Post-Weaning Treatment with Probiotic Inhibited Stress-Induced Amnesia in Adulthood Rats: The Mediation of GABAergic System and BDNF/c-Fos Signaling Pathways.

The current study aimed to examine the effect of post-weaning treatment with probiotics on memory formation under stress during the adult period in male Wistar rats. Considering GABA is a potential mediator between probiotics and the host, the present study also investigated the involvement of the GABAergic system in the probiotic response. The hippocampal and prefrontal cortical (PFC) expression levels of BDNF and c-Fos were also assessed to show whether the treatments affect the memory-related signaling pathway. Three weeks after birth, the post-weaning rats were fed with probiotic water (PW) or tap water (TW) for 2, 3, 4, or 5 weeks. Exposure to acute stress impaired memory formation in a passive avoidance learning task. Feeding the post-weaning animals with probiotic strains (3, 4, or 5 weeks) inhibited stress-induced amnesia of the adult period. Post-training intracerebroventricular (ICV) microinjection of muscimol improved stress-induced amnesia in the animals fed with TW. ICV microinjection of muscimol inhibited probiotic treatment's significant effect on the stress response in the memory task. The expression levels of BDNF and c-Fos in the PFC and the hippocampus were significantly decreased in the stress animal group. The levels of BDNF and c-Fos were increased in the PW/stress animal group. The muscimol response was compounded with the decreased levels of BDNF and c-Fos in the PFC and the hippocampus. Thus, the GABA-A receptor mechanism may mediate the inhibitory effect of this probiotic mixture on stress-induced amnesia, which may be associated with the PFC and hippocampal BDNF/c-Fos signaling changes.

COVID-19 Vaccination in Patients With Malignancy; A Systematic Review and Meta-Analysis of the Efficacy and Safety.

Background: Data on the efficacy and safety of COVID-19 vaccines in patients with malignancy are immature. In this paper, we assessed the literature involving the use of COVID-19 vaccines in cancer patients and reported the seroconversion rates as the main outcome and severity of COVID-19 infection and side effects following COVID-19 vaccination as the secondary outcomes. Methods: A systematic review with meta-analysis was performed. Searches were conducted in electronic websites, databases, and journals, including Scopus, PubMed, Embase, and Web of Science from January 01, 2019, to November 30, 2021. Studies reporting data on the safety and efficacy of COVID vaccine in cancer patients using any human samples were included. The risk of bias was assessed using the NEWCASTLE-OTTAWA scale in the included studies. Results: A total of 724 articles were identified from databases, out of which 201 articles were duplicates and were discarded. Subsequently, 454 articles were excluded through initial screening of the titles and abstracts. Moreover, 41 studies did not report the precise seroconversion rate either based on the type of cancer or after injection of a second dose of COVID vaccine. Finally, 28 articles met all the inclusion criteria and were included in this systematic review. The overall seroconversion rates after receiving a second dose of COVID-19 vaccine, based on type of cancer were 88% (95% CI, 81%-92%) and 70% (95% CI, 60%-79%) in patients with solid tumors and hematologic malignancies, respectively. Conclusion: Overall, we conclude that vaccination against COVID-19 in patients with active malignancies using activated and inactivated vaccines is a safe and tolerable procedure that is also accompanied by a high efficacy.

The Roles of Neutrophils in Cytokine Storms.

A cytokine storm is an abnormal discharge of soluble mediators following an inappropriate inflammatory response that leads to immunopathological events. Cytokine storms can occur after severe infections as well as in non-infectious situations where inflammatory cytokine responses are initiated, then exaggerated, but fail to return to homeostasis. Neutrophils, macrophages, mast cells, and natural killer cells are among the innate leukocytes that contribute to the pathogenesis of cytokine storms. Neutrophils participate as mediators of inflammation and have roles in promoting homeostatic conditions following pathological inflammation. This review highlights the advances in understanding the mechanisms governing neutrophilic inflammation against viral and bacterial pathogens, in cancers, and in autoimmune diseases, and how neutrophils could influence the development of cytokine storm syndromes. Evidence for the destructive potential of neutrophils in their capacity to contribute to the onset of cytokine storm syndromes is presented across a multitude of clinical scenarios. Further, a variety of potential therapeutic strategies that target neutrophils are discussed in the context of suppressing multiple inflammatory conditions.

Functional Characterization of Multiple Ehrlichia chaffeensis Sodium (Cation)/Proton Antiporter Genes Involved in the Bacterial pH Homeostasis.

Ehrlichia chaffeensis causes human monocytic ehrlichiosis. Little is known about how this and other related tick-borne rickettsia pathogens maintain pH homeostasis in acidified phagosomes and the extracellular milieu. The membrane-bound sodium (cation)/proton antiporters are found in a wide range of organisms aiding pH homeostasis. We recently reported a mutation in an antiporter gene of E. chaffeensis (ECH_0379) which causes bacterial in vivo attenuation. The E. chaffeensis genome contains 10 protein coding sequences encoding for predicted antiporters. We report here that nine of these genes are transcribed during the bacterial growth in macrophages and tick cells. All E. chaffeensis antiporter genes functionally complemented antiporter deficient Escherichia coli. Antiporter activity for all predicted E. chaffeensis genes was observed at pH 5.5, while gene products of ECH_0179 and ECH_0379 were also active at pH 8.0, and ECH_0179 protein was complemented at pH 7.0. The antiporter activity was independently verified for the ECH_0379 protein by proteoliposome diffusion analysis. This is the first description of antiporters in E. chaffeensis and demonstrates that the pathogen contains multiple antiporters with varying biological functions, which are likely important for the pH homeostasis of the pathogen's replicating and infectious forms.