• 제목/요약/키워드: New drugs

검색결과 976건 처리시간 0.037초

Transcriptome sequencing revealed the inhibitory mechanism of ketoconazole on clinical Microsporum canis

  • Wang, Mingyang;Zhao, Yan;Cao, Lingfang;Luo, Silong;Ni, Binyan;Zhang, Yi;Chen, Zeliang
    • Journal of Veterinary Science
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    • 제22권1호
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    • pp.4.1-4.13
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    • 2021
  • Background: Microsporum canis is a zoonotic disease that can cause dermatophytosis in animals and humans. Objectives: In clinical practice, ketoconazole (KTZ) and other imidazole drugs are commonly used to treat M. canis infection, but its molecular mechanism is not completely understood. The antifungal mechanism of KTZ needs to be studied in detail. Methods: In this study, one strain of fungi was isolated from a canine suffering with clinical dermatosis and confirmed as M. canis by morphological observation and sequencing analysis. The clinically isolated M. canis was treated with KTZ and transcriptome sequencing was performed to identify differentially expressed genes in M. canis exposed to KTZ compared with those unexposed thereto. Results: At half-inhibitory concentration (½MIC), compared with the control group, 453 genes were significantly up-regulated and 326 genes were significantly down-regulated (p < 0.05). Quantitative reverse transcription polymerase chain reaction analysis verified the transcriptome results of RNA sequencing. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the 3 pathways of RNA polymerase, steroid biosynthesis, and ribosome biogenesis in eukaryotes are closely related to the antifungal mechanism of KTZ. Conclusions: The results indicated that KTZ may change cell membrane permeability, destroy the cell wall, and inhibit mitosis and transcriptional regulation through CYP51, SQL, ERG6, ATM, ABCB1, SC, KER33, RPA1, and RNP genes in the 3 pathways. This study provides a new theoretical basis for the effective control of M. canis infection and the effect of KTZ on fungi.

골다공증 다빈도 처방과 구성 약물의 네트워크 분석 - 오아시스 검색을 중심으로 (Network Analysis of Herbs that are Frequently Prescribed for Osteoporosis with a Focus on Oasis Platform Research)

  • 신선미;고흥
    • 대한한방내과학회지
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    • 제42권4호
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    • pp.628-644
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    • 2021
  • Objectives: This study analyzed, through network analysis and data mining analysis, the relationship between herbs used in osteoporosis prescriptions, diversified the analysis of osteoporosis-related prescriptions, and analyzed the combination of herbs used in osteoporosis-related prescriptions. Methods: The prescriptions used in osteoporosis treatment and experiments were established by conducting a full survey of the papers published by the OASIS site. A database for osteoporosis-related prescriptions was established, herbs were extracted, and the frequency of frequent herbs and prescriptions were investigated using Excel (MS offices ver. 2013). Using the freeware R version 4.0.3 (2020-10-10), igraph, and arules package, network analysis was performed in the first second of prescription composition. Results: Among the osteoporosis-related prescriptions, the most studied prescriptions are as follows.: Yukmijihwang-tang (六味地黃湯) and Samul-tang (四物湯). In the osteoporosis prescription network, herbs with connection centrality, proximity centrality, mediation centrality, and eigenvector centrality appeared in the order of Rehmanniae Radix Preparata, Angelicae Gigantis Radix, Poria Sclerotium, Paeoniae Radix, and Glycyrrhizae Radix et Rhizoma. After extracting the herbal combination network, including the corresponding herbs, and clustering it, it can be divided into drugs of the Yukmijihwang-tang (六味地黃湯) series and the Samul-tang (四物湯). Conclusions: This study could assist researchers in diversifyingy formula analysis in future studies. Moreover, the herbal combination used in osteoporosis prescriptions could be used to search for osteoporosis prescriptions in other databases or to create a new prescription.

Functional Prediction of Hypothetical Proteins from Shigella flexneri and Validation of the Predicted Models by Using ROC Curve Analysis

  • Gazi, Md. Amran;Mahmud, Sultan;Fahim, Shah Mohammad;Kibria, Mohammad Golam;Palit, Parag;Islam, Md. Rezaul;Rashid, Humaira;Das, Subhasish;Mahfuz, Mustafa;Ahmeed, Tahmeed
    • Genomics & Informatics
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    • 제16권4호
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    • pp.26.1-26.12
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    • 2018
  • Shigella spp. constitutes some of the key pathogens responsible for the global burden of diarrhoeal disease. With over 164 million reported cases per annum, shigellosis accounts for 1.1 million deaths each year. Majority of these cases occur among the children of the developing nations and the emergence of multi-drug resistance Shigella strains in clinical isolates demands the development of better/new drugs against this pathogen. The genome of Shigella flexneri was extensively analyzed and found 4,362 proteins among which the functions of 674 proteins, termed as hypothetical proteins (HPs) had not been previously elucidated. Amino acid sequences of all these 674 HPs were studied and the functions of a total of 39 HPs have been assigned with high level of confidence. Here we have utilized a combination of the latest versions of databases to assign the precise function of HPs for which no experimental information is available. These HPs were found to belong to various classes of proteins such as enzymes, binding proteins, signal transducers, lipoprotein, transporters, virulence and other proteins. Evaluation of the performance of the various computational tools conducted using receiver operating characteristic curve analysis and a resoundingly high average accuracy of 93.6% were obtained. Our comprehensive analysis will help to gain greater understanding for the development of many novel potential therapeutic interventions to defeat Shigella infection.

Spinal Hydatid Cyst Disease : Challenging Surgery - an Institutional Experience

  • Caglar, Yusuf Sukru;Ozgural, Onur;Zaimoglu, Murat;Kilinc, Cemil;Eroglu, Umit;Dogan, Ihsan;Kahilogullari, Gokmen
    • Journal of Korean Neurosurgical Society
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    • 제62권2호
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    • pp.209-216
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    • 2019
  • Objective : Hydatid cyst disease is caused by the parasite Echinococcus granulosus. It is rarely seen in the vertebral system, occurring at a rate of 0.2-1%. The aim of this study is to present 12 spinal hydatid cyst cases, and propose a new type of drainage of the cyst. Methods : Twelve cases of spinal hydatid cysts, surgical operations, multiple operations, chronic recurrences, and spinal hydatic cyst excision methods are discussed in the context of the literature. Patients are operated between 2005 and 2016. All the patients are kept under routine follow up. Patient demographic data and clinicopathologic characteristics are examined. Results : Six male and six female patients with a median age of 38.6 at the time of surgery were included in the study. Spinal cyst hydatid infection sites were one odontoid, one cervical, five thoracic, two lumbar, and three sacral. In all cases, surgery was performed, with the aim of total excision of the cyst, decompression of the spinal cord, and if necessary, stabilization of the spinal column. Mean follow up was 61.3 months (10-156). All the patients were prescribed Albendazole. Three patients had secondary hydatid cyst infection (one lung and two hepatic). Conclusion : The two-way drainage catheter placed inside a cyst provides post-operative chlorhexidine washing inside the cavity. Although a spinal hydatid cyst is a benign pathology and seen rarely, it is extremely difficult to achieve a real cure for patients with this disease. Treatment modalities should be aggressive and include total excision of cyst without rupture, decompression of spinal cord, flushing of the area with scolicidal drugs, and ensuring spinal stabilization. After the operation the patients should be kept under routine follow up. Radiological and clinical examinations are useful in spotting a recurrence.

Reverting Gene Expression Pattern of Cancer into Normal-Like Using Cycle-Consistent Adversarial Network

  • Lee, Chan-hee;Ahn, TaeJin
    • International Journal of Advanced Culture Technology
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    • 제6권4호
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    • pp.275-283
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    • 2018
  • Cancer show distinct pattern of gene expression when it is compared to normal. This difference results malignant characteristic of cancer. Many cancer drugs are targeting this difference so that it can selectively kill cancer cells. One of the recent demand for personalized treating cancer is retrieving normal tissue from a patient so that the gene expression difference between cancer and normal be assessed. However, in most clinical situation it is hard to retrieve normal tissue from a patient. This is because biopsy of normal tissues may cause damage to the organ function or a risk of infection or side effect what a patient to take. Thus, there is a challenge to estimate normal cell's gene expression where cancers are originated from without taking additional biopsy. In this paper, we propose in-silico based prediction of normal cell's gene expression from gene expression data of a tumor sample. We call this challenge as reverting the cancer into normal. We divided this challenge into two parts. The first part is making a generator that is able to fool a pretrained discriminator. Pretrained discriminator is from the training of public data (9,601 cancers, 7,240 normals) which shows 0.997 of accuracy to discriminate if a given gene expression pattern is cancer or normal. Deceiving this pretrained discriminator means our method is capable of generating very normal-like gene expression data. The second part of the challenge is to address whether generated normal is similar to true reverse form of the input cancer data. We used, cycle-consistent adversarial networks to approach our challenges, since this network is capable of translating one domain to the other while maintaining original domain's feature and at the same time adding the new domain's feature. We evaluated that, if we put cancer data into a cycle-consistent adversarial network, it could retain most of the information from the input (cancer) and at the same time change the data into normal. We also evaluated if this generated gene expression of normal tissue would be the biological reverse form of the gene expression of cancer used as an input.

Effect of fractional ablative carbon dioxide laser with lidocaine spray on skin flap survival in rats

  • Choi, Manki;Park, Youngsoo;Kim, Yong-Ha;Chung, Kyu Jin
    • 대한두개안면성형외과학회지
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    • 제20권4호
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    • pp.239-245
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    • 2019
  • Background: Lidocaine spray is a local anesthetic that improves random-pattern skin flap survival. The fractional ablative carbon dioxide laser (FxCL) produces vertical microchannels that delivers topically applied drugs to the skin. In this study, we hypothesized that FxCL therapy would enhance the lidocaine effect to improve random-pattern skin flap survival in rats. Methods: McFarlane random-pattern skin flaps were elevated in 48 rats, which were divided into four groups according to treatment: FxCL+lidocaine, FxCL, lidocaine, and nontreatment (control). On postoperative day 7, necrotic flap areas, the number of capillary vessels, and neutrophil count were evaluated. Anti-rat vascular endothelial growth factor (VEGF) and CD31 antibody activity were also evaluated by immunohistochemical staining. Results: Flap survival rate was $53.41%{\pm}5.43%$, $58.16%{\pm}4.80%$, $57.08%{\pm}5.91%$, and $69.08%{\pm}3.20%$ in the control, lidocaine, FxCL, and FxCL+lidocaine groups, respectively. Mean neutrophil count in the intermediate zone excluding the necrotic tissue was $41.70{\pm}8.40$, $35.43{\pm}6.41$, $37.23{\pm}7.15$, and $27.20{\pm}4.24cells/field$ in the control, lidocaine, FxCL, and FxCL+lidocaine groups, respectively. Anti-rat VEGF and CD31 antibody activity were the highest in the FxCL+lidocaine group. Conclusion: FxCL with lidocaine had a positive effect on random-pattern skin flap survival in rats. Thus, FxCL with lidocaine spray should be considered as a new treatment option to improve flap viability.

삼신환(三神丸) 에탄올 추출물(SSH)의 MRSA에 대한 항균활성 연구 (A study on Antibacterial Activity of Samsinhwan Ethanol Extract against MRSA)

  • 우학식;이영주
    • 디지털융복합연구
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    • 제17권8호
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    • pp.271-282
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    • 2019
  • 이번 연구의 목적은 MRSA에 대하여 삼신환(三神丸)의 항균효과와 기존 항생제인 Oxacillin과 Ciprofloxacin과의 synergy effect를 확인하고 그 기전을 밝히는 것이다. 이에 삼신환(三神丸)의 Disc 확산 실험 및 최소억제농도(MIC)를 측정하여 MARA에 대한 항균 활성 및 활성농도를 검증하고, 항생제와 삼신환(三神丸) 에탄올 추출물을 병행 처리하여 병용 효과를 확인하고, 시간에 따른 생장 억제 효과를 확인하는 절차와 방법을 통해 삼신환(三神丸)이 MARA에 대한 항균 활성으로 oxacillin 또는 ciprofloxacin과 결합 되었을 때, 시너지 및 부분 시너지 효과를 보임으로써 in vitro에서 우수한 항균물질임이 연구 결과로 나타났음을 시사하는 바이다. 아울러 MARA 내성의 제어를 위한 신약 개발에 본 연구가 의미있는 자료가 되기를 기대할 뿐 아니라, 내성 균주를 극복하기 위한 항생물질의 연구와 개발에 더욱 박차를 가하는 계기가 되기를 바란다.

Clinical and molecular characterization of Korean children with infantile and late-onset Pompe disease: 10 years of experience with enzyme replacement therapy at a single center

  • Kim, Min-Sun;Song, Ari;Im, Minji;Huh, June;Kang, I-Seok;Song, Jinyoung;Yang, Aram;Kim, Jinsup;Kwon, Eun-Kyung;Choi, Eu-Jin;Han, Sun-Ju;Park, Hyung-Doo;Cho, Sung Yoon;Jin, Dong-Kyu
    • Clinical and Experimental Pediatrics
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    • 제62권6호
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    • pp.224-234
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    • 2019
  • Purpose: Pompe disease (PD) is an autosomal recessive disorder caused by a deficiency of acid alpha-glucosidase resulting from pathogenic GAA variants. This study describes the clinical features, genotypes, changes before and after enzyme replacement therapy (ERT), and long-term outcomes in patients with infantile-onset PD (IOPD) and late-onset PD (LOPD) at a tertiary medical center. Methods: The medical records of 5 Korean patients (2 male, 3 female patients) diagnosed with PD between 2002 and 2013 at Samsung Medical Center in Seoul, Republic of Korea were retrospectively reviewed for data, including clinical and genetic characteristics at diagnosis and clinical course after ERT. Results: Common initial symptoms included hypotonia, cyanosis, and tachycardia in patients with IOPD and limb girdle weakness in patients with LOPD. Electrocardiography at diagnosis revealed hypertrophic cardiomyopathy in all patients with IOPD who showed a stable disease course during a median follow-up period of 10 years. Patients with LOPD showed improved hepatomegaly and liver transaminase level after ERT. Conclusion: As ERT is effective for treatment of PD, early identification of this disease is very important. Thus, patients with IOPD should be considered candidates for clinical trials of new drugs in the future.

유방암 줄기세포 개념 및 제한점 (Concept and limitation of breast cancer stem cells)

  • 김종빈;안정신;임우성;문병인
    • Journal of Medicine and Life Science
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    • 제15권2호
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    • pp.46-50
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    • 2018
  • Cancer, a leading mortality disease following cardiovascular disease worldwide, has high incidence as one out of every four adults in Korea. It was known to be caused by several reasons including somatic mutation, activation of oncogene and chromosome aneuploidy. Cancer cells show a faster growth rate and have metastatic and heterogeneous cell populations compared to normal cells. Cancer stem cells, the most invested field in cancer biology, is a theory to explain heterogeneous cell populations of cancer cells among several characteristics of cancer cells, which is providing the theoretical background for incidence of cancer and treatment failure by drug resistance. Cancer stem cells initially explain heterogeneous cell populations of cancer cells based on the same markers of normal stem cells in cancer, in which only cancer stem cells showed heterogeneity of cancer cells and tumor initiating ability of leukemia. Based on these results, cancer stem cells were reported in various solid cancers such as breast cancer, liver cancer, and lung cancer. Breast cancer stem cells were first reported in solid cancer which had tumor initiating ability and further identified as anti-cancer drug resistance. There were several identification methods in breast cancer stem cells such as specific surface markers and culture methods. The discovery of cancer stem cells not only explains heterogeneity of cancer cells, but it also provides theoretical background for targeting cancer stem cells to complete elimination of cancer cells. Many institutes have been developing new anticancer drugs targeting cancer stem cells, but there have not been noticeable results yet. Many researchers also reported a necessity for improvement of current concepts and methods of research on cancer stem cells. Herein, we discuss the limitations and the perspectives of breast cancer stem cells based on the current concept and history.

Quality Control of Majoon-e-Nisyan and its Acute Oral Toxicity Study in Experimental Rats

  • Shaikh, Masud;Husain, Gulam M.;Naikodi, Mohammed Abdul Rasheed;Kazmi, Munawwar H.;Viquar, Uzma
    • 셀메드
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    • 제11권1호
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    • pp.2.1-2.8
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    • 2021
  • The clinical condition Amnesia causes difficulty in learning new information and the inability to recall past events. It is primarily concerned with recent memory loss. Majoon-e-Nisyan (MJN) is a polyherbal Unani formulation, present in a semi-solid form. It is widely used potent drug of the Unani System of Medicine (USM) for treating Nisyan (amnesia). In the present study polyherbal Unani formulation, MJN has been studied for its quality control and acute toxicity. Standardization (quality control) of drugs deals with drug identity, drug quality and purity determination. Standardization of MJN had been done as per the Unani pharmacopoeial parameters approved by World Health Organization (WHO) - Pharmacognostical parameters, Physico-chemical parameters, high-performance thin-layer chromatography (HPTLC), microbial load, aflatoxin, and heavy metals. Solvents and chemicals used in the study were of analytical grade and used instrument were calibrated. By conducting an acute oral toxicity study in rats, the safety of MJN was assessed. The limit test method of OECD guideline 425 was followed in the study. Results of standardization and standard operating procedures (SOPs) for preparation of MJN may serve as the standard reference in the future. The data generated in the study for the quality control of MJN proved the quality of formulation and shows that MJN is not toxic in rats following acute dosing up to 2000 mg/kg bw. The data obtained in the paper for MJN may be used as a standard guideline for preparation of the formulation which can save time, cost, and resources for future research endeavours.