Myocarditis is an inflammatory lesion of the myocardium that is caused by a variety of factors. At present, treatment of symptoms remains the main clinical intervention, but it cannot reduce the myocarditis damage caused by inflammation. M1 macrophages are thought to contribute significantly to the occurrence and development of inflammation by secreting a large number of proinflammatory factors. Puerarin is an isoflavone derivative isolated from pueraria that can be used as a dietary supplement and exerts wide range of anti-inflammatory and antioxidant effects. However, the mechanism underlying its anti-inflammatory effects needs to be further studied. The objective of this study was to investigate whether puerarin inhibited M1 polarization by affecting the JAK-STAT signaling pathway in a mouse model of autoimmune myocarditis, thus inhibiting the occurrence of inflammation in experimental autoimmune myocarditis (EAM) model mice. The results showed that EAM model mice treated with puerarin showed milder clinical symptoms and inflammatory infiltration than EAM model mice. Puerarin suppressed the in vivo and in vitro JAK1/2-STAT1 signal transduction in macrophages, thus inhibiting M1 polarization, reducing the secretion of proinflammatory factors, and ultimately decreasing IFN-γ and TNF-α levels in vivo, which led to myocardial apoptosis. Thus, puerarin could alleviate myocardial damage caused by inflammation. The conclusion of this study was that puerarin reduced myocardial damage in EAM model mice by regulating the polarization of macrophages toward M1, and this inhibitory effect may be achieved by inhibiting JAK1/2-STAT1 signaling.

BackgroundThe experimental autoimmune myocarditis (EAM) model is valuable for investigating myocarditis pathogenesis. M1-type macrophages and CD4+ T cells exert key pathogenic effects on EAM initiation and progression. Baicalein (5,6,7-trihydroxyflavone, C15H10O5, BAI), which is derived from the Scutellaria baicalensis root, is a primary bioactive compound with potent anti-inflammatory and antioxidant properties. BAI exerts good therapeutic effects against various autoimmune diseases; however, its effect in EAM has not been thoroughly researched.PurposeThis study aimed to explore the possible inhibitory effect of BAI on M1 macrophage polarisation and CD4+ T cell differentiation into Th1 cells via modulation of the JAK-STAT1/4 signalling pathway, which reduces the secretion of pro-inflammatory factors, namely, TNF-α and IFN-γ, and consequently inhibits TNF-α- and IFN-γ-triggered apoptosis in cardiomyocytes of the EAM model mice.Study design and MethodsFlow cytometry, immunofluorescence, real-time quantitative polymerase chain reaction (q-PCR), and western blotting were performed to determine whether BAI alleviated M1/Th1-secreted TNF-α- and IFN-γ-induced myocyte death in the EAM model mice through the inhibition of the JAK-STAT1/4 signalling pathway.ResultsThese results indicate that BAI intervention in mice resulted in mild inflammatory infiltrates. BAI inhibited JAK-STAT1 signalling in macrophages both in vivo and in vitro, which attenuated macrophage polarisation to the M1 type and reduced TNF-α secretion. Additionally, BAI significantly inhibited the differentiation of CD4+ T cells to Th1 cells and IFN-γ secretion both in vivo and in vitro by modulating the JAK-STAT1/4 signalling pathway. This ultimately led to decreased TNF-α and IFN-γ levels in cardiac tissues and reduced myocardial cell apoptosis.ConclusionThis study demonstrates that BAI alleviates M1/Th1-secreted TNF-α- and IFN-γ-induced cardiomyocyte death in EAM mice by inhibiting the JAK-STAT1/4 signalling pathway.

Objective To explore the effects of polydopamine (PDA) plus luteolin (LUT) with photothermal therapy on tumor killing by cytotoxic lymphocytes (CTL). Methods The synthesized PDA was characterized by using a scanning electron microscope (SEM) and a contact angle analyzer. RAW264.7 cells were divided into control group, LPS group (2 μg/L), and PDA' group (50 000 μg/L). After 48 h culture, cell viability was determined by cell counting kit-8. The effect of LUT on the differentiation of RAW264.7 cells was determined by flow cytometry. Female C57BL/6 mice were randomly divided into model group, PDA group, LUT group, and PDA+LUT group. B16F10 melanoma cells were subcutaneously injected into the back of mice in each group. On the 10th day after modeling, the PDA and PDA+LUT groups received injection of PDA into the tumor as well as photothermal therapy. The mice in the four groups received injection of PBS, PDA (2.5 μg/piece), LUT (500 μg/piece), and PDA (2.5 μg/piece) plus LUT (500 μg/piece) into the muscle of the right thigh, respectively. We observed the tumor growth and survival of the model mice. On days 3 and 7 after treatment, the spleen of each mouse was taken to prepare a single cell suspension for analysis of macrophage differentiation and T cell expression by flow cytometry. Results SEM showed that the synthesized PDA had good adhesion and affinity for water. CCK8 showed that the PDA did not affect cell viability (P>0.05). Significant differences were found in the mean fluorescence intensities of CD206 and iNOS between different groups of RAW264.7 cells (F=30.72,1 516.00,P<0.05). There were significant differences in tumor size and the expression levels of iNOS, CD206, IFN-γ+CD4+, and TNF-α+CD8+ of immune cells between mice with and without LUT injection, under the condition of either injecting or not injecting PDA (F=23.10-235.52,P<0.05). There were significant differences in tumor size and the expression levels of iNOS, CD206, IFN-γ+CD4+, and TNF-α+CD8+ of immune cells between mice with and without PDA injection, under the condition of either injecting or not injecting LUT (F=8.98-200.67,P<0.05). The survival rate of the PDA+LUT group was significantly higher than those of the other groups (χ2=9.70,P<0.01). Conclusion LUT could inhibit the differentiation of macrophages to M2 and promote the differentiation to M1 in mice. PDA combined with LUT could effectively inhibit tumor growth, improve survival rate, and enhance the tumor-kil-ling effect of CTL in mice.

Exudate management and bioelectric signals are critical to promoting wound healing. In this study, the thermoplastic polyurethane (TPU) nanofiber is directly electrospun on the cotton microfibers (Cotton) to prepare a Janus dressing (TPU/Cotton), which can unidirectionally drain the excess exudate. Then, Ag/Zn dot electrodes are deposited on the TPU layer, which can produce an electric field penetrating the wound when activated by wound exudate. The hydro‐activated Ag/Zn's electrical stimulation (ES) can promote the migration of fibroblast cells and shows excellent antibacterial activity against E. coli and S. aureus . Furthermore, in vivo experiments show that the exudate management coupled with ES accelerated wound healing at multiple stages by promoting re‐epithelization, collagen deposition, and vascularization. Moreover, the Ag/Zn@TPU/Cotton dressing shows excellent biocompatibility in the vitro cytotoxicity experiments. These findings may shed some light on developing the next generation of wound dressings with self‐activated electrical stimulation and exudate management.

Developing functional dressings for promoting cellular activities and monitoring the healing progress is receiving increasingly widespread attention. In this study, Ag/Zn electrodes were deposited on the surface of a polylactic acid (PLA) nanofibrous membrane which can mimic the extracellular matrix. When wetted by wound exudate, the Ag/Zn electrodes could generate an electric stimulation (ES), promoting the migration of fibroblasts that heal wounds. Moreover, the Ag/Zn@PLA dressing showed excellent antibacterial activity against E. coli (95%) and S. aureus (97%). The study found that the electrostatic (ES) effect and the release of metal ions mainly contribute to the wound healing properties of Ag/Zn@PLA. In vivo mouse models demonstrated that Ag/Zn@PLA could promote wound healing by improving re-epithelialization, collagen deposition, and neovascularization. Additionally, the integrated sensor within the Ag/Zn@PLA dressing can monitor the wound site's temperature in real-time, providing timely information on wound inflammatory reactions. Overall, this work suggests that combining electroactive therapy and wound temperature monitoring may provide a new strategy for designing functional wound dressings.

Adjuvants are an indispensable component of vaccines, but there are few adjuvants for human vaccines. H2 receptor blockers, inhibiting gastric acid secretion, have immune enhancement effects. Ranitidine (RAN) is a water-soluble H2 receptor blocker, and whether it has an immune-enhancing effect is still unknown. In this study, flow cytometry, western blotting, and immunofluorescence methods were used to analyze whether RAN could activate macrophage polarization to the M1 phenotype in vivo and in vitro. Here, we found that the M1 inflammatory cytokine levels and surface markers in RAW264.7 cells were upregulated by NF-κB activation, possibly through the PI3K-Akt2 signaling pathway, after RAN treatment. Endocytic function was also enhanced by feedback regulation of Akt2/GSK3β/Dynmin1 signaling. Furthermore, to evaluate the adjuvant function of RAN, we used OVA plus RAN as a vaccine to inhibit the growth of B16-OVA tumors in mice. We also found that in the RAN adjuvant group, macrophage polarization to M1, Th1 cell differentiation, and cytotoxic T lymphocyte (CTL) activation were significantly upregulated. The tumor growth of mice was inhibited, and the survival rate of mice was significantly improved. This study provides new evidence for the mechanism by which RAN activates the immune response and is expected to provide a new strategy for the research and development of tumor vaccine adjuvants.

Chrysin (CHR) is a flavonoid with extensive pharmacological activity. The molecular formula of CHR is C15H10O4. CHR is reported to have antioxidative, antitumour and antiviral functions. To evaluate its potential function as a vaccine adjuvant, we prepared a melanoma vaccine using a soluble protein extract of B16F10 melanoma cells as antigen and CHR as an adjuvant. The melanoma model was developed after two immunizations, and it was discovered that combining B16F10 soluble protein antigen-mixed CHR vaccine could inhibit tumour growth in the mouse model, and the overall survival rate was higher than that of the B16F10 antigen vaccine alone. In vivo and in vitro experiments were conducted to determine whether CHR functioned as an adjuvant by activating antigen-presenting cells (APCs). We discovered that CHR activated APCs both in vivo and in vitro and may enhance Th1 cell function by activating the IL12-STAT4 signal pathway, thereby enhancing the antitumour response of cytotoxic T lymphocytes (CTLs) in vivo. Next, to verify the critical role of CD8(+) T cells in suppressing melanoma development, we transplanted CD8(+) T cells from immunized mice to B16F10 tumour-bearing mice and discovered that the survival rate of tumour-bearing mice was significantly prolonged. In summary, our experimental results indicate that CHR can be used as a potential adjuvant to enhance antigen immunogenicity, inhibit B16F10 tumour growth in mice and improve tumour immune response.

Abstract The Collagen Type VII Alpha 1 Chain (COL7A1) is associated with a variety of cancers, however, COL7A1 gene expression in human lung squamous cell carcinoma (LUSC) and its prognostic value have not been well studied. In this study, we used bioinformatics database to analyze the relationship between COL7A1 expression and survival in LUSC patients such as Oncomine, GEPIA, UALCAN, and STRING. And we used Kaplan–Meier plotter to analyze the prognosis of high or low expression of COL7A1 in different patients. We found that COL7A1 was significantly overexpressed in patients with LUSC. Additionally, in the survival analysis, COL7A1 expression was significantly associated with worse overall survival (OS), first progression (FP), Post-progression survival (PPS) in LUSC patients. Moreover, COL7A1 is closely associated with known biomarkers and key factors of LUSC. We used functional annotation enrichment analysis to show that genes co-expressed with COL7A1 were enriched in biological process (BP), cellular component (CC), molecular function (MF) and KEGG pathways. Furthermore, Laminin 332 and its association with COL7A1 may lead to the activation of the PI3K signaling pathway, ultimately leading to squamous cell carcinoma (SCC). This has also been mentioned in other people's research. Therefore, our work was designed to demonstrate the potential of COL7A1 as a prognostic biomarker in LUSC.

The primary functions of the bladder are storing urine under low and stable pressure and micturition. Various forms of trauma, tumors, and iatrogenic injuries can cause the loss of or reduce bladder function or capacity. If such damage is not treated in time, it will eventually lead to kidney damage and can even be life-threatening in severe cases. The emergence of tissue engineering technology has led to the development of more possibilities for bladder repair and reconstruction, in which the selection of scaffolds is crucial. In recent years, a growing number of tissue-engineered bladder scaffolds have been constructed. Therefore, this paper will discuss the development of tissue-engineered bladder scaffolds and will further analyze the limitations of and challenges encountered in bladder reconstruction.

Background Cyclin B (CCNB) family plays key roles in the cell cycle, cell division and proliferation. Three members of CCNB family have been identified, including CCNB1, CCNB2 and CCNB3. Many studies have explored the roles of CCNBs in the tumorigenesis and pathogenesis of different types of cancer. However, the expression level, function, and prognostic value of CCNBs in breast caner (BC) are still unclear. Methods We explored the specific alterations of CCNBs in BC and predicted their prognostic value for BC patients. Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier plotter, cBioPortal, STRING, Database for Annotation,Visualization and Integrated Discovery (DAVID) databases were used for above analyses. Results We found that CCNB1 amd CCNB2 were significantly overexpressed in BC compared with normal samples, but not CCNB3. Survival analysis showed that upregulated CCNB1 and CCNB2 expression levels were associated with poor prognosis of BC patients, while high CCNB3 expression was related to good prognosis for BC patients. Furthermore, gene oncology (GO) enrichment analysis was performed to reveal the functions of CCNBs and the interacted genes related to CCNBs. In addition, hsa-miR-139-5p and has-miR-944 were identified to be potentially involved in the regulation of CCNB1. Conclusion Our study suggests that CCNB1, CCNB2 are potential targets of precise therapy for BC patients and that CCNB3 is a novel biomarker for the good prognosis of BC patients.