Design of a Mechatronics Model of Urinary Bladder and Realization and Evaluation of Its Prototype.

Annually, there are many bladder cancer patients undergoing radical cystectomy (RC) with urinary diversion worldwide. Until 2019, intestinal cystoplasty is still the gold standard for bladder replacement, but this therapy is always associated with severe complications. An ideal bladder substitute without using intestinal tissue remains a challenge today. In this work, an artificial mechatronics bladder (AMB) as a brand new bladder replacement approach is developed. We studied the main physiological function characteristics of a natural urinary bladder from teaching books and relevant papers. According to these characteristics, we completed an overall design of AMB and made a prototype in lab. The prototype successfully realized the functions of a natural bladder in vitro. It can expand to store urine in real time when urine is flowing into it. It can send a urination alarm when it is fully filled and can void urine automatically after receiving remote control signals. According to relevant papers and our test experience, if the prototype could be smaller and lighter and manufactured with good biocompatibility materials such as PTFE, we think it is possible for AMB to be implanted in an animal's body, and we deduce AMB could realize the functions of a natural urinary bladder in vivo. After thorough validation from animal testing, we hope AMB can be a good clinical option for bladder removal patients in the future.

Anti-Interleukin-1 Beta/Tumor Necrosis Factor-Alpha IgY Antibodies Reduce Pathological Allergic Responses in Guinea Pigs with Allergic Rhinitis.

This study aims to determine whether the combined blockade of IL-1ß and TNF-α can alleviate the pathological allergic inflammatory reaction in the nasal mucosa and lung tissues in allergic rhinitis (AR) guinea pigs. Healthy guinea pigs treated with saline were used as the healthy controls. The AR guinea pigs were randomly divided into (1) the AR model group treated with intranasal saline; (2) the 0.1% nonspecific IgY treatment group; (3) the 0.1% anti-TNF-α IgY treatment group; (4) the 0.1% anti-IL-1ß IgY treatment group; (5) the 0.1% combined anti-IL-1ß and TNF-α IgY treatment group; and (6) the fluticasone propionate treatment group. The inflammatory cells were evaluated using Wright's staining. Histopathology was examined using hematoxylin-eosin staining. The results showed that the number of eosinophils was significantly decreased in the peripheral blood, nasal lavage fluid, and bronchoalveolar lavage fluid (P < 0.05), and eosinophil, neutrophil, and lymphocyte infiltration and edema were significantly reduced or absent in the nasal mucosa and lung tissues (P < 0.05) in the combined 0.1% anti-IL-1ß- and TNF-α IgY-treated guinea pigs. The data suggest that topical blockade of IL-1ß and TNF-α could reduce pathological allergic inflammation in the nasal mucosa and lung tissues in AR guinea pigs.

Therapeutic potential of combined anti-IL-1ß IgY and anti-TNF-α IgY in guinea pigs with allergic rhinitis induced by ovalbumin.

We have previously demonstrated that anti-IL-1ß immunoglobulin yolk(IgY) inhibits pathological responses in allergic asthma guinea pigs induced by ovalbumin(OVA). This study aims to determine whether the combined blockade of IL-1ß and TNF-α can more effectively inhibit allergic inflammation in allergic rhinitis(AR) guinea pigs induced by OVA. Healthy guinea pigs treated with saline were used as the healthy control. The AR guinea pigs induced by OVA were randomly divided into (1) the AR model group containing negative control animals treated with intranasal saline; (2) the 0.1% non-specific IgY treatment group treated with non-specific IgY; (3) the 0.1% anti-TNF-α IgY treatment group treated with 0.1% anti-TNF-α IgY; (4) the 0.1% anti-IL-1ß IgY treatment group treated with 0.1% anti-IL-1ß IgY; (5) the 0.1% combined anti-IL-1ß IgY and anti-TNF-α IgY treatment group treated with 0.1% combined anti-IL-1ß IgY and anti-TNF-α IgY; and (6) the fluticasone propionate treatment group treated with fluticasone propionate. Cytokines were measured using an enzyme-linked immunosorbent assay. The results showed that IL-1ß, IL-5, IL-9, IL-13, IL-18, IL-22, IL-33, TNF-α, TGF-ß1 and OVA-specific IgE levels in the peripheral blood (PB) and nasal lavage fluid (NLF) significantly decreased at 2h, 4h or 8h in the 0.1% combined anti-IL-1ß IgY and anti-TNF-α IgY treatment group compared to the AR model group and the 0.1% non-specific IgY treatment group (P<0.05). The data suggest that blockade of IL-1ß and TNF-α by intranasal instillation of combined anti-IL-1ß IgY and anti-TNF-α IgY could be a potential alternative strategy for preventing and treating allergic rhinitis.

Therapeutic potential of anti-IL-1ß IgY in guinea pigs with allergic asthma induced by ovalbumin.

BACKGROUND: Interleukin-1 beta (IL-1ß) plays pivotal roles in the progression of allergic airway inflammation. This study aims to determine whether the blockade of IL-1ß can inhibit airway inflammation in guinea pigs with allergic asthma induced by the inhalation of aerosolized ovalbumin (OVA). METHODS: Healthy guinea pigs treated with saline were used as normal controls (group C). The guinea pigs with allergic asthma induced by the inhalation of aerosolized OVA were randomly divided into three groups: (1) the M group containing negative control animals treated with saline; (2) the Z1 group containing animals treated by the inhalation of atomized 0.1% anti-IL-1ß immunoglobulin yolk (IgY); and (3) the Z2 group containing positive control animals that were treated with budesonide. The inflammatory cells in the peripheral blood (PB) and bronchoalveolar lavage fluid (BALF) were evaluated using methylene blue and eosin staining. Cytokine concentrations were measured using an enzyme-linked immunosorbent assay. Pulmonary sections were examined using hematoxylin-eosin staining. RESULTS: Allergic inflammation and damage to the pulmonary tissues were decreased in the Z1 group compared to the M group. Eosinophils and neutrophils in the PB and BALF were significantly decreased in the Z1 group compared to the M group (P<0.05). Treatment with anti-IL-1ß IgY significantly reduced the levels of IL-1ß, IL-4, IL-8, IL-13, TNF-α, TGF-ß1 and IgE in the BALF (P<0.05). CONCLUSION: The inhalation of aerosolized anti-IL-1ß IgY inhibits pathological responses in the pulmonary tissues of guinea pigs with allergic asthma. The inhibitory activity may be due to the decrease in the numbers of eosinophils and neutrophils and the reduced levels of inflammatory cytokines and IgE in the PB and BALF.

Calcitriol restores renovascular function in estrogen-deficient rats through downregulation of cyclooxygenase-2 and the thromboxane-prostanoid receptor.

Cardiovascular risks increase in postmenopausal women. While vitamin D is supplemented for osteoporosis, it is not known whether it protects renal arterial function during estrogen deficiency. Here we measured changes in renovascular reactivity induced by ovariectomy in rats and examined whether calcitriol, the most active form of vitamin D, was able to correct such changes. The impairment of endothelium-dependent relaxation in renal arteries from ovariectomized rats was effectively reversed by long-term calcitriol treatment. It was also corrected by acute exposure to cyclooxygenase-2 (COX-2) inhibitors and a thromboxane-prostanoid receptor antagonist, respectively. Calcitriol normalized the overexpression of COX-2 and thromboxane-prostanoid receptors in intralobal renal artery segments and aortic endothelial cells isolated from ovariectomized rats. In vitro exposure of the arterial segments to calcitriol for 12 h improved relaxation and downregulated thromboxane-prostanoid receptors. The attenuated nitric oxide production in ovariectomized rat aortic endothelial cells was restored following a 12-h treatment with calcitriol, COX-2 inhibition, or thromboxane-prostanoid receptor antagonism. Thus, impaired endothelium-dependent renal artery relaxation in ovariectomized rats is mediated largely through increased activity and expression of COX-2 and the thromboxane-prostanoid receptor. Calcitriol restores endothelial function through downregulating both signaling proteins during estrogen deficiency.

Suppression of EBNA1 expression inhibits growth of EBV-positive NK/T cell lymphoma cells.

Extranodal nasal-type NK cell lymphoma (ENKL) is a high-grade malignancy and associated with EBV latent infection. An optimal therapy has not been discovery. Here, we investigated whether cell proliferation was inhibited by silencing Epstein-Barr virus nuclear antigen 1 (EBNA1) using RNA interference (RNAi) method in an EBV-positive ENKL cell line, HANK1 cells. We found that silencing EBNA1 expression by RNAi strategy inhibited cell growth and increased the expression of p27 protein and caused cell cycle arrest at G(1)-phase in HANK1 cells. In conclusions, low-level expression of p27 protein may partially attribute to latent EBV infection in ENKL. EBNA1 may be a good target for the treatment of EBV associated ENKL.

Skp2/p27 expression profile is correlated with Epstein-Barr virus status in extranodal nasal-type natural killer cell lymphoma.

Extranodal nasal-type natural killer cell lymphoma (ENKL) is a high-grade malignancy and is associated with Epstein-Barr virus (EBV) latent infection. Little is known about its molecular abnormalities. Here, we studied the expression of Skp2 and p27 proteins in 48 cases of ENKL, and we evaluated their correlations with EBV status and clinical outcomes. EBV infection was observed in 90% of the cases. In all, 71% of the ENKLs were positive to Skp2 and 73% were negative to p27. A significant negative correlation was observed between the expression of Skp2 and p27 proteins (P = 0.022). Fifty-eight percent of the cases were Skp2+/p27- phenotype and correlated with EBV status (P = 0.047). The overall survival was influenced by the expression of Skp2, p27, and Skp2/p27. Patients with Skp2+, p27-, and Skp2+/p27- phenotypes had worse overall survival (P < 0.01, P = 0.016, and P < 0.01, respectively). Multivariance analysis showed the Skp2/p27 expression profile was an independent prognostic factor for overall survival (RR = 3.09, P < 0.01, 95% CI: 1.27-7.51). In conclusion, the Skp2/p27 expression profile is a helpful prognostic factor for ENKL. Latent EBV infection may increase the expression levels of Skp2, and consequently, p27 protein degradation is accelerated. EBV may be a good target for treatment of EBV-associated ENKL.