• Title/Summary/Keyword: $ERR\

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The estrogen-related receptor γ modulator, GSK5182, inhibits osteoclast differentiation and accelerates osteoclast apoptosis

  • Kim, Hyun-Ju;Yoon, Hye-Jin;Lee, Dong-Kyo;Jin, Xian;Che, Xiangguo;Choi, Je-Yong
    • BMB Reports
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    • v.54 no.5
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    • pp.266-271
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    • 2021
  • Estrogen-related receptor γ (ERRγ), a member of the orphan nuclear receptor family, is a key mediator in cellular metabolic processes and energy homeostasis. Therefore, ERRγ has become an attractive target for treating diverse metabolic disorders. We recently reported that ERRγ acts as a negative regulator of osteoclastogenesis induced by receptor activator of nuclear factor-κB ligand (RANKL). In the present study, we explored the effects of an ERRγ-specific modulator, GSK5182, on ERRγ-regulated osteoclast differentiation and survival. Interestingly, GSK5182 increased ERRγ protein levels much as does GSK4716, which is an ERRγ agonist. GSK5182 inhibited osteoclast generation from bone-marrow-derived macrophages without affecting cytotoxicity. GSK5182 also attenuated RANKL-mediated expression of cFos and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), pivotal transcription factors for osteoclastogenesis. Arrested osteoclast differentiation was associated with reduced RANK expression, but not with the M-CSF receptor, c-Fms. GSK5182 strongly blocked the phosphorylation of IκBα, c-Jun N-terminal kinase, and extracellular signal-regulated kinase in response to RANKL. GSK5182 also suppressed NF-κB promoter activity in a dose-dependent manner. In addition to osteoclastogenesis, GSK5182 accelerated osteoclast apoptosis by caspase-3 activation. Together, these results suggest that GSK5182, a synthetic ERRγ modulator, may have potential in treating disorders related to bone resorption.

Review: Distribution, Lactose Malabsorption, and Alleviation Strategies of Lactose Intolerance (유당불내증(Lactose Intolerance)의 발생 원인과 경감 방안에 대한 고찰)

  • Yoon, Sung-Sik
    • 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.

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The Effect of the Optical Points Difference between Finished-Reading Glasses and Dispensing Reading Glasses (완성품 돋보기와 조제가공된 돋보기가 광학적 요소에 미치는 영향)

  • Shim, Young-Cheol;Yoo, Gun-Chang;Kim, In-Suk
    • Journal of Korean Ophthalmic Optics Society
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    • v.13 no.3
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    • pp.65-71
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    • 2008
  • Purpose: This paper studied the effect of eyes on the comparison between the distance optical centers problem of dispensing reading glasses made by optician and finished reading glasses in the current market. Methods: The method of this study has been measured by eleven different categories from +1.00D to +4.00D. This study also separated into three groups by their optical frame size and measured optical center point (O.C) and optical center height (O.H) with 200 peoples of man and females over 40 years old without ocular disease living in Gwang-san gu, Gwang-Ju city. Results: As a result, optical center point ranged from 57 mm to 80 mm and it turned to be most common range is from 61 mm to 65 mm (64.6%). Moreover, the optical center height ranged from 1 mm to 8mm and most common ranged (23%) were 4 mm. In other words, finished reading glasses have irregular optical ranges. After observing 200 people who are over 40 years old men and women, result shows that more than 75.5% (151 people) currently use finished reading glasses. Survey of 151 people, most common error between the finished reading glasses's O.C and the wearers P.D were 4 mm (45%). Furthermore, the most common error between the finished reading glassses's O.H and the wearers O.H ranged from 3 mm to 4 mm. Astonishingly, the entire 151 people who wear finished reading glasses appeal that they feel tiredness on their eyes when they wear finished reading glasses. 53 people (35%) claimed that they feel tiredness on their eyes after 10 to 20 minutes wearing finished reading glasses. Base on the research, We conducted more experiment to find the value of prism of optical centers err because it will tell us whether the finished reading glasses are good enough to wear or not. We multiplied diopter by the difference between finished reading glasses's O.C. and wearer's P.D. Consequently, We found out that the finished reading glasses counter to the German RAL-RG 915 policy. And We also found that it is relative to the diopter of lenses. In conclusion, based on the researched that wearing finished reading glasses have a dangerous factor for our vision. Therefore optician must need to recommend correctly made dispensing reading glasses based on the optical center point.

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