Nicotine Protects Kidney from Renal Ischemia/Reperfusion Injury through the Cholinergic Anti-Inflammatory Pathway

Kidney ischemia/reperfusion injury (I/R) is characterized by renal dysfunction and tubular damages resulting from an early activation of innate immunity. Recently, nicotine administration has been shown to be a powerful inhibitor of a variety of innate immune responses, including LPS-induced toxaemia. This cholinergic anti-inflammatory pathway acts via the α7 nicotinic acetylcholine receptor (α7nAChR). Herein, we tested the potential protective effect of nicotine administration in a mouse model of renal I/R injury induced by bilateral clamping of kidney arteries. Renal function, tubular damages and inflammatory response were compared between control animals and mice receiving nicotine at the time of ischemia. Nicotine pretreatment protected mice from renal dysfunction in a dose-dependent manner and through the α7nAChR, as attested by the absence of protection in α7nAChR-deficient mice. Additionally, nicotine significantly reduced tubular damages, prevented neutrophil infiltration and decreased productions of the CXC-chemokine KC, TNF-α and the proinflammatory high-mobility group box 1 protein. Reduced tubular damage in nicotine pre-treated mice was associated with a decrease in tubular cell apoptosis and proliferative response as attested by the reduction of caspase-3 and Ki67 positive cells, respectively. All together, these data highlight that nicotine exerts a protective anti-inflammatory effect during kidney I/R through the cholinergic α7nAChR pathway. In addition, this could provide an opportunity to overcome the effect of surgical cholinergic denervation during kidney transplantation

Опыт применения вено-венозной экстракорпоральной мембранной оксигенации у беременной с тяжелым острым респираторным дистресс-синдромом, вызванным вирусом SARS-CoV-2

 Pregnant women occupy a special place in the incidence structure of the new coronavirus infection COVID -19. Taking into account the likelihood of a more severe course of acute respiratory syndrome (ARDS) in this group, it is worth remembering the possibility of timely use of veno-venous extracorporeal membrane oxygenation (IV ECMO) in order to correct life-threatening hypoxia. At the Lapino Clinical Hospital, a cesarean section was successfully performed in a 37-year-old female patient at 20–21 weeks of gestation against the background of IV ECMO with further decannulation  and discharge from the hospital.  Особое место в структуре заболеваемости новой коронавирусной инфекцией COVID-19 занимают беременные. Принимая во внимание вероятность более тяжелого течения острого респираторного синдрома  (ОРДС) у данной группы, стоит помнить о возможности своевременного  применения вено-венозной экстракорпоральной мембранной оксигенации  (ВВ ЭКМО) с целью коррекции жизнеугрожающей гипоксии. В клиническом госпитале «Лапино» было успешно выполнено кесарево сечение у пациентки 37 лет на 20–21-й неделе гестации на фоне ВВ ЭКМО с дальнейшей деканюляцией и выпиской из стационара.

Cholinergic receptor pathways involved in apoptosis, cell proliferation and neuronal differentiation

Acetylcholine (ACh) has been shown to modulate neuronal differentiation during early development. Both muscarinic and nicotinic acetylcholine receptors (AChRs) regulate a wide variety of physiological responses, including apoptosis, cellular proliferation and neuronal differentiation. However, the intracellular mechanisms underlying these effects of AChR signaling are not fully understood. It is known that activation of AChRs increase cellular proliferation and neurogenesis and that regulation of intracellular calcium through AChRs may underlie the many functions of ACh. Intriguingly, activation of diverse signaling molecules such as Ras-mitogen-activated protein kinase, phosphatidylinositol 3-kinase-Akt, protein kinase C and c-Src is modulated by AChRs. Here we discuss the roles of ACh in neuronal differentiation, cell proliferation and apoptosis. We also discuss the pathways involved in these processes, as well as the effects of novel endogenous AChRs agonists and strategies to enhance neuronal-differentiation of stem and neural progenitor cells. Further understanding of the intracellular mechanisms underlying AChR signaling may provide insights for novel therapeutic strategies, as abnormal AChR activity is present in many diseases

Genomic Profiles of Diversification and Genotype–Phenotype Association in Island Nematode Lineages

Understanding how new species form requires investigation of evolutionary forces that cause phenotypic and genotypic changes among populations. However, the mechanisms underlying speciation vary and little is known about whether genomes diversify in the same ways in parallel at the incipient scale. We address this using the nematode, Pristionchus pacificus, which resides at an interesting point on the speciation continuum (distinct evolutionary lineages without reproductive isolation), and inhabits heterogeneous environments subject to divergent environmental pressures. Using whole genome re-sequencing of 264 strains, we estimate FST to identify outlier regions of extraordinary differentiation (∼1.725 Mb of the 172.5 Mb genome). We find evidence for shared divergent genomic regions occurring at a higher frequency than expected by chance among populations of the same evolutionary lineage. We use allele frequency spectra to find that, among lineages, 53% of divergent regions are consistent with adaptive selection, whereas 24% and 23% of such regions suggest background selection and restricted gene flow, respectively. In contrast, among populations from the same lineage, similar proportions (34-48%) of divergent regions correspond to adaptive selection and restricted gene flow, whereas 13-22% suggest background selection. Because speciation often involves phenotypic and genomic divergence, we also evaluate phenotypic variation, focusing on pH tolerance, which we find is diverging in a manner corresponding to environmental differences among populations. Taking a genome-wide association approach, we functionally validate a significant genotype-phenotype association for this trait. Our results are consistent with P. pacificus undergoing heterogeneous genotypic and phenotypic diversification related to both evolutionary and environmental processes