Comparative Study of Liposomal and Ethosomal Formulations of Curcuma heyneana Rhizome Extract in a Transdermal Delivery System.

AIM: This study aimed to develop an anti-aging nanoformulation with Curcuma heyneana extract as bioactive substance. BACKGROUND: Curcuma heyneana Valeton & Zipj extract has been proven in previous research to have antioxidant, anti-ageing, anti-inflammatory, and wound healing properties, which makes it a potential bioactive material for anti-ageing and sunscreen cosmetic products. Phytoantioxidants need to penetrate into deeper skin layers to ensure effectivity. Thus, a transdermal delivery system is needed to deliver the extract to a deeper skin layer. OBJECTIVE: The objective of the study was to compare the permeability and anti-ageing activity of liposomal and ethosomal formulations of C. heynena rhizome ethanolic extract. METHODS: In this study, C. heyneana extract was loaded into a phospholipid vesicular system in the form of liposome and ethosome formulations using the ethanolic injection method. The anti-ageing activity was assessed by analyzing the epidermal thickness, number of sunburn cells, distance between collagen fibres, and number of fibroblasts. While the histologic specimen scoring was carried out for the in vivo penetration study. RESULTS: The ethosomal formulation had been found to have better penetration ability since it was able to reach the lower dermis area compared to the liposomes, which only reached the upper dermis. The ethosomal formulation of C. heyneana extract exhibited a better anti-ageing activity based on the parameters of epidermal thickness, sunburn cell count, fibroblast count, and the distance between collagen fibres in rat skin histology. CONCLUSION: Ethosomes have been found to be a more proficient carrier system for transdermal delivery of C. heyneana extract compared to liposomes. Meanwhile, their penetration correlated with the effectivity of the formulation, suggesting that the vesicular system enhanced the penetration ability of the extract.

Allergic rhinitis behavioral changes after Indonesian house dust mites allergenic extract administration as immunotherapy.

Background: Allergy is a hypersensitivity reaction that is generally mediated by Immunoglobulin E (IgE). More than 25% of the world's population is suspected of having these various diseases, and the prevalence and progression of these diseases have continued to increase significantly in recent years. Among these allergyrelated diseases, allergic rhinitis and food allergy are the types of allergies with the highest prevalence. Clinical manifestations of allergic rhinitis include sneezing, rhinorrhea, nasal itching, and nasal congestion. Objective: This study aimed to determine the behavioral changes of allergic rhinitis after Indonesian House Dust Mites (IHDM) allergenic extract administration as an immunotherapy. Methods: Eight male BALB/c mice aged 6-8 weeks in each group were treated for seven groups. The sensitization phase is given intraperitoneal, the desensitization phase is given by subcutaneous, and the challenge phase is given intranasal. The allergic parameters were observed, such as nose rubbing and sneezing. The parameters were observed for 15 minutes after the challenge administration. Results: The results showed that the administration of Indonesian House Dust Mites as immunotherapy decreased the frequency of nose rubbing and sneezing after the administration of immunotherapy compared to the allergic rhinitis model. Conclusions: The administration of the Indonesian House Dust Mites as immunotherapy decreased the allergic rhinitis immune response by altering the behavioral parameter.

Development of gastro-food allergy model in shrimp allergen extract-induced sensitized mice promotes mast cell degranulation.

Background: Food allergies have become more common in the last decade. Shrimp is one of the most dominant food allergy triggers in Asian countries, including Indonesia. After ingesting allergens, B cells will produce allergen-specific Immunoglobin E (IgE). In the sensitization period, repeated allergen exposure promotes Mast Cell (MC) degranulation in intestinal tissue and releases several inflammatory mediators, thereby causing hypersensitivity reactions. Shrimp Allergen Extract (SAE) is an immunotherapy and diagnostic agent currently being developed in Indonesia. In this study, we investigated the effect of SAE administration on eliciting an MC immunological response. Methods: Mice were divided into a non-sensitized and sensitized group. The non-sensitized group only received 1 mg of alum (i.p), whereas the sensitized group received 1 mg of alum and 100 µg of SAE on days 0, 7, and 14. Then, both groups were challenged with 400 µg SAE (p.o) on days 21, 22, and 23 following systemic allergic symptom observation. Results: We showed that SAE was able to increase systemic allergic symptoms significantly in the sensitized mice through repeated challenge (1.33±0.21; 1.83±0.17; and 2.00±0.00), compared to non-sensitized mice (0.17±0.17). Moreover, histopathological analysis showed that the SAE administration causes an increase of MC degranulation in the ileum tissue of the sensitized mice (44.43%±0.01), compared to non-sensitized mice (35.45%±0.01). Conclusions: This study found that SAE could induce allergic reactions in mice by influencing critical effector cells, MCs.

Differentiation of osteoblasts: the links between essential transcription factors.

Osteoblasts, cells derived from mesenchymal stem cells (MSCs) in the bone marrow, are cells responsible for bone formation and remodeling. The differentiation of osteoblasts from MSCs is triggered by the expression of specific genes, which are subsequently controlled by pro-osteogenic pathways. Mature osteoblasts then differentiate into osteocytes and are embedded in the bone matrix. Dysregulation of osteoblast function can cause inadequate bone formation, which leads to the development of bone disease. Various key molecules are involved in the regulation of osteoblastogenesis, which are transcription factors. Previous studies have heavily examined the role of factors that control gene expression during osteoblastogenesis, both in vitro and in vivo. However, the systematic relationship of these transcription factors remains unknown. The involvement of ncRNAs in this mechanism, particularly miRNAs, lncRNAs, and circRNAs, has been shown to influence transcriptional factor activity in the regulation of osteoblast differentiation. Here, we discuss nine essential transcription factors involved in osteoblast differentiation, including Runx2, Osx, Dlx5, ß-catenin, ATF4, Ihh, Satb2, and Shn3. In addition, we summarize the role of ncRNAs and their relationship to these essential transcription factors in order to improve our understanding of the transcriptional regulation of osteoblast differentiation. Adequate exploration and understanding of the molecular mechanisms of osteoblastogenesis can be a critical strategy in the development of therapies for bone-related diseases.Communicated by Ramaswamy H. Sarma.

Effectiveness of Indonesian house dust mite allergenic extract in triggering allergic rhinitis sensitivity in a mouse model: A preliminary study.

Background and Aim: Perennial allergic rhinitis (AR) is a chronic upper respiratory disease, with inflammation mediated by immunoglobulin E in the nasal mucosa caused by house dust mites. Recently, allergen immunotherapy showed promising allergic healing in patients with a definite history of sensitization. Based on this finding, a product was developed using Indonesian house dust mite (IHDM). This study aimed to optimize the allergenic rhinitis mouse model that was generated using IHDM to test the in vivo sensitivity and safety of this product. Materials and Methods: Seven groups of mice were used for effectiveness testing - normal, negative control with IHDM challenge, positive control with 0.1% histamine challenge, and AR group by both IHDM-induced sensitization at 12.5, 50, 250, or 500 µg and IHDM challenge. Mice were sensitized by intraperitoneal administration of IHDM once a week for 3 consecutive weeks. Thereafter, the challenge was given intranasally 5 times on alternate days. The number of nose rubbing and sneezing was noted. Eosinophil infiltration was assessed histologically using hematoxylin and eosin staining. The expression of interleukin-5 (IL-5) mRNA in the nasal mucosa was determined using semi-quantitative reverse transcription-polymerase chain reaction. Results: The induction of AR with IHDM significantly increased the number of nose rubbing and sneezing in the mouse model. Eosinophil infiltration was observed in the nasal mucosa; however, no significant change occurred in the expression of IL-5 mRNA. Conclusion: Overall, these data indicate that IHDM allergenic extract could be an effective sensitizing agent in a mouse model of AR. Although the use of IHDM is a limitation of this study because other sources of house dust mites might have different effects, this study provides a proper model for immunotherapy effectivity testing for in vivo pre-clinical studies.

Acceleration of Bone Fracture Healing through the Use of Bovine Hydroxyapatite or Calcium Lactate Oral and Implant Bovine Hydroxyapatite-Gelatin on Bone Defect Animal Model.

Bone grafts a commonly used therapeutic technique for the reconstruction and facilitation of bone regeneration due to fractures. BHA-GEL (bovine hydroxyapatite-gelatin) pellet implants have been shown to be able accelerate the process of bone repair by looking at the percentage of new bone, and the contact between the composite and bone. Based on these results, a study was conducted by placing BHA-GEL (9:1) pellet implants in rabbit femoral bone defects, accompanied by 500 mg oral supplement of BHA or calcium lactate to determine the effectiveness of addition supplements. The research model used was a burr hole defect model with a diameter of 4.2 mm in the cortical part of the rabbit femur. On the 7th, 14th and 28th days after treatment, a total of 48 New Zealand rabbits were divided into four groups, namely defect (control), implant, implant + oral BHA, and implant + oral calcium lactate. Animal tests were terminated and evaluated based on X-ray radiology results, Hematoxylin-Eosin staining, vascular endothelial growth Factor (VEGF), osteocalcin, and enzyme-linked immunosorbent assay (ELISA) for bone alkaline phosphatase (BALP) and calcium levels. From this research can be concluded that Oral BHA supplementation with BHA-GEL pellet implants showed faster healing of bone defects compared to oral calcium lactate with BHA-GEL pellet implants.