• Title/Summary/Keyword: human mortality

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LOXL1-AS1 Aggravates Myocardial Ischemia/Reperfusion Injury Through the miR-761/PTEN Axis

  • Wenhua He;Lili Duan;Li Zhang
    • Korean Circulation Journal
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    • v.53 no.6
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    • pp.387-403
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    • 2023
  • Background and Objectives: Myocardial ischemia and reperfusion injury (MIRI) has high morbidity and mortality worldwide. We aimed to explore the role of long noncoding RNA lysyl oxidase like 1 antisense RNA 1 (LOXL1-AS1) in cardiomyocyte pyroptosis. Methods: Hypoxia/reoxygenation (H/R) injury was constructed in human cardiomyocyte (HCM). The level of LOXL1-AS1, miR-761, phosphatase and tensin homolog (PTEN) and pyroptosis-related proteins was monitored by quantitative real-time polymerase chain reaction or western blot. Flow cytometry examined the pyroptosis level. Lactate dehydrogenase (LDH), creatine kinase-MB and cardiac troponin I levels were detected by test kits. Enzyme-linked immunosorbent assay measured the release of inflammatory cytokines. Dual-luciferase assay validated the binding relationship among LOXL1-AS1, miR-761, and PTEN. Finally, ischemia/reperfusion (I/R) animal model was constructed. Hematoxylin and eosin staining assessed morphological changes of myocardial tissue. NOD-like receptor pyrin domain-containing protein 3 (NLRP3) and casepase-1 expression was determined by immunohistochemistry. Results: After H/R treatment, LOXL1-AS1 and PTEN were highly expressed but miR-761 level was suppressed. LOXL1-AS1 inhibition or miR-761 overexpression increased cell viability, blocked the release of LDH and inflammatory cytokines (interleukin [IL]-1β, IL-18), inhibited pyroptosis level, and downregulated pyroptosis-related proteins (ASC, cleaved caspase-1, gasdermin D-N, NLRP3, IL-1β, and IL-18) levels in HCMs. LOXL1-AS1 sponged miR-761 to up-regulate PTEN. Knockdown of miR-761 reversed the effect of LOXL1-AS1 down regulation on H/R induced HCM pyroptosis. LOXL1-AS1 aggravated the MIRI by regulating miR-761/PTEN axis in vivo. Conclusions: LOXL1-AS1 targeted miR-761 to regulate PTEN expression, then enhance cardiomyocyte pyroptosis, providing a new alternative target for the treatment of MIRI.

Structure of SARS-CoV-2 Spike Glycoprotein for Therapeutic and Preventive Target

  • Jaewoo Hong;Hyunjhung Jhun;Yeo-Ok Choi;Afeisha S. Taitt;Suyoung Bae;Youngmin Lee;Chang-seon Song;Su Cheong Yeom;Soohyun Kim
    • IMMUNE NETWORK
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    • v.21 no.1
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    • pp.8.1-8.17
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    • 2021
  • The global crisis caused by the coronavirus disease 2019 (COVID-19) led to the most significant economic loss and human deaths after World War II. The pathogen causing this disease is a novel virus called the severe acute respiratory syndrome coronavirus 2 (SARSCoV-2). As of December 2020, there have been 80.2 million confirmed patients, and the mortality rate is known as 2.16% globally. A strategy to protect a host from SARS-CoV-2 is by suppressing intracellular viral replication or preventing viral entry. We focused on the spike glycoprotein that is responsible for the entry of SARS-CoV-2 into the host cell. Recently, the US Food and Drug Administration/EU Medicines Agency authorized a vaccine and antibody to treat COVID-19 patients by emergency use approval in the absence of long-term clinical trials. Both commercial and academic efforts to develop preventive and therapeutic agents continue all over the world. In this review, we present a perspective on current reports about the spike glycoprotein of SARS-CoV-2 as a therapeutic target.

A Hybrid Multi-Level Feature Selection Framework for prediction of Chronic Disease

  • G.S. Raghavendra;Shanthi Mahesh;M.V.P. Chandrasekhara Rao
    • International Journal of Computer Science & Network Security
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    • v.23 no.12
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    • pp.101-106
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    • 2023
  • Chronic illnesses are among the most common serious problems affecting human health. Early diagnosis of chronic diseases can assist to avoid or mitigate their consequences, potentially decreasing mortality rates. Using machine learning algorithms to identify risk factors is an exciting strategy. The issue with existing feature selection approaches is that each method provides a distinct set of properties that affect model correctness, and present methods cannot perform well on huge multidimensional datasets. We would like to introduce a novel model that contains a feature selection approach that selects optimal characteristics from big multidimensional data sets to provide reliable predictions of chronic illnesses without sacrificing data uniqueness.[1] To ensure the success of our proposed model, we employed balanced classes by employing hybrid balanced class sampling methods on the original dataset, as well as methods for data pre-processing and data transformation, to provide credible data for the training model. We ran and assessed our model on datasets with binary and multivalued classifications. We have used multiple datasets (Parkinson, arrythmia, breast cancer, kidney, diabetes). Suitable features are selected by using the Hybrid feature model consists of Lassocv, decision tree, random forest, gradient boosting,Adaboost, stochastic gradient descent and done voting of attributes which are common output from these methods.Accuracy of original dataset before applying framework is recorded and evaluated against reduced data set of attributes accuracy. The results are shown separately to provide comparisons. Based on the result analysis, we can conclude that our proposed model produced the highest accuracy on multi valued class datasets than on binary class attributes.[1]

Nationwide surveillance of acute interstitial pneumonia in Korea (급성 간질성 폐렴의 전국적 현황 조사)

  • Kim, Byoung-Ju;Kim, Han-A;Song, Young-Hwa;Yu, Jinho;Kim, Seonguk;Park, Seong Jong;Kim, Kyung Won;Kim, Kyu-Earn;Kim, Dong Soo;Park, June Dong;Ahn, Kang Mo;Kim, Hyo-Bin;Jung, Hyang-Min;Kang, Chun;Hong, Soo-Jong
    • Clinical and Experimental Pediatrics
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    • v.52 no.3
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    • pp.324-329
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    • 2009
  • Purpose : Acute interstitial pneumonia (AIP) is a rare disease, but its prognosis is fatal because of lack of efficient treatment modality. Recently, it has been reported that there was epidemic AIP in Korea. This study aims to investigate the past and current status of AIP in Korea. Methods : We performed a nationwide survey and a prospective study. From August 6 to 15, 2008, a questionnaire survey was conducted to identify the prevalence, local distribution, and response to current treatments. The questionnaire was answered by pediatrician working in 23 referral centers in Korea. In addition, 5 referral centers in Seoul performed a preliminary prospective observational study by obtaining clinical data and specimens from appropriate patients. The Korea Centers for Disease Control and Prevention analyzed the samples for possible pathogens. Results : The survey showed 78 AIP cases had occurred and 36 patients had died. Lung biopsy was performed only on 20 patients. In 2008, 9 AIP cases developed. In a prospective study, 9 (M:F=5:4) patients developed AIP in spring and 7 (78%) died, with the mean rate of death occurring 46 days after diagnosis. Human corona virus 229E, cytomegalovirus, influenza A virus, influenza B virus, and parainfluenza virus were isolated from the respiratory specimens. Conclusion : This study showed nationwide prevalence of AIP in Korea. In addition, because of the high mortality rate and rapid progress, pediatricians need to be aware of the disease. Further studies and a nationwide network are required for reducing the morbidity and mortality rates related to AIP.

Effectiveness of Intravenous Isoniazid and Ethambutol Administration in Patients with Tuberculosis Meningoencephalitis and HIV Infection

  • Butov, Dmytro;Feshchenko, Yurii;Kuzhko, Mykhailo;Gumenuik, Mykola;Yurko, Kateryna;Grygorova, Alina;Tkachenko, Anton;Nekrasova, Natalia;Tlustova, Tetiana;Kikinchuk, Vasyl;Peshenko, Alexandr;Butova, Tetiana
    • Tuberculosis and Respiratory Diseases
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    • v.83 no.1
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    • pp.96-103
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    • 2020
  • Background: The aim of this study was to investigate the effectiveness of intravenous isoniazid (H) and ethambutol (E) administered in patients with new sputum positive drug-susceptible pulmonary tuberculosis (TB) with tuberculous meningoencephalitis (TM) and human immunodeficiency virus (HIV) co-infection in the intensive phase of treatment. Methods: Fifty-four patients with TB/TM and HIV co-infection were enrolled for this study. Group 1 comprised of 23 patients treated with E and H intravenously, while rifampicin and pyrazinamide were prescribed orally. Group 2 consisted of 31 patients treated with the first-line anti-TB drugs orally. The concentrations of H and E in blood serum were detected using a chromatographic method. Results: A significant improvement in the clinical symptoms and X-ray signs in patients treated intravenously with H and E was observed and compared to group 2. The sputum Mycobacterium tuberculosis positivity was observed during the second month of the treatment in 25.0% of patients from group 1 and 76.1% of the patients from the control group (p=0.003). In addition, nine patients (39.1%) died up to 6 months when H and E were prescribed intravenously compared with 22 (70.9%) in group 2 (p=0.023). Conclusion: In TB/TM with HIV, the intravenous H and E treatment was more effective than oral H and E treatment at 2 months of intensive treatment in sputum conversion as well as in clinical improvement, accompanied by significantly higher mean serum concentrations. In addition, the mortality rate was lower in intravenous H and E treatment compared to oral treatment.

Screening and isolation of antibacterial proteinaceous compounds from flower tissues: Alternatives for treatment of healthcare-associated infections

  • de Almeida, Renato Goulart;Silva, Osmar Nascimento;de Souza Candido, Elizabete;Moreira, Joao Suender;Jojoa, Dianny Elizabeth Jimenez;Gomes, Diego Garces;de Souza Freire, Mirna;de Miranda Burgel, Pedro Henrique;de Oliveira, Nelson Gomes Junior;Valencia, Jorge William Arboleda;Franco, Octavio Luiz;Dias, Simoni Campos
    • CELLMED
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    • v.4 no.1
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    • pp.5.1-5.8
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    • 2014
  • Healthcare-associated infection represents a frequent cause of mortality that increases hospital costs. Due to increasing microbial resistance to antibiotics, it is necessary to search for alternative therapies. Consequently, novel alternatives for the control of resistant microorganisms have been studied. Among them, plant antimicrobial protein presents enormous potential, with flowers being a new source of antimicrobial molecules. In this work, the antimicrobial activity of protein-rich fractions from flower tissues from 18 different species was evaluated against several human pathogenic bacteria. The results showed that protein-rich fractions of 12 species were able to control bacterial development. Due its broad inhibition spectrum and high antibacterial activity, the protein-rich fraction of Hibiscus rosa-sinensis was subjected to DEAE-Sepharose chromatography, yielding a retained fraction and a non-retained fraction. The retained fraction inhibits 29.5% of Klebsiella pneumoniae growth, and the non-retained fraction showed 31.5% of growth inhibition against the same bacteria. The protein profile of the chromatography fractions was analyzed by using SDS-PAGE, revealing the presence of two major protein bands in the retained fraction, of 20 and 15 kDa. The results indicate that medicinal plants have the biotechnological potential to increase knowledge about antimicrobial protein structure and action mechanisms, assisting in the rational design of antimicrobial compounds for the development of new antibiotic drugs.

Growth Inhibitory Effect of Extracts of Propolis on Epithelial Ovarian Cancer Cells (상피성 난소암 세포에서 프로폴리스 추출물의 세포 증식 저해 효과)

  • Yang, Ga Ram;Yoon, Kyung Mi;Oh, Hyun Ho;Kim, Min Sung;Hwang, Tae Ho;An, Won Gun
    • Journal of Life Science
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    • v.27 no.7
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    • pp.834-839
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    • 2017
  • Propolis is a natural product collected from plants by honey bees product used extensively in traditional medicine for its antioxidant, anti-inflammatory, immunomodulatory and anti-cancer effects. Propolis exhibits a broad spectrum of biological activities because it is a complex mixture of natural substances. Ovarian cancer is the second most common newly diagnosed cancer from all cancers among women in Korea and the leading cause of death from gynecological malignancies. While most ovarian cancer patients initially respond to surgical debulking and chemotherapy, patients later succumb to the disease. Thus, there is an urgent need to test novel therapeutic agents to counteract the high mortality rate associated with ovarian cancer. In this study, we investigated the anti-cancer properties and the active mechanism of Australian propolis in human epithelial ovarian cancer A2780 cells. Our data revealed that propolis showed a cytotoxic activity in a dose-dependent manner. Flow cytometric analysis for cell cycle arrest and apoptosis using propidium iodide staning and annexin V-FITC indicated that propolis could induce cycle arrest in the G0/G1 phase and apoptosis in a dose-dependent manner on human epithelial ovarian cancer cells. These results suggest that the Australian propolis is potential alternative agent on ovarian cancer prevention and treatment.

Coronaviruses: SARS, MERS and COVID-19 (코로나바이러스: 사스, 메르스 그리고 코비드-19)

  • Kim, Eun-Joong;Lee, Dongsup
    • Korean Journal of Clinical Laboratory Science
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    • v.52 no.4
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    • pp.297-309
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    • 2020
  • Coronaviruses were originally discovered as enzootic infections that limited to their natural animal hosts, but some strains have since crossed the animal-human species barrier and progressed to establish zoonotic diseases. Accordingly, cross-species barrier jumps resulted in the appearance of SARS-CoV, MERS-CoV, and SARS-CoV-2 that manifest as virulent human viruses. Coronaviruses contain four main structural proteins: spike, membrane, envelope, and nucleocapsid protein. The replication cycle is as follows: cell entry, genome translation, replication, assembly, and release. They were not considered highly pathogenic to humans until the outbreaks of SARS-CoV in 2002 in Guangdong province, China. The consequent outbreak of SARS in 2002 led to an epidemic with 8,422 cases, and a reported worldwide mortality rate of 11%. MERS-CoVs is highly related to camel CoVs. In 2019, a cluster of patients infected with 2019-nCoV was identified in an outbreak in Wuhan, China, and soon spread worldwide. 2019-nCoV is transmitted through the respiratory tract and then induced pneumonia. Molecular diagnosis based on upper respiratory region swabs is used for confirmation of this virus. This review examines the structure and genomic makeup of the viruses as well as the life cycle, diagnosis, and potential therapy.

Efficacy and Safety of Human Bone Marrow-Derived Mesenchymal Stem Cells according to Injection Route and Dose in a Chronic Kidney Disease Rat Model

  • Han Kyu Chae;Nayoung Suh;Myong Jin Jang;Yu Seon Kim;Bo Hyun Kim;Joomin Aum;Ha Chul Shin;Dalsan You;Bumsik Hong;Hyung Keun Park;Choung-Soo Kim
    • International Journal of Stem Cells
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    • v.16 no.1
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    • pp.66-77
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    • 2023
  • Background and Objectives: We compared the efficacy and safety of human bone marrow-derived mesenchymal stem cells (hBMSC), delivered at different doses and via different injection routes in an animal model of chronic kidney disease. Methods and Results: A total of ninety 12-week-old rats underwent 5/6 nephrectomy and randomized among nine groups: sham, renal artery control (RA-C), tail vein control (TV-C), renal artery low dose (RA-LD) (0.5×106 cells), renal artery moderate dose (RA-MD) (1.0×106 cells), renal artery high dose (RA-HD) (2.0×106 cells), tail vein low dose (TV-LD) (0.5×106 cells), tail vein moderate dose (TV-MD) (1.0×106 cells), and tail vein high dose (TV-HD) (2.0×106 cells). Renal function and mortality of rats were evaluated after hBMSC injection. Serum blood urea nitrogen was significantly lower in the TV-HD group at 2 weeks (p<0.01), 16 weeks (p<0.05), and 24 weeks (p<0.01) than in the TV-C group, as determined by one-way ANOVA. Serum creatinine was significantly lower in the TV-HD group at 24 weeks (p<0.05). At 8 weeks, creatinine clearance was significantly higher in the TV-MD and TV-HD groups (p<0.01, p<0.05) than in the TV-C group. In the safety evaluation, we observed no significant difference among the groups. Conclusions: Our findings confirm the efficacy and safety of high dose (2×106 cells) injection of hBMSC via the tail vein.

Anticarcinogenic Effects of Sargassum fulvellum Fractions on Several Human Cancer Cell Lines in vitro (모자반 분획물의 in vitro에서의 항발암효과)

  • 배송자
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.33 no.3
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    • pp.480-486
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    • 2004
  • Despite many therapeutic advances in the understanding of the processes in carcinogenesis, overall mortality statistics are unlikely to change until there is reorientation of the concepts for the use of natural products as new anticarcinogenic agents. In this study, we investigated the anticarcinogenic activity, antioxidant and DPPH scavenging activity of Sargassum fulvellum (SF). SF was extracted with methanol, which was further fractionated into five different types: hexane (SFMH), ethylether (SFMEE), ethyl acetate (SFMEA), butanol (SFMB) and aqueous (SFMA) partition layers. We determined the cytotoxic effect of these layers on human cancer cells by MTT assay. Among various partition layers of SF, at starting concentration of 100 $\mu\textrm{g}$/mL, SFMEE showed very high cytotoxicity which were 92, 90 and 84% and kept high throughout 5 concentration levels sparsed by 100 $\mu\textrm{g}$/mL against all three human cancer cell lines: HepG2, HT-29 and HeLa. SFMEA showed a low cytotoxicity at the beginning concentration level, but as the concentration became denser, growth inhibition effect of cancer cell lines started to increase and at 500 $\mu\textrm{g}$/mL, it hit the highest, which were 91, 96 and 98% against the same three cell lines as above. We observed QR induced effect in all fraction layers of SF. SFMEE showed similar tendensy of QR induced effect as did against cytotoxicity. The QR induced effect of SFMEE on HepG2 cells at 25 $\mu\textrm{g}$/mL concentration indicated 3 times higher than the control value of 1.0 and SFMH tended to be concentration-dependent on HepG2 cells. At 100 $\mu\textrm{g}$/mL, the QR induced effects resulted a ratio, which was 2.5 times higher than the control value. In search for antioxidation effects of SF extract and partition layer, the reducing activity on the 1, 1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging potential was sequentially screened. The SFM has similar antioxidant activity as to BHT and vitamin C groups.