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Late-onset hypogonadism (LOH) is an age-related disease in men characterized by decreased testosterone levels with symptoms such as decreased libido, erectile dysfunction, and depression. Thymus quinquecostatus Celakovski (TQC) is a plant used as a volatile oil in traditional medicine, and its bioactive compounds have anti-inflammatory potential. Based on this knowledge, the present study aimed to investigate the effects of TQC extract (TE) on LOH in TM3 Leydig cells and in an in vivo aging mouse model. The aqueous extract of T. quinquecostatus Celakovski (12.5, 25, and 50 µg/mL concentrations) was used to measure parameters such as cell viability, testosterone level, body weight, and gene expression, via in vivo studies. Interestingly, TE increased testosterone levels in TM3 cells in a dose-dependent manner without affecting cell viability. Furthermore, TE significantly increased the expression of genes involved in the cytochrome P450 family (Cyp11a1, Cyp17a1, Cyp19a1, and Srd5a2), which regulate testosterone biosynthesis. In aging mouse models, TE increased testosterone levels without affecting body weight and testicular tissue weight tissue of an aging animal group. In addition, the high-dose TE-treated group (50 mg/kg) showed significantly increased expression of the cytochrome p450 enzymes, similar to the in vitro results. Furthermore, HPLC-MS analysis confirmed the presence of caffeic acid and rosmarinic acid as bioactive compounds in TE. Thus, the results obtained in the present study confirmed that TQC and its bioactive compounds can be used for LOH treatment to enhance testosterone production.

Allergic rhinitis (AR) is defined allergic disease that is mediated by Th2 cells. Its incidence rate is showing a growing tendency worldwide. Research on traditional medicine for AR is also being increasingly conducted. Thymus quinquecostatus Celakovski (TQ) has been used as an important medicinal and aromatic plant in the world. The purpose of this study was to assess whether TQ can alleviate AR. BALB/c mice were sensitized and challenged with ovalbumin (OVA) to provoke AR. Mice were treated with ethanol extract of TQ at 10 or 100 mg/kg after the intranasal OVA challenge. Their clinical symptoms such as nasal rubbing and sneezing were significantly reduced in the ethanol extract group (10 or 100 mg/kg) compared to the OVA group. Serum levels of Th1 (TNF-α) and Th2 (IL-4, IL-5, and IL-6) cytokines and IgE levels (both total and OVA-specific) were significantly reduced by administration of ethanol extract of TQ at 100 mg/kg. The thicknesses of the nasal septum and epithelium were significantly reduced by the administration of ethanol extract of TQ. These results suggest that TQ may inhibit early and late phases of AR reactions.

Gastritis and gastric ulcers caused by stressors such as drinking are common. The ability of functional foods to protect the stomach more effectively and reduce the risk of side effects is of interest. The fermentation process can increase the preservation and bioactive compound content of kiwi fruits. This study produced fermented kiwi powder using two lactic acids separated from gold kiwi fruits. Gold kiwi puree (Actinidia chinensis L.) was fermented using beneficial bacteria. Fermentation increased the content of bioactive compounds such as organic acids, flavonoids, and carotenoids. We investigated whether fermented gold kiwi (FGK) extract had antioxidant and gastric protective effects in an HCl/EtOH-induced gastritis animal model and pyloric ligation animal model. FGK increased radical scavenging activity in a dose-dependent manner. In the gastritis model, FGK inhibited inflammation-related factors such as iNOS, COX-2, IL-6, and TNF-α, while increasing the expression of the protective molecule PGE2. Furthermore, FGK administration improved gastric lesion site appearance, clinical symptoms, and mucosal thickness in rats. FGK also reduced gastric fluid volume, free acidity, total acidity, and pepsin activity in the pyloric ligation model. These results suggest that FGK can decrease the inflammatory response and protect the gastric mucosa. FGK therefore has the potential to prevent and treat gastritis and gastric ulcers.

Embryonic stem (ES) cells have been regarded as a powerful resource for cell replacement therapy. In recent reports mouse ES cells have been successfully applied in the treatment of spinal cord injury, hereditary myelin disorder of the central nervous system, and diabetes mellitus. Another type of disease that could benefit from the availability of stem cell therapy is liver disease. However, for this potential to be realized, it is necessary to demonstrate the differentiation of ES cells into hepatocytes. To demonstrate the in vivo differentiation potential of mouse ES cells, we injected ES cells into the spleen of immunosuppressed nude mice. Histological analysis of teratomas derived from injected ES cells revealed that some areas contained typical hepatocytes arranged in a sinusoidal structure. The hepatic nature of these cells was further confirmed by showing that transcripts of liver-specific genes were present in the differentiated teratoma using reverse transcriptase-polymerase chain reaction and immunohistochemistry using several liver-specific antibodies including HEP-PAR, phenylalanine hydroxylase, and mouse N-system aminotransferase to identify the respective proteins in the differentiated hepatocytes. This is the first demonstration that mouse ES cells can differentiate in vivo into a mixed population of hepatocytes of varying maturity. This finding extends the potential use of ES cells in the cell replacement therapy by including its possible application for treating liver diseases.

Abstract The protozoan parasite Toxoplasma gondii (T. gondii) causes one of the most common human zoonotic diseases and infects approximately one-third of the global population. T. gondii infects nearly every cell type and causes severe symptoms in susceptible populations. In previous laboratory animal studies, T. gondii movement and transmission were not analyzed in real time. In a three-dimensional (3D) microfluidic assay, we successfully supported the complex lytic cycle of T. gondii in situ by generating a stable microvasculature. The physiology of the T. gondii-infected microvasculature was monitored in order to investigate the growth, paracellular and transcellular migration, and transmission of T. gondii, as well as the efficacy of T. gondii drugs.

Background: The primary cause of treatment failure in medulloblastomas (MB) is the development of leptomeningeal dissemination (seeding). For translational research on MB seeding, one of the major challenges is the development of reliable experimental models that simulate the seeding and growth characteristics of MBs. To overcome this obstacle, we improved an experimental mouse model by intracisternal inoculation of human MB cells and monitoring with in vivo live images.Methods: Human MB cells (UW426, D283 and MED8A) were transfected with a firefly luciferase gene and a Thy1.1 (CD90.1) marker linked with IRES under the control of the CMV promoter in a retroviral DNA backbone (effLuc). The MB-effLuc cells were injected into the cisterna magna using an intrathecal catheter, and bioluminescence images were captured. We performed histopathological analysis to confirm the extent of tumor seeding.Results: The luciferase activity of MB-effLuc cells displayed a gradually increasing pattern, which correlated with a quantitative luminometric assay. Live imaging showed that the MB-effLuc cells were diffusely distributed in the cervical spinal cord and the lumbosacral area. All mice injected with UW426-effLuc, D283-effLuc and MED8A-effLuc died within 51 days. The median survival was 22, 41 and 12 days after injection of 1.2 × 10(6) UW426-effLuc, D283-effLuc and MED8A-effLuc cells, respectively. The histopathological studies revealed that the MB-effLuc cells spread extensively and diffusely along the leptomeninges of the brain and spinal cord, forming tumor cell-coated layers. The tumor cells in the subarachnoid space expressed a human nuclei marker and Ki-67. Compared with the intracerebellar injection method in which the subfrontal area and distal spinal cord were spared by tumor cell seeding in some mice, the intracisternal injection model more closely resembled the widespread leptomeningeal seeding observed in MB patients.Conclusion: The results and described method are valuable resources for further translational research to overcome MB seeding. [ABSTRACT FROM AUTHOR]

The article presents information on a study conducted for isolating cellulolytic Bacillus subtilis strains from agricultural environments. It informs that the bioconversion of hemicellulose and cellulose to soluble sugars is important for global stabilization and sustainability. It further informs that the cellulolytic microorganisms play an important role in the biosphere by recycling cellulose.

This randomised double-blind placebo-controlled trial evaluated the efficacy and safety of fermented gold kiwi (FGK) in improving gastrointestinal health. A total of 100 participants were enrolled and randomly assigned to treatment or placebo groups. Over 8 weeks, the participants consumed an FGK or placebo preparation daily. Primary outcomes included changes in gastrointestinal symptoms assessed using the Gastrointestinal Symptom Rating Scale (GSRS) and the Korean version of the Nepean Dyspepsia Index (NDI-K), as well as quality of life assessed using the Functional Dyspepsia-related Quality of Life questionnaire. The FGK group showed significant improvements in GSRS and NDI-K total and subdomain scores compared with the placebo group. Moreover, the quality of life scores were significantly better in the FGK group than in the placebo group. Safety evaluations revealed no significant adverse events or clinically meaningful changes upon assessing laboratory test results. This study demonstrated that FGK is a safe and effective dietary supplement for improving gastrointestinal health in adults with gastrointestinal symptoms.

7-MEGATM is a food product made from purified Alaska pollack fish oil containing palmitoleic acid (16:1), commonly referred to as omega-7. We sought to quantitatively evaluate whether this substance inhibits skin aging. A total of 101 middle-aged females were randomly allocated to the intervention (N = 50) or placebo group (N = 51). Each participant was advised to take either 500 mg of 7-MEGATM or a placebo twice daily for 12 weeks. The primary outcomes were the degree of improvement in wrinkles and the degree of moisture filling after consumption for 12 weeks compared to baseline. The secondary outcomes were improvement in skin wrinkles; moisture changes at 4 and 8 weeks from baseline; changes in transdermal water loss, skin elasticity, the melanin index, the erythema index, and the Global Photo Damage Score. We found a significant improvement in skin wrinkles and elasticity at 12 weeks in the 7-MEGATM-consuming group compared to that in the placebo group; skin moisture, elasticity, and the melanin index were also improved. No supplement-related adverse reactions were observed and 7-MEGATM was identified as safe. 7-MEGATM was effective for human skin function in terms of wrinkles, moisture, elasticity, and melanin production and may be useful as a skin nutritional supplement.

Phenylketonuria (PKU) is an inherited metabolic disorder caused by a deficiency of phenylalanine hydroxylase. The accumulation of phenylalanine leads to severe mental and psychomotor retardation. Phenylalanine restriction diet can prevent irreversible damage if instituted from birth. Recently, we reported the cognitive outcome of biochemical and phenotypic reversal of PKU mouse model, Pahenu2, by the AAV 2-mediated gene delivery of a human PAH transgene (Pediatr Res 56:278-284, 2004). However, the therapeutic effectiveness had been observed only in male PKU mice. No normalization in coat color or plasma phenylalanine level was observed in gene therapy on female PKU mice. In this study, we generated pseudotyped AAV2/8 vector encoding the human PAH gene. The rAAV2/8-hPAH vector was infused into female PKU mice via the hepatic portal vein. Six weeks after injection, the coat color change to black was clearly observed in female PKU as in male. Plasma phenylalanine level in female PKU mice decreased to 120〉|µM/L. The PAH enzyme activities of treated mouse liver increased to 65-70% of wild-type in female PKU mice, to 90-95% in male PKU mice. These corrections were sustained over 6 month. Furthermore, we observed rAAV2/8-hPAH treated female PKU mice can overcome maternal PKU syndrome. These results indicate that recombinant AAV 2/8 mediated gene therapy can be a useful therapeutic candidate for patients with PKU. [ABSTRACT FROM AUTHOR]

Abstract Blood vessels in central nervous system act as a great hurdle for drug delivery to the human brain. They only allow passage of water, some gases, lipid molecules, glucose and amino acid by selective transporter while restricting most of solutes and pathogens to protect brain. A lot of studies have tried to overcome this hurdle by discovering and optimizing brain deliverable drugs however the platforms used for preclinical stage are still limited. In this study, we constructed an in vitro 3-dimensional model for brain endothelial monolayer using hydrogel incorporated microfluidic device that provides an 3D extracellular matrix scaffold. We confirmed the stable endothelial barrier by staining a tight junction marker, VE-Cadherin, and strong block ability by comparing permeability with normal endothelial cells. Also, we succeed in verifying the strong permeability of angiopep-2 using our device that is known as a brain permeable peptide by utilizing receptor-mediated transcytosis. We propose our microfluidic device as an in vitro platform for evaluating various brain drugs or drug carrier candidates.