Cost-effective treatment strategies for liver fibrosis or cirrhosis are limited. Many clinical trials of stem cells for liver disease shown that stem cells might be a potential therapeutic approach. This review will summarize the published clinical trials of stem cells for the treatment of liver fibrosis/cirrhosis and provide the latest overview of various cell sources, cell doses, and delivery methods. We also describe the limitations and strengths of various stem cells in clinical applications. Furthermore, to clarify how stem cells play a therapeutic role in liver fibrosis, we discuss the molecular mechanisms of stem cells for treatment of liver fibrosis, including liver regeneration, immunoregulation, resistance to injury, myofibroblast repression, and extracellular matrix degradation. We provide a perspective for the prospects of future clinical implementation of stem cells.

Background and Objectives: Androgenetic alopecia is one of the common types of hair loss and has become a medical and social problem due to its increasingly young onset. Existing therapies, although effective, have serious side effects and therefore better treatments need to be sought. The aim of this study was to evaluate the efficacy of umbilical cord mesenchymal stem cell-derived exosomes in the treatment of androgenetic alopecia and to investigate the mechanism of exosome regulation of hair growth. Methods: First, we randomly divided 20 C57BL/6J mice into blank group, model group, positive control group and exosomal hydrogel group, and mice were treated with hair removal on the back. The mice were injected intraperitoneally with dihydrotestosterone solution except for the blank group. At the end of the experiment, new hairs were collected and the differences in length, diameter and number of hair follicles were compared among the groups; the histopathological changes of hair follicles were observed by HE staining; the expression of androgen receptor mRNA and protein in skin tissues were compared; and the skin tissues were analyzed by real-time PCR, western blotting, immunofluorescence staining and transcriptome sequencing. Finally, the results of transcriptome sequencing experiments were verified by real-time PCR, western blotting and other techniques for the corresponding genes and proteins. Results: Compared with the blank group, mice in the model group had shorter hair length and reduced hair diameter, and pathological observation showed that the total number of hair follicles was significantly reduced and the hair follicles were miniaturized; compared with the model group, mice in the positive control and exosome groups had longer hair length, larger hair diameter and more hair follicles; the androgen receptor mRNA content and protein expression in the skin tissue of mice in the model group were significantly higher than those in the blank group, and the protein expression in the exosome gel group was lower than that in the model group. Similarly, compared with the model group, the expression of stemness-related proteins K15 and CD200 in the skin tissues of mice in the exosome group increased, and the expression of PCNA, a protein related to cell proliferation, increased. The KEGG data showed that the differential genes were mainly enriched in the RAS/ERK pathway. Conclusions: In this study, we demonstrated the therapeutic effect of umbilical cord MSC-derived exosomes on androgenetic alopecia and verified that exosomes regulate hair follicle stem cell stemness through the RAS/ERK pathway to promote hair proliferation and thus hair growth in mice with androgenetic alopecia, providing a potential therapeutic strategy for androgenetic alopecia.

Endometriosis (EMS) is a common gynecological disease. Prostaglandin E2 (PGE2), which induces chronic pelvic inflammation and cell pyroptosis, a form of programmed cell death based on inflammasome activation, are involved in EMS, but the extent of their involvement and roles remain unclear. The present study aimed to evaluate PGE2-induced pyroptosis in EMS and the influence of PGE2 in EMS progression. Using western blotting, it was found that the expressions of PGE2 and pyroptosis-related proteins (NLRP3, cleaved caspase-1, interleukin (IL)-1β and IL-18) were higher in EMS tissues than in normal endometrial tissues. The levels of PGE2, IL-1β, and IL-18 in the serum of patients with EMS and cell culture fluids were also detected. Using the transwell assay, we verified that PGE2 promoted hEM15A migration via the NLRP3/caspase-1 pyroptotic pathway, and PGE2-induced pyroptosis upregulated the expressions of high mobility group box 1 (HMGB1), E-cadherin, and vimentin. Immunohistochemistry analysis confirmed that PGE2-induced pyroptosis contributed to EMS invasion. These results suggest that PGE2-induced pyroptosis affects the progression of EMS by changing the migration ability of pyroptotic cells and upregulating the expression of HMGB1, E-cadherin, and vimentin. Our findings provide crucial evidence for new treatment pathways and use of anti-inflammatory drugs in EMS.

Cholangiocarcinoma (CCA) is a bile duct malignancy with a dismal prognosis. This study systematically investigated the role of the ribosomal protein S6 (RPS6) gene, which is dependent in CCA. We found that RPS6 upregulation in CCA tissues was correlated with a poor prognosis. Functional investigations have shown that alterations in RPS6 expression, both gain- and loss-of function could affect the proliferation of CCA cells. In xenograft tumor models, RPS6 overexpression enhances tumorigenicity, whereas RPS6 silencing reduces it. Integration analysis using RNA-seq and proteomics elucidated downstream signaling pathways of RPS6 depletion by affecting the cell cycle, especially DNA replication. Immunoprecipitation followed by mass spectrometry has identified numerous spliceosome complex proteins associated with RPS6. Transcriptomic profiling revealed that RPS6 affects numerous alternative splicing (AS) events, and combined with RNA immunoprecipitation sequencing, revealed that minichromosome maintenance complex component 7 (MCM7) binds to RPS6, which regulates its AS and increases oncogenic activity in CCA. Targeting RPS6 with vivo phosphorodiamidate morpholino oligomer (V-PMO) significantly inhibited the growth of CCA cells, patient-derived organoids, and subcutaneous xenograft tumor. Taken together, the data demonstrate that RPS6 is an oncogenic regulator in CCA and that RPS6-V-PMO could be repositioned as a promising strategy for treating CCA.

Due to the rise of antibiotic-resistant bacteria around the world, AMPs (antimicrobial peptides), depending on non-specific membrane mechanism and low tendency to develop bacterial resistance, attract widespread attentions as novel antimicrobial alternatives for treating bacterial infections. In this study, a series of new β-Ala modified-antimicrobial peptide analogues of anoplin were designed and synthesized, and their biological activities were described. Most of the new peptides showed perfect antimicrobial activities against two antibiotic-sensitive Pseudomonas aeruginosa strains and three clinical isolates of multidrug-resistant P. aeruginosa strains without significant hemolysis or cytotoxicity. More significantly, Ano-1β and Ano-8β (substituting positions 1 and 8 of anoplin with β-Ala, respectively) exhibited the best antimicrobial potency. Additionally, the two new peptides were stable under physiological conditions and displayed preferable in vivo antimicrobial activity with less acute toxicity. Notably, Ano-1β and Ano-8β hardly generated resistance in contrast to conventional antibiotics rifampicin and gentamicin, and they exhibited better anti-biofilm activity and synergistic or additive effects in combination with conventional antibiotics. What's more, Ano-1β and Ano-8β had strong membrane disruption as evidenced by outer membrane permeabilization and cytoplasmic membrane depolarization assays. Confocal laser scanning microscopy and scanning electron microscopy further demonstrated that the two new peptides could destroy the bacterial membrane integrity. Collectively, the incorporation of β-Ala was a reasonable approach for new antimicrobial peptides design, and the new peptides Ano-1β and Ano-8β might be promising antimicrobial candidates in combating the increasing antibiotic-resistant bacteria.

Stem cell-based regenerative research has highlighted the therapeutic potential of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exos) for hepatic tissue regeneration and repair. However, exosomes undergo rapid clearance following systemic administration, limiting their therapeutic potential because of insufficient retention and sustained release. In this study, an innovative hydrogel-mediated delivery platform encapsulating aminoethyl anisamide (AEAA)-functionalized exosomes was developed to mitigate hepatic fibrosis. By synthesizing a hydrogel (CMC-OD/TA-Fe(III), Gel) composed of carboxymethyl chitosan, oxidized dextran, and iron tannate, and then encapsulating umbilical cord mesenchymal stem cell-derived exosomes functionalized by AEAA (AEAA-Exos), we implanted this Gel/AEAA-Exos into mice with hepatic fibrosis by intraperitoneal injection to evaluate the therapeutic effect of the hydrogel. The hydrogel had favorable physical properties, optimal biocompatibility, and a sustained-release profile. And Gel/AEAA-Exos system significantly reduced oxidative stress and alleviated hepatic fibrosis. Additionally, RNA-seq revealed that the Gel/AEAA-Exos system ameliorates hepatic fibrogenesis mainly by modulating oxidative stress, collagen deposition, and inflammatory cascade in liver tissues. This strategy offers a targeted and efficient approach for treating liver fibrosis induced by chronic hepatic injury and improves targeting efficiency and therapeutic outcomes through engineered exosome delivery.