Affinage

PROS1

Vitamin K-dependent protein S · UniProt P07225

Length
676 aa
Mass
75.1 kDa
Annotated
2026-06-10
100 papers in source corpus 9 papers cited in narrative 9 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/6 claims corpus-supported (83%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PROS1 (Protein S) is a secreted ligand for the TAM-family receptor tyrosine kinases Tyro3 and Mer/MERTK — but not Axl — through which it regulates innate immune polarization and cancer-cell survival (PMID:29708510, PMID:31766614). In macrophages, tumor- or myeloid-derived PROS1 engages Mer and Tyro3 to suppress M1 pro-inflammatory polarization, an effect requiring a PTP1b-Mer complex and lost in PTP1b-, Mer-, or Tyro3-deficient (but not Axl-deficient) macrophages (PMID:29708510). Myeloid-specific PROS1 acts via MERTK kinase activity and the Socs3/NF-κB pathway to restrain TNF-α and IL-6, while restraining IL-10 in a MERTK-independent manner; loss of myeloid PROS1 drives a pro-metastatic, EMT-promoting, IL-10-dependent macrophage secretome (PMID:33848267). In epithelial and gingival cells, exogenous PROS1 dampens LPS-induced inflammatory cytokine and MMP production in a Tyro3-dependent fashion through SOCS1/3 upregulation and STAT1/3 modulation, with protective effects in a rat periodontitis model (PMID:30729671). In cancer cells, PROS1 preferentially activates Tyro3-Erk signaling (and Akt where Tyro3 is expressed alone), promoting survival and suppressing apoptosis, and its loss triggers both extrinsic and intrinsic apoptotic pathways and reduces migration, invasion, and proliferation (PMID:31766614, PMID:27840905). Hereditary protein S deficiency arises from PROS1 point mutations that cause defective folding, instability, and impaired secretion despite normal transcript levels (PMID:11776305), and from large genomic deletions and duplications that account for roughly one-third of mutation-negative cases (PMID:19466456, PMID:16363235).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2000 Low

    Establishing the spectrum of disease-causing PROS1 variants was needed to define the genetic basis of hereditary protein S deficiency; cataloging missense, nonsense, and frameshift mutations and clarifying that the P460 variant is a non-causal polymorphism sharpened genotype interpretation.

    Evidence SSCP/heteroduplex mutation detection across all PROS1 exons with co-segregation analysis in 31 propositi

    PMID:10790208

    Open questions at the time
    • Mutation catalog by SSCP without biochemical demonstration of the consequence of each variant
    • No functional assay distinguishing folding versus secretion defects
  2. 2001 Medium

    The molecular mechanism by which point mutations cause protein S deficiency was unresolved; demonstrating that mutant transcripts are present at normal levels reframed the defect as one of protein folding/stability and impaired secretion rather than absent mRNA.

    Evidence Sequencing of five novel mutations, platelet mRNA RT-PCR, and computational structural modeling across multiple families

    PMID:11776305

    Open questions at the time
    • Folding/secretion defect inferred from modeling and mRNA presence, not directly measured biochemically
    • No cellular trafficking or degradation assay for the mutant proteins
  3. 2005 Medium

    A substantial fraction of protein S-deficient families lack detectable point mutations; identifying large genomic deletions in 38% of such families established gross rearrangements as a distinct disease mechanism.

    Evidence SNP/microsatellite segregation mapping confirmed by qPCR, with haplotype analysis showing independent deletion events

    PMID:16363235

    Open questions at the time
    • Small family number
    • Breakpoint architecture and recurrence mechanism not defined
  4. 2009 Medium

    The frequency and types of PROS1 copy number variation in mutation-negative patients were unknown; systematic MLPA confirmed complete/partial deletions and duplications in roughly one-third of cases, consolidating CNVs as a common mechanism.

    Evidence MLPA with confirmatory qPCR for copy number analysis across 18 protein S-deficient probands

    PMID:19466456

    Open questions at the time
    • Single-laboratory cohort
    • Functional consequence of duplications not characterized
  5. 2016 Medium

    Whether PROS1 has a cell-autonomous role in tumor survival was unclear; silencing PROS1 in glioblastoma cells showed it supports proliferation, migration, invasion, and survival, linking its loss to apoptosis via both extrinsic and intrinsic pathways and to downregulation of GAS6 and TAM receptors.

    Evidence siRNA knockdown in LN18 glioblastoma cells with apoptosis, migration, invasion, proliferation, and pathway assays

    PMID:27840905

    Open questions at the time
    • Single cell line, single laboratory
    • Autocrine/paracrine TAM signaling inferred, not directly demonstrated
    • Receptor specificity not resolved
  6. 2018 High

    The receptor and downstream wiring of PROS1 immune signaling was undefined; reciprocal genetic knockouts established PROS1 as a ligand for Mer and Tyro3 (not Axl) that suppresses macrophage M1 polarization via a PTP1b-Mer complex, defining a tumor immune-evasion axis.

    Evidence CRISPR deletion of tumor Pros1, macrophage Mer/Tyro3/Axl/PTP1b knockouts, cytokine assays, and in vivo tumor/survival models

    PMID:29708510

    Open questions at the time
    • Structural basis of Tyro3/Mer selectivity over Axl not defined
    • Direct PROS1-receptor binding affinities not quantified
  7. 2019 Medium

    Whether PROS1-TAM signaling is restricted to immune cells was open; in cancer cells PROS1 was shown to preferentially activate Tyro3-Erk (and Akt when Tyro3 is alone) while Gas6 drives Axl-Akt, and to protect cells from apoptosis, establishing ligand-receptor specificity within the TAM family.

    Evidence Receptor/kinase phosphorylation Western blots across multiple cancer cell lines with ligand traps, warfarin controls, and apoptosis assays

    PMID:31766614

    Open questions at the time
    • Single laboratory
    • Mechanism of context-dependent Akt activation when Tyro3 is alone not resolved
  8. 2019 Medium

    The anti-inflammatory mechanism of PROS1 in non-immune epithelium was unknown; exogenous PROS1 was shown to suppress LPS-induced cytokines and MMPs in a Tyro3-dependent manner via SOCS1/3 and STAT1/3 modulation, with protective effects in vivo.

    Evidence LPS stimulation of human gingival epithelial cells with Tyro3 knockdown, molecular readouts, and a rat periodontitis model

    PMID:30729671

    Open questions at the time
    • Single laboratory
    • Direct Tyro3 engagement by PROS1 in epithelium not biochemically demonstrated
  9. 2021 High

    The in vivo source and effector pathway of immunosuppressive PROS1 in metastasis were unresolved; conditional myeloid Pros1 deletion showed MERTK kinase-dependent control of TNF-α/IL-6 via Socs3/NF-κB and MERTK-independent IL-10 regulation, linking the PROS1/MERTK axis to suppression of metastatic seeding.

    Evidence Myeloid-specific conditional Pros1 knockout, BMDM conditioned-medium EMT/invasion assays, MERTK inhibition, and two metastasis models

    PMID:33848267

    Open questions at the time
    • Mechanism of MERTK-independent IL-10 regulation not identified
    • Receptor mediating IL-10 control not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the same PROS1 ligand achieves cell-type- and context-dependent selectivity among Tyro3/Mer/MERTK receptors and divergent downstream outputs (Erk vs Akt; MERTK-dependent vs -independent cytokines) remains unresolved.
  • No structural model of PROS1-receptor binding
  • Determinants of receptor selectivity unknown
  • Connection between coagulation function and TAM-ligand function not addressed in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005576 extracellular region 2
Pathway
R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-162582 Signal Transduction 2 R-HSA-5357801 Programmed Cell Death 2
Partners
MERTKPTPN1TYRO3

Evidence

Reading pass · 9 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 Tumor-secreted Protein S (PROS1) acts as a ligand for Mer and Tyro3 (but not Axl) receptor tyrosine kinases on macrophages, suppressing M1 polarization (inhibiting IFN-γ/LPS-induced pro-inflammatory cytokine expression). The suppressive signaling involves PTP1b complexing with Mer, as M1 cytokine suppression was lost in PTP1b-KO macrophages and Mer-KO or Tyro3-KO macrophages but not Axl-KO macrophages. CRISPR-based deletion of Pros1 in tumor cells, macrophage KO mice (Mer, Tyro3, Axl, PTP1b), in vitro cytokine assays, in vivo tumor models with survival readout The Journal of Clinical Investigation High 29708510
2021 Myeloid cell-derived PROS1 suppresses metastatic seeding via the PROS1/MERTK axis in bone marrow-derived macrophages. Pros1 deletion in myeloid cells elevated TNF-α, IL-6, Nos2, and IL-10 through modulation of the Socs3/NF-κB pathway. Conditioned medium from PROS1-cKO macrophages promoted tumor cell EMT and invasion in an IL-10-dependent manner. Notably, MERTK kinase activity was required for PROS1-mediated suppression of TNF-α and IL-6, but IL-10 regulation by PROS1 was MERTK-independent. Conditional myeloid-specific Pros1 knockout mice, bone marrow-derived macrophage conditioned medium assays, MERTK kinase inhibition, Western blot (Socs3/NF-κB pathway), lung and breast cancer metastasis models The Journal of Clinical Investigation High 33848267
2019 PROS1 (ProS1) is a functional ligand for Tyro3 receptor tyrosine kinase in cancer cells, primarily coupling to Erk signaling rather than Axl/Akt signaling. In cells expressing both Tyro3 and Axl, ProS1 preferentially activated Tyro3-Erk phosphorylation while Gas6 was the sole activator of Axl-Akt. In cells expressing Tyro3 alone, ProS1 additionally activated Akt. ProS1-Tyro3 signaling protected cancer cells from apoptosis (staurosporine-induced and serum starvation-induced). Western blotting of receptor and kinase phosphorylation in multiple cancer cell lines (SCC-25, MGH-U3, 786-0), conditioned medium from ProS1-secreting cells, ProS1 ligand traps and warfarin specificity controls, apoptosis assays Cancers Medium 31766614
2016 Knockdown of PROS1 in glioblastoma LN18 cells induced apoptosis via activation of both extrinsic (FasL/death receptor) and intrinsic apoptotic pathways, reduced migration and invasion, and decreased proliferation. PROS1 silencing also caused downregulation of GAS6 and TAM family receptors, suggesting PROS1 supports GBM cell survival partly through autocrine/paracrine TAM receptor signaling. siRNA knockdown of PROS1 in LN18 glioblastoma cells, apoptosis assays, wound-healing migration assay, invasion assay, proliferation assay, pathway analysis International Journal of Oncology Medium 27840905
2019 Exogenous PROS1 inhibited P. gingivalis LPS-induced production of TNF-α, IL-6, IL-1β, MMP9/2, and RANKL in human gingival epithelial cells in a Tyro3-dependent manner. The anti-inflammatory mechanism involved SOCS1/3 upregulation and modulation of STAT1/3 signaling. PROS1 also restored Tyro3 expression downregulated by LPS stimulation. In a rat periodontitis model, PROS1 administration attenuated gingival inflammation and alveolar bone loss. In vitro LPS stimulation of human gingival epithelial cells, Tyro3 dependency established by knockdown, PCR/Western blot/ELISA/gelatin zymography, rat ligature+LPS periodontitis model with PROS1 administration Journal of Cellular and Molecular Medicine Medium 30729671
2001 Five novel PROS1 mutations (W108C, W342R, E349K, L485S missense and a 4 bp deletion causing frameshift) cause protein S type I or III deficiency. Analysis of platelet mRNA showed mutant transcripts are expressed in significant amounts, suggesting the molecular disease mechanism is defective protein folding/instability and impaired secretion with intracellular degradation, rather than absence of mRNA. Structural modeling predicted the substitutions disrupt protein folding and/or stability. PROS1 mutation identification by sequencing, haplotype analysis with microsatellite markers, platelet mRNA analysis (RT-PCR), computer-based structural modeling of protein S Thrombosis and Haemostasis Medium 11776305
2009 Gross copy number variations (CNVs) including complete deletions, partial deletions, and duplications of the PROS1 gene are found in approximately one-third of hereditary protein S-deficient patients who are negative for point mutations by conventional sequencing, establishing large genomic rearrangements as a common molecular mechanism of PROS1-associated protein S deficiency. Multiplex ligation-dependent probe amplification (MLPA) and confirmatory quantitative PCR for copy number analysis of PROS1 in 18 protein S-deficient probands Human Genetics Medium 19466456
2005 Large genomic deletions of PROS1 (encompassing at least 35 kb to 449 kb) were identified in 3 of 8 (38%) protein S-deficient families lacking detectable point mutations, confirming that large deletions are a relatively common and distinct molecular mechanism causing hereditary protein S deficiency. SNP and microsatellite marker segregation analysis to identify deletions, confirmed by quantitative PCR; haplotype analysis showed all three deletions were independent events Thrombosis and Haemostasis Medium 16363235
2000 Seven novel PROS1 mutations causing protein S deficiency were identified including missense, nonsense, and frameshift variants. The P460 allele (S/P460 variant) was found in heterozygous form in type III PS-deficient patients but also in normal individuals, suggesting it does not co-segregate as a disease-causing mutation for type III deficiency. Optimized non-isotopic SSCA/SSCP mutation detection across 15 PCR segments covering all PROS1 exons and boundaries, heteroduplex analysis, co-segregation analysis in 31 propositi Human Mutation Low 10790208

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 The proPO-system: pros and cons for its role in invertebrate immunity. Trends in immunology 808 18457993
2014 PIK3CA-related overgrowth spectrum (PROS): diagnostic and testing eligibility criteria, differential diagnosis, and evaluation. American journal of medical genetics. Part A 429 25557259
2010 The pros and cons of phytoestrogens. Frontiers in neuroendocrinology 422 20347861
2019 The Pros and Cons of Mesenchymal Stem Cell-Based Therapies. Cell transplantation 398 31018669
2022 Tumor immunotherapies by immune checkpoint inhibitors (ICIs); the pros and cons. Cell communication and signaling : CCS 396 35392976
2006 Nanoparticles: health effects--pros and cons. Environmental health perspectives 293 17185269
2017 Blocking CGRP in migraine patients - a review of pros and cons. The journal of headache and pain 218 28948500
2008 Are tests of sperm DNA damage clinically useful? Pros and cons. Journal of andrology 199 19059901
2015 From in vitro Experiments to in vivo and Clinical Studies; Pros and Cons. Current drug discovery technologies 194 26778084
2020 Pros and Cons: Magnetic versus Optical Microrobots. Advanced materials (Deerfield Beach, Fla.) 179 32053227
2015 Cell-Free Protein Synthesis: Pros and Cons of Prokaryotic and Eukaryotic Systems. Chembiochem : a European journal of chemical biology 171 26478227
2018 Tumor-secreted Pros1 inhibits macrophage M1 polarization to reduce antitumor immune response. The Journal of clinical investigation 148 29708510
2018 Pros and cons of different therapeutic antibody formats for recombinant antivenom development. Toxicon : official journal of the International Society on Toxinology 137 29534892
2017 Statins: pros and cons. Medicina clinica 137 29292104
2019 Genome-Editing Technologies: Concept, Pros, and Cons of Various Genome-Editing Techniques and Bioethical Concerns for Clinical Application. Molecular therapy. Nucleic acids 129 30965277
2006 Cannabinoids and cancer: pros and cons of an antitumour strategy. British journal of pharmacology 124 16501583
1994 Gamma-hydroxybutyrate: an overview of the pros and cons for it being a neurotransmitter and/or a useful therapeutic agent. Neuroscience and biobehavioral reviews 123 7914688
2021 Engineered TCR-T Cell Immunotherapy in Anticancer Precision Medicine: Pros and Cons. Frontiers in immunology 119 33859650
2002 The pros and cons of apoptosis assays for use in the study of cells, tissues, and organs. Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada 100 12533214
2017 Maillard reaction in food allergy: Pros and cons. Critical reviews in food science and nutrition 98 26980434
2015 The pros and cons of vertebrate animal models for functional and therapeutic research on inherited retinal dystrophies. Progress in retinal and eye research 94 25936606
2013 Lysosomal multienzyme complex: pros and cons of working together. Cellular and molecular life sciences : CMLS 93 24337808
2016 CLOVES syndrome: review of a PIK3CA-related overgrowth spectrum (PROS). Clinical genetics 91 27426476
2018 Stem-cell therapy and platelet-rich plasma in regenerative medicines: A review on pros and cons of the technologies. Journal of oral and maxillofacial pathology : JOMFP 89 30651682
2016 In vitro evolution of chemically-modified nucleic acid aptamers: Pros and cons, and comprehensive selection strategies. RNA biology 85 27715478
2018 The Properties of Cytokines in Multiple Sclerosis: Pros and Cons. The American journal of the medical sciences 83 30447707
2019 Pros and Cons of Chaperone-Mediated Autophagy in Cancer Biology. Trends in endocrinology and metabolism: TEM 76 31699565
2000 Pros and cons of inhibiting cholesteryl ester transfer protein. Current opinion in lipidology 71 11086331
2020 Pros and Cons of Denosumab Treatment for Osteoporosis and Implication for RANKL Aptamer Therapy. Frontiers in cell and developmental biology 65 32478071
2021 Myeloid cell-derived PROS1 inhibits tumor metastasis by regulating inflammatory and immune responses via IL-10. The Journal of clinical investigation 64 33848267
2015 Pros and cons of using biomarkers versus clinical decisions in start and stop decisions for antibiotics in the critical care setting. Intensive care medicine 62 26194026
2015 Heat shock proteins and heat therapy for type 2 diabetes: pros and cons. Current opinion in clinical nutrition and metabolic care 57 26049635
2001 Plant calcium signaling and monitoring: pros and cons and recent experimental approaches. Protoplasma 57 11732314
2023 Simultaneous Detection of Tumor Derived Exosomal Protein-MicroRNA Pairs with an Exo-PROS Biosensor for Cancer Diagnosis. ACS nano 53 37129374
2020 Pros and cons for use of statins in people with coronavirus disease-19 (COVID-19). Diabetes & metabolic syndrome 52 32683320
2008 PROC, PROCR and PROS1 polymorphisms, plasma anticoagulant phenotypes, and risk of cardiovascular disease and mortality in older adults: the Cardiovascular Health Study. Journal of thrombosis and haemostasis : JTH 50 18680534
2020 Current methods for diagnosis of human coronaviruses: pros and cons. Analytical and bioanalytical chemistry 44 33219449
2013 The pros and the cons of mTOR inhibitors in kidney transplantation. Expert review of clinical immunology 44 24377908
2023 Revisiting Two Decades of Research Focused on Targeting APE1 for Cancer Therapy: The Pros and Cons. Cells 43 37508559
2006 Bioartificial liver: its pros and cons. Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 41 16684219
2020 CD40/CD40L and Related Signaling Pathways in Cardiovascular Health and Disease-The Pros and Cons for Cardioprotection. International journal of molecular sciences 39 33198327
2002 Pros and cons of existing treatment modalities in osteoporosis: a comparison between tibolone, SERMs and estrogen (+/-progestogen) treatments. The Journal of steroid biochemistry and molecular biology 39 12650712
2019 Models of Intracellular Transport: Pros and Cons. Frontiers in cell and developmental biology 37 31440506
2015 Pros and Cons of Antigen-Presenting Cell Targeted Tumor Vaccines. Journal of immunology research 37 26583156
2020 Wnt/β-Catenin Signaling Pathway as Chemotherapeutic Target in Breast Cancer: An Update on Pros and Cons. Clinical breast cancer 36 32416986
2019 The Yin and Yang of the Bone Marrow Microenvironment: Pros and Cons of Mesenchymal Stromal Cells in Acute Myeloid Leukemia. Frontiers in oncology 36 31709192
2022 Liver-on-a-chip devices: the pros and cons of complexity. American journal of physiology. Gastrointestinal and liver physiology 35 35819853
2016 Pros and Cons of Clinical Basophil Testing (BAT). Current allergy and asthma reports 35 27411319
2014 Pros and cons of current approaches for detecting peroxynitrite and their applications. Biomedical journal 35 24923569
2012 Pregabalin in clinical psychiatry and addiction: pros and cons. Expert opinion on investigational drugs 35 22725618
2009 Gross deletions/duplications in PROS1 are relatively common in point mutation-negative hereditary protein S deficiency. Human genetics 35 19466456
2015 Pros and cons of fatty acids in bone biology. Progress in lipid research 32 25835096
2015 Pros and cons of methylation-based enrichment methods for ancient DNA. Scientific reports 32 26134828
2022 Pros and cons of causative association between periodontitis and rheumatoid arthritis. Periodontology 2000 30 35262966
2016 Silencing of PROS1 induces apoptosis and inhibits migration and invasion of glioblastoma multiforme cells. International journal of oncology 30 27840905
2019 Tumour-Secreted Protein S (ProS1) Activates a Tyro3-Erk Signalling Axis and Protects Cancer Cells from Apoptosis. Cancers 29 31766614
2015 Emerging role for αB-crystallin as a therapeutic agent: pros and cons. Current molecular medicine 28 25601468
2011 Noise in biological systems: pros, cons, and mechanisms of control. Methods in molecular biology (Clifton, N.J.) 28 21863500
2024 Pros and Cons in Various Immobilization Techniques and Carriers for Enzymes. Applied biochemistry and biotechnology 27 38175415
2018 Pros and Cons of the New Edition of TNM Classification of Head and Neck Squamous Cell Carcinoma. Oncology 27 29975952
2017 Acid-Suppressive Therapy and Risk of Infections: Pros and Cons. Clinical drug investigation 27 28361440
2005 Large deletions of the PROS1 gene in a large fraction of mutation-negative patients with protein S deficiency. Thrombosis and haemostasis 27 16363235
2023 CDK4/6 inhibitors: basics, pros, and major cons in breast cancer treatment with specific regard to cardiotoxicity - a narrative review. Therapeutic advances in medical oncology 26 37841752
2022 Pros and Cons of In Vitro Methods for Circular RNA Preparation. International journal of molecular sciences 26 36362032
2018 Inducible HIV RNA transcription assays to measure HIV persistence: pros and cons of a compromise. Retrovirology 25 29343255
2012 Is EPCR a multi-ligand receptor? Pros and cons. Thrombosis and haemostasis 25 22318610
2021 HtrA family proteases of bacterial pathogens: pros and cons for their therapeutic use. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 23 33359376
2020 The pROS of Autophagy in Neuronal Health. Journal of molecular biology 23 32006535
2017 Balancing Ethical Pros and Cons of Stem Cell Derived Gametes. Annals of biomedical engineering 23 28091967
2013 Multipotent (adult) and pluripotent stem cells for heart regeneration: what are the pros and cons? Stem cell research & therapy 23 24476362
2000 Optimization of a simple and rapid single-strand conformation analysis for detection of mutations in the PROS1 gene: identification of seven novel mutations and three novel, apparently neutral, variants. Human mutation 23 10790208
2024 Neoadjuvant and Adjuvant Immune-based Approach for Renal Cell Carcinoma: Pros, Cons, and Future Directions. European urology oncology 22 39327187
2023 ProS-GNN: Predicting effects of mutations on protein stability using graph neural networks. Computational biology and chemistry 22 37643501
2018 Yeast arming systems: pros and cons of different protein anchors and other elements required for display. Applied microbiology and biotechnology 22 29435617
2017 [PIK3CA-related overgrowth syndrome (PROS)]. Nephrologie & therapeutique 22 28577738
2016 Measurement of free light chains - pros and cons of current methods. Clinical chemistry and laboratory medicine 22 26812876
2015 Pros and cons of pDNA and mRNA transfection to study mRNA translation in mammalian cells. Gene 22 26680098
2020 Inflammation and Inflammasomes: Pros and Cons in Tumorigenesis. Journal of immunology research 21 33015196
2017 Protein Supplements: Pros and Cons. Journal of dietary supplements 21 28937838
2023 New insights in application of mesenchymal stem cells therapy in tumor microenvironment: pros and cons. Frontiers in cell and developmental biology 20 37849741
2022 Immunotherapy in liver transplantation for hepatocellular carcinoma: Pros and cons. World journal of gastrointestinal oncology 20 35116109
2022 Targeting C-Reactive Protein by Selective Apheresis in Humans: Pros and Cons. Journal of clinical medicine 20 35407379
2019 The Pros1/Tyro3 axis protects against periodontitis by modulating STAT/SOCS signalling. Journal of cellular and molecular medicine 20 30729671
2022 Extracellular vesicles in cancer pros and cons: The importance of the evidence-based medicine. Seminars in cancer biology 19 35124195
2020 In Search of Effective Treatments Targeting α-Synuclein Toxicity in Synucleinopathies: Pros and Cons. Frontiers in cell and developmental biology 19 33015057
2001 Characterization and structural impact of five novel PROS1 mutations in eleven protein S-deficient families. Thrombosis and haemostasis 18 11776305
2007 Leukotriene synthesis inhibitors versus antagonists: the pros and cons. Current allergy and asthma reports 17 17437683
2019 The Pros and Cons of Using Oat in a Gluten-Free Diet for Celiac Patients. Nutrients 16 31581722
2018 Methylenedioxymethamphetamine (MDMA) in Psychiatry: Pros, Cons, and Suggestions. Journal of clinical psychopharmacology 16 30303861
2024 Administration of methylene blue in septic shock: pros and cons. Critical care (London, England) 15 38365828
2022 Unraveling the pros and cons of various in vitro methodologies for ruminant nutrition: a review. Translational animal science 15 36213308
2021 Pros and cons for the evidence of adaptive non-shivering thermogenesis in marsupials. Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology 15 33860348
2021 Early approval of COVID-19 vaccines: Pros and cons. Human vaccines & immunotherapeutics 15 34283001
2021 Pros and Cons of Pharmacological Manipulation of cGMP-PDEs in the Prevention and Treatment of Breast Cancer. International journal of molecular sciences 15 35008687
2020 Recurrent PROC and novel PROS1 mutations in Vietnamese patients diagnosed with idiopathic deep venous thrombosis. International journal of laboratory hematology 15 32964666
2011 Pros and cons of using aberrant glycosylation as companion biomarkers for therapeutics in cancer. BMB reports 15 22189678
1996 Oral vs inhaled asthma therapy. Pros, cons and combinations. Drugs 15 8941500
2024 The rise of medical influencers: The pros and the cons. The journal of the Royal College of Physicians of Edinburgh 14 38867442
2022 EBCC-13 manifesto: Balancing pros and cons for contralateral prophylactic mastectomy. European journal of cancer (Oxford, England : 1990) 14 36641897
2014 Pros and cons of phospholipid asymmetry in erythrocytes. Journal of pharmacy & bioallied sciences 14 24741274

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