Background: Liver fibrosis is a common outcome of chronic liver disease and is primarily driven by hepatic stellate cell (HSC) activation. Irisin, a myokine released during physical exercise, is beneficial for metabolic disorders and mitochondrial dysfunction. This study aimed to explore the effects of irisin on liver fibrosis in HSCs, a bile duct ligation (BDL) mouse model, and the associated mitochondrial dysfunction. Methods: In vitro experiments utilized LX-2 cells, a human HSC line, stimulated with transforming growth factor-β1 (TGF-β1), a major regulator of HSC fibrosis, with or without irisin. Mitochondrial function was assessed using mitochondrial fission markers, transmission electron microscopy, mitochondrial membrane potential, and adenosine triphosphate (ATP) production. In vivo, liver fibrosis was induced in mice via BDL, followed by daily intraperitoneal injections of irisin (100 μg/kg/day) for 10 days. Results: In vitro, irisin mitigated HSC activation and reduced reactive oxygen species associated with the TGF-β1/Smad signaling pathway. Irisin restored TGF-β1-induced increases in fission markers (Fis1, p-DRP1) and reversed the decreased expression of TFAM and SIRT3. Additionally, irisin restored mitochondrial membrane potential and ATP production lowered by TGF-β1 treatment. In vivo, irisin ameliorated the elevated liver-to-body weight ratio induced by BDL and alleviated liver fibrosis, as evidenced by Masson’s trichrome staining. Irisin also improved mitochondrial dysfunction induced by BDL surgery. Conclusion Irisin effectively attenuated HSC activation, ameliorated liver fibrosis in BDL mice, and improved associated mitochondrial dysfunction. These findings highlight the therapeutic potential of irisin for the treatment of liver fibrosis.

Background: Liver fibrosis is a common outcome of chronic liver disease and is primarily driven by hepatic stellate cell (HSC) activation. Irisin, a myokine released during physical exercise, is beneficial for metabolic disorders and mitochondrial dysfunction. This study aimed to explore the effects of irisin on liver fibrosis in HSCs, a bile duct ligation (BDL) mouse model, and the associated mitochondrial dysfunction. Methods: In vitro experiments utilized LX-2 cells, a human HSC line, stimulated with transforming growth factor-β1 (TGF-β1), a major regulator of HSC fibrosis, with or without irisin. Mitochondrial function was assessed using mitochondrial fission markers, transmission electron microscopy, mitochondrial membrane potential, and adenosine triphosphate (ATP) production. In vivo, liver fibrosis was induced in mice via BDL, followed by daily intraperitoneal injections of irisin (100 μg/kg/day) for 10 days. Results: In vitro, irisin mitigated HSC activation and reduced reactive oxygen species associated with the TGF-β1/Smad signaling pathway. Irisin restored TGF-β1-induced increases in fission markers (Fis1, p-DRP1) and reversed the decreased expression of TFAM and SIRT3. Additionally, irisin restored mitochondrial membrane potential and ATP production lowered by TGF-β1 treatment. In vivo, irisin ameliorated the elevated liver-to-body weight ratio induced by BDL and alleviated liver fibrosis, as evidenced by Masson’s trichrome staining. Irisin also improved mitochondrial dysfunction induced by BDL surgery. Conclusion Irisin effectively attenuated HSC activation, ameliorated liver fibrosis in BDL mice, and improved associated mitochondrial dysfunction. These findings highlight the therapeutic potential of irisin for the treatment of liver fibrosis.

Background: Liver fibrosis is a common outcome of chronic liver disease and is primarily driven by hepatic stellate cell (HSC) activation. Irisin, a myokine released during physical exercise, is beneficial for metabolic disorders and mitochondrial dysfunction. This study aimed to explore the effects of irisin on liver fibrosis in HSCs, a bile duct ligation (BDL) mouse model, and the associated mitochondrial dysfunction. Methods: In vitro experiments utilized LX-2 cells, a human HSC line, stimulated with transforming growth factor-β1 (TGF-β1), a major regulator of HSC fibrosis, with or without irisin. Mitochondrial function was assessed using mitochondrial fission markers, transmission electron microscopy, mitochondrial membrane potential, and adenosine triphosphate (ATP) production. In vivo, liver fibrosis was induced in mice via BDL, followed by daily intraperitoneal injections of irisin (100 μg/kg/day) for 10 days. Results: In vitro, irisin mitigated HSC activation and reduced reactive oxygen species associated with the TGF-β1/Smad signaling pathway. Irisin restored TGF-β1-induced increases in fission markers (Fis1, p-DRP1) and reversed the decreased expression of TFAM and SIRT3. Additionally, irisin restored mitochondrial membrane potential and ATP production lowered by TGF-β1 treatment. In vivo, irisin ameliorated the elevated liver-to-body weight ratio induced by BDL and alleviated liver fibrosis, as evidenced by Masson’s trichrome staining. Irisin also improved mitochondrial dysfunction induced by BDL surgery. Conclusion Irisin effectively attenuated HSC activation, ameliorated liver fibrosis in BDL mice, and improved associated mitochondrial dysfunction. These findings highlight the therapeutic potential of irisin for the treatment of liver fibrosis.

Background: Liver fibrosis is a common outcome of chronic liver disease and is primarily driven by hepatic stellate cell (HSC) activation. Irisin, a myokine released during physical exercise, is beneficial for metabolic disorders and mitochondrial dysfunction. This study aimed to explore the effects of irisin on liver fibrosis in HSCs, a bile duct ligation (BDL) mouse model, and the associated mitochondrial dysfunction. Methods: In vitro experiments utilized LX-2 cells, a human HSC line, stimulated with transforming growth factor-β1 (TGF-β1), a major regulator of HSC fibrosis, with or without irisin. Mitochondrial function was assessed using mitochondrial fission markers, transmission electron microscopy, mitochondrial membrane potential, and adenosine triphosphate (ATP) production. In vivo, liver fibrosis was induced in mice via BDL, followed by daily intraperitoneal injections of irisin (100 μg/kg/day) for 10 days. Results: In vitro, irisin mitigated HSC activation and reduced reactive oxygen species associated with the TGF-β1/Smad signaling pathway. Irisin restored TGF-β1-induced increases in fission markers (Fis1, p-DRP1) and reversed the decreased expression of TFAM and SIRT3. Additionally, irisin restored mitochondrial membrane potential and ATP production lowered by TGF-β1 treatment. In vivo, irisin ameliorated the elevated liver-to-body weight ratio induced by BDL and alleviated liver fibrosis, as evidenced by Masson’s trichrome staining. Irisin also improved mitochondrial dysfunction induced by BDL surgery. Conclusion Irisin effectively attenuated HSC activation, ameliorated liver fibrosis in BDL mice, and improved associated mitochondrial dysfunction. These findings highlight the therapeutic potential of irisin for the treatment of liver fibrosis.

IL-1β plays critical roles in the priming and effector phases of immune responses such as the differentiation, commitment, and memory formation of T cells. In this context, several reports have suggested that the IL-1β signal is crucial for CTL-mediated immune responses to viral infections and tumors. However, little is known regarding whether IL-1β acts directly on CD8 + T cells and what the molecular mechanisms underlying expression of IL-1 receptors (IL-1Rs) on CD8 + T cells and features of IL-1R + CD8 + T cells are. Here, we provide evidence that the expression of IL-1R type I (IL-1RI), the functional receptor of IL-1β, is preferentially induced by IL-21 on TCR-stimulated CD8 + T cells. Further, IL-1β enhances the effector function of CD8 + T cells expressing IL-21-induced IL-1RI by increasing cytokine production and release of cytotoxic granules containing granzyme B. The IL-21-IL-1RI-IL-1β axis is involved in an augmented effector function through regulation of transcription factors BATF, Blimp-1, and IRF4. Moreover, this axis confers a unique effector function to CD8 + T cells compared to conventional type 1 cytotoxic T cells differentiated with IL-12. Chemical inhibitor and immunoprecipitation assay demonstrated that IL-21 induces a unique pattern of STAT activation with the formation of both STAT1:STAT3 and STAT3:STAT5 heterodimers, which are critical for the induction of IL-1RI on TCR-stimulated CD8 +T cells. Taken together, we propose that induction of a novel subset of IL-1RI-expressing CD8 + T cells by IL-21 may be beneficial to the protective immune response against viral infections and is therefore important to consider for vaccine design.

This survey was performed to analyze the usability of the third edition of the Korean breast cancer clinical practice guidelines (KBCCPG) in clinical practice. We made a questionnaire composed of 18 general and 82 specific questions regarding benign breast disease (B; 1 question); non-invasive disease (N; 12 questions); early-stage disease (E; 26 questions); advanced disease (A; 24 questions); and metastatic (M) breast cancer-related problems (19 questions). A total of 100 questionnaires, with a link to an online survey, were delivered via e-mail to over 700 members of the Korean Breast Cancer Society (KBCS), and associated academy members, over 20 days between 26th February and 16th May 2010. Out of 270 respondents who read the e-mail, 96 answered the questionnaire. Participants included 87 surgical oncologists, 5 radiation oncologists, 2 oncoplastic surgeons, 1 pathologist, and 1 medical oncologist. The third KBCCPG were perceived as differing from the second guidelines in terms of the level of clinical evidence required before choosing a recommendation. For the progress of the KBCCPG, the guideline committee should try to reinforce all courses of guideline development with several elements including data from clinical trials of Korean breast cancer patients, securing a multidisciplinary approach, developing consistent and reasonable processes for each step of the revision of the guidelines, induction of liberal scientific and ethical discussion about all issues with all KBCS members. The cost-effectiveness of healthcare and the logical development of the KBCCPG would also be ensured. Timely updates of the clinical guidelines for breast cancer treatment are essential to facilitate optimal decision-making in daily practice, and to ensure adequate patient feedback.
Aluminum Hydroxide ; Breast ; Breast Diseases ; Breast Neoplasms ; Carbonates ; Surveys and Questionnaires ; Delivery of Health Care ; Dietary Sucrose ; Electronic Mail ; Humans ; Korea ; Logic

Elevated plasma level of the sulfur amino acid homocysteine, termed hyperhomocysteinemia, is now recognized as a contributing factor to various pathological states of the brain including vascular, degenerative and other neurologic disorders. Endothelial dysfunction may be one of the underlying mechanisms leading to proatherogenic and neurotoxic effects associated hyperhomocysteinemia. We conducted electron microscopic studies to investigate microvascular changes in hyperhomocysteinemic rat brain due to folate deficiency. Dietary folate deprivation caused an increase in plasma Hcy by 317% from 6.15 +/- 0.9 micro mol/l to 19.5 +/- 3.2 micro mol/l with time up to 8 weeks of folate deprivation. In electron microscopic study, perivascular amorphous fibrosis, and pericytic and endothelial cell degenerative appearance were frequently found in hyperhomocysteinemic microvasculature. These findings are very similar with the typical cerebral microvascular pathology observed in neurodegenerative and aging processes. From these results, it can be suggested that hyperhomocysteinemia -induced blood -brain barrier disruption give rise to subsequent neuronal dysfunction in hyperhomocysteinemia.
Aging ; Animals ; Brain ; Endothelial Cells ; Fibrosis ; Folic Acid ; Homocysteine ; Hyperhomocysteinemia* ; Microscopy, Electron ; Microvessels* ; Nervous System Diseases ; Neurons ; Pathology ; Plasma ; Rats ; Sulfur

OBJECTIVES: Retinopathy of prematurity (ROP) is one of the major cause of vision loss among children. Recently, the prevalence of ROP is markedly increasing as the survival rate of very-low-birth-weight premature infants has been improved. It is widely accepted that retinal hypoxia results in the release of factors influencing new blood vessel growth. But, it is little known about the morphological changes of retinal astrocytes and Muller cells in the ROP model. So, we planned to investigate the morphological changes of those retinal glial cells induced by alternating hyperoxic and hypoxic injury in ROP. METHODS: Newborn rats (postnatal day 6) were exposed to two different oxygen concentrations alternating every 24 hours until postnatal day 14. Used oxygen concentrations were 10~15% for hypoxic episode and 55~80% for hyperoxic episode. Afterthen, they were returned to room air. A group of animal served as a room air control. Retinal vascularity was assessed by ADPase reaction and morphology of retinal glial cells was observed using transmisson electron microscope. RESULTS: Preretinal neovascular tufts were observed in 2 out of 12 animals of group III (75/10%) and 4 out of 12 animals of group IV (80/10%), respectively. There was no remarkable structural change of astrocytes. But we could observe some morphological changes of Muller cells. Retraction of the radial processes of Muller cells and breaking of basal lamina were noted at the site of preretinal neovascularization. Decrease in the space occupied by the cytoplasmic processes of Muller cells was observed in the inner nuclear layer of group IV retinae. Infiltration of microglia or macrophage into the vitreo-retinal interface and the site of extravasation was noted. Findings suggestive of neuronal cell death were also observed especially in the inner nuclear layer. CONCLUSIONS: Morphological change of Muller cells and resultant loss of integrity of internal limiting membrane seemed to be the most important step for preretinal neovascularization. But, no structural changes of astrocytes were noted.
Animals ; Anoxia ; Apyrase ; Astrocytes* ; Basement Membrane ; Blood Vessels ; Cell Death ; Child ; Cytoplasm ; Ependymoglial Cells* ; Humans ; Infant, Newborn ; Infant, Premature ; Macrophages ; Membranes ; Microglia ; Models, Animal* ; Neuroglia ; Neurons ; Oxygen ; Prevalence ; Rats* ; Retina ; Retinaldehyde ; Retinopathy of Prematurity* ; Survival Rate

Eventhough surmountable amounts of genes are being cloned and a number of methods are being developed by human genome project, it's not easy to predict possible functions of genes and determine the chromosomal locations of genes. In this experiment, cDNA pool was made from 18 weeks old human fetal brain and analyzed the sequences. FB174 clone was chosen, in situ hybridization histochemistry was performed on developing and adult rat tissue section to observe the tissue specificity and developmental expression of this gene. To observe the chromosomal location of FB174 clone, the genomic DNA from human genomic library was isolated and fluorescence in situ hybridization was carried out. By sequencing and sequence search with GenBank data it was revealed that cloned FB174 cDNA was quite similar to translationally controlled tumor protein which is known to locate to human chromosome 13q14. The expression of FB174 mRNA was not detected in rat tissue sections by in situ hybridization histochemistry. Fluorescence in situ hybridization using biotin labeled FB174 probe resulted in specific labeling of human chromosome 7q22. These results and high sequence homology of FB174 to known translationally controlled tumor protein suggest that FB174 clone may be a new translationally controlled tumor protein-related gene.
Adult ; Animals ; Biotin ; Brain* ; Chromosomes, Human ; Clone Cells ; Databases, Nucleic Acid ; DNA* ; DNA, Complementary* ; Fluorescence ; Genomic Library ; Human Genome Project ; Humans* ; In Situ Hybridization ; Organ Specificity ; Rats ; RNA, Messenger ; Sequence Homology

The cholinergic neurons in the striatal complex are the major interneurons that integrate the informations incoming to and outflowing from the striatum. The shape of synapses may change even after birth and the synaptic morphology reflects the functional state of synapse. However, it is not well known about the synaptic morphology of the mouse striatal cholinergic neurons in their early postnatal life. Thus, we investigated the synaptic morphology of the mouse striatal cholinergic neurons in their early postnatal life by the electron microscopy combined with immunohis-tochemistry. In addition, we investigated the trends of change in synaptic morphology and whether the difference between two compartments exists or not. Experimental animals which are ICR mice, were divided into 5 groups according to their postnatal age: 3-day, 1-week, 2-week, 4-week, and 6-week. Pre-embedding immunohisto-chemistry was done with anti-choline acetyl transferase antibody. The results were as follows. 1. In synapses that immunoreactive terminals constitute the presynaptic components, most of synapses are symmetric type in all age groups (p<0.05). Most of synapses in the dorsal striatum are symmetric form from 1-week of postnatal age, but it is not prominent in the ventral striatum until 2-week of postnatal age. 2. In synapses that immunoreactive terminals constitute the postsynaptic components, both symmetric and asymmetric synapses are noted in similar proportions (p<0.05). There are no difference in the synaptic morphology between dorsal and ventral striatum. 3. No specific findings are observed in synaptic curve according to the postnatal age or compartment. In conclusion, the synaptic morphology of mouse striatal cholinergic neurons is similar to mature pattern from 2-week of postnatal age. And it is thought that period between birth and 2-week of postnatal age is the critical period for synaptogenesis. The synaptic curve does not reflect the degree of synaptic maturity. Further investigations will be required to generalize the synaptic curve as a marker for synaptic maturity.
Animals ; Basal Ganglia ; Cholinergic Neurons* ; Critical Period (Psychology) ; Humans ; Immunohistochemistry ; Interneurons ; Mice* ; Mice, Inbred ICR ; Microscopy, Electron ; Parturition ; Synapses ; Transferases