LncRNA NPTN-IT1-201 Ameliorates Depressive-like Behavior by Targeting miR-142-5p and Regulating Inflammation and Apoptosis via BDNF

Objective Long noncoding RNAs(lncRNAs)and microRNAs(miRNAs)are widely expressed in the brain and are associated with the development of neurological and neurodegenerative diseases.However,their roles and molecular mechanisms in major depressive disorder(MDD)remain largely unknown.This study aimed to identify lncRNAs and miRNAs involved in the development of MDD and elucidate their molecular mechanisms.Methods Transcriptome and bioinformatic analyses were performed to identify miRNAs and lncRNAs related to MDD.C57 mice were subjected to chronic unpredictable mild stress(CUMS)to establish a depression model.Lentiviruses containing either lncRNA NPTN-IT1-201 or miR-142-5p were microinjected into the hippocampal region of these mice.Behavioral tests including the sucrose preference test(SPT),tail suspension test(TST),and forced swim test(FST)were conducted to evaluate depressive-like behaviors.Results The results revealed that overexpression of lncRNA NPTN-IT1-201 or inhibition of miR-142-5p significantly ameliorated depressive-like behaviors in CUMS-treated mice.Dual-luciferase reporter assays confirmed interactions between miR-142-5p with both brain-derived neurotrophic factor(BDNF)and NPTN-IT1-201.ELISA analysis revealed significant alterations in relevant biomarkers in the blood samples of MDD patients compared to healthy controls.Histological analyses,including HE and Nissl staining,showed marked structural changes in brain tissues following CUMS treatment,which were partially reversed by lncRNA NPTN-IT1-201 overexpression or miR-142-5p inhibition.Immunofluorescence imaging demonstrated significant differences in the levels of BAX,Bcl2,p65,Iba1 among different treatment groups.TUNEL assays confirmed reduced apoptosis in brain tissues following these interventions.Western blotting showed the significant differences in BDNF,BAX,and Bcl2 protein levels among different treatment groups.Conclusion NPTN-IT1-201 regulates inflammation and apoptosis in MDD by targeting BDNF via miR-142-5p,making it a potential therapeutic target for MDD.

Ability of Helicobacter pylori to internalize into Candida

The following are our views regarding the“letter to the editor”(Helicobacter is preserved in yeast vacuoles!Does Koch’s postulates confirm it?)by Alipour and Gaeini,and the response“letter to the editor”(Candida accommodates nonculturable Helicobacter pylori in its vacuole-Koch’s postulates aren’t applicable)by Siavoshi and Saniee.Alipour and Gaeini rejected the methods,results,discussion,and conclusions summarized in a review article by Siavoshi and Saniee.The present article reviews and discusses evidence on the evolutionary adaptation of Helicobacter pylori(H.pylori)to thrive in Candida cell vacuoles and concludes that Candida could act as a Trojan horse,transporting potentially infectious H.pylori into the stomach of humans.

Antibacterial activity evaluation of a novel K3-specific phage against Acinetobacter baumannii and evidence for receptor-binding domain transfer across morphologies

Acinetobacter baumannii(A.baumannii)poses a serious public health challenge due to its notorious antimicrobial resistance,particularly carbapenem-resistant A.baumannii(CRAB).In this study,we isolated a virulent phage,named P1068,from medical wastewater capable of lysing CRAB,primarily targeting the K3 capsule type.Basic characterization showed that P1068 infected the A.baumannii ZWAb014 with an optimal MOI of 1,experienced a latent period of 10 min and maintained stability over a temperature range of 4–37C and pH range of 3–10.Phylogenetic and average nucleotide identity analyses indicate that P1068 can be classified as a novel species within the genus Obolenskvirus of the Caudoviricetes class as per the most recent virus classification released by the International Committee on Taxonomy of Viruses(ICTV).Additionally,according to classical morphological classification,P1068 is identified as a T4-like phage(Myoviridae).Interestingly,we found that the tail fiber protein(TFP)of P1068 shares 74%coverage and 88.99%identity with the TFP of a T7-like phage(Podoviridae),AbKT21phiIII(NC_048142.1).This finding suggests that the TFP gene of phages may undergo horizontal transfer across different genera and morphologies.In vitro antimicrobial assays showed that P1068 exhibited antimicrobial activity against A.baumannii in both biofilm and planktonic states.In mouse models of intraperitoneal infection,P1068 phage protected mice from A.baumannii infection and significantly reduced bacterial loads in various tissues such as the brain,blood,lung,spleen,and liver compared to controls.In conclusion,this study demonstrates that phage P1068 might be a potential candidate for the treatment of carbapenem-resistant and biofilmforming A.baumannii infections,and expands the understanding of horizontal transfer of phage TFP genes.