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Background: Remnant cholesterol (RC) is implicated in the risk of cardiovascular disease. However, comprehensive population-based studies elucidating its association with aortic valve calcium (AVC) progression are limited, rendering its precise role in AVC ambiguous. Methods: From the Multi-Ethnic Study of Atherosclerosis database, we included 5597 individuals (61.8 ± 10.1 years and 47.5% men) without atherosclerotic cardiovascular disease at baseline for analysis. RC was calculated as total cholesterol minus high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), as estimated by the Martin/Hopkins equation. Using the adjusted Cox regression analyses, we examined the relationships between RC levels and AVC progression. Furthermore, we conducted discordance analyses to evaluate the relative AVC risk in RC versus LDL-C discordant/concordant groups. Results: During a median follow-up of 2.4 ± 0.9 years, 568 (10.1%) participants exhibited AVC progression. After adjusting for traditional cardiovascular risk factors, the HRs (95% CIs) for AVC progression comparing the second, third, and fourth quartiles of RC levels with the first quartile were 1.195 (0.925–1.545), 1.322 (1.028–1.701) and 1.546 (1.188–2.012), respectively. Notably, the discordant high RC/low LDL-C group demonstrated a significantly elevated risk of AVC progression compared to the concordant low RC/LDL-C group based on their medians (HR, 1.528 [95% CI 1.201–1.943]). This pattern persisted when clinical LDL-C threshold was set at 100 and 130 mg/dL. The association was consistently observed across various sensitivity analyses. Conclusions: In atherosclerotic cardiovascular disease-free individuals, elevated RC is identified as a residual risk for AVC progression, independent of traditional cardiovascular risk factors. The causal relationship of RC to AVC and the potential for targeted RC reduction in primary prevention require deeper exploration. [ABSTRACT FROM AUTHOR]

In this work, various surfactants and cosurfactants were selected to develop nanoemulsions of finger citron essential oil (FCEO). Five suitable mixtures of surfactants were obtained: Cremophor EL/1, 2-propanediol (1:1, m/m), Cremophor EL/glycerol (1:1, m/m), Tween 80/ethanol (3:2, m/m), Tween 80/PEG-400 (3:2, m/m) and Tween 80/1, 2-propanediol (3:1, m/m). These five nanoemulsions showed a good stability with average droplet sizes kept below 20 nm for at least 28 days. All of them had low polydispersity index. Antimicrobial activities of these five nanoemulsions against bacteria ( E. coli , B. subtilis and S. aureus ) and molds ( A. niger and P. citrinum ) were tested, in which the nanoemulsion with Cremophor EL enhanced the antibacterial ability. However, the antifungal activities of these nanoemulsions were weaker than expected. These developed FCEO loaded nanoemulsions have good physical stability and antibacterial activity, suggesting their potential application in food and beverage fields. [ABSTRACT FROM AUTHOR]

CaO sorbent is one of the most promising sorbents for CO 2 capture. However, the reactivity of CaO sorbent decreased rapidly with carbonation-calcination cycles. Steam activation is a feasible approach to improve the sorbent reactivity. In this study, the effects of steam on CaCO 3 calcination (CaO regeneration), CaO carbonation and CaO hydration were both investigated. Compared with pure CO 2 calcination atmosphere, introducing steam into calcination atmosphere enhanced CaCO 3 decomposition rate, which was because that (1) the partial pressure of CO 2 decreased; (2) the absorption of H 2 O by active site CaO* weakened the binding ability between CO 2 and CaO*; (3) the amount of heat-transfer between steam and CaCO 3 was higher. Lower decomposition temperature in steam/CO 2 calcination atmosphere resulted in lower sorbent sintering and higher sorbent reactivity. Besides, the carbonation reactivity of CaO sorbent was over doubled when steam was introduced into carbonation atmosphere, which was due to the formation of OH – . In CaO hydration reaction, sorbent particle pore structure was also developed by hydration treatment. The hydrated Ca(OH) 2 sorbent reactivity as well as cyclic reactivity of CaO sorbent was therefore enhanced. [ABSTRACT FROM AUTHOR]

In this work, antibacterial activity of finger citron essential oil (FCEO, Citrus medica L. var. sarcodactylis) and its mechanism against food-borne bacteria were evaluated. A total of 28 components in the oil were identified by gas chromatography-mass spectrometry, in which limonene (45.36%), γ-terpinene (21.23%), and dodecanoic acid (7.52%) were three main components. For in vitro antibacterial tests, FCEO exhibited moderately antibacterial activity against common food-borne bacteria: Escherichia coli, Staphylococcus aureus, Bacillus subtilis and Micrococcus luteus. It showed a better bactericidal effect on Gram-positive bacteria than Gram-negative. Mechanisms of the antibacterial action were investigated by observing changes of bacteria morphology according to scanning electron microscopy, time-kill analysis, and permeability of cell and membrane integrity. Morphology of tested bacteria was changed and damaged more seriously with increased concentration and exposure time of FCEO. FCEO showed a significant reduction effect on the growth rate of surviving bacteria and lead to lysis of the cell wall, intracellular ingredient leakage, and consequently, cell death. [ABSTRACT FROM AUTHOR]

Simple Summary: The clinical implementation of novel precision medicine strategies in high-grade serous ovarian cancer (HGSOC), the most common and aggressive ovarian cancer subtype, are urgently needed. Targeted immunotherapeutic combinations that maximize drug benefits are of particular interest. Unlike lung cancer and melanoma, immunotherapeutic responses using immune checkpoint blockade (ICB) in high-grade serous ovarian cancer have been lower than expected and longer-term remissions are uncommon. Evidence now demonstrates that global DNA hypermethylation plays a critical role in immune evasion. Consequently, epigenetic reprogramming strategies could be beneficial in potentiating immunotherapeutic responses by reversing tumor escape mechanisms and enhancing immune cell activation. The current study details the development of ex vivo 3D patient-derived platforms for rapid testing of immunotherapeutic combinations in high-grade serous ovarian tumor metastases and tumor ascites. It further proposes the implementation of epigenetic adjuvants to potentiate systemic ICB responses and eradicate circulating tumor cells responsible for wide, aggressive metastases in this poor prognostic disease. High-grade serous ovarian cancer (HGSOC) is responsible for the majority of gynecology cancer-related deaths. Patients in remission often relapse with more aggressive forms of disease within 2 years post-treatment. Alternative immuno-oncology (IO) strategies, such as immune checkpoint blockade (ICB) targeting the PD-(L)1 signaling axis, have proven inefficient so far. Our aim is to utilize epigenetic modulators to maximize the benefit of personalized IO combinations in ex vivo 3D patient-derived platforms and in vivo syngeneic models. Using patient-derived tumor ascites, we optimized an ex vivo 3D screening platform (PDOTS), which employs autologous immune cells and circulating ascites-derived tumor cells, to rapidly test personalized IO combinations. Most importantly, patient responses to platinum chemotherapy and poly-ADP ribose polymerase inhibitors in 3D platforms recapitulate clinical responses. Furthermore, similar to clinical trial results, responses to ICB in PDOTS tend to be low and positively correlated with the frequency of CD3+ immune cells and EPCAM+/PD-L1+ tumor cells. Thus, the greatest response observed with anti-PD-1/anti-PD-L1 immunotherapy alone is seen in patient-derived HGSOC ascites, which present with high levels of systemic CD3+ and PD-L1+ expression in immune and tumor cells, respectively. In addition, priming with epigenetic adjuvants greatly potentiates ICB in ex vivo 3D testing platforms and in vivo tumor models. We further find that epigenetic priming induces increased tumor secretion of several key cytokines known to augment T and NK cell activation and cytotoxicity, including IL-6, IP-10 (CXCL10), KC (CXCL1), and RANTES (CCL5). Moreover, epigenetic priming alone and in combination with ICB immunotherapy in patient-derived PDOTS induces rapid upregulation of CD69, a reliable early activation of immune markers in both CD4+ and CD8+ T cells. Consequently, this functional precision medicine approach could rapidly identify personalized therapeutic combinations able to potentiate ICB, which is a great advantage, especially given the current clinical difficulty of testing a high number of potential combinations in patients. [ABSTRACT FROM AUTHOR]

Adipose-derived stem cells (ADSCs) have been documented as possible candidates for skin rejuvenation. However, the effects of ADSC-derived exosomes on photoaged skin remain to be fully elucidated. This study was aimed at determining the antiaging effects of ADSC-derived exosomes on photoaged skin. Human ADSCs were isolated from the adipose tissue of healthy women and cultured in vitro. Then, exosomes were extracted from the cultured ADSCs, purified by ultracentrifugation, and verified by examination of cell morphology using transmission electron microscopy and the identification of specific biomarkers. Meanwhile, the optimal exosome concentration and treatment time were selected. The photoaged skin model was created by subjecting Sprague-Dawley rats to ultraviolet B radiation. Exosomes were injected into the photoaged skin in a single therapeutic dose. The thickness of the epidermis and dermis was observed by HE staining. The relative mRNA expression of type I collagen, type III collagen, and matrix metalloproteinases (MMP-1 and MMP-3) was determined by real-time PCR. In the rat model of photoaged skin, the injected exosomes markedly decreased the epidermal thickness and increased the dermal thickness of the photoaged skin 7 days after treatment. Moreover, the proportion of the stratum corneum of the epidermis was decreased. Furthermore, real-time RT-PCR showed that the mRNA expression of type I collagen was increased and that of type III collagen, MMP-1, and MMP-3 was decreased. Our results demonstrate that ADSC-derived exosome treatment could significantly improve skin photodamage and that ADSC-derived exosomes may be a potential agent for photoaged skin treatment. [ABSTRACT FROM AUTHOR]

Background: Recent evidence suggests that angiotensin II (Ang II) plays a role in cutaneous wound healing. Mesenchymal stem cells (MSCs) are known as a rich source of cells that re‐establish healed skin. However, the potential impact of Ang II on MSC differentiation into keratinocytes is still unknown. Objective: The present study was conducted to explore the effect of Ang II on the differentiation of bone marrow‐derived MSCs (BM‐MSCs) into keratinocytes. Methods: Bone marrow‐derived MSCs were isolated from rat bone marrow and cultured. The expression of Ang II type 1 (AT1) and type 2 (AT2) receptors was examined by immunofluorescence staining. The differentiation of BM‐MSCs into keratinocytes was investigated by flow cytometry or/and histological observation. Results: The BM‐MSCs constitutively expressed both AT1 and AT2 receptors. The differentiation of BM‐MSCs into keratinocytes was successfully induced. Interestingly, incubation of BM‐MSCs with Ang II further promoted the differentiation of BM‐MSCs into keratinocyte, which was abolished by pretreament with losartan, an AT1 receptor antagonist, but not by PD123319, an AT2 receptor antagonist. Moreover, the p38 mitogen‐activated protein kinase (MAPK) inhibitor SB203580, the c‐Jun N‐terminal kinase (JNK) inhibitor SP600125 and the Janus‐activated kinase (JAK)2 inhibitor AG490 suppressed Ang II‐induced differentiation of BM‐MSCs into keratinocytes. The phosphoinositide‐3 kinase (PI3K) inhibitor wortmannin and MEK1/2 inhibitor U0126 had no effect on BM‐MSC differentiation into keratinocytes. Conclusions: Our data demonstrated for the first time that Ang II plays a promotive role in the differentiation of BM‐MSC into keratinocytes through the AT1 receptor, and that the p38 MAPK, JNK and JAK2 signalling pathways are involved in this process. [ABSTRACT FROM AUTHOR]