Clinical Peptidomics: Advances in Instrumentation, Analyses, and Applications

Extensive effort has been devoted to the discovery,development,and validation of biomarkers for early disease diagnosis and prognosis as well as rapid evaluation of the response to therapeutic interventions.Genomic and transcriptomic profiling are well-established means to identify disease-associated biomarkers.However,analysis of disease-associated peptidomes can also identify novel peptide biomarkers or signatures that provide sensitive and specific diagnostic and prognostic information for specific malignant,chronic,and infectious diseases.Growing evidence also suggests that peptidomic changes in liquid biopsies may more effectively detect changes in disease pathophysiology than other molecular methods.Knowledge gained from peptide-based diagnostic,therapeutic,and imaging approaches has led to promising new theranostic applications that can increase their bioavailability in target tissues at reduced doses to decrease side effects and improve treatment responses.However,despite major advances,multiple factors can still affect the utility of peptidomic data.This review summarizes several remaining challenges that affect peptide biomarker discovery and their use as diagnostics,with a focus on technological advances that can improve the detection,identification,and monitoring of peptide biomarkers for personalized medicine.

Recent advances to address challenges in extracellular vesicle-based applications for lung cancer

Lung cancer,highly prevalent and the leading cause of cancer-related death globally,persists as a significant challenge due to the lack of definitive tumor markers for early diagnosis and personalized therapeutic interventions.Recently,extracellular vesicles(EVs),functioning as natural carriers for intercellular communication,have received increasing attention due to their ability to traverse biological barriers and deliver diverse biological cargoes,including cytosolic proteins,cell surface proteins,microRNA,lncRNA,circRNA,DNA,and lipids.EVs are increasingly recognized as a valuable resource for non-invasive liquid biopsy,as well as drug delivery platforms,and anticancer vaccines for precision medicine in lung cancer.Herein,given the diagnostic and therapeutic potential of tumor-associated EVs for lung cancer,we discuss this topic from a translational standpoint.We delve into the specific roles that EVs play in lung cancer carcinogenesis and offer a particular perspective on how advanced engineering technologies can overcome the current challenges and expedite and/or enhance the translation of EVs from laboratory research to clinical settings.

Strategies for advanced personalized tuberculosis diagnosis:Current technologies and clinical approaches

Diagnosis of tuberculosis can be difficult as advances in molecular diagnosis approaches(especially nanoparticles combined with high-throughput mass spectrometry for detecting mycobacteria peptide)and personalized medicine result in many changes to the diagnostic framework.This review will address issues concerning novel technologies from bench to bed and new strategies for personalized tuberculosis diagnosis.

Nanotechnology Powered CRISPR-Cas Systems for Point of Care Diagnosis and Therapeutic

Inspired by the successful application of Cas9 gene editing for“genome surgery,”we are looking back at what has been accomplished in the ten years of CRISPR editing.Intense effort is now focused on how to utilize the unique functions of CRISPR-Cas systems for molecular diagnostics and the next generation of therapeutic tools.CRISPR-Cas systems have two major advantages for gene editing that render them attractive for these new applications,specifically the ability to easily control their target recognition specificity and to couple this specificity to a targeted or secondary cleavage activity.However,despite the great potential of CRISPR/Cas for both gene editing and diagnosis,its medical applications have yet to be fully realized due factors that limit their delivery or utility for point-of-care(POC)applications.In this editorial note,we discuss how nanotechnology can address challenges associated with new CRISPR applications and what nanotechnology-specific advances are needed to circumvent remaining barriers that limit the development or use of new CRISPR/CAS-based genome editing and diagnostic approaches.

Integrated proteomic profiling identifies amino acids selectively cytotoxic to pancreatic cancer cells

Pancreatic adenocarcinoma(PDAC)is one of the most deadly cancers,characterized by extremely limited therapeutic options and a poor prognosis,as it is often diagnosed during late disease stages.Innovative and selective treatments are urgently needed,since current therapies have limited efficacy and significant side effects.Through proteomics analysis of extracellular vesicles,we discovered an imbalanced distribution of amino acids secreted by PDAC tumor cells.Our findings revealed that PDAC cells preferentially excrete proteins with certain preferential amino acids,including isoleucine and histidine,via extracellular vesicles.These amino acids are associated with disease progression and can be targeted to elicit selective toxicity to PDAC tumor cells.Both in vitro and in vivo experiments demonstrated that supplementation with these specific amino acids effectively eradicated PDAC cells.Mechanistically,we also identified XRN1 as a potential target for these amino acids.The high selectivity of this treatment method allows for specific targeting of tumor metabolism with very low toxicity to normal tissues.Furthermore,we found this treatment approach is easy-to-administer and with sustained tumor-killing effects.Together,our findings reveal that exocytosed amino acids may serve as therapeutic targets for designing treatments of intractable PDAC and potentially offer alternative treatments for other types of cancers.