GDF15 restrains myocardial ischemia-reperfusion injury through inhibiting GPX4 mediated ferroptosis.

BACKGROUND: Growth and differentiation factor 15 (GDF15) has been proved to regulate the process of Myocardial ischemia-reperfusion injury (MIRI), which is a serious complication of reperfusion therapy. The present study aimed to explore if GDF15 could regulate the MIRI-induced ferroptosis. METHOD: MIRI animal model was established by ligating the left anterior descending coronary artery. Oxygen-glucose deprivation/reoxygenation (OGD/R) cell model was established to imitate MIRI in vitro. The indicators of ferroptosis including mitochondrial damage, GPX4, FACL4, XCT4, and oxidative stress markers were evaluated. RESULTS: Overexpression of GDF15 greatly inhibited MIRI, improved cardiac function, alleviated MIRI-induced ferroptosis. pc-DNA-GDF15 significantly inhibited the oxidative stress condition and inflammation response. The OGD/R-induced ferroptosis was also inhibited by pc-DNA-GDF15. CONCLUSION: We proved that the MIRI-induced ferroptosis could by inhibited by pc-DNA-GDF15 through evaluating mitochondrial damage, MDA, GSH, and GSSG. Our research provides a new insight for the prevention and treatment of MIRI, and a new understanding for the mechanism of MIRI-induced ferroptosis.

Interleukin-33 as a Potential Diagnostic and Prognostic Factor in Human Brucellosis.

BACKGROUND: The balance between T-helper 1 (Th1) and T-helper 2 (Th2) cells plays an important role in the pathogenesis of brucellosis. Interleukin (IL)-33 induces the activation of Th2 cells while soluble suppression of tumorigenicity 2 (sST2) is a decoy receptor to antagonize the effect of IL-33. Herein, we aimed to identify whether plasma IL-33/sST2 levels could reflect the state of brucellosis and help to monitor the treatment. METHODS: A total of 78 patients were recruited and divided into acute, subacute, and chronic groups. The chronic group was further divided into chronic active brucellosis and chronic stable brucellosis according to the clinical manifestation. Twenty-six volunteers were assigned to the healthy control (HC) group. Plasma IL-33/sST2 levels were detected by enzyme linked immunosorbent assay (ELISA) and other routine laboratory parameters were obtained from the clinical central laboratory. RESULTS: The level of IL-33 in acute (49.48 ± 18.92), subacute (41.35 ± 17.12), chronic active (44.99 ± 16.80), and the chronic stable (28.92 ± 13.12) groups were higher than that in the HC group (11.66 ± 3.26) (p < 0.001). The IL-33 level in the acute group decreased significantly after treatment (49.48 ± 18.92 vs. 29.89 ± 12.92) (p < 0.001). Furthermore, the IL-33 level in the chronic active group (44.99 ± 16.80) was higher than that in the chronic stable group (28.92 ± 13.12) (p < 0.01). Interestingly, IL-33 correlated with white blood cells (WBC) (r = 0.268, p < 0.05) and C-reactive protein (CRP) (r = 0.272, p < 0.05). The level of sST2 increased in the acute (3,717.76 ± 2,036.25), subacute (3,130.41 ± 1,931.71), chronic active (3,381.43 ± 1,394.83), and the chronic stable group (2,707.03 ± 1,260.26) groups compared with the HC group (297.76 ± 290.93) (p < 0.001). However, the sST2 plasma level showed no differences among the groups and did not significantly change after treatment in the acute group. CONCLUSIONS: IL-33 can reflect the state of brucellosis and may be a potential biomarker for diagnosis and monitoring treatment for brucellosis.

Increased Plasma Levels of Heme Oxygenase-1 in Human Brucellosis.

BACKGROUND: Brucellosis is associated with inflammation and the oxidative stress response. Heme oxygenase-1 (HO-1) is a cytoprotective stress-responsive enzyme that has anti-inflammatory and anti-oxidant effects. Nevertheless, the role of HO-1 in human brucellosis has not yet been studied. The aim of this study was to examine the plasma levels of HO-1 in patients with brucellosis and to evaluate the ability of plasma HO-1 levels as an auxiliary diagnosis, a severity predictor, and a monitor for brucellosis treatments. METHODS: A total of 75 patients with brucellosis were divided into the acute, subacute, chronic active, and chronic stable groups. An additional 20 volunteers were included as the healthy control group. The plasma HO-1 levels and other laboratory parameters were measured in all groups. Furthermore, the plasma levels of HO-1 in the acute group were compared before and after treatment. RESULTS: The plasma HO-1 levels were considerably increased in the acute (4.97 ± 3.55), subacute (4.98 ± 3.23), and chronic active groups (4.43 ± 3.00) with brucellosis compared to the healthy control group (1.03 ± 0.63) (p < 0.01). In the acute group, the plasma HO-1 levels in the post-treatment group (2.33 ± 2.39) were significantly reduced compared to the pre-treatment group (4.97 ± 3.55) (p < 0.01). On the other hand, the plasma HO-1 levels were higher in the chronic active group (4.43 ± 3.00) than the chronic stable group (2.74 ± 2.23) (p < 0.05). However, the plasma HO-1 levels in the chronic stable group (2.74 ± 2.23) remained higher than the levels in the healthy control group (1.03 ± 0.63) (p < 0.05). The HO-1 levels were positively correlated with the C-reactive protein (CRP) levels in patients with brucellosis (r = 0.707, p < 0.01). CONCLUSIONS: The plasma HO-1 levels can reflect patients' brucellosis status and may be used as a supplementary plasma marker for diagnosing brucellosis and monitoring its treatment.

Autologous platelet­rich plasma promotes proliferation and chondrogenic differentiation of adipose­derived stem cells.

Cartilage regeneration is a promising potential therapy for articular cartilage defects and adult stem cells serve a key role in regenerative medicine. Adipose­derived stem cells (ADSCs) have been identified as an alternative source of adult stem cells in recent years and can be differentiated into numerous types of cell, including chondrocytes, adipocytes and osteoblasts. However, their clinical use is restricted by the proliferation of cells, and their tendency to dedifferentiate. Platelet­rich plasma (PRP) has recently emerged as a potential bioactive material to promote cell proliferation and differentiation, based on the release of growth factors. In the current study, the effect of autologous PRP on the proliferation and chondrogenic differentiation of ADSCs was examined. The results indicated that PRP promotes ADSC proliferation and suggested that PRP leads to chondrogenic differentiation of ADSCs in vitro. When co­cultured with chondrocytes, the ADSCs on three­dimensional PRP scaffolds were able to form neocartilage, with positive staining of safranine O, which indicated the production of glycosaminoglycan, and type II collagen.

[ARTHROSCOPIC SINGLE BUNDLE POSTERIOR CRUCIATE LIGAMENT RECONSTRUCTION USING HAMSTRING TENDONS THROUGH POSTERIOR TRANS-SEPTUM PORTAL APPROACH WITH PRESERVATION OF REMNANT POSTERIOR CRUCIATE LIGAMENT FIBERS].

OBJECTIVE: To introduce the arthroscopic single bundle posterior cruciate ligament (PCL) reconstruction using hamstring tendons through posterior trans-septum portal approach with preservation of the remnant PCL fibers, and to evaluate the clinical results. METHODS: Between June 2010 and April 2014, 57 patients with PCL rupture were treated with arthroscopic single bundle PCL reconstruction using hamstring tendons through posterior trans-septum portal approach with preservation of the remnant PCL fibers. There were 41 males and 16 females, aged 19-42 years (mean, 27.7 years). All the patients had history of injury. The results of posterior drawer test were positive, including 9 cases of grade II and 48 cases of grade III. The disease duration ranged from 2 weeks to 25 months (mean, 13 months). The Lysholm score and the range of motion of knee joint were used to evaluate the knee function. RESULTS: The operation performed smoothly, and no complications of blood vessel and nerve injuries and infection occurred. Primary healing was obtained in all incisions; no early complication occurred after operation. The patients were followed up 16.6 months on average (range, 12-20 months). At last follow-up, the knee range of motion returned to normal in all cases (120-130° in flexion). MRI at last follow-up showed good continuity of the PCL graft and complete healing of the remnant PCL tissues between the femoral and tibial attachments. The Lysholm score was significantly improved when compared with preoperative score (t= -27.429, P = 0.000). CONCLUSION: Arthroscopic single bundle PCL reconstruction using hamstring tendons through posterior trans-septum portal approach with preservation of the remnant PCL fibers has the advantages of firm fixation, simple operation, and good knee function recovery.

Arthroscopic tenodesis through positioning portals to treat proximal lesions of the biceps tendon.

Arthroscopic biceps tenodesis is a good choice for treating proximal lesions of the biceps tendon. However, there are few descriptions of the surgical approach. We introduce a technique for proximal biceps tenodesis using positioning portals and placing suture anchors. Our patients had a minimum of 12 months of follow-up. Between January 2010 and June 2012, a total of 49 patients (21 men, 28 women) underwent arthroscopic biceps tenodesis. The pathology was mainly associated with proximal lesions of the biceps tendon, with the diagnosis confirmed in all patients. Patients were evaluated preoperatively and then up to and including the final follow-up. Their pain and conditions were assessed using the Constant, American Shoulder and Elbow Surgeons (ASES), and University of California at Los Angeles (UCLA) scores for pain; range of active forward flexion; and active range of motion. All data were analyzed statistically. All patients were operated on successfully. They achieved good healing during the follow-up (mean 14 months; range 12-34 months). Before surgery the ASES, Constant, and UCLA scores were 17.0, 39.4, and 15.4, respectively. After surgery they were 33.6, 89.1, and 31.2, respectively. The scores had significantly improved: ASES scores from 17.0 to 33.6 (P < 0.05); Constant scores from 39.4 to 89.1 (P < 0.05); UCLA scores from 15.4 to 31.2 (P < 0.05). Arthroscopic tenodesis through positioning portals to treat proximal lesions of the biceps tendon produces satisfactory clinical outcomes. This technique is convenient and safe.

[Survey of infection of Toxoplasma gondii in infertile couples in Suzhou countryside].

OBJECTIVES: To determine the level of anti-Toxoplasma antibody in serum of infertile couples to explore the relationship between toxoplasma infection and infertility. METHODS: Enzyme-linked immunosorbent assay (ELISA) was applied to detect the anti-Toxoplasma antibody, antisperm antibody (AsAb) and anticardiolipin antibody (ACA) in serum of 178 couples with infertility and 190 couples who had normal pregnant history. RESULTS: The positive result of Toxoplasma infection in the infertile couples was significantly higher than that in fertile couples which was 34.83% vs 12.11% (chi 2 = 26.72, P < 0.01) with the odds ratio 3.88. The positive result of serum AsAb in the Toxoplasma infected group was significantly higher than that in the no Toxoplasma infected group (32.50% vs 15.94%, chi 2 = 10.76, P < 0.01) with the odds ratio 2.54. CONCLUSIONS: Toxoplasma infection was related to infertility. The Toxoplasma infection and was posibly related to the antisperm antibodies which can be involved in the pathogenisis of infertility.