Trans-Differentiation of Neural Stem Cells: A Therapeutic Mechanism Against the Radiation Induced Brain Damage

Radiation therapy is an indispensable therapeutic modality for various brain diseases. Though endogenous neural stem cells (NSCs) would provide regenerative potential, many patients nevertheless suffer from radiation-induced brain damage. Accordingly, we tested beneficial effects of exogenous NSC supplementation using in vivo mouse models that received whole brain irradiation. Systemic supplementation of primarily cultured mouse fetal NSCs inhibited radiation-induced brain atrophy and thereby preserved brain functions such as short-term memory. Transplanted NSCs migrated to the irradiated brain and differentiated into neurons, astrocytes, or oligodendrocytes. In addition, neurotrophic factors such as NGF were significantly increased in the brain by NSCs, indicating that both paracrine and replacement effects could be the therapeutic mechanisms of NSCs. Interestingly, NSCs also differentiated into brain endothelial cells, which was accompanied by the restoration the cerebral blood flow that was reduced from the irradiation. Inhibition of the VEGF signaling reduced the migration and trans-differentiation of NSCs. Therefore, trans-differentiation of NSCs into brain endothelial cells by the VEGF signaling and the consequential restoration of the cerebral blood flow would also be one of the therapeutic mechanisms of NSCs. In summary, our data demonstrate that exogenous NSC supplementation could prevent radiation-induced functional loss of the brain. Therefore, successful combination of brain radiation therapy and NSC supplementation would provide a highly promising therapeutic option for patients with various brain diseases

Impaired learning and memory in CD38 null mutant mice

CD38 is an enzyme that catalyzes the formation of cyclic ADP ribose and nicotinic acid adenine dinucleotide phosphate, both of which are involved in the mobilization of Ca2+ from intracellular stores. Recently, CD38 has been shown to regulate oxytocin release from hypothalamic neurons. Importantly, CD38 mutations are associated with autism spectrum disorders (ASD) and CD38 knockout (CD38(-/-)) mice display ASD-like behavioral phenotypes including deficient parental behavior and poor social recognition memory. Although ASD and learning deficits commonly co-occur, the role of CD38 in learning and memory has not been investigated. We report that CD38(-/-)mice show deficits in various learning and memory tasks such as the Morris water maze, contextual fear conditioning, and the object recognition test. However, either long-term potentiation or long-term depression is not impaired in the hippocampus of CD38(-/-)mice. Our results provide convincing evidence that CD38(-/-)mice show deficits in various learning and memory tasks including spatial and non-spatial memory tasks. Our data demonstrate that CD38 is critical for regulating hippocampus-dependent learning and memory without modulating synaptic plasticity.open1

Cutting-edge knowledge on the roles of phytobiotics and their proposed modes of action in swine

With the ban on antibiotics in the swine industry, the exploration of alternative options has highlighted phytobiotics as a promising substitute for antibiotic growth promoters, aiming to foster a more sustainable swine industry. Phytobiotics are non-nutritive natural bioactive components derived from plants that offer numerous health benefits. They exhibit antioxidative, antimicrobial, and anti-inflammatory effects. Phytobiotics can be utilized in various forms, including solid, dried, ground, or as extracts, either in crude or concentrated form. They are characterized by low residual levels, a lack of resistance development, and minimal adverse effects. These qualities make phytobiotics an attractive choice for enhancing health and productivity in swine, presenting them as a viable alternative to antibiotics. While there is a general understanding of the effects of phytobiotics, there is still a need for detailed information regarding their effectiveness and mechanisms of action in practical settings. Therefore, the purpose of this mini review was to summarize the current knowledge supporting the roles of phytobiotics and their proposed modes of action, with a specific focus on swine

Swine gut microbiome associated with non-digestible carbohydrate utilization

Non-digestible carbohydrates are an unavoidable component in a pig’s diet, as all plant-based feeds contain different kinds of non-digestible carbohydrates. The major types of non-digestible carbohydrates include non-starch polysaccharides (such as cellulose, pectin, and hemicellulose), resistant starch, and non-digestible oligosaccharides (such as fructo-oligosaccharide and xylo-oligosaccharide). Non-digestible carbohydrates play a significant role in balancing the gut microbial ecology and overall health of the swine by promoting the production of short chain fatty acids. Although non-digestible carbohydrates are rich in energy, swine cannot extract this energy on their own due to the absence of enzymes required for their degradation. Instead, they rely on gut microbes to utilize these carbohydrates for energy production. Despite the importance of non-digestible carbohydrate degradation, limited studies have been conducted on the swine gut microbes involved in this process. While next-generation high-throughput sequencing has aided in understanding the microbial compositions of the swine gut, specific information regarding the bacteria involved in non-digestible carbohydrate degradation remains limited. Therefore, it is crucial to investigate and comprehend the bacteria responsible for the breakdown of non-digestible carbohydrates in the gut. In this mini review, we have discussed the major bacteria involved in the fermentation of different types of non-digestible carbohydrates in the large intestine of swine, shedding light on their potential roles and contributions to swine nutrition and health

Albuminuria, Cerebrovascular Disease and Cortical Atrophy: among Cognitively Normal Elderly Individuals

We tested the hypothesis that decreased glomerular filtration rate and albuminuria have different roles in brain structure alterations. We enrolled 1,215 cognitively normal individuals, all of whom underwent high-resolution T1-weighted volumetric magnetic resonance imaging scans. The cerebral small vessel disease burdens were assessed with white matter hyperintensities (WMH), lacunes, and microbleeds. Subjects were considered to have an abnormally elevated urine albumin creatinine ratio if the value was ≥17 mg/g for men and ≥25 mg/g for women. Albuminuria, but not estimated glomerular filtration rate (eGFR), was associated with increased WMH burdens (p = 0.002). The data was analyzed after adjusting for age, sex, education, history of hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease, stroke, total cholesterol level, body mass index, status of smoking and alcohol drinking, and intracranial volume. Albuminuria was also associated with cortical thinning, predominantly in the frontal and occipital regions (both p < 0.01) in multiple linear regression analysis. However, eGFR was not associated with cortical thickness. Furthermore, path analysis for cortical thickness showed that albuminuria was associated with frontal thinning partially mediated by WMH burdens. The assessment of albuminuria is needed to improve our ability to identify individuals with high risk for cognitive impairments, and further institute appropriate preventive measures

Identifying novel genetic variants for brain amyloid deposition: a genome-wide association study in the Korean population

Background: Genome-wide association studies (GWAS) have identified a number of genetic variants for Alzheimer's disease (AD). However, most GWAS were conducted in individuals of European ancestry, and non-European populations are still underrepresented in genetic discovery efforts. Here, we performed GWAS to identify single nucleotide polymorphisms (SNPs) associated with amyloid β (Aβ) positivity using a large sample of Korean population. Methods: One thousand four hundred seventy-four participants of Korean ancestry were recruited from multicenters in South Korea. Discovery dataset consisted of 1190 participants (383 with cognitively unimpaired [CU], 330 with amnestic mild cognitive impairment [aMCI], and 477 with AD dementia [ADD]) and replication dataset consisted of 284 participants (46 with CU, 167 with aMCI, and 71 with ADD). GWAS was conducted to identify SNPs associated with Aβ positivity (measured by amyloid positron emission tomography). Aβ prediction models were developed using the identified SNPs. Furthermore, bioinformatics analysis was conducted for the identified SNPs. Results: In addition to APOE, we identified nine SNPs on chromosome 7, which were associated with a decreased risk of Aβ positivity at a genome-wide suggestive level. Of these nine SNPs, four novel SNPs (rs73375428, rs2903923, rs3828947, and rs11983537) were associated with a decreased risk of Aβ positivity (p < 0.05) in the replication dataset. In a meta-analysis, two SNPs (rs7337542 and rs2903923) reached a genome-wide significant level (p < 5.0 × 10-8). Prediction performance for Aβ positivity increased when rs73375428 were incorporated (area under curve = 0.75; 95% CI = 0.74-0.76) in addition to clinical factors and APOE genotype. Cis-eQTL analysis demonstrated that the rs73375428 was associated with decreased expression levels of FGL2 in the brain. Conclusion: The novel genetic variants associated with FGL2 decreased risk of Aβ positivity in the Korean population. This finding may provide a candidate therapeutic target for AD, highlighting the importance of genetic studies in diverse populations

Comparison between GlideRite® rigid stylet and Parker Flex-It™ stylet to facilitate GlideScope intubation in simulated difficult intubation: a randomized controlled study

Background The GlideScope® videolaryngoscope (GVL) is widely used in patients with difficult airways and provides a good glottic view. However, the acute angle of the blade can make insertion and advancement of an endotracheal tube (ETT) more difficult than direct laryngoscopy, and the use of a stylet is recommended. This randomized controlled trial compared Parker Flex-It™ stylet (PFS) with GlideRite® rigid stylet (GRS) to facilitate intubation with the GVL in simulated difficult intubations. Methods Fifty-four patients were randomly allocated to undergo GVL intubation using either GRS (GRS group) or PFS (PFS group). The total intubation time (TIT), 100-mm visual analog scale (VAS) for ease of intubation, success rate at the first attempt, use of laryngeal manipulation, tube advancement rate by assistant, and complications were recorded. Results There was no significant difference between the GRS and PFS groups regarding TIT (50.3 ± 12.0 s in the GRS group and 57.8 ± 18.8 s in the PFS group, P = 0.108). However, intubation was more difficult in the PFS group than in the GRS group according to VAS score (P = 0.011). Cases in which the ETT was advanced from the stylet by an assistant, were more frequent in the GRS group than in the PFS group (P = 0.002). The overall incidence of possible complications was not significantly different. Conclusions In patients with a simulated difficult airway, there was no difference in TIT using either the PFS or GRS. However, endotracheal intubation with PFS is more difficult to perform than GRS