Advanced biology最新文献

Neurosensory circuits of the gastrointestinal tract sense microbial and nutrient changes in the gut; however, studying these circuits in vivo is hindered by invasive techniques and ethical concerns. Here, an in vitro model of enteroendocrine cells (EECs) and calcium reporting enteric neurons (ENs) is established and validated for functional signaling. Both mechanical and sucrose stimulation of co-cultures increased the percentage of neurons undergoing a calcium flux, indicating an action potential. Neuronal activation is blocked with either a piezo or insulin receptor blocker. At baseline, a flow only stimulus elicited 51.9% of neurons to activate in co-culture, which is decreased to 15.1% with a piezo blocker. Piezo blocked and sucrose stimulated EECs increased neuronal activation to 43.9%, and an insulin blocker reduced response to 12.4%. Since a cell line is used to model the EEC in the previous experiments, primary rat duodenal epithelium enriched for EECs are also stimulated and found to produced measurable insulin. This work shows the ability of EECs to produce insulin and for ENs to sense insulin. These results inspire further work on how insulin production outside the pancreas effects diabetes, insulin as a neurotransmitter, and exploration of additional nutritional and microbiotic stimuli on enteroendocrine-to-neuronal signaling.

Malaria kills millions of people annually, and it is one of the major causes of preventable mortality in the world. Of the different plasmodium species that induce malaria, Plasmodium falciparum and Plasmodium vivax account for the most severe form of malarial disease in humans. This review focuses on understanding preventive measures, mutation-based disease evolution, malaria-related biomarkers, and potential plant bioactive components for the treatment and management of malaria. The burden of malaria drug resistance has made it necessary for scientists to focus on alternative therapeutics, with particular interests in those involving plant-based bioactive components that could mediate biochemical pathways, consisting of metabolic interactions essential for parasitic inhibition. To avoid artefacts or false positives, these bioactive components from plant sources are further filtered using the “pan-assay-interfering compounds” (PAINS) tool. This review discussed the history of malaria treatment, current treatment options, malaria preventive measures, and challenges associated with current treatment strategies. Additionally, this work discusses the barriers while developing drugs from phytochemicals and the steps needed to accelerate the development of new antimalarial from the lead compounds.

Background: Recurrent implantation failure (RIF) is characterized by the repeated failure of implantation, often linked to impaired endometrial receptivity. This study investigates how granulocyte colony-stimulating factor (G-CSF) promotes endometrial stromal cell decidualization. Methods: THESCs (human telomerase reverse transcriptase-immortalized endometrial stromal cells) were used as an in vitro cell model to induce decidualization. The effects of G-CSF on the expression of decidualization genes and apoptosis during decidualization were examined. Additionally, a chemical inhibitor of signal transducer and activator of transcription 3 (STAT3) and the small interfering RNA (siRNA) targeting Homeobox A10 (Hoxa10) were employed to explore the involvement of the STAT3/HOXA10 axis in the action of G-CSF. Results: G-CSF promoted decidualization markers expression and suppressed apoptosis in THESCs Treatment with G-CSF enhanced STAT3 activation during decidualization induction. STAT3 inhibition diminished the effects of G-CSF on decidualization marker expression and apoptosis suppression. Furthermore, it was demonstrated that G-CSF increased Hoxa10 expression in a STAT3-dependent manner. Silencing Hoxa10 abrogated the effects of G-CSF on promoting decidualization. Conclusion: G-CSF enhances decidualization of endometrial stromal cells via STAT3/HOXA10 axis activation. These findings suggest that optimal G-CSF delivery strategies could improve endometrial receptivity in RIF patients.

This study investigates the formation and properties of vesicles produced via biocatalytic Polymerization-Induced Self-Assembly (bioPISA) as artificial cells. Methods for achieving size uniformity, including gentle centrifugation and sucrose gradient centrifugation, are explored, and the effects of stirring speed on vesicle morphology is investigated. The internal structure of the vesicles, characterized by a polymer-rich matrix, is analyzed using fluorescence correlation spectroscopy (FCS). Additionally, the feasibility of loading macromolecules into pre-formed vesicles is demonstrated using electroporation, and a fluorescent protein as well as enzymes for a cascade reaction were sucesfully incorporated into the fully assembled polymersomes. These findings provide a foundation for developing enzyme-synthesized polymeric vesicles with controlled morphologies for various applications, e.g., in synthetic biology.

Stimuli-responsive hydrogels have the capability to alter their state in response to changes in physiological signals within their application environment, providing distinct benefits in drug delivery applications. Here, the acidic pH typically found in acutely infected wounds can be effectively managed by incorporating a pH-responsive Ag⁺ loaded system within the hydrogel, thereby ensuring efficient drug use and preventing potential toxicity from the sudden release of silver ions. The antimicrobial composite hydrogel HAMA/GelMA-CA/Ag⁺ provides some tissue adhesion and accelerates wound healing. GelMA-CA is synthesized by modifying gelatin methacryloyl (GelMA) with caffeic acid (CA), while hyaluronic acid methacryloyl (HAMA) is introduced to prepare a double network hydrogel. Silver nitrate is then introduced to make it pH-responsive through the formation of coordination between the polyphenolic structure of caffeic acid and the silver ions. The composite hydrogel exhibited excellent antioxidant properties and strong antimicrobial activity against both Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Furthermore, the composite hydrogel accelerated the promotion of wound healing in a rat model of S. aureus-infected wounds. In conclusion, the HAMA/GelMA-CA/Ag⁺ hydrogel is a promising bioactive material that can be used as a wound dressing to promote the healing of acutely infected wounds.

Intrauterine adhesion (IUA) can negatively impact on pregnancy outcomes, leading to reduced pregnancy rates, secondary infertility, and an increased risk of pregnancy complications. Studies have shown that the application of platelet-rich plasma (PRP) in IUA patients is effective. However, the clinical readhesive rate of IUA after treatment is still high, especially in severe cases. Platelet-rich plasma double-network hydrogel (DN gel) is an engineered PRP double network hydrogel, which is a sodium alginate (SA) based PRP hydrogel with egg carton ion cross-linking and fibrin double network. The results of this study show that intrauterine injection of DN gel has a better effect on promoting endometrial regeneration and enhancing endometrial receptivity than PRP gel. The mechanism is analyzed through single-cell sequencing, which may be achieved by increasing the expression of neutrophils (Neut), natural killer cells (NK), and type I classical dendritic cells (cDC1) in the endometrium and inhibiting the infiltration of M2 macrophages. Overall, based on the good healing efficiency and good biocompatibility of DN gel, it is expected to become a method of treating IUA with better efficacy and faster clinical translation.

Tissue Engineered Muscle Grafts

Finding balance: Human myogenic progenitors grown on electrospun fibrin microfiber bundles stimulated skeletal muscle regeneration following volumetric muscle loss. The delivery of FAP-like ASCs requires optimization to increase muscle regeneration while minimizing the adipose tissue growth in vivo. More details can be found in article number 2400113 by Warren L. Grayson and co-workers.

In this study, the effectiveness of combining short-term starvation (STS or fasting) is investigated with blue light illumination therapy in delaying the progression of various types of cancer, including osteosarcoma, cervical, breast, liver carcinoma, and melanoma cancer in animal models. Moreover, the comparative analysis between cancerous (including HeLa, 143B, MDA-MB-231, and HepG2) and normal cell lines (including NCM460, HEKa, and L-O2), highlights the selectivity of the treatment's cytotoxic effects, favoring cancer cells while largely sparing normal cells. In HeLa cancer cells, treatment with the STS and blue light illumination combination resulted in increased phosphorylation of JNK and p38, which led to the activation of downstream signalling substrates, such as p53 and H2AX. This activation induced mitochondrial and nuclear damage, ultimately leading to tumor cell death. The combination treatment also caused metabolic disorders in tumor cells, which interfered with biomolecule availability and selectively induced lethal effects in tumor cells. Therefore, the combination treatment can be an effective strategy for eliminating cancer.

Cholangiocarcinoma (CCA) is an aggressive cancer with poor response to chemotherapy or radiation, necessitating novel therapeutic approaches. Epigenetic regulation, which is reversible, plays a significant role in cancer progression. CBX3 (HP1γ), a key heterochromatin protein, regulates gene expression by interacting with histone H3 lysine 9 trimethyl (H3K9me3) markers. While CBX3 is linked to tumor progression in various cancers, its role in CCA remains unclear. This study reveals that CBX3 and H3K9me3 enrich the HLTF promoter, a gene involved in chromatin remodeling and DNA repair. HLTF is often inactivated by hypermethylation in other cancers, suggesting tumor-suppressive properties. Depleting CBX3 in CCA cells elevates HLTF expression, reducing proliferation, while HLTF silencing reverses this effect. Furthermore, HLTF overexpression inhibits PI3K-AKT signaling activated by CBX3. These findings suggest CBX3 promotes CCA progression by suppressing HLTF expression.