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Pericytes are multipotent mesenchymal precursor cells that demonstrate tissue-specific properties. In this study, by comparing human adipose tissue– and periosteum-derived pericyte microarrays, we identified T cell lymphoma invasion and metastasis 1 (TIAM1) as a key regulator of cell morphology and differentiation decisions. TIAM1 represented a tissue-specific determinant between predispositions for adipocytic versus osteoblastic differentiation in human adipose tissue–derived pericytes. TIAM1 overexpression promoted an adipogenic phenotype, whereas its downregulation amplified osteogenic differentiation. These results were replicated in vivo, in which TIAM1 misexpression altered bone or adipose tissue generation in an intramuscular xenograft animal model. Changes in pericyte differentiation potential induced by TIAM1 misexpression correlated with actin organization and altered cytoskeletal morphology. Small molecule inhibitors of either small GTPase Rac1 or RhoA/ROCK signaling reversed TIAM1-induced morphology and differentiation in pericytes. In summary, our results demonstrate that TIAM1 regulates the cellular morphology and differentiation potential of human pericytes, representing a molecular switch between osteogenic and adipogenic cell fates.

Background/Objectives: The beneficial effects of the flavonoid chrysin can be reduced by its poor oral bioavailability. It has been shown that chrysin-8-C-glucoside (1) has a better absorption capability. The aim of this study was to evaluate the antioxidant and anti-inflammatory activity of this glucoside, as well as the respective hexa-acetate derivative 1a and the hexa-ethyl carbonate derivative 1b since the inclusion of moieties in bioactive molecules may increase or modify their biological effects. Methods: THP-1 macrophages were used to determine the viability in the presence of chrysin derivatives, and non-cytotoxic concentrations were selected. Subsequently, lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) production and inflammatory mediators were examined. The involvement of chrysin derivatives with the Keap1 and Nrf2 antioxidant system was determined by docking and Western blotting studies. Results: Our data demonstrated, for the first time, that pretreatment with the three compounds caused a significant reduction in LPS-induced reactive oxygen species (ROS) production and pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin 1β (IL-1β) levels, as well as in cyclooxygenase 2 (COX-2) expression. The mechanisms underlying these protective effects were related, at least in part, to the competitive molecular interactions of these phenolic compounds with Kelch-like ECH-associated protein 1 (Keap1)–nuclear factor erythroid 2-related factor 2 (Nrf2), which would allow the dissociation of Nrf2 and its translocation into the nucleus and the subsequent up-regulation of hemo-oxygenase 1 (HO-1) expression. Conclusions: Compared to the 8-C-glucoside parent chrysin, compound 1a exhibited the strongest antioxidant and anti-inflammatory activity. We hypothesized that the incorporation of an acetate group (1a) may reduce its polarity and, thus, increase membrane permeability, leading to better pharmacological activity. These findings support the potential use of these phenolic compounds as Nrf2 activators against oxidative-stress-related inflammatory diseases.

In this essay, I recover queer Indigenous P’urhépecha histories in Michoacán, México, by claiming queer P’urhépecha research methods. To do so, I introduce the Indigenous methodology of talking-while-walking, which refers to how I learned to connect with P’urhépecha knowledge and traditions through the voice of my P’urhépecha grandfather. Since the colonial system eradicated queer histories from my land, I seek historical narratives about queer people in Michoacán from any source available to me, including oral histories, archives, information in the media, and interviews. I argue that queer P’urhépecha histories are unstable and non-linear, and that P’urhépecha bodies have been hunted and their histories distorted, provoking fear and false speculations about queerness among the collective. I also examine the attachment of P’urhépecha people to gender binary traditions and heteronormativity and how the narratives behind these practices relate to colonial violence and the persecution of queer P’urhépechas. Thus, I demonstrate how P’urhépecha queerness has been marginalized and simultaneously displaced from the archival records while I claim queer P’urhépecha histories and build queer P’urhépecha archives. Finally, I propose a sensitive and personal approach to queer histories guided by the voices of my queer P’urhépecha interlocutors and the histories that my P’urhépecha abuelo passed to me.

Ultraviolet (UV) radiation harms the skin, causing oxidative damage, inflammation, and disruption of the skin’s barrier function. There is considerable interest in identifying new natural ingredients with antioxidant and anti-inflammatory properties to serve as adjuvants in sunscreens. The flavonoid morin (1) can undergo structural modifications to enhance its biological properties. The aim of this study was to synthesize two new morin-Schiff base derivatives, morin oxime (2) and morin semicarbazone (3), comparing their photoprotective effects with that of the parent compound on UVB-exposed HaCaT keratinocytes. The chemical structure of the novel compounds was revealed based on spectroscopic data analysis. Our findings demonstrated that derivatives 2 and 3 enhanced the light absorption capability in the UV–visible (vis) range compared to 1. Tested compounds exhibited a higher scavenger capacity than Trolox. Moreover, pre-treatment with all compounds protected HaCaT cells from UVB-induced cell death. Compound 3 demonstrated the strongest antioxidant effect, reducing reactive oxygen species (ROS) generation and, subsequently, malondialdehyde (MDA) levels. Additionally, compounds 2 and 3 exhibited greater anti-inflammatory effects than compound 1, significantly reducing interleukin (IL)-6 production levels at all tested concentrations. These findings have demonstrated, for the first time, a promising photoprotective activity of two new Schiff base derivatives and suggest their use as natural sunscreen ingredients.

Transesterification is a synthetic chemistry strategy promoted in acid or alkaline conditions, yielding a structural diversity of organic compounds. Epoxythymols comprise a class of chiral natural compounds with biological relevance, and the literature describes their chiral purity loss during acid transesterification reactions. This work reports the basic transesterification of the natural derivative (8S)-10-benzoylxy-8,9-epoxy-6-hydroxythymol under alkaline conditions. Herein, the formation of (8S)-10-benzoylxy-6-isobutyryloxy-8,9-epoxythymol isobutyrate is gained, avoiding the loss of optical purity. 1H NMR-BINOL experiments revealed the enantiomeric purity of the product reaction. These results highlight that the implemented strategy promotes transesterification, preserving optical purity.

A semi-synthetic strategy and a new operationally simple-to-obtain heterocyclic system, imidazo-5α-hydroxyvouacapane, was developed in two-step reactions. The first reaction step is a Vilsmeier–Haack formylation at the furan ring of the 5α-hydroxyvouacapane isolated from Caesalpinia pulcherrima stems to obtain the 5α-hydroxyvouacapane-aldehyde in 33% yield. The second reaction step is a Groebke–Blackburn–Bienaymé reaction to synthesize the imidazo-5α-hydroxyvouacapane by using 2-aminopyridine and tert-butyl isocyanide in 75% yield. This work contributes significantly to research on semi-synthesis through multicomponent reactions, an area with limited coverage in the literature.

A semisynthesis of 6β-acetoxyvouacapane-1,5-disusbtituted tetrazoles derivatives from the leaves of Caesalpinia platyloba by using the Ugi-azide multicomponent reaction as a key step reaction is described. To our knowledge, this is the first report where a non-natural product such as 1,5-disusbtituted tetrazole has been linked to a natural product or derivate of a natural product, and beyond the biological relevance that the target molecules present, this work contributes to the area of natural products as well as multicomponent reactions.

Platform chemicals obtained from biomass will play an important role in chemical industry. Already existing compounds or not yet established chemicals are produced from this renewable feedstock. Using photochemical reactions as sustainable method for the conversion of matter furthermore permits to develop processes that are interesting from the ecological and economical point of view. Furans or levoglucosenone are thus obtained from carbohydrate containing biomass. Photochemical rearrangements, photooxygenation reactions or photocatalytic radical reactions can be carried out with such compounds. Also, sugars such pentoses or hexoses can be more easily transformed into heterocyclic target compounds when such photochemical reactions are used. Lignin is an important source for aromatic compounds such as vanillin. Photocycloaddition of these compounds with alkenes or the use light supported multicomponent reactions yield interesting target molecules. Dyes, surfactants or compounds possessing a high degree of molecular diversity and complexity have been synthesized with photochemical key steps. Alkenes as platform chemicals are also produced by fermentation processes, for example, with cyanobacteria using biological photosynthesis. Such alkenes as well as terpenes may further be transformed in photochemical reactions yielding, for example, precursors of jet fuels.

Support of somatic growth is a fundamental requirement of tissue-engineered valves. However, efforts thus far have been unable to maintain this support long term. A key event that will determine the valve's long-term success is the extent to which healthy host tissue remodeling can occur on the valve soon after implantation. The construct's phenotypic-status plays a critical role in accelerating tissue remodeling and engineered valve integration with the host via chemotaxis. In the current study, human bone-marrow-derived mesenchymal stem cells were utilized to seed synthetic, biodegradable scaffolds for a period of 8 days in rotisserie culture. Subsequently, cell-seeded scaffolds were exposed to physiologically relevant oscillatory shear stresses (overall mean, time-averaged shear stress, ~7.9 dynes/cm2; overall mean, oscillatory shear index, ~0.18) for an additional 2 weeks. The constructs were found to exhibit relatively augmented endothelial cell expression (CD31; compared to static controls) but concomitantly served to restrict the level of the activated smooth muscle phenotype (α-SMA) and also produced very low stem cell secretion levels of fibronectin (p < 0.05 compared to static and rotisserie controls). These findings suggest that fluid-induced oscillatory shear stresses alone are important in regulating a healthy valve phenotype of the engineered tissue matrix. Moreover, as solid stresses could lead to increased α-SMA levels, they should be excluded from conditioning during the culture process owing to their associated potential risks with pathological tissue remodeling. In conclusion, engineered valve tissues derived from mesenchymal stem cells revealed both a relatively robust valvular phenotype after exposure to physiologically relevant scales of oscillatory shear stress and may thereby serve to accelerate healthy valve tissue remodeling in the host post-implantation.

The aim of the study was to describe an optical coherence tomography finding in Vogt–Koyanagi–Harada (VKH) disease and discuss its physiopathology. A 34-year-old Hispanic male was referred to the retina clinic, with 2 weeks of “drowsiness,” headache, photopsia, and blurred vision. He was diagnosed with incomplete VKH. Optical coherence tomography, among other studies, was obtained, and a focal separation of the photoreceptor outer segments (OSs) from the inner neuroepithelium was observed. Here, we report a rare finding associated with VKH disease, which we called photoreceptor stretching and hypothesize it results from the presence of a spot of strong adherence between the OS of the photoreceptors and the retinal pigment epithelium.