Protective role of exosomes derived from regulatory T cells against inflammation and apoptosis of BV-2 microglia under oxygen-glucose deprivation/reperfusion challenge.

Regulatory T cells (Tregs) are found to participate in the pathogenesis of cerebral ischemic stroke. Exosomes derived from Tregs (Treg-Exos) were found to mediate the mechanism of Tregs' roles under various physiological and pathological conditions. But the roles of Treg-Exos in cerebral ischemic stroke are still unclear. Here, we explored the protective effects of Treg-Exos against microglial injury in response to oxygen-glucose deprivation/reperfusion (OGD/R) exposure. The results showed that Tregs-Exos relieved OGD/R-caused increases in LDH release and caspase-3 activity in BV-2 cells. The decreased cell viability and increased percentage of TUNEL-positive cells in OGD/R-exposed BV-2 cells were attenuated by Tregs-Exos treatment. Tregs-Exos also suppressed OGD/R-induced increase in production of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 in BV-2 microglia. Furthermore, Tregs-Exos induced the expression levels of phosphorylated phosphatidylinositol-3-kinase (p-PI3K) and phosphorylated protein kinase B (p-Akt) in BV-2 microglia under the challenge of OGD/R. Inhibition of the PI3K/Akt signaling by LY294002 partly reversed the effects of Tregs-Exos on cell apoptosis and inflammation in OGD/R-exposed BV-2 microglia. These results indicated that Tregs-Exos exerted protective effects against the OGD/R-caused injury of BV-2 microglia by activating the PI3K/Akt signaling.

Protective Effects of Shrimp Peptide on Dextran Sulfate Sodium-Induced Colitis in Mice.

Inflammatory bowel disease, an intestinal relapsing inflammatory disease, not only impairs gastrointestinal function but also increases the chances of developing colon cancer. Currently, the effects of shrimp peptide (SP) in mice model of ulcerative colitis (UC) are still unclear. In particular, it is uncertain whether SP affects the gut flora with UC mice. In this study, we investigated the anti-inflammatory effects of SP on a dextran sulfate sodium (DSS)-induced mouse model of UC. Firstly, the molecular weight of SP was mainly distributed in the range of 180-1,000 Da (61.95% proportion), and the amino acid composition showed that SP contained 17 amino acids, of which, the essential amino acids accounted for 54.50%. In vivo, oral SP significantly attenuated the severity of colitis, such as diarrhea, weight loss, and rectal bleeding. Furthermore, treatment with SP remarkably ameliorated intestinal barrier integrity, thus lowering the levels of the inflammatory cytokines and ameliorating antioxidant indices and intestinal injury indicators in the serum and colon. Lastly, the cecal contents were used to sequence and analyze the 16S rRNA genes of bacteria. Results suggested that treatment with SP could restore the balance of intestinal flora in modeled mice by regulating the abundance of pathogenic and beneficial bacteria. Furthermore, SP could significantly improve intestinal flora dysfunction in mice with UC. In summary, our findings show that SP has a prophylactic and therapeutic effect in UC in vivo, thereby highlighting its broad medicinal applications.

Concentrations and Related Health Risk Assessment of Pesticides, Phthalates, and Heavy Metals in Strawberries from Shanghai, China.

ABSTRACT: In the present study, a risk assessment of pesticides, phthalates, and heavy metals in strawberries (n = 335) in recent years was conducted by determining the estimated daily intake, target hazard quotient, and hazard index. The study used 128 pesticides, 18 phthalates, and three heavy metals in this determination. It detected 51 pesticide residues in the strawberry samples, and 97.91% samples had levels of at least 1 of the 51 pesticides above the limit of detection. In addition, 2.39% of samples had pesticides higher than the Chinese maximum residue limit. Multiple pesticide residues were detected in most samples. Bis-2-ethylhexyl phthalate, diisobutyl phthalate, and dibutyl phthalate were detected in the strawberry samples, with a high frequency of detection. Their detectable rates were 100, 100, and 89.9%, respectively. In most samples, lead, cadmium, and nickel were detected, with detectable rates 75.76, 92.93, and 92.93%, respectively. The estimated daily intake of analyzed pesticide, phthalate, and heavy metal residues appears to be relatively low compared with the acceptable daily intake. The average target hazard quotients and hazard indices were less than 1. That means that customers who are exposed to the average contaminant levels may not pose a significant health risk. Our results show that the strawberries may be polluted by many kinds of contaminants. Therefore, monitoring of pesticide, phthalate, and heavy metal residues in strawberries should be increasingly developed to fully protect the health of the consumer.

Effect of exogenous spastin combined with polyethylene glycol on sciatic nerve injury.

Polyethylene glycol can connect the distal and proximal ends of an injured nerve at the cellular level through axonal fusion to avoid Wallerian degeneration of the injured distal nerve and promote peripheral nerve regeneration. However, this method can only prevent Wallerian degeneration in 10% of axons because the cytoskeleton is not repaired in a timely fashion. Reconstruction of the cytoskeletal trunk and microtubule network has been suggested to be the key for improving the efficiency of axonal fusion. As a microtubule-severing protein, spastin has been used to enhance cytoskeletal reconstruction. Therefore, we hypothesized that spastin combined with polyethylene glycol can more effectively promote peripheral nerve regeneration. A total of 120 male Sprague-Dawley rats were randomly divided into sham, suture, polyethylene glycol, and polyethylene glycol + spastin groups. In suture group rats, only traditional nerve anastomosis of the end-to-end suture was performed after transection of the sciatic nerve. In polyethylene glycol and polyethylene glycol + spastin groups, 50 µL of polyethylene glycol or 25 µL of polyethylene glycol + 25 µL of spastin, respectively, were injected immediately under the epineurium of the distal suture. Sensory fiber regeneration distance, which was used to assess early nerve regeneration at 1 week after surgery, was shortest in the suture group, followed by polyethylene glycol group and greatest in the polyethylene glycol + spastin group. Behavioral assessment of motor function recovery in rats showed that limb function was restored in polyethylene glycol and polyethylene glycol + spastin groups at 8 weeks after surgery. At 1, 2, 4 and 8 weeks after surgery, sciatic functional index values and percentages of gastrocnemius muscle wet weight were highest in the sham group, followed by polyethylene glycol + spastin and polyethylene glycol groups, and lowest in the suture group. Masson staining was utilized to assess the morphology of muscle tissue. Morphological changes in skeletal muscle were detectable in suture, polyethylene glycol, and polyethylene glycol + spastin groups at 1, 2, 4, and 8 weeks after surgery. Among them, muscular atrophy of the suture group was most serious, followed by polyethylene glycol and polyethylene glycol + spastin groups. Ultrastructure of distal sciatic nerve tissue, as detected by transmission electron microscopy, showed a pattern of initial destruction, subsequent disintegration, and gradual repair in suture, polyethylene glycol, and polyethylene glycol + spastin groups at 1, 2, 4, and 8 weeks after surgery. As time proceeded, axonal ultrastructure gradually recovered. Indeed, the polyethylene glycol + spastin group was similar to the sham group at 8 weeks after surgery. Our findings indicate that the combination of polyethylene glycol and spastin can promote peripheral nerve regeneration. Moreover, the effect of this combination was better than that of polyethylene glycol alone, and both were superior to the traditional neurorrhaphy. This study was approved by the Animal Ethics Committee of the Second Military Medical University, China (approval No. CZ20170216) on March 16, 2017.

Long-term outcome of infliximab combined with surgery for perianal fistulizing Crohn's disease.

AIM: To evaluate the efficacy and long-term outcome of infliximab combined with surgery to treat perianal fistulizing Crohn's disease (CD). METHODS: The work was performed as a prospective study. All patients received infliximab combined with surgery to treat perianal fistulizing CD, which was followed by an immunosuppressive agent as maintenance therapy. RESULTS: A total of 28 patients with perianal fistulizing CD were included. At week 30, 89.3% (25/28) of the patients were clinically cured with an average healing time of 31.4 d. The CD activity index decreased to 70.07±77.54 from 205.47±111.13 (P<0.01) after infliximab treatment. The perianal CD activity index was decreased to 0.93±2.08 from 8.54±4.89 (P<0.01). C-reactive protein, erythrocyte sedimentation rate, platelets, and neutrophils all decreased significantly compared with the pretreatment levels (P<0.01). Magnetic resonance imaging results for 16 patients after therapy showed that one patient had a persistent presacral-rectal fistula and another still had a cavity without clinical symptoms at follow-up. After a median follow-up of 26.4 mo (range: 14-41 mo), 96.4% (27/28) of the patients had a clinical cure. CONCLUSION: Infliximab combined with surgery is effective and safe in the treatment of perianal fistulizing CD, and this treatment was associated with better long-term outcomes.

Decreasing pro-inflammatory cytokine and reversing the immunosenescence with extracts of Pu-erh tea in senescence accelerated mouse (SAM).

Immunosenescence, the progressive decline of adaptive immunity and chronic inflammation with ageing has been demonstrated to be the main factor responsible for infections, cancer and autoimmune conditions in the elderly. Senescence-accelerated mouse (SAM) was used to study the protective effects of Pu-erh tea in the elderly. The senile-prone sub-strain, SAM-P8 mice were administered individually with ripened or crude Pu-erh tea at 125, 250 or 500mg/kg. The results showed that Pu-erh tea significantly increased the fractions of naïve T lymphocytes, CD8(+)CD28(+) T lymphocytes and NK cells in the peripheral blood, but decreased the levels of IL-6 in aged mice. These data suggested that the Pu-erh tea reversed the immunosenescence by restoring the immune deficiency and decreasing pro-inflammatory cytokine. Thus, long term drinking of Pu-erh tea may be beneficial for the aged population in terms of increasing the body's resistance to infection and cancer.

Retrorectal tumors in adults: magnetic resonance imaging findings.

AIM: To retrospectively evaluate the magnetic resonance imaging (MRI) features of adult retrorectal tumors and compare with histopathologic findings. METHODS: MRI features of 21 patients with preoperative suspicion of retrorectal tumors were analyzed based on the histopathological and clinical data. RESULTS: Fourteen benign cystic lesions appeared hypointense on T1-weighted images, and hyperintense on T2-weighted images with regular peripheral rim. Epidermoid or dermoid cysts were unilocular, and tailgut cysts were multilocular. Presence of intracystic intermediate signal intensity was observed in one case of tailgut cyst with a component of adenocarcinoma. Six solid tumors were malignant lesions and showed heterogeneous intensity on MRI. Mucinous adenocarcinomas showed high signal intensity on T2-weighted and mesh-like enhancing areas on fat-suppressed T2-weighted images. There was a fistula between the mass and anus with an internal opening in mucinous adenocarcinomas arising from anal fistula. Gastrointestinal stromal tumors displayed low signal intensity on T1-weighted images, and intermediate to high signal intensity on T2-weighted images. Central necrosis could be seen as a high signal on T2-weighted images. CONCLUSION: MRI is a helpful technique to define the extent of the retrorectal tumor and its relationship to the surrounding structures, and also to demonstrate possible complications so as to choose the best surgical approach.

Perianal mucinous adenocarcinoma arising from chronic anorectal fistulae: a review from single institution.

BACKGROUND: Mucinous adenocarcinoma arising from a chronic anorectal fistula is rare, with few reports in the literature. Such lesions can be misdiagnosed for the more common benign perianal abscess or fistula. METHODS: From our retrospective chart review, we identified three patients with chronic perianal fistula-in-ano who were subsequently found to have developed perianal mucinous adenocarcinoma on biopsy. We recorded the symptomatology, subsequent management and further follow-up of each patient. RESULTS: Two of three patients who received irradiation and chemotherapy were still alive during 28 and 24 months of follow-up, respectively without any evidence of distant metastasis. One patient with inguinal lymph node metastases died due to distant metastasis 6 months after diagnosis. CONCLUSIONS: Fistula-associated perianal mucinous adenocarcinoma is an uncommon malignant transformation of chronic fistula-in-ano. MRI can provide important diagnostic information on patient with this suspicious inflammatory condition. Although radical resection of the tumour with abdominoperineal resection remains the surgical treatment of choice. Combined chemoradiotherapy may be appropriate for these patients with promising results.

[Application of magnetic resonance imaging in the diagnosis of complex anal fistula].

OBJECTIVE: To evaluate the value of magnetic resonance imaging (MRI) in the diagnosis of complex anal fistula. METHODS: The preoperative digital examination and MRI with the phased-array coil were implemented for 28 patients who were clinically suspected with complex anal fistula. The final diagnosis were based on surgical findings. Outcomes of MRI and digital examination were compared with surgical results. RESULTS: Twenty-five patients were diagnosed as complex anal fistula, 1 presacral cyst and 2 chronic anorectal fistula combined with perianal mucinous adenocarcinoma. All the patients were correctly diagnosed by MRI,while the patients with presacral cyst and perianal mucinous adenocarcinoma could not be diagnosed correctly by digital examination. According to the Parks classification, 3 patients were suffered from trans-sphincteric fistula, 10 intersphincteric, 5 supra- sphincteric and 7 extra-sphincteric. The diagnosis rates of the internal opening with digital examination and MRI were 48% and 84%, the rates of the primary tract were 76% and 100%, and the rates of the secondary extensions were 57.9% and 94.7% respectively. The differences in detection of internal opening, primary tract and secondary extensions between MRI and digital examination were significant (P<0.01). CONCLUSION: MRI with the phased-array coil can correctly orient the internal opening and direction of the complex anal fistula, and find the relationship between anorectal sphincters and the complex fistula.