Last update 01 Nov 2024

HTN1

Last update 01 Nov 2024

Basic Info

Synonyms

HIS1, His1 12/38, His1 31/57

+ [9]

Introduction

Histatins are salivary proteins that are considered to be major precursors of the protective proteinaceous structure on tooth surfaces (enamel pellicle). In addition, histatins exhibit antibacterial and antifungal activities.

Drugs associated with HTN1

DB2-121

Target

HTN1

Mechanism

HTN1 modulators

Active Org.-

Originator Org.

University of Western Ontario

Active Indication-

Inactive Indication

Infectious Diseases [+1]

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with HTN1

100 Translational Medicine associated with HTN1

0 Patents (Medical) associated with HTN1

228

Literatures (Medical) associated with HTN1

01 Nov 2024·Free Radical Biology and Medicine

Human salivary histatin 1 regulating IP3R1/GRP75/VDAC1 mediated mitochondrial-associated endoplasmic reticulum membranes (MAMs) inhibits cell senescence for diabetic wound repair

Article

Author: Zhang, Jiaqing ; Ye, Yongsheng ; Huang, Jie ; Xian, Tinghui ; Peng, Bohua ; Lin, Zhen ; Liu, Yi ; Liang, Lin ; Wu, Hao

RATIONALEDifficulty in skin wound healing is a concern for diabetic patients across the world. Impaired mitochondrial dysfunction and aging-related vascular dysfunction in human umbilical vein endothelial cells (HUVECs) caused by oxidative stress are major impediments to diabetic wound healing. However, research on skin repair at the mechanistic level by improving mitochondrial function and inhibiting oxidative stress-induced HUVEC senescence remains lacking.METHODS AND RESULTSHuman saliva effectively inhibits the natural aging of HUVECs through immunodepletion experiments. Histatin 1 (Hst1), a short peptide comprising 38 amino acids, is the primary component of human saliva that prevents HUVEC aging. Based on in vitro findings, Hst1 decreased staining for senescence-associated β-galactosidase activity and expression of mediators of senescence signaling, including p53, p21, and p16. Mechanistically, HUVEC senescence is associated with Hst1-modulated nuclear factor Nrf2 signaling as Hst1 induces ERK-mediated Nrf2 nuclear translocation through NADPH oxidase-dependent ROS regulation, reinforced Nrf2 antioxidant response, and suppressed oxidative stress. RNA sequencing identified that the mitochondrial-related gene set was enriched in the Hst1 group. Coimmunoprecipitation indicated that Hst1 delayed hydrogen peroxide-induced HUVEC senescence by inhibiting mitochondria-associated endoplasmic reticulum (ER) membrane formation mediated by inositol 1,4,5-trisphosphate receptor 1-glucose-regulated protein 75-voltage-dependent anion channel 1 (VDAC1) complex interactions. Furthermore, in aging HUVECs, Hst1 treatment or VDAC1 silencing with small interfering RNA hindered calcium (Ca²⁺) transfer from the ER to the mitochondria, thereby ameliorating mitochondrial Ca²⁺ overload and restoring mitochondrial function. In an in vivo mouse model of diabetes mellitus skin defects, Hst1 facilitated wound healing by stimulating the new blood vessel formation and impeding the expression of senescent biomarkers.CONCLUSIONSThis study proposes a theoretical solution that Hst1 can restore mitochondrial function by inhibiting oxidative stress or cellular senescence, thereby promoting angiogenesis and diabetic wound repair.

01 Sep 2024·Archives of Oral Biology

In vivo modification of the enamel pellicle and saliva resveratrol levels after use of resveratrol-containing orodispersible capsules

Article

Author: Iano, Flávia ; Levy, Flávia Mauad ; Carvalho, Thamyris de Souza ; Pavan, Nathalia Mariana ; Buzalaf, Marília Afonso Rabelo ; Ventura, Talita Mendes Oliveira ; Câmara, João Victor Frazão ; Araujo, Tamara Teodoro ; Ximenes, Valdecir Farias ; Pelá, Vinícius Taioqui

OBJECTIVESTo evaluate in vivo 1) the bioavailability of trans-resveratrol when administered through sublingual capsules; 2) the effect of resveratrol on the protein composition of the acquired enamel pellicle (AEP).DESIGNTen volunteers received a sublingual capsule containing 50 mg of trans-resveratrol. Unstimulated saliva was then collected after 0, 30, 60, and 120 min and AEP was collected after 120 min following administration of the capsule. In the next week, the volunteers received a placebo sublingual capsule, and saliva and AEP were collected again. Saliva samples were analyzed for free trans-resveratrol using high-performance liquid chromatopgraphy (HPLC), and AEP samples were subjected to proteomic analysis (nLC-ESI-MS/MS).RESULTSTrans-resveratrol was detected in saliva at all the time points evaluated, with the peak at 30 min. A total of 242 proteins were identified in both groups. Ninety-six proteins were increased and 23 proteins were decreased in the Resveratrol group. Among the up-regulated proteins, isoforms of cystatins, PRPs, Mucin-7, Histatin-1, Lactotrasnferrin and Lysozyme-C were increased and the isoforms of Protein S100, Neutrophil defensins, Albumin, PRPs, and, Statherin were decreased in Resveratrol group.CONCLUSIONThe sublingual capsule is effective at increasing the bioavailability of trans-resveratrol in saliva. Several proteins involved in important processes to maintain systemic and oral health homeostasis were identified. These proteins differently expressed due to the presence of trans-resveratrol deserve attention for future studies, since they have important functions, mainly related to antimicrobial action.

01 Jul 2024·Journal of Allergy and Clinical Immunology

Allergic fungal rhinosinusitis linked to other hyper-IgE syndromes through defective TH17 responses

Article

Author: Yao, William C ; Sun, Hua ; Citardi, Martin J ; Corry, David B ; Ashoori, Faramarz ; Luong, Amber U ; Li, Yi-Dong ; Knight, J Morgan

BACKGROUNDIn a gene expression analysis comparing sinus mucosa samples from allergic fungal rhinosinusitis (AFRS) patients with samples from non-AFRS chronic rhinosinusitis with nasal polyp (CRSwNP) patients, the antimicrobial peptide (AMP) histatin 1 (HTN1) was found to be the most differentially downregulated gene in AFRS.OBJECTIVEWe sought to identify the molecular etiology of the downregulated expression of HTN1.METHODSWe used RT-PCR to compare the expression of AMPs and a fungistasis assay to evaluate the antifungal activity of sinus secretions. Using flow cytometry, we characterized the presence of T_H17/T_H22 cells and signal transducer and activator of transcription (STAT) signaling from AFRS patients, non-AFRS CRSwNP patients, and healthy controls.RESULTSWe confirmed decreased expression of AMPs in AFRS sinus mucosa with concordant decrease in antifungal activity in sinus secretions. IL-22 and IL-22-producing T cells were deficient within sinus mucosa of AFRS patients. In vitro studies demonstrated a defect in IL-6/STAT3 signaling critical for T_H17/T_H22 differentiation. Epithelial cells from AFRS patients could express AMPs when stimulated with exogenous IL-22/IL-17 and circulating T_H17 cell abundance was normal.CONCLUSIONSSimilar to other hyper-IgE syndromes, but distinct from CRSwNP, AFRS patients express a defect in STAT3 activation limited to IL-6-dependent STAT3 phosphorylation that is critical for T_H17/T_H22 differentiation. This defect leads to a local deficiency of IL-17/IL-22 cytokines and deficient AMP expression within diseased sinus mucosa of AFRS patients. Our findings support evaluation of therapeutic approaches that enhance airway AMP production in AFRS.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

HTN1

Basic Info

Related

Analysis