Identification of key proteins in the signaling crossroads between wound healing and cancer hallmark phenotypes

AbstractWound healing (WH) and cancer seem to share common cellular and molecular processes that could work in a tight balance to maintain tissue homeostasis or, when unregulated, drive tumor progression. The “Cancer Hallmarks” comprise crucial biological properties that mediate the advancement of the disease and affect patient prognosis. These hallmarks have been proposed to overlap with essential features of the WH process. However, common hallmarks and proteins actively participating in both processes have yet to be described. In this work we identify 21 WH proteins strongly linked with solid tumors by integrated TCGA Pan-Cancer and multi-omics analyses. These proteins were associated with eight of the ten described cancer hallmarks, especially avoiding immune destruction. These results show that WH and cancer's common proteins are involved in the microenvironment modification of solid tissues and immune system regulation. This set of proteins, between WH and cancer, could represent key targets for developing therapies.

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Characterization of the Survival Influential Genes in Carcinogenesis

International Journal of Molecular Sciences ◽

10.3390/ijms22094384 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4384

Author(s):

Divya Sahu ◽

Yu-Lin Chang ◽

Yin-Chen Lin ◽

Chen-Ching Lin

Keyword(s):

Cell Cycle ◽

Cox Regression ◽

Monte Carlo Algorithm ◽

Functional Modules ◽

Protective Genes ◽

Cancer Types ◽

Underlying Mechanisms ◽

Patient Prognosis ◽

Pan Cancer

The genes influencing cancer patient mortality have been studied by survival analysis for many years. However, most studies utilized them only to support their findings associated with patient prognosis: their roles in carcinogenesis have not yet been revealed. Herein, we applied an in silico approach, integrating the Cox regression model with effect size estimated by the Monte Carlo algorithm, to screen survival-influential genes in more than 6000 tumor samples across 16 cancer types. We observed that the survival-influential genes had cancer-dependent properties. Moreover, the functional modules formed by the harmful genes were consistently associated with cell cycle in 12 out of the 16 cancer types and pan-cancer, showing that dysregulation of the cell cycle could harm patient prognosis in cancer. The functional modules formed by the protective genes are more diverse in cancers; the most prevalent functions are relevant for immune response, implying that patients with different cancer types might develop different mechanisms against carcinogenesis. We also identified a harmful set of 10 genes, with potential as prognostic biomarkers in pan-cancer. Briefly, our results demonstrated that the survival-influential genes could reveal underlying mechanisms in carcinogenesis and might provide clues for developing therapeutic targets for cancers.

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Development of Spanish Broom and Flax Dressings with Glycyrrhetinic Acid-Loaded Films for Wound Healing: Characterization and Evaluation of Biological Properties

Pharmaceutics ◽

10.3390/pharmaceutics13081192 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1192

Author(s):

Angela Abruzzo ◽

Concettina Cappadone ◽

Valentina Sallustio ◽

Giovanna Picone ◽

Martina Rossi ◽

...

Keyword(s):

Wound Healing ◽

Drug Loading ◽

Healing Process ◽

In Vitro Release ◽

Sodium Hyaluronate ◽

Biological Properties ◽

Glycyrrhetinic Acid ◽

Wound Dressings ◽

Biological Studies

The selection of an appropriate dressing for each type of wound is a very important procedure for a faster and more accurate healing process. So, the aim of this study was to develop innovative Spanish Broom and flax wound dressings, as alternatives to cotton used as control, with polymeric films containing glycyrrhetinic acid (GA) to promote wound-exudate absorption and the healing process. The different wound dressings were prepared by a solvent casting method, and characterized in terms of drug loading, water uptake, and in vitro release. Moreover, biological studies were performed to evaluate their biocompatibility and wound-healing efficacy. Comparing the developed wound dressings, Spanish Broom dressings with GA-loaded sodium hyaluronate film had the best functional properties, in terms of hydration ability and GA release. Moreover, they showed a good biocompatibility, determining a moderate induction of cell proliferation and no cytotoxicity. In addition, the wound-healing test revealed that the Spanish Broom dressings promoted cell migration, further facilitating the closure of the wound.

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Polymer-Based Scaffolds Loaded with Aloe vera Extract for the Treatment of Wounds

Pharmaceutics ◽

10.3390/pharmaceutics13070961 ◽

2021 ◽

Vol 13 (7) ◽

pp. 961

Author(s):

Sibusiso Alven ◽

Vuyolwethu Khwaza ◽

Opeoluwa O. Oyedeji ◽

Blessing A. Aderibigbe

Keyword(s):

Wound Healing ◽

Chronic Wounds ◽

Mechanical Performance ◽

Healing Process ◽

Aloe Vera ◽

Antimicrobial Properties ◽

Biological Properties ◽

Wound Management ◽

Wound Healing Process ◽

Treatment Of Wounds

The treatment of wounds is one challenging biomedical field due to delayed wound healing common in chronic wounds. Several factors delay wound healing, including microbial infections, malnutrition, underlying physiological conditions, etc. Most of the currently used wound dressing materials suffer from poor antimicrobial properties, poor biodegradability and biocompatibility, and weak mechanical performance. Plant extracts, such as Aloe vera, have attracted significant attention in wound management because of their interesting biological properties. Aloe vera is composed of essential constituents beneficial for the wound healing process, such as amino acids, vitamins C and E, and zinc. Aloe vera influences numerous factors that are involved in wound healing and stimulates accelerated healing. This review reports the therapeutic outcomes of aloe vera extract-loaded polymer-based scaffolds in wound management.

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The Pan-Cancer Landscape of Prognostic Germline Variants in 10,582 Patients

10.1101/19010264 ◽

2019 ◽

Author(s):

Ajay Chatrath ◽

Roza Przanowska ◽

Shashi Kiran ◽

Zhangli Su ◽

Shekhar Saha ◽

...

Keyword(s):

Patient Outcome ◽

Cox Regression ◽

Clinical Information ◽

Tumor Aggressiveness ◽

Sequencing Data ◽

Germline Variants ◽

Outcome Information ◽

Germline Variation ◽

Patient Prognosis ◽

Pan Cancer

AbstractWhile clinical data provides physicians with information about patient prognosis, genomic data can further improve these predictions. We analyzed sequencing data from over 10,000 cancer patients and identified hundreds of prognostic germline variants using multivariate Cox regression models. These variants provide information about patient outcomes beyond clinical information currently in use and may augment clinical decisions based on expected tumor aggressiveness. Molecularly, at least twelve of the germline variants are likely associated with patient outcome through perturbation of protein structure and at least five through association with gene expression differences. About half of these germline variants are in previously reported tumor suppressors or oncogenes, with the other half pointing to loci of previously unstudied genes in the literature that should be further investigated for roles in cancers. Our results suggest that germline variation contributes to tumor progression across most cancers and contains patient outcome information not captured by clinical factors.

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Identification of Structurally Similar Phytochemicals to Quercetin with High SIRT1 Binding Affinity and Improving Diabetic Wound Healing by Using In silico Approaches

Biointerface Research in Applied Chemistry ◽

10.33263/briac126.76217632 ◽

2021 ◽

Vol 12 (6) ◽

pp. 7621-7632

Keyword(s):

Wound Healing ◽

In Silico ◽

Binding Free Energy ◽

Biological Properties ◽

In Vivo Studies ◽

Diabetic Wound ◽

Binding Modes ◽

Diabetic Wound Healing

Diabetes Mellitus is the most prevalent metabolic disorder that is increasing at an alarming rate worldwide. The unregulated glucose level leads to various types of health disorders, and one of the major diabetic complications is delayed wound healing. Due to the more side effects of synthetic drugs, there is a need to explore plants and their phytochemicals for medicinal purposes. It was found that Quercetin, a flavonoid, increases the rate of diabetic wound healing by enhancing the expression of SIRT1. This demands more insight towards Quercetin and its similar compounds, as it is hypothesized that similar compounds may have similar biological properties. Thus similarity searching was done to identify the most similar compounds of Quercetin, and then the molecular docking of the screened compounds was performed using AutoDock Vina. The unique ligands were docked into the active site of SIRT1 protein (PDB ID: 4ZZJ). The binding free energy of the interacting ligand with the protein was estimated. Six compounds were identified which possess the maximum structural similarity with Quercetin, and upon docking, it was found that gossypetin and herbacetin have similar binding modes and binding energy as that of Quercetin (-7.5 kcal/mol). Therefore, the hypothesis has been validated by in silico analysis. Our study identified two phytochemicals, Gossypetin, and Herbacetin which can prove beneficial for improving diabetic wound healing but needs to be validated further by in vitro and in vivo studies.

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A New Generation of Electrospun Fibers Containing Bioactive Glass Particles for Wound Healing

Materials ◽

10.3390/ma13245651 ◽

2020 ◽

Vol 13 (24) ◽

pp. 5651

Author(s):

Rachele Sergi ◽

Valeria Cannillo ◽

Aldo R. Boccaccini ◽

Liliana Liverani

Keyword(s):

Mechanical Properties ◽

Wound Healing ◽

Bioactive Glass ◽

Flexible Structures ◽

Biological Properties ◽

Cellular Viability ◽

Bioactive Glasses ◽

Electrospinning Technique ◽

Potential Applications ◽

Biological Performance

Chitosan fibers blended with polyethylene oxide (CHIT_PEO) and crosslinked with genipin were fabricated by electrospinning technique. Subsequently, CHIT_PEO bioactive glass composite electrospun mats were fabricated with the aim to achieve flexible structures with adequate mechanical properties and improved biological performance respect to CHIT_PEO fibers, for potential applications in wound healing. Three different compositions of bioactive glasses (BG) were selected and investigated: 45S5 BG, a Sr and Mg containing bioactive glass (BGMS10) and a Zn-containing bioactive glass (BGMS_2Zn). Particulate BGs (particles size < 20 μm) were separately added to the starting CHIT_PEO solution before electrospinning. The two recently developed bioactive glasses (BGMS10 and BGMS_2Zn) showed very promising biological properties in terms of bioactivity and cellular viability; thus, such compositions were added for the first time to CHIT_PEO solution to fabricate composite electrospun mats. The incorporation of bioactive glass particles and their distribution into CHIT_PEO fibers were assessed by SEM and FTIR analyses. Furthermore, CHIT_PEO composite electrospun mats showed improved mechanical properties in terms of Young’s Modulus compared to neat CHIT_PEO fibers; on the contrary, the values of tensile strain at break (%) were comparable. Biological performance in terms of cellular viability was investigated by means of WST-8 assay and CHIT_PEO composite electrospun mats showed cytocompatibility and the desired cellular viability.

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The Complex Interplay between Metabolic Reprogramming and Epigenetic Alterations in Renal Cell Carcinoma

Genes ◽

10.3390/genes10040264 ◽

2019 ◽

Vol 10 (4) ◽

pp. 264 ◽

Cited By ~ 3

Author(s):

Ana Lameirinhas ◽

Vera Miranda-Gonçalves ◽

Rui Henrique ◽

Carmen Jerónimo

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Biological Properties ◽

Metabolic Reprogramming ◽

Epigenetic Alterations ◽

Cancer Hallmarks ◽

Current Therapies ◽

Localized Disease ◽

Common Malignancy

Renal cell carcinoma (RCC) is the most common malignancy affecting the kidney. Current therapies are mostly curative for localized disease, but do not completely preclude recurrence and metastization. Thus, it is imperative to develop new therapeutic strategies based on RCC biological properties. Presently, metabolic reprograming and epigenetic alterations are recognized cancer hallmarks and their interactions are still in its infancy concerning RCC. In this review, we explore RCC biology, highlighting genetic and epigenetic alterations that contribute to metabolic deregulation of tumor cells, including high glycolytic phenotype (Warburg effect). Moreover, we critically discuss available data concerning epigenetic enzymes’ regulation by aberrant metabolite accumulation and their consequences in RCC emergence and progression. Finally, we emphasize the clinical relevance of uncovering novel therapeutic targets based on epigenetic reprograming by metabolic features to improve treatment and survival of RCC patients.

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Amniotic membrane allografts maintain key biological properties post SCCO2 and lyophilization processing

Journal of Biomaterials Applications ◽

10.1177/0885328220952585 ◽

2020 ◽

Vol 35 (6) ◽

pp. 592-601

Author(s):

Jennifer S McDaniel ◽

Jennifer L Wehmeyer ◽

Lauren E Cornell ◽

Anthony J Johnson ◽

David O Zamora

Keyword(s):

Wound Healing ◽

Amniotic Membrane ◽

Biological Tissues ◽

Storage Conditions ◽

Biological Properties ◽

Biochemical Properties ◽

Specific Storage ◽

Ecm Proteins ◽

Corneal Wound ◽

Processing Techniques

Amniotic membrane (AM) has been shown to enhance corneal wound healing due to the abundance of growth factors, cytokines, and extracellular matrix (ECM) proteins inherent to the tissue. As such, AM has garnered widespread clinical utility as a biological dressing for a number of ophthalmic and soft tissue applications. The preparation, sterilization, and storage procedures used to manufacture AM grafts are extremely important for the conservation of inherent biological components within the membrane. Current processing techniques use harsh chemicals and sterilization agents that can compromise the fundamental wound healing properties of AM. Furthermore, commercially available cryopreserved AM products require specific storage conditions (e.g., ultra-low freezers) thereby limiting their clinical availability in austere environments. Supercritical carbon dioxide (SCCO2) technology allows for the sterilization of biological tissues without the resulting degradation of integral ECM proteins and other factors often seen with current tissue sterilization processes. With this study we demonstrate that lyophilized AM, sterilized using SCCO2, maintains similar biochemical properties and biocompatibility as that of commercially available AM products requiring specialized cold storage conditions.

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Integrative Analysis Reveals the Landscape of Hypoxia-Inducible Factor (HIF) Family Genes in Pan-Cancer

Journal of Oncology ◽

10.1155/2020/8873104 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Qian-Kun Yang ◽

Xue-Xin Wang ◽

Yang Wang ◽

Ni Ni

Keyword(s):

Cancer Progression ◽

Full Range ◽

Hypoxia Inducible Factor ◽

Copy Number Variations ◽

Drug Effectiveness ◽

Cancer Hallmarks ◽

Mechanism Research ◽

O2 Concentration ◽

Transcriptomic Level ◽

Pan Cancer

Inside the cancer microenvironment, reduced O2 concentration, termed as hypoxia, is a common phenotype and leads to cancer progression. However, little is known about how and when those HIF members are dysregulated in distinct cancers. Here, by integrating a full range of data of thousands of patients, we comprehensively analyzed the genetics, epigenetics, and transcriptomic level of HIF genes and further defined pathways triggered by disrupted hypoxia-inducible factors. We reveal the expression landscape of HIF family genes and further demonstrate that copy number variations underlie such dysregulation. Further analysis indicates that HIF genes associate with cancer hallmarks such as cell cycle and DNA damage response. Drug resistance analysis showed that HIF globally impacts drug effectiveness such as docetaxel. In summary, the overall analysis reveals the landscape of HIF genes in pan-cancer and may assist mechanism research about hypoxia.

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A Comprehensive Review on Physiological Effects of Curcumin

Drug Research ◽

10.1055/a-1207-9469 ◽

2020 ◽

Vol 70 (10) ◽

pp. 441-447

Author(s):

Rabiya Ahsan ◽

Md Arshad ◽

Mohammad Khushtar ◽

Mohd Afroz Ahmad ◽

Mohammad Muazzam ◽

...

Keyword(s):

Wound Healing ◽

Curcuma Longa ◽

Biological Properties ◽

In Vivo Studies ◽

Intracellular Signalling Pathways ◽

Excellent Safety Profile ◽

Cardiac Disorders ◽

Indian Food

AbstractTurmeric (Curcuma longa Linn) is an herbal medicine which is traditionally used as a spice, food colouring or flavouring agent and widely used for several diseases such as biliary disorders, cough, hepatic disorders, rheumatism, wound healing, sinusitis, diabetes, cardiac disorders and neurological disorder. It belongs to the Zingiberaceae family. Turmeric is a popular domicile remedy used in Indian food, is mainly a native of south-east Asia, is widely cultivated in India, Sri Lanka, Indonesia, China, Jamaica , Peru, Haiti and Taiwan and it is very less expensive. Curcumin is the main principle of turmeric. Curcumin has shown various biological properties pre-clinically and clinically. Curcumin is a highly pleiotropic molecule which can be modulators of various intracellular signalling pathways that maintain cell growth. It has been reported as anti-inflammatory, anti-angiogenic, antioxidant, wound healing, anti-cancer, anti-Alzheimer and anti-arthritis and possesses an excellent safety profile. All previous review articles on curcumin have collected the biological/pharmacological activities but this review article summarises the most interesting in vitro and in vivo studies of curcumin on most running diseases around the whole world.

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