Investigating the mechanism and the effect of aquaporin 5 (AQP5) on the self-renewal capacity of gastric cancer stem cells.

Aquaporin 5 (AQP5) has been shown to have a pro-carcinogenic effect in numerous types of malignancies. This research intends to investigate the role and the molecular mechanism of AQP5 on enriched gastric cancer stem cells (GCSCs). Methods: Immunohistochemistry, western blot (WB), and RT-qPCR techniques were employed to identify the presence of AQP5 in gastric cancer (GC) and the neighboring paracancerous tissues. Additionally, a statistical analysis was conducted to determine the correlation between AQP5 expression and the pathological and histological parameters. Furthermore, the study aimed to assess the predictive value of AQP5 expression in long-term survival after GC surgery. GCSCs were enriched using the serum-free culture method. The expression of AQP5 in enriched GCSCs was explored using RT-qPCR and WB. Plate cloning, transwell, WB, RT-qPCR, and the sphere-forming assay were utilized to monitor the proliferation, migration, and self-renewal capability of GCSCs after AQP5 knockdown. WB and Immunofluorescence for Detecting the Effect of AQP5 on Autophagy. WB, RT-qPCR, and other experiments were used for in-depth investigation of the potential molecular regulatory mechanism of AQP5 in GC. Results: AQP5 was highly expressed in GC tissues and GC cells, and overexpression of AQP5 was associated with lymph node metastasis, increased tumor size, and low 5-year postoperative survival in GC patients; other studies have shown that the AQP5 was highly expressed in GCSCs. Knockdown of AQP5 suppressed tumorigenesis in vivo and inhibited the proliferative, migratory, and self-renewal capability of GCSCs. It was also found that AQP5 could activate the autophagy phenomenon of GCSCs, and mechanistically, we found that AQP5 could regulate TRPV4 to affect the self-renewal ability of GCSCs. Conclusion: AQP5 can be further explored for GC therapy, as it has shown a significant impact on the self-renewal capability of GCSCs, which prevents GC progression.

Advances in PGD2/PTGDR2 signaling pathway in tumors: A review.

Studies have shown that the prostaglandin (PG) family acts as allergic inflammatory mediator in malignant diseases. Furthermore, prostaglandin E2 (PGE2) and its related receptors, as well as the prostaglandin D2 (PGD2)/PGD2 receptor (PTGDR2), play irreplaceable roles in tumorigenesis and anti-tumor therapy. Several experiments have demonstrated that PGD2 signaling through PTGDR2 not only directly inhibits cancer cell survival, proliferation, and migration but also reduces resistance towards conventional chemotherapeutic agents. Recent studies from our and other laboratories have shown that PGD2, its ligands, and related metabolites can significantly alter the tumor microenvironment (TME) by promoting the secretion of chemokines and cytokines, thereby inhibiting tumor progression. Additionally, reduced PGD2 expression has been associated with poor prognosis in patients with gastric, breast, lung, and pancreatic cancers, validating the preclinical findings and their clinical relevance. This review focuses on the current understanding of PGD2/PTGDR2 expression patterns and biological activity in cancer, proposing questions to guide the assessment of PGD2 and its receptors as potential targets for effective cancer therapies.

Human Umbilical Cord Mesenchymal Stem Cell-derived Exosomes Induce Macrophage M2 Polarization by Antagonizing LPS-mediated Stimulation of the NF-κB and STAT3 Pathways.

BACKGROUND: Many studies have documented the protective effects of regulating macrophage M1/M2 polarization in inflammatory diseases characterized by their imbalance state. In pathological diseases associated with inflammation, mesenchymal stem cells (MSCs) regulate macrophages, thereby having anti-inflammatory and tissue regenerative effects. Exosomes have been suggested as an alternative mechanism that underlies the paracrine function of MSCs. Thus, this study explored the anti-inflammatory impact of human umbilical cord MSCssecreted exosomes (hucMSCs-EX) by influencing macrophage polarization in normal and inflammatory environments in vitro. METHODS: In this study, hucMSCs-conditioned medium (hucMSCs-CM) and hucMSCs- EX were used to treat RAW264.7 macrophages with or without LPS. The expressions of TNF- α, IL-10, IL-6, IL-1ß, and Arg-1 were quantified by qPCR. The expressions of IL-6 and IL-10 were evaluated by ELISAs. Western blots (WB) were performed to observe the expressions of CD206, NF-κB P65, NF-κB p-p65, p-STAT3, STAT3, and NF-κB phosphorylation. The number of cells expressing CD206 and the fluorescence intensity were measured via flow cytometry (FC) and immunofluorescence staining. Cell propagation and migration were examined via MTT and transwell assays, respectively. RESULTS: The inhibition of LPS-induced inflammatory polarization by hucMSCs-EX or hucMSCs- CM led to increases in IL-10 and arginase (Arg) levels and decreases in those of IL-6 and TNF-α. Moreover, hucMSCs-EX enhanced the CD206 expression in RAW264.7 cells and accelerated the propagation and migration of LPS-induced cells. The suppressive impact of hucMSCs-EX on the LPS-induced phenotypic polarization of M1 macrophages was linked with the reduction of NF-κB signaling. They stimulated the transition of M2 macrophages by enhancing the activity of STAT3 in RAW264.7 cells. CONCLUSION: This study indicated that hucMSCs-EX enhances the macrophage transition into the M2 phenotype by inhibiting the NF-κB p65 axis and stimulating that of STAT3.

PGD2/PTGDR2 Signal Affects the Viability, Invasion, Apoptosis, and Stemness of Gastric Cancer Stem Cells and Prevents the Progression of Gastric Cancer.

BACKGROUND: Prostaglandin D2 (PGD2) has been shown to restrict the occurrence and development of multiple cancers; nevertheless, its underlying molecular mechanism has not been fully elucidated. The present study investigated the effect of PGD2 on the biological function of the enriched gastric cancer stem cells (GCSCs), as well as its underlying molecular mechanism, to provide a theoretical basis and potential therapeutic drugs for gastric cancer (GC) treatment. METHODS: The plasma PGD2 levels were detected by Enzyme-linked immunosorbent assay (ELISA). Silencing of lipocalin prostaglandin D synthetases (L-PTGDS) and prostaglandin D2 receptor 2 (PTGDR2) was carried out in GCSCs from SGC-7901 and HGC-27 cell lines. Cell Counting Kit-8, transwell, flow cytometry, and western blotting assays were used to determine cell viability, invasion, apoptosis, and stemness of GCSCs. In vivo xenograft models were used to assess tumor growth. RESULTS: Clinically, it was found that the plasma PGD2 level decreased significantly in patients with GC. PGD2 suppressed viability, invasion, and stemness and increased the apoptosis of GCSCs. Downregulating L-PTGDS and PTGDR2 promoted viability, invasion, and stemness and reduced the apoptosis of GCSCs. Moreover, the inhibition of GCSCs induced by PGD2 was eliminated by downregulating the expression of PTGDR2. The results of in vivo experiments were consistent with those of in vitro experiments. CONCLUSION: Our data suggest that PGD2 may be an important marker and potential therapeutic target in the clinical management of GC. L-PTGDS/PTGDR2 may be one of the critical targets for GC therapy. The PGD2/PTGDR2 signal affects the viability, invasion, apoptosis, and stemness of GCSCs and prevents the progression of GC.

[Clinical application of the free anterolateral thigh myocutaneous flap with the tensor fascia lata for one-stage repair of soft tissues defects at the dorsum of hands (feets)].

Objective: To explore the method and the therapeutic effect of the free anterolateral thigh myocutaneous flap with the tensor fascia lata for one-stage repair of soft tissues defects at the dorsum of hands (feets). Method: Between Jan.2010 and Dec.014,8 patients with finger (toe) extensor tendon and dorsal foot defect were treated with anterolateral thigh myocutaneous flap. The defect area ranged from 6 cm ×5cm to 18 cm× 10cm.All of the soft tissues defects at the dorsum of hands (feets) combined with tendon colobomam. The free anterolateral thigh myocutaneous flap (ranged from 8 cm × 7cm to 20 cm × 12cm) were applied for one-stage repair of the soft tissues defects. The anterolateral thigh flap was used to repair defect and fascia lata was used to bridge two ends of digitorum longus tendon. The defects at donor sites were sutured directly or repaired with the split-thickness skin graft.2-3 months after the surgery, tenolysis for tendon was performed, and fascia lata was split into tendon-like shape and the finger (toe) functional exercises were done. Results: All flaps survived completely after the first stage.Postoperative follow-up time was 6-12 months (average,8 months).Except 4 flaps with somewhat swelling, the other flaps had satisfactory appearance with soft texture. During the follow-up, part of the dorsiflexion function of hand recovered in 3 patients (5°-40°),and flexion function was normal;5 patients with soft tissues defects at the dorsum of foots could walk normally with no toe ptosis. Conclusions: Application of the free anterolateral thigh myocutaneous flap with the tensor fascia lata can repair soft tissues defects at the dorsum of hands (feets) combined with tendon colobomam. It can repair soft tissues defect combined with finger (toe) extensor tendon defects. Excellent clinical results can be achieved with short treatment time and less damage to the donor site.