Pre-Incisional and Multiple Intradermal Injection of N-Acetylcysteine Slightly Improves Incisional Wound Healing in an Animal Model.

The objective of this study was to investigate if delivering multiple doses of N-acetylcysteine (NAC) post-surgery in addition to pre-incisional administration significantly impacts the wound healing process in a rat model. Full-thickness skin incisions were carried out on the dorsum of 24 Sprague-Dawley rats in six locations. Fifteen minutes prior to the incision, half of the sites were treated with a control solution, with the wounds on the contralateral side treated with solutions containing 0.015%, 0.03% and 0.045% of NAC. In the case of the NAC treated group, further injections were given every 8 h for three days. On days 3, 7, 14 and 60 post-op, rats were sacrificed to gather material for the histological analysis, which included histomorphometry, collagen fiber organization analysis, immunohistochemistry and Abramov scale scoring. It was determined that scars treated with 0.015% NAC had significantly lower reepithelization than the control at day 60 post-op (p = 0.0018). Scars treated with 0.045% NAC had a significantly lower collagen fiber variance compared to 0.015% NAC at day 14 post-op (p = 0.02 and p = 0.04) and a lower mean scar width than the control at day 60 post-op (p = 0.0354 and p = 0.0224). No significant differences in the recruitment of immune cells and histological parameters were found. The results point to a limited efficacy of multiple NAC injections post-surgery in wound healing.

VEGF and Other Gene Therapies Improve Flap Survival-A Systematic Review and Meta-Analysis of Preclinical Studies.

Surgical flaps are basic tools in reconstructive surgery. Their use may be limited by ischemia and necrosis. Few therapies address or prevent them. Genetic therapy could improve flap outcomes, but primary studies in this field present conflicting results. This systematic review and meta-analysis aimed to appraise the efficacy of external gene delivery to the flap for its survival in preclinical models. This review was registered with PROSPERO (CRD42022359982). PubMed, Embase, Web of Science, and Scopus were searched to identify studies using animal models reporting flap survival outcomes following any genetic modifications. Random-effects meta-analysis was used to calculate mean differences in flap survival with accompanying 95% CI. The risk of bias was assessed using the SYRCLE tool. Subgroup and sensitivity analyses were performed to ascertain the robustness of primary analyses, and the evidence was assessed using the GRADE approach. The initial search yielded 690 articles; 51 were eventually included, 36 of which with 1576 rats were meta-analyzed. VEGF gene delivery to different flap types significantly improved flap survival area by 15.66% (95% CI 11.80-19.52). Other interventions had smaller or less precise effects: PDGF-13.44% (95% CI 3.53-23.35); VEGF + FGF-8.64% (95% CI 6.94-10.34); HGF-5.61% (95% CI 0.43-10.78); FGF 3.84% (95% CI 1.13-6.55). Despite considerable heterogeneity, moderate risk of bias, and low quality of evidence, the efficacy of VEGF gene therapy remained significant in all sensitivity analyses. Preclinical data indicate that gene therapy is effective for increasing flap survival, but further animal studies are required for successful clinical translation.

Anthropometry and Current Aesthetic Concept of the Lower Third of the Face and Lips in Caucasian Adult Population: A Systematic Review and Meta-Analysis.

BACKGROUND: The lack of standardization of the norms and aesthetic concept of the lower third of the face and lips creates challenges in reconstructive surgery and aesthetic procedures. A large-scale, anthropometric measurements summary poses an alternative for establishing universal patterns. METHODS: A systematic review was conducted by searching PubMed, Embase, Google Scholar and Web of Science using keywords: lip, face, aesthetics, beauty, anthropometry and Caucasian. Seventy records were included in the review and checked in detail in terms of available data. RESULTS: The study contains a meta-analysis of twelve parameters with sufficient quantitative data-lip width, nose width, facial width, lower third of the face height, midline mandible height, total height of the upper and lower lip, upper and lower vermilion height, cutaneous upper lip height and nasolabial and mentolabial angle. CONCLUSIONS: The review provides a detailed database of primary anthropometric studies of lips and perioral regions of the healthy Caucasian population. The attractiveness of the region is focused on uniformity of proportions. Notably, results acquired with different methods of measurement are not interchangeable. Despite many published anthropometric studies, systems for conducting the measurements and reporting the results are not sufficiently unified to quantitatively assess meticulous key aesthetic clinical parameters. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine Ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266 .

Wound Healing Impairment in Type 2 Diabetes Model of Leptin-Deficient Mice-A Mechanistic Systematic Review.

Type II diabetes mellitus (T2DM) is one of the most prevalent diseases in the world, associated with diabetic foot ulcers and impaired wound healing. There is an ongoing need for interventions effective in treating these two problems. Pre-clinical studies in this field rely on adequate animal models. However, producing such a model is near-impossible given the complex and multifactorial pathogenesis of T2DM. A leptin-deficient murine model was developed in 1959 and relies on either dysfunctional leptin (ob/ob) or a leptin receptor (db/db). Though monogenic, this model has been used in hundreds of studies, including diabetic wound healing research. In this study, we systematically summarize data from over one hundred studies, which described the mechanisms underlying wound healing impairment in this model. We briefly review the wound healing dynamics, growth factors' dysregulation, angiogenesis, inflammation, the function of leptin and insulin, the role of advanced glycation end-products, extracellular matrix abnormalities, stem cells' dysregulation, and the role of non-coding RNAs. Some studies investigated novel chronic diabetes wound models, based on a leptin-deficient murine model, which was also described. We also discussed the interventions studied in vivo, which passed into human clinical trials. It is our hope that this review will help plan future research.

The Impact of Cytokines on Neutrophils' Phagocytosis and NET Formation during Sepsis-A Review.

Sepsis is an overwhelming inflammatory response to infection, resulting in multiple-organ injury. Neutrophils are crucial immune cells involved in innate response to pathogens and their migration and effector functions, such as phagocytosis and neutrophil extracellular trap (NET) formation, are dependent on cytokine presence and their concentration. In the course of sepsis, recruitment and migration of neutrophils to infectious foci gradually becomes impaired, thus leading to loss of a crucial arm of the innate immune response to infection. Our review briefly describes the sepsis course, the importance of neutrophils during sepsis, and explains dependence between cytokines and their activation. Moreover, we, for the first time, summarize the impact of cytokines on phagocytosis and NET formation. We highlight and discuss the importance of cytokines in modulation of both processes and emphasize the direction of further investigations.

Role of Lipopolysaccharide, Derived from Various Bacterial Species, in Pulpitis-A Systematic Review.

Lipopolysaccharide (LPS) is widely used for induction of inflammation in various human tissues, including dental pulp. The purpose of this study was to summarize current medical literature focusing on (1) cell types used by researchers to simulate dental pulp inflammation, (2) LPS variants utilized in experimental settings and how these choices affect the findings. Our study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched for studies reporting outcomes of lipopolysaccharide application on dental pulp cells in vitro using electronic databases: MEDLINE, Web of Science and Scopus. Having gathered data from 115 papers, we aimed to present all known effects LPS has on different cell types present in dental pulp. We focused on specific receptors and particles that are involved in molecular pathways. Our review provides an essential foundation for further research using in vitro models of pulpitis.

Single Dose of N-Acetylcysteine in Local Anesthesia Increases Expression of HIF1α, MAPK1, TGFß1 and Growth Factors in Rat Wound Healing.

In this study, we aimed to investigate the influence of N-acetylcysteine (NAC) on the gene expression profile, neoangiogenesis, neutrophils and macrophages in a rat model of incisional wounds. Before creating wounds on the backs of 24 Sprague-Dawley rats, intradermal injections were made. Lidocaine-epinephrin solutions were supplemented with 0.015%, 0.03% or 0.045% solutions of NAC, or nothing (control group). Scars were harvested on the 3rd, 7th, 14th and 60th day post-surgery. We performed immunohistochemical staining in order to visualize macrophages (anti-CD68), neutrophils (anti-MPO) and newly formed blood vessels (anti-CD31). Additionally, RT-qPCR was used to measure the relative expression of 88 genes involved in the wound healing process. On the 14th day, the number of cells stained with anti-CD68 and anti-CD31 antibodies was significantly larger in the tissues treated with 0.03% NAC compared with the control. Among the selected genes, 52 were upregulated and six were downregulated at different time points. Interestingly, NAC exerted a significant effect on the expression of 45 genes 60 days after its administration. In summation, a 0.03% NAC addition to the pre-incisional anesthetic solution improves neovasculature and increases the macrophages' concentration at the wound site on the 14th day, as well as altering the expression of numerous genes that are responsible for the regenerative processes.

The Use of Adipose-Derived Stem Cells (ADSCs) and Stromal Vascular Fraction (SVF) in Skin Scar Treatment-A Systematic Review of Clinical Studies.

In recent years, lipofilling became a popular scar treatment method. Its beneficial outcomes have been partly attributed to the regenerative capacity of adipose-derived stem cells (ADSCs), suspended in an extracellular matrix-the stromal vascular fraction (SVF). The aim of this review was to verify if existing data support the clinical use of ADSC-related interventions in scar treatment. A systematic search of the literature was performed in July 2020 in five databases (Medline, Cochrane, Web of Science, Scopus and Embase). Articles written in English, except for reviews, letters and editorials, were identified and screened for eligibility. We looked for reports of any outcomes in scars treated with ADSCs or SVF. Data from selected articles were extracted and the quality of each study was assessed. Five hundred and fourteen studies were identified in the primary search, of which nineteen were eventually included in the systematic review. Extracted data pointed to beneficial microscopic, functional and aesthetic outcomes in a total of 665 patients. Six studies included comparative interventions-platelet-rich plasma or CO2 fractional laser. Collected data give low-to-average quality evidence for beneficial effects of ADSC-related interventions in scar treatment. Some studies suggest that these interventions are noninferior to PRP or fractional CO2 laser.

N-Acetylcysteine Added to Local Anesthesia Reduces Scar Area and Width in Early Wound Healing-An Animal Model Study.

The aim of the study was to evaluate if a pre-incisional N-acetylcysteine (NAC) treatment altered the process of wound healing in a rat model. The dorsal skin of 24 Sprague-Dawley rats was incised in six locations. Before the incisions were made, skin was injected either with lidocaine and epinephrine (one side) or with these agents supplemented with 0.015%, 0.03%, or 0.045% NAC (contralaterally). Photographic documentation of the wound healing process was made at 11 time points. Rats were sacrificed 3, 7, 14, or 60 days after incision to excise scars for histological analysis. They included: Abramov scale scoring, histomorphometry analysis, and collagen fiber arrangement assessment. Skin pretreated with 0.03% NAC produced the shortest scars at all analyzed time points, though this result was statistically insignificant. At this NAC concentration the scars had smaller areas on the third day and were narrower on the day 4 compared with all the other groups (p < 0.05). On day 7, at the same concentration of NAC, the scars had a higher superficial concentration index (p = 0.03) and larger dermal proliferation area (p = 0.04). NAC addition to pre-incisional anesthetic solution decreased wound size and width at an early stage of scar formation at all concentrations; however, with optimal results at 0.03% concentration.

Phagocytosis, Degranulation and Extracellular Traps Release by Neutrophils-The Current Knowledge, Pharmacological Modulation and Future Prospects.

Neutrophils are crucial elements of innate immune system, which assure host defense via a range of effector functions, such as phagocytosis, degranulation, and NET formation. The latest literature clearly indicates that modulation of effector functions of neutrophils may affect the treatment efficacy. Pharmacological modulation may affect molecular mechanisms activating or suppressing phagocytosis, degranulation or NET formation. In this review, we describe the role of neutrophils in physiology and in the course of bacterial and viral infections, illustrating the versatility and plasticity of those cells. This review also focus on the action of plant extracts, plant-derived compounds and synthetic drugs on effector functions of neutrophils. These recent advances in the knowledge can help to devise novel therapeutic approaches via pharmacological modulation of the described processes.

Predictors of euthyreosis in hyperthyroid patients treated with radioiodine 131I-: a retrospective study.

BACKGROUND: Radioiodine (RAI) treatment for hyperthyroidism is a very common modality, chosen by physicians worldwide. The outcome of the therapy, however, is not always predictable. While rendering a patient hypo- or euthyroid is meant as a therapeutic success, the latter does not require lifelong hormonal supplementation. The aim of our study is to determine predictors of euthyreosis in patients who underwent RAI treatment. METHODS: Medical records of 144 patients who had undergone RAI therapy were examined. Laboratory and clinical data were analyzed statistically. Ultrasonography findings, such as thyroid volume, nodules' size and characteristics had been collected at the beginning of treatment and 6 months after the administration of radioiodine 131I-. Moreover, scintigraphy results were taken into account. Multivariate logistic regression analysis model has been used to find predictors of euthyroidism after 12 months of follow-up. The predictors of normal thyroid function have also been analyzed separately for patients with GD (Graves' disease) and TMNG (toxic multinodular goiter). RESULTS: The analysis showed that age (OR 1,06; 95%CI 1.025-1.096, p = 0,001), thyroid gland volume (OR 1,04; 95%CI 1,02-1,06; p < 0.001) and iodine uptake level (OR 0,952; 95%CI 0,91-0,98; p = 0,004) were significant factors of achieving normal thyroid function after RAI therapy. According to multivariate logistic regression analysis, in GD patients only age has been shown to be a significant factor (OR 1,06; 95%CI 1,001-1,13; p = 0.047), while in TMNG patients' age (OR 1,04; 95%CI 1-1,09; p = 0.048), thyroid gland volume (OR 1.038; 95%CI 1.009-1.068; p = 0.009) and iodine uptake level (OR 0.95; 95%CI 0.9-0.99; p = 0.02) all have been proven to be significant predictors of achieving euthyroidism. CONCLUSIONS: The more advanced age, larger volume of thyroid gland and lower iodine uptake level are predictors of euthyreosis after RAI treatment.