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PURPOSE: This study investigated the effect of gabapentin on lower urinary tract dysfunction focusing on urethral activities and cystitis-induced hyperalgesia in a mouse model of painful bladder syndrome/interstitial cystitis (PBS/IC). The electromyography (EMG) of external urethral sphincter (EUS) was difficult to obtain, but contained useful information to examine the drug effect in mice. METHODS: Female C57BL/6J mice were intraperitoneally (ip) administration with either saline or 200 mg/kg of cyclophosphamide (CYP) 48 h before experimental evaluation. Cystitis mice were treated with administration of gabapentin (25 or 50 mg/kg, ip). Cystometry and EUS EMG were obtained and analyzed during continuous bladder infusion. The visceral pain-related visceromotor reflex (VMR) was recorded in response to isotonic bladder distension. RESULTS: Cystitis mice showed shorter inter-contraction intervals and increased occurrence of non-voiding contractions during bladder infusion, with increased VMR during isotonic bladder distension, indicating cystitis-induced bladder hyperalgesia. Gabapentin (50 mg/kg) suppressed effects of CYP on cystometry, but not on EUS EMG activity, during bladder infusion. The effect on urodynamic recordings lasted 4 h. VMR was significantly reduced by gabapentin. CONCLUSIONS: The present study showed that CYP-induced cystitis in mice is a model of visceral hyperalgesia affecting detrusor contractions, not urethral activations. The technique of using EUS EMG to evaluate the drug effects on urethral activities is novel and useful for future investigations. Gabapentin can be as a potential treatment for detrusor overactivity and PBS/IC.

Background Clinical and preclinical observations indicate that Lactobacillus plantarum has anti-inflammatory activity and may regulate the immune responses of its hosts when ingested. Recently, modification of teichoic acids (TAs) produced by L. plantarum was reported as a key to regulating the systemic immune response in mice. However, data linking TA-related genetic determinants and the immunomodulatory effect are limited. To provide genomic information for elucidating the underlying mechanism of immunomodulation by L. plantarum, we sequenced the genome of L. plantarum strain PS128. Results The PS128 genome contains 11 contigs (3,325,806 bp; 44.42% GC content) after hybrid assembly of sequences derived with Illumina MiSeq and PacBio RSII systems. The most abundant functions of the protein-coding genes are carbohydrate, amino acid, and protein metabolism. The 16S rDNA sequences of PS128 are closest to the sequences of L. plantarum WCFS1 and B21; these three strains form a distinct clade based on 16S rDNA sequences. PS128 shares core genes encoding the metabolism, transport, and modification of TAs with other sequenced L. plantarum strains. Compared with the TA-related genes of other completely sequenced L. plantarum strains, the PS128 contains more lipoteichoic acid exporter genes. Conclusions We determined the draft genome sequence of PS128 and compared its TA-related genes with those of other L. plantarum strains. Shared genomic features with respect to TA-related subsystems may be important clues to the mechanism by which L. plantarum regulates its host immune responses, but unique TA-related genetic determinants should be further investigated to elucidate strain-specific immunomodulatory effects. Keywords: Lactobacillus plantarum, Probiotics, Immunomodulation, PS128, Draft genome sequence, Author(s): Wei-Hsien Liu[sup.1] , Chih-Hsien Yang[sup.2,3] , Ching-Ting Lin[sup.4] , Shiao-Wen Li[sup.2] , Wei-Shen Cheng[sup.2] , Yi-Ping Jiang[sup.1] , Chien-Chen Wu[sup.1] , Chuan-Hsiung Chang[sup.2,3] and Ying-Chieh Tsai[sup.1,5] Background Lactobacillus plantarum [...]

The transcription factor PsrA regulates fatty acid metabolism, the type III secretion system, and quinolone signaling quorum sensing system in Pseudomonas aeruginosa . To explore additional roles of PsrA in P. aeruginosa , this study engineered a P. aeruginosa PAO1 strain to carry a recombinant plasmid with the psrA gene (pMMB psrA ) and examined the impact of elevated psrA expression to the bacterium. Transcriptomic analysis revealed that PsrA significantly downregulated genes encoding the master quorum-sensing regulators, RhlR and LasR, and influenced many quorum-sensing-associated genes. The role of PsrA in quorum sensing was further corroborated by testing autoinducer synthesis in PAO1 [pMMB psrA ] using two reporter bacteria strains Chromobacterium violaceum CV026 and Escherichia coli [pSB1075], which respond to short- and long-chain acyl homoserine lactones, respectively. Phenotypic comparisons of isogenic Δ psrA , Δ lasR , and Δ psrA Δ lasR mutants revealed that the reduced elastase, caseinase, and swarming activity in PAO1 [pMMB psrA ] were likely mediated through LasR. Additionally, electrophoretic mobility shift assays demonstrated that recombinant PsrA could bind to the lasR promoter at a 5'-AAACGTTTGCTT-3' sequence, which displays moderate similarity to the previously reported consensus PsrA binding motif. Furthermore, the PsrA effector molecule oleic acid inhibited PsrA binding to the lasR promoter and restored several quorum sensing-related phenotypes to wild-type levels. These findings suggest that PsrA regulates certain quorum-sensing phenotypes by negatively regulating lasR expression, with oleic acid acting as a crucial signaling molecule., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kok, Tsai, Liao, Lo, Cheng, Lin and Chang.)

The bidirectional communication between the gastrointestinal tract and the central nervous system appears to be functionally linked to the intestinal microbiome, namely the microbiome-gut-brain axis (MGBA). Probiotics with health benefits on psychiatric or neurological illnesses are generally called psychobiotics, and some of them may also be able to improve sleep by targeting the MGBA. This study aimed to investigate the effects of a psychobiotic strain, Lactobacillus fermentum PS150 TM (PS150 TM ), on sleep improvement by using a pentobarbital-induced sleep mouse model. Compared with the vehicle control group, the oral administration of PS150 TM , but not the other L. fermentum strains, significantly decreased the sleep latency and increased the sleep duration of mice, suggesting strain-specific sleep-improving effects of PS150 TM . Moreover, the ingestion of diphenhydramine, an antihistamine used to treat insomnia, as a drug control group, only increased the sleep duration of mice. We also found that the sleep-improving effects of PS150 TM are time- and dose-dependent. Furthermore, the oral administration of PS150 TM could attenuate a caffeine-induced sleep disturbance in mice, and PS150 TM appeared to increase the expression of the gene encoding the adenosine 1 receptor in the hypothalamus of mice, as assessed by quantitative real-time polymerase chain reaction. Taken together, our results present a potential application of PS150 TM as a dietary supplement for sleep improvement.

Purpose: This study investigated the effect of gabapentin on lower urinary tract dysfunction focusing on urethral activities and cystitis-induced hyperalgesia in a mouse model of painful bladder syndrome/interstitial cystitis (PBS/IC). The electromyography (EMG) of external urethral sphincter (EUS) was difficult to obtain, but contained useful information to examine the drug effect in mice., Methods: Female C57BL/6J mice were intraperitoneally (ip) administration with either saline or 200 mg/kg of cyclophosphamide (CYP) 48 h before experimental evaluation. Cystitis mice were treated with administration of gabapentin (25 or 50 mg/kg, ip). Cystometry and EUS EMG were obtained and analyzed during continuous bladder infusion. The visceral pain-related visceromotor reflex (VMR) was recorded in response to isotonic bladder distension., Results: Cystitis mice showed shorter inter-contraction intervals and increased occurrence of non-voiding contractions during bladder infusion, with increased VMR during isotonic bladder distension, indicating cystitis-induced bladder hyperalgesia. Gabapentin (50 mg/kg) suppressed effects of CYP on cystometry, but not on EUS EMG activity, during bladder infusion. The effect on urodynamic recordings lasted 4 h. VMR was significantly reduced by gabapentin., Conclusions: The present study showed that CYP-induced cystitis in mice is a model of visceral hyperalgesia affecting detrusor contractions, not urethral activations. The technique of using EUS EMG to evaluate the drug effects on urethral activities is novel and useful for future investigations. Gabapentin can be as a potential treatment for detrusor overactivity and PBS/IC.

Carrier transport in layered transition-metal dichalcogenides is highly sensitive to surrounding charges because of the atomically thin thickness. By exploiting this property, we report a new internal current amplification mechanism through positive feedback induced by dielectric hole trapping in a MoS 2 back-gate transistor on a tantalum oxide substrate. The device exhibits an extremely steep subthreshold slope of 17 mV/decade, which is strongly dependent on the substrate material and drain bias. The steep subthreshold slope is attributed to the internal current amplification arising from the positive feedback between hole generation in MoS 2 triggered by large lateral electric field and Schottky barrier narrowing induced by localized hole trapping in tantalum oxide near the source contact.

Klebsiella pneumoniae is the most common pathogen of community-acquired meningitis in Taiwan. However, the lack of a physiologically relevant meningitis model for K. pneumoniae has impeded research into its pathogenesis mechanism. Based on the core genome MLST analyses, the hypervirulent K1 K. pneumoniae strains, which are etiologically implicated in adult meningitis, mostly belong to a single clonal complex, CC23. Some K1 CC23 K. pneumoniae strains carry a gene cluster responsible for colibactin production. Colibactin is a small genotoxic molecule biosynthesized by an NRPS-PKS complex, which is encoded by genes located on the pks island. Compared to other hypervirulent K. pneumoniae which primarily infect the liver, the colibactin-producing ( pks + ) K1 CC23 strains had significant tropism toward the brain of BALB/c mice. We aimed in this study to develop a physiologically relevant meningitis model with the use of pks + K1 CC23 K. pneumoniae . Acute meningitis was successfully induced in adult BALB/c male mice through orogastric, intranasal, and intravenous inoculation of pks + K1 CC23 K. pneumoniae . Besides the typical symptoms of bacterial meningitis, severe DNA damages, and caspase 3-independent cell death were elicited by the colibactin-producing K1 CC23 K. pneumoniae strain. The deletion of clbA , which abolished the production of colibactin, substantially hindered K. pneumoniae hypervirulence in the key pathogenic steps toward the development of meningitis. Our findings collectively demonstrated that colibactin was necessary but not sufficient for the meningeal tropism of pks + K1 CC23 K. pneumoniae , and the mouse model established in this study can be applied to identify other virulence factors participating in the development of this life-threatening disease.