Inhibition of the CoREST Repressor Complex Promotes Wound Re-Epithelialization through the Regulation of Keratinocyte Migration.

Wound healing is a complex process involving phases of hemostasis, inflammation, proliferation, and remodeling. The regenerative process in the skin requires coordination between many regulators, including signaling molecules, transcription factors, and the epigenetic machinery. In this study, we show that chromatin regulators HDAC1 and LSD1, key components of the CoREST repressor complex, are upregulated in the regenerating epidermis during wound repair. We also show that corin, a synthetic dual inhibitor of the CoREST complex and HDAC1/LSD1 activities, significantly accelerates wound closure through enhanced re-epithelialization in a mouse tail wound model. Acetylated H3K9 (methylation of histone H3 at lysine 9) expression, a histone modification targeted by HDAC1, is increased in keratinocytes after topical treatment with 100 nM and 1 µM of corin. In vitro experiments demonstrate that corin promotes migration and inhibits the proliferation of human keratinocytes. Furthermore, expression levels of genes promoting keratinocyte migration, such as AREG, CD24, EPHB2, ITGAX, PTGS, SCT1, SERPINB2, SERPINE1, SLPI, SNAI2, and TWIST, increased in keratinocytes treated with corin. These data demonstrate that dual inhibition of class I histone deacetylases and LSD1 by corin may serve as a new approach for promoting wound re-epithelialization and provide a platform for further applications of corin for the treatment of chronic wounds.

DNA dioxygenases Tet2/3 regulate gene promoter accessibility and chromatin topology in lineage-specific loci to control epithelial differentiation.

Execution of lineage-specific differentiation programs requires tight coordination between many regulators including Ten-eleven translocation (TET) family enzymes, catalyzing 5-methylcytosine oxidation in DNA. Here, by using Keratin 14-Cre-driven ablation of Tet genes in skin epithelial cells, we demonstrate that ablation of Tet2/Tet3 results in marked alterations of hair shape and length followed by hair loss. We show that, through DNA demethylation, Tet2/Tet3 control chromatin accessibility and Dlx3 binding and promoter activity of the Krt25 and Krt28 genes regulating hair shape, as well as regulate interactions between the Krt28 gene promoter and distal enhancer. Moreover, Tet2/Tet3 also control three-dimensional chromatin topology in Keratin type I/II gene loci via DNA methylation-independent mechanisms. These data demonstrate the essential roles for Tet2/3 in establishment of lineage-specific gene expression program and control of Dlx3/Krt25/Krt28 axis in hair follicle epithelial cells and implicate modulation of DNA methylation as a novel approach for hair growth control.

Efficient Red Light Emitting Diodes Based on a Zero-Dimensional Organic Antimony Halide Hybrid.

Zero-dimensional (0D) organic metal halide hybrids (OMHHs) have recently emerged as a new class of light emitting materials with exceptional color tunability. While near-unity photoluminescence quantum efficiencies (PLQEs) are routinely obtained for a large number of 0D OMHHs, it remains challenging to apply them as emitter for electrically driven light emitting diodes (LEDs), largely due to the low conductivity of wide bandgap organic cations. Here, the development of a new OMHH, triphenyl(9-phenyl-9H-carbazol-3-yl) phosphonium antimony bromide (TPPcarzSbBr4 ), as emitter for efficient LEDs, which consists of semiconducting organic cations (TPPcarz+ ) and light emitting antimony bromide anions (Sb2 Br8 2- ), is reported. By replacing one of the phenyl groups in a well-known tetraphenylphosphonium cation (TPP+ ) with an electroactive phenylcarbazole group, a semiconducting TPPcarz+ cation is developed for the preparation of red emitting 0D TPPcarzSbBr4 single crystals with a high PLQE of 93.8%. With solution processed TPPcarzSbBr4 thin films (PLQE of 86.1%) as light emitting layer, red LEDs are fabricated to exhibit an external quantum efficiency (EQE) of 5.12%, a peak luminance of 5957 cd m-2 , and a current efficiency of 14.2 cd A-1 , which are the best values reported to date for electroluminescence devices based on 0D OMHHs.

Skin Aging in Long-Lived Naked Mole-Rats Is Accompanied by Increased Expression of Longevity-Associated and Tumor Suppressor Genes.

Naked mole-rats (NMRs) (Heterocephalus glaber) are long-lived mammals that possess a natural resistance to cancer and other age-related pathologies, maintaining a healthy life span >30 years. In this study, using immunohistochemical and RNA-sequencing analyses, we compare skin morphology, cellular composition, and global transcriptome signatures between young and aged (aged 3‒4 vs. 19‒23 years, respectively) NMRs. We show that similar to aging in human skin, aging in NMRs is accompanied by a decrease in epidermal thickness; keratinocyte proliferation; and a decline in the number of Merkel cells, T cells, antigen-presenting cells, and melanocytes. Similar to that in human skin aging, expression levels of dermal collagens are decreased, whereas matrix metalloproteinase 9 and matrix metalloproteinase 11 levels increased in aged versus in young NMR skin. RNA-sequencing analyses reveal that in contrast to human or mouse skin aging, the transcript levels of several longevity-associated (Igfbp3, Igf2bp3, Ing2) and tumor-suppressor (Btg2, Cdkn1a, Cdkn2c, Dnmt3a, Hic1, Socs3, Sfrp1, Sfrp5, Thbs1, Tsc1, Zfp36) genes are increased in aged NMR skin. Overall, these data suggest that specific features in the NMR skin aging transcriptome might contribute to the resistance of NMRs to spontaneous skin carcinogenesis and provide a platform for further investigations of NMRs as a model organism for studying the biology and disease resistance of human skin.

Exploring biocontrol and growth-promoting potential of multifaceted PGPR isolated from natural suppressive soil against the causal agent of chickpea wilt.

Chickpea is an important nutritive food crop both for humans and animals. Chickpea wilt caused by Fusarium oxysporum f.sp. ciceris (Foc) results in huge yield losses every year. Chickpea being a food crop requires the development of an eco-friendly bio-pesticide to effectively control the chickpea wilt disease. In this study, more than 50 bacterial stains isolated from the rhizosphere of healthy plants growing in wilt sick soil were examined for their Foc antagonist activities. Out of these, 17 strains showing > 90% growth inhibition of Foc were then characterized for their plant growth-promoting (PGP) and biocontrol traits. The biocontrol and PGP traits identified include amylase, hydrogen cyanide, protease, cellulase, chitinase activities, p-solubilization, nitrogen-fixing, and indole-3-acetic acid production. Two bacterial strains, IR-27 and IR-57, exhibiting the highest Foc proliferation inhibition and the PGP potential along with a consortium of four different strains (Serratia sp. IN-1, Serratia sp. IS-1, Enterobacter sp. IN-2, Enterobacter sp. IN-6) were used for controlling the chickpea wilt disease and growth promotion of the chickpea plants. Confocal laser scanning microscopy revealed their root colonization ability with partial or complete elimination of broken Foc mycelia and hyphae from roots. The bacterial inoculations particularly the consortium significantly suppressed the disease and improved the overall root morphology traits (root length, root surface area, root volume, forks, tips, and crossings), resulting in enhanced growth of the chickpea plants. Significant changes in growth (107% increase in root length, 23% increase in shoot length, and 54% increase in branches) in Foc-challenged plants were observed when inoculated with the consortium. Further investigations revealed that the chickpea plants inoculated with bacterial strains induced the expression of a number of key defence enzymes, including the phenylalanine ammonia lyase, peroxidase, polyphenol peroxidase, ß-1,3 glucanase, which might have helped the plants to thwart the pathogen attack. These findings indicate the potential of our identified bacterial strains to be used as a natural biopesticide for controlling the chickpea wilt disease.

Fluorescent-based nanosensors for selective detection of a wide range of biological macromolecules: A comprehensive review.

Thanks to their unique attributes, such as good sensitivity, selectivity, high surface-to-volume ratio, and versatile optical and electronic properties, fluorescent-based bioprobes have been used to create highly sensitive nanobiosensors to detect various biological and chemical agents. These sensors are superior to other analytical instrumentation techniques like gas chromatography, high-performance liquid chromatography, and capillary electrophoresis for being biodegradable, eco-friendly, and more economical, operational, and cost-effective. Moreover, several reports have also highlighted their application in the early detection of biomarkers associated with drug-induced organ damage such as liver, kidney, or lungs. In the present work, we comprehensively overviewed the electrochemical sensors that employ nanomaterials (nanoparticles/colloids or quantum dots, carbon dots, or nanoscaled metal-organic frameworks, etc.) to detect a variety of biological macromolecules based on fluorescent emission spectra. In addition, the most important mechanisms and methods to sense amino acids, protein, peptides, enzymes, carbohydrates, neurotransmitters, nucleic acids, vitamins, ions, metals, and electrolytes, blood gases, drugs (i.e., anti-inflammatory agents and antibiotics), toxins, alkaloids, antioxidants, cancer biomarkers, urinary metabolites (i.e., urea, uric acid, and creatinine), and pathogenic microorganisms were outlined and compared in terms of their selectivity and sensitivity. Altogether, the small dimensions and capability of these nanosensors for sensitive, label-free, real-time sensing of chemical, biological, and pharmaceutical agents could be used in array-based screening and in-vitro or in-vivo diagnostics. Although fluorescent nanoprobes are widely applied in determining biological macromolecules, unfortunately, they present many challenges and limitations. Efforts must be made to minimize such limitations in utilizing such nanobiosensors with an emphasis on their commercial developments. We believe that the current review can foster the wider incorporation of nanomedicine and will be of particular interest to researchers working on fluorescence technology, material chemistry, coordination polymers, and related research areas.

Bacterial microbiome of faecal samples of naked mole-rat collected from the toilet chamber.

OBJECTIVE: The naked mole rats (NMRs, Heterocephalus glaber) are subterranean rodents that belong to the family Bathyergidae. They gained the attention of the scientific community for their exceptionally long lifespan of up to 30 years and have become an animal model of biomedical research on neurodegenerative diseases, aging and cancer. NMRs dig and survive in a maze of underground tunnels and chambers and demarcate toilet chambers for defecation and urination. Due to their coprophagic behaviours, we believed that the toilet chamber might play a role in maintaining optimal health of the NMRs. A 16S rRNA gene amplicon sequencing was performed to characterize the bacterial microbiome of faecal samples collected from the toilet chamber of a laboratory NMR colony. RESULTS: Four faecal samples were collected at different time points from the same toilet chamber of a laboratory NMR colony for analysis. The 16S rRNA gene amplicon sequencing revealed that bacterial phyla Firmicutes and Bacteroidetes were the dominant taxa in the bacterial microbiome of NMRs. The relative abundance of the bacterial taxa shifted substantially between time points, indicating a dynamic microbiome in the toilet chamber. The data provided an insight to the faecal microbiome of NMRs in the toilet chamber.

Quantum Dots: Synthesis, Antibody Conjugation, and HER2-Receptor Targeting for Breast Cancer Therapy.

Breast cancer is becoming one of the main lethal carcinomas in the recent era, and its occurrence rate is increasing day by day. There are different breast cancer biomarkers, and their overexpression takes place in the metastasis of cancer cells. The most prevalent breast cancer biomarker is the human epidermal growth factor receptor2 (HER2). As this biomarker is overexpressed in malignant breast tissues, it has become the main focus in targeted therapies to fight breast cancer. There is a cascade of mechanisms involved in metastasis and cell proliferation in cancer cells. Nanotechnology has become extremely advanced in targeting and imaging cancerous cells. Quantum dots (QDs) are semiconductor NPs, and they are used for bioimaging, biolabeling, and biosensing. They are synthesized by different approaches such as top-down, bottom-up, and synthetic methods. Fully human monoclonal antibodies synthesized using transgenic mice having human immunoglobulin are used to target malignant cells. For the HER2 receptor, herceptin® (trastuzumab) is the most specific antibody (Ab), and it is conjugated with QDs by using different types of coupling mechanisms. This quantum dot monoclonal antibody (QD-mAb) conjugate is localized by injecting it into the blood vessel. After the injection, it goes through a series of steps to reach the intracellular space, and bioimaging of specifically the HER2 receptor occurs, where apoptosis of the cancer cells takes place either by the liberation of Ab or the free radicals.

Novel Perspectives towards RNA-Based Nano-Theranostic Approaches for Cancer Management.

In the fight against cancer, early diagnosis is critical for effective treatment. Traditional cancer diagnostic technologies, on the other hand, have limitations that make early detection difficult. Therefore, multi-functionalized nanoparticles (NPs) and nano-biosensors have revolutionized the era of cancer diagnosis and treatment for targeted action via attaching specified and biocompatible ligands to target the tissues, which are highly over-expressed in certain types of cancers. Advancements in multi-functionalized NPs can be achieved via modifying molecular genetics to develop personalized and targeted treatments based on RNA interference. Modification in RNA therapies utilized small RNA subunits in the form of small interfering RNAs (siRNA) for overexpressing the specific genes of, most commonly, breast, colon, gastric, cervical, and hepatocellular cancer. RNA-conjugated nanomaterials appear to be the gold standard for preventing various malignant tumors through focused diagnosis and delivering to a specific tissue, resulting in cancer cells going into programmed death. The latest advances in RNA nanotechnology applications for cancer diagnosis and treatment are summarized in this review.