• Journal of the Korean Applied Science and Technology
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• v.41 no.1
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• pp.58-68
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• 2024

The purpose of this study was to investigate the effects of treadmill exercise treadmill exercise (TE) and environmental enrichment (EE) interventions on cognitive function, muscle function, and the expression of tight junction proteins in an Alzheimer's disease (AD) animal model. To create the AD animal model, aluminum chloride (AlCl₃) was administered for 90 days (40mg/kg/day), while simultaneously exposing the animals to TE (10-12m/min, 40-60min/day) or EE. The results showed that cognitive impairment and muscle dysfunction induced by AlCl₃ administration were alleviated by TE and EE. Furthermore, TE and EE reduced the increased expression of β-amyloid(Aβ), alpha-synuclein, and tumor necrosis factor-α (TNF-α) proteins observed in AD pathology. Additionally, TE and EE significantly increased the expression of decreased adhesive adjacent proteins (Occludin, Claudin-5, and ZO-1) induced by AlCl₃ administration. Lastly, correlation analysis between Aβ protein and tight junction proteins showed negative correlations (Occludin: r=-0.853, p=0.001; Claudin-5: r=-0.352, p=0.915; ZO-1: r=-0.424, p=0.0390). In conclusion, TE or EE interventions are considered effective exercise methods that partially alleviate pathological features of AD, improving cognitive and muscle function.

• International Journal of Stem Cells
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• v.17 no.3
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• pp.319-329
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• 2024

Leucine-rich repeat kinase 2 (LRRK2), a large GTP-regulated serine/threonine kinase, is well-known for its mutations causing late-onset Parkinson's disease. However, the role of LRRK2 in glioblastoma (GBM) carcinogenesis has not yet been fully elucidated. Here, we discovered that LRRK2 was overexpressed in 40% of GBM patients, according to tissue microarray analysis, and high LRRK2 expression correlated with poor prognosis in GBM patients. LRRK2 and stemness factors were highly expressed in various patient-derived GBM stem cells, which are responsible for GBM initiation. Canonical serum-induced differentiation decreased the expression of both LRRK2 and stemness factors. Given that LRRK2 is a key regulator of glioma stem cell (GSC) stemness, we developed DNK72, a novel LRRK2 kinase inhibitor that penetrates the blood-brain barrier. DNK72 binds to the phosphorylation sites of active LRRK2 and dramatically reduced cell proliferation and stemness factors expression in in vitro studies. Orthotopic patient-derived xenograft mouse models demonstrated that LRRK2 inhibition with DNK72 effectively reduced tumor growth and increased survival time. We propose that LRRK2 plays a significant role in regulating the stemness of GSCs and that suppression of LRRK2 kinase activity leads to reduced GBM malignancy and proliferation. In the near future, targeting LRRK2 in patients with high LRRK2-expressing GBM could offer a superior therapeutic strategy and potentially replace current clinical treatment methods.

• Journal of Life Science
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• v.29 no.6
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• pp.747-753
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• 2019

Cognitive decline is characterized by reduced long-/short-term memory and attention span, and increased depression and anxiety. Such decline is associated with various degenerative brain disorders, especially Alzheimer's disease (AD) and Parkinson's disease (PD). The increases in elderly populations suffering from cognitive decline create social problems and impose economic burdens, and also pose safety threats; all of these problems have been extensively researched over the past several decades. Possible causes of cognitive decline include metabolic and hormone imbalance, infection, medication abuse, and neuronal changes associated with aging. However, no treatment for cognitive decline is available. In neurodegenerative diseases, changes in the gut microbiota and gut metabolites can alter molecular expression and neurobehavioral symptoms. Changes in the gut microbiota affect memory loss in AD via the downregulation of NMDA receptor expression and increased glutamate levels. Furthermore, the use of probiotics resulted in neurological improvement in an AD model. PD and gut microbiota dysbiosis are linked directly. This interrelationship affected the development of constipation, a secondary symptom in PD. In a PD model, the administration of probiotics prevented neuron death by increasing butyrate levels. Dysfunction of the blood-brain barrier (BBB) has been identified in AD and PD. Increased BBB permeability is also associated with gut microbiota dysbiosis, which led to the destruction of microtubules via systemic inflammation. Notably, metabolites of the gut microbiota may trigger either the development or attenuation of neurodegenerative disease. Here, we discuss the correlation between cognitive decline and the gut microbiota.

• Journal of Dairy Science and Biotechnology
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• v.27 no.2
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• pp.55-62
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• 2009

Milk is called an almost complete food in terms of nutrition, especially for the younger generations because it contains a number of nutrients required for growth and development. Lactose intolerance is defined as a malabsorption of lactose in the intestine with some typical symptoms of abdominal pains and bloating, and occurred at 75% of global populations, which hampers milk consumption worldwide. Lacks of milk consumption in the underdeveloped countries frequently lead to many nutrients deficiencies, so that diseases including osteoporosis, hypertension, and colon cancer are more prevalent in the recent days. Lactose in foods needs to be hydrolyzed prior to intestinal absorption. The hydrolytic enzyme responsible for splitting lactose into its monomeric forms, glucose and galactose, is called as lactase or $\beta$-galactosidase. The former is primarily used as blood sugar and energy source and the latter used in glycolipid synthesis of brain tissues in infants. Lactose is clinically diagnosed with the breath hydrogen production test as well as intestinal biopsy. Reportedly, symptoms of lactose intolerance are widely prevalent at 25% of Europeans, 50 to 80% of Hispanics, South Indians, Africans, and Jews, almost 100% of Asians and native Americans. For the adults, phenotype of lactase persistence, which is able to hydrolyse lactose, is more common in the northern Europeans, but in the other area lactase non-persistence or adult-type hypolactasia is dominant. Genetic analysis on human lactase gene continued that lactase persistence was closely related to the err site of 1390 single nucleotide polymorphism from the 5'-end. To alleviate severity of lactose intolerance symptoms, some eating patterns including drinking milk a single cup or less, consumption along with other foods, whole milk rather than skimmed milk, and drink with live yogurt cultures, are highly recommended for the lactose maldigesters. Also, delay of gastric emptying is effective to avoid the symptoms from lactose intolerance. Frequency of lactose intolerance with conventional diagnosis is thought overestimated mainly because the subjects are exposed to too much lactose of 50 g rather than a single serving amount. Thus simple and accurate diagnostic method for lactose intolerance need to be established. It is thought that fermented milk products and low- or free lactose milks help improve currently stagnant milk consumption due to lactose intolerance which contributes to major barrier in milk marketing especially in Asian countries.

• Journal of Microbiology and Biotechnology
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• v.25 no.10
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• pp.1751-1760
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• 2015

Mucin2 (MUC2), an important regulatory factor in the immune system, plays an important role in the host defense system against bacterial translocation. Probiotics known to regulate MUC2 gene expression have been widely studied, but the interactions among probiotic, pathogens, and mucin gene are still not fully understood. The aim of this study was to investigate the role of MUC2 in blocking effects of probiotics on meningitic E. coli-induced pathogenicities. In this study, live combined probiotic tablets containing living Bifidobacterium, Lactobacillus bulgaricus, and Streptococcus thermophilus were used. MUC2 expression was knocked down in Caco-2 cells by RNA interference. 5-Aza-2'-deoxycytidine (5-Aza-CdR), which enhances mucin-promoted probiotic effects through inducing production of Sadenosyl-L-methionine (SAMe), was used to up-regulate MUC2 expression in Caco-2 cells. The adhesion to and invasion of meningitic E. coli were detected by competition assays. Our studies showed that probiotic agents could block E. coli-caused intestinal colonization, bacteremia, and meningitis in a neonatal sepsis and meningitis rat model. MUC2 gene expression in the neonatal rats given probiotic agents was obviously higher than that of the infected and uninfected control groups without probiotic treatment. The prohibitive effects of probiotic agents on MUC2-knockdown Caco-2 cells infected with E44 were significantly reduced compared with nontransfected Caco-2 cells. Moreover, the results also showed that 5-Aza-CdR, a drug enhancing the production of SAMe that is a protective agent of probiotics, was able to significantly suppress adhesion and invasion of E44 to Caco-2 cells by upregulation of MUC2 expression. Taken together, our data suggest that probiotic agents can efficiently block meningitic E. coli-induced pathogenicities in a manner dependent on MUC2.