Novel insights into the augmented effect of curcumin and liraglutide in ameliorating cisplatin-induced nephrotoxicity in rats: Effects on oxidative stress, inflammation, apoptosis and pyroptosis via GSK-3ß.

Cisplatin dose-dependent nephrotoxicity is a major issue limiting its proper use in cancer treatment. Inflammation, redox imbalance, and dysregulated cell death are the most plausible underlying pathomechanics. Curcumin and the glucagon-like peptide-1 receptor agonist, liraglutide, have been investigated in various experimental models for their antioxidant, anti-inflammatory, and cell death modulatory effects. Hence, this work was designed to investigate curcumin and liraglutide nephroprotective effects and how they behave together against cisplatin-induced acute kidney injury (AKI) in an experimental Wistar rat model. The study comprised 61 rats divided randomly into 6 unequal groups: control I and II, cisplatin-induced nephrotoxicity, curcumin-treated, liraglutide-treated, and co-treated groups. Renal index, serum nephrotoxicity markers (Cr, BUN, NGAL), renal glycogen synthase kinase-3 ß (GSK-3ß), oxidant/antioxidant parameters (MDA, MPO, GSH, NQO1, HO-1), and inflammatory biomolecules (TNF-α, IL-1ß) were assayed. Moreover, renal cleaved-caspase3 and the pyroptotic biomolecules (nod-like receptor family pyrin domain containing 3, gasdermin D N-terminal fragment) were immunoassayed. Furthermore, relative renal expression of both nuclear factor erythroid 2-related factor 2 (Nr-F2) and caspase1 was evaluated by qRT-PCR. Histopathological examination of renal tissue was carried out along with detection of Bcl-2 and Bax immunoreactivity. Cisplatin induced acute renal damage, augmented inflammation, dysregulated redox balance and induced apoptosis and pyroptosis. On the other hand, curcumin and liraglutide corrected the dysregulated mechanisms and normalized results to a great extent. Mutual use of curcumin and liraglutide exerted the greatest effect in the co-treatment group. Nr-F2/HO-1 axis and GSK-3ß play a master role in their nephroprotective effect. In conclusion, curcumin and liraglutide have an ameliorative effect against cisplatin-induced nephrotoxicity and can be used alone or better in combination owing to their augmented effect launching promising avenues for cancer patients under cisplatin treatment, retarding AKI and enabling them to gain the best protocol effectiveness.

Treatment of Surgical Scars With Combination Pulsed Dye and Fractional Nonablative Laser: A Randomized Controlled Trial.

OBJECTIVE: To assess the effectiveness and safety of combined pulsed-dye laser (PDL) and NAFL for treatment of surgical scars. SUMMARY BACKGROUND DATA: PDL and NAFL have not been compared to healing by time alone. METHODS: Randomized controlled, single-blinded clinical trial at an urban, university hospital. Healthy adults' status post skin surgery with primary closure were randomized to either 3 sessions of combination PDL and NAFL every 2 to 8 weeks, or control of no treatment. At baseline and 36-week follow-up, Patient and observer Scar Assessment Scale and Scar Cosmesis Assessment and Rating were completed by participants and blinded physicians. The primary outcome was scar improvement, as measured by the score difference over time. RESULTS: Of 76 participants, 52 completed the study (July 2017 to June 2019). No severe adverse events were reported. Patient and observer Scar Assessment Scale assessments demonstrated improvement in total score in the laser group compared to controls, as reported by patients [mean difference (standard deviation), laser: 12.86 (6.91) vs control: 7.25 (6.34); P = 0.004] and blinded physicians [18.32 (8.69) vs 13.08 (9.63); P = 0.044]. Patients observed a greater improvement in scar thickness [3.68 (2.04) vs 1.88 (1.85); P = 0.002] and stiffness [3.57 (2.78) vs 1.50 (2.11); P = 0.004] with lasers, and physicians reported greater improvement in vascularity [3.71 (1.98) vs 1.71 (1.52); P = 0.0002]. The live Scar Cosmesis Assessment and Rating subscore for erythema improved significantly with lasers [1.04 (0.79) vs 0.42 (0.50); P = 0.001]. CONCLUSIONS AND RELEVANCE: Combined PDL and NAFL resulted in scar improvement. Scar thickness, stiffness, and erythema were improved. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03057964).

Treatment of traumatic hypertrophic scars and keloids: a systematic review of randomized control trials.

Exaggerated healing and remodeling after skin injury may cause hypertrophic and keloidal scars, which are associated with functional and quality of life impairment. There is limited guidance available regarding the relative effectiveness of therapies for hypertrophic scars and keloids. In this review, we aim to compare the effectiveness of treatments for hypertrophic scars and keloids. MEDLINE, Embase, Scopus, and the Cochrane Collaboration database were searched from inception to March 2019 for randomized control trials of treatments for hypertrophic and keloid scars that included 20 or more patients. Outcomes evaluated included the standardized mean reduction in scarring and adverse events. The type of scar and the demographic features were analyzed for their effect on clinical outcome. Based on 25 included clinical trials, intralesional injection (64.1% [95% CI 60.8-67.5%]) may be more effective than physical (29.9% [95% CI 28.9-30.9%]) or topical treatments (34% [95% CI 31.8-36.8%]). Combination of 5-fluorouracil and triamcinolone (9:1 dilution) appeared superior among intralesional treatments for keloids. Ablative laser and pulsed-dye laser were the most useful laser treatments. Regression modeling showed laser treatment response was linked to Fitzpatrick skin type (p = 0.002). Adverse events were uncommon for all treatments and mostly transient. Intralesional treatments for keloid and hypertrophic scars may be the most reliable treatment option to improve pathologic scars, while laser treatment may have specific benefits for Fitzpatrick skin types I-III over types IV-VI. Management of pathological scars is an area of critical need, where appropriate treatment can have a significant impact on quality of life.

Effect of Diabetes Health Coaching on Glycemic Control and Quality of Life in Adults Living With Type 2 Diabetes: A Community-Based, Randomized, Controlled Trial.

OBJECTIVES: Health coaching for type 2 diabetes (T2DM) represents a promising addition toward efforts to improve clinical health outcomes and quality of life. The purpose of this study was to evaluate the effect of a 12-month telephone diabetes health coaching (DHC) intervention on glycemic control in persons living with T2DM. METHODS: In this community-based, randomized, controlled trial, adults with T2DM, glycated hemoglobin (A1C) ≥7.5% and telephone access were assigned to either usual diabetes education (DE) or DHC and access to DE. The primary outcome was change in A1C after 1 year, and secondary outcomes included score on the 19-item Audit of Diabetes-Dependent Quality of Life (ADDQoL-19) instrument and self-care behaviours. Safety was assessed in all participants (NCT02128815 at www.clinicaltrials.gov). RESULTS: Three hundred sixty-five participants (50% females; mean age, 57 years; mean A1C, 8.98%) were randomized to control (DE, n=177) or intervention (DHC, n=188) groups. The A1C level decreased by an absolute amount of 1.8% and 1.3% in the intervention and control groups, respectively. DHC plus DE reduced A1C by 0.49% more than DE alone (95% confidence interval, -0.80 to -0.18; p<0.01) and improved ADDQoL-19 scores, with between-group differences for the average weighted score of 0.28 (95% confidence interval, 0.04 to 0.52; p=0.02). There were no differences between groups for proportion of participants having an emergency department visit or hospitalization. CONCLUSIONS: Providing frequent telephone-based DHC and access to DE to adults living with T2DM for 1 year supports improvements in glycemic control and quality of life.