Abnormal Cell Repsonses and Role of TNF-α in Impaired Diabetic Wound Healing

Impaired diabetic wound healing constitutes a major health problem. The impaired healing is caused by complex factors such as abnormal keratinocyte and fibroblast migration, proliferation, differentiation, and apoptosis, abnormal macrophage polarization, impaired recruitment of mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs), and decreased vascularization. Diabetes-enhanced and prolonged expression of TNF-α also contributes to impaired healing. In this paper, we discuss the abnormal cell responses in diabetic wound healing and the contribution of TNF-α

Central cholinergic signal-mediated neuroendocrine regulation of vasopressin and oxytocin in ovine fetuses

<p>Abstract</p> <p>Background</p> <p>The hypothalamic-neurohypophysial system plays a fundamental role in the maintenance of body fluid homeostasis by secreting arginine vasopressin (AVP) and oxytocin (OT) in response to a variety of signals, including osmotic and nonosmotic stimuli. It is well established that central cholinergic mechanisms are critical in the regulation of cardiovascular responses and maintenance of body fluid homeostasis in adults. Our recent study demonstrated that intracerebroventricular (i.c.v.) injection of carbachol elicited an increase of blood pressure in the near-term ovine fetuses. However, <it>in utero </it>development of brain cholinergic mechanisms in the regulation of the hypothalamic neuropeptides is largely unknown. This study investigated AVP and OT neural activation in the fetal hypothalamus induced by central carbachol.</p> <p>Results</p> <p>Chronically prepared near-term ovine fetuses (0.9 gestation) received an i.c.v. carbachol (3 μg/kg). Fetal blood samples were collected for AVP and OT assay, and brains were used for c-fos mapping studies. I.c.v. carbachol significantly increased fetal plasma AVP and OT concentrations. Intense FOS immunoreactivity (FOS-ir) was observed in the fetal supraoptic nuclei (SON) and paraventricular nuclei (PVN) in the hypothalamus. Double labeling demonstrated that a number of AVP- and OT-containing neurons in the fetal SON and PVN were expressing c-fos in response to central carbachol.</p> <p>Conclusion</p> <p>The results indicate that the central cholinergic mechanism is established and functional in the regulation of the hypothalamic neuropeptides during the final trimester of pregnancy. This provides evidence for a functional link between the development of central cholinergic mechanisms and hypothalamic neuropeptide systems in the fetus.</p

FOXO1 Promotes Wound Healing Through the Up-Regulation of TGF-β1 and Prevention of Oxidative Stress

Keratinocyte mobilization is a critical aspect of wound re-epithelialization, but the mechanisms that control its precise regulation remain poorly understood. We set out to test the hypothesis that forkhead box O1 (FOXO1) has a negative effect on healing because of its capacity to inhibit proliferation and promote apoptosis. Contrary to expectations, FOXO1 is required for keratinocyte transition to a wound-healing phenotype that involves increased migration and up-regulation of transforming growth factor β1 (TGF-β1) and its downstream targets, integrin-α3 and -β6 and MMP-3 and -9. Furthermore, we show that FOXO1 functions in keratinocytes to reduce oxidative stress, which is necessary to maintain cell migration and prevent cell death in a TGF-β1–independent manner. Thus, our studies identify a novel function for FOXO1 in coordinating the response of keratinocytes to wounding through up-regulation of TGF-β1 and other factors needed for keratinocyte migration and protection against oxidative stress, which together promote migration and decrease apoptosis

Effect of Bacteria on the Wound Healing Behavior of Oral Epithelial Cells

Wounded tissue offers opportunity to microflora to adhere, colonize, invade and infect surrounding healthy tissue. The bacteria of the oral cavity have the potential to alter the wound healing process by interacting with keratinocytes. The aim of this study was to investigate mechanisms through which oral bacteria may influence re-epithelialization by interacting with gingival keratinocytes. By an in vitro scratch assay we demonstrate that primary gingival keratinocytes have impaired closure when exposed to two well characterized oral bacteria, P. gingivalis, and to a lesser extent, F. nucleatum. P. gingivalis reduced wound closure by ~40%, which was partially dependent on proteolytic activity, and bacteria was still present within infected cells 9 days later despite exposure to bacteria for only 24 h. Both oral bacteria caused keratinocyte apoptosis at the wound site with cell death being greatest at the wound edge. P. gingivalis and F. nucleatum adversely affected cell proliferation and the effect also had a spatial component being most striking at the edge. The impact of the bacteria was long lasting even when exposure was brief. Cell migration was compromised in bacteria challenged keratinocytes with P. gingivalis having more severe effect (pF. nucleatum. Quantitative real time PCR of bacteria challenged cells showed that P. gingivalis and to a lesser extent F. nucleatum significantly downregulated cell cycle genes cyclin1, CDK1, and CDK4 (pP. gingivalis (p\u3c0.05)

Linear Regression Side Channel Attack Applied on Constant XOR

Linear regression side channel attack (LRA) used to be known as a robust attacking method as it makes use of independent bits leakage. This leakage assumption is more general than Hamming weight/ Hamming distance model used in correlation power attack (CPA). However, in practice, Hamming weight and Hamming distance model suit most devices well. In this paper, we restudy linear regression attack under Hamming weight/ Hamming distance model and propose our novel LRA methods. We find that in many common scenarios LRA is not only an alternative but also a more efficient tool compared with CPA. Two typical cases are recovering keys with XOR operation leakage and chosen plaintext attack on block ciphers with leakages from round output. Simulation results are given to compare with traditional CPA in both cases. Our LRA method achieves up to 400% and 300% improvements for corresponding case compared with CPA respectively. Experiments with AES on SAKURA-G board also prove the efficiency of our methods in practice where 128 key bits are recovered with 1500 traces using XOR operation leakage and one key byte is recovered with only 50 chosen-plaintext traces in the other case

FOXO1 Deletion in Keratinocytes Improves Diabetic Wound Healing through MMP9 Regulation

Keratinocyte migration is a key aspect of re-epithelialization during wound healing. Matric metalloproteinase 9 (MMP9) contributes to this process and deificiencies in the MMP9 lead to impaired healing. Inappropriate expression of MMP9 also contributes to impaired re-epithelialization. Previously we demonstrated that FOXO1 was activated in wound healing but to higher levels in diabetic wounds. To address mechanisms of impaired re-epithelialization we examined MMP0 expression in vivo in full thickness dermal scalp wounds creared in experimental K14.Cre+.Foxo1L/L mice with lineage-specific Cre recombinase deletion of floxed FOXO1 and compared the results to control littermates. MMP9 was induced during wound healing but at a significantly higher level in diabetic compared to normal wounds. FOXO1 deletion substantially blocked this increase. By chromatin immunoprecipitation FOXO1 was shown to bind to the MMP9 promoter, FOXO1 overexpression increased MMP9 transcriptional activity and increased MMP9 expression simulated by high glucose that was blocked by FOXO1 deletion or FOXO1 knockdown. We also show for the first time that high glucose impairs keratinocyte migration by inducing high levels of MMP9 expression in diabetic wound healing, which represents a novel mechanism for impaired re-epithelialization in diabetic wounds

Mapping global acceptance and uptake of COVID-19 vaccination: A systematic review and meta-analysis.

BACKGROUND: The COVID-19 pandemic exit strategies depend on widespread acceptance of COVID-19 vaccines. We aim to estimate the global acceptance and uptake of COVID-19 vaccination, and their variations across populations, countries, time, and sociodemographic subgroups. METHODS: We searched four peer-reviewed databases (PubMed, EMBASE, Web of Science, and EBSCO) for papers published in English from December 1, 2019 to February 27, 2022. This review included original survey studies which investigated acceptance or uptake of COVID-19 vaccination, and study quality was assessed using the Appraisal tool for Cross-Sectional Studies. We reported the pooled acceptance or uptake rates and 95% confidence interval (CI) using meta-analysis with a random-effects model. RESULTS: Among 15690 identified studies, 519 articles with 7,990,117 participants are eligible for meta-analysis. The global acceptance and uptake rate of COVID-19 vaccination are 67.8% (95% CI: 67.1-68.6) and 42.3% (95% CI: 38.2-46.5), respectively. Among all population groups, pregnant/breastfeeding women have the lowest acceptance (54.0%, 46.3-61.7) and uptake rates (7.3%, 1.7-12.8). The acceptance rate varies across countries, ranging from 35.9% (34.3-37.5) to 86.9% (81.4-92.5) for adults, and the lowest acceptance is found in Russia, Ghana, Jordan, Lebanon, and Syria (below 50%). The acceptance rate declines globally in 2020, then recovers from December 2020 to June 2021, and further drops in late 2021. Females, those aged < 60 years old, Black individuals, those with lower education or income have the lower acceptance than their counterparts. There are large gaps (around 20%) between acceptance and uptake rates for populations with low education or income. CONCLUSION: COVID-19 vaccine acceptance needs to be improved globally. Continuous vaccine acceptance monitoring is necessary to inform public health decision making

Analysis of C3 Suggests Three Periods of Positive Selection Events and Different Evolutionary Patterns between Fish and Mammals

BACKGROUND: The third complement component (C3) is a central protein of the complement system conserved from fish to mammals. It also showed distinct characteristics in different animal groups. Striking features of the fish complement system were unveiled, including prominent levels of extrahepatic expression and isotypic diversity of the complement components. The evidences of the involvement of complement system in the enhancement of B and T cell responses found in mammals indicated that the complement system also serves as a bridge between the innate and adaptive responses. For the reasons mentioned above, it is interesting to explore the evolutionary process of C3 genes and to investigate whether the huge differences between aquatic and terrestrial environments affected the C3 evolution between fish and mammals. METHODOLOGY/PRINCIPAL FINDINGS: Analysis revealed that these two groups of animals had experienced different evolution patterns. The mammalian C3 genes were under purifying selection pressure while the positive selection pressure was detected in fish C3 genes. Three periods of positive selection events of C3 genes were also detected. Two happened on the ancestral lineages to all vertebrates and mammals, respectively, one happened on early period of fish evolutionary history. CONCLUSIONS/SIGNIFICANCE: Three periods of positive selection events had happened on C3 genes during history and the fish and mammals C3 genes experience different evolutionary patterns for their distinct living environments

Abnormal Cell Responses and Role of TNF-α in Impaired Diabetic Wound Healing

Impaired diabetic wound healing constitutes a major health problem. The impaired healing is caused by complex factors such as abnormal keratinocyte and fibroblast migration, proliferation, differentiation, and apoptosis, abnormal macrophage polarization, impaired recruitment of mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs), and decreased vascularization. Diabetes-enhanced and prolonged expression of TNF-α also contributes to impaired healing. In this paper, we discuss the abnormal cell responses in diabetic wound healing and the contribution of TNF-α

An Analytic Model of Transient Heat Conduction for Bi-Layered Flexible Electronic Heaters by Symplectic Superposition

In a flexible electronic heater (FEH), periodic metal wires are often encapsulated into the soft elastic substrate as heat sources. It is of great significance to develop analytic models on transient heat conduction of such an FEH in order to provide a rapid analysis and preliminary designs based on a rapid parameter analysis. In this study, an analytic model of transient heat conduction for bi-layered FEHs is proposed, which is solved by a novel symplectic superposition method (SSM). In the Laplace transform domain, the Hamiltonian system-based governing equation for transient heat conduction is introduced, and the mathematical techniques incorporating the separation of variables and symplectic eigen expansion are manipulated to yield the temperature solutions of two subproblems, which is followed by superposition for the temperature solution of the general problem. The Laplace inversion gives the eventual temperature solution in the time domain. Comprehensive time-dependent temperatures by the SSM are presented in tables and figures for benchmark use, which agree well with their counterparts by the finite element method. A parameter analysis on the influence of the thermal conductivity ratio is also studied. The exceptional merit of the SSM is on a direct rigorous derivation without any assumption/predetermination of solution forms, and thus, the method may be extended to more heat conduction problems of FEHs with more complex structures