Influence of the brain­gut axis on neuroinflammation in cerebral ischemia­reperfusion injury (Review).

Stroke, a debilitating cerebrovascular ailment, poses significant threats to human life and health. The intricate interplay between the gut­brain­microbiota axis (GBMA) and cerebral ischemia­reperfusion has increasingly become a focal point of scientific exploration, emerging as a pivotal research avenue in stroke pathophysiology. In the present review, the authors delved into the nexus between the GBMA and neuroinflammation observed post­stroke. The analysis underscored the pivotal roles of histone deacetylase 3 and neutrophil extracellular traps subsequent to stroke incidents. The influence of gut microbial compositions and their metabolites, notably short­chain fatty acids and trimethylamine N­oxide, on neuroinflammatory processes, was further elucidated. The involvement of immune cells, especially regulatory T­cells, and the intricate signaling cascades including cyclic GMP­AMP synthase/stimulator of interferon genes/Toll­like receptor, further emphasized the complex regulatory mechanisms of GBMA in cerebral ischemia/reperfusion injury (CI/RI). Collectively, the present review offered a comprehensive perspective on the metabolic, immune and inflammatory modulations orchestrated by GBMA, augmenting the understanding of its role in neuroinflammation following CI/RI.

Diprotin A TFA Exerts Neurovascular Protection in Ischemic Cerebral Stroke.

Background: It has been established that the dipeptidyl peptidase-4 (DPP-4) inhibitor Diprotin A TFA can reduce vascular endothelial (VE)-cadherin disruption by inhibiting the increase in cleaved ß-catenin in response to hypoxia, thereby protecting the vascular barrier of human umbilical vein endothelial cells. In this study, we sought to investigate the possible effect of Diprotin A TFA on the VE barrier after cerebral ischemic stroke in mice. Methods: C57BL/6J mice were divided into five groups, namely, (1) sham, (2) stroke, (3) stroke + dimethyl sulfoxide (DMSO), (4) stroke + Diprotin A TFA, and (5) stroke + Diprotin A TFA + XAV-939. First, the cerebral ischemia model was established by photothrombotic ischemia, followed by intraperitoneal injection with Diprotin A TFA and XAV-939 at doses of 70 µg/kg and 40 mg/kg 30 min once in the morning and once in the evening for 3 days. Immunofluorescence staining and Western blot methods were used to analyze the expression of vascular and blood-brain barrier (BBB)-associated molecular markers in the peri-infarct area. Results: Compared with the vehicle control group, we found that mice injected with Diprotin A TFA exhibited reduced cerebral infarction volume, increased vascular area and length around the brain injury, increased pericyte and basement membrane coverage, upregulated expression of BBB tight junction proteins, and improved their BBB permeability, whereas the group injected with both drug and inhibitor exhibited significantly aggravated vascular injury and BBB permeability. Conclusion: Diprotin A TFA can reduce VE-cadherin disruption by inhibiting ischemia-hypoxia-induced ß-catenin cleavage to protect blood vessels.

[Effect of P53 Expression on Prognosis of Patients with Double Expressor Lymphoma].

OBJECTIVE: To investigate the effect of P53 expression on prognosis of patients with double expressor lymphoma(DEL) and the interaction between the expression of MYC, BCL2 and P53 in diffuse large B-cell lymphoma(DLBCL). METHODS: Eighty-eight patients with newly diagnosed DLBCL from 1st September 2012 to 31th May 2018 in Shanxi Dayi Hospital affiliated to Shanxi Medical University were selected. The expressions of MYC、BCL2、P53、CD10、BCL6、MUM and Ki-67 were tested by immunohistochemistry method. The overall survival of patients was analyzed by the Kaplan-Meier method and compared by the log-rank test. The prognostic effect of MYC, BCL2 and P53 expression was analyzed by univariate and multivariate analysis. RESULTS: Compared with patients without P53 expression, the patients with P53 expression had higher LDH level, higher NCCN-IPI scores, lower response to chemotherapy，poorer overall survival(OS) and a higher rate of death(P<0.05). In patients who had diffuse large B-cell lymphoma associated with MYC, BCL2 expression or MYC+/BCL2+ double expression， compared with the patients whom without P53 expression, P53 expression associated with a significant worse OS (P<0.05). The patients with concurrent MYC and P53 expression had a worse OS, compared with patients with either P53 or MYC expression(P<0.05). In patients with MYC+/P53+ co-expression, BCL2 expression did not correlate with poorer survival significantly(P>0.05). Among lymphoma patients with MYC+/P53+, MYC+/BCL2+ and BCL2+/P53+ co-expression, the patients with MYC+/P53+ co-expression had the worse OS (3 year OS rate：31.6%), followed by the subgroup of patients with MYC-/BCL2+/P53+(3 year OS rate：46.2%), patients with MYC+/BCL2+/P53- expression(3 year OS rate： 636%) showed a longer OS compared with the other two subgroups（P<0.05）. Multivariate analysis demonstrated that P53 expression and NCCN-IPI were independent prognostic factors in this patient cohort. CONCLUSION: P53 and MYC expressions have a synergistically negative prognostic effect in DLBCL patients. P53 expression augments the negative prognostic effect of MYC+/BCL2+ double expression. Patients with MYC+/P53+ co-expression have a worse prognosis in comparison with the patients with MYC+/BCL2+ double expression.

Efficacy and Safety of Multiband Mucosectomy Versus Cap-assisted Endoscopic Resection For Early Esophageal Cancer and Precancerous Lesions: A Systematic Review and Meta-Analysis.

BACKGROUND: The effectiveness of multiband mucosectomy (MBM) for early esophageal cancer and precancerous lesions is still in uncertainty. We aimed to evaluate the efficacy and safety of this procedure and to compare it with cap-assisted endoscopic resection (EMR-cap). METHODS: A systematic search of both English and Chinese databases was performed from inception to April 30, 2019. Complete resection rate, local recurrence rate, and procedure time were considered the primary outcome measures. Prevalence of complications was considered the secondary outcome measure. All data analyses were performed using Review Manager Software. RESULTS: Two randomized controlled trials (RCTs) and 3 non-RCTs were included in the final meta-analysis. When compared with the EMR-cap technique, MBM had a similar complete resection rate [odds ratio (OR)=2.09, 95% confidence interval (CI): 0.78-5.60, P=0.14], a similar local recurrence rate (OR=0.50, 95% CI: 0.09-2.67, P=0.42), a shorter resection time (mean difference: -9.08, 95% CI: -13.86 to -4.30, P=0.0002), a shorter procedure time (mean difference: -13.36, 95% CI: -17.85 to -8.86, P<0.00001), a lower bleeding rate (OR=0.45, 95% CI: 0.24-0.83, P=0.01), a similar perforation rate (OR=0.55, 95% CI: 0.15-2.06, P=0.37), and a similar stricture rate (OR=0.77, 95% CI: 0.10-5.84, P=0.80). The results of non-RCTs were consistent with those of RCTs. CONCLUSIONS: MBM is similar to EMR-cap in terms of efficacy and safety for endoscopic resection of early cancer and precancerous lesions of the esophagus. However, MBM is less time-consuming.

Repression of Slc24a5 can reduce pigmentation in chicken.

Slc24a5 is a putative cation transporter, which is a member of the potassium-dependent sodium-calcium ion exchanger family. Association of the Slc24a5 gene with pigmentation has been established in Zebrafish, mice and humans. Despite these findings, its function in chicken remains unknown. The intent of this study was to describe the association of Slc24a5 with respect to melanin deposition in the chicken using RNAi. The objective was to detect the variety of melanin deposition caused by the down-regulation of Slc24a5 in chicken retinal pigment epithelium (RPE) cells. Nine siRNAs that targeted against Slc24a5 mRNA were found to be effective in suppressing Slc24a5 gene expression in 293FT cells. The most effective target tested effectively inhibited Slc24a5 expression in mRNA and subsequently reduced protein levels in RPE cells. These results show that down-regulation of Slc24a5 results in a reduction of melanin content, as well as a decrease of melaeneous type ß and type χ melanosomes simultaneously. Taken together, this work suggests that Slc24a5 function is conserved in the chicken, and necessary for melanin synthesis.

Remarkable reduction of irreversible fouling and improvement of the permeation properties of poly(ether sulfone) ultrafiltration membranes by blending with pluronic F127.

Hydrophilic modification of ultrafiltration membranes was achieved through blending of Pluronic F127 with poly(ether sulfone) (PES). The chemical composition and morphology changes of the membrane surface were confirmed by water contact angle, X-ray photoelectron spectroscopy, scanning electron microscopy, and protein adsorption measurements. The decreased static water contact angle with an increase in the Pluronic F127 content indicated an increase of surface hydrophilicity. XPS analysis revealed enrichment of PEO segments of Pluronic F127 at the membrane surface. The apparent protein adsorption amount decreased significantly from 56.2 to 0 microg/cm(2) when the Pluronic F127 content varied from 0% to 10.5%, which indicated that the blend membrane had an excellent ability to resist protein adsorption. The ultrafiltration experiments revealed that the Pluronic F127 content had little influence on the protein rejection ratio and pure water flux. Most importantly, at a high Pluronic F127 content membrane fouling, especially irreversible fouling, has been remarkably reduced. The flux recoveries of blend membranes reached as high as 90% after periodic cleaning in three cycles.

Improved protein-adsorption-resistant property of PES/SPC blend membrane by adjustment of coagulation bath composition.

To improve surface protein-adsorption-resistant property of polyethersulfone (PES) membranes, soybean phosphatidylcholine (SPC) was added to PES casting solution. The blend membranes were prepared by a phase inversion method in a wet process. The surface of PES/SPC blend membranes was characterized by X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). XPS data revealed that the phosphorylcholine (PC) groups were concentrated at the surface by changing the composition of coagulation bath. Addition of N,N-dimethylformamide (DMF) in coagulation bath could prolong coagulation time and facilitate the migration of SPC from polymer bulk to membrane surface. The PES/SPC blend membranes dramatically reduced BSA and fibrinogen adsorption compared to PES control membrane due to effective immobilization of PC groups at the surface of PES/SPC blend membranes.

[Membrane used for separation of the effective parts and components of traditional Chinese medicine].

Membrane separation, as an efficient and green technology, has found more and more research and development reports in the separation and purification of the effective parts and components of traditional Chinese medicine. The basic principle and mechanism was first described in this paper, and the applicability and technological advantage was analyzed accordingly. Then, the separation performance of commonly employed membrane materials including polymeric materials such as polysulfones, cellulose acetate, polyacrylonitrile as well as inorganic materials was compared out and the application examples were presented. Finally, the major considerations in choosing the membrane materials were tentatively listed, including the physical and chemical stability, the flux and selectivity, membrane fouling, and pretreatment of membrane surface.