• Journal of Food Hygiene and Safety
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• v.31 no.1
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• pp.59-66
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• 2016

It has been generally accepted that obesity and overweight are associated with metabolic diseases and cancer incidence. In fact, obesity increased risks of cancers i.e. breast, liver, pancreatic and prostate. Celastrol is a pentacyclic triterpenoid isolated from Thunder god vine, was used as a Chinese traditional medicine for treatment of inflammatory disorders such as arthritis, lupus erythematosus and Alzheimer's disease. Also, celastrol has various biological properties of chemo-preventive, neuro-protective, and anti-oxidant effects. Recent studies demonstrated that celastrol has anti-proliferation effects in different type of obesity-related cancers and suppresses tumor progression and metastasis. Anticancer effects of celastrol include regulation of $NF-{\kappa}B$, heat shock protein, JNK, VEGF, CXCR4, Akt/mTOR, MMP-9 and so on. For these reasons, celastrol has shown to be a promising anti-tumor agent. In this review, we will address the anticancer activities and multiple mechanisms of celastrol in obesity-related cancers.

• Journal of Veterinary Clinics
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• v.32 no.2
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• pp.191-195
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• 2015

A 7-year-old castrated male Korean Shorthair cat was referred with lethargy and anorexia. Laboratory examination revealed moderate degenerative changes of peripheral neutrophils on blood smear examination and decreased levels of free and total thyroxine ($T_4$) as well as bacterial growth on blood culture. Molecular analyses of the 16S ribosomal RNA gene and heat shock protein 60 gene confirmed the bacterium as Enterobacter cloacae. A minimal inhibitory concentration test showed multidrug resistance of the bacterium against 16 antibiotics. Polymerase chain reaction (PCR) and subsequent sequencing specifically for $bla_{TEM}$, $bla_{SHV}$, $bla_{CTX-M}$, and plasmid-mediated ampC genes revealed positive results to $bla_{TEM-1}$, $bla_{CTX-M-15}$, and plasmid-mediated $bla_{ACT-1}$ genes, indicating that the isolated bacterium contains plasmids containing genes encoding extended-spectrum beta-lactamase and plasmid-mediated ampC beta-lactamase. After 1 month of treatment with antibiotics and levothyroxine, the cat's condition improved; both the thyroid function test and the blood culture showed no abnormalities. This is the first report of community-acquired multidrug-resistant E. cloacae-induced euthyroid sick syndrome in a cat. By the prompt diagnostic procedures and properly selected antibiotic therapy, the cat was recovered from the multidrug-resistant bacterium-induced septicaemia.

• Korean Journal of Microbiology
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• v.46 no.2
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• pp.134-139
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• 2010

Mycobacterium tuberculosis (Mtb) is one of the most successful pathogens to infect one third of world population. Th1-mediated immunity against Mtb infection is known as critical to express mycobacteriostatic function but it is not sufficient to resolve the infection. In this study, to verify the possibility Mtb itself change the gene expression to survive against host immune response, expression pattern of selected H37Rv genes, 16S rRNA, acr, fbpA, aceA, and ahpC, during the course of infection was measured with absolute quantitation method using real-time RT-PCR. The total number of transcripts of 16S rRNA increased during the course of infection, which was coincide with the increasing CFU. The total number of fbpA transcripts per CFU, which encode typical secreted Mtb antigen, Ag85A, increased for 10 days of infection before decreasing. The number of transcripts of acr per CFU, which encode heat shock protein, ${\alpha}$-crystallin, increased during the infection, and ahpC and aceA, they both are enzymes produced in oxidative stressful condition, increased for 20 days and then slightly decreased on day 30. These findings are one of survival strategy of pathogen evading host immune response lead to persistent infection inside host cells.

• Journal of Life Science
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• v.28 no.10
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• pp.1212-1219
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• 2018

The critical role of heat shock protein 90 (Hsp90) in tumorigenesis led to the development of several first- and second-generation Hsp90 inhibitors, which have demonstrated promising responses in cancers. In this study, we found second-generation Hsp90 inhibitor BIIB021-resistant multidrug-resistant (MDR) human cancer cells, although BIIB021 was shown to be active in first-generation Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG)-resistant MDR cells. MCF7-MDR and HeyA8- MDR cells were more resistant to BIIB021 than their parental counterparts, indicating that BIIB021 cannot be applicable to all cancer cells expressing MDR proteins. We revealed that dimethyl-celecoxib (DMC), one of the non-steroidal anti-inflammatory drugs (NSAIDs), potentiated cytotoxicity of BIIB021 against both BIIB021-resistant and BIIB021-sensitive MDR cells. The effectiveness of NSAIDs involving celecoxib and DMC in combination with BIIB021 led to the autophagic degradation/down-regulation of mutant p53 (mutp53) that overexpressed MDR cells and the suppression of Hsp70 induction. This resulted in sensitization of MDR cells to BIIB021. Moreover, autophagy induction by sulindac sulfide, another type of NSAID, and niclosamide, an FDA-approved anthelmintic drug, potentiated 17-AAG-mediated autophagic degradation/down-regulation of mutp53 and c-Myc, client proteins of Hsp90. Therefore, our results suggest that NSAIDs and niclosamide positively enhance the anticancer activity of Hsp90 inhibitors through an autophagic pathway. They may also be new candidates for sensitizing MDR cells to Hsp90 inhibitors.

• Clinical and Experimental Reproductive Medicine
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• v.26 no.1
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• pp.103-109
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• 1999

Objective: Heat shock protein 70-2 (Hsp70-2) gene knockout mice are found to have premeiotic arrest at the primary spermatocyte stage with a complete absence of spermatids and spermatozoa. This observation led to the hypothesis that hspA2 may be disrupted in human testes with abnormal spermatogenesis. To test this hypothesis, we studied the mRNA expression of hspA2 in infertile men with azoospermia. Design: The mRNA expression were analyzed by competitive RT-PCR among testes with normal spermatogenesis, pachytene spermatocyte arrest, and sertoli-cell only syndrome. Materials and methods: Testicular biopsy was performed in men with azoospermia (n=15). Specimens were subdivided into three groups: (group 1) normal spermatogenesis (n=5), (group 2) spermatocyte arrest (n=5), (group 3) Sertoli-cell only syndrome (n=5). Total RNA was extracted by Trizol reagent. Total extracted RNA was reverse transcribed into cDNA and amplified by PCR using specific primers for hspA2 target cDNAs. A competitive cDNA fragment was constructed by deleting a defined fragment from the target cDNA sequence, and then coamplified with the target cDNA for competitive PCR. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene was used as an internal control. Results: On Competitive RT-PCR analyses for hspA2 mRNA, significant amount of hspA2 expression was observed in group 1, whereas a constitutively low level of hspA2 was expressed in groups 2 and 3. Conclusion(s): The study demonstrates that the hspA2 gene expression is down-regulated in human testes with abnormal spermatogenesis, which in turn suggests that hspA2 gene may play a specific role during meiosis in human testes.

• Journal of Life Science
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• v.15 no.4 s.71
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• pp.607-612
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• 2005

Heat shock protein 70 (HSP70) is a multigene family composed of constitutively expressed members(Hsc70) and stress-inducible members (Hsp70). In the mammalian nervous system, a considerable amount of HSPs is also synthesized under normal conditions suggesting that they play an important role in the metabolism of unstressed cells. In this study we examined the expression of Hsp70 in the synapses of rat cerebellar neurons. Immunohistochemistry using specific antibodies revealed that both Hsp70 and Hsc70 are expressed in the cerebellar tissue, with strongest expression in Purkinje cells followed by granule cells. Neurons in deep cerebellar nuclei were also intensely stained by Hsp70 antibody. Immunocytochemical stainings of cultured cerebellar cells showed that Hsp70 is expressed in both Purkinje and granule cells. The expression was punctate in the soma and along dendritic trees, and the punctae were colocalized with those of PSD95, a postsynaptic marker. Immunoblotting also indicates that Hsp70 is associated with the postsynaptic density fraction. Taken together, our results indicate that the Hsp70 is expressed in cerebellar neurons in normal conditions, and that some are localized in the synapses.

• Journal of Pharmacopuncture
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• v.3 no.2
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• pp.191-212
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• 2000

Objective: This study was perfomled to examine the therapeutic effect of aqua-acupuncture solution of Hominis Placenta(HP) on kidney and liver intoxicated by $HgCI_2$ in rats. Methods: $10\%$ and $25\%$ HP aqua-acupuncture were carried out everyday for 8 days on corresponding bilateral loci of Shinsu(BL23) and Kansu(BL18), respectively, after mercuric chloride intoxication in rats. Thereafter BUN, creatinine, GOT, GPT, ALP, ${\gamma}$-GT, albumin and total bilirubin were measured before intoxication, and at the 4th and the 8th experimental day. Histopathological and immunochemical observation were also carried out. Results: 1. It showed significant decreases of BUN in the group of $10\%$ HP aqua-acupuncture into Shinsu on the 4th experimental day as compared with the control group. 2. It showed significant decreases of creatinine in the group of $10\%$ HP aqua-acupuncture into Shinsu on the 4th and the 8th experimental days as compared with the control group. 3. There were not any significant changes of GOT, GPT, ALP,${\gamma}$-GT, albumin and total bilirubin in the HP aqua-acupuncture groups compared with the control group. 4. By the histopathological observations on kidney under a light microscope, alt the $10\%$ and $25\%$ HP aqua-acupuncture into Shinsu showed the preventive effect on tubulo-interstitial necrosis and muItifocal calcification in tubular lumen respectively compared with the control group. 5. By the histopathological observations on liver under a light mIcroscope, the groups $10\%$ and $25\%$ HP aqua--acupuncture into Kansu did not show any significant changes in the liver compared with the control group. 6. By the immunochemical analysis of heat shock protein(hsp) and glucose-regulated protein(grp) in rat renal cortex, the expressions of hsp70 and grp78 were decreased in the $10\%$ and $25\%$ HP aqua-acupuncture into Shinsu respectively compared with the control group. Conclusion: These results suggest that Hominis Placenta aqua-acupuncture have an effect on prevention and protection of renal intoxication by $HgCI_2$ in rats.

• Radiation Oncology Journal
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• v.28 no.2
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• pp.91-98
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• 2010

Purpose: Troglitazone (TRO), a PPAR-$\gamma$ agonist, can reduce heat shock protein (HSP) 70 and increase the antioxidant enzymes, such as superoxide dismutase (SOD) and catalase, which might affect thermal sensitivity. Here, we investigated whether TRO modifies thermal sensitivity in uterine cervical cancer cells, which is most commonly treated by hyperthermia (HT). Materials and Methods: HeLa cells were treated with $5{\mu}M$ TRO for 24 hours before HT at $42^{\circ}C$ for 1 hour. Cell survival was analyzed by clonogenic assay. The expression of HSPs was analyzed by Western blot. SOD and catalase activity was measured and reactive oxygen species (ROS) was measured using 2',7'-dichlorofluorescin diacetate and dihydroethidium. Results: The decreased cell survival by HT was increased by preincubation with TRO before HT. Expression of HSP 70 was increased by HT however, it was not decreased by preincubation with TRO before HT. The decreased Bcl-2 expression by HT was increased by preincubation with TRO. SOD and catalase activity was increased by 1.2 and 1.3 times,respectively with TRO. Increased ROS by HT was decreased by preincubation with TRO. Conclusion: TRO decreases thermal sensitivity through increased SOD and catalase activity, as well as scavenging ROS in HeLa cells.

• Journal of Veterinary Clinics
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• v.28 no.5
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• pp.516-518
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• 2011

A survey was conducted to examine the normal intestinal bacterial flora of captive Oriental white storks (Ciconia boyciana) maintained at the Korea Institute of Oriental White Stork Rehabilitation Research, Cheongwon, South Korea. From the cloaca of 44 healthy storks, 44 fecal samples were collected and cultured under aerobic and anaerobic conditions. The 16S ribosomal RNA gene sequences and the heat shock protein 60 gene were cloned and sequenced for bacterial identification. Under aerobic conditions, Enterococcus faecalis, Escherichia coli, Bacillus spp., Enterococcus avium, Enterococcus gallinarum, Pseudomonas spp., Alcaligenes spp., Enterobacter spp., Corynebacterium spp., and Proteus mirabilis were identified. Under anaerobic conditions, E. coli, Clostridium tertium, En. faecalis, and P. mirabilis were identified. E. coli, En. faecalis, or both were isolated from all samples. These results will add to the information available on this stork species and help for the interpretation of fecal culture results.

• Journal of Life Science
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• v.21 no.2
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• pp.251-256
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• 2011

EGCG, catechins in green tea, is a kind of phytochemical. Through the regulation of signal pathways, EGCG has been known to show anti-oxidant and anti-tumor effects in cells. In this study, we investigated the apoptotic effects of EGCG through AMP-activated protein kinase (AMPK) signal pathways, including hypoxia inducible factor-1 alpha (HIF-$1{\alpha}$). The experiments were performed in B16F10 melanoma cells in a hypoxic state. AMPK is activated by ATP consumption such as nutrient deficiency, exercise, heat shock, etc. The activated AMPK that plays an important role as an energy sensor inhibits proliferation of cancer cells, as well as inducing apoptosis. HIF-$1{\alpha}$, the primary transcriptional regulator of the response to oxygen deprivation, plays a critical role in modulating tumor growth and angiogenesis in a hypoxic state. The apoptotic effects of EGCG were studied in B16F10 cells in a hypoxic state. The results show that EGCG inhibits the transcriptional activity of HIF-$1{\alpha}$ and induces apoptosis. These observations suggest that EGCG may exert inhibitory effects of angiogenesis and control tumor cell growth in hypoxic melanoma cells.