Rotating Magnetic Field Mitigates Ankylosing Spondylitis Targeting Osteocytes and Chondrocytes via Ameliorating Immune Dysfunctions.

Ankylosing spondylitis (AS) is clinically characterized by bone fusion that is induced by the pathological formation of extra bone. Unfortunately, the fundamental mechanism and related therapies remain unclear. The loss of SHP-2 (encoded by Ptpn11) in CD4-Cre;Ptpn11f/f mice resulted in the induction of AS-like pathological characteristics, including spontaneous cartilage and bone lesions, kyphosis, and arthritis. Hence, this mouse was utilized as an AS model in this study. As one of the basic physical fields, the magnetic field (MF) has been proven to be an effective treatment method for articular cartilage degeneration. In this study, the effects of a rotating magnetic field (RMF; 0.2 T, 4 Hz) on an AS-like mouse model were investigated. The RMF treatment (2 h/d, 0.2 T, 4 Hz) was performed on AS mice from two months after birth until the day before sampling. The murine specimens were subjected to transcriptomics, immunomics, and metabolomics analyses, combined with molecular and pathological experiments. The results demonstrated that the mitigation of inflammatory deterioration resulted in an increase in functional osteogenesis and a decrease in dysfunctional osteolysis due to the maintenance of bone homeostasis via the RANKL/RANK/OPG signaling pathway. Additionally, by regulating the ratio of CD4+ and CD8+ T-cells, RMF treatment rebalanced the immune microenvironment in skeletal tissue. It has been observed that RMF interventions have the potential to alleviate AS, including by decreasing pathogenicity and preventing disease initiation. Consequently, RMF, as a moderately physical therapeutic strategy, could be considered to alleviate the degradation of cartilage and bone tissue in AS and as a potential option to halt the progression of AS.

Antitumor effect and mechanism of FZD7 polypeptide vaccine.

The resistant cells that proliferate after radiotherapy and chemotherapy are primarily tumor stem cells with high stem marker expression, and their presence is the primary cause of tumor dispersion. The Wnt signaling receptor Frizzled family receptor 7 (FZD7) is linked to the maintenance of stem cell features as well as cancer progression. Frizzled-7 (FZD7), a key receptor for Wnt/-catenin signaling, is overexpressed in TNBC, suggesting that it could be a viable target for cancer therapy. We employed bioinformatics to find the best-scoring peptide, chemically synthesized FZD7 epitope antigen, and binding toll-like receptor 7 agonists (T7). Under GMP conditions, peptides for vaccines were produced and purified (>95%). In vivo and vitro tests were used to assess tumor cell inhibition. In vitro, the FZD7-T7 vaccination can boost the maturity of BMDC cells considerably. In mice, the FZD7 - T7 vaccine elicited the greatest immunological response. Significant tumor development inhibition was seen in BALB/c mice treated with FZD7 - T7 in prevention experiments (P < 0.01). Multiple cytokines that promote cellular immune responses, such as interferon (IFN)-γ (P < 0.05), interleukin (IL)-12 (P < 0.05), and IL-2 (P < 0.01), were shown to be considerably elevated in mice inoculated with FZD7- T7. Furthermore, we evaluated safety concerns in terms of vaccine composition to aid in the creation of successful next-generation vaccines. In conclusion, the FZD7-T7 vaccine can activate the immune response in vivo and in vitro, and play a role in tumor suppression. Our findings reveal a unique tumor-suppressive role for the FZD7 peptide in TNBC.

BIX-01294 enhances the effect of chemotherapy on colorectal cancer by inhibiting the expression of stemness genes.

During the development of colorectal cancer, tumor cells will generate some cancer stem cells with self-renewal ability because they adapt to the environment. Therefore, in the treatment of colorectal cancer, it has certain potential clinical application value to effectively inhibit cancer stem cells. A small molecule EHMT-2 inhibitor, BIX-01294, was evaluated for its activity in inhibiting cancer stem cells in human colorectal cancer by in vitro and in vivo experiments. Transcriptome analysis was performed on BIX-01294 treated cells for holistic analysis to elucidate how BIX-01294 inhibits the expression of genes related to cancer stem cells. The results show that BIX-01294 significantly inhibited the proliferative phenotype of human colorectal cancer in vivo and in vitro, reduced the proportion of cancer stem cells, and inhibited some stemness-related gene. Morever, it is synergistic with 5-fluorouracil in inhibiting the proliferation of colorectal cancer. In summary, EHMT-2 is a novel target of anti-tumor drugs. The combination of BIX-01294 and 5-fluorouracil has a synergistic therapeutic effect on human colorectal cancer.