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Caffeine attenuates spermatogenic disorders in mice with induced chronic scrotal hyperthermia

  • Amir Raoofi;Omid Gholami;Hossein Mokhtari;Fatemeh Bagheri;Auob Rustamzadeh;Davood Nasiry;Alireza Ghaemi
    • Clinical and Experimental Reproductive Medicine
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    • v.51 no.1
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    • pp.28-41
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    • 2024
  • Objective: Chronic scrotal hyperthermia (SHT) can lead to serious disorders of the male reproductive system, with oxidative stress playing a key role in the onset of these dysfunctions. Thus, we evaluated the impact of caffeine, a potent antioxidant, on cellular and tissue disorders in mice with chronic SHT. Methods: In this experimental study, 56 adult male NMRI mice were allocated into seven equal groups. Apart from the non-treated control group, all were exposed to heat stress. Two groups, termed "preventive" and "curative," were orally administered caffeine. The preventive mice began receiving caffeine immediately prior to heat exposure, while for the curative group, a caffeine regimen was initiated 15 consecutive days following cessation of heat exposure. Each treated group was subdivided based on pairing with a positive control (Pre/ curative [Cur]+PC) or a vehicle (Pre/Cur+vehicle). Upon conclusion of the study, we assessed sperm characteristics, testosterone levels, stereological parameters, apoptosis, antioxidant and oxidant levels, and molecular markers. Results: Sperm parameters, testosterone levels, stereological parameters, biochemical factors (excluding malondialdehyde [MDA]), and c-kit gene expression were significantly elevated in the preventive and curative groups, especially the former, relative to the other groups. Conversely, expression levels of the heat shock protein 72 (HSP72) and nuclear factor kappa beta (NF-κβ) genes, MDA levels, and apoptotic cell density were markedly lower in both caffeine-treated groups relative to the other groups, with more pronounced differences observed in the preventive group. Conclusion: Overall, caffeine attenuated cellular and molecular abnormalities induced by heat stress in the testis, particularly in the mice treated under the preventive condition.

Evaluating the Usefulness of the ICT Tuberculosis Test Kit for the Diagnosis of Tuberculosis (결핵 진단에서 ICT Tuberculosis Test Kit의 효용성)

  • Chang, Chul-Hun;Son, Han-Chul;Ryu, Ki-Chan;Park, Soon-Kew;Lee, Seon-Ho;Kim, Sung-Ryul;Park, Ki-Hyung;Kim, Woo-Seok;Koo, Kyong-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.46 no.4
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    • pp.473-480
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    • 1999
  • Background: Early diagnosis of tuberculosis is critical, especially in Korea, an area where tuberculosis is endemic. Because antibody responses to some membrane proteins of Mycobacterium tuberculosis are not comparable, and the policy of BCG vaccination and the prevalence of tuberculosis are different from country to country, the usefulness of the serological diagnostic tests is questionable in Korea, even though they have been confirmed to be useful in other countries. In the specific context of Korea, we tried to evaluate the validity of the ICT Tuberculosis Test (ICT), a membrane-based antibody kit that purports to detect the 5 M. tuberculosis complex-specific antigens including 38-kDa protein. Method: 68 patients with tuberculosis were tested : 37 had no history of previous tuberculosis, and 31 were reactivated cases. The control group comprised 77 subjects : 25 healthy adults, 35 hospital workers with frequent contact with tuberculosis patients, and 17 in-patients with non-tuberculous respiratory diseases. Results: The diagnostic sensitivities of the ICT were 87% and 73% in patients with versus without previous history of tuberculosis, respectively. The sensitivities of smear-positive and smear-negative patient groups were 81% and 73%, respectively. Both of the two patients with extrapulmonary tuberculosis tested positive through the ICT. The specificities of the ICT were 88%, 94%, and 94% in healthy adults, hospital workers, and non-tuberculous patients, respectively, with an overall specificity of 92%. Conclusion: It is suggested that when combined with traditional techniques, the ICT is an useful tool for the diagnosis of pulmonary tuberculosis. The procedure is simple, easy to perform, rapid, and needs no equipment. It shows 73% sensitivity and 92% specificity for the diagnosis of tuberculosis.

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Anti-inflammatory Effect of Injinho-tang in RAW 264.7 Cells (마우스 대식세포인 RAW 264.7 세포에서 인진호탕(茵陳蒿湯)의 항염증 효과)

  • Yun, Hyun-Jeong;Heo, Sook-Kyoung;Yi, Hyo-Seung;Kim, Chang-Hyun;Kim, Byung-Wan;Park, Sun-Dong
    • The Korea Journal of Herbology
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    • v.23 no.2
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    • pp.169-178
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    • 2008
  • Objectives : Inflammation is important event in the development of vascular diseases including hypertension, atherosclerosis, and restenosis. Injinho-tang(IJHT) has been used as a traditional Korean herbal medicine since ancient times, and today it is widely used as a medication for jaundice associated with inflammation of the liver. The aim of this study was to determine whether IJHT and its components inhibit production of nitrite, an index of NO, and proinflammatory cytokines in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Methods : Cytotoxic activity of IJHT and its components on RAW 264.7 cells was using 5-(3-caroboxymeth-oxyphenyl)-2H-tetra-zolium inner salt (MTS) assay. The nitric oxide (NO) production was measured by Griess reagent system. And proinflammatory cytokines were measured by ELISA kit. The levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression were detected by western blot. Results : IJHT and its components significantly inhibited the LPS-induced NO production and iNOS expression accompanied by an attenuation of tumor necrosis factor-alpha (TNF-${\alpha}$), interleukin-6 (1L-6), IL-$1{\beta}$ and monocyte chemoattractant protein-1 (MCP-1) formation in macrophages. Conclusions : IJHT and its components inhibit LPS-induced inflammation via decreasing cytokines production. These results indicate that IJHT and its components have potential as an anti-inflammation and anti-artherosclerosis agent.

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Evaluation of Recombinant SAG1, SAG2, and SAG3 Antigens for Serodiagnosis of Toxoplasmosis

  • Khanaliha, Khadijeh;Motazedian, Mohammad Hossein;Kazemi, Bahram;Shahriari, Bahador;Bandehpour, Mojgan;Sharifniya, Zarin
    • Parasites, Hosts and Diseases
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    • v.52 no.2
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    • pp.137-142
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    • 2014
  • Serologic tests are widely accepted for diagnosing Toxoplasma gondii but purification and standardization of antigen needs to be improved. Recently, surface tachyzoite and bradyzoite antigens have become more attractive for this purpose. In this study, diagnostic usefulness of 3 recombinant antigens (SAG1, SAG2, and SAG3) were evaluated, and their efficacy was compared with the available commercial ELISA. The recombinant plasmids were transformed to JM109 strain of Escherichia coli, and the recombinants were expressed and purified. Recombinant SAG1, SAG2, and SAG3 antigens were evaluated using different groups of sera in an ELISA system, and the results were compared to those of a commercial IgG and IgM ELISA kit. The sensitivity and specificity of recombinant surface antigens for detection of anti-Toxoplasma IgG in comparison with commercially available ELISA were as follows: SAG1 (93.6% and 92.9%), SAG2 (100.0% and 89.4%), and SAG3 (95.4% and 91.2%), respectively. A high degree of agreement (96.9%) was observed between recombinant SAG2 and commercial ELISA in terms of detecting IgG anti-Toxoplasma antibodies. P22 had the best performance in detecting anti-Toxoplasma IgM in comparison with the other 2 recombinant antigens. Recombinant SAG1, SAG2, and SAG3 could all be used for diagnosis of IgG-specific antibodies against T. gondii.

Identification of specifically activated angiogenic molecules in HMGB-1-induced angiogenesis

  • Kim, Won Kyu;Kwon, Yujin;Park, Minhee;Yun, Seongju;Kwon, Ja-Young;Kim, Hoguen
    • BMB Reports
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    • v.50 no.11
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    • pp.590-595
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    • 2017
  • High-mobility group box-1 (HMGB-1) is expressed in almost all cells, and its dysregulated expression correlates with inflammatory diseases, ischemia, and cancer. Some of these conditions accompany HMGB-1-mediated abnormal angiogenesis. Thus far, the mechanism of HMGB-1-induced angiogenesis remains largely unknown. In this study, we performed time-dependent DNA microarray analysis of endothelial cells (ECs) after HMGB-1 or VEGF treatment. The pathway analysis of each gene set upregulated by HMGB-1 or VEGF showed that most HMGB-1-induced angiogenic pathways were also activated by VEGF, although the activation time and gene sets belonging to the pathways differed. In addition, HMGB-1 upregulated some VEGFR signaling-related angiogenic factors including EGR1 and, importantly, novel angiogenic factors, such as ABL2, CEACAM1, KIT, and VIPR1, which are reported to independently promote angiogenesis under physiological and pathological conditions. Our findings suggest that HMGB-1 independently induces angiogenesis by activating HMGB-1-specific angiogenic factors and also functions as an accelerator for VEGF-mediated conventional angiogenesis.

Protective Effect of PineXol® against Amyloid-β-induced Cell Death (아밀로이드 베타로 유도된 신경세포 사멸에 대한 PineXol®의 보호효과)

  • Han, Kyung-Hoon;Lee, Seung-Hee;Park, Kwang-Sung;Song, Kwan-Young;Kim, Jung-Hee;Park, Eun-Kuk;Han, Sung-Hee
    • The Korean Journal of Food And Nutrition
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    • v.30 no.6
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    • pp.1279-1285
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    • 2017
  • $Amyloid-{\beta}$ protein ($A{\beta}$) is known to increase free radical production in neuronal cells, leading to cell death by oxidative stress. The purpose of this study was to evaluate the protective effects of $PineXol^{(R)}$ on $A{\beta}_{25-35}$ induced neuronal cell death. Rat pheochromocytoma (PC-12) cells were pre-treated with $100{\mu}g/mL$ of $PineXol^{(R)}$ for 2 h. The cells were exposed to single dose of $30{\mu}M$ $A{\beta}_{25-35}$ for 24 h. Cell death was assessed by a cell count kit-8 (CCK-8) assay, lactate and dehydrogenase (LDH) release assay. An Apoptotic process was analyzed by a protein expression of the Bcl-2 family using western blotting. Cell viability increased in PC-12 cells treated with both $A{\beta}_{25-35}$ and $PineXol^{(R)}$, compared to the control group. $PineXol^{(R)}$ induced a decrease of the Bcl-2 protein expression (p<0.05), while Bax and Sod1 increased (p<0.05), indicating attenuation of $A{\beta}_{25-35}$ induced apoptosis. These results suggest that $PineXol^{(R)}$ may be a good candidate for the prevention of Alzheimer's disease(AD).

Efficacy of Serum PIVKA-II in the Diagnosis and Follow-up after Treatment of Hepatocellular Carcinoma

  • Lee, Sang-Hee;Gu, Gum-Gyoung;Han, Tae-Jin;Paik, Byung-Yoon;Chun, Sail;Min, Won-Ki
    • Korean Journal of Clinical Laboratory Science
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    • v.43 no.4
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    • pp.150-155
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    • 2011
  • It is a very important diagnosis and evalution of Hepatocellular carcinoma (HCC) in Korea where hepatitis B-virus is endemic. Protein induced by vitamin K absence or antagonist II (PIVKA-II) appears to be a useful tumor marker. This study was purposed to investigate usefulness of PIVKA-II in the diagnosis and fallow-up after treatment of HCC. A total of 418 patients were included in 187 patients (44.7%) of HCC, 83 patients (19.9%) of liver cirrhosis, 74 patients (17.7%) of chronic hepatitis and 74 patients (17.7%) of other liver diseases with serum PIVKA-II levels by Hicatch PIVKA-II kit. PIVKA-II level were analysed for difference of groups and the comparison of treatment responses. The sensitivity and specificity of PIVKA-II in the diagnosis of HCC were 80.2%, 87.0% at the cut-off value of 40 mAU/mL. There were statistically significant difference between the HCC and other groups (p<0.001), before and after PIVKA-II levels after treatment in HCC (p<0.001). PIVKA-II can be used as a useful tumor marker for patients with HCC, especially early diagnosis in high risk groups, treatment response assesment and monitoring of recurrence.

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Study on the Protective Mechanism of Vitamin C in the SH-SY5Y Cell Death Induced by the Streptozotocin (스트렙토조토신으로 유도된 신경세포사멸에서 비타민 C의 보호 기전 연구)

  • Lee, Seung-Hee;Han, Kyung-Hoon;Kim, Hyun-Jun;Park, Kwang-Sung;Han, Sung-Hee;Kim, Jung-Hee;Heo, Jae-Hyeok
    • The Korean Journal of Food And Nutrition
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    • v.31 no.4
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    • pp.457-463
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    • 2018
  • In this study, we analyzed the protective effects of the vitamin C in the streptozotocin (STZ)-induced apoptosis using the SH-SY5Y, a neuroblastoma cell line. The cells were pretreated with the vitamin C ($100{\mu}g$) for 30 min, followed by the 24-hr treatment with the 2.5-mM STZ. The cell-viability assay using the Cell Counting Kit (CCK)-8 revealed the cell-survival rate increased by 15% following the vitamin-C pretreatment compared to the STZ-only treatment. Moreover, we conducted the western-blot analysis to determine the protective effect of the vitamin C regarding the apoptosis. Compared to those in the STZ-only-treatment group, the p-ERK and Bcl-2 expressions increased in the vitamin-C-pretreatment group, whereas the p-JNK and Bax expressions decreased. The vitamin-C pretreatment increased the expression of the SOD-1, an antioxidant enzyme, by more than 30%, indicating its protective role in the STZ-induced oxidative stress. Also, we found both the intrinsic- and extrinsic-pathway mechanisms of the STZ-induced apoptosis. The results of this study $s{\mu}ggest$ vitamin C may help prevent the neurodegenerative diseases.

Comparative Serum Proteomic Analysis of Serum Diagnosis Proteins of Colorectal Cancer Based on Magnetic Bead Separation and MALDI-TOF Mass Spectrometry

  • Deng, Bao-Guo;Yao, Jin-Hua;Liu, Qing-Yin;Feng, Xian-Jun;Liu, Dong;Zhao, Li;Tu, Bin;Yang, Fan
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.6069-6075
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    • 2013
  • Background: At present, the diagnosis of colorectal cancer (CRC) requires a colorectal biopsy which is an invasive procedure. We undertook this pilot study to develop an alternative method and potential new biomarkers for diagnosis, and validated a set of well-integrated tools called ClinProt to investigate the serum peptidome in CRC patients. Methods: Fasting blood samples from 67 patients diagnosed with CRC by histological diagnosis, 55 patients diagnosed with colorectal adenoma by biopsy, and 65 healthy volunteers were collected. Division was into a model construction group and an external validation group randomly. The present work focused on serum proteomic analysis of model construction group by ClinProt Kit combined with mass spectrometry. This approach allowed construction of a peptide pattern able to differentiate the studied populations. An external validation group was used to verify the diagnostic capability of the peptidome pattern blindly. An immunoassay method was used to determine serum CEA of CRC and controls. Results: The results showed 59 differential peptide peaks in CRC, colorectal adenoma and health volunteers. A genetic algorithm was used to set up the classification models. Four of the identified peaks at m/z 797, 810, 4078 and 5343 were used to construct peptidome patterns, achieving an accuracy of 100% (> CEA, P<0.05). Furthermore, the peptidome patterns could differentiate the validation group with high accuracy close to 100%. Conclusions: Our results showed that proteomic analysis of serum with MALDI-TOF MS is a fast and reproducible approach, which may provide a novel approach to screening for CRC.

Induction of Apoptosis in Human Leukemic Cell Lines by Diallyl Disulfide via Modulation of EGFR/ERK/PKM2 Signaling Pathways

  • Luo, Nian;Zhao, Lv-Cui;Shi, Qing-Qiang;Feng, Zi-Qiang;Chen, Di-Long;Li, Jing
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.8
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    • pp.3509-3515
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    • 2015
  • Background: Diallyl disulfide (DADS) may exert potent anticancer action both in vitro and in vivo. Although its effects on cancer are significant, the underlying mechanisms remain unknown. In this study, we sought to elucidate possible links between DADS and pyruvate kinase (PKM2). Materials and Methods: $KG1{\alpha}$, a leukemia cell line highly expressing PKM2 was used with a cell counting kit (CCK)-8 and flow cytometry (FCM) to investigate the effects of DADS. Relationships between PKM2 and DADS associated with phosphorylation of EGFR, ERK1/2 and MEK, were assessed by western blot analysis. Results: In $KG1{\alpha}$ cells highly expressing PKM2, we found that DADS could affect proliferation, apoptosis and EGFR/ERK/PKM2 signaling pathways, abrogating EGF-induced nuclear accumulation of PKM2. Conclusions: These results suggested that DADS suppressed the proliferation of $KG1{\alpha}$ cells, providing evidence that its proapoptotic effects are mediated through the inhibition of EGFR/ERK/PKM2 signaling pathways.