• Title/Summary/Keyword: Clinical pathways

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Challenging the Hypothesis of de novo Biosynthesis of Bile Acids by Marine Bacteria

  • Tueros, Felipe Gonzalo;Ellabaan, Mostafa M. Hashim;Henricsson, Marcus;Vazquez-Uribe, Ruben;Backhed, Fredrik;Sommer, Morten Otto Alexander
    • Microbiology and Biotechnology Letters
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    • v.50 no.1
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    • pp.102-109
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    • 2022
  • Bile acids are essential molecules produced by vertebrates that are involved in several physiological roles, including the uptake of nutrients. Bacterial isolates capable of producing bile acids de novo have been identified and characterized. Such isolates may provide access to novel biochemical pathways suitable for the design of microbial cell factories. Here, we further characterized the ability of Maribacter dokdonensis, Dokdonia donghaensis, and Myroides pelagicus to produce bile acids. Contrary to previous reports, we did not observe de novo production of bile acids by these isolates. Instead, we found that these isolates deconjugated the amino acid moiety of bile acids present in the growth medium used in previous reports. Through genomic analysis, we identified putative bile salt hydrolases, which could be responsible for the different bile acid modifications observed. Our results challenge the hypothesis of de novo microbial bile acid production, while further demonstrating the diverse capacity of bacteria to modify bile acids.

Presentation of potential genes and deleterious variants associated with non-syndromic hearing loss: a computational approach

  • Ray, Manisha;Rath, Surya Narayan;Sarkar, Saurav;Sable, Mukund Namdev
    • Genomics & Informatics
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    • v.20 no.1
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    • pp.5.1-5.10
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    • 2022
  • Non-syndromic hearing loss (NSHL) is a common hereditary disorder. Both clinical and genetic heterogeneity has created many obstacles to understanding the causes of NSHL. The present study has attempted to ravel the genetic aetiology in NSHL progression and to screen out potential target genes using computational approaches. The reported NSHL target genes (2009-2020) have been studied by analyzing different biochemical and signaling pathways, interpretation of their functional association network, and discovery of important regulatory interactions with three previously established miRNAs in the human inner ear as well as in NSHL such as miR-183, miR-182, and miR-96. This study has identified SMAD4 and SNAI2 as the most putative target genes of NSHL. But pathogenic and deleterious non-synonymous single nucleotide polymorphisms discovered within SMAD4 is anticipated to have an impact on NSHL progression. Additionally, the identified deleterious variants in the functional domains of SMAD4 added a supportive clue for further study. Thus, the identified deleterious variant i.e., rs377767367 (G491V) in SMAD4 needs further clinical validation. The present outcomes would provide insights into the genetics of NSHL progression.

Ginsenoside Rb2: A review of pharmacokinetics and pharmacological effects

  • Miao, Longxing;Yang, Yijun;Li, Zhongwen;Fang, Zengjun;Zhang, Yongqing;Han, Chun-chao
    • Journal of Ginseng Research
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    • v.46 no.2
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    • pp.206-213
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    • 2022
  • Ginsenoside Rb2 is an active protopanaxadiol-type saponin, widely existing in the stem and leave of ginseng. Rb2 has recently been the focus of studies for pharmaceutical properties. This paper provides an overview of the preclinical and clinical pharmacokinetics for Rb2, which exhibit poor absorption, rapid tissue distribution and slow excretion through urine. Pharmacological studies indicate a beneficial role of Rb2 in the prevention and treatment of diabetes, obesity, tumor, photoaging, virus infection and cardiovascular problems. The underlying mechanism is involved in an inhibition of oxidative stress, ROS generation, inflammation and apoptosis via regulation of various cellular signaling pathways and molecules, including AKT/SHP, MAPK, EGFR/SOX2, TGF-β1/Smad, SIRT1, GPR120/AMPK/HO-1 and NF-κB. This work would provide a new insight into the understanding and application of Rb2. However, its therapeutic effects have not been clinically evaluated. Further studies should be aimed at the clinical treatment of Rb2.

Knowledge Based Recommender System for Disease Diagnostic and Treatment Using Adaptive Fuzzy-Blocks

  • Navin K.;Mukesh Krishnan M. B.
    • KSII Transactions on Internet and Information Systems (TIIS)
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    • v.18 no.2
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    • pp.284-310
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    • 2024
  • Identifying clinical pathways for disease diagnosis and treatment process recommendations are seriously decision-intensive tasks for health care practitioners. It requires them to rely on their expertise and experience to analyze various categories of health parameters from a health record to arrive at a decision in order to provide an accurate diagnosis and treatment recommendations to the end user (patient). Technological adaptation in the area of medical diagnosis using AI is dispensable; using expert systems to assist health care practitioners in decision-making is becoming increasingly popular. Our work architects a novel knowledge-based recommender system model, an expert system that can bring adaptability and transparency in usage, provide in-depth analysis of a patient's medical record, and prescribe diagnostic results and treatment process recommendations to them. The proposed system uses a set of parallel discrete fuzzy rule-based classifier systems, with each of them providing recommended sub-outcomes of discrete medical conditions. A novel knowledge-based combiner unit extracts significant relationships between the sub-outcomes of discrete fuzzy rule-based classifier systems to provide holistic outcomes and solutions for clinical decision support. The work establishes a model to address disease diagnosis and treatment recommendations for primary lung disease issues. In this paper, we provide some samples to demonstrate the usage of the system, and the results from the system show excellent correlation with expert assessments.

Identifying and Solving Gaps in Pre- and In-Hospital Acute Myocardial Infarction Care in Asia-Pacific Countries

  • Paul Jie Wen Tern;Amar Vaswani;Khung Keong Yeo
    • Korean Circulation Journal
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    • v.53 no.9
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    • pp.594-605
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    • 2023
  • Acute myocardial infarction (AMI) is a major cause of morbidity and mortality in the Asia-Pacific region, and mortality rates differ between countries in the region. Systems of care have been shown to play a major role in determining AMI outcomes, and this review aims to highlight pre-hospital and in-hospital system deficiencies and suggest possible improvements to enhance quality of care, focusing on Korea, Japan, Singapore and Malaysia as representative countries. Time to first medical contact can be shortened by improving patient awareness of AMI symptoms and the need to activate emergency medical services (EMS), as well as by developing robust, well-coordinated and centralized EMS systems. Additionally, performing and transmitting pre-hospital electrocardiograms, algorithmically identifying patients with high risk AMI and developing hospital networks that appropriately divert such patients to percutaneous coronary intervention-capable hospitals have been shown to be beneficial. Within the hospital environment, developing and following clinical practice guidelines ensures that treatment plans can be standardised, whilst integrated care pathways can aid in coordinating care within the healthcare institution and can guide care even after discharge. Prescription of guideline directed medical therapy for secondary prevention and patient compliance to medications can be further optimised. Finally, the authors advocate for the establishment of more regional, national and international AMI registries for the formal collection of data to facilitate audit and clinical improvement.

Recent Advances in Cell Therapeutics for Systemic Autoimmune Diseases

  • Youngjae Park;Seung-Ki Kwok
    • IMMUNE NETWORK
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    • v.22 no.1
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    • pp.10.1-10.17
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    • 2022
  • Systemic autoimmune diseases arise from loss of self-tolerance and immune homeostasis between effector and regulator functions. There are many therapeutic modalities for autoimmune diseases ranging from conventional disease-modifying anti-rheumatic drugs and immunosuppressants exerting nonspecific immune suppression to targeted agents including biologic agents and small molecule inhibitors aiming at specific cytokines and intracellular signal pathways. However, such current therapeutic strategies can rarely induce recovery of immune tolerance in autoimmune disease patients. To overcome limitations of conventional treatment modalities, novel approaches using specific cell populations with immune-regulatory properties have been attempted to attenuate autoimmunity. Recently progressed biotechnologies enable sufficient in vitro expansion and proper manipulation of such 'tolerogenic' cell populations to be considered for clinical application. We introduce 3 representative cell types with immunosuppressive features, including mesenchymal stromal cells, Tregs, and myeloid-derived suppressor cells. Their cellular definitions, characteristics, mechanisms of immune regulation, and recent data about preclinical and clinical studies in systemic autoimmune diseases are reviewed here. Challenges and limitations of each cell therapy are also addressed.

Case Analysis on AI-Based Learning Assistance Systems (인공지능 기반 학습 지원 시스템에 관한 사례 분석)

  • Chee, Hyunkyung;Kim, Minji;Lee, Gayoung;Huh, Sunyoung;Kim, Myung sun
    • Journal of Engineering Education Research
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    • v.27 no.4
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    • pp.3-11
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    • 2024
  • This study classified domestic and international systems by type, presenting their key features and examples, with the aim of outlining future directions for system development and research. AI-based learning assistance systems can be categorized into instructional-learning evaluation types and academic recommendation types, depending on their purpose. Instructional-learning evaluation types measure learners' levels through initial diagnostic assessments, provide customized learning, and offer adaptive feedback visualized based on learners' misconceptions identified through learning data. Academic recommendation types provide personalized academic pathways and a variety of information and functions to assist with overall school life, based on the big data held by schools. Based on these characteristics, future system development should clearly define the development purpose from the planning stage, considering data ethics and stability, and should not only approach from a technological perspective but also sufficiently reflect educational contexts.

Clinical and Neurobiological Relevance of Current Animal Models of Autism Spectrum Disorders

  • Kim, Ki Chan;Gonzales, Edson Luck;Lazaro, Maria T.;Choi, Chang Soon;Bahn, Geon Ho;Yoo, Hee Jeong;Shin, Chan Young
    • Biomolecules & Therapeutics
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    • v.24 no.3
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    • pp.207-243
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    • 2016
  • Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication impairments, as well as repetitive and restrictive behaviors. The phenotypic heterogeneity of ASD has made it overwhelmingly difficult to determine the exact etiology and pathophysiology underlying the core symptoms, which are often accompanied by comorbidities such as hyperactivity, seizures, and sensorimotor abnormalities. To our benefit, the advent of animal models has allowed us to assess and test diverse risk factors of ASD, both genetic and environmental, and measure their contribution to the manifestation of autistic symptoms. At a broader scale, rodent models have helped consolidate molecular pathways and unify the neurophysiological mechanisms underlying each one of the various etiologies. This approach will potentially enable the stratification of ASD into clinical, molecular, and neurophenotypic subgroups, further proving their translational utility. It is henceforth paramount to establish a common ground of mechanistic theories from complementing results in preclinical research. In this review, we cluster the ASD animal models into lesion and genetic models and further classify them based on the corresponding environmental, epigenetic and genetic factors. Finally, we summarize the symptoms and neuropathological highlights for each model and make critical comparisons that elucidate their clinical and neurobiological relevance.

Suppression Effect of the Inflammatory Response in Macrophages by Paeoniae Radix Rubra Extracts (적작약 추출물의 대식세포에 대한 염증억제 효과)

  • Bak, Jong-Phil;Son, Jung-Hyun;Kim, Yong-Min;Jung, Joon-Hee;Leem, Kang-Hyun;Lee, Eun-Yong;Kim, Ee-Hwa
    • Korean Journal of Medicinal Crop Science
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    • v.19 no.5
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    • pp.373-379
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    • 2011
  • Paeoniae Radix Rubra is a preparation consisting of desiccated roots of Paeonia lactiflora PALL (belonging to Ranunculaceae). Paeoniae Radix Rubra is used as a medicinal herb in Asian countries to treat many diseases. Ethanol- or water-based extracts of Paeoniae Radix Rubra were prepared and tested on RAW 264.7 cells, a murine macrophage cell line. The expression of some pro-inflammatory proteins, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphorylated ERK1/2 was detected by Western blot analyses, while PGE2 expression was quantified by ELISA. Both the water and ethanol extracts of Paeoniae Radix Rubra suppressed LPS-induced nitric oxide (NO) production and exhibited cell toxicity in accordance with increased NO production. Also, both extracts reduced the expression of COX-2 and iNOS, and inhibited phosphorylation of ERK1/2 in LPS-stimulated RAW 264.7 cells. Extracts prepared from Paeoniae Radix Rubra contain anti-inflammatory agents that inhibit the iNOS and MAPK pathways.

Effects of Schisandra chinensis fruit extract and gomisin A on the contractility of penile corpus cavernosum smooth muscle: a potential mechanism through the nitric oxide - cyclic guanosine monophosphate pathway

  • Choi, Bo Ram;Kim, Hye Kyung;Park, Jong Kwan
    • Nutrition Research and Practice
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    • v.12 no.4
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    • pp.291-297
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    • 2018
  • BACKGROUND/OBJECTIVES: This study evaluated the effects and molecular mechanisms of the Schisandra chinensis fruit extract (SC) and its major compound gomisin A (GA), on the contractility of rabbit penile corpus cavernosum smooth muscle (PCCSM). MATERIALS/METHODS: PCCSM was exposed to SC or GA after appropriate pretreatment with nitric oxide synthase (NOS) blocker, guanylate cyclase blocker, adenylyl cyclase blocker or protein kinase A blocker. Subsequently, we evaluated the cyclic nucleotide in the perfusate by radioimmunoassay, protein expression level of neuronal NOS (nNOS) and endothelial NOS (eNOS) by western blot, and the interaction of SC or GA with udenafil and rolipram. RESULTS: Both SC and GA induce PCCSM relaxations in a concentration-dependent manner. Pretreatment with NOS blocker, guanylate cyclase blocker, adenylyl cyclase blocker or protein kinase A blocker result in significantly decreased relaxation. SC and GA also induce the levels of cyclic nucleotide in the perfusate in a concentration-dependent manner. Perfusion with GA also showed significantly higher levels of eNOS protein. Furthermore, the udenafil and rolipram induced relaxations of PCCSM were enhanced after exposure to SC and GA. Our results indicate that SC and GA induce the relaxation of PCCSM via the nitric oxide (NO)-cGMP and cAMP signaling pathways. CONCLUSIONS: The SC and GA are potential alternative treatments for men who want to consume natural products to ameliorate erectile function, or who do not respond to the commercially available medicines.