Endometrial damage is an important factor leading to infertility and traditional conventional treatments have limited efficacy. As an emerging technology in recent years, stem cell therapy has provided new hope for the treatment of this disease. By comparing the advantages of stem cells from different sources, it is believed that menstrual blood endometrial stem cells have a good application prospect as a new source of stem cells. However, the clinical utility of stem cells is still limited by issues such as colonization rates, long-term efficacy, tumor formation, and storage and transportation. This paper summarizes the mechanism by which stem cells repair endometrial damage and clarifies the material basis of their effects from four aspects: replacement of damaged sites, paracrine effects, interaction with growth factors, and other new targets. According to the pathological characteristics and treatment requirements of intrauterine adhesion (IUA), the research work to solve the above problems from the aspects of functional bioscaffold preparation and multi-functional platform construction is also summarized. From the perspective of scaffold materials and component functions, this review will provide a reference for comprehensively optimizing the clinical application of stem cells.

Changes in the cerebral microenvironment caused by acute ischemic stroke-reperfusion are the main obstacle to the recovery of neurological function and an important cause of stroke recurrence after thrombolytic therapy. The intracerebral microenvironment after ischemia-reperfusion reduces the neuroplasticity of the penumbra and ultimately leads to permanent neurological damage. To overcome this challenge, we developed a triple-targeted self-assembled nanodelivery system, which combines the neuroprotective drug rutin with hyaluronic acid through esterification to form a conjugate, and then connected SS-31, a small peptide that can penetrate the blood brain barrier and target mitochondria. Brain targeting, CD44-mediated endocytosis, hyaluronidase 1-mediated degradation, and the acidic environment synergistically promoted the enrichment of nanoparticles and drug release in the injured area. Results demonstrate that rutin has a high affinity for ACE2 receptors on the cell membrane and can directly activate ACE2/Ang1-7 signaling, maintain neuroinflammation, and promote penumbra angiogenesis and normal neovascularization. Importantly, this delivery system enhanced the overall plasticity of the injured area and significantly reduced neurological damage after stroke. The relevant mechanism was expounded from the aspects of behavior, histology, and molecular cytology. All results suggest that our delivery system may be an effective and safe strategy for the treatment of acute ischemic stroke-reperfusion injury.

Background: Multidrug resistance (MDR) is the main challenge of successful chemotherapy for ovarian cancer patients, with 50% to 75% of ovarian cancer patients eventually relapsed due to it. One of the effective strategies for treating MDR and improving therapeutic efficiency of ovarian cancer is to use nanotechnology-based targeted drug delivery systems. In this study, a novel nano targeted co-delivery system modified by hyaluronic acid (HA) was developed by using gold nanorods coated with functionalized mesoporous silica nanoparticles (HA-PTX/let-7a-GNR@MSN) for combined delivery of hydrophobic chemotherapy drug Paclitaxel (PTX) andlethal-7a(let-7a), a microRNA (miR), to overcome MDR in ovarian cancer. Furthermore, we also analyzed the molecular mechanism of this nanotherapeutic system in the treatment of ovarian cancer.Results: HA-modified nanocomplexes can specifically bind to the CD44 receptor, which is highly expressed in SKOV3/SKOV3_TRcells, achieving effective cell uptake and 150% enhancement of tumor site permeability. The nanosystem realized the stable combination and protective transportation of PTX and miRs. Analysis of drug-resistant SKOV3_TRcells and an SKOV3_TRxenograft model in BALB/c-nude mice showed significant downregulation of P-glycoprotein in heterogeneous tumor sites, PTX release, and subsequent induction of apoptosis. More importantly, this nanosystem could synergistically inhibit the growth of ovarian tumors. Further studies suggest that mTOR-mediated signaling pathways play an important role in reversing drug resistance and inducing apoptosis.Conclusions: To sum up, these data provide a model for overcoming PTX resistance in ovarian cancer.Graphical

Hydrogen sulfide (H₂S), a colorless gas smelling of rotten egg, has long been recognized as a toxic gas and environment pollutant. However, increasing evidence suggests that H₂S acts as a novel gasotransmitter and plays important roles in a variety of physiological and pathological processes in mammals. H₂S is involved in many hepatic functions, including the regulation of oxidative stress, glucose and lipid metabolism, vasculature, mitochondrial function, differentiation, and circadian rhythm. In addition, H₂S contributes to the pathogenesis and treatment of a number of liver diseases, such as hepatic fibrosis, liver cirrhosis, liver cancer, hepatic ischemia/reperfusion injury, nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, hepatotoxicity, and acute liver failure. In this review, the biosynthesis and metabolism of H₂S in the liver are summarized and the role and mechanism of H₂S in liver health and disease are further discussed.

Numerous studies have demonstrated that microRNAs are very important in cancer development and progression. However, the complex relationship between the size of microRNA delivery systems, cellular uptake, biodistribution and therapeutic efficiency remains unclear. Herein, we have successfully constructed a series of differently-sized microRNA delivery systems, miR-26a-loaded, hyaluronic acid-modified, polyetherimide-conjugated PEGylated gold nanocage ternary nanocomplexes (PPHAuNCs-TNCs), which can be monitored optically by fluorescence and photoacoustic tomography imaging. We evaluated the effect of the particle size on the cellular uptake and biodistribution in the BEL-7402 cell line in vitro and in the subcutaneous and orthotopic hepatocellular carcinoma (HCC) mouse models. Our findings showed that the cellular uptake and biodistribution were optimal for cancer therapy with the PPHAuNCs-30-TNCs (30 nm AuNCs in edge length) in comparison with their 50 nm and 70 nm counterparts. PPHAuNCs-30-TNCs could accumulate in the liver for a longer time in an orthotopic mouse model of HCC than that in normal mice and could considerably restrain tumor growth in an orthotopic HCC mouse model under near-infrared radiation. This study may provide insightful information for developing novel non-viral microRNA vectors, and PPHAuNCs-30-TNCs have great potential for application in tumor diagnosis and cancer therapy in the future.