Seminal plasma S100A8/A9 as a potential biomarker of genital tract inflammation.

ABSTRACT: Infections and inflammatory reactions in the male genital tract are the leading causes of male infertility with a prevalence of 6%-10%, primarily affecting testicular and epididymal function and ultimately compromising sperm quality. However, most infertile patients with genital infection/inflammation are asymptomatic and easily overlooked. Traditional indicators, including white blood cells, elastase, and other components in semen, can reflect inflammation of the genital tract, but there is still a lack of a uniform standard method of detection. Therefore, it is necessary to explore reliable markers in semen that reflect the inflammatory status of the genital tract. Using the experimental autoimmune orchitis (EAO) model to simulate noninfectious chronic orchitis, we successfully collected ejaculated seminal fluid from EAO rats using optimized electrical stimulation devices. Proteomic analysis was performed using isobaric tags for relative and absolute quantification (iTRAQ). Compared to the control group, 55 upregulated and 105 downregulated proteins were identified in seminal plasma samples from the EAO group. In a preliminary screening, the inflammation-related protein S100A8/A9 was upregulated. We further verified that S100A8/A9 was increased in seminal plasma and highly expressed in testicular macrophages of the EAO model. In patients with oligoasthenospermia and genital tract infections, we also found that S100A8/A9 levels were remarkably increased in seminal plasma and testicular macrophages. S100A8/A9 in semen may be a potential biomarker for chronic genital inflammation. Our study provides a new potential biomarker for early diagnosis and further understanding of male infertility caused by genital inflammation.

Melanin inspired microcapsules delivering immune metabolites for hepatic fibrosis management.

Patients with hepatic fibrosis (HF) have a high risk of developing liver cirrhosis and hepatocellular carcinoma, and there is an urgent need for preventive strategies to block this process. Previous studies have found that disordered inflammation and oxidative damage play important roles in HF progression, suggesting two attractive therapeutic targets. Herein, a new kind of bioinspired microcapsules with a core-shell structure is generated using microfluidics. Polydopamine nanoparticles (PDANPs), a synthetic analogue of natural melanin, are embedded in the polymer shell to provide antioxidative properties for these microcapsules. The aqueous core is used to encapsulate ketone body ß-hydroxybutyrate (BHB), an energy metabolite recently known to have regulating effects of cellular signals involved in chronic inflammation. In a HF mouse model, the BHB-encapsulated PDANPs-embedded microcapsules (BHB-PDA-MCs) can not only decrease the severity of inflammatory response, but also the level of oxidative stress. As a result, this combinational strategy is demonstrated to prevent the activation of hepatic stellate cells, the accumulation of extracellular matrix, and the damage of hepatic lobules. These findings indicate that BHB-PDA-MCs can be a promising drug delivery system and have a synergistic effect on HF management.

EPS8L3 promotes pancreatic cancer proliferation and metastasis by activating GSK3B.

Background: We intended to investigate the role and regulatory mechanism of EPS8L3 in increase the development of pancreatic cancer (PC). Methods: In order to analyze the relationship between EPS8L3 level and clinicopathological indicators of PC patients, qRT-PCR was used to detect the expression of EPS8L3 in tumor specimens of 40 PC patients. EPS8L3 knockdown models were then constructed in PC cell lines. Furthermore, the effect of EPS8L3 on PC cell function was analyzed by CCK-8 and Transwell assay. Dual luciferase reporter gene assay and recovery assay were used to further investigate the underlying mechanism. Results: qRT-PCR results indicated that EPS8L3 was highly expressed in PC tissues compared with adjacent ones. At the same time, the incidence of distant metastasis was higher in PC patients with high EPS8L3 level. In vitro analysis such as CCK-8 and Transwell experimentations indicated that knockdown of EPS8L3 markedly inhibited the proliferative and metastatic ability. Bio-informatics together with luciferase report assay proposing that EPS8L3 can target GSK3B. Western Blot results revealed that knockdown of EPS8L3 markedly reduced the GSK3B expression in PC cells, and there was a positively associated between the two in PC cells. In addition, the recovery experimentation proved that EPS8L3 and GSK3B have a mutual regulation effect. Overexpression of GSK3B can reversal the prohibitive effect of EPS8L3 knockdown on the malignant development of PC cells, thereby jointly regulating the occurrence and development of PC. Conclusions: EPS8L3 promotes the development of PC by regulating GSK3B, suggesting that EPS8L3 can be used as a biomarker for early diagnosis and treatment of PC.

Endoscopic treatment of benign biliary stricture using different stents: a systematic review and meta-analysis.

INTRODUCTION: Biodegradable biliary stents (BDBSs), fully covered self-expanded metal stents (FCSEMSs) and multiple plastic stents (MPSs) were common stents in endoscopic treatment of benign biliary stricture (BBS). AIM: To evaluate the effectiveness of these 3 stents in BBS management. MATERIAL AND METHODS: The PubMed, Web of Science, Cochrane Library, and Wiley Library databases were searched for studies that provided data about BBS and stent therapy. RESULTS: We found that BDBSs were associated with the highest clinical success rate (0.76, 95% CI: 0.71-0.80), followed by MPSs (0.69, 95% CI: 0.63-0.74), and FCSEMSs (0.67, 95% CI: 0.63-0.71). BDBSs also had a relatively high probability of technical success, at 1.00 (95% CI: 1.00-1.00), superior to MPSs (0.95, 95% CI: 0.88-0.99) and FCSEMSs (0.90, 95% CI: 0.85-0.94). The treatment success rate for BDBSs (1.00, 95% CI: 1.00-1.00) was also higher than for MPSs (0.88, 95% CI: 0.72-0.98) and FCSMESs (0.82, 95% CI: 0.76-0.87). However, BDBSs had the highest stricture recurrence rate (0.21, 95% CI: 0.16-0.26), compared with FCSEMSs (0.11, 95% CI: 0.08-0.15) and MPSs (0.07, 95% CI: 0.03-0.13). CONCLUSIONS: Patients with BBS are likely to receive a satisfied outcome when treated with BDBSs.

Cell-based therapies for reinforcing the treatment efficacy of meshes in abdominal wall hernias：A systematic review and meta-analysis.

To achieve a tension-free repair and reduce the recurrence rate of abdominal wall hernias (AWHs), various kinds of meshes have been applied in surgery. However, these meshes are reported to have problems with adhesion, infection, chronic pain and foreign body sensation. Recently, the introduction of cellular components on meshes seems to provide a new alternative to resolve these problems. This study aimed to evaluate the treatment efficacy of meshes seeded with cells (mesh-cell group) for AWHs, compared to meshes without cells (mesh group). Cochrane Library, Web of Science and PubMed were searched for studies that provided data about meshes, cells and AWHs. Twenty-six studies involving 578 animals were included. We found that the mesh-cell group could better control hernia recurrent than the mesh group (OR = 0.25, 95% CI = 0.15-0.42). Although the mesh-cell group did not reduce the incidence of adhesions (OR = 0.67, 95% CI = 0.26-1.74), it alleviated the extent of adhesions (WMD = -1.48, 95% CI = -1.86 to -1.10). In addition, the capillary density of mesh-cell group was also higher than that of mesh group (WMD = 26.27, 95% CI = 14.45-38.09). For incidence of infection, the two groups had no significant differences (OR = 0.94, 95% CI = 0.39-2.31). On the basis of our current evidence, AWHs were likely to receive a satisfied outcome in animal models when treated by meshes seeded with cells. Future studies with human trial data are needed to validate these findings.

S100A9 Activates the Immunosuppressive Switch Through the PI3K/Akt Pathway to Maintain the Immune Suppression Function of Testicular Macrophages.

Macrophages are functionally plastic and can thus play different roles in various microenvironments. Testis is an immune privileged organ, and testicular macrophages (TMs) show special immunosuppressive phenotype and low response to various inflammatory stimuli. However, the underlying mechanism to maintain the immunosuppressive function of TMs remains unclear. S100A9, a small molecular Ca2+ binding protein, is associated with the immunosuppressive function of macrophages. However, no related research is available about S100A9 in mouse testis. In the present study, we explored the role of S100A9 in TMs. We found that S100A9 was expressed in TMs from postnatal to adulthood and contributed to maintaining the immunosuppressive phenotype of TMs, which is associated with the activation of PI3K/Akt pathway. S100A9 treatment promotes the polarization of bone marrow-derived macrophages from M0 to M2 in vitro. S100A9 was significantly increased in TMs following UPEC-infection and elevated S100A9 contributed to maintain the M2 polarization of TMs. Treatment with S100A9 and PI3K inhibitor decreased the proportion of M2-type TMs in control and UPEC-infected mouse. Our findings reveal a crucial role of S100A9 in maintaining the immunosuppressive function of TMs through the activation of PI3K/Akt pathway, and provide a reference for further understanding the mechanism of immunosuppressive function of TMs.