Sesamol serves as a p53 stabilizer to relieve rheumatoid arthritis progression and inhibits the growth of synovial organoids.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease known as a leading cause of disability with considerable mortality. Developing alternative drugs and targets for RA treatment is an urgent issue. Sesamol is a phenolic compound isolated from natural food sesame (Sesamum indicum L.) with various biological activities. PURPOSE: The current research intended to illuminate the bioactivity and mechanisms of sesamol in RA fibroblast-like synoviocytes (FLS), and aimed to estimate the potential clinical application value of sesamol in RA treatment. METHODS: CCK-8, EdU, and flow cytometry assays, as well as transwell tests were applied to observe the effects of sesamol on the abnormal functions of RA-FLS. Moreover, synovial organoids and a collagen-induced arthritis (CIA) mouse model were constructed to further explore the therapeutic capacity of sesamol on RA. Furthermore, RNA sequencing combined with quantitative real-time PCR assay, Western blot as well as co-immunoprecipitation were employed to clarify the mechanism of sesamol in regulating RA progression. RESULTS: Sesamol suppressed the proliferation through inhibiting DNA replication, triggering cell cycle arrest and apoptosis of RA-FLS. Besides, sesamol impaired RA-FLS migration and invasion. Interestingly, sesamol inhibited the growth of constructed synovial organoids and alleviated RA symptoms in CIA mice. Moreover, RNA sequencing further implicated p53 signaling as a downstream pathway of sesamol. Furthermore, sesamol was shown to decrease p53 ubiquitination and degradation, thereby activating p53 signaling. Finally, bioinformatics analyses also highlighted the importance of sesamol-regulated networks in the progression of RA. CONCLUSIONS: Our investigation demonstrated that sesamol served as a novel p53 stabilizer to attenuate the abnormal functions of RA-FLS via facilitating the activation of p53 signaling. Moreover, our study highlighted that sesamol might be an effective lead compound or candidate drug and p53 could be a promising target for the therapy of RA.

Living Chinese Herbal Scaffolds from Microfluidic Bioprinting for Wound Healing.

Biological scaffolds have been widely employed in wound healing applications, while their practical efficiency is compromised by insufficient oxygen delivery to the 3-dimensional constructs and inadequate nutrient supply for the long-term healing process. Here, we present an innovative living Chinese herbal scaffold to provide a sustainable oxygen and nutrient supply for promoting wound healing. Through a facile microfluidic bioprinting strategy, a traditional Chinese herbal medicine (Panax notoginseng saponins [PNS]) and a living autotrophic microorganism (microalgae Chlorella pyrenoidosa [MA]) were successfully encapsulated into the scaffolds. The encapsulated PNS could be gradually released from the scaffolds, which promoted cell adhesion, proliferation, migration, and tube formation in vitro. In addition, benefiting from the photosynthetic oxygenation of the alive MA, the obtained scaffolds would produce sustainable oxygen under light illumination, exerting a protective effect against hypoxia-induced cell death. Based on these features, we have demonstrated through in vivo experiments that these living Chinese herbal scaffolds could efficiently alleviate local hypoxia, enhance angiogenesis, and thereby accelerate wound closure in diabetic mice, indicating their great potential in wound healing and other tissue repair applications.

Effects of Dietary Supplementation with Epigallocatechin Gallate on Meat Quality and Muscle Antioxidant Capacity of Broilers Subjected to Acute Heat Stress.

This study evaluated epigallocatechin gallate's (EGCG's, 400 mg/kg) effect on meat quality and muscle antioxidant status of broilers under acute heat stress (AHS). A total of 144 21-day-old male Huainan partridge chickens were randomly allocated to the EGCG-free group (12 replicates) and the EGCG group (6 replicates). On day 94, the EGCG-free group was divided into the control group (CON) and the AHS group, and then AHS group and EGCG group (identified as AHS + EGCG group) were treated with AHS (33 ± 1 °C for 12 h). AHS increased (p < 0.05) L*24h, drip loss, muscle lactic acid, malondialdehyde (MDA) contents, and kelch-like ECH-associated protein 1 (Keap1) mRNA level, and decreased (p < 0.05) eviscerated percentage, pH24h, a*, muscle total superoxide dismutase (T-SOD) activity, the ratio of T-SOD/MDA and glutathione peroxidase /MDA, glycogen content, and nuclear factor erythroid 2-related 2 (Nrf2), catalase (CAT), NAD(P)H/quinone dehydrogenase 1 (NQO1) mRNA levels. The AHS + EGCG group exhibited lower (p < 0.05) L*24h, drip loss, muscle lactic acid, MDA contents and Keap1 mRNA level, and greater (p < 0.05) eviscerated percentage, pH24h, a*, muscle T-SOD activity, the ratio of T-SOD/MDA, Nrf2, and NQO1 mRNA levels compared with the AHS group. In conclusion, EGCG protects against AHS-impaired meat quality by improving muscle antioxidant capacity, which seems to be associated with the activation of the Nrf2 signaling pathway.

3D printed intelligent scaffold prevents recurrence and distal metastasis of breast cancer.

Rationale: Tumors are commonly treated by resection, which usually leads to massive hemorrhage and tumor cell residues, thereby increasing the risk of local recurrence and distant metastasis. Methods: Herein, an intelligent 3D-printed poly(lactic-co-glycolic acid), gelatin, and chitosan scaffold loaded with anti-cancer drugs was prepared that showed hemostatic function and good pH sensitivity. Results: Following in situ implantation in wounds, the scaffolds absorbed hemorrhage and cell residues after surgery, and promoted wound healing. In an in vivo environment, the scaffold responded to the slightly acidic environment of the tumor to undergo sustained drug release to significantly inhibit the recurrence and growth of the tumor, and reduced drug toxicity, all without causing damage to healthy tissues and with good biocompatibility. Conclusions: The multifunctional intelligent scaffold represents an excellent treatment modality for breast cancer following resection, and provides great potential for efficient cancer therapy.

Defective Black Nano-Titania Thermogels for Cutaneous Tumor-Induced Therapy and Healing.

Current challenges in cutaneous tumor therapy are healing the skin wounds resulting from surgical resection and eliminating possible residual tumor cells to prevent recurrence. To address this issue, bifunctional biomaterials equipped with effective tumor therapeutic capacity for skin cancers and simultaneous tissue regenerative ability for wound closure are highly recommended. Herein, we report an injectable thermosensitive hydrogel (named BT-CTS thermogel) with the integration of nanosized black titania (B-TiO2- x, ∼50 nm) nanoparticles into a chitosan (CTS) matrix. The B-TiO2- x nanocrystal exhibits a crystalline/amorphous core-shell structure with abundant oxygen vacancies, which endows the BT-CTS thermogels with simultaneous photothermal therapy (PTT) and photodynamic therapy (PDT) effects under single-wavelength near-infrared laser irradiation, leading to an excellent therapeutic effect on skin tumors in vitro and in vivo. Moreover, the BT-CTS thermogel not only supports the adhesion, proliferation, and migration of normal skin cells but also facilitates skin tissue regeneration in a murine chronic wound model. Therefore, such BT-CTS thermogels with easy injectability, excellent thermostability, and simultaneous PTT and PDT efficacy as well as tissue regenerative activity offers a promising pathway for the healing of cutaneous tumor-induced wounds.

Stable isotope signatures and nutritional sources of some dominant species from the PACManus hydrothermal area and the Desmos caldera.

Deep-sea hydrothermal vents in the western Pacific are increasingly explored for potential mineral extraction. The study of the composition of the food web plays an important guiding role in the ecological protection and restoration of potential mining areas. The general picture of the nutritional sources of species should be established to assess the potential impacts of future mining activities on the biological composition and food sources. To provide basic information, we analyzed the carbon and nitrogen stable isotope ratios of the dominant macrofauna (mussels, commensal scale worms, crustaceans, gastropods, and vestimentiferans) at three different sites in the PACManus hydrothermal area and the Desmos caldera. The δ13C ratio was significantly different between species: mussels and commensal scale worms showed lighter δ13C ratios, whereas crustaceans showed heavier ratios. In terms of δ15N, mussels had the lowest values and the crustaceans had the highest values. By taking into account these stable isotope signatures, we were able to develop inferences of the food sources for vent community organisms. We found that the food web was based on various species of chemoautotrophic bacteria. Mussels appeared to rely primarily on sulfur-based endosymbionts, which use the Calvin-Benson-Bassham (CBB) cycle and RuBisCO form I as the CO2-fixing enzyme. Commensal polychaetes mostly obtained their nutrition from their hosts. Crustacean species were omnivorous, feeding on chemosynthetic bacteria, sedimentary debris, or even animals according to the local environment. In contrast, gastropods relied mainly on symbiotic bacteria with some supplementary consumption of detritus. Vestimentiferans obtained food from symbiotic bacteria using the RuBisCO form II enzyme in the CBB cycle and may have several symbionts using different fixation pathways. Although most macrofauna relied on symbiotic chemoautotrophic bacteria, our study suggested a closer trophic relationship between animals. Therefore, to evaluate the potential impacts of deep sea mining, it is necessary to study the cascade effects on the food web of the whole ecosystem. Before exploiting deep-sea resources, further systematic investigations concerning the protection of deep-sea ecosystems are necessary.

Copper Silicate Hollow Microspheres-Incorporated Scaffolds for Chemo-Photothermal Therapy of Melanoma and Tissue Healing.

The treatment of melanoma requires complete removal of tumor cells and simultaneous tissue regeneration of tumor-initiated cutaneous defects. Herein, copper silicate hollow microspheres (CSO HMSs)-incorporated bioactive scaffolds were designed for chemo-photothermal therapy of skin cancers and regeneration of skin tissue. CSO HMSs were synthesized with interior hollow and external nanoneedle microstructure, showing excellent drug-loading capacity and photothermal effects. With incorporation of drug-loaded CSO HMSs into the electrospun scaffolds, the composite scaffolds exhibited excellent photothermal effects and controlled NIR-triggered drug release, leading to distinctly synergistic chemo-photothermal therapy of skin cancer both in vitro and in vivo. Furthermore, such CSO HMSs-incorporated scaffolds could promote proliferation and attachment of normal skin cells and accelerate skin tissue healing in tumor-bearing and diabetic mice. Taken together, CSO HMSs-incorporated scaffolds may be used for complete eradication of the remaining tumor cells after surgery and simultaneous tissue healing, which offers an effective strategy for therapy and regeneration of tumor-initiated tissue defects.

A bifunctional scaffold with CuFeSe2 nanocrystals for tumor therapy and bone reconstruction.

Bone tumor is one of major challenging issues clinically. After surgical intervention, a few bone tumor cells still remain around bone defects and then proliferate over days. Fabrication of specific biomaterials with dual functions of bone tumor therapy and bone regeneration is of great significance. In order to achieve this aim, we managed to prepare bioactive glass (BG) scaffolds functionalized by the CuFeSe2 nanocrystals (BG-CFS) by combining 3D printing technique with solvothermal method. During the solvothermal reaction process, CuFeSe2 nanocrystals could in situ grow on the strut surface of BG scaffolds and thus endow BG scaffolds excellent photothermal performance. The photothermal performance of BG-CFS scaffolds could be well regulated through altering the content of CuFeSe2 nanocrystals and laser power density when exposed to the near infrared laser (808 nm). The BG-CFS scaffolds could not only effectively ablate the bone tumor cells (Saos-2 cells) in vitro, but also significantly inhibit bone tumor growth in vivo. Moreover, BG-CFS scaffolds could stimulate osteogenic gene expressions of rabbit bone marrow stromal cells (rBMSCs) and finally facilitate the formation of new bone in the bone defects. Our study, for the first time, combined the photothermal performance of semiconductor CuFeSe2 nanocrystals with the bone-forming activity of bioactive glass scaffolds, which can offer a more extensive horizon for developing novel biomaterials with dual functions of bone tumor therapy and bone regeneration.

Are the Therapeutic Effects of Huangqi (Astragalus membranaceus) on Diabetic Nephropathy Correlated with Its Regulation of Macrophage iNOS Activity?

OBJECTIVE: To investigate the correlation between the clinical effects of Huangqi (Astragalus membranaceus) on different stages of diabetic nephropathy (DN) and the pharmacological effect of Huangqi on the activity of inducible nitric oxide synthase (iNOS) in macrophages in different states. METHODS: The PubMed, China National Knowledge Infrastructure, and Wanfang databases were searched. Clinical data was sourced from papers on treatment of different stages of DN with Huangqi, and pharmacological data was from papers on the effects of Huangqi on the iNOS activity of macrophages in a resting or an activated state. RESULTS: Meta-analysis of Huangqi injections on stages III and III-IV DN and randomized controlled trials on other stages showed that Huangqi had therapeutic effects on different stages of DN and on macrophages in different states: inducing normal macrophages in a resting state to generate nitric oxide (NO), tumor necrosis factor-α, and so forth upon iNOS activation; inhibiting NO generation by normal lipopolysaccharide- (LPS-) activated macrophages; and enhancing NO generation by LPS-induced macrophages from patients with renal failure. CONCLUSIONS: Huangqi can regulate iNOS activity of macrophages in different states in vitro. These biphasic or antagonistic effects may explain why Huangqi can be used to treat different stages of DN.

Electrospun Micropatterned Nanocomposites Incorporated with Cu2S Nanoflowers for Skin Tumor Therapy and Wound Healing.

Surgical excision of skin cancers can hardly remove the tumor tissues completely and simultaneously result in cutaneous defects. To avoid tumor recurrence and heal the tumor-induced wounds, we designed a tissue engineering membrane possessing bifunctions of tumor therapy and skin tissue regeneration. The micropatterned nanocomposite membrane was successfully fabricated by incorporating Cu2S nanoflowers into biopolymer fibers via a modified electrospinning method. With uniformly embedded Cu2S nanoparticles, the membranes exhibited excellent and controllable photothermal performance under near-infrared irradiation, which resulted in high mortality (>90%) of skin tumor cells and effectively inhibited tumor growth in mice. Moreover, the membranes supported the adhesion, proliferation, and migration of skin cells as well as significantly stimulated angiogenesis and healed full-thickness skin defects in vivo. This proof-of-concept study offers a facile and reliable strategy for localized skin tumor therapy and tissue regeneration using bifunctional tissue engineering biomaterials, showing great promise for tumor-induced wound healing applications.

Energy metabolism in intestinal epithelial cells during maturation along the crypt-villus axis.

Intestinal epithelial cells continuously migrate and mature along crypt-villus axis (CVA), while the changes in energy metabolism during maturation are unclear in neonates. The present study was conducted to test the hypothesis that the energy metabolism in intestinal epithelial cells would be changed during maturation along CVA in neonates. Eight 21-day-old suckling piglets were used. Intestinal epithelial cells were isolated sequentially along CVA, and proteomics was used to analyze the changes in proteins expression in epithelial cells along CVA. The identified differentially expressed proteins were mainly involved in cellular process, metabolic process, biological regulation, pigmentation, multicellular organizational process and so on. The energy metabolism in intestinal epithelial cells of piglets was increased from the bottom of crypt to the top of villi. Moreover, the expression of proteins related to the metabolism of glucose, most of amino acids, and fatty acids was increased in intestinal epithelial cells during maturation along CVA, while the expression of proteins related to glutamine metabolism was decreased from crypt to villus tip. The expression of proteins involved in citrate cycle was also increased intestinal epithelial cells during maturation along CVA. Moreover, dietary supplementation with different energy sources had different effects on intestinal structure of weaned piglets.