• Journal of Microbiology and Biotechnology
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• v.31 no.11
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• pp.1576-1582
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• 2021

Bacterial β-glucuronidase in the intestine is involved in the conversion of 7-ethyl-10-hydroxycamptochecin glucuronide (derived from irinotecan) to 7-ethyl-10-hydroxycamptothecin, which causes intestinal bleeding and diarrhea (side effects of anti-cancer drugs). Twelve compounds (1-12) from Polygala tenuifolia were evaluated in terms of β-glucuronidase inhibition in vitro. 4-O-Benzoyl-3'-O-(O-methylsinapoyl) sucrose (C3) was highly inhibitory at low concentrations. C3 (an uncompetitive inhibitor) exhibited a k_i value of 13.4 μM; inhibitory activity increased as the substrate concentration rose. Molecular simulation revealed that C3 bound principally to the Gln158-Tyr160 enzyme loop. Thus, C3 will serve as a lead compound for development of new β-glucuronidase inhibitors.

• Genomics & Informatics
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• v.19 no.1
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• pp.7.1-7.13
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• 2021

Levodopa (L-DOPA) therapy is normally practised to treat motor pattern associated with Parkinson disease (PD). Additionally, several inhibitory drugs such as Entacapone and Opicapone are also cosupplemented to protect peripheral inactivation of exogenous L-DOPA (~80%) that occurs due to metabolic activity of the enzyme catechol-O-methyltransferase (COMT). Although, both Entacapone and Opicapone have U.S. Food and Drug Administration approval but regular use of these drugs is associated with high risk of side effects. Thus, authors have focused on in silico discovery of phytochemicals and evaluation of their effectiveness against human soluble COMT using virtual screening, molecular docking, drug-like property prediction, generation of pharmacophoric property, and molecular dynamics simulation. Overall, study proposed, nine phytochemicals (withaphysalin D, withaphysalin N, withaferin A, withacnistin, withaphysalin C, withaphysalin O, withanolide B, withasomnine, and withaphysalin F) of plant Withania somnifera have strong binding efficiency against human COMT in comparison to both of the drugs i.e., Opicapone and Entacapone, thus may be used as putative bioenhancer in L-DOPA therapy. The present study needs further experimental validation to be used as an adjuvant in PD treatment.

• Molecules and Cells
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• v.45 no.12
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• pp.869-876
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• 2022

Methylglyoxal (MG) is a dicarbonyl compound formed in cells mainly by the spontaneous degradation of the triose phosphate intermediates of glycolysis. MG is a powerful precursor of advanced glycation end products, which lead to strong dicarbonyl and oxidative stress. Although divergent functions of MG have been observed depending on its concentration, MG is considered to be a potential antitumor factor due to its cytotoxic effects within the oncologic domain. MG detoxification is carried out by the glyoxalase system. Glyoxalase 1 (Glo1), the ubiquitous glutathionedependent enzyme responsible for MG degradation, is considered to be a tumor promoting factor due to it catalyzing the removal of cytotoxic MG. Indeed, various cancer types exhibit increased expression and activity of Glo1 that closely correlate with tumor cell growth and metastasis. Furthermore, mounting evidence suggests that Glo1 contributes to cancer stem cell survival. In this review, we discuss the role of Glo1 in the malignant progression of cancer and its possible use as a promising therapeutic target for tumor therapy. We also summarize therapeutic outcomes of Glo1 inhibitors as prospective treatments for the prevention of cancer.

• Journal of Medicine and Life Science
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• v.19 no.3
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• pp.79-89
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• 2022

Whereas systolic blood pressure (SBP) continuously rises with age, diastolic blood pressure (DBP) gradually decreases after the age of 55 years. Therefore, hypertension in the elderly shows the pattern of isolated systolic hypertension. There is evidence on the benefits of controlling blood pressure (BP) in elderly patients with hypertension. The BP lowering effect has also been demonstrated in patients over 80 years of age with hypertension. The BP threshold for the initiation of antihypertensive drug treatment for older adults with hypertension is gradually decreasing. The antihypertensive treatment is recommended if, despite therapeutic lifestyle modifications, SBP ≥140 mmHg or DBP ≥90 mmHg in those aged 65-79 years old, and SBP ≥140-160 mmHg or DBP ≥90 mmHg in those aged ≥80 years old. Although there is no consensus on the target BP for older adults with hypertension, a target SBP of <130-140 mmHg and DBP of <80-90 mmHg are recommended. In older adults over 80 years of age with hypertension, the target SBP is <140-150 mmHg. When the dose of antihypertensive drugs is increased to reach the target SBP, DBP may decrease to less than 70 mmHg, but it should not be <60 mmHg. Thiazide diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers can be selected as the first-line drug for older adults with hypertension. Beta-blockers may be selected in case of compelling indications.

• Childhood Kidney Diseases
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• v.27 no.2
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• pp.121-126
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• 2023

The administration of angiotensin type 2 receptor blockers (ARBs) during pregnancy is known to cause ARB fetopathy, including renal insufficiency. We aimed to analyze the outcomes of two patients who survived ARB fetopathy and perform an accompanying literature review. Case 1 was exposed antenatally from a gestational age of 30 weeks to valsartan because of maternal pregnancy-induced hypertension. The patient presented with oliguria immediately after birth, and renal replacement therapy was administered for 24 days. Seven years after birth, renal function was indicative of stage 2 chronic kidney disease (CKD) with impaired urinary concentration. Case 2 had a maternal history of hypertension and transient ischemic attack and was treated with olmesartan until 30 weeks of pregnancy. Renal replacement therapy was performed for 4 days since birth. After 8 years, the patient is with CKD stage 2, with intact tubular function. Recent reports suggest that ARB fetopathy might manifest as renal tubular dysgenesis and nephrogenic diabetes insipidus, in contrast to mild alterations of glomerular filtration. Tubular dysfunction may induce CKD progression and growth retardation. Patients with ARB fetopathy should be monitored until adulthood. The ARB exposure period might be a critical factor in determining the severity and manifestations of fetopathy.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2020.12a
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• pp.3-13
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• 2020

Pseudomonas aeruginosa is a ubiquitous gram-negative bacterium causing serious infections. The P. aeruginosa T3SS is a syringe-like apparatus on the bacterial surface, with 4 effector toxins: ExoS, ExoT, ExoY, and ExoU. Here, we investigated the effect of ExoS and ExoT of the T3SS of P. aeruginosa K strain (PAK). The type three secretion system (T3SS) is a major virulence system of Pseudomonas aeruginosa (P. aeruginosa). The effector protein Exotoxin S (ExoS) produced by P. aeruginosa is secreted into the host cells via the T3SS. For the purpose of screening the inhibitors with regard to ExoS secretion, we developed the sandwich-type enzyme-linked immunosorbent assay (ELISA) system. PAK clinical strains induce proinflammatory cytokine production through the T3SS, and this involves NF-κB activation in pneumonia mouse models. We tried to confirm the role of the NF-κB transcription factor in ExoS- and ExoT-induced pneumonia mouse models. pro-inflammatory cytokines induction in response to ExoS and ExoT infection relied on NF-κB activation. Our findings highlight the roles of natural poduct in inhibiting proinflammatory cytokine expression during ExoS and ExoT exposure in PAK infections, paving the way for a novel therapeutic approach for the treatment of pulmonary infections.

• Journal of agricultural medicine and community health
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• v.22 no.1
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• pp.61-74
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• 1997

In case of tissue invading nematode, proteolytic enzyme was required at their parasitic life. Proteinases obtained from these parasites(Toxocara canis, Ansakis spp. and Trichinella spiralis) were extracted, isolated and further purified. And then the analysis for activity and inhibitory effect of proteinases were performed by appropriate substrate. Determination of protein as a circulating antigen was done in use of infected animal serum with above parasites, respectively. For above experimental objects, following procedures were performed. First, enzymatic activity was measured in use of azocasein and inhibitory effect of porteinase were studied by various inhibitors. Second, partially purified proteins containing enzymatic activity were obtained by ion exchange chromatography, ultrafiltration and electrophoretic elution. Third, role of the partially purified protein as a circulating antigen. The results obtained were as follows : 1. Enzymatic activity of each nematode proteinase was varied according to pH. Optimal pH of Toxocara canis, Ansakis spp. and Trichinella spiralis were pH 6.0, pH 5.5 and pH 6.5, respectively. The optimal molarity of buffer was 0.1M phosphate buffer. Although little difference between these proteinases was observed, temperature stability was at least maintained at $4^{\circ}C$ until 5 days. 2. In case of Ansakis spp. and Toxocara canis, enzymatic activity of these proteinases was considerably inhibited by Leupeptin and EDTA. For maximum enzymatic activity of above proteinases, it was required that cysteine residue of enzyme should be protected. And it was suggested that metallo type was contained in enzyme active site. Proteinase of Trichinella spiralis contained metallo type also. 3. Although partial purification was performed in Ansakis spp. and Toxocara canis, proteins maintaining enzymatic activity were identified as a circulating antigen. From SDS-PAGE and immunoblot, 25 kDa was presented in Ansakis spp.. Specific antigen of Toxocara cains was 110 kDa protein fraction. 55 and 42 kDa proteins were reacted with normal serum. Trichinella spiralis 60 kDa protein fraction was successfully purified from excretory materials in culture. As a result of immune-reaction with Trichinella spiralis infected serum, highly purified 60 kDa protein was maintained antigenicity until final purification step.

• The Korean Journal of Mycology
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• v.15 no.1
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• pp.29-37
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• 1987

Cellulolytic mocrooganisms were isolated from the cellulose-cultural properties. Among them, Aspergillus clavatus with the highest cellulase activity was identified by the morphological characteristics and it's enzyme activities were compared on the various cultural conditions. It was found that the induction of carboxymethylcellulase(CMCase), avicelase and salicinase in CMC liquid media showed the highest enzyme acitivity on five day's cultivation at $30^{\circ}C$ and thereafter their activities were gradually decreased with time. After crude extracellular enzymes precipitated with the 70% saturated ammonium sulfate solution were dialyzed with 20 mM acetate buffer pH 6.0, each crude enzyme was examined. The optimal activities of CMCase and avicelase were both found to be at $50^{\circ}C$ and pH 6.0. Their thermal stability was appeared at the $50^{\circ}C$. CMCase and avicelase had the maxima activities with 1.5% and 2.2% substrate concentration, respectively. The concentration of 5 mM $Mg^{++}$ or $Ca^{++}$ was found to have a maximum cellulase activity and its activity was inhibited with more than 5 mM $Cu^{++}$ and $Zn^{++}$ concentration. Cellulase activity was also inhibited sensitively by the inhibitors such as 2-mercaptoethanol, iodine and sodium azide.

• Biomedical Science Letters
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• v.6 no.3
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• pp.209-221
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• 2000

The purpose of this study was to investigate the practical availability of pretense production that can be used at home after isolating Serratia sp.2000-1 which produced extracellular pretense from clinical specimen. Basic production conditions and partial enzymatic characteristics of pretense produced by Serratia sp. 2000-1 was as follows: The kind and concentration of carbohydrate, nitrogen and metal salts for optimal enzyme production condition were each identified as the concentration of 1.5% glucose, 2.0% CSP, and 0.1% CaCl$_2$, and the optimal temperature, time and initial pH for culture were each 3$0^{\circ}C$, 72 hours, and pH 8.0. The final enzymatic yeild that was purified by 3 steps with ammonium sulfate precipitation (45~80%), DEAE-cellulose column chromatography, and Sephadex G-200 gel chromatography was 14.4%, and enzyme inactivity rate increased approximately 291314s. The optimal temperature and pH for purified pretense activity were 35$^{\circ}C$ and pH 7.0~8.0, and purified pretense activity was relatively stable by 4$0^{\circ}C$ at pH 6~10 for 30 min, however heating at 6$0^{\circ}C$ for 30 min, it liminated detectable pretense activity. The pretense activity was activated by $Mg^{2+}$, $Ba^{2+}$, $Ca^{2+}$, Mn$^{2+}$, but inactiviaed by Hg$^{2+}$, Ag$^{2+}$, Cu$^{2+}$, and the pretense activity was inhibited strongly by SDS among enzyme activity inhibitors. Further study is required to evaluate the practical availability of pretense production that can be used at home by isolating Serratia sp. from more clinical specimen and examining pretense more in details.

• Applied Biological Chemistry
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• v.42 no.4
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• pp.310-316
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• 1999

BBPI contents in domestic soybean and soybean products were investigated by the measurement of chymotrypsin inhibiting activity(C.I.A) and competitive ELISA method. In order to produce polyclonal antibody, BBPI was purified from soybean trypsin-chymotrypsin inhibitor by ion exchange chromatography and electrophoretic gel slicing. Rabbit anti-BBPI polyclonal antibody was produced with the purified BBPI as immunogen. This antibody showed relatively specific binding to BBPI and then used for the establishment of competitive ELISA method to measure BBPI contents in extracts of soybean and soybean products. The standard curve for the measurement of BBPI in soybean extracts was drawn up within the range 0.03 to $30\;{\mu}g/ml$ of BBPI. The C.I.A. and BBPI contents of 12 soybean cultivars were $8,462{\sim}12,428\;U/g$ and $482{\sim}692\;mg%$, respectively. The C.I.A. and BBPI contents were not detected in most of soybean products except soybean sprouts, which contained $10,695{\sim}13,249\;U/g$ of C.I.A. and $529{\sim}803\;mg%$ of BBPI.