7,721,079 results match your criteria Diseases of Tetrapyrrole Metabolism: Refsum Disease and the Hepatic Porphyrias


chromMAGMA: regulatory element-centric interrogation of risk variants.

Life Sci Alliance 2022 Oct 1;5(10). Epub 2022 Jul 1.

Women's Cancer Research Program at the Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA

Candidate causal risk variants from genome-wide association studies reside almost exclusively in noncoding regions of the genome and innovative approaches are necessary to understand their biological function. Multi-marker analysis of genomic annotation (MAGMA) is a widely used program that nominates candidate risk genes by mapping single-nucleotide polymorphism summary statistics from genome-wide association studies to gene bodies. We augmented MAGMA to create chromatin-MAGMA (chromMAGMA), a method to nominate candidate risk genes based on the presence of risk variants within noncoding regulatory elements (REs). Read More

View Article and Full-Text PDF
October 2022

The relationship between interstitial lung abnormalities, mortality, and multimorbidity: a cohort study.

Thorax 2022 Jul 1. Epub 2022 Jul 1.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA

Background: Interstitial lung abnormalities (ILAs) are associated with increased mortality. It is unclear whether multimorbidity accounts for the mortality association or how strongly ILA is associated with mortality relative to other common age-associated diseases. We determined the association of ILA with all-cause mortality adjusted for multimorbidity, compared mortality associated with ILA and prevalent cardiovascular disease (CVD), diabetes mellitus, chronic kidney disease, chronic obstructive pulmonary disease and cancer and also determined the association between ILA and these diseases. Read More

View Article and Full-Text PDF

Multi-omics profiling identifies a deregulated FUS-MAP1B axis in ALS/FTD-associated UBQLN2 mutants.

Life Sci Alliance 2022 Nov 1;5(11). Epub 2022 Jul 1.

Munich Cluster for Systems Neurology, Medical Faculty, Ludwig-Maximilians-University München, Munich, Germany

Ubiquilin-2 (UBQLN2) is a ubiquitin-binding protein that shuttles ubiquitinated proteins to proteasomal and autophagic degradation. UBQLN2 mutations are genetically linked to the neurodegenerative disorders amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). However, it remains elusive how UBQLN2 mutations cause ALS/FTD. Read More

View Article and Full-Text PDF
November 2022

Disorders of gut-brain interaction in post-acute COVID-19 syndrome.

Postgrad Med J 2022 Jul 1. Epub 2022 Jul 1.

Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, Delhi, India

The novel coronavirus SARS-CoV-2 is responsible for the devastating pandemic which has caused more than 5 million deaths across the world until today. Apart from causing acute respiratory illness and multiorgan dysfunction, there can be long-term multiorgan sequalae after recovery, which is termed 'long COVID-19' or 'post-acute COVID-19 syndrome'. Little is known about long-term gastrointestinal (GI) consequences, occurrence of post-infection functional gastrointestinal disorders and impact the virus may have on overall intestinal health. Read More

View Article and Full-Text PDF

Exploring the availability of specialist health workforce education in East and Southern Africa: a document analysis.

BMJ Glob Health 2022 Jul;7(Suppl 1)

Health Workforce Unit, Universal Health Coverage Life - Course Cluster, World Health Organization Regional Office for Africa, Brazzaville, Congo.

Background: Specialist health professionals improve health outcomes. Most low-income and middle-income countries do not have the capacity to educate and retain all types of specialists across various health professions. This study sought to explore and describe the opportunities available for specialist health professions education and the pathways to becoming a specialist health professional in East and Southern Africa (ESA). Read More

View Article and Full-Text PDF

Gender-related factors and out-of-hospital cardiac arrest incidence in women and men: analysis of a population-based cohort study in the Netherlands.

J Epidemiol Community Health 2022 Jul 1. Epub 2022 Jul 1.

Public and Occupational Health, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands.

Background: The incidence of out-of-hospital cardiac arrest (OHCA) differs consistently between women and men. Besides sex-related (biological) factors, OHCA risk may relate to gender-related (sociocultural) factors. We explored the association of selected gender-related factors with OHCA incidence in women and men. Read More

View Article and Full-Text PDF

Harnessing microbial iron chelators to develop innovative therapeutic agents.

J Adv Res 2022 Jul 1;39:89-101. Epub 2021 Nov 1.

LEPABE - Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal. Electronic address:

Background: Bacterial infections involving multidrug-resistant Gram-negative bacteria have become critically involved in the current antibiotic crisis. This, together with the bacterial evolution ability, prioritizes the discovery of new antibiotics. Research on microbial iron acquisition pathways and metabolites, particularly siderophores, has highlighted hopeful aspects for the design of advanced antimicrobial approaches. Read More

View Article and Full-Text PDF

Temporal metabolite responsiveness of microbiota in the tea plant phyllosphere promotes continuous suppression of fungal pathogens.

J Adv Res 2022 Jul 18;39:49-60. Epub 2021 Oct 18.

College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, China; Key Laboratory of Biology of Crop Pathogens and Insects of Zhejiang Province, Key Laboratory of Molecular Biology of Crop Pathogens and Insects, Ministry of Agriculture, Zhejiang University, Hangzhou 310058, China. Electronic address:

Introduction: A broad spectrum of rhizosphere bacteria and fungi were shown to play a central role for health, fitness and productivity of their host plants. However, implications of host metabolism on microbiota assembly in the phyllosphere and potential consequences for holobiont functioning were sparsely addressed. Previous observations indicated that tea plants might reduce disease occurrence in various forests located in their proximity; the underlying mechanisms and potential implications of the phyllosphere microbiota remained elusive. Read More

View Article and Full-Text PDF

Gut microbiota and host Cyp450s co-contribute to pharmacokinetic variability in mice with non-alcoholic steatohepatitis: Effects vary from drug to drug.

J Adv Res 2022 Jul 18;39:319-332. Epub 2021 Oct 18.

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, China. Electronic address:

Introduction: Pharmacokinetic variability in disease state is common in clinical practice, but its underlying mechanism remains unclear. Recently, gut microbiota has been considered to be pharmacokinetically equivalent to the host liver. Although some studies have explored the roles of gut microbiota and host Cyp450s in drug pharmacokinetics, few have explored their effects on pharmacokinetic variability, especially in disease states. Read More

View Article and Full-Text PDF

Polymeric nanocarriers: A promising tool for early diagnosis and efficient treatment of colorectal cancer.

J Adv Res 2022 Jul 20;39:237-255. Epub 2021 Nov 20.

Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates.

Background: Colorectal cancer (CRC) is the third most prevalent type of cancer for incidence and second for mortality worldwide. Late diagnosis and inconvenient and expensive current diagnostic tools largely contribute to the progress of the disease. The use of chemotherapy in the management of CRC significantly reduces tumor growth, metastasis, and morbidity rates. Read More

View Article and Full-Text PDF

Emerging strategies for the improvement of chemotherapy in bladder cancer: Current knowledge and future perspectives.

J Adv Res 2022 Jul 24;39:187-202. Epub 2021 Nov 24.

Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China; Guangdong Provincial Clinical Research Center for Urological Diseases, China. Electronic address:

Background: Chemotherapy is a first-line treatment for advanced and metastatic bladder cancer, but the unsatisfactory objective response rate to this treatment yields poor 5-year patient survival. Only PD-1/PD-L1-based immune checkpoint inhibitors, FGFR3 inhibitors and antibody-drug conjugates are approved by the FDA to be used in bladder cancer, mainly for platinum-refractory or platinum-ineligible locally advanced or metastatic urothelial carcinoma. Emerging studies indicate that the combination of targeted therapy and chemotherapy shows better efficacy than targeted therapy or chemotherapy alone. Read More

View Article and Full-Text PDF

The role of mild and asymptomatic infections on COVID-19 vaccines performance: A modeling study.

J Adv Res 2022 Jul 16;39:157-166. Epub 2021 Nov 16.

Basque Center for Applied Mathematics (BCAM), Bilbao, Spain; Dipartimento di Matematica, Università degli Studi di Trento, Italy.

Introduction: Different COVID-19 vaccine efficacies are reported, with remarkable effectiveness against severe disease. The so called sterilizing immunity, occurring when vaccinated individuals cannot transmit the virus, is still being evaluated. It is also unclear to what extent people with no symptoms or mild infection transmit the disease, and estimating their contribution to outbreaks is challenging. Read More

View Article and Full-Text PDF

Salicylic acid fights against Fusarium wilt by inhibiting target of rapamycin signaling pathway in Fusarium oxysporum.

J Adv Res 2022 Jul 2;39:1-13. Epub 2021 Nov 2.

Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu National Agricultural Science and Technology Center, Chengdu 610000, China; Zhengzhou Research Base, State Key Laboratory of Cotton Biology, School of Agricultural Science of Zhengzhou University, Zhengzhou 450000, China; Hainan Yazhou Bay Seed Laboratory, Sanya 572025, China. Electronic address:

Introduction: Biofungicides with low toxicity and high efficiency are a global priority for sustainable agricultural development. Phytohormone salicylic acid (SA) is an ancient medicine against various diseases in humans and activates the immune system in plants, but little is known of its function as a biofungicide.

Objectives: Here, Fusarium oxysporum, the causal agent of devastating Fusarium wilt and immunodepressed patients, was used as a model system to explore whether SA can enter the pathogen cells and suppress key targets of the pathogen. Read More

View Article and Full-Text PDF

Application of a data-driven XGBoost model for the prediction of COVID-19 in the USA: a time-series study.

BMJ Open 2022 Jul 1;12(7):e056685. Epub 2022 Jul 1.

Department of Epidemiology, China Medical University, Shenyang, China

Objective: The COVID-19 outbreak was first reported in Wuhan, China, and has been acknowledged as a pandemic due to its rapid spread worldwide. Predicting the trend of COVID-19 is of great significance for its prevention. A comparison between the autoregressive integrated moving average (ARIMA) model and the eXtreme Gradient Boosting (XGBoost) model was conducted to determine which was more accurate for anticipating the occurrence of COVID-19 in the USA. Read More

View Article and Full-Text PDF

Prevalence and determinants of persistent symptoms after infection with SARS-CoV-2: protocol for an observational cohort study (LongCOVID-study).

BMJ Open 2022 Jul 1;12(7):e062439. Epub 2022 Jul 1.

National Institute for Public Health and the Environment (RIVM), Center for Infectious Disease Control, Bilthoven, The Netherlands.

Introduction: A substantial proportion of individuals infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), report persisting symptoms weeks and months following acute infection. Estimates on prevalence vary due to differences in study designs, populations, heterogeneity of symptoms and the way symptoms are measured. Common symptoms include fatigue, cognitive impairment and dyspnoea. Read More

View Article and Full-Text PDF

Xpert Ultra stool testing to diagnose tuberculosis in children in Ethiopia and Indonesia: a model-based cost-effectiveness analysis.

BMJ Open 2022 Jul 1;12(7):e058388. Epub 2022 Jul 1.

Technical Division, KNCV Tuberculosis Foundation, Den Haag, The Netherlands.

Objectives: The WHO currently recommends stool testing using GeneXpert MTB/Rif (Xpert) for the diagnosis of paediatric tuberculosis (TB). The simple one-step (SOS) stool method enables processing for Xpert testing at the primary healthcare (PHC) level. We modelled the impact and cost-effectiveness of implementing the SOS stool method at PHC for the diagnosis of paediatric TB in Ethiopia and Indonesia, compared with the standard of care. Read More

View Article and Full-Text PDF

Integrating hepatitis B care and treatment with existing HIV services is possible: cost of integrated HIV and hepatitis B treatment in a low-resource setting: a cross-sectional hospital-based cost-minimisation assessment.

BMJ Open 2022 Jul 1;12(7):e058722. Epub 2022 Jul 1.

Makerere University College of Health Sciences, School of Medicine, Kampala, Uganda

Background: Hepatitis B and HIV care share health system challenges in the implementation of primary prevention, screening, early linkage to care, monitoring of therapeutic success and long-term medication adherence.

Setting: Arua regional referral hospital (RRH) and Koboko district hospital (DH), the West Nile region of Uganda.

Design: A cross-sectional hospital-based cost minimisation study from the providers' perspective considers financial costs to measure the amount of money spent on resources used in the stand-alone and integrated pathways. Read More

View Article and Full-Text PDF

Does an increase in physiological indexes predict better cognitive performance: the PhyCog randomised cross-over protocol in type 2 diabetes.

BMJ Open 2022 Jul 1;12(7):e060057. Epub 2022 Jul 1.

Psychology, University Clermont Auvergne, CNRS, LAPSCO, F-63000, Clermont-Ferrand, France

Introduction: There has been a growing interest towards cognitive-training programmes to improve cognition and prevent cognitive impairment despite discrepant findings. Physical activity has been recognised in maintaining or improving cognitive ability. Based on a psychoneurophysiological approach, physiological indexes should partly determine neuronal dynamics and influence cognition as any effects of cognitive training. Read More

View Article and Full-Text PDF

Anticalin®-based therapeutics: Expanding new frontiers in drug development.

Int Rev Cell Mol Biol 2022 31;369:89-106. Epub 2022 May 31.

Pieris Pharmaceuticals GmbH, Hallbergmoos, Germany. Electronic address:

Anticalin proteins are a novel class of clinical-stage biopharmaceuticals with high potential in various disease areas. Anticalin proteins, derived from extracellular human lipocalins are single-chain proteins, with a highly stable structure that can be engineered to bind with high specificity and potency to targets of therapeutic relevance. The small size and stable structure support their development as inhalable biologics in the field of respiratory diseases as already demonstrated for PRS-060/AZD1402, an Anticalin protein currently undergoing clinical development for the treatment of asthma. Read More

View Article and Full-Text PDF

Opportunities and challenges of bi-specific antibodies.

Int Rev Cell Mol Biol 2022 30;369:45-70. Epub 2022 May 30.

Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom; Department of Immune Medicine, University Regensburg, Regensburg, Germany; Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg, Germany; Institute of Pathology, University Regensburg, Regensburg, Germany. Electronic address:

The recent clinical approval of different Bi-specific antibodies (BsAbs) has revealed the great therapeutic potential of this novel class of biologicals. For example, the bispecific T-cell engager (BiTE), Blinatumomab, demonstrated the unique capacity of BsAbs to link T-cells with tumor cells, inducing targeted tumor cell removal. Additionally, Amivantamab, recognizing the EGFR and cMet in cis, revealed a substantial improvement of therapeutic efficacy by concomitantly targeting two tumor antigens. Read More

View Article and Full-Text PDF

Emerging applications of nanobodies in cancer therapy.

Int Rev Cell Mol Biol 2022 18;369:143-199. Epub 2022 May 18.

Laboratory for Molecular and Cellular Therapy, Department of Biomedical Sciences, Vrije Universiteit Brussel, Brussels, Belgium. Electronic address:

Cancer is a heterogeneous disease, requiring treatment tailored to the unique phenotype of the patient's tumor. Monoclonal antibodies (mAbs) and variants thereof have enabled targeted therapies to selectively target cancer cells. Cancer cell-specific mAbs have been used for image-guided surgery and targeted delivery of radionuclides or toxic agents, improving classical treatment strategies. Read More

View Article and Full-Text PDF

Current innovative engineered antibodies.

Authors:
José Yélamos

Int Rev Cell Mol Biol 2022 31;369:1-43. Epub 2022 May 31.

Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Unidad Asociada IIBB-CSIC, Barcelona, Spain; Immunology Unit, Department of Pathology, Hospital del Mar, Barcelona, Spain. Electronic address:

Antibody engineering has developed very intensively since the invention of the hybridoma technology in 1975, and it now can generate therapeutic agents with high specificity and reduced adverse effects. Indeed, antibodies have become one of the most innovative therapeutic agents in recent years, with some landing in the top 10 bestselling pharmaceutical drugs. New antibodies are being approved every year, in different formats and for treating various illnesses, including cancer, autoimmune inflammatory diseases, metabolic diseases and infectious diseases. Read More

View Article and Full-Text PDF

Adenosine Alleviates Necrotizing Enterocolitis by Enhancing the Immunosuppressive Function of Myeloid-Derived Suppressor Cells in Newborns.

J Immunol 2022 Jul 1. Epub 2022 Jul 1.

Key Laboratory of Immune Microenvironment and Disease of the Ministry of Education, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China; and

Necrotizing enterocolitis (NEC) is a common disorder in premature infants that is characterized by hyperinflammation and severe necrosis in the intestine. The pathogenesis of NEC remains to be elucidated. In this study, we demonstrate that adenosine, a metabolite more abundant in infants than in adults, plays an important role in the prevention of NEC. Read More

View Article and Full-Text PDF

Comparison of Neutralizing Antibody Response Kinetics in Patients with Hand, Foot, and Mouth Disease Caused by Coxsackievirus A16 or Enterovirus A71: A Longitudinal Cohort Study of Chinese Children, 2017-2019.

J Immunol 2022 Jul 1. Epub 2022 Jul 1.

School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China;

Hand, foot, and mouth disease (HFMD), which is mainly caused by coxsackievirus A16 (CVA16) or enterovirus A71 (EV-A71), poses a serious threat to children's health. However, the long-term dynamics of the neutralizing Ab (NAb) response and ideal paired-serum sampling time for serological diagnosis of CVA16-infected HFMD patients were unclear. In this study, 336 CVA16 and 253 EV-A71 PCR-positive HFMD inpatients were enrolled and provided 452 and 495 sera, respectively, for NAb detection. Read More

View Article and Full-Text PDF

The Porcine and Chicken Innate DNA Sensing cGAS-STING-IRF Signaling Axes Exhibit Differential Species Specificity.

J Immunol 2022 Jul 1. Epub 2022 Jul 1.

Comparative Medicine Research Institute, Yangzhou University, Yangzhou, China;

The innate immune DNA sensing cyclic GMP-AMP synthase (cGAS)-stimulator of IFN genes (STING) signaling pathway plays a key role in host antiviral function. Although the cGAS-STING pathway has been extensively studied, the cGAS-STING signaling in livestock and poultry is not well understood, and whether the species specificity exists is still unknown. In this study, we found that porcine and chicken STING, but not cGAS, exhibit species differences in regulation of IFN; that is, porcine (p)STING mediates good induction of IFN in mammalian cells and low IFN induction in chicken DF-1 cells; on the contrary, chicken (ch)STING mediates IFN induction only in chicken cells but not in mammalian cells. Read More

View Article and Full-Text PDF

Characterization of -Specific Th22 Cells and the Effect of Tuberculosis Disease and HIV Coinfection.

J Immunol 2022 Jul 1. Epub 2022 Jul 1.

Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa;

The development of a highly effective tuberculosis (TB) vaccine is likely dependent on our understanding of what constitutes a protective immune response to TB. Accumulating evidence suggests that CD4 T cells producing IL-22, a distinct subset termed "Th22" cells, may contribute to protective immunity to TB. Thus, we characterized -specific Th22 (and Th1 and Th17) cells in 72 people with latent TB infection or TB disease, with and without HIV-1 infection. Read More

View Article and Full-Text PDF

Unraveling a challenging diagnosis: Role of a TNF inhibitor.

Cleve Clin J Med 2022 Jul 1;89(7):368-370. Epub 2022 Jul 1.

Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH; Rheumatology Fellowship Program Director, Staff, Department of Rheumatic and Immunologic Diseases, Orthopaedic and Rheumatology Institute, Cleveland Clinic, Cleveland, OH

View Article and Full-Text PDF

Mondor disease of the breast.

Cleve Clin J Med 2022 Jul 1;89(7):371-372. Epub 2022 Jul 1.

Department of Surgery, Division of Breast Diseases, Asama Nanroku Komoro Medical Center, Nagano, Japan

View Article and Full-Text PDF

Metastatic bone disease: Early referral for multidisciplinary care.

Cleve Clin J Med 2022 Jul 1;89(7):393-399. Epub 2022 Jul 1.

Department of Orthopaedic Surgery, South West London Elective Orthopaedic Centre, London, UK; Department of Orthopaedic Surgery, Cleveland Clinic London, UK.

It is estimated that more than half of all cancers develop bony metastases, exacting a substantial cost in terms of patient quality of life and healthcare expenses. Prompt diagnosis and management have been shown to reduce morbidity and costs. When a patient with a history of cancer presents with musculoskeletal pain, heightened awareness of the risk of bone metastasis should prompt immediate referral to an orthopedic specialist. Read More

View Article and Full-Text PDF