Integration of Functional Polymers and Biosensors to Enhance Wound Healing.

Biosensors have led to breakthroughs in the treatment of chronic wounds. Since the discovery of the oxygen electrode by Clarke, biosensors have evolved into the design of smart bandages that dispense drugs to treat wounds in response to physiological factors, such as pH or glucose concentration, which indicate pathogenic tendencies. Aptamer-based biosensors have helped identify and characterize pathogenic bacteria in wounds that often form antibiotic-resistant biofilms.

Activates Quorum Sensing, Antioxidant Enzymes and Type VI Secretion in Response to Oxidative Stress to Initiate Biofilm Formation and Wound Chronicity.

() is an opportunistic pathogen frequently isolated from cutaneous chronic wounds. How , in the presence of oxidative stress (OS), colonizes chronic wounds and forms a biofilm is still unknown. The purpose of this study is to investigate the changes in gene expression seen when PA is challenged with the high levels of OS present in chronic wounds.

Assessing Animal Models to Study Impaired and Chronic Wounds.

Impaired healing wounds do not proceed through the normal healing processes in a timely and orderly manner, and while they do eventually heal, their healing is not optimal. Chronic wounds, on the other hand, remain unhealed for weeks or months. In the US alone, chronic wounds impact ~8.

Targeting Anaerobic Respiration in with Chlorate Improves Healing of Chronic Wounds.

is an opportunistic pathogen that can establish chronic infections and form biofilm in wounds. Because the wound environment is largely devoid of oxygen, may rely on anaerobic metabolism, such as nitrate respiration, to survive in wounds. While nitrate reductase (Nar) typically reduces nitrate to nitrite, it can also reduce chlorate to chlorite, which is a toxic oxidizing agent.

Catalase as a novel drug target for metastatic castration-resistant prostate cancer.

Prostate Cancer (PCa) is the second most prevalent cancer in the world. Currently, most treatments for PCa involve Androgen Deprivation Therapy (ADT) which inhibits androgen-dependent tumor cell growth. When PCa is diagnosed early and is still Androgen Dependent, ADT is effective.

Hydrogel-Encapsulated Heterogenous Mesoporous Resin Catalyst for In Situ Anti-Cancer Agent Production under Biological Conditions.

A heterogenous Palladium anchored Resorcinol-formaldehyde-hyperbranched PEI mesoporous catalyst, made by one-pot synthesis, was used successfully for in situ Suzuki-Miyaura cross coupling synthesis of anticancer prodrug PP-121 from iodoprazole and boronic ester precursors. The mesoporous catalyst with the non-cytotoxic precursors were tested in 2D in vitro model with excellent cytocompatibility and a strong suppression of PC3 cancer cell proliferation, underscored by 50% reduction in PC3 cells viability and 55% reduction in cell metabolism activity and an enhanced rate of early and late apoptosis in flow cytometry, that was induced only by successful in situ pro drug PP121 synthesis from the precursors. The 3D gelatin methacrylate hydrogel encapsulated in vitro cell models underscored the results with a 52% reduction in cell metabolism and underscored apoptosis of PC3 cells when the Pd anchored catalyst was combined with the precursors.

Developmental exposure to indoor flame retardants and hypothalamic molecular signatures: Sex-dependent reprogramming of lipid homeostasis.

Polybrominated diphenyl ethers (PBDEs) are a class of flame-retardant organohalogen pollutants that act as endocrine/neuroendocrine disrupting chemicals (EDCs). In humans, exposure to brominated flame retardants (BFR) or other environmentally persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) and novel organophosphate flame retardants has been associated with increasing trends of diabetes and metabolic disease. However, the effects of PBDEs on metabolic processes and their associated sex-dependent features are poorly understood.

Animal models for the study of acute cutaneous wound healing.

The process of wound healing is critical to maintaining homeostasis after injury. Although a considerable amount has been learned about this complex process, much remains unknown. Whereas, studies with human volunteers are ideal given the unique nature of the human skin anatomy and immune system, the lack of such clinical access has made animal models prime candidates for use in preclinical studies.

Signaling Pathways Associated with Chronic Wound Progression: A Systems Biology Approach.

Previously we have shown that several oxidative stress-driven pathways in cutaneous chronic wounds are dysregulated in the first 48 h post-wounding. Here, we performed an RNASeq analysis of tissues collected up to day 20 after wounding, when we have determined full chronicity is established. Weighted Gene Correlation Network Analysis was performed in R segregating the genes into 14 modules.

Thirdhand Exposures to Tobacco-Specific Nitrosamines through Inhalation, Dust Ingestion, Dermal Uptake, and Epidermal Chemistry.

Tobacco-specific nitrosamines (TSNAs) are emitted during smoking and form indoors by nitrosation of nicotine. Two of them, '-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are human carcinogens with No Significant Risk Levels (NSRLs) of 500 and 14 ng day, respectively. Another TSNA, 4-(methylnitrosamino)-4-(3-pyridyl) butanal (NNA), shows genotoxic and mutagenic activity .

Chronic wounds: Treatment consensus.

The Wound Healing Foundation (WHF) recognised a need for an unbiased consensus on the best treatment of chronic wounds. A panel of 13 experts were invited to a virtual meeting which took place on 27 March 2021. The proceedings were organised in the sub-sections diagnosis, debridement, infection control, dressings, grafting, pain management, oxygen treatment, outcomes and future needs.

Using systems biology approaches to identify signalling pathways activated during chronic wound initiation.

Chronic wounds are a significant health problem worldwide. However, nothing is known about how chronic wounds initiate and develop. Here we use a chronic wound model in diabetic mice and a Systems Biology Approach using nanoString nCounter technology and weighted gene correlation network analysis (WGCNA), with tissues collected at 6, 12, 24 and 48 h post-wounding, to identify metabolic signalling pathways involved in initiation of chronicity.

A Bayesian longitudinal trend analysis of count data with Gaussian processes.

The context of comparing two different groups of subjects that are measured repeatedly over time is considered. Our specific focus is on highly variable count data which have a nonnegligible frequency of zeros and have time trends that are difficult to characterize. These challenges are often present when analyzing bacteria or gene expression data sets.

Unravelling the metabolic alterations of liver damage induced by thirdhand smoke.

Background: Thirdhand smoke (THS) is the accumulation of tobacco smoke gases and particles that become embedded in materials. Previous studies concluded that THS exposure induces oxidative stress and hepatic steatosis in liver. Despite the knowledge of the increasing danger of THS exposure, the metabolic disorders caused in liver are still not well defined.

High Levels of Oxidative Stress Create a Microenvironment That Significantly Decreases the Diversity of the Microbiota in Diabetic Chronic Wounds and Promotes Biofilm Formation.

Diabetics chronic wounds are characterized by high levels of oxidative stress (OS) and are often colonized by biofilm-forming bacteria that severely compromise healing and can result in amputation. However, little is known about the role of skin microbiota in wound healing and chronic wound development. that high OS levels lead to chronic wound development by promoting the colonization of biofilm-forming bacteria over commensal/beneficial bacteria.

-Acetyl-cysteine and Mechanisms Involved in Resolution of Chronic Wound Biofilm.

Chronic wounds are a major global health problem with the presence of biofilm significantly contributing to wound chronicity. Current treatments are ineffective in resolving biofilm and simultaneously killing the bacteria; therefore, effective biofilm-resolving drugs are needed. We have previously shown that, together with -tocopherol, -acetyl-cysteine (NAC) significantly improves the healing of biofilm-containing chronic wounds, in a diabetic mouse model we developed, by causing disappearance of the bacteria and breakdown of the extracellular polymeric substance (EPS).

High Levels of Oxidative Stress and Skin Microbiome are Critical for Initiation and Development of Chronic Wounds in Diabetic Mice.

A balanced redox state is critical for proper healing. Although human chronic wounds are characterized by high levels of oxidative stress (OS), whether OS levels are critical for chronic wound development is not known. For these studies, we used our chronic wound model in diabetic mice that has similar characteristics as human chronic wounds, including naturally developed biofilm.

Protocol to Create Chronic Wounds in Diabetic Mice.

Chronic wounds develop as a result of defective regulation in one or more complex cellular and molecular processes involved in proper healing. They impact ~6.5M people and cost ~$40B/year in the US alone.

rMSIKeyIon: An Ion Filtering R Package for Untargeted Analysis of Metabolomic LDI-MS Images.

Many MALDI-MS imaging experiments make a case versus control studies of different tissue regions in order to highlight significant compounds affected by the variables of study. This is a challenge because the tissue samples to be compared come from different biological entities, and therefore they exhibit high variability. Moreover, the statistical tests available cannot properly compare ion concentrations in two regions of interest (ROIs) within or between images.

Correction: A Health Threat to Bystanders Living in the Homes of Smokers: How Smoke Toxins Deposited on Surfaces Can Cause Insulin Resistance.

[This corrects the article DOI: 10.1371/journal.pone.

Biological markers of harm can be detected in mice exposed for two months to low doses of Third Hand Smoke under conditions that mimic human exposure.

Third-hand smoke (THS) is a recently discovered environmental health hazard that results from accumulation and aging of second-hand smoke (SHS) toxins on surfaces of environments where smoking has occurred. Our objective was to determine whether there is a dose-dependent effect of THS exposure on biological markers of harm (BMH) using an in vivo exposure system that mimics exposure of humans to THS. THS exposure generated from as low as the 10 cigarettes-smoking regimen, resulted in increased circulating inflammatory cytokines, tumor necrosis factor alpha, interleukin 1 alpha, and granulocyte macrophage colony-stimulating factor.

Insulin regulates multiple signaling pathways leading to monocyte/macrophage chemotaxis into the wound tissue.

Wound healing is a complex process that involves sequential phases that overlap in time and space and affect each other dynamically at the gene and protein levels. We previously showed that insulin accelerates wound healing by stimulating faster and regenerative healing. One of the processes that insulin stimulates is an increase in monocyte/macrophage chemotaxis.

Biomarkers of disease can be detected in mice as early as 4 weeks after initiation of exposure to third-hand smoke levels equivalent to those found in homes of smokers.

Third-hand smoke (THS) is a newly discovered environmental health hazard that results from accumulation and aging of second-hand smoke (SHS) toxins on surfaces where smoking has occurred. Our objective was to determine whether there is a time-dependent effect of THS exposure on health. Using an exposure mouse system that mimics exposure of humans to THS, we investigated its effects on biomarkers found in serum, and in liver and brain tissues.

Red-shifted luciferase-luciferin pairs for enhanced bioluminescence imaging.

Red-shifted bioluminescence reporters are desirable for biological imaging. We describe the development of red-shifted luciferins based on synthetic coelenterazine analogs and corresponding mutants of NanoLuc that enable bright bioluminescence. One pair in particular showed superior in vitro and in vivo sensitivity over commonly used bioluminescence reporters.