The VraSR two-component signal transduction system contributes to the damage of blood-brain barrier during Streptococcus suis meningitis.

Streptococcus suis (S. suis) is an important zoonotic pathogen that can cause high morbidity and mortality in both humans and swine. As the most important life-threatening infection of the central nervous system (CNS), meningitis is an important syndrome of S. suis infection. The vancomycin resistance associated sensor/regulator (VraSR) is a critical two-component signal transduction system that affects the ability of S. suis to resist the host innate immune system and promotes its ability to adhere to brain microvascular endothelial cells (BMECs). Prior work also found mice infected with ΔvraSR had no obvious neurological symptoms, unlike mice infected with wild-type SC19. Whether and how VraSR participates in the development of S. suis meningitis remains unknown. Here, we found ΔvraSR-infected mice did not show obvious meningitis, compared with wild-type SC19-infected mice. Moreover, the proinflammatory cytokines and chemokines in serum and brains of ΔvraSR-infected mice, including IL-6, TNF-α, MCP-1 and IFN-γ, were significantly lower than wild-type infected group. Besides, blood-brain barrier (BBB) permeability also confirmed that the mutant had lower ability to disrupt BBB. Furthermore, in vivo and in vitro experiments showed that SC19 could increase BBB permeability by downregulating tight junction (TJ) proteins such as ZO-1, ß-Catenin, Occludin, and Clauidn-5, compared with mutant ΔvraSR. These findings provide new insight into the influence of S. suis VraSR on BBB disruption during the pathogenic process of streptococcal meningitis, thereby offering potential targets for future preventative and therapeutic strategies against this disease.

Impact of bone marrow mesenchymal stem cell immunomodulation on the osteogenic effects of laponite.

BACKGROUND: With the development of osteoimmunology and bone tissue engineering (BTE), it has been recognized that the immunomodulatory properties of bone biomaterials have considerable impact in determining their fate after implantation. In this regard, the polarization of macrophages secondary to biomaterials is postulated to play a crucial role in modulating their osteogenesis; thus, strategies that may facilitate this process engender increasing levels of attention. Whereas a variety of reports highlight the immunomodulation of bone marrow mesenchymal stem cells (BMSCs) in cell therapy or their osteogenesis in BTE, few have focused on the effect of BMSCs in promoting osteogenesis in BTE through regulating the phenotype of macrophages. Accordingly, there is an urgent need to clarify the immunomodulatory properties of agents such as laponite (Lap), which is comprised of bioactive silicate nanoplatelets with excellent osteogenesis-inducing potential, to enhance their use in BTE. METHODS: In the present study, we analyzed the osteoimmunomodulatory properties of Lap alone, as well as following the introduction of BMSCs into Lap, to determine whether BMSCs could modulate its immunomodulatory properties and promote osteogenesis. RESULTS: It was found that the BMSCs reversed the polarization of murine-derived macrophage RAW 264.7 cells from M1 as induced by pure Lap to M2 and promoted osteogenesis. In vivo study confirmed that BMSCs combined with Lap initiated a less severe immune response and had an improved effect on bone regeneration compared with Lap alone, which corresponded with the in vitro evaluation. CONCLUSION: These results suggest that BMSCs could ameliorate the inflammation induced by Lap and enhance its bone formation. The immunomodulatory characteristics of BMSCs suggest that these might be tailored as a new strategy to promote the osteogenic capacity of biomaterials.

Three-dimensional vs two-dimensional video assisted thoracoscopic esophagectomy for patients with esophageal cancer.

AIM: To define the benefits of three-dimensional video-assisted thoracoscopic esophagectomy (3D-VATE) over 2D-VATE for esophageal cancer. METHODS: A total of 93 patients with esophageal cancer including 45 patients receiving 3D-VATE and 48 receiving 2D-VATE were evaluated. Data related to patient and cancer characteristics, operating time, intraoperative bleeding, morbidity and mortality, postoperative inflammatory markers, Numerical Rating Scale for postoperative pain, Constant-Murley rating system for shoulder recovery and oxygenation index (OI) were collected. All medical records were retrieved from a prospectively maintained oncological database at our institution. A retrospective study was performed to compare the short-term surgical outcomes between the two groups. RESULTS: No significant differences were found between the two groups in either morbidity or mortality (P = 0.328). An enhanced surgical recovery was noted in the 3D group as indicated by shortened thoracoscopic operation time (3D vs 2D: 68 ± 13.79 min vs 83 ± 13 min, P < 0.01), minor intraoperative blood loss (3D vs 2D: 68.2 ± 10.7 mL vs 89.8 ± 10.4 mL, P < 0.01), earlier chest tube removal (3D vs 2D: 2.67 ± 1.01 vs 3.75 ± 1.15 d, P < 0.01), shorter length of hospital stay (3D vs 2D: 9.07 ± 2.00 vs 10.85 ± 3.40 d, P < 0.01), lower in-hospital expenses (3D vs 2D: 74968.4 ± 9637.8 vs 86211.1 ± 8519.7 RMB, P < 0.01), lower pain intensity (P < 0.01) and faster recovery of the left shoulder function (P < 0.01). Better preservation of the pulmonary function was also found in the 3D group as the decline of the OI post operation was significantly lower than that of the 2D group (P < 0.01). Changes of postoperative inflammatory markers, including procalcitonin [postoperative days (PODs) 4 and 7: P < 0.01], peripheral granulocytes (PODs 1, 4 and 7: P < 0.01) and hypersensitive C-reactive protein (POD 4: P < 0.01) in 3D-VATE patients were less than those in the 2D group. Moreover, utilization of the 3D technique extended the dissection of the thoracic lymph nodes (P < 0.01), with better exposure of nodes in the left recurrent laryngeal nerve (P = 0.031). CONCLUSION: 3D-VATE could be a more viable technique over 2D-VATE in terms of short-term outcomes for patients with esophageal cancer.