145,834 results match your criteria development progression


Syringe Filling of High-Concentration mAb Products Using Peristaltic Pump-Based Mechanism: Challenges and Mitigation Strategies.

J Pharm Sci 2021 Sep 19. Epub 2021 Sep 19.

New Product Introduction and Product Technology, Pharma Supply Chain, GlaxoSmithKline, Strada Asolana 90, San Polo di Torrile, Parma, 43046, Italy.

Syringe filling of high-concentration mAb formulation during manufacturing of large-scale drug product batches may present challenges such as product deposition onto the area of the syringe barrel where the stopper is inserted, product splashing or dripping, droplets left after the fill cycle, filling needle clogging, product build-up inside the needle during line stoppages, variation in fill weight/volume, and potential impact on product quality attributes. In this article, a summary of these issues and approaches to overcome them are summarized. Potential failure modes of the syringe filling process and appropriate in-process controls are provided. Read More

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September 2021

Type 2 diabetes mellitus promotes the proliferation, metastasis and suppresses the apoptosis in oral squamous cell carcinoma.

J Oral Pathol Med 2021 Sep 22. Epub 2021 Sep 22.

Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya hospital of Central South University, Changsha, Hunan, 410008, China.

Background: Our previous study revealed that patients with oral squamous cell carcinoma and concomitant type 2 diabetes mellitus presented a lower 5-year survival rate. Hyperglycemia has been increasingly recognized as a risk factor for more advanced disease and poorer prognosis in patients with oral squamous cell carcinoma. However, its role remains unclear. Read More

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September 2021

Poziotinib for Patients With Exon 20 Mutant Non-Small-Cell Lung Cancer: Results From a Phase II Trial.

J Clin Oncol 2021 Sep 22:JCO2101113. Epub 2021 Sep 22.

Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.

Purpose: Targeted therapies against non-small-cell lung cancer (NSCLC) harboring mutations remain an unmet need. In this study, we assessed the efficacy and safety of poziotinib in patients with exon 20 mutant advanced NSCLC in a single-arm, open-label, phase II study.

Patients And Methods: Patients with advanced exon 20 mutant NSCLC were enrolled to receive poziotinib at a dose of 16 mg/d for 28-day cycles. Read More

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September 2021

Clinical features and outcomes of anti-neutrophil cytoplasmic autoantibody-associated vasculitis in Chinese childhood-onset patients.

Clin Exp Med 2021 Sep 22. Epub 2021 Sep 22.

Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China.

Data on anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) are limited in children. This study is to determine the clinical features and outcomes of childhood-onset AAV. A retrospective study was performed on patients who were diagnosed with AAV before 18 years old in Xiangya Hospital. Read More

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September 2021

Two-faced Janus: The dual role of macrophages in atherosclerotic calcification.

Cardiovasc Res 2021 Sep 22. Epub 2021 Sep 22.

Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, Netherlands.

Calcification is an independent predictor of atherosclerosis-related cardiovascular events. Microcalcification is linked to inflamed, unstable lesions, in comparison to the fibrotic stable plaque phenotype generally associated with advanced calcification. This paradox relates to recognition that calcification presents in a wide spectrum of manifestations that differentially impact plaque's fate. Read More

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September 2021

Gut microbiota, dysbiosis and atrial fibrillation. Arrhythmogenic mechanisms and potential clinical implications.

Cardiovasc Res 2021 Sep 22. Epub 2021 Sep 22.

Department of Cardiology, Maastricht University Medical Centre and Cardiovascular Research Institute Maastricht, Maastricht, the Netherlands.

Recent preclinical and observational cohort studies have implicated imbalances in gut microbiota composition as a contributor to atrial fibrillation (AF). The gut microbiota is a complex and dynamic ecosystem containing trillions of microorganisms, which produces bioactive metabolites influencing host health and disease development. In addition to host-specific determinants, lifestyle-related factors such as diet and drugs are important determinants of the gut microbiota composition. Read More

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September 2021

Temporo-spatial distribution of stem cell markers CD146 and p75NTR during odontogenesis in mice.

J Appl Oral Sci 2021 20;29:e20210138. Epub 2021 Sep 20.

Universidade de São Paulo, Faculdade de Odontologia, Departamento de Estomatologia, Disciplina de Patologia Oral e Maxilofacial, Laboratório de Biologia de Células-Tronco em Odontologia LABITRON, São Paulo, SP, Brasil.

Mesenchymal and epithelial stem cells were identified in dental tissues; however, knowledge about the odontogenic stem cells is limited, and there are some questions regarding their temporo-spatial dynamics in tooth development.

Objective: Our study aimed to analyze the expression of the stem cell markers CD146 and p75NTR during the different stages of odontogenesis.

Methodology: The groups consisted of 13. Read More

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September 2021

Cerebral small vessel disease, systemic vascular characteristics and potential therapeutic targets.

Aging (Albany NY) 2021 Sep 22;13(undefined). Epub 2021 Sep 22.

Institute of Biomedical and Clinical Science and NIHR Exeter Clinical Research Facility, University of Exeter Medical School, Exeter EX2 5AX, UK.

Introduction: Cerebral small vessel disease (SVD) is prevalent in the elderly population and is associated with increased risk of dementia, stroke and disability. Currently there are no clear targets or strategies for the treatment of cerebral SVD. We set out to identify modifiable vascular treatment targets. Read More

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September 2021

A Road Map for Remote Digital Health Technology for Motor Neuron Disease.

J Med Internet Res 2021 Sep 22;23(9):e28766. Epub 2021 Sep 22.

Department of Neuroscience, Sheffield Institute for Translational Neuroscien, University of Sheffield, Sheffield, United Kingdom.

Despite recent and potent technological advances, the real-world implementation of remote digital health technology in the care and monitoring of patients with motor neuron disease has not yet been realized. Digital health technology may increase the accessibility to and personalization of care, whereas remote biosensors could optimize the collection of vital clinical parameters, irrespective of patients' ability to visit the clinic. To facilitate the wide-scale adoption of digital health care technology and to align current initiatives, we outline a road map that will identify clinically relevant digital parameters; mediate the development of benefit-to-burden criteria for innovative technology; and direct the validation, harmonization, and adoption of digital health care technology in real-world settings. Read More

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September 2021

Smoldering Myeloma Treatment: Who, What, and When.

Cancer J 2021 May-Jun 01;27(3):185-189

From the Division of Hematology/Oncology, Department of Medicine, Weill Medical College of Cornell University, New York-Presbyterian Hospital, New York, NY.

Abstract: Smoldering multiple myeloma (MM) is a clonal plasma cell disorder characterized by excess marrow involvement and immunoglobulin production. It is the precursor of MM, differing by the lack of end-organ damage. Smoldering MM encompasses a heterogeneous group of patients, with a median risk of progression to active disease of 50% in the first 5 years. Read More

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September 2021

Polymorphisms in NQO1 and MPO genes and risk for bladder cancer in Tunisian population.

Mol Genet Genomic Med 2021 Sep 22:e1819. Epub 2021 Sep 22.

Laboratory of Protein Engineering and Bio-active Molecules, National Institute of Applied Science and Technology - University of Carthage, Tunis, Tunisia.

Background: NAD (P) H: quinone oxidoreductase (1) (NQO1-HGNC: 2874) and myeloperoxidase (MPO-HGNC: 7218) are two enzymes involved in phase II of the xenobiotic metabolism pathway.

Methods: In this study, a case-control analysis was conducted to investigate the relationship between genetic variations in the NQO1 (C609T, rs1800566; IVS1-27 C >G, rs689452) and MPO (G463A, rs2333227) genes and the risk for bladder cancer among Tunisian population.

Results: We have found that the MPO 463GA genotype was associated with a decreased risk of developing bladder cancer (p = 0. Read More

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September 2021

Creld2 function during unfolded protein response is essential for liver metabolism homeostasis.

FASEB J 2021 Oct;35(10):e21939

Developmental Biology of the Immune System, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.

The unfolded protein response (UPR) is associated with hepatic metabolic function, yet it is not well understood how endoplasmic reticulum (ER) disturbance might influence metabolic homeostasis. Here, we describe the physiological function of Cysteine-rich with EGF-like domains 2 (Creld2), previously characterized as a downstream target of the ER-stress signal transducer Atf6. To this end, we generated Creld2-deficient mice and induced UPR by injection of tunicamycin. Read More

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October 2021

Mitotic timing is differentially controlled by A- and B-type cyclins and by CDC6 associated with a CDK inhibitor Xic1 in cell-free extract.

Int J Dev Biol 2021 ;65(7-8-9):487-496

Univ Rennes, UMR 6290, CNRS, Institute of Genetics and Development of Rennes - IGDR, Cell Cycle Group, Faculty of Medicine, Rennes, France.

The timing of the M-phase is precisely controlled by a CDC6-dependent mechanism inhibiting the mitotic histone H1 kinase. Here, we describe the differential regulation of the dynamics of this mitotic kinase activity by exogenous cyclin A or cyclin B in the cycling extracts. We show that the experimental increase in cyclin A modifies only the level of histone H1 kinase activity, while the cyclin B increase modifies two parameters: histone H1 kinase activity and the timing of its full activation, which is accelerated. Read More

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January 2021

Exosomes and the Extracellular Matrix: a dynamic interplay in cancer progression.

Int J Dev Biol 2021 Sep 20. Epub 2021 Sep 20.

Biochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory ofBiochemistry, Department of Chemistry, University of Patras, Greece.

Exosomes are a subtype of extracellular vesicle (EVs) composed of a lipid bilayer which carry various cargoes such as nucleic acids, proteins, and bioactive lipids. Cancer cells release exosomes to promote cell communication and interaction with the extracellular matrix (ECM). ECM regulates the secretion and uptake of exosomes. Read More

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September 2021

Characterization of cell cycle and apoptosis in CHO cell culture using flow cytometry for bioprocess monitoring.

Biotechnol Prog 2021 Sep 22:e3211. Epub 2021 Sep 22.

Biopharm Process Development, GlaxoSmithKline.

Chinese Hamster Ovary cells are by far the most important mammalian cell lines used for producing antibodies and other therapeutic proteins. It is critical to fully understand their physiological conditions during a bioprocess in order to achieve the highest productivity and the desired product quality. Flow cytometry technology possesses unique advantages for measuring multiple cellular attributes for a given cell and examining changes in cell culture heterogeneity over time that can be used as metrics for enhanced process understanding and control strategy. Read More

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September 2021

Chronic inflammation and long-lasting changes in the gastric mucosa after Helicobacter pylori infection involved in gastric cancer.

Inflamm Res 2021 Sep 21. Epub 2021 Sep 21.

Department of Gastroenterology, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, People's Republic of China.

Objective: Helicobacter pylori (H. pylori) infects approximately half of the world's population, as one of the most common chronic infections. H. Read More

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September 2021

Frailty in Young and Middle-Aged Adults: An Integrative Review.

J Frailty Aging 2021 ;10(4):327-333

Courtney Loecker, MSN, APRN-NP, AGACNP-BC, 985330 Nebraska Medical Center, Omaha, NE, USA, 402-559-6571 phone, 402-472-7345 fax.

Background: Frailty is a public health priority resulting in poor health outcomes and early mortality in older adults. Early identification, management, and prevention of frailty may reduce frailty trajectory into later life. However, little is known about frailty in younger adults. Read More

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January 2021

Configural Analysis of Oscillating Progression.

J Pers Oriented Res 2021 26;7(1):14-21. Epub 2021 Aug 26.

University of Furtwangen, Germany.

Oscillating series of scores can be approximated with locally optimized smoothing functions. In this article, we describe how such series can be approximated with locally estimated (loess) smoothing, and how Configural Frequency Analysis (CFA) can be used to evaluate and interpret results. Loess functions are often hard to describe because they cannot be represented by just one function that has interpretable parameters. Read More

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Endolysosomal ion channel MCOLN2 (Mucolipin-2) promotes prostate cancer progression via IL-1β/NF-κB pathway.

Br J Cancer 2021 Sep 21. Epub 2021 Sep 21.

School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.

Background: Prostate cancer (Pca) is the most common cancer type among males worldwide. Dysregulation of Ca signaling plays important roles during Pca progression. However, there is lack of information about the role of endolysosomal Ca -permeable channels in Pca progression. Read More

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September 2021

Single-cell transcriptome analysis reveals cellular heterogeneity in the ascending aortas of normal and high-fat diet-fed mice.

Exp Mol Med 2021 Sep 21. Epub 2021 Sep 21.

Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China.

The aorta contains numerous cell types that contribute to vascular inflammation and thus the progression of aortic diseases. However, the heterogeneity and cellular composition of the ascending aorta in the setting of a high-fat diet (HFD) have not been fully assessed. We performed single-cell RNA sequencing on ascending aortas from mice fed a normal diet and mice fed a HFD. Read More

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September 2021

Risk factors associated with durable progression-free survival in relapsed or refractory multiple myeloma patients treated with anti-BCMA CAR-T cell therapy.

Clin Cancer Res 2021 Sep 21. Epub 2021 Sep 21.

Bone Marrow Transplantation Center, the first Affiliated Hospital, School of Medicine, Zhejiang University

Purpose: B-cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T) cell therapy results in high remission rates in patients with relapsed/refractory (R/R) multiple myeloma (MM). However, the factors associated with prognosis following CAR-T cell therapy are unknown.

Experimental Design: Between July 1, 2018, and July 31, 2020, 61 patients with R/R MM received anti-BCMA CAR-T cell therapy (Chictr. Read More

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September 2021

Mechanosensitive cation channel Piezo1 contributes to ventilator-induced lung injury by activating RhoA/ROCK1 in rats.

Respir Res 2021 Sep 21;22(1):250. Epub 2021 Sep 21.

Department of Anesthesiology, Institute of Anesthesia, Emergency and Critical Care, Yangzhou University Affiliated Northern Jiangsu People's Hospital, 98 Nan Tong Western Road, Yangzhou, 225001, Jiangsu, China.

Background: Mechanical ventilation can induce or aggravate lung injury, which is termed ventilator-induced lung injury (VILI). Piezo1 is a key element of the mechanotransduction process and can transduce mechanical signals into biological signals by mediating Ca influx, which in turn regulates cytoskeletal remodeling and stress alterations. We hypothesized that it plays an important role in the occurrence of VILI, and investigated the underlying mechanisms. Read More

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September 2021

Single-cell DNA and RNA sequencing reveals the dynamics of intra-tumor heterogeneity in a colorectal cancer model.

BMC Biol 2021 Sep 21;19(1):207. Epub 2021 Sep 21.

Division of Bioinformatics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.

Background: Intra-tumor heterogeneity (ITH) encompasses cellular differences in tumors and is related to clinical outcomes such as drug resistance. However, little is known about the dynamics of ITH, owing to the lack of time-series analysis at the single-cell level. Mouse models that recapitulate cancer development are useful for controlled serial time sampling. Read More

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September 2021

Canine mammary cancer in overweight or obese female dogs is associated with intratumoral microvessel density and macrophage counts.

Vet Pathol 2021 Sep 21:3009858211040481. Epub 2021 Sep 21.

Konkuk University, Gwangjin-gu, Seoul, Republic of Korea.

Obesity is a major health condition owing to its effects on chronic diseases and cancers in humans, but little information is available regarding the role of obesity in canine mammary cancer (CMC). In the present study, we performed immunohistochemistry to investigate the effect of obesity on CMC by analyzing the number of tumor-associated macrophages, intratumoral microvessel density (iMVD), and the expression of prognostic factors including epidermal growth factor receptor (EGFR), cyclooxygenase 2 (COX-2), and Ki67 in CMC specimens. These data were compared in CMC specimens from lean or ideal body weight (Group 1) versus overweight or obese (Group 2) female dogs ( = 60 for each group). Read More

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September 2021

Increasing of matrix metalloproteinase 3 in bovine endometritis.

Theriogenology 2021 Sep 4;175:83-88. Epub 2021 Sep 4.

Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou, 730050, PR China; Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou, 730050, PR China.

Matrix metalloproteinase 3 (MMP3), a key member of the MMPs family, is involved in the modulation of endometrial inflammation and innate immunity. However, the role of MMP3 in bovine endometritis remains unknown. To investigate the role of MMP3 in bovine endometritis, endometrial MMP3 expression were determined in uterine biopsies from twenty 40-60 days postpartum dairy cows, which six were healthy cows and fourteen were endometritic cows. Read More

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September 2021

Artificial intelligence approach towards assessment of condition of COVID-19 patients - Identification of predictive biomarkers associated with severity of clinical condition and disease progression.

Comput Biol Med 2021 Sep 14;138:104869. Epub 2021 Sep 14.

University of Kragujevac, Faculty of Engineering, Sestre Janjić 6, 34000, Kragujevac, Serbia; Bioengineering Research and Development Center (BioIRC), Prvoslava Stojanovića 6, 34000, Kragujevac, Serbia. Electronic address:

Background And Objectives: Although ML has been studied for different epidemiological and clinical issues as well as for survival prediction of COVID-19, there is a noticeable shortage of literature dealing with ML usage in prediction of disease severity changes through the course of the disease. In that way, predicting disease progression from mild towards moderate, severe and critical condition, would help not only to respond in a timely manner to prevent lethal results, but also to minimize the number of patients in hospitals where this is not necessary.

Methods: We present a methodology for the classification of patients into 4 distinct categories of the clinical condition of COVID-19 disease. Read More

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September 2021

Trifluridine/tipiracil in combination with oxaliplatin and either bevacizumab or nivolumab in metastatic colorectal cancer: a dose-expansion, phase I study.

ESMO Open 2021 Sep 18;6(5):100270. Epub 2021 Sep 18.

Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Barcelona, Spain; UVic-UCC, IOB-Quiron, Barcelona, Spain.

Background: In preclinical studies trifluridine/tipiracil (FTD/TPI) plus oxaliplatin (Industriestrasse, Holzkirchen, Germany) sensitised microsatellite stable (MSS) metastatic colorectal cancer (mCRC) to anti-programmed cell death protein-1; the addition of oxaliplatin or bevacizumab (F Hoffmann- la ROCHE AG, Kaiseraugst, Switzerland) enhanced the antitumour effects of FTD/TPI. This study aimed to investigate the safety and efficacy of FTD/TPI plus oxaliplatin and either bevacizumab or nivolumab (Uxbridge business Park, Uxbridge, United Kingdom) in patients with mCRC who had progressed after at least one prior line of treatment.

Patients And Methods: In 14-day cycles, patients received FTD/TPI 35 mg/m (twice daily, days 1-5) plus oxaliplatin 85 mg/m (day 1), and, on day 1, either bevacizumab 5 mg/kg (cohort A) or nivolumab 3 mg/kg (cohort B). Read More

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September 2021

Alternative Splicing and Liver Disease.

Ann Hepatol 2021 Sep 18:100534. Epub 2021 Sep 18.

Fondazione Italiana Fegato-Onlus, Bldg. Q, AREA Science Park, ss14, Km 163.5, Basovizza, 34149 Trieste, Italy. Electronic address:

Alternative splicing produces complex and dynamic changes in the protein isoforms that are necessary for the proper biological functioning of the metabolic pathways involved in liver development and hepatocyte homeostasis. Changes in the physiological state of alternatively spliced forms are increasingly linked to liver pathologies. This may occur when the expression or function of the set of proteins controlling the alternative splicing processes are altered by external effectors such as oxidative stress and other environmental variations. Read More

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September 2021

Characterizing the role of the dark kinome in neurodegenerative disease - A mini review.

Authors:
Alison D Axtman

Biochim Biophys Acta Gen Subj 2021 Sep 18:130014. Epub 2021 Sep 18.

UNC Eshelman School of Pharmacy, Division of Chemical Biology and Medicinal Chemistry, Structural Genomics Consortium, Chapel Hill, NC, USA. Electronic address:

Background: Drugs that modulate previously unexplored targets could potentially slow or halt the progression of neurodegenerative diseases. Several candidate proteins lie within the dark kinome, those human kinases that have not been well characterized. Much of the kinome (~80%) remains poorly studied, and these targets likely harbor untapped biological potential. Read More

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September 2021

New concepts on immunology of Multiple Sclerosis.

Presse Med 2021 Sep 18:104072. Epub 2021 Sep 18.

Univ Rennes, CHU Rennes, Neurology, Inserm, CIC 1414 (Centre d'Investigation Clinique de Rennes), F-35000 Rennes, France; Unité Mixte de Recherche (UMR) S1236, INSERM, University of Rennes, Etablissement Français du Sang, Rennes, France; Suivi Immunologique des Thérapeutiques Innovantes, Centre Hospitalier Universitaire de Rennes, Etablissement Français du Sang, Rennes, France. Electronic address:

Multiple sclerosis (MS) is a chronic inflammatory and immune-driven demyelinating disease of the central nervous system (CNS). During the past decade, major advances have been made to understand the development of MS as well as its progressive stage. Here, we discuss some emerging concepts on immunology of MS, including the growing interest in the involvement of gut microbiota and the recent pathological concepts on the progression phase. Read More

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September 2021