Immune-Stimulating Potential of Lacticaseibacillus rhamnosus LM1019 in RAW 264.7 Cells and Immunosuppressed Mice Induced by Cyclophosphamide.

Probiotics, including Lacticaseibacillus rhamnosus (L. rhamnosus), have gained recognition for their potential health benefits, such as enhancing immune function, maintaining gut health, and improving nutrient absorption. This study investigated the effectiveness of L. rhamnosus LM1019 (LM1019) in enhancing immune function. In RAW 264.7 cells, LM1019 demonstrated dose-dependent immune stimulation by increasing nitric oxide production, gene expression of proinflammatory cytokines, and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). These effects were mediated through the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) translocation without inducing cytotoxicity. Furthermore, orally administered LM1019 was evaluated in immunosuppressed mice induced by cyclophosphamide (CTX). High-dose administration of LM1019 significantly increased the subpopulations of lymphocytes, specifically helper T cells (CD4+), as well as two subtypes of natural killer (NK) cells, namely, IFN-γ+ and granzyme B+ NK cells. Additionally, LM1019 at a high dose led to elevated levels of proinflammatory cytokines, including IFN-γ and IL-12, compared to CTX-treated mice. These findings highlight the potential of LM1019 in enhancing the immune system. The study contributes to the growing body of research on the beneficial effects of probiotics on immune function.

In vivo Trial of Bifidobacterium longum Revealed the Complex Network Correlations Between Gut Microbiota and Health Promotional Effects.

Complete genome sequence analysis of Bifidobacterium longum subsp. longum BCBL-583 isolated from a Korean female fecal sample showed no virulence factor or antibiotic resistance gene, suggesting human safety. In addition, this strain has oxygen and heat tolerance genes for food processing, and cholesterol reduction and mucin adhesion-related genes were also found. For in vivo evaluations, a high fat diet (HFD) mouse model was used, showing that BCBL-583 administration to the model (HFD-583) reduced the total cholesterol and LDL-cholesterol in the blood and decreased pro-inflammatory cytokines but increased anti-inflammatory cytokines, substantiating its cholesterol reduction and anti-inflammation activities. Subsequent microbiome analysis of the fecal samples from the HFD mouse model revealed that BCBL-583 administration changed the composition of gut microbiota. After 9 weeks feeding of bifidobacteria, Firmicutes, Actinobacteria, and Bacteroidetes increased, but Proteobacteria maintained in the HFD mouse models. Further comparative species-level compositional analysis revealed the inhibitions of cholesterol reduction-related Eubacterium coprostanoligenes and obesity-related Lactococcus by the supplementation of B. longum BCBL-583, suggesting its possible cholesterol reduction and anti-obesity activities. The correlation analysis of HFD-583 between the gut microbiota compositional change and cholesterol/immune response showed that Verrucomicrobia, Firmicutes, Actinobacteria, and Bacteroidetes may play an important role in cholesterol reduction and anti-inflammation. However, correlation analysis of Proteobacteria showed the reverse correlation in HFD-583. Interestingly, the correlation analysis of B. longum ATCC 15707 administration to HFD model showed similar patterns of cholesterol but different in immune response patterns. Therefore, this correlation analysis suggests that the microbial composition and inflammatory cytokine/total-cholesterol may be closely related in the administration of BCBL-583 in the HFD mice group. Consequently, BCBL-583 could be a good probiotic strain for gut health promotion through gut microbiota modulation.

Experimental Rat Model of Bony Defects in the Facet Joint Maintained with Bone Wax for the Study of Spinal Pain.

PURPOSE: Studies using experimental rat models for low back pain due to facet-joint defects are scarce. This study used a novel experimental rat model to determine whether bony defects induced by facetectomy could be maintained by bone wax, thus mimicking spondylolysis, and to analyze the effect of the facetectomy on rat behavior. PATIENTS AND METHODS: Twelve 10-week-old male Wistar rats weighing 300-350 g were divided into group A (n = 6) that underwent unilateral facetectomy of the right L5-6 facet joint and group B (n = 6) that additionally applied water-soluble bone wax at the facetectomy site. The difference in the left and right stride length, detected by the footprint test, and change in the left and right facet joint area were compared before and 4 weeks after the experiment. RESULTS: Even though the difference between the left and right stride lengths of groups A and B was not statistically significant, in contrast to group A, group B showed a shorter stride length on the right side (p = 0.22 and 0.46, in group A and group B, respectively). The right facet joint area, where the facetectomy was performed, was significantly smaller in group B 4 weeks after surgery, but not in group A (p = 0.50 and < 0.01, in group A and group B, respectively). CONCLUSION: Based on the results, we concluded that the bony defects, induced by facetectomy at the L5-6 facet joint, were maintained with bone wax. This study will provide an experimental model for bony defects in the facet joint.

Automatically Attributing Mobile Threat Actors by Vectorized ATT&CK Matrix and Paired Indicator.

During the past decade, mobile attacks have been established as an indispensable attack vector adopted by Advanced Persistent Threat (APT) groups. The ubiquitous nature of the smartphone has allowed users to use mobile payments and store private or sensitive data (i.e., login credentials). Consequently, various APT groups have focused on exploiting these vulnerabilities. Past studies have proposed automated classification and detection methods, while few studies have covered the cyber attribution. Our study introduces an automated system that focuses on cyber attribution. Adopting MITRE's ATT&CK for mobile, we performed our study using the tactic, technique, and procedures (TTPs). By comparing the indicator of compromise (IoC), we were able to help reduce the false flags during our experiment. Moreover, we examined 12 threat actors and 120 malware using the automated method for detecting cyber attribution.

Design, Synthesis, and Anti-RNA Virus Activity of 6'-Fluorinated-Aristeromycin Analogues.

The 6'-fluorinated aristeromycins were designed as dual-target antiviral compounds aimed at inhibiting both the viral RNA-dependent RNA polymerase (RdRp) and the host cell S-adenosyl-l-homocysteine (SAH) hydrolase, which would indirectly target capping of viral RNA. The introduction of a fluorine at the 6'-position enhanced the inhibition of SAH hydrolase and the activity against RNA viruses. The adenosine and N6-methyladenosine analogues 2a-e showed potent inhibition against SAH hydrolase, while only the adenosine derivatives 2a-c exhibited potent antiviral activity against all tested RNA viruses such as Middle East respiratory syndrome-coronavirus (MERS-CoV), severe acute respiratory syndrome-coronavirus, chikungunya virus, and/or Zika virus. 6',6'-Difluoroaristeromycin (2c) showed the strongest antiviral effect for MERS-CoV, with a ∼2.5 log reduction in infectious progeny titer in viral load reduction assay. The phosphoramidate prodrug 3a also demonstrated potent broad-spectrum antiviral activity, possibly by inhibiting the viral RdRp. This study shows that 6'-fluorinated aristeromycins can serve as starting points for the development of broad-spectrum antiviral agents that target RNA viruses.

Isolation and Characterization of Bifidobacterium longum subsp. longum BCBL-583 for Probiotic Applications in Fermented Foods

Recent human gut microbiome studies have supported that the genus Bifidobacterium is one of the most beneficial bacteria for human intestinal health. To develop a new probiotic strain for functional food applications, fourteen fecal samples were collected from healthy Koreans and the strain BCBL-583 was newly selected and isolated from a 25-year-old Korean woman's fecal sample using the selective medium for Bifidobacterium. Subsequent fructose-6-phosphate phosphoketolase (F6PPK) test and 16S rRNA gene sequencing analysis of the strain BCBL-583 confirmed that it belongs to B. longum subsp. longum. The stress resistance tests showed that it has oxygen and heat tolerance activities (5- and 3.9-fold increase for 24 h at 60 and 120 rpm, respectively; 78.61 ± 6.67% survival rate at 45°C for 24 h). In addition, gut environment adaptation tests revealed that this strain may be well-adapted in the gut habitat, with gastric acid/bile salt resistance (85.79 ± 1.53%, survival rate under 6 h treatments of gastric acid and bile salt) and mucin adhesion (73.72 ± 7.36%). Furthermore, additional tests including cholesterol lowering assay showed that it can reduce 86.31 ± 1.85% of cholesterol. Based on these results, B. longum BCBL-583 has various stress resistance for survival during food processing and environmental adaptation activities for dominant survival in the gut, suggesting that it could be a good candidate for fermented food applications as a new probiotic strain.