Escherichia coli BarA-UvrY regulates the pks island and kills Staphylococci via the genotoxin colibactin

Wound infections are often polymicrobial in nature and are associated with poor disease prognoses. Escherichia coli and Staphylococcus aureus are among the top five most cultured pathogens from wound infections. However, little is known about the polymicrobial interactions between E. coli and S. aureus during wound infections. In this study, we show that E. coli kills S. aureus both in vitro and in a mouse excisional wound model via the genotoxin, colibactin. We also show that the BarA-UvrY two component system (TCS) is a novel regulator of the pks island, which acts through the carbon storage global regulatory (Csr) system. Together, our data demonstrate the role of colibactin in inter-species competition and show that it is regulated by BarA-UvrY TCS, a previously uncharacterized regulator of the pks island.

The Effect of Topically Applied Boric Acid on Ephrin-Eph Pathway in Wound Treatment: An Experimental Study

Background: Wound healing has a vital importance for the organism and various agents are used to accelerate wound healing. Although the effect of boron on wound healing is known, its mechanisms are not completely clear yet. In this study, the effect of boron in the Ephrin /Eph pathway will be evaluated. Methods: Forty adult female rats were used in the study. A full-thickness excisional wound model was created in all groups divided as Control, Fito, Boron and Plu groups. After the applications performed twice a day and lasting 7 days, skin tissues obtained and evaluated histopathological (inflammatory cell infiltration, oedema, and fibroblast proliferation density) and immunohistochemical (TNF-α, EphrinA1, EphrinB1, EphrinB2 and EphB4). Results: Inflammatory cell infiltration score was found to be higher in the Fito group compared to Boron group (p = .018). Fibroblast proliferation density was higher in Plu group than Boron group (p = .012). While TNF-α was lower in boron group than Plu (p = .027) and Fito (p = .016) groups, EphrinA1 was higher in Boron group than Plu group (p = .005). EphrinB1 expression was higher in Boron group compared to Plu (p = .015) and Fito (p = .015) groups, and the same difference was also observed in EphrinB2 (p values .000). Similarly, EphB4 immunoreactivity was higher in the Boron group compared to Plu (p = .000) and Fito (p = .002). Conclusion: One of the mechanisms of action of boron in wound healing is to increase EphrinB1, EphrinB2 and EphB4. Low TNF-α and histopathological findings indicate that boron limits extensive wound healing.

Hyaluronan Functions in Wound Repair That Are Captured to Fuel Breast Cancer Progression

Signaling from an actively remodeling extracellular matrix (ECM) has emerged as a critical factor in regulating both the repair of tissue injuries and the progression of diseases such as metastatic cancer. Hyaluronan (HA) is a major component of the ECM that normally functions in tissue injury to sequentially promote then suppress inflammation and fibrosis, a duality in which is featured, and regulated in, wound repair. These essential response-to-injury functions of HA in the microenvironment are hijacked by tumor cells for invasion and avoidance of immune detection. In this review, we first discuss the numerous size-dependent functions of HA and emphasize the multifunctional nature of two of its receptors (CD44 and RHAMM) in regulating the signaling duality of HA in excisional wound healing. This is followed by a discussion of how HA metabolism is de-regulated in malignant progression and how targeting HA might be used to better manage breast cancer progression.

The Protective Effect of Snail Secretion Filtrate in an Experimental Model of Excisional Wounds in Mice

Wound healing is a physiological process comprising several coordinated phases, such as inflammation, proliferation, and remodeling. For centuries, Helix aspersa Muller mucus has been known to have biological properties that are useful for treating skin disorders. In this study, we used a full-thickness excisional wound model in mice to test the hypothesis that Snail Secretion Filtrate (SSF) can improve the wound healing process. The mucus from Helix aspersa Muller was obtained mechanically by manually stimulating snails with a sterile cotton swab tip, and then the mucus was subjected to a series of filtrations to obtain SSF. After wounding, the mice were treated topically with SSF for 14 days. Our macroscopic results show that the SSF treatment significantly improved the speed and percentage of wound area closure. Furthermore, SSF improved several markers of proper wound healing, such as collagen deposition (Masson, COL3A1, matrix metalloproteinases (MMPs)) and the tissue remodeling process (α-sma, vascular-endothelial growth factor (VEGF)). SSF was also able to counteract the inflammatory process in injured wound tissue (myeloperoxidase (MPO) IL-1β, IL-6, TNF-α). In conclusion, our results show that SSF is able to enhance the speed and efficiency of wound healing and positively regulate several aspects of the wound healing process, such as the proliferative and remodeling phases.

Stable Gastric Pentadecapeptide BPC 157 and Wound Healing

Significance: The antiulcer peptide, stable gastric pentadecapeptide BPC 157 (previously employed in ulcerative colitis and multiple sclerosis trials, no reported toxicity (LD1 not achieved)), is reviewed, focusing on the particular skin wound therapy, incisional/excisional wound, deep burns, diabetic ulcers, and alkali burns, which may be generalized to the other tissues healing.Recent Advances: BPC 157 has practical applicability (given alone, with the same dose range, and same equipotent routes of application, regardless the injury tested).Critical Issues: By simultaneously curing cutaneous and other tissue wounds (colocutaneous, gastrocutaneous, esophagocutaneous, duodenocutaneous, vesicovaginal, and rectovaginal) in rats, the potency of BPC 157 is evident. Healing of the wounds is accomplished by resolution of vessel constriction, the primary platelet plug, the fibrin mesh which acts to stabilize the platelet plug, and resolution of the clot. Thereby, BPC 157 is effective in wound healing much like it is effective in counteracting bleeding disorders, produced by amputation, and/or anticoagulants application. Likewise, BPC 157 may prevent and/or attenuate or eliminate, thus, counteract both arterial and venous thrombosis. Then, confronted with obstructed vessels, there is circumvention of the occlusion, which may be the particular action of BPC 157 in ischemia/reperfusion.Future Directions: BPC 157 rapidly increases various genes expression in rat excision skin wound. This would define the healing in the other tissues, that is, gastrointestinal tract, tendon, ligament, muscle, bone, nerve, spinal cord, cornea (maintained transparency), and blood vessels, seen with BPC 157 therapy.

The Effect of Topically Applied Boric Acid on Ephrin-Eph Pathway in Wound Treatment: An Experimental Study

Background: Wound healing has a vital importance for the organism and various agents are used to accelerate wound healing. Although the effect of boron on wound healing is known, its mechanisms are not completely clear yet. In this study, the effect of boron in the Ephrin /Eph pathway will be evaluated.Methods and Results: Forty adult female rats were used in the study. A full-thickness excisional wound model was created in all groups divided as control, Fito cream, Boric acid and Pluronic gel groups. Histopathologically, inflammatory cell infiltration(ICI), edema and fibroblast proliferation density(FPD); immunohistochemically TNF-α(Tumor necrosis factor α), EphrinA1, EphrinB1, EphrinB2 and EphB4 antibodies were evaluated in the skin tissues obtained after the applications performed twice a day and lasting 7 days.The ICI score was found to be higher in the Fito group compared to the boron group(p=0.018). FPD was higher in Plu group than boron group(p=0.012). While TNF-α was lower in boron group than Plu(p=0.027) and Fito(p=0.016) groups, EphrinA1 was higher in Boron group than plu group(p=0.005). EphrinB1 expression was higher in Boron group compared to Plu(p=0.015) and Fito(p=0.015) groups, and the same difference was also observed in EphrinB2 (p values 0.000). Similarly, EphB4 immunoreactivity was higher in the Boron group compared to the plu(p=0.000) and Fito(p=0.002).Coclusion: One of the mechanisms of action of boron in wound healing is to increase EphrinB1, EphrinB2 and EphB4. Low TNF-α and histopathological findings indicate that boron limits extensive wound healing.