Association of HMGB1, S100A12 and IL-17A Expression with Immunoglobulin-Resistant in Kawasaki Disease and the Comparisons Between Different Adjunctive Therapeutic Approaches

Objective: The DAMPs such as HMGB1, S100A12 and IL-17A have been reported to predict poor response to IVIG. The aim of this study was to analyze the role of HMGB1,S100A12 and IL-17A in the detection of inflammation in KD patients with IVIG-resistant, and to investigate the value of different adjunctive therapy.Method: This study enrolled 126 patients diagnosed with KD, as well as age-matched 16 febrile control subjects. The demographic or clinical data, laboratory parameter and blood sample were collected. Various laboratory parameters as predictive factors for IVIG-resistant were calculated. And the serum levels of IL-17A and mRNA expression levels of HMGB1 and S100A12 were tested in all patients. For patients with acute KD in IVIG-resistant, we studied the levels of laboratory variables when using of IVIG retreatment, methylprednisolone, infliximab for children patients. Result: The variance of laboratory parameters between the febrile control group and KD group were analyzed. Regarding laboratory parameters, KD individuals were found to have lower levels of L%, PA, CD4+, CD8+ and higher levels of WBC, N%, CRP, ESR, NT-proBNP, ALT, CD4+/CD8+ (P<0.05 or P<0.01). For KD group, the 53 IVIG-resistant patients had significantly higher levels of blood S100A12, HMGB1, serum IL-17A levels And N%, CRP, NT-pro BNP, TBIL, ALT, AST and lower levels of L%, PLT (P<0.05 or P<0.01) in comparison to the IVIG-responsive patients. For patients with acute KD in IVIG-resistant, after initial IVIG-treatment, the adjunctive therapy of IVIG, methyl prednisolone or infliximab were used, the inflammatory symptoms and laboratory inflammatory markers were improved when treated with those drugs. Conclusion: IVIG-resistant was associated with higher levels of HMGB1, S100A12, IL-17A, CRP, NT-pro BNP, TBIL, ALT, AST and lower levels of L%, PLT before IVIG, especially when combined, were useful predictors for IVIG-resistant in KD. In addition, the adjunctive therapy of methylprednisolone and infliximab showed more effective in relief clinical symptoms than IVIG retreatment.

The Influence of Hyaluronic Acid Adjunctive Therapy of Periodontitis on Salivary Markers of Oxidative Stress: Randomized, Controlled Clinical Trial

Periodontitis is a common oral disease affecting the tooth-supporting tissues. Bacteria have been long viewed as the main causative factor in its development; however, many investigations have proved that aberrant immune and inflammatory response and the resulting misbalance between the damage caused by reactive oxygen species and the antioxidant capacity of tissues may be an underlying factor in disease progression that reduces healing potential. The objective of the current trial is to assess the outcomes of the addition of hyaluronic acid (HA) to standard non-surgical periodontal therapy (NST) on some major oxidative stress markers in saliva. HA-based gel designed for dental application was used and the measurements were taken after 3 months. HA adjunctive therapy had a significantly greater increase in markers with antioxidant properties as well as total antioxidant capacity compared to standard NST alone. Furthermore, clinically measured levels of gingival inflammation (bleeding on probing-BOP) and periodontal destruction (clinical attachment loss-CAL) were significantly correlated with these markers, and the correlation was negative. This investigation demonstrates that HA may indeed express antioxidant properties and improve the antioxidant capacity of periodontal tissues, thus improving the prognosis for the teeth and the results of periodontal therapy. Further investigations will be necessary to determine the duration of these effects over time.

Effectiveness of Acupuncture as Adjunctive Therapy in Type 2 Diabetic: Study Protocol for a Randomized Controlled Trial

Background: The incidence of type 2 diabetes mellitus is increasing worldwide. The literature suggests that acupuncture is a possible complementary therapy for type 2 diabetes mellitus. This study aims to determine the effect of acupuncture as an adjunctive therapy on homeostasis model assessment-insulin resistance (HOMA-IR), adiposity and health-related quality of life (HRQOL) in patients with type 2 diabetes mellitus. Method and design: This randomised, double-blind, placebo controlled and parallel design trial will be carried out in three public university teaching hospitals in Malaysia. Eligible type 2 diabetes mellitus subjects will be randomly assigned to receive either acupuncture (n=30) or a placebo (n=30). The intervention is carried out using acupuncture ‘press’ needle on abdomen area (10 sessions of treatment), twice a week over 6 weeks. Both groups will continue with their routine diabetes care. Primary outcome of HOMA-IR and secondary outcomes of body mass index and waist circumference will be measured at the time of recruitment (baseline) and after completion of 10 sessions (week 7) of the treatment. Additionally, secondary outcome of HRQOL will be measured at the time of recruitment (baseline), after completion of 5 sessions (week 3/4) and 10 sessions (week 7) of the treatment. Any adverse event will be recorded at every visit.Discussion: The findings of this study will provide important clinical evidence for the effect of acupuncture as adjunctive therapy on HOMA-IR, adiposity and HRQOL of type 2 diabetes mellitus. Name of the registry: US National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov). Trial registration Number: NCT04829045 Date of registration: 2 April 2021URL of trial registry record: https://clinicaltrials.gov/ct2/show/NCT04829045?cond=Type+2+diabetes%2C+acupuncture&draw=2&rank=1

Safety and Long-term Improvement of Mesenchymal Stromal Cell Infusion in Critically COVID-19 Patients: A Randomized Clinical Trial.

Background: COVID-19 is a multisystem disease that presents acute and persistent symptoms, the PostAcute Sequelae (PASC). Long-term symptoms may be due to consequences from organ or tissue injury caused by SARS-CoV-2, associated clotting or inflammatory processes during acute COVID-19. Various strategies are being chosen for by clinicians to prevent severe cases of COVID-19; however, a single treatment would not be efficient in treating such a complex disease. Mesenchymal stromal cells (MSCs) are known for their immunomodulatory properties and regeneration ability; therefore, they are a promising tool for treating disorders involving immune dysregulation and extensive tissue damage, as is the case with COVID-19. This study aimed to assess the safety and explore the long-term efficacy of three intravenous doses of UC-MSCs (umbilical cord-MSCs) as an adjunctive therapy in the recovery and postacute sequelae reduction caused by COVID-19. To our knowledge, this is the first report that presents the longest follow-up after MSC treatment in COVID-19 patients. Methods: This was a phase I/II, prospective, single-center, randomized, double-blind, placebo-controlled clinical trial. Seventeen patients diagnosed with COVID-19 who require intensive care surveillance and invasive mechanical ventilation – critically ill patients – were included. The patient infusion was three doses of 5x105 cells/kg UC-MSCs, with a dosing interval of 48 hours (n=11) or placebo (n=6). These evaluations consisted of a clinical assessment, viral load, laboratory testing, including blood count, serologic, biochemical, cell subpopulation, cytokines and CT scan. Results: The results revealed that in the UC-MSC group, there was a reduction in the levels of ferritin, IL-6 and MCP1-CCL2 on the fourteen day. In the second month, a decrease in the levels of reactive C-protein, D-dimer, and neutrophils and an increase in the numbers of TCD3, TCD4 and NK lymphocytes were observed. A decrease in lung extension was observed at the fourth month. The improvement in all these parameters was maintained until the end of patient follow-up. Conclusions: UC-MSCs infusion is safe and can play an important role as an adjunctive therapy, both in the early stages, preventing severe complications and in the chronic phase with postacute sequelae reduction in critically ill COVID-19 patients. Trial registration: Brazilian Registry of Clinical Trials (ReBEC), UTN code - U1111-1254-9819. Registered 31 October 2020 - Retrospectively registered, https://ensaiosclinicos.gov.br/rg/RBR-3fz9yr

Aloe Vera in Dentistry: A Review

Aloe Vera is a tender and succulent type of plant belonging to the Liliaceae family and genus Aloe. It has been used as a medicinal plant for its healing and soothing properties for more than 2000 years. Properties of the Aloe Vera are not only specie dependent but also on how it is handled after being collected. Due to the adverse effects associated with conventional drugs, researchers are again interested in pursuing plant-based therapies for diseases. Aloe Vera possesses number of beneficial ingredients whilst some studies have also reported its potentially harmful effects. Presence of Aloe Vera in the scaffold material increases viability of the regenerating cells. It is crucial to understand how Aloe Vera interacts with the human body and its physiology when used for dental diseases and discomforts. Components like anthraquinones, aloe-emodin, and aloin present in the Aloe Vera leaves are responsible for their strong anti-bacterial and anti-viral properties. Therefore, this article reviews the current literature related to Aloe Vera use as a replacement or adjunctive therapy in dental diseases.