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1.
Bioorg Chem ; 119: 105550, 2022 02.
Article in English | MEDLINE | ID: covidwho-1561636

ABSTRACT

Infectious diseases caused by new or unknown bacteria and viruses, such as anthrax, cholera, tuberculosis and even COVID-19, are a major threat to humanity. Thus, the development of new synthetic compounds with efficient antimicrobial activity is a necessity. Herein, rationally designed novel multifunctional cationic alternating copolymers were directly synthesized through a step-growth polymerization reaction using a bivalent electrophilic cross-linker containing disulfide bonds and a diamine heterocyclic ring. To optimize the activity of these alternating copolymers, several different diamines and cross-linkers were explored to find the highest antibacterial effects. The synthesized nanopolymers not only displayed good to excellent antibacterial activity as judged by minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, and Escherichia coli, but also reduced the number of biofilm cells even at low concentrations, without killing mammalian cells. Furthermore, in vivo experiments using infected burn wounds in mice demonstrated good antibacterial activity and stimulated wound healing, without causing systemic inflammation. These findings suggest that the multifunctional cationic nanopolymers have potential as a novel antibacterial agent for eradication of multidrug resistant bacterial infections.


Subject(s)
Anti-Bacterial Agents/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Biofilms/drug effects , Cations/pharmacology , Polymers/pharmacology , Wound Healing/drug effects , Amines/chemistry , Animals , Bacteria/drug effects , Bacterial Infections/drug therapy , Bacterial Infections/etiology , Burns/complications , COVID-19 , Cell Survival/drug effects , Cross-Linking Reagents , Drug Resistance, Multiple, Bacterial/drug effects , HEK293 Cells/drug effects , Humans , Mice , Microbial Sensitivity Tests , Polymers/chemistry
2.
Inflamm Bowel Dis ; 27(Supplement_2): S25-S32, 2021 Nov 15.
Article in English | MEDLINE | ID: covidwho-1522203

ABSTRACT

BACKGROUND: Patients with Crohn's disease (CD) undergo frequent endoscopic procedures, with visualization of the gastrointestinal mucosa central to treatment decision-making. Subsequently, a noninvasive alternative to optical colonoscopy (OC) would be welcomed. One such technology is capsule endoscopy, including the PillCam COLON 2 (PCC2), though research validating its use in ileocolonic CD is limited. This study aims to compare PCC2 with ileocolonoscopy (OC) in assessing mucosal CD through use of a standardized scoring system. METHODS: At an Australian tertiary hospital, same-day PCC2 and ileocolonoscopy results of 47 CD patients, with known nonstricturing disease, were prospectively collected and analyzed for correlation and agreement. Deidentified recordings were reported by a single expert gastroenterologist. Mucosal disease was quantified using the Simple Endoscopic Score for Crohn's Disease (SES-CD). The SES-CD results of paired endoscopic modalities were compared in total per bowel segment and per SES-CD variable. RESULTS: Of 47 PCC2 recordings, 68% were complete, fully assessing terminal ileum to rectum, and OC was complete in 89%. Correlation (r) between total SES-CD scores was strongest in the terminal ileum (r = 0.77, P < .001), with the SES-CD variable of "ulcer detection" showing the strongest agreement. The PCC2 (vs OC) identified additional ulcers in the terminal ileum; ascending, transverse, and descending colon; and rectum; scores were 5 (1), 5 (3), 1 (1), 2 (1), and 2 (2), respectively. CONCLUSIONS: The PCC2 shows promise in assessing ileocolonic mucosa, especially in proximal bowel segments, with greater reach of visualization in the small bowel. Given the resource and safety considerations raised by the Coronavirus disease 2019 pandemic, capsule endoscopy has particular significance.This article aims to contribute to the limited body of research surrounding the validity of capsule endoscopy technology in assessing ileocolonic mucosa in Crohn's Disease patients. In doing so, an alternative option for patients enduring frequent endoscopies is given potential.


Subject(s)
Capsule Endoscopy/methods , Colon/diagnostic imaging , Colonoscopy/methods , Crohn Disease/diagnostic imaging , Intestinal Mucosa/diagnostic imaging , Ulcer/diagnostic imaging , Wound Healing , Australia , COVID-19 , Capsule Endoscopes , Colon/drug effects , Humans , Immunosuppressive Agents/therapeutic use , Intestinal Mucosa/drug effects , SARS-CoV-2 , Severity of Illness Index , Treatment Outcome , Ulcer/drug therapy , Wound Healing/drug effects , Wound Healing/physiology
3.
Drug Deliv Transl Res ; 11(4): 1340-1351, 2021 08.
Article in English | MEDLINE | ID: covidwho-1047033

ABSTRACT

Infectious diseases, such as the coronavirus disease-19, SARS virus, Ebola virus, and AIDS, threaten the health of human beings globally. New viruses, drug-resistant bacteria, and fungi continue to challenge the human efficacious drug bank. Researchers have developed a variety of new antiviral and antibacterial drugs in response to the infectious disease crisis. Meanwhile, the development of functional materials has also improved therapeutic outcomes. As a natural material, chitosan possesses good biocompatibility, bioactivity, and biosafety. It has been proven that the cooperation between chitosan and traditional medicine greatly improves the ability of anti-infection. This review summarized the application and design considerations of chitosan-composed systems for the treatment of infectious diseases, looking forward to providing the idea of infectious disease therapy.


Subject(s)
Anti-Infective Agents/administration & dosage , Biocompatible Materials/administration & dosage , COVID-19/drug therapy , Chitosan/administration & dosage , Communicable Diseases/drug therapy , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/immunology , Anti-Bacterial Agents/pharmacokinetics , Anti-Infective Agents/immunology , Anti-Infective Agents/pharmacokinetics , Bandages/microbiology , Biocompatible Materials/pharmacokinetics , COVID-19/immunology , COVID-19/metabolism , Chitosan/immunology , Chitosan/pharmacokinetics , Communicable Diseases/immunology , Communicable Diseases/metabolism , Humans , Wound Healing/drug effects , Wound Healing/physiology
4.
Int J Mol Sci ; 21(22)2020 Nov 10.
Article in English | MEDLINE | ID: covidwho-917002

ABSTRACT

Pro-inflammatory cytokines like interleukin-1ß (IL-1ß) are upregulated during early responses to tissue damage and are expected to transiently compromise the mechanical microenvironment. Fibroblasts are key regulators of tissue mechanics in the lungs and other organs. However, the effects of IL-1ß on fibroblast mechanics and functions remain unclear. Here we treated human pulmonary fibroblasts from control donors with IL-1ß and used Atomic Force Microscopy to unveil that IL-1ß significantly reduces the stiffness of fibroblasts concomitantly with a downregulation of filamentous actin (F-actin) and alpha-smooth muscle (α-SMA). Likewise, COL1A1 mRNA was reduced, whereas that of collagenases MMP1 and MMP2 were upregulated, favoring a reduction of type-I collagen. These mechanobiology changes were functionally associated with reduced proliferation and enhanced migration upon IL-1ß stimulation, which could facilitate lung repair by drawing fibroblasts to sites of tissue damage. Our observations reveal that IL-1ß may reduce local tissue rigidity by acting both intracellularly and extracellularly through the downregulation of fibroblast contractility and type I collagen deposition, respectively. These IL-1ß-dependent mechanical effects may enhance lung repair further by locally increasing pulmonary tissue compliance to preserve normal lung distension and function. Moreover, our results support that IL-1ß provides innate anti-fibrotic protection that may be relevant during the early stages of lung repair.


Subject(s)
Interleukin-1beta/physiology , Lung/physiology , Actins/metabolism , Adolescent , Adult , Biomechanical Phenomena , Cell Movement/drug effects , Cell Movement/physiology , Cell Proliferation/drug effects , Cell Proliferation/physiology , Cells, Cultured , Collagen Type I/genetics , Collagen Type I/metabolism , Collagen Type III/genetics , Collagen Type III/metabolism , Cyclooxygenase 2/metabolism , Elasticity/drug effects , Elasticity/physiology , Female , Fibroblasts/cytology , Fibroblasts/drug effects , Fibroblasts/physiology , Humans , Interleukin-1beta/pharmacology , Lung/cytology , Lung/drug effects , Male , Microscopy, Atomic Force , RNA, Messenger/genetics , RNA, Messenger/metabolism , Regeneration/genetics , Regeneration/physiology , Wound Healing/drug effects , Wound Healing/genetics , Wound Healing/physiology , Young Adult
6.
Cell Metab ; 32(5): 704-709, 2020 11 03.
Article in English | MEDLINE | ID: covidwho-753751

ABSTRACT

SARS-CoV-2 pneumonitis can quickly strike to incapacitate the lung, leading to severe disease and sometimes death. In this perspective, we suggest that vitamin D deficiency and the failure to activate the vitamin D receptor (VDR) can aggravate this respiratory syndrome by igniting a wounding response in stellate cells of the lung. The FDA-approved injectable vitamin D analog, paricalcitol, suppresses stellate cell-derived murine hepatic and pancreatic pro-inflammatory and pro-fibrotic changes. Therefore, we suggest a possible parallel program in the pulmonary stellate cells of COVID-19 patients and propose repurposing paricalcitol infusion therapy to restrain the COVID-19 cytokine storm. This proposed therapy could prove important to people of color who have higher COVID-19 mortality rates and lower vitamin D levels.


Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Drug Repositioning/methods , Ergocalciferols/pharmacology , Ergocalciferols/therapeutic use , Pneumonia, Viral/drug therapy , Receptors, Calcitriol/agonists , Wound Healing/drug effects , Animals , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/virology , Cytokines/metabolism , Humans , Mice , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Receptors, Calcitriol/metabolism , SARS-CoV-2 , Vitamin D Deficiency/drug therapy , Vitamin D Deficiency/epidemiology
7.
Macromol Biosci ; 21(1): e2000252, 2021 01.
Article in English | MEDLINE | ID: covidwho-740854

ABSTRACT

Bacterial infectious diseases and bacterial-infected environments have been threatening the health of human beings all over the world. In view of the increased bacteria resistance caused by overuse or improper use of antibiotics, antibacterial biomaterials are developed as the substitutes for antibiotics in some cases. Among them, antibacterial hydrogels are attracting more and more attention due to easy preparation process and diversity of structures by changing their chemical cross-linkers via covalent bonds or noncovalent physical interactions, which can endow them with various specific functions such as high toughness and stretchability, injectability, self-healing, tissue adhesiveness and rapid hemostasis, easy loading and controlled drug release, superior biocompatibility and antioxidation as well as good conductivity. In this review, the recent progress of antibacterial hydrogel including the fabrication methodologies, interior structures, performances, antibacterial mechanisms, and applications of various antibacterial hydrogels is summarized. According to the bacteria-killing modes of hydrogels, several representative hydrogels such as silver nanoparticles-based hydrogel, photoresponsive hydrogel including photothermal and photocatalytic, self-bacteria-killing hydrogel such as inherent antibacterial peptides and cationic polymers, and antibiotics-loading hydrogel are focused on. Furthermore, current challenges of antibacterial hydrogels are discussed and future perspectives in this field are also proposed.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Hydrogels/therapeutic use , Metal Nanoparticles/chemistry , Anti-Bacterial Agents/chemistry , Antioxidants/chemistry , Antioxidants/therapeutic use , Bacterial Infections/microbiology , Biocompatible Materials/chemistry , Biocompatible Materials/therapeutic use , Delayed-Action Preparations/therapeutic use , Humans , Hydrogels/chemistry , Silver/chemistry , Wound Healing/drug effects
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