Materials-based hair follicle engineering: Basic components and recent advances.

The hair follicle (HF) is a significant skin appendage whose primary function is to produce the hair shaft. HFs are a non-renewable resource; skin damage or follicle closure may lead to permanent hair loss. Advances in biomaterials and biomedical engineering enable the feasibility of manipulating the HF-associated cell function for follicle reconstruction via rational design. The regeneration of bioengineered HF addresses the issue of limited resources and contributes to advancements in research and applications in hair loss treatment, HF development, and drug screening. Based on these requirements, this review summarizes the basic and recent advances in hair follicle regulation, including four components: acquisition of stem cells, signaling pathways, materials, and engineering methods. Recent studies have focused on efficiently combining these components and reproducing functionality, which would boost fabrication in HF rebuilding ex vivo, thereby eliminating the obstacles of transplantation into animals to promote mature development.

Outer membrane vesicle-wrapped manganese nanoreactor for augmenting cancer metalloimmunotherapy through hypoxia attenuation and immune stimulation.

Tumor hypoxia, high oxidative stress, and low immunogenic create a deep-rooted immunosuppressive microenvironment, posing a major challenge to the therapeutic efficiency of cancer immunotherapy for solid tumor. Herein, an intelligent nanoplatform responsive to the tumor microenvironment (TME) capable of hypoxia relief and immune stimulation has been engineered for efficient solid tumor immunotherapy. The MnO2@OxA@OMV nanoreactor, enclosing bacterial-derived outer membrane vesicles (OMVs)-wrapped MnO2 nanoenzyme and the immunogenic cell death inducer oxaliplatin (OxA), demonstrated intrinsic catalase-like activity within the TME, which effectively catalyzed the endogenous H2O2 into O2 to enable a prolonged oxygen supply, thereby alleviating the tumor's oxidative stress and hypoxic TME, and expediting OxA release. The combinational action of OxA-caused ICD effect and Mn2+ from nanoreactor enabled the motivation of the cGAS-STING pathway to significantly improve the activation of STING and dendritic cells (DCs) maturation, resulting in metalloimmunotherapy. Furthermore, the immunostimulant OMVs played a crucial role in promoting the infiltration of activated CD8+T cells into the solid tumor. Overall, the nanoreactor offers a robust platform for solid tumor treatment, highlighting the significant potential of combining relief from tumor hypoxia and immune stimulation for metalloimmunotherapy. STATEMENT OF SIGNIFICANCE: A tailor-made nanoreactor was fabricated by enclosing bacterial-derived outer membrane vesicles (OMVs) onto MnO2 nanoenzyme and loading with immunogenic cell death inducer oxaliplatin (OxA) for tumor metalloimmunotherapy. The nanoreactor possesses intrinsic catalase-like activity within the tumor microenvironment, which effectively enabled a prolonged oxygen supply by catalyzing the conversion of endogenous H2O2 into O2, thereby alleviating tumor hypoxia and expediting OxA release. Furthermore, the TME-responsive release of nutritional Mn2+ sensitized the cGAS-STING pathway and collaborated with OxA-induced immunogenic cell death (ICD). Combing with immunostimulatory OMVs enhances the uptake of nanoreactors by DCs and promotes the infiltration of activated CD8+T cells. This nanoreactor offers a robust platform for solid tumor treatment, highlighting the significant potential of combining relief from tumor hypoxia and immune stimulation for metalloimmunotherapy.

Metformin Hydrochloride Significantly Inhibits Rotavirus Infection in Caco2 Cell Line, Intestinal Organoids, and Mice.

Rotavirus is one of the main pathogens that causes severe diarrhea in children under the age of 5, primarily infecting the enterocytes of the small intestine. Currently, there are no specific drugs available for oral rehydration and antiviral therapy targeting rotavirus. However, metformin hydrochloride, a drug known for its antiviral properties, shows promise as it accumulates in the small intestine and modulates the intestinal microbiota. Therefore, we formulated a hypothesis that metformin hydrochloride could inhibit rotavirus replication in the intestine. To validate the anti-rotavirus effect of metformin hydrochloride, we conducted infection experiments using different models, ranging from in vitro cells and organoids to small intestines in vivo. The findings indicate that a concentration of 0.5 mM metformin hydrochloride significantly inhibits the expression of rotavirus mRNA and protein in Caco-2 cells, small intestinal organoids, and suckling mice models. Rotavirus infections lead to noticeable pathological changes, but treatment with metformin has been observed to mitigate the lesions caused by rotavirus infection in the treated group. Our study establishes that metformin hydrochloride can inhibit rotavirus replication, while also affirming the reliability of organoids as a virus model for in vitro research.

Targeted delivery and apoptosis induction of trans-resveratrol-ferulic acid loaded chitosan coated folic acid conjugate solid lipid nanoparticles in colon cancer cells.

The present study is aimed to study and to evaluate the colon cancer targeting efficacy of chitosan-coated-trans-resveratrol (RSV) and ferulic acid (FER) loaded SLNs (solid lipid nanoparticles) that conjugated with folic acid (FA) (C-RSV-FER-FA-SLNs) in suitable models (in vitro). The FA conjugation is performed using co-encapsulation method of stearic acid. Similarly, the prepared SLNs are exhibited better stability even under acidic conditions to exhibit their potentials to use as drug delivery system. Further, the optimized formulations (SLNs) are tested for physiochemical characterizations, which include FTIR, XRD, 1HNMR, particle size, zeta potential, and drug release. In vitro anti-cancer studies using HT-29 cells including, fluorescence staining, flow cytometry, and western blot analysis revealed that the C-RSV-FER-FA-SLNs effectively involved and increased cytotoxicity in cancer cells that leads to induction of apoptosis as compared to free RSV-FER. Thus, it is reported that, the good stability under acidic conditions of this C-RSV-FER-FA-SLNs may serve as a promising candidate for novel nanodrug formulations in cancer therapy.