDNF mRNA level in the adult male and female rats. Assessment of NORM and anxiety-like behaviors has been done by novel objective recognition task, open field (OF), and elevated plus maze (EPM), respectively. The expression of BDNF mRNA level was also evaluated by quantitative RT-PCR. Our findings demonstrated that housing in the EE during adolescence improves NORM in adult male rats. Also, exposure to EE during adolescence had a different effect on anxiety-like behaviors in both sexes. Additionally, our results indicated an augmented BDNF level in the hippocampus of male and female rats. In conclusion, adolescent exposure to EE has sex-dependent effects on cognitive functions and anxiety-like behaviors and increases BDNF mRNA expression in the hippocampus of both male and female rats; thus, BDNF is an important factor that can mediate the beneficial effects of EE and running exercise on cognitive functions and psychiatric traits.

Allicin prevents the formation of Proteus-induced urinary crystals and the blockage of catheter in a bladder model in vitro.

Stone formation and catheter blockage are major complications of Proteus UTIs. In this study, we investigated the ability of allicin to inhibit P. mirabilis-induced struvite crystallization and catheter blockage using a synthetic bladder model. Struvite crystallization inhibition study was carried out using P. mirabilis lysate as urease enzyme source in synthetic urine (SU). Struvite productions were monitored by phase contrast light microscopy and measurements of pH, Mg2+ and Ca2+ precipitation and turbidity. A catheter blockage study was performed in a synthetic bladder model mimicking natural UTI in the presence of allicin at sub-MIC concentrations (MIC = 64 µg/ml). The results of crystallization study showed that allicin inhibited pH rise and consequently turbidity and precipitation of ions in a dose-dependent manner. The results of catheter blockage study showed that allicin at sub-MIC concentrations (2, 4, 8 µg/ml) significantly increased the time for catheter blockage to occur to 61, 74 and 92 h respectively compared to allicin-free control (48 h). In a similar way, the results showed that allicin delayed the increase of SU pH level in bladder model in a dose-dependent manner compared to allicin-free control. The results also showed that following the increase of allicin concentration, Mg2+ and Ca2+ deposition in catheters were much lower compared to allicin-free control, further confirmed by direct observation of the catheters' eyehole and cross sections. We conclude that allicin prevents the formation of Proteus-induced urinary crystals and the blockage of catheters by delaying pH increase and lowering Mg2+ and Ca2+ deposition in a dose-dependent manner.

Renoprotective effects of the methanolic extract of Tanacetum parthenium against carbon tetrachloride-induced renal injury in rats.

OBJECTIVE: Studies have demonstrated that carbon tetrachloride (CCl4) increases the generation of reactive oxygen species (ROS) in many tissues including the kidney, heart, lung, brain, and liver. The major aim of the present study was to evaluate the protective activity of Tanacetum parthenium extract (TPE) in renal tissues of CCl4-intoxicated rats. MATERIALS AND METHODS: Animals were divided into seven groups of six rats. Group 1 was the control group that was not treated with CCl4. The rats in the other groups were intraperitoneally injected with CCl4 (1.5 ml/kg, 1:1 in olive oil) on day 14. Rats in the groups bTPE40, bTPE80, and bTPE120 were gavaged with 40, 80, and 120 mg/kg of TPE, respectively for 14 constitutive days on a daily basis, before CCl4 administration. Rats in groups aTPE80 and aTPE120 were gavaged with 80 and 120 mg/kg of TPE, respectively, 2, 6, 24 and 48 hr after receiving CCl4. Blood samples were collected at the end of the 16th day through an intracardiac puncture and then serums were separated. RESULTS: CCl4 increased urea, creatinine, uric acid and creatinine: albumin (C/A) ratio level in serum and decreased total antioxidant and antioxidant enzymes (SOD and GPx) when compared to the control group (p<0.001). But administration of TPE to rats either before or after exposure to CCl4, attenuated these changes when compared with CCl4 control group (p<0.05 - p<0.001). CONCLUSION: TPE had potent nephroprotective effects against oxygen free radicals produced through CCl4 metabolism.

Effect of troxerutin on synaptic plasticity of hippocampal dentate gyrus neurons in a ß-amyloid model of Alzheimer׳s disease: an electrophysiological study.

Alzheimer׳s disease (AD) is a neurodegenerative disorder with a progressive cognitive decline and memory loss. Multiple pathogenetic factors including aggregated ß-amyloid (Aß), neurofibrillary tangles (NFTs), cholinergic dysfunction and oxidative stress are involved in AD. Aß, a major constituent of the senile plaques, is a potent neurotoxic peptide and has a pivotal role in cognitive deficit and reduced synaptic plasticity in AD. In the present study we examined the protective effect of troxerutin, as a multipotent bioflavonoid, on Aß (1-42)-induced impairment of evoked field potential in hippocampal DG neurons. Male Wistar rats were divided into four groups including Aß (42-1), Aß (1-42), Aß (1-42) plus troxerutin and Aß (42-1) plus troxerutin groups. Aß was injected intracerebroventricularly (i.c.v.) into right lateral ventricle and after two weeks the evoked field potential recorded from perforant path-DG synapses to assess paired pulse paradigm and long term potentiation (LTP). Administration of Aß (1-42) drastically attenuated the LTP of DG neurons, while there was no significant difference in evoked field potentials between Aß (1-42) plus troxerutin group with respect to Aß (42-1) group. This study revealed that troxerutin improves the synaptic failure induced by Aß peptide and can be introduced as a promising multi-potent pharmacological agent in prevention or treatment of AD in the future.