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Preprint REVIEW | doi:10.20944/preprints202103.0699.v1

Bismuth-213 for Targeted Radionuclide Therapy: From Atom to Bedside

Stephen Ahenkorah, Irwin Cassells, Christophe M Deroose, Thomas Cardinaels, Andrew R Burgoyne, Guy Bormans, Maarten Ooms, Frederik Cleeren

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Bismuth-213; Targeted Radionuclide Therapy; Targeted alpha Therapy; radiopharmaceutical; bifunctional chelator; vector molecule

Online: 29 March 2021 (14:43:57 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202204.0077.v1

Cannabinoids Alleviate the LPS-Induced Cytokine Storm via Attenuating NLRP3 Inflammasome Signalling and TYK2-Mediated STAT3 Signalling Pathways In Vitro

Santosh V Suryavanshi, Mariia Zaiachuk, Nazar Pryimak, Igor Kovalchuk, Olga Kovalchuk

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Delta-9-tetrahydrocannabinol; cannabidiol; cannabinoids; NLRP3 inflammasome; STAT3; TYK2; cytokine storm; interleukins; TNF-α; macrophages; primary lung bronchial epithelial cells

Online: 8 April 2022 (08:51:26 CEST)

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Cannabinoids, mainly cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), are the most studied group of compounds obtained from Cannabis sativa because of their several pharmaceutical properties. Current evidence suggests a crucial role of cannabinoids as potent anti-inflammatory agents for the treatment of chronic inflammatory diseases; however, the mechanisms remain largely unclear. Cytokine storm, a dysregulated severe inflammatory response by our immune system, is involved in the pathogenesis of numerous chronic inflammatory disorders, including coronavirus disease 2019 (COVID-19), which results in the accumulation of pro-inflammatory cytokines. Therefore, we hypothesized that CBD and THC reduce the levels of pro-inflammatory cytokines by inhibiting key inflammatory signalling pathways. The nucleotide-binding and oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome signalling has been implicated in a variety of chronic inflammatory diseases, which results in the release of pyroptotic cytokines, interleukin-1β (IL-1β) and IL-18. Likewise, the activation of the signal transducer and activator of transcription-3 (STAT3) causes increased expression of pro-inflammatory cytokines. We studied the effects of CBD and THC on lipopolysaccharide (LPS)-induced inflammatory response in human THP-1 macrophages and primary human bronchial epithelial cells (HBECs). Our results revealed that CBD and, for the first time, THC, significantly inhibited NLRP3 inflammasome activation following LPS + ATP stimulation, leading to a reduction in the levels of IL-1β in THP-1 macrophages and HBECs. CBD attenuated the phosphorylation of nuclear factor-κB (NF-κB) and both cannabinoids inhibited the generation of oxidative stress post-LPS. Our multiplex ELISA data revealed that CBD and THC significantly diminished the levels of IL-6, IL-8, and tumor necrosis factor-α (TNF-α) after LPS treatment in THP-1 macrophages and HBECs. In addition, the phosphorylation of STAT3 was significantly downregulated by CBD and THC in THP-1 macrophages and HBECs, which was in turn, attributed to the reduced phosphorylation of tyrosine kinase-2 (TYK2) by CBD and THC after LPS stimulation in these cells. Overall, CBD and THC were found to be effective in alleviating the LPS-induced cytokine storm in human macrophages and primary HBECs, at least via modulation of NLRP3 inflammasome and STAT3 signalling pathways. The encouraging results from this study warrant further investigation of these cannabinoids in vivo.

Preprint ARTICLE | doi:10.20944/preprints202401.1829.v1

Is this the Simplest Possible Biosensor? A Surface Imprinted Polymer EIS Sensor for Detecting Alpha-synuclein, a Parkinson’s Disease Biomarker

Roslyn Massey, Rishabh Appadurai, Ravi Prakash

Subject: Chemistry And Materials Science, Biomaterials Keywords: surface imprinted polymers; electroimpedance spectroscopy; label-free biosensors; parkinson’ s disease; α -synuclein

Online: 25 January 2024 (15:47:20 CET)

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Preprint ARTICLE | doi:10.20944/preprints202312.0918.v1

Glutathione Non-covalent Binding Sites on Hemoglobin and Major Glutathionylation Target betaCys94 Are Conservative among Both Hypoxia-Sensitive and Hypoxia-Tolerant Mammal Species

Anastasia A. Anashkina, Sergey Yurievich Simonenko, Yury L. Orlov, Irina Yu. Petrushanko

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: hypoxia; hemoglobin; glutathione; redox sensitivity; hypoxia-tolerant species; alpha subunit; beta-subunit; cysteine residues

Online: 13 December 2023 (04:59:33 CET)

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Preprint ARTICLE | doi:10.20944/preprints202311.1891.v1

Quantitative Analysis and Molecular Docking Simulation of Flavonols from Eruca sativa Mill. And Their Effect on Skin Barrier Function

Jihye Park, Wonchul Choi, Jayoung Kim, Hye Won Kim, Jee-Young Lee, Jongsung Lee, Bora Kim

Subject: Medicine And Pharmacology, Complementary And Alternative Medicine Keywords: Eruca sativa; Skin barrier function; Peroxisome proliferator activated receptor-α ; Anti-inflammation; Docking simulation

Online: 29 November 2023 (12:16:32 CET)

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Preprint ARTICLE | doi:10.20944/preprints202307.0238.v1

Polymerizationof alpha,omega-Bis(o-methoxyphenyl)arenes with trans-1,4-Cyclohexanedicarboxylic acid: Yielding Organosoluble Semi-Aromatic Polyketones

Katsuya Maeyama, Ayumu Katada

Subject: Chemistry And Materials Science, Polymers And Plastics Keywords: aromatic polyketones; alpha,omega-bis(o-methoxyphenyl)arenes; Suzuki-Miyaura coupling; thermal stability; transparency

Online: 4 July 2023 (13:42:57 CEST)

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Preprint COMMUNICATION | doi:10.20944/preprints202109.0133.v1

Fluid and Tissue Biomarkers of Lewy Body Dementia: Report of an LBDA Symposium

Gregory D. Scott, Moriah R. Arnold, Thomas G. Beach, Christopher H. Gibbons, Anumantha G. Kanthasamy, Russell M. Lebovitz, Afina W. Lemstra, Leslie M. Shaw, Charlotte E. Teunissen, Henrik Zetterberg, Angela S. Taylor, Todd C. Graham, Bradley F. Boeve, Stephen N. Gomperts, Neill R. Graff-Radford, Charbel E.-H. Moussa, Kathleen L. Poston, Liana S. Rosenthal, Marwan N. Sabbagh, Ryan R. Walsh, Miriam T. Weber, Melissa J. Armstrong, Jee A. Bang, Andrea C. Bozoki, Kimiko Domoto-Reilly, John E. Duda, Jori E. Fleisher, Douglas R. Galasko, James E. Galvin, Jennifer G. Goldman, Samantha K. Holden, Lawrence S. Honig, Daniel E. Huddleston, James B. Leverenz, Irene Litvan, Carol A. Manning, Karen S. Marder, Alexander Y. Pantelyat, Victoria S. Pelak, Douglas W. Scharre, Sharon J. Sha, Holly A. Shill, Mari Zoltan, Joseph F. Quinn, David J. Irwin

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: cerebrospinal fluid; alpha-synuclein; skin biopsy; seeded aggregation assays; tau, amyloid; Lewy body dementia

Online: 7 September 2021 (16:26:51 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202104.0137.v1

Gross Alpha and Gross Beta Activity Concentrations in Dust Fraction of Urban Surface Deposited Sediment in Russian Cities

Mohamed Y. Hanfi, Andrian A. Seleznev, Ilia Yarmoshenko

Subject: Environmental And Earth Sciences, Atmospheric Science And Meteorology Keywords: urban surface deposited sediments (USDS); gross alpha activity (GA); gross beta activity (GB); dust

Online: 5 April 2021 (13:00:40 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202011.0385.v1

mySORT: A Web Framework by using Deconvolution Approach to Estimating Immune Cell Composition from Complex Tissues

Shu-Hwa Chen, Bo-Yi Yu, Wen-Yu Kuo, Ya-Bo Lin, Sheng-Yao Su, I-Hsuan Lu, Chung-Yen Lin

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Cancer; Immunotherapy; Deconvolution; Alpha diversity; Beta diversity; Precision medicine; Microenvironment; Single-cell RNA sequencing

Online: 13 November 2020 (14:18:40 CET)

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Cancer immunotherapy reaches a remarkable achievement in various cancer types and brings new possibilities to improve cancer patients’ long-term survival. However, outcomes vary from case to case, and the present protocol benefits a small fraction of patients. One notable factor is the tumor microenvironment, especially the immune cell components, that may reflect the immune response's status quo on site. Thus, understanding the content of infiltrating immune cells in tumors is not only for research interesting but also a crucial subject toward precision medicine. We implement an algorithm for resolving relative proportions of twenty-one immune cell subclasses from a human tissue profiled transcriptome by microarray technology to reach the goal above. By selecting gene features and then adopting ?-Support Vector Regression, we can construct a deconvolution model and resolve the immune cell context. The excellent consistency between the estimated values and the correct immune-cell composition further demonstrates this approach provides a more natural alternative to revealing samples' immune cell content and reliable results like recent single-cell technologies. Based on this algorithm, the web-based deconvolution tool implemented named mySORT provides a user-friendly interface for estimating the immune cell content by uploading gene expression profiling. We also present comprehensive visualization 2D/3D plots in mySORT so that users can easily make a comparison between different samples. Finally, we synthesized pseudo-bulk expression data from single-cell transcriptomic datasets of 17 melanoma and 16 head and neck cancer patients. The deconvolution results of microarray-based data in the previous study and synthetic pseudo-bulk data all proved the excellent performance of mySORT. We believe that mySORT can help researchers in all fields easily understand complex immune microenvironment. The website of mySORT is freely accessible on https://symbiosis.iis.sinica.edu.tw/mySORT/.

Preprint ARTICLE | doi:10.20944/preprints202009.0251.v1

Influence of Different Light Regimes on the Mycoparasitic Activity and the Production of the Secondary Metabolite 6-Pentyl-α-Pyrone in Two Strains of Trichoderma Atroviride

Dubraska Moreno-Ruiz, Alessandro Fuchs, Kristina Missbach, Rainer Schuhmacher, Susanne Zeilinger

Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: Trichoderma atroviride; mycoparasitism; secondary metabolites; 6-pentyl-alpha-pyrone; Tmk3 MAP kinase; light; dark

Online: 11 September 2020 (08:49:15 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202001.0295.v1

Suppression of Hepatocyte Nuclear Factor 4 Alpha by Long-Term Infection of Hepatitis B Virus Contributes to Tumor Cell Proliferation

Soree Park, Yea Na Ha, Mehrangiz Dezhbord, Ah Ram Lee, Eun-Sook Park, Yong Kwang Park, Juhee Won, Na Yeon Kim, Soo Yeun Choo, Jae Jin Shin, Chang Hyun Ahn, Kyun-Hwan Kim

Subject: Biology And Life Sciences, Virology Keywords: Hepatitis B virus; hepatocyte nuclear factor 4 alpha; long-term infection; ERK signaling pathway

Online: 25 January 2020 (15:25:57 CET)

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Preprint ARTICLE | doi:10.20944/preprints201809.0058.v1

Integrative Proteomic and Metabolomic Analysis Reveals the Cotton Plant Defense Mechanisms Induced by Insect (Adelphocoris suturalis Jakovlev) Feeding

Hui Lu, Shuai Zhang, Junyu Luo, Chunyi Wang, Limin Lv, Lijuan Zhang, Xiangzhen Zhu, Li Wang, Xueke Gao, Hongxia Hua, Jinjie Cui

Subject: Biology And Life Sciences, Plant Sciences Keywords: Gossypium hirsutum L.; Adelphocoris suturalis (Jakovlev); alpha-linolenic acid pathway; tryptophan metabolism; plant defence

Online: 4 September 2018 (06:29:16 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201710.0180.v1

Low Levels of IgG Recognizing the Alpha-1-Antitrypsin (A1AT) ^50-63 Peptide and Its Association with Taiwanese Women with Primary Sjögren's Syndrome

Yu-Sheng Chang, Chih-Hong Pan, Che-Chang Chang, Kai-Leun Tsai, Han-Wen Chou, Jin-Hua Chen, Sheng-Hong Lin, Yi-Ying Lu, Chih-Chun Tai, Yi-Fang Lin, Ching-Yu Lin

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: primary Sjögren's syndrome; alpha-1-antitrypsin; inhibitor; 4-hydroxy-2-nonenal; autoantibody isotypes; serum

Online: 30 October 2017 (04:30:59 CET)

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Preprint ARTICLE | doi:10.20944/preprints202404.0641.v1

Structure-Activity Relationship of Synthetic Linear KTS-Peptides Containing Meta-Aminobenzoic Acid as Antagonists of α1β1 Integrin with Antiangiogenic and Melanoma’ Antitumor Activities

Majdi Saleem Naamneh, Tatjana Momic, Michal Klazas, Julius Grosche, Johannes A Eble, Cezary Marcinkiewicz, Netaly Khazanov, Hanoch Senderowitz, Amnon Hoffman, Chaim Gilon, Jehoshua Katzhendler, Philip Lazarovici

Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: MABA; KTS; peptide synthesis; modeling; conformation; stability; integrin α 1; cell adhesion; angiogenesis; melanoma tumor

Online: 9 April 2024 (09:51:33 CEST)

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Preprint REVIEW | doi:10.20944/preprints202401.1365.v1

Role of the Alpha-B-Crystallin Protein in Cardiomyopathic Disease

Andres Thorkelsson, Michael T. Chin

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: alpha-B-crystallin; cryab; molecular chaperone; desminopathy; hypertrophic cardiomyopathy; dilated cardiomyopathy; restrictive cardiomyopathy; calcineurin; NFAT

Online: 18 January 2024 (10:30:11 CET)

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Preprint ARTICLE | doi:10.20944/preprints202303.0230.v1

Attenuation of Dopaminergic Neurodegeneration in a C. elegans Parkinson’s Model through Regulation of Xanthine Dehydrogenase (XDH-1) Expression by the RNA Editase, ADR-2

Lindsey A. Starr, Luke E. McKay, Kylie N. Peter, Lena M. Seyfarth, Laura A. Berkowitz, Kim A. Caldwell, Guy A. Caldwell

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: alpha-synuclein; ADAR; C. elegans; dopamine; neurodegeneration; Parkinson's disease; RNA editing; xanthine dehydrogenase; ABC transporter

Online: 13 March 2023 (10:34:06 CET)

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Preprint REVIEW | doi:10.20944/preprints202211.0448.v1

COVID-19 Pathology Sheds New Light on Balance between Neutrophil Proteases and Their Inhibitors

Marko Radic, Vasuki Vindiya Silva

Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: alpha-1-antitrypsin (AAT); neutrophil elastase (NE); NETosis, PAD4, ARDS, COPD; neutrophils; COVID-19; TMPRSS2.

Online: 24 November 2022 (02:50:25 CET)

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Preprint ARTICLE | doi:10.20944/preprints202209.0197.v1

Alpha-Synuclein at the Interface between Depression, Parkinson’s Disease and Dementia: Evidence from Epidemiology, Population Genetics and Gene-Environment Interactions

Ravi Philip Rajkumar

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: alpha-synuclein; SNCA; major depression; dysthymia; Parkinson’s disease; dementia; neurodegeneration; gene-environment interaction; PM2.5; pesticides

Online: 14 September 2022 (08:38:38 CEST)

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Preprint REVIEW | doi:10.20944/preprints202207.0100.v1

From Minor Mutant to Dominance, the Evolution of SARS-CoV-2 Variants

Thomas Caspari

Subject: Biology And Life Sciences, Virology Keywords: omicron; alpha; delta; deltacron; recombination; RNA editing; intra-host variants; tropisms; ox-idative damage; Wuhan

Online: 6 July 2022 (15:27:32 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202401.0771.v1

Collembola Communities Reflect Soil Recovery After Fire in Mediterranean Pinus pinaster Forests

María José Luciáñez, Alicia Serena

Subject: Biology And Life Sciences, Ecology, Evolution, Behavior And Systematics Keywords: Collembola; edaphic communities recovery; Alpha diversity indexes; burned forest; removal and burning of wood after fire

Online: 10 January 2024 (08:12:52 CET)

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Preprint ARTICLE | doi:10.20944/preprints202311.1407.v1

Evaluation of Phα1β Interaction on the Kv11.1 Potassium Channel in HEK293 Cells Trans-fected with the Human ERG Channel

Joao Batista Calixto, Adara Aurea Santos, Juliano Ferreira, Alessandra Hubner Souza, Célio José Castro Junior, Marcus Vinicius Gomez

Subject: Biology And Life Sciences, Other Keywords: Phα 1β ; analgesic; dofetilide; Kv11.1 potassium channel; hERG channel interaction; HEK293-hERG; cells viability

Online: 22 November 2023 (09:48:35 CET)

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Preprint REVIEW | doi:10.20944/preprints202308.0519.v1

Alpha-Linolenic Acid and Cardiovascular Events: A Narrative Review

Camilla Bertoni, Martina Abodi, Veronica D’Oria, Gregorio P. Milani, Carlo Agostoni, Alessandra Mazzocchi

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: alpha-linolenic acid; hempseed oil; cardiovascular events; LDL-cholesterol; TCcholesterol; cardioprotective effect; heart disorders; linoleic acid

Online: 7 August 2023 (11:37:39 CEST)

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Preprint REVIEW | doi:10.20944/preprints202306.2029.v1

Inflammatory Cytokines in Psoriatic Arthritis: Understanding Pathogenesis and Implications for Treatment

Bong-Woo Lee, Su-Jin Moon

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: psoriatic arthritis; inflammatory cytokines; tumor necrosis factor-alpha; interleukin-17; interleukin-23; JAK/STAT signaling pathway

Online: 28 June 2023 (12:30:45 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202306.0295.v1

Multi-criterion Sampling Matting Algorithm via Gaussian Process

Yuan Yang, Hong shan Gou, Mian Tan, Fu Jian Feng, Yi hui Liang, Yi Xiang, Lin Wang, Han Huang

Subject: Computer Science And Mathematics, Computer Vision And Graphics Keywords: computing resources; Gaussian process fitting model; multi-criterion sampling strategy; high-quality pixel pairs; alpha matte

Online: 5 June 2023 (10:00:19 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202304.0534.v1

Micro Injection Molding of Drug-Loaded Round Window Niche Implants for an Animal Model using 3D Printed Molds

Robert Mau, Thomas Eickner, Gabór Jüttner, Ziwen Gao, Chunjiang Wei, Nicklas Fiedler, Volkmar Senz, Thomas Lenarz, Niels Grabow, Verena Scheper, Hermann Seitz

Subject: Medicine And Pharmacology, Otolaryngology Keywords: micro injection molding; 3D printing; rapid tooling; digital light processing; implant; drug delivery system; dexamethasone; anti-inflammatory; TNF-α; biocompatibility; inner ear therapy

Online: 19 April 2023 (03:57:41 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202312.1205.v1

Pro-Fibrotic Effects of CCL18 on Human Lung Fibroblasts Are Mediated via CCR6

Kerstin Höhne, Annett Wagenknecht, Corinna Maier, Peggy Engelhard, Torsten Goldmann, Stephan J Schließmann, Till Plönes, Martin Trepel, Hermann Eibel, Joachim Mueller-Quernheim, Gernot Zissel

Subject: Biology And Life Sciences, Cell And Developmental Biology Keywords: idiopathic pulmonary fibrosis; fibrogenesis; chemokine receptor; ligand-induced internalization; co-immunoprecipitation; collagen; alpha-smooth muscle actin; FGF2

Online: 15 December 2023 (16:01:32 CET)

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Preprint ARTICLE | doi:10.20944/preprints202311.0115.v1

Exploring the Efficacy of AHA-BHA Infused Nanofiber Skin Masks as a Topical Treatment for Acne Vulgaris

Elçin Tören, Matěj Buzgo

Subject: Chemistry And Materials Science, Biomaterials Keywords: Acne vulgaris; hydroxy acids; alpha-hydroxy acids; beta-hydroxy acids; pullulan-collagen nanofibers; electrospinning; biocompatibility, topical treatment

Online: 2 November 2023 (04:09:05 CET)

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Acne vulgaris is a prevalent skin condition that affects people of all ages and can have significant physical and psychological impacts. Hydroxy acids, such as alpha-hydroxy acids (AHA) and beta-hydroxy acids (BHA), have demonstrated potential as effective ingredients for topical acne treatments due to their exfoliating and skin-rejuvenating properties. This study assessed the effectiveness of encapsulating AHA and BHA in pullulan-collagen nanofibers as a novel approach to acne treatment. The study involved preparing Pullulan and polyvinyl alcohol (PVA) solutions combined with sodium chloride (NaCl) to create a stable mixture. Collagen and Pullulan were then dissolved in deionized water and mixed to form a collagen-pullulan solution. Various weight ratios of Collagen to Pullulan were tested to optimize nanofiber formation. This research achieved electrospinning of nanofibers, confirmed by scanning electron microscopy (SEM) analysis, which revealed well-formed and continuous nanofiber structures in acidic solutions. Fourier transform infrared spectroscopy (FTIR) analysis provided insights into the chemical composition of the nanofibers, indicating the presence of ester, carboxylic acid, hydroxyl, and phenolic groups. Contact angle measurements demonstrated that the pullulan-collagen nanocomposite exhibited hydrophilic properties, albeit less hydrophilic than pure Collagen. Biocompatibility assays using mesenchymal stem cells (MSCs) and human skin fibroblasts (HSFs) revealed that the pullulan-collagen nanocomposite promoted higher cell viability compared to pure Collagen, suggesting its potential as a supportive matrix for cell growth and tissue regeneration. AHA-BHA-infused nanofiber skin masks hold promise as effective topical treatments for acne vulgaris. The successful encapsulation of hydroxy acids within pullulan-collagen nanofibers, in conjunction with their favourable chemical composition, hydrophilicity, and biocompatibility, positions them as promising candidates for delivering active ingredients and enhancing skin health. Further nanofiber formulation optimisation is necessary to exploit their therapeutic potential in skincare applications.

Preprint ARTICLE | doi:10.20944/preprints202304.0522.v1

A Tiny Viral Protein, SARS-CoV-2-ORF7b: Structural Features.

Giovanni Colonna

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: ORF7b; SARS-CoV-2; COVID-19; 3D-structure; molecular dynamics; dipole vector; Electrostatic properties of alpha-helix.

Online: 18 April 2023 (11:14:01 CEST)

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ORF7b-2 is an accessory protein of the SARS-CoV-2 virus of only 43 amino acids. It has been implicated in various functional hypotheses, some of which predict its involvement as a trans-membrane protein. In this study, ORF7b-2 has often been compared to ORF7b-1 of the SARS virus to highlight differences and similarities with a protein that should have a similar biological role. Structural analysis of ORF7b-2 and its electrostatic characteristics show a polypeptide with both ends negatively charged and a diffuse negative charge over the entire structure. Therefore, its behavior in solution is like that of a weak negative polyelectrolyte, more precisely a polyanion with a net charge of – 4 at neutral pH. Its structure was modeled with two different modeling systems, one of which was ab initio. The two best models are similar, as confirmed by the Ramachandran plot, and show a central alpha-helical structure with two disordered and mobile ends. A normal mode analysis characterized the low-frequency dynamic aspects of the protein. The analysis of the structural shows a rigid central segment with mobile and fluctuating extremities, involved in a conformational equilibrium of the helix ↔ coil type. The calculation of the dipole moment shows its vector is not aligned with the main axis of the structure with an outward tilt of 24°. Molecular dynamics simulations were also conducted and the one in water is in good agreement with the previous results. While, the simulation performed by inserting a pre-oriented dimer (OMP) into a solvated lipid showed the low tendency of the protein to solvate in the apolar environment of the membrane. ORF7b-2 also shows a widespread distribution of negative surfaces that dynamically adjust to changes in structural organization. The BioGrid platform's [Biological General Repository for Interaction Datasets] through the BioGrid COVID-19 Coronavirus Curation Project shows a very large number of experimentally proven physical interactions unique to ORF7b-2, some of them with cytoplasmic proteins. These features of ORF7b-2, evaluated together, suggest a remarkable propensity of ORF7b-2 to interact with multiple molecular partners on both an electrostatic and hydrophobic basis. All this makes it unreasonable that the only biological function of this protein should be that exerted as an intramembrane protein.

Preprint ARTICLE | doi:10.20944/preprints202112.0453.v1

Detection of Novel Biomarkers in Saliva of Rheumatoid Arthritis Model Mice by Proteomics and Pathological Analysis

Wakako Sakaguchi, Juri Saruta, Shinya Fuchida, Yuko Yamamoto, Masahiro To, Tomoko Shimizu, Mayumi Yakeishi, Keiichi Tsukinoki

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: anti-citrullinated protein antibody (ACPA); alpha-1-antitrypsin (A1AT); DBA/1JJmsSlc mice Proteome analysis; rheumatoid arthritis (RA)

Online: 28 December 2021 (14:44:54 CET)

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Preprint REVIEW | doi:10.20944/preprints202007.0334.v1

The Role of Alpha-Synuclein And Other Parkinson’s Genes in Neurodevelopmental and Neurodegenerative Disorders

C. Alejandra Morato Torres, Zinah Wassouf, Faria Zafar, Danuta Sastre, Tiago Fleming Outeiro, Birgitt Schüle

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: alpha-synuclein; SNCA; PARK2; 22q11.2 deletion syndrome; autism spectrum disorders; neuronal development; Parkinson’s disease; neurodegeneration; synaptic dysfunction

Online: 15 July 2020 (11:36:30 CEST)

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Preprint REVIEW | doi:10.20944/preprints202402.0674.v1

Immunomodulation through Nutrition Should Be a Key Trend in Type 2 Diabetes Treatment

Katarzyna Napiórkowska-Baran, Paweł Treichel, Marta Czarnowska, Magdalena Drozd, Kinga Koperska, Agata Węglarz, Oskar Schmidt, Samira Darwish, Zbigniew Bartuzi

Subject: Medicine And Pharmacology, Internal Medicine Keywords: type 2 diabetes; immunomodulation; immune system; nutrients; macroelements; microelements; vitamins; omega-3 acids; coenzyme Q10; alpha-lipoic acid

Online: 12 February 2024 (13:24:40 CET)

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Preprint ARTICLE | doi:10.20944/preprints202306.0120.v1

Pioneering PGC-1α-Boosted Secretome: A Novel Approach to Combating Liver Fibrosis

Chang Ho Seo, Gun Hyung Na, Dosang Lee, Jung Hyun Park, Tae Ho Hong, Ok-Hee Kim, Sang Chul Lee, Kee-Hwan Kim, Ho Joong Choi, Say-June Kim

Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: Adipose-derived stem cells (ASCs); Liver fibrosis; Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α); Secretome

Online: 2 June 2023 (03:49:55 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202008.0316.v1

Next-Generation Multimodality of Nanomedicine Therapy: Folic Acid Conjugated Copolymer and Folate Receptor Interactions Disrupt Receptor Functionality Resulting in Dual Therapeutic Anti-Cancer Potential in Triple-Negative Breast Cancer

Alexandria DeCarlo, Cecile Malardier-Jugroot, Myron R Szewczuk

Subject: Chemistry And Materials Science, Nanotechnology Keywords: nanoparticles; FA-DABA-SMA; drug delivery systems; folic acid receptor alpha; intracellular disruptions; invasion and migration; breast cancer

Online: 14 August 2020 (09:49:17 CEST)

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The development of a highly specific drug delivery system (DDS) for anti-cancer therapeutics is an area of intense research focus. Chemical engineering of a “smart” DDS to specifically target tumor cells has gained interest, designed for safer, more efficient, and effective use of chemotherapeutics for the treatment of cancer. However, the selective targeting and choosing the critical cancer surface biomarker are essential for targeted treatments to work. The folic acid receptor alpha (FRalpha) has gained popularity as a potential target in triple-negative breast cancer (TNBC). We have previously reported on a functionalized folic acid (FA)-conjugated amphiphilic alternating copolymer poly(styrene-alt-maleic anhydride) (FA-DABA-SMA) via a biodegradable linker 2,4-diaminobutyric acid (DABA) that has the essential features for efficient “smart” DDS. This biocompatible DDS self-assembles in a pH-dependent manner, providing stimuli-responsive, active targeting, extended-release of hydrophobic chemotherapeutic agents, and can effectively penetrate the inner core of 3-dimensional cancer spheroid models. The empty FA-DABA-SMA decreased spheroid volume, revealing a previously unknown mechanism of action. Upon further investigation, a size- and shape-dependent interaction FA-DABA-SMA with FR reduced the expression of p53, the product of the highly mutated TP53 gene, and additional oncogenic c-Myc and STAT3 proteins. Here, we investigated how this copolymer influences FR behavior and disrupting the receptor’s functions. Results indicate that FA-DABA-SMA increases FR expression levels in breast MDA MB-231 cancer cells and disrupting FR signaling by the reduction in HES1 and NOTCH1 protein expression levels. Also, FA-DABA-SMA induces apoptosis and further causes a change in the morphology of the MDA MB-231 cells, as well as significantly reduces their ability to migrate in a Scratch wound assay. Collectively, these findings provide a novel insight into the functionalized FA-DABA-SMA copolymer. The 350 kDa and 20 kDa copolymers actively target FRα to initialize internationalization. However, only the large size and sheet-shaped 350 kDa copolymers disrupt FRα signaling. The significance of these novel findings reveals the intracellular activity of the copolymer that is critically dependent on the size and structural shape. This report offers novel therapeutic insight into a dual mechanism of FA-DABA-SMA copolymer for its therapeutic potential for the treatment of cancer.

Preprint ARTICLE | doi:10.20944/preprints201912.0374.v1

Elucidating Binding Sites and Affinities of ERα Agonist and Antagonist to Human Alpha-Fetoprotein by in silico Modeling and Point Mutagenesis

Nurbubu T. Moldogazieva, Daria S. Ostroverkhova, Nikolai N. Kuzmich, Vladimir V. Kadochnikov, Alexander A. Terentiev, Yuri B. Porozov

Subject: Biology And Life Sciences, Biophysics Keywords: alpha-fetoprotein; estrogens; selective estrogen receptor modulators; homology-based modeling; molecular docking; protein-ligand interaction; amino acid substitutions

Online: 29 December 2019 (08:08:23 CET)

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Alpha-fetoprotein (AFP) is a major embryo- and tumor-associated protein capable of binding and transporting variety of hydrophobic ligands including estrogens. AFP has been shown to inhibit estrogen receptor (ER)-positive tumor growth and this can be attributed to its estrogen-binding ability. Despite AFP has long been investigated, its three-dimensional (3D) structure has not been experimentally resolved and molecular mechanisms underlying AFP-ligand interaction remain obscure. In our study we constructed homology-based 3D model of human AFP (HAFP) with the purpose to perform docking of ERα ligands, three agonists (17β-estradiol, estrone and diethylstilbestrol) and three antagonists (tamoxifen, afimoxifene and endoxifen) into the obtained structure. Based on ligand docked scoring function, we identified three putative estrogen- and antiestrogen-binding sites with different ligand binding affinities. Two high-affinity sites were located in (i) a tunnel formed within HAFP subdomains IB and IIA and (ii) opposite side of the molecule in a groove originating from cavity formed between domains I and III, while (iii) the third low-affinity site was found at the bottom of the cavity. 100 ns MD simulation allowed studying their geometries and showed that HAFP-estrogen interactions occur due to van der Waals forces, while both hydrophobic and electrostatic interactions were almost equally involved in HAFP-antiestrogen binding. MM/GBSA rescoring method estimated binding free energies (ΔG_bind) and showed that antiestrogens have higher affinities to HAFP as compared to estrogens. We performed in silico point substitutions of amino acid residues to confirm their roles in HAFP-ligand interactions and showed that Thr132, Leu138, His170, Phe172, Ser217, Gln221, His266, His316, Lys453, and Asp478 residues along two disulfide bonds, Cys224-Cys270 and Cys269-Cys277 have key roles in both HAFP-estrogen and HAFP-antiestrogen binding. Data obtained in our study contribute to understanding mechanisms underlying protein-ligand interactions and anti-cancer therapy strategies based on ER-binding ligands.

Preprint ARTICLE | doi:10.20944/preprints202112.0041.v1

Genetics of Vascular Inflammation in Lower Limb Ischemia: The TNF-α Hypothesis in Peripheral Arterial Disease

Diego Caicedo, Clara V. Álvarez, Sihara Pérez, Jesús Devesa

Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: Vascular inflammation; Peripheral arterial disease (PAD); Chronic limb-threatening ischemia (CLTI); GHAS trial; TNF-α; hs-CRP; Neutrophil-to-lymphocyte ratio (NLR); NOX4; eNOS; VEGF-A.

Online: 3 December 2021 (09:44:42 CET)

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Preprint REVIEW | doi:10.20944/preprints202401.2149.v2

Nicotinic Acetylcholine Receptors in Glial Cells as Molecular Target for Parkinson’s Disease

Érica Novaes Soares, Ana Carla dos Santos Costa, Gabriel de Jesus Ferrolho, Rodrigo Portes Ureshino, Bruk Getachew, Silvia Lima Costa, Victor Diogenes Amaral Da Silva, Yousef Tizabi

Subject: Biology And Life Sciences, Neuroscience And Neurology Keywords: Parkinson’ s disease, Dopamine, Acetylcholine, Nicotine, Nicotinic receptors, Microglia, Astroglia, Oligodendrocyte, NG2 Cells, Alpha-Synuclein, Toll-Like receptors, Neuroinflammation, Neuroprotection

Online: 4 March 2024 (09:56:14 CET)

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Preprint ARTICLE | doi:10.20944/preprints202101.0149.v1

Transcript Variants of Genes Involved in Neurodegeneration Are Differentially Regulated by the Apoe and Mapt Haplotypes

Sulev Koks, Abigail Pfaff, Vivien Bubb, John Quinn

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Apolipoprotein E (ApoE); microtubule associated protein (MAPT); synuclein alpha (SNCA); eQTL; TOMM40; KANSL1; mitochondria; Parkinson’s Progression Markers Initiative (PPMI)

Online: 8 January 2021 (11:45:19 CET)

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Preprint REVIEW | doi:10.20944/preprints201702.0020.v1

Potential Modes of Intercellular Alpha-Synuclein Transmission

Dario Valdinocci, Rowan A. W. Radford, Sue Maye Siow, Roger S. Chung, Dean L. Pountney

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: alpha-synuclein; Parkinsons disease; dementia with Lewy bodies; multiple system atrophy; tunelling nanotube; glymphatic system; cell-to-cell spread

Online: 7 February 2017 (03:24:21 CET)

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Preprint ARTICLE | doi:10.20944/preprints202402.0600.v1

Synthesis of α,ω-Bis-mercaptoacyl poly(alkyl oxide)s and Development of Thioether Cross-Linked Liposome Scaffolds for Sustained Release of Drugs

Spyridon Mourtas, Georgios Kourmoulakis, Stavros Kremezis, Pavlos Klepetsanis, Sophia G. Antimisiaris

Subject: Chemistry And Materials Science, Organic Chemistry Keywords: S-4-methoxytityl mercapto acids; α ,ω -homofunctional mercaptoacyl poly(alkyl oxide)s; thia-Michael addition; thioether cross-linked liposomes

Online: 9 February 2024 (16:14:11 CET)

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Preprint ARTICLE | doi:10.20944/preprints202306.0068.v1

Interaction of carbon nanotube, capped carbon nanotube, C60 fullerene, and C70 fullerene with virulence factors of Gram-negative and Gram-positive bacteria: The potential application for 3D-printed scaffolds

Mehran Alavi, Morahem Ashengroph, M. R. Mozafari

Subject: Medicine And Pharmacology, Other Keywords: 3D printed scaffolds; carbon nanotube; capped carbon nanotube; protein kinase A; pseudomonas elastase; exotoxin A; alpha-hemolysin; shiga toxin 2a

Online: 5 June 2023 (02:56:10 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202201.0174.v1

Pathological Relevance of Post-translationally Modified Alpha-Synuclein (pSer87, pSer129, nTyr39) in Idiopathic Parkinson’s Disease and Multiple System Atrophy

Berkiye Sonustun, Firat M Altay, Catherine Strand, Geshanthi Hondhamuni, Thomas T Warner, Hilal A Lashuel, Rina Bandopadhyay

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: alpha-synuclein; post-translational modifications; Parkinson’s disease; Multiple system atrophy; Lewy bodies; Lewy neurites; Glial cytoplasmic inclusions; phosphorylation; nitration; immunohistochemistry

Online: 12 January 2022 (14:31:13 CET)

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Preprint REVIEW | doi:10.20944/preprints202402.1401.v1

3-D structure of Novel Liver Cancer Biomarker LC-SPIK and its Performance in Clinical Diagnosis of HCC

Xuanyong Lu, Felix Lu, Connor Ott, Prabha Bista

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Biomarker; HCC (Hepatocellular Carcinoma); LC-SPIK (Liver Cancer specific Serine Protease Inhibitor Kazal); AFP (Alpha-Fetoprotein); NAFLD (nonalcoholic fatty liver disease)

Online: 26 February 2024 (12:01:59 CET)

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LC-SPIK is a liver cancer-specific isoform of Serine Protease Inhibitor Kazal and has been proposed as a new biomarker for the detection of HCC given its unique 3-D structure which differs from normal pancreatic SPIK. An ELISA technology based on its unique structure was developed to use LC-SPIK as an effective biomarker for the clinical diagnosis of HCC. AFP, the most widely used biomarker for HCC surveillance currently, suffers from poor clinical performance, especially in the detection of early-stage HCC. In one case-control study, which included 164 HCC patients and 324 controls, LC-SPIK had an AUC of 0.87 compared to only 0.70 for AFP in distinguishing HCC from liver disease controls (cirrhosis, HBV/HCV). LC-SPIK also performed significantly better than AFP for the 81 patients with early-stage HCC (BCLC stage 0 and A), with an AUC of 0.85 compared to only 0.61 for AFP. Cirrhosis is the major risk factor for HCC, about 80% of patients with newly diagnosed HCC have preexisting cirrhosis. LC-SPIK’s clinical performance was also studied in HCC patients with viral and non-viral cirrhosis including cirrhosis caused by nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). In a total of 163 viral cirrhosis patients with 93 HCC patients (50 early-stage), LC-SPIK had an AUC of 0.85, while AFP had an AUC of 0.70. For patients with early-stage HCC, LC-SPIK had a similar AUC of 0.83, while AFP had an AUC of only 0.60. For 120 patients with nonviral cirrhosis, including 62 HCC (23 early-stage) patients, LC-SPIK had an AUC of 0.84 while AFP had an AUC of only 0.72. For the 23 patients with early-stage HCC, LC-SPIK had a similar AUC of 0.83, while the AUC for AFP decreased to 0.65. All these results suggest that LC-SPIK has significantly better performance in the detection of HCC than AFP in all etiologies of liver diseases. In addition, LC-SPIK accurately detected the presence of HCC in 71%-91% of HCC patients with false-negative AFP test results in viral associated HCC and non-viral associated HCC.

Preprint ARTICLE | doi:10.20944/preprints202401.0965.v2

Synthesis, Crystal Structure, and Electrochemistry of Mono- and Bis-Homoannular Ferrocene Derivatives

Uttam R. Pokharel, Derek Daigle, Stone Naquin, Gwyneth Engeron, Mary Lo, Frank R. Fronczek

Subject: Chemistry And Materials Science, Organic Chemistry Keywords: 1,2-(α -ketotetramethylene)-ferrocene; 1,2-(tetramethylene)-ferrocene; ferrocene; Friedel-Crafts acylation; Clemmensen reduction; X-ray crystallography; planar chirality; puckering parameters; electrochemistry

Online: 29 January 2024 (04:43:43 CET)

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Preprint REVIEW | doi:10.20944/preprints202309.1647.v1

Cholinergic Polarization of Human Macrophages

Natalia Roa-Vidal, Adriana S Rodriguez-Aponte, José Antonio Lasalde-Dominicci, Coral M Capó-Vélez, Manuel Delgado-Vélez

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: macrophage; inflammation; acetylcholine receptor; cholinergic receptor; polarization, cholinergic agonist; alpha 7 nicotinic acetylcholine receptor; CHRFAM7A, cholinergic machinery, cholinergic anti-inflammatory pathway

Online: 25 September 2023 (09:28:51 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202308.1676.v1

Buddy System Based Alpha Numeric Weight Based Clustering Algorithm with User Threshold

M PRASAD, Srikanth Thota

Subject: Computer Science And Mathematics, Computer Science Keywords: Clustering; hierarchical agglomerative clustering; Alpha numeric Weight based of Object Positional Value for a Term / Field / Attribute; Clustering Ranges; Buddy System

Online: 24 August 2023 (03:11:55 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202104.0413.v2

Total Face Irregularity Strength of Type (Alpha, Beta, Gamma) of Grid Graphs

Abdul Aleem Mughal, Raja Noshad Jamil

Subject: Computer Science And Mathematics, Computer Vision And Graphics Keywords: Total Face labeling of type (Alpha, Beta, Gamma); Total face irregularity strength; artesian product of path graphs; Graph Labeling; Graph theory

Online: 21 April 2021 (12:46:29 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201807.0224.v2

Pseudopterosin Inhibits Proliferation and 3D Invasion in Triple Negative Breast Cancer by Agonizing Glucocorticoid Receptor Alpha

Julia Sperlich, Nicole Teusch

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: pseudopterosin; triple negative breast cancer; glucocorticoid receptor alpha; dexamethasone; cell proliferation; 3D invasion; tumor spheroid; co-culture; interleukin 6; interleukin 8

Online: 2 August 2018 (06:08:31 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202312.1198.v1

Regeneration of Non-Alcoholic Fatty Liver Cells Using Chimeric FGF21/HGFR: A Novel Therapeutic Approach

Sung-Jun Kim, So-Jung Kim, Jeongeun Hyun, Hae-Won Kim, Jun-Hyeog Jang

Subject: Medicine And Pharmacology, Gastroenterology And Hepatology Keywords: keyword 1 alpha mouse liver 12(AML12), fibroblast growth factor 21 (FGF21), Hepatocyte Growth Factor Receptor (HGFR), chimeric FGF21/HGFR, liver regeneration

Online: 15 December 2023 (14:38:56 CET)

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Preprint REVIEW | doi:10.20944/preprints202312.0580.v2

Computational Approaches to Quark-Gluon Dynamics

Kamil Khan, Muhammad Sher Shah, Sardar Nabi, Marwa BiBi, Amir Hamza, Laibaali Reshael, Muhammad Bilal, Jawad khan

Subject: Physical Sciences, Particle And Field Physics Keywords: Quantum Chromo dynamics (QCD); Parton distribution functions (PDFs); DGLAP evolution equation; Quarks and gluons; Monte Carlo simulations; Uncertainties in α s (MZ)

Online: 12 December 2023 (17:27:25 CET)

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Preprint ARTICLE | doi:10.20944/preprints202307.1220.v1

PGC-1α Regulates the Interplay between Oxidative Stress, Senescence and Autophagy in the Aging Retina Important in Age-Related Macular Degeneration

Iswariyaraja Sridevi Gurubaran, Cezary Watala, Joanna Kostanek, Joanna Szczepanska, Elzbieta Pawlowska, Kai Kaarniranta, Janusz Blasiak

Subject: Biology And Life Sciences, Life Sciences Keywords: age-related macular degeneration; aging retina; peroxisome proliferator-activated receptor gamma coactivator 1-alpha; PGC-1 AMD; cellular senescence; autophagy; oxidative stress

Online: 18 July 2023 (11:09:42 CEST)

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Preprint COMMUNICATION | doi:10.20944/preprints202210.0383.v2

Pioneering Organelle Structural Biology: Golgi Apparatus Dysfunction in Parkinson’s Disease, Neurodevelopmental Disorders, and Cancer

Daniel Gómez

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: structural biology; organelles; Golgi Apparatus (GA); Parkinson’s disease (PD); cryo-ET; alpha-synuclein; neurodegenerative diseases; soft X-ray tomography (SXT); cancer; NDDs

Online: 5 December 2022 (02:27:26 CET)

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Preprint ARTICLE | doi:10.20944/preprints202403.1156.v1

A High-Homology Region in Bacterial β-Barrel Pore-Forming Toxins

Alexey S. Nagel, Olesya Vetrova, Natalia V. Rudenko, Anna P. Karatovskaya, Anna Zamyatina, Zhanna I. Andreeva-Kovalevskaya, Vadim Salyamov, Nadezhda Egorova, Alexander V. Siunov, Tatiana D. Ivanova, Khanafi M. Boziev, Fedor A. Brovko, Alexander S. Solonin

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Staphylococcus aureus α -toxin; Bacillus cereus hemolysin II; cytotoxin K2; suppression of hemolytic activity; monoclonal antibodies; enzyme immunoassay

Online: 20 March 2024 (12:23:07 CET)

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Preprint ARTICLE | doi:10.20944/preprints202205.0280.v1

Analysis of the Structural Protein Effects Caused by the PURA p.Phe233del Mutation Associated to Cognitive Developmental Delay Using Artificial Intelligence and Hybrid Quantum Mechanics-Molecular Mechanics Modelling

Juan Javier Lopez-Rivera, Luna Rodríguez-Salazar, Alejandro Soto-Ospina, Carlos Estrada-Serrato, David Serrano, Henry Mauricio Chaparro-Solano, Olga Londoño, Paula A. Rueda, Geraldine Ardila, Andrés Villegas-Lanau, Marcela Godoy-Corredor, Mauricio Cuartas, Jorge I. Vélez, Oscar M. Vidal, Mario A. Isaza-Ruget, Mauricio Arcos-Burgos

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: purine-rich element binding protein A gene; PURA; MIM: 600473; transcriptional activator protein Pur-alpha; cognitive developmental delay; mental retardation; Mutation c.697_699del p.Phe233del

Online: 20 May 2022 (16:58:04 CEST)

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A whole-exome capture and next-generation sequencing applied to an 11 y/o patient with a clinical history of congenital hypotonia, generalized motor and cognitive neurodevelopmental delay, severe cognitive deficit, without any identifiable Syndromic pattern, and to her parents, disclosed a de novo heterozygous pathogenic mutation, c.697_699del p.Phe233del (rs786204835)(ACMG classification PS2, PM1, PM2, PP5), harbored in the PURA gene (MIM*600473) (5q31.3), associated to Autosomal Dominant Mental Retardation 31 (MIM # 616158). We used the significant improvement in the accuracy of protein structure prediction recently implemented in AlphaFold that incorporates novel neural network architectures and training procedures based on the evolutionary, physical, and geometric constraints of protein structures. The wild-type (WT) sequence and the mutated one, missing the Phe233, were reconstructed. The predicted local Distance Difference Test (lDDT) for the PURA WT and the PURA-Phe233del showed that the occurrence of the Phe233del affects between 220-320 amino acids. The distortion in the PURA structural confor-mation in the ~5Å surrounding area after the p.Phe233del produces a conspicuous disruption of the repeat III, where the DNA and RNA helix unwinding capability occurs. PURA Protein-DNA Docking corroborated these results in silico Analysis that showed a loss of the contact of the PURA-Phe233del III repeat domain model with the DNA. Together, i) the energetic and stereochemical, ii) the hydropathic indices and polarity surfaces, and iii) the hybrid Quantum Mechanics-Molecular Mechanics (QM-MM) analyses of the PURA molecular models demarcate at the atomic resolution the specific surrounding region affected by these mutations and paves the way for future cell-based functional analysis. To the best of our knowledge, this is the first report of a de novo mutation underpinning a PURA syndrome in a Latin American patient and highlights the importance of predicting the molecular effects in protein structure using artificial intelligence algorithms and molecular and atomic resolution stereochemical analyses.

Preprint REVIEW | doi:10.20944/preprints202212.0032.v1

S protein, ACE2 and Host Cell Proteases in SARS-CoV2 Cell Entry and Infectivity; Is Soluble ACE2 a Two Blade Sword?

Reza Nejat, Maziar Fayaz Torshizi, David J. Najafi

Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: ACE2; Ang II; angiotensin(1-7); AT1R; Cathepsin; cell entry; COVID-19; Endocytosis; ERK1/2; Furin; IL-1β; IL-6; MAPK; MasR; NF-κB; PLC; PKC; RAS; RBD; SARS-CoV2; S protein; TMPRSS2; TNF-α

Online: 2 December 2022 (02:19:48 CET)

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Preprint ARTICLE | doi:10.20944/preprints202312.0543.v1

Fekete-Szego and Zalcman Functional Estimates for Subclasses of Alpha-Convex Functions Related to Trigonometric Functions

Krishnan Marimuthu, Uma Jayaraman, TEODOR BULBOACA

Subject: Computer Science And Mathematics, Analysis Keywords: Analytic functions; subordination; Carathé; odory functions; sine function; cosine function; alpha-convex functions; starlike and convex functions; coefficient bounds; Fekete-Szeg˝o functional; Zalcman functional

Online: 8 December 2023 (08:04:52 CET)

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Preprint HYPOTHESIS | doi:10.20944/preprints202005.0144.v1

Pyridoxal 5'-phosphate to mitigate immune dysregulation and coagulopathy in COVID-19

Julie Desbarats

Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: COVID-19, SARS-CoV-2, pyridoxal 5'-phosphate, pyridoxine, vitamin B6, immune response, IL-6, TNF, type I interferon, lymphopenia, blood clotting, coagulopathy, cytokine storm, sphingosine-1-phosphate, kynurenine, inflammasome, serine hydroxymethyltransferase 2 (SHMT2), hypertension, angiotensin

Online: 8 May 2020 (12:36:03 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202005.0001.v1

Using High-Content Screening Technology as a Tool to Generate Single-Cell Patient-Derived Gene-Corrected Isogenic iPS Clones for Parkinson’s Disease Research

Peter A. Barbuti, Paul M. Antony, Bruno F.R. Santos, François Massart, Gérald Cruciani, Claire M. Dording, Jonathan Arias, Jens C. Schwamborn, Rejko Krüger

Subject: Biology And Life Sciences, Cell And Developmental Biology Keywords: CRISPR-Cas9; high-content screening (HCS); fluorescent-activated cell sorting (FACS); Parkinson's disease (PD); patient-derived iPS; single-cell clones; isogenic cell lines; SNCA; alpha-synuclein; A30P

Online: 2 May 2020 (11:20:20 CEST)

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Preprint REVIEW | doi:10.20944/preprints201703.0093.v1

Potential Impact of Diet on Treatment Effect from Anti-TNF Drugs in Inflammatory Bowel Disease

Vibeke Andersen, Axel Kornerup Hansen, Berit Lilienthal Heitmann

Subject: Medicine And Pharmacology, Gastroenterology And Hepatology Keywords: lifestyle factors; chronic inflammatory diseases; treatment result; treatment response; diet; meat intake; dietary pattern; food; mucosa associated bacteria; epithelium-associated bacteria; microbiome; fibre intake; personalized medicine; mucus; sulphate-reducing bacteria; mucin-degrading bacteria; Western style diet; anti-TNF

Online: 15 March 2017 (07:29:13 CET)

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Preprint REVIEW | doi:10.20944/preprints202312.0185.v1

Antibody Dependent Enhancement (ADE) of Infection into Macrophages Validates the Importance of HERV-K102 Particle Production for Pandemic Preparedness

Marian Laderoute

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: ADE, HERV-K102, HERV-K HML-2, immunosenescence, foamy macrophages, virus-anti-virus, pandemic preparedness, mRNA COVID-19 vaccines, alpha-fetoprotein antagonists, virus strategies, anti-viral, trained (innate) immunity

Online: 4 December 2023 (10:53:40 CET)

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Preprint REVIEW | doi:10.20944/preprints202306.1113.v1

Inflammatory Bowel Disease-Associated Colorectal Cancer: Translational and Transformational Risks from Exogenous Free Hemoglobin Alpha Chain: A By-product of Extravasated Erythrocyte Macrophage Erythrophagocytosis

Maya A Bragg, William A Breaux, Amosy E M'Koma

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Inflammatory bowel disease; Colitis-associated colorectal cancer; exogenous frees hemoglobin alpha chain; Fenton reaction; DNA damage; haptoglobin; deferoxamine; flavonoids; hydrogen peroxide; hygiene; iron; nanomedicine; oxidative stress; polyphenol; pharmaceutical therapy

Online: 16 June 2023 (07:11:38 CEST)

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The aggregate aftermath of persistent inflammation in patients with inflammatory bowel disease (IBD) places them at increased risk for the advancement to colitis-associated colorectal cancer (CACRC). CACRC is preceded by IBD, the highly heterogenous, pharmacologically incurable, pertinacious, reverting/worsening, and immune-mediated inflammatory pathologies of the colon and rectum. The molecular and immunological basis of CACRC is highly correlated with the length/duration and stringency/severity of colon inflammation predisposed by the exogenous/free hemoglobin alpha chain (HbαC) the byproduct of infiltrating immune cells, extravasated erythrocytes, and macrophage erythrophagocytosis. The exogenous free HbαC prompts oxygen-free radical-arbitrated DNA damage (DNAD) through increased cellular reactive oxygen species (ROS) exacerbated by decreased tissue antioxidant defenses. Mitigation of Fenton reaction via pharmaceutical therapy would attenuate the ROS, promote apoptosis, DNAD repair, and subsequent prevent the incidence of CACRC. Three pharmaceutical options that attenuate hemoglobin toxicity include haptoglobin, deferoxamine, and flavonoids (vitamins C/E). Haptoglobin’s clearance rare from plasma is inversely correlated with its size; the smaller the size, the faster the clearance. Thus, the administration of Hp1-1 may prove to be beneficial. Furthermore, deferoxamine’s hydrophilic structure limits its ability to cross cell membranes. Thus, it may be beneficial if administered intracellularly to avoid the higher plasma concentrations and longer incubation periods associated with extracellular administration. Finally, the effectiveness of flavonoids and natural herb antioxidants is associated with high reactivity of hydroxyl substituents. Multiple analyses are currently underway to assess the clinical context of CACRC and outline the molecular basis of HbαC-induced ROS pathogenesis by exposing colonocytes and/or colonoids to HbαC. These cells are then treated with haptoglobin, deferoxamine (DFO), and flavonoids in order to separate free HbαC and measure their impact on hydroxyl radical formation therapies. The molecular pathogenesis of sporadic colorectal cancer (SCRC) i.e., “inflammation-dysplasia-carcinoma” progression sequence is well described, but the immunopathogenesis of CACRC herein reviewed is broadly still in prodromal stage/phase to be validated and understood. Therefore this timely review outlines the molecular and immunological basis of disease pathogenesis and the pharmaceutical intervention as a protective measure for CACRC.

Preprint ARTICLE | doi:10.20944/preprints202401.1905.v1

Novel Lipid Mediator 7S,14R-Docosahexaenoic Acid: Biogenesis and Harnessing Mesenchymal Stem Cells to Ameliorate Diabetic Mellitus and Retinal Pericyte Loss

Yan Lu, Haibin Tian, Hongying Peng, Nicolas G. Bazan, Song Hong

Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: diabetic mellitus and complications; mesenchymal stem cell; 7S,14R-diHDHA; db/db mice; blood glucose level; β -cell and α -cell; macrophage; insulin; pancreas and islets; retinopathy

Online: 29 January 2024 (02:08:38 CET)

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Preprint ARTICLE | doi:10.20944/preprints202307.0476.v1

Meta-Analysis of the Mechanisms Underlying COVID-19 Modulation of Parkinson’s Disease

Jonathan Zhang, Muhammed Bishir, Sharman Barbhuiya, Sulie L Chang

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: QIAGEN Knowledge Base (QKB); Ingenuity Pathway Analysis (IPA); Network Meta-analysis (NMA); Parkinson’s disease (PD); severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2); Coronavirus Disease-2019 (COVID-19); Neuroinflammation; Synuclein Alpha (SNCA); Angiotensin-converting enzyme-2 (ACE2)

Online: 7 July 2023 (10:55:52 CEST)

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