Development and Characterization of a Gel Formulation Containing Golden Cherry Exosomes (Physalis minima) as a Potential Anti-Photoaging.

AIM: The present study aims to produce a novel therapeutic approach for the treatment of photoaging. BACKGROUND: Plant-derived exosome-like nanoparticles (PDENs) are nano-sized vesicles containing biomolecules released by multivesicular bodies. Recently, studies have shown the efficacy of exosomes in treating photoaging through increasing collagen synthesis and decreasing collagen degradation. In addition, some PDENs were also proven to contain bioactive metabolites, which also have potential antioxidant activity to mitigate the risk of photoaging. OBJECTIVE: Formulating and developing a gel and incorporating it with exosomes derived from golden cherry (Physalis minima). METHOD: The formulation was developed by first preparing various base formulations with different compositions and selecting the best through evaluation tests. The results showed that only polymer base natrosol with a concentration of 0.25% was suitable for incorporating exosomes. The selected base was then incorporated with various concentrations of golden cherry exosomes and was evaluated regarding its physical and stability profile. RESULT: The result demonstrates that the incorporated gel displayed pleasant organoleptic properties and a pH compatible with the skin, with pseudoplastic flow and a suitable viscosity for topical application. The stability study also only revealed minor changes in viscosity and pH without affecting the general stability of the formulation. Formulation incorporating 0.25% golden cherry exosomes had shown the best stability profile compared to other concentrations. On characterization, although the incorporated exosomes showed heterogeneous particle size distribution (PI > 0.3), they still maintained their structural integrity. In addition, the incorporated exosomes showed antioxidant activity with IC 50 of 372.435 µg/mL, which can help mitigate the risk of photoaging. CONCLUSION: Golden cherry exosomes have been successfully incorporated into gel and, thus, can be potentially utilized as a novel therapeutic approach for the treatment of photoaging.

Adverse Reactions of COVID-19 Vaccines: A Scoping Review of Observational Studies.

The COVID-19 pandemic had a severe global impact. A range of campaigns and activities, including vaccines, are being implemented to counteract this pandemic. Using observational data, the goal of this scoping review is to identify adverse events connected with COVID-19 vaccinations. We conduct a scoping study and searched three databases from the start of the COVID-19 pandemic in 2020 through June 2022. Based on our criteria and searched keywords, the review included eleven papers in total, with the majority of the studies being conducted in developed countries. The study populations varied and included general community populations, healthcare professionals, military forces, and patients with systemic lupus and cancer. This study includes vaccines from Pfizer-BioNTech, Oxford-AstraZeneca, Sinopharm, and Moderna. The COVID-19 vaccine-related adverse events were classified into three types: local side effects, systemic side effects, and other side effects such as allergies. The adverse reactions to COVID-19 vaccines are mild to moderate in severity, with no significant influence or interference in individual daily activities and no unique patterns in cause of death among vaccine-related deaths. According to the findings of these investigations, the COVID-19 vaccine is safe to administer and induces protection. It is vital to convey accurate information to the public about vaccination side effects, potential adverse responses, and the safety level of the vaccines supplied. Multiple strategies must be implemented at the individual, organizational, and population levels to eliminate vaccine hesitance. Future studies could investigate the vaccine's effect on people of various ages and medical conditions.

The Effect of E-Learning on the Attitude Toward Dengue Prevention and the Acceptance of Dengue Vaccination.

BACKGROUND: A community's attitude toward dengue prevention and its acceptance of dengue vaccine and vaccination play an essential role in the success of the dengue infection prevention program. To develop their attitude and acceptance, the implementation of learning media is required. OBJECTIVE: The objective of the study was to examine the effectiveness of e-learning for developing the community's attitude toward dengue prevention and its acceptance of dengue vaccine and vaccination. METHODS: This study employed a quasi-experimental method with pre- and post-test design by involving 85 subjects that were purposively selected from the low-prevalence area of dengue infection in the City of Bandung, West Java Province, Indonesia. A valid and reliable questionnaire was delivered during pre- (day 1) and post-test (day 7). For the e-learning, it was given on day 1 after completing the pre-test. A descriptive statistical method was applied to describe the research variables, to analyze the correlation between the subjects' attitude and acceptance, and to examine the significant differences (pre- and post-test) between the subjects' attitude toward dengue prevention and their acceptance of dengue vaccine and vaccination. RESULTS: Approximately 88.24% and 11.76% of subjects have good and fair knowledge about dengue disease, respectively. Concerning knowledge about dengue vaccine, 44.71% and 55.29% of them them have good and fair knowledge, respectively. In particular, there is an increase in their attitude toward dengue prevention (p-value <0.05), their acceptance of dengue vaccine (p-value <0.05) and their acceptance of dengue vaccination program (p-value <0.05) after they got information from e-learning. CONCLUSION: E-learning could have significant effects to increase the community's attitude toward dengue prevention and their acceptance of dengue vaccine and vaccination.

Vitamin E-based Folic Acid Nanoemulsion: Formulation and Physical Evaluation for Oral Administration.

BACKGROUND: Folic acid is essential in many metabolic processes and DNA synthesis. Nevertheless, folic acid is not stable, pH-sensitive, and deteriorated upon light exposure. OBJECTIVE: This work was aimed to improve folic acid stability within vitamin E-based nanoemulsion. METHODS: The nanoemulsion was prepared with self-nanoemulsification method by mixing vitamin E oil, Tween 20, and PEG 400. A pseudoternary phase diagram was constructed with aqueous titration to determine the optimum ratio for the mixture. The globule size, pH and entrapment efficiency were included in the nanoemulsion characterizations. In addition, the influence of centrifugation, storage, and pH on physical and chemical stabilities of folic acid nanoemulsion was evaluated. RESULTS: Optimum formula was obtained from vitamin E, Tween 20, and PEG 400 with the ratio of 1:11:1, and the folic acid amount was 8 mg. The size of folic acidloaded oil globule was 15.10 ± 1.51 nm, and the nanoemulsion pH was 6.24 ± 0.01. The nanoemulsion system was able to load the folic acid completely. Folic acid in nanoemulsion was stable after 14 days at room temperature, and it was more stable compared to folic acid in solution. In addition, the physical and chemical characteristics of folic acid in nanoemulsion was not affected by the simulated gastric condition. CONCLUSION: Hence, nanoemulsion is a promising strategy to enhance folic acid stability.

Antifibrotic Activity and In Ovo Toxicity Study of Liver-Targeted Curcumin-Gold Nanoparticle.

Conjugation of curcumin and gold with green chemistry is an approach to improve the effectiveness of curcumin as anti-fibrosis. In this work, curcumin and gold were conjugated to deliver curcumin to the liver. Curcumin-gold nanoparticles (cAuNPs) were prepared by varying curcumin pH and concentration. The successful of cAuNPs formation were identified by using UV-visible and FTIR spectrophotometers. The particle size and morphology were analyzed using particle size analyzer and cryo-TEM respectively. In vitro antioxidant assay was performed to determine the curcumin activity after conjugation. Physical and chemical stabilities of cAuNPs were studied for one month at 5 °C, 25 °C, and 40 °C. Furthermore, the cAuNPs activity to modulate early marker of fibrosis was tested on NIH/3T3 cells. The optimum condition for cAuNPs synthesis was by using 1.5 mM curcumin at pH 9.3. As compared to free curcumin, cAuNPs showed higher antioxidant activity and maintained the nanosize after stored for one month. In line with the antioxidant activity, cAuNPs 0.25⁻1 µg/mL reduced the collagen production by NIH/3T3 cells. More importantly, cAuNPs did not demonstrate any effect on the development of chicken embryo. Taken together, the attachment of gold to curcumin in the form of cAuNPs is promising for curcumin targeting to treat hepatic fibrosis.

In vitro and ex vivo anti-fibrotic effects of LY2109761, a small molecule inhibitor against TGF-ß.

Fibrosis is a pathophysiological state characterized by the excessive formation/deposition of fibrous extracellular matrix. Transforming growth factor-beta (TGF-ß) is a central profibrotic mediator, and targeting TGF-ß is a promising strategy in the development of drugs for the treatment of fibrosis. Therefore, the effect of LY2109761, a small molecule inhibitor against TGF-ß with targets beyond TGF-ß signaling, on fibrogenesis was elucidated in vitro (HepG2 cells and LX-2 cells) and ex vivo (human and rat precision-cut liver slices). Our results displayed an anti-fibrotic effect of LY2109761, as it markedly down-regulated gene and protein expression of collagen type 1, as well as gene expression of the inhibitor of metalloproteinases 1. This effect on fibrosis markers was partially mediated by targeting TGF-ß signaling, seeing that LY2109761 inhibited TGF-ß1 gene expression and SMAD2 protein phosphorylation. Interestingly, particularly at a high concentration, LY2109761 decreased SMAD1 protein phosphorylation and gene expression of the inhibitor of DNA binding 1, which appeared to be TGF-ß-independent effects. In conclusion, LY2109761 exhibited preclinical anti-fibrotic effects via both TGF-ß-dependent and -independent pathways. These results illustrate that small molecule inhibitors directed against TGF-ß could possibly influence numerous signaling pathways and thereby mitigate fibrogenesis.

Removing a Cystein Group On Interferon Alpha 2b at Position 2 and 99 does Not Diminish Antitumor Activity of the Protein, Even Better.

Interferon alpha 2b is the only standard therapeutic protein for hepatitis virus infections. Further study demonstrated that this protein also posseses antitumor activity in several cancerous organs. One main pathway of this antitumor activity is mediated through antiproliferation as well as proapoptotic effects. Previously, we have successfully developed recombinant human interferon alpha 2b (rhIFNα2b) by using a synthetic gene. In addition, two mutein forms of rhIFNα2b were generated to improve the characteristics of this protein. Two point mutations showed better pharmacokinetic profiles than one point mutation as well as the native form. In the present study, this mutein form was studied for ist antitumor effect in vitro using HepG2 cells. As a comparison, the native form as well as a commercial rIFNα2b were used. Several parameters were investigated including the MTT assay, cell viability test, cell cycle using flow cytometric analysis, and the genes and protein expressions involved in cell growth. The latest was observed to study the mechanism of rhIFNα2b. There was no significant difference in the MTT assay and cell viability after cells were treated with both forms of rhIFNα2b. However, the mutein rhIFNα2b tended to show better proapoptotic activity reflected by flow cytometric data, protein expression of pSTAT1, and DNA expression of caspase 3.