γ-Mangosteen, an autophagy enhancer, prevents skin-aging via activating KEAP1/NRF2 signaling and downregulating MAPKs/AP-1/NF-κB-mediated MMPs.

BACKGROUND: Mangosteens, a naturally occurring xanthones, found abundantly in mangosteen fruits. The anti-skin aging potential of γ-mangosteen (GM) remains unexplored; therefore, we investigated the UVB-induced anti-skin aging of GM via activation of autophagy. HYPOTHESIS: We hypothesized that GM exerts antioxidant and anti-aging capabilities both in vitro and in vivo through activation of autophagy as well as control of KEAP1/NRF2 signaling and MAPKs/AP-1/NF-κB-mediated MMPs pathways. METHODS: The anti-skin aging effects of GM were studied using HDF cells and a mice model. Various assays, such as DPPH, ABTS, CUPRAC, FRAP, and ROS generation, assessed antioxidant activities. Kits measured antioxidant enzymes, SA-ß-gal staining, collagen, MDA content, si-RNA experiments, and promoter assays. Western blotting evaluated protein levels of c-Jun, c-Fos, p-IκBα/ß, p-NF-κB, MAPK, MMPs, collagenase, elastin, KEAP1, NRF2, HO-1, and autophagy-related proteins. RESULTS: GM exhibited strong antioxidant, collagenase and elastase enzyme inhibition activity surpassing α- and ß-mangosteen. GM competitively inhibited elastase with a Ki value of 29.04 µM. GM orchestrated the KEAP1-NRF2 pathway, enhancing HO-1 expression, and suppressed UVB-induced ROS in HDF cells. NRF2 knockdown compromised GM's antioxidant efficacy, leading to uncontrolled ROS post-UVB. GM bolstered endogenous antioxidants, curbing lipid peroxidation in UVB-exposed HDF cells and BALB/c mice. GM effectively halted UVB-induced cell senescence, and reduced MMP-1/-9, while elevated TIMP-1 levels, augmented COL1A1, ELN, and HAS-2 expression in vitro and in vivo. Additionally, it suppressed UVB-induced MAPKs, AP-1, NF-κB phosphorylation. Pharmacological inhibitors synergistically enhanced GM's anti-skin aging potential. Moreover, GM inhibited UVB-induced mTOR activation, upregulated LC3-II, Atg5, Beclin 1, and reduced p62 in both UVB induced HDF cells and BALB/c mice, while blocking of autophagy successfully halt the GM effects against the UVB-induced increase of cell senescence, degradation of collagen through upregulation of MMP-1, underscoring GM's substantial anti-skin aging impact via autophagy induction in vitro and in vivo. CONCLUSION: Together, GM has potent antioxidant and anti-skin aging ingredients that can be used to formulate skin care products for both the nutraceutical and cosmeceutical industries.

Follow-up imaging and surgical costs associated with different guidelines for management of incidentally detected gallbladder polyps.

RATIONALE AND OBJECTIVES: To compare follow-up imaging and surgical cost implications of the Society of Radiologists in Ultrasound (SRU) guidelines, 2017 and 2022 European (EUR) guidelines, 2020 Canadian Association of Radiologists (CAR) recommendations, and 2013 American College of Radiology (ACR) White Paper for managing incidentally detected gallbladder polyps. MATERIALS AND METHODS: 253 consecutive patients with gallbladder polyps identified on ultrasound were independently reviewed by three radiologists for polyp size and morphology. Electronic medical records were reviewed for patient demographics, cholecystectomy (if performed) pathological findings, or any subsequent diagnosis of gallbladder cancer. For each patient, the following were calculated for each of the 5 guidelines studied: 1) number of recommended follow-up ultrasounds based on initial presentation, 2) number of surgical consultations recommended based on initial presentation, 3) number of surgical consultations recommended based on growth, and 4) associated imaging and surgical costs. Interrater agreement was calculated. RESULTS: The SRU 2022 guidelines suggested significantly fewer follow-up ultrasounds and surgical consultations, leading to a cost reduction of 96.5 % and 96.7 % compared to European 2022 and 2017, respectively; 86.5 % compared to CAR; and 86.2 % compared to ACR guidelines. With SRU Recommendations, the majority of gallbladder polyps would be classified as extremely low risk (68.4 %), 30.8 % low risk, and 0.8 % indeterminate risk. In our cohort, a single case of gallbladder cancer was identified (26 mm) which would be recommended for surgical consult by all guidelines. CONCLUSION: The SRU 2022 guidelines can lead to significant savings for patients, health systems, and society, while reducing unnecessary medical interventions for managing incidentally detected gallbladder polyps.

Glycoprotein from Sargassum fusiforme exhibiting anti-inflammatory responses in vitro and in vivo via modulation of TLR4/MyD88 and NF-κB signaling.

This study focuses on the identification and characterization of a glycoprotein from Sargassum fusiforme (Harvey) Setchell (SFGP), as well as investigating its potential anti-inflammatory properties both in vitro and in vivo, along with the underlying mechanism. SDS-PAGE analysis revealed a prominent band with a molecular weight of <10 kDa, consisting of 58.39 % protein and 41.61 % carbohydrates, which was confirmed through glycoprotein staining and Coomassie blue staining. Various analytical techniques, including high-resolution mass spectrometry (HRMS), FTIR, amino acid analysis, and UV-visible spectrometry, provided evidence for the presence of monosaccharides (such as d-glucose and mannose) and 17 amino acids linked by an O-glycopeptide bond. In vitro and in vivo studies were conducted to assess the anti-inflammatory activities of SFGP. The results demonstrated that SFGP effectively attenuated nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions in LPS-treated RAW264.7 cells. Moreover, SFGP administration significantly and dose-dependently suppressed TLR4/MyD88 signaling as well as the phosphorylation of MAPKs, IκB, and NF-κB, leading to a reduction in the production of TNF-α, IL-1ß, and IL-6 in LPS-stimulated RAW264.7 cells. Furthermore, the anti-inflammatory efficacy of SFGP was validated in a carrageenan-induced inflammatory mouse model. These findings indicate that SFGP exhibits anti-inflammatory characteristics and has the potential to be utilized as a novel anti-inflammatory agent.

Contrast-Enhanced Ultrasound as a Problem-Solving Modality: Tips and Tricks.

ABSTRACT: Contrast-enhanced ultrasound (CEUS) continues to be an ever-growing tool in radiation-free imaging. While it has been widely used in cardiac imaging, CEUS has only recently become an Food and Drug Administration-approved and viable modality for evaluation of abdominal structures. Ultrasound contrast agents are nontoxic, microbubble-based vascular agents and can be used to reliably assess enhancement patterns of various lesions in real time. In particular, it's non nephrotoxic nature makes CEUS a particularly important tool in renal failure patients requiring serial follow-up. This review provides a comprehensive discussion on the utility of CEUS agents, imaging techniques, comparison with traditional cross-sectional imaging modalities, and its application in diagnosing kidney and liver lesions. This pictorial review is illustrated with cases of renal and hepatic lesions that the practicing radiologist should become familiar with as CEUS becomes increasingly popular.

Machine Learning Analysis for Phenolic Compound Monitoring Using a Mobile Phone-Based ECL Sensor.

Machine learning (ML) can be an appropriate approach to overcoming common problems associated with sensors for low-cost, point-of-care diagnostics, such as non-linearity, multidimensionality, sensor-to-sensor variations, presence of anomalies, and ambiguity in key features. This study proposes a novel approach based on ML algorithms (neural nets, Gaussian Process Regression, among others) to model the electrochemiluminescence (ECL) quenching mechanism of the [Ru(bpy)3]2+/TPrA system by phenolic compounds, thus allowing their detection and quantification. The relationships between the concentration of phenolic compounds and their effect on the ECL intensity and current data measured using a mobile phone-based ECL sensor is investigated. The ML regression tasks with a tri-layer neural net using minimally processed time series data showed better or comparable detection performance compared to the performance using extracted key features without extra preprocessing. Combined multimodal characteristics produced an 80% more enhanced performance with multilayer neural net algorithms than a single feature based-regression analysis. The results demonstrated that the ML could provide a robust analysis framework for sensor data with noises and variability. It demonstrates that ML strategies can play a crucial role in chemical or biosensor data analysis, providing a robust model by maximizing all the obtained information and integrating nonlinearity and sensor-to-sensor variations.

Prunus mume Seed Exhibits Inhibitory Effect on Skin Senescence via SIRT1 and MMP-1 Regulation.

The Prunus mume seed is a by-product of the food industry, and we studied its potential as a food biomaterial, particularly for nutraceutical and inner beauty products. Alternative animal tests showed that an extract of P. mume ripened seed (PmRS) was not toxic on the skin. PmRS exhibited protective effects against ultraviolet- (UV-) induced skin aging in mice, confirmed by phenotypic indications, including increased collagen levels and decreased skin thickness. Compared with the UV-saline group, the UV-PmRS group showed increased levels of silent mating type information regulation 2 homolog 1 (SIRT1) and collagen and decreased matrix metalloproteinase- (MMP-) 1 expression. The protective effect of PmRS treatment against UVB-mediated cell viability was observed in vitro without any cytotoxicity, and PmRS prevented UVB-induced reactive oxygen species generation in HaCaT cells. PmRS downregulated MMP-1 and MMP-13 compared with the UVB-irradiated group. However, mRNA expressions of tissue inhibitor of metalloproteinase-1 and SIRT1 were upregulated by PmRS treatment. MMP-1 and SIRT1 treated with PmRS were decreased and increased, respectively, at the protein level. Moreover, PmRS treatment reduced c-Jun N-terminal kinase and p38 phosphorylation compared with the UVB-treated group. We postulate that P. mume seed could be a useful ingredient in nutraceuticals and inner beauty-purpose foods.

A derivative of L-allo threonine alleviates 2,4-dinitrofluorobenzene-induced atopic dermatitis indications.

LX519290, a synthetic derivative from a combinatorial chemistry library, has been screened for anti-atopic activity, but its biological activities have not yet been elucidated. To assess whether LX519290 has the potential to lessen 2,4-dinitrofluorobenzene-induced atopic dermatitis symptoms in mice, first we sensitized the skin in the dorsal neck of C57BL/6 mice and re-sensitized the ear skin to determine the ear thickness. Then, we tested to determine whether LX519290 affect atopic dermatitis symptoms in vivo. The results indicate that LX519290 significantly mitigated inflammation indications including ear thickness, total T-cell numbers, and eosinophils. Moreover, the treatment drastically inhibited the levels of mediators such as interleukin-17E and histamine by 52% and 37% of control, respectively. Taken together, the data suggest that LX519290 can alleviate atopic parameters in mice.