Comparative effectiveness of plant-derived compounds in keloid management: a review.

Laser-assisted drug delivery in the treatment of keloids: A case of extensive refractory keloids successfully treated with fractional carbon dioxide laser followed by topical application and intralesional injection of steroid suspension

Despite the availability of various treatment modalities, the treatment of keloids is often incomplete, with a high recurrence rate. The present study was undertaken to assess the efficacy and safety of cryotherapy combined with intralesional steroid injections (Cy + ILS), intralesional combined bleomycin and steroids (ILB + S), and fractional carbon dioxide laser (Fr CO2) in keloid management. Ninety cases with keloids were enrolled and randomly divided into three groups of 30 patients each. The baseline severity of keloids was graded using the Vancouver scar scale (VSS) and high-frequency ultrasonography (HFUS). Group A, B, and C patients were treated with Cy + ILS, ILB + S, and Fr CO2, respectively for four sittings at 4-week intervals. Improvement in VSS score was calculated after 4, 8, 12, and 16 weeks, and with HFUS after 16 weeks. At each visit, adverse effects, if any, were noted. Statistical analysis was done using Chi-square test and ANOVA. At the end of 16 weeks, the reductions in VSS in Cy + ILS, ILB + S, and Fr CO2 groups were 5.12 (60.09%), 5.84 (69.30%), and 3.06 (38.3%), respectively (P = 0.00). The difference in mean VSS reduction after 16 weeks between ILB + S and Cy + ILS was not significant (P = 0.28), whereas ILB + S and Cy + ILS were more efficacious than Fr CO2 (P = 0.01 and P = 0.02, respectively). The incidence of adverse effects was comparable between ILB + S and Fr CO2 (P = 0.11) but higher with Cy + ILS (P = 0.04). Small sample size, non-blinded design, and short follow-up period. ILB + S may be considered as the first-line treatment option for keloids in view of its satisfactory efficacy, and excellent safety profile.

Do antioxidant supplements benefit patients with multiple sclerosis?

Background: Management of keloid is difficult as well as challenging. Intralesional triamcinolone acetonide (TAC) injections have remained a gold standard in non-surgical management of keloid. TAC is generally used in the concentration of 40mg/ml, which causes adverse effects such as local dermal atrophy and hypopigmentation. Aim was to study efficacy and adverse effects of TAC in treatment of keloid, in a lesser concentration of 20mg/ml.Methods: An open label study was conducted from November 2015 to May 2017 on 25 subjects of either gender, in the age group 11-55 years, at a medical college hospital. Intralesional injection TAC 20 was administered in the keloid at an interval of 3 weeks, for a total of 6 sessions, over a period of 18 weeks. Vancouver scar scale (VSS) was used to assess the improvement and SPSS 21 for statistical analysis.Results: Mean age of keloid subjects was 30.72 years and median duration of keloid was 8 months. The mean VSS score before treatment was 8.36 which reduced to 3.20 after treatment. Mean percentage change in VSS score was 62.79%, which was very highly significant (p <0.001). Physician’s assessment was ‘Very Good’ in 52.0% and ‘Excellent’ in 5 (20%). Adverse effect of atrophy was seen in 3 (12%), hypopigmentation in 11 (44%) and telangiectasia in 4 (16%).Conclusions: Intralesional injection triamcinolone acetonide 20mg/ml gives very good to excellent improvement in the majority of patients of keloid. Local adverse effects seen were hypopigmentation, atrophy and telengiectasia.

Introduction: Keloids are the result of excessive scar tissue formation. Besides their poor aesthetic appearance, keloids can be associated with severe clinical symptoms such as pain, itching, and rigidity. Unfortunately, most therapeutic approaches remain clinically unsatisfactory. Recently, injections with botulinum toxin A (BTA) were proposed for the treatment of established keloids in a clinical trial. In this study, we aimed to verify the effects of intralesional BTA for the treatment of therapy-resistant keloids using objective measurements. In addition, the underlying molecular mechanisms were investigated using cultured keloid-derived fibroblasts. Materials and Methods: Four patients received BTA (doses varying from 70 to 140 Speywood units per session) injected directly into their keloids every 2 months for up to 6 months. Differences in height and volume were evaluated clinically and measured with a 3-D optical profiling system. Keloid-derived fibroblasts were treated with different concentrations of BTA, and expression of collagen (COL)1A1, COL1A2, COL3A1, TGF-β1, TGF-β2, TGF-β3, fibronectin-1, laminin-β2, and α-SMA was determined by real-time quantitative PCR. MTT and BrdU assays were used to analyze the effects of BTA on fibroblast proliferation and metabolism. Results: Intralesional administration of BTA did not result in regression of keloid tissue. No differences in expression of ECM markers, collagen synthesis, or TGF-β could be observed after BTA treatment of keloid fibroblasts. In addition, cell proliferation and metabolism of keloid fibroblasts was not affected by BTA treatment. Conclusion: The suggested clinical efficiency of intralesional BTA for the therapy of existent keloids could not be confirmed in this study. Based on our data, the potential mechanisms of action of BTA on keloid-derived fibroblasts remain unclear.

Objective: To compare the efficacy and tolerability of surgical excision and radiotherapy with those of cryotherapy and intralesional steroid treatment of keloids. Subjects and Methods: Twenty-six patients with a total of 76 keloids were enrolled in this study. Nineteen patients with 44 keloids underwent surgical excision combined with immediate 12-Gy irradiation (group A) while the remaining 9 patients with 32 keloids received multiple sessions of intralesional steroid treatment after cryotherapy which continued until flattening of lesion(s) occurred (group B). Two patients were included in both treatment groups. All patients were followed up at regular intervals for at least 1 year. Results: In both treatment groups, keloids responded well without any major side effect. While patients of group A were all satisfied, those of group B (with a mean number of treatment sessions of 5.84 ± 2.51) experienced more side effects, a more prolonged course, a higher recurrence rate and less satisfaction. Conclusion: This study showed that surgery plus immediate postoperative irradiation was an effective and relatively safe choice for treatment of keloids. Although cryotherapy combined with intralesional steroids was associated with more side effects and higher relapse rates, it could be a good choice for small and newly formed keloids.

Keloid and hypertrophic scars are difficult to manage and remain a therapeutic challenge. Verapamil has shown a great potential in the management of keloid and hypertrophic scars. Comparing with conventional corticosteroid injections, verapamil could improve the appearance of keloid and hypertrophic scars, and is associated with a lower incidence of adverse effects. Is verapamil an effective alternative modality in the prevention and treatment of keloid and hypertrophic scars? The aim of this study was to assess the effectiveness of verapamil in preventing and treating keloid and hypertrophic scars. Searches were conducted in Medline, EMbase and Cochrane databases from 1974 to January 2015. The selection of articles was limited to human subjects. Five randomised controlled trials (RCTs) or cluster-randomised trials or controlled clinical trials (CCTs) comparing the efficacy of verapamil with conventional treatments were identified. The results showed that verapamil could improve keloid and hypertrophic scars, and was not significantly different from conventional corticosteroid injections. Few adverse effects were observed. However, this result should be considered carefully, as most of the included studies have a high risk of bias because of issues with randomization, allocation concealment, blinding, incomplete outcomes and selective reporting. In conclusion, verapamil could act as an effective alternative modality in the prevention and treatment of keloid and hypertrophic scars. More high-quality, multiple-centre, large-sample (RCTs) are required to define the role of verapamil in preventing and treating keloid and hypertrophic scars.

The limited available effective treatments make the management of keloids challenging. Intralesional triamcinolone and pulsed dye laser have been used for the treatment of keloids. We sought to assess the efficacy of a treatment regime using rotational intralesional triamcinolone and pulsed dye laser in the management of keloids. Materials (Subjects) and Methods: Case notes and photographic records of 99 patients with keloids treated with pulsed dye laser (PDL) alone or rotational PDL and intralesional triamcinolone (ILT) at our centre between 2005 and 2010 were reviewed. Patients with raised, erythematous and/or symptomatic keloids unresponsive to ILT alone (usually 6 treatments) are referred for consideration of PDL. Patients are offered repeated rotational treatments of three PDL (4-15 J/cm(2), 7 mm spot, 1.5 msec pulse duration, 595 nm wavelength, DCD, 30 msec spray: 20 msec delay; spaced at 6-8 weeks intervals) followed by one ILT (10 mg or 40 mg/dl). ILT-treated flat but erythematous and/or symptomatic keloids are treated with PDL alone at 6-8 week intervals. Response after each laser treatment is documented as a percentage improvement from baseline. Based on the improvement in redness, thickness and pruritus the operator classified the response to treatment as mild (0-49%), moderate (50-75%) or excellent (>75%). Patients are reviewed at 6 months following last treatment. A patient satisfaction questionnaire was also sent out to all patients who received treatments between 2005 and 2010 and this was compared with the information gathered from the notes. Of the 99 patients, 58 were women and 41 were men and most were Caucasian (n=84). A total of 755 keloids were treated. The average number of PDL treatments to achieve a moderate-excellent result was 14 in male and 12 in females. Moderate-excellent improvement was seen in 76% patients. The average number of ILT required to achieve a moderate-excellent result was 5 in males and 4 in females. All patients were sent a satisfaction questionnaire and 33 responses were received wherein patients reported an average of 70% improvement in the redness and thickness of the keloids. Localised cutaneous atrophy, self-limiting erythema and injection site discomfort were noted in 3 female patients whilst no side-effects noted in the male cohort. Pulsed dye laser with or without intralesional triamcinolone is a moderately effective treatment of keloid scars with a very good side-effect profile and high patient satisfaction.

Keloid treatment: Is there a role for acellular human dermis (Alloderm)?

To investigate the effects of epigallocatechin gallate (EGCG) on pressure overload and hydrogen peroxide (H2O2) induced cardiac myocyte apoptosis. Cardiac hypertrophy was established in rats by abdominal aortic constriction. EGCG 25, 50 and 100 mg/kg were administered intragastrically (ig). Cultured newborn rat cardiomyocytes were preincubated with EGCG, and oxidative stress injury was induced by H2O2. In cardiac hypertrophy induced by AC in rats, relative to the model group, EGCG 25, 50 and 100 mg/kg ig for 6 weeks dose-dependently reduced systolic blood pressure (SBP) and heart weight indices, decreased malondialdehyde (MDA) content, and increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activity, both in serum and in the myocardium. Also, treatment with EGCG 50 and 100 mg/kg markedly improved cardiac structure and inhibited fibrosis in HE and van Gieson (VG) stain, and reduced apoptotic myocytes in the hypertrophic myocardium detected by terminal transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay. In the Western blot analysis, EGCG significantly inhibited pressure overload-induced p53 increase and bcl-2 decrease. In H2O2-induced cardiomyocyte injury, when preincubated with myocytes for 6-48 h, EGCG 12.5-200 mg/L increased cell viability determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. EGCG also attenuated H2O2-induced lactate dehydrogenase (LDH) release and MDA formation. Meanwhile, EGCG 50 and 100 mg/L significantly inhibited the cardiomyocyte apoptotic rate in flow cytometry. EGCG inhibits cardiac myocyte apoptosis and oxidative stress in pressure overload induced cardiac hypertrophy. Also, EGCG prevented cardiomyocyte apoptosis from oxidative stress in vitro. The mechanism might be related to the inhibitory effects of EGCG on p53 induction and bcl-2 decrease.

Epigallocatechin gallate (EGCG) has anti-inflammatory and antioxidative stress effects in periodontitis. However, the specific mechanisms involved remain unclear. Our study explored whether the mechanism by which EGCG on alleviates inflammation and oxidative stress in human periodontal ligament fibroblasts (hPDLCs) involves HDAC6. We treated hPDLCs with lipopolysaccharide (LPS) and EGCG, and detected the resultant effects on cell proliferation by the CCK-8 method. Cells were divided into three groups: control, LPS, and EGCG + LPS. The expression of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) was detected by enzyme-linked immunosorbent assay (ELISA), and the expression of reactive oxygen species (ROS) was detected using 2',7'-dichlorofluorescein diacetate. The expression of histone deacetylase 6 (HDAC6), p62, heat shock protein 70 (Hsp70), Kelch-like ECH-associating protein (Keap1), nuclear factor E2-related factor 2 (Nrf2), and heme oxygenase-1(HO-1) mRNA was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The protein expression of HDAC6, Nrf2, and nod-like receptor protein 3 (NLRP3) was detected by western blotting. At concentrations of less than 100 μmol/L, EGCG can promote cell proliferation and significantly inhibit the levels of TNF-α and IL-1β. Moreover, EGCG can activate the Nrf2 pathway and inhibit ROS production. Furthermore, EGCG inhibited the expression of HDAC6 and promoted the expression of p62 and Hsp70, indicating that the anti-inflammatory and antioxidant effects of EGCG are closely related to HDAC6. EGCG can regulate LPS-induced oxidative stress levels of hPDLCs through the Keap1/Nrf2/HO-1 pathway and reduce the expression of HDAC6-related factors. Therefore, HDAC6 may be a potential target for EGCG in the treatment of periodontal inflammation and oxidative stress.

Oxidative stress induces bone loss and osteoporosis, and epigallocatechin-3-gallate (EGCG) may be used to combat these diseases due to its antioxidative property. Herein, oxidative stress in human bone marrow-derived mesenchymal stem cells (BM-MSCs) was induced by H2O2, resulting in an adverse effect on their osteogenic differentiation. However, this H2O2-induced adverse effect was nullified when the cells were treated with EGCG. In addition, treatment of BM-MSCs with EGCG alone also resulted in the enhancement of osteogenic differentiation of BM-MSCs. After EGCG treatment, expressions of β-catenin and cyclin D1 were upregulated, suggesting that the Wnt pathway was involved in the effects of EGCG on the osteogenic differentiation of BM-MSCs. This was also confirmed by the fact that the Wnt pathway inhibitor, Dickkopf-1 (DKK-1), can nullify the EGCG-induced enhancement effect on BM-MSC's osteogenic differentiation. Hence, our results suggested that EGCG can reduce the effects of oxidative stress on Wnt pathway in osteogenic cells, which supported a potentially promising therapy of bone disorders induced by oxidative stress. Considering its positive effects on BM-MSCs, EGCG may also be beneficial for stem cell-based bone repair.

We have recently reported that epigallocatechin gallate (EGCG) could extend lifespan in healthy rats. This study aimed to investigate the effects and mechanisms of a high dose of EGCG in extending the lifespan of obese rats. Ninety adult male Wistar rats were randomly divided into the control (NC), high‐fat (HF) and EGCG groups. Serum glucose and lipids, inflammation and oxidative stress were dynamically determined from adulthood to death, and the transcriptome and proteome of the liver were also examined. The median lifespans of the NC, HF and EGCG groups were 693, 599 and 683 days, respectively, and EGCG delayed death by 84 days in obese rats. EGCG improved serum glucose and lipids and reduced inflammation and oxidative stress associated with aging in obese rats induced by a high‐fat diet. EGCG also significantly decreased the levels of total free fatty acids (FFAs), SFAs and the n‐6/n‐3 ratio but significantly increased the n‐3 FFAs related to longevity. The joint study of the transcriptome and proteome in liver found that EGCG exerted its effects mainly by regulating the suppression of hydrogen peroxide and oxygen species metabolism, suppression of oxidative stress, activation of fatty acid transport and oxidation and cholesterol metabolism. EGCG significantly increased the protein expression of FOXO1, Sirt1, CAT, FABP1, GSTA2, ACSL1 and CPT2 but significantly decreased NF‐κB, ACC1 and FAS protein levels in the livers of rats. All the results indicate that EGCG extends lifespan by improving FFA metabolism and reducing the levels of inflammatory and oxidative stress in obese rats.

The treatment of keloids, particularly in high‐tension areas, is challenging due to their extension beyond the original wound boundaries and high recurrence rates, thereby rendering traditional treatments ineffective. In this study, we investigated the effectiveness of a novel single‐stage treatment approach that combined acellular dermal matrix (ADM) with keloid‐specific epidermal skin grafting. To further prevent recurrence after neo‐skin formation, the treatment was followed by fractionated laser and radiation therapy (LCR). Seven patients with high‐tension keloids, including one with keloids at two locations, were treated and followed‐up for an average of 15.9 months. The patients showed significant improvements in wound healing and skin appearance, with a marked reduction in the Patient and Observer Scar Assessment Scale (POSAS) (scores from 91.1 ± 5.6 to 23.8 ± 6.1 (p < 0.001)). This approach effectively minimizes tension, reduces the likelihood of keloid recurrence, and serves as a viable alternative to conventional methods that often involve challenges related to donor‐site acquisition. No recurrence was observed during the follow‐up period, indicating a promising innovation in the management of extensive keloids and offering improved healing and esthetic outcomes, particularly in high‐tension areas.

Exposure to water-pipe smoking, whether flavored or unflavored, has been shown to instigate inflammation and oxidative stress in BALB/c mice. This consequently results in alterations in the expression of inflammatory markers and antioxidant genes. This study aimed to scrutinize the impact of Epigallocatechin gallate (EGCG)—a key active component of green tea—on inflammation and oxidative stress in BALB/c mice exposed to water-pipe smoke. The experimental setup included a control group, a flavored water-pipe smoke (FWP) group, an unflavored water-pipe smoke (UFWP) group, and EGCG-treated flavored and unflavored groups (FWP + EGCG and UFWP + EGCG). Expression levels of IL-6, IL1B, TNF-α, CAT, GPXI, MT−I, MT−II, SOD−I, SOD−II, and SOD-III were evaluated in lung, liver, and kidney tissues. Histopathological changes were also assessed. The findings revealed that the EGCG-treated groups manifested a significant decline in the expression of inflammatory markers and antioxidant genes compared to the FWP and UFWP groups. This insinuates that EGCG holds the capacity to alleviate the damaging effects of water-pipe smoke-induced inflammation and oxidative stress. Moreover, enhancements in histopathological features were observed in the EGCG-treated groups, signifying a protective effect against tissue damage induced by water-pipe smoking. These results underscore the potential of EGCG as a protective agent against the adverse effects of water-pipe smoking. By curbing inflammation and oxidative stress, EGCG may aid in the prevention or mitigation of smoking-associated diseases.