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Current Molecular Medicine 2020The market segment of new biological drugs (monoclonal antibodies, fusion proteins, antibody-drug conjugates, and new modality protein therapeutics) is rapidly growing,... (Review)
Review
The market segment of new biological drugs (monoclonal antibodies, fusion proteins, antibody-drug conjugates, and new modality protein therapeutics) is rapidly growing, especially after the patent expiration of the original biologics, initiating the emergence of biosimilars. N-glycosylation of therapeutic proteins has high importance on their stability, safety, immunogenicity, efficacy, and serum half-life. Therefore, Nglycosylation is considered to be one of the critical quality attributes. Consequently, it should be rigorously monitored during the development, manufacturing, and release of glycoprotein biologicals. In this review, first, the regulatory considerations for biosimilars are shortly summarized, followed by conferring the analytical techniques needed for monitoring and characterization of the N-glycosylation of biological drugs. Particular respect is paid to liquid phase separation techniques with high sensitivity and highresolution detection methods, including laser-induced fluorescence and mass spectrometry.
Topics: Biological Therapy; Biosimilar Pharmaceuticals; Glycosylation; Humans; Molecular Medicine; Polysaccharides
PubMed: 33272172
DOI: 10.2174/1566524020999201203212352 -
International Journal of Molecular... Mar 2023Molecular pathology, diagnostics and therapeutics are three closely related topics of critical importance in medical research and clinical practice [...].
Molecular pathology, diagnostics and therapeutics are three closely related topics of critical importance in medical research and clinical practice [...].
Topics: Pathology, Molecular
PubMed: 36902493
DOI: 10.3390/ijms24055063 -
JAMA Pediatrics Nov 2023Currently, the diagnostic yield of exome sequencing (ES) and chromosomal microarray analysis (CMA) for short stature cohorts is uncertain. Despite previous studies...
IMPORTANCE
Currently, the diagnostic yield of exome sequencing (ES) and chromosomal microarray analysis (CMA) for short stature cohorts is uncertain. Despite previous studies reporting the widespread use of ES and CMA, a definitive diagnostic yield has not been established.
OBJECTIVE
To investigate the diagnostic yield of ES and CMA in short stature.
DATA SOURCES
A systematic literature search was conducted using relevant keywords in 3 databases (PubMed, Embase, and Web of Science) in February 2023.
STUDY SELECTION
Eligible studies for meta-analysis were those that had at least 10 participants with short stature who were diagnosed using either ES or CMA and the number of diagnosed patients was reported. Of 5222 identified studies, 20 were eventually included in the study.
DATA EXTRACTION AND SYNTHESIS
Two independent investigators extracted relevant information from each study, which was then synthesized using proportional meta-analysis to obtain the overall diagnostic yield of ES and CMA.
MAIN OUTCOMES AND MEASURES
The primary outcome measure was to determine the overall diagnostic yield of ES and CMA. A subgroup meta-analysis was also performed to assess if the diagnostic yield varied depending on whether ES was used as a first-tier or last-resort test. Additionally, a meta-regression was carried out to investigate how the diagnostic yield varied over time.
RESULTS
Twenty studies were included, comprising 1350 patients with short stature who underwent ES and 1070 patients who completed CMA. The overall diagnostic yield of ES among the cohorts and CMA among the cohorts was found to be 27.1% (95% CI, 18.1%-37.2%) and 13.6% (95% CI, 9.2%-18.7%), respectively. No statistically significant difference was observed between the first-tier (27.8%; 95% CI, 15.7%-41.8%) and last-resort groups (25.6%; 95% CI, 13.6%-39.6%) (Pā=ā.83) or in the percentage of positively diagnosed patients over time. No statistically significant difference was observed between the first-tier (27.8%; 95% CI, 15.7%-41.8%) and last-resort groups (25.6%; 95% CI, 13.6%-39.6%) (Pā=ā.83) or in the percentage of positively diagnosed patients over time.
CONCLUSION AND RELEVANCE
This systematic review and meta-analysis provides high-level evidence supporting the diagnostic efficacy of ES and CMA in patients with short stature. The findings serve as a solid reference for clinicians when making informed decisions about recommending these genetic tests.
Topics: Humans; Exome Sequencing; Pathology, Molecular; Genetic Testing; Microarray Analysis
PubMed: 37695591
DOI: 10.1001/jamapediatrics.2023.3566 -
Neurochemical Research Sep 2022Ischemic stroke leads to acute neuron death and forms an injured core, triggering delayed cell death at the penumbra. The impaired brain functions after ischemic stroke... (Review)
Review
Ischemic stroke leads to acute neuron death and forms an injured core, triggering delayed cell death at the penumbra. The impaired brain functions after ischemic stroke are hardly recovered because of the limited regenerative properties. However, recent rodent intervention studies manipulating the extracellular environments at the subacute phase shed new light on the regenerative potency of the injured brain. This review introduces the rational design of artificial extracellular matrix (ECM) mimics using supramolecular peptidic scaffolds, which self-assemble via non-covalent bonds and form hydrogels. The facile customizability of the peptide structures allows tuning the hydrogels' physical and biochemical properties, such as charge states, hydrophobicity, cell adhesiveness, stiffness, and stimuli responses. Supramolecular peptidic materials can create safer and more economical drugs than polymer materials and cell transplantation. We also discuss the importance of activating developmental programs for the recovery at the subacute phase of ischemic stroke. Self-assembling molecular medicine mimicking the ECMs and activating developmental programs may stand as a new drug modality of regenerative medicine in various tissues.
Topics: Extracellular Matrix; Humans; Hydrogels; Ischemic Stroke; Molecular Medicine; Peptides; Regenerative Medicine; Tissue Engineering
PubMed: 35666393
DOI: 10.1007/s11064-022-03638-5 -
Military Medical Research Mar 2022Traditional diagnostic strategies for infectious disease detection require benchtop instruments that are inappropriate for point-of-care testing (POCT). Emerging... (Review)
Review
Traditional diagnostic strategies for infectious disease detection require benchtop instruments that are inappropriate for point-of-care testing (POCT). Emerging microfluidics, a highly miniaturized, automatic, and integrated technology, are a potential substitute for traditional methods in performing rapid, low-cost, accurate, and on-site diagnoses. Molecular diagnostics are widely used in microfluidic devices as the most effective approaches for pathogen detection. This review summarizes the latest advances in microfluidics-based molecular diagnostics for infectious diseases from academic perspectives and industrial outlooks. First, we introduce the typical on-chip nucleic acid processes, including sample preprocessing, amplification, and signal read-out. Then, four categories of microfluidic platforms are compared with respect to features, merits, and demerits. We further discuss application of the digital assay in absolute nucleic acid quantification. Both the classic and recent microfluidics-based commercial molecular diagnostic devices are summarized as proof of the current market status. Finally, we propose future directions for microfluidics-based infectious disease diagnosis.
Topics: Communicable Diseases; Humans; Lab-On-A-Chip Devices; Microfluidic Analytical Techniques; Microfluidics; Pathology, Molecular
PubMed: 35300739
DOI: 10.1186/s40779-022-00374-3 -
International Journal of Molecular... Dec 2021Female infertility is the main reason for involuntary childlessness nowadays [...].
Female infertility is the main reason for involuntary childlessness nowadays [...].
Topics: Embryonic Development; Female; Humans; Infertility, Female; Molecular Medicine; Oogenesis
PubMed: 34948313
DOI: 10.3390/ijms222413517 -
Psychological Medicine Oct 2021Suicidal ideation, suicide attempt (SA) and suicide are significantly heritable phenotypes. However, the extent to which these phenotypes share genetic architecture is... (Review)
Review
Suicidal ideation, suicide attempt (SA) and suicide are significantly heritable phenotypes. However, the extent to which these phenotypes share genetic architecture is unclear. This question is of great relevance to determining key risk factors for suicide, and to alleviate the societal burden of suicidal thoughts and behaviors (STBs). To help address the question of heterogeneity, consortia efforts have recently shifted from a focus on suicide within the context of major psychopathology (e.g. major depressive disorder, schizophrenia) to suicide as an independent entity. Recent molecular studies of suicide risk by members of the Psychiatric Genomics Consortium and the International Suicide Genetics Consortium have identified genome-wide significant loci associated with SA and with suicide death, and have examined these phenotypes within and outside of the context of major psychopathology. This review summarizes important insights from epidemiological and biometrical research on suicide, and discusses key empirical findings from molecular genetic examinations of STBs. Polygenic risk scores for these phenotypes have been observed to be associated with case-control status and other risk phenotypes. In addition, estimated shared genetic covariance with other phenotypes suggests specific medical and psychiatric risks beyond major depressive disorder. Broadly, molecular studies suggest a complexity of suicide etiology that cannot simply be accounted for by depression. Discussion of the state of suicide genetics, a growing field, also includes important ethical and clinical implications of studying the genetic risk of suicide.
Topics: Genome-Wide Association Study; Humans; Molecular Epidemiology; Phenotype; Risk Factors; Suicidal Ideation; Suicide, Attempted
PubMed: 34030748
DOI: 10.1017/S0033291721001720 -
Pathologie (Heidelberg, Germany) Mar 2024With the advancements in precision medicine, the demands on pathological diagnostics have increased, requiring standardized, quantitative, and integrated assessments of... (Review)
Review
With the advancements in precision medicine, the demands on pathological diagnostics have increased, requiring standardized, quantitative, and integrated assessments of histomorphological and molecular pathological data. Great hopes are placed in artificial intelligence (AI) methods, which have demonstrated the ability to analyze complex clinical, histological, and molecular data for disease classification, biomarker quantification, and prognosis estimation. This paper provides an overview of the latest developments in pathology AI, discusses the limitations, particularly concerning the black box character of AI, and describes solutions to make decision processes more transparent using methods of so-called explainable AI (XAI).
Topics: Artificial Intelligence; Pathology, Molecular; Hope; Precision Medicine
PubMed: 38315198
DOI: 10.1007/s00292-024-01308-7 -
Angewandte Chemie (International Ed. in... Feb 2021The advent of SELEX (systematic evolution of ligands by exponential enrichment) technology has shown the ability to evolve artificial ligands with affinity and... (Review)
Review
The advent of SELEX (systematic evolution of ligands by exponential enrichment) technology has shown the ability to evolve artificial ligands with affinity and specificity able to meet growing clinical demand for probes that can, for example, distinguish between the target leukemia cells and other cancer cells within the matrix of heterogeneity, which characterizes cancer cells. Though antibodies are the conventional and ideal choice as a molecular recognition tool for many applications, aptamers complement the use of antibodies due to many unique advantages, such as small size, low cost, and facile chemical modification. This Minireview will focus on the novel applications of aptamers and SELEX, as well as opportunities to develop molecular tools able to meet future clinical needs in biomedicine.
Topics: Aptamers, Nucleotide; Humans; Nucleic Acids; Pathology, Molecular
PubMed: 32282107
DOI: 10.1002/anie.202003563 -
Journal Der Deutschen Dermatologischen... Apr 2023Molecular diagnostics (MDx) has become an indispensable pillar of diagnostics in dermatology. Modern sequencing technologies allow for identification of rare... (Review)
Review
Molecular diagnostics (MDx) has become an indispensable pillar of diagnostics in dermatology. Modern sequencing technologies allow for identification of rare genodermatoses, analysis of somatic mutations in melanoma are prerequisite for targeted therapies, and cutaneous infectious pathogens are quickly detected by PCR and other amplification methods. However, to push innovation in molecular diagnostics and tackle so far unmet clinical needs, research activities need to be bundled and the pipeline from idea to MDx product clearly rolled out. Only then, the requirements for technical validity and clinical utility of novel biomarkers can be fulfilled and the long-term vision of personalized medicine will be realized.
Topics: Humans; Dermatology; Pathology, Molecular; Melanoma; Biomarkers; Precision Medicine
PubMed: 36892267
DOI: 10.1111/ddg.15010