Multicomponent Pathogen-Mimicking Nanoparticles Induce Intestinal Immune Responses against Paratuberculosis.

Given the worldwide problem posed by enteric pathogens, the discovery of safe and efficient intestinal adjuvants combined with novel antigen delivery techniques is essential to the design of mucosal vaccines. In this work, we designed poly (lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) to codeliver all-trans retinoic acid (atRA), novel antigens, and CpG. To address the insolubility of the intestinal adjuvant atRA, we utilized PLGA to encapsulate atRA and form a "nanocapsid" with polydopamine. By leveraging polydopamine, we adsorbed the water-soluble antigens and the TLR9 agonist CpG onto the NPs' surface, resulting in the pathogen-mimicking PLPCa NPs. In this study, the novel fusion protein (HBf), consisting of the Mycobacterium avium subspecies paratuberculosis antigens HBHA, Ag85B, and Bfra, was coloaded onto the NPs. In vitro, PLPCa NPs were shown to promote the activation and maturation of bone marrow-derived dendritic cells. Additionally, we found that PLPCa NPs created an immune-rich microenvironment at the injection site following intramuscular administration. From the results, the PLPCa NPs induced strong IgA levels in the gut in addition to enhancing powerful systemic immune responses. Consequently, significant declines in the bacterial burden and inflammatory score were noted in PLPCa NPs-treated mice. In summary, PLPCa can serve as a novel and safe vaccine delivery platform against gut pathogens, such as paratuberculosis, capable of activating both systemic and intestinal immunity.

Meta-analysis of the Correlation between Helicobacter Pylori Infection and the risk of Colorectal Neoplasia.

Objective: To study the association of H. pylori infection with colorectal adenomas. Methods: Web searches of PubMed, Embase, and Scopus databases for randomized controlled trials, class-experimental studies, and cohort studies on the association between H. pylori and colorectal adenomas were performed from May 2000 to May 2023. Literature was screened based on inclusion and exclusion criteria, data were extracted and evaluated for quality, and statistical analyses were performed using RevMan 5.2 software. Results: A total of 15 studies were included, and meta-analysis showed a statistically significant difference between colorectal neoplastic polyp cases in the H. pylori-positive and H. pylori-negative groups [OR=1.80, 95%CI: (1.31, 2.47), P < .01, I2 = 95%]. Analysis based on subgroups of different H. pylori detection methods showed that the correlation between H. pylori infection and colorectal polyp incidence is not affected by their detection methods, with serological detection subgroup: [OR=0.13, 95%CI: (0.05, 0.21), P < .01, I2 = 88%], and non-serological detection subgroup: [OR=0.13, 95%CI: (0.04, 0.22), P < .01, I2 = 95%]. Subgroup analysis of pathological types showed that H. pylori infection is not significantly associated with the development of non-neoplastic polyps [OR=1.47, 95%CI: 0.98-2.22, P = .06], whereas it is correlated with the development of neoplastic polyps [95%CI: 1.69-3.22, P < .01]. In the subgroup analysis of geographic differences in the population, H. pylori infection was correlated with the development of colorectal polyps in different geographic populations (P < .01). Conclusion: H. pylori infection is a risk factor for colorectal polyp neoplasia, its infection is associated with colorectal neoplasia, and the correlation is not affected by the different methods of H. pylori detection and the different geographic regions of the population.

Remediation of petroleum hydrocarbons-contaminated soil: Analysis based on Chinese patents.

Increasing soil petroleum hydrocarbons (PHs) pollution have caused world-wide concerns. The removal of PHs from soils mainly involves physical, chemical, biological processes and their combinations. To date, most reviews in this field based on research articles, but limited papers focused on the integration of remediation technologies from the perspective of patents. In this study, 20-years Chinese patents related to the remediation of soil PHs were comprehensively analyzed. It showed an increasing number of patent applications and the patents' quantity were positively correlated with Chinese GDP over the years, suggesting the more the economy developed the more environmental problems and corresponding solutions emerged. In addition, chemical technologies were mostly used in a combination to achieve faster and better effects, while the physical technologies were often used alone due to high costs. In all PHs remediation techniques, bacteria-based bioremediation was the most used from 2000 to 2019. Bacillus spp. and Pseudomonas spp. were the most used bacteria for PHs treatment because these taxa were widely harboring functions such as biosurfactant production and hydrocarbon degradation. The future research on joint technologies combining microbial and physicochemical ones for better remediation effect and application are highly encouraged.

A Novel Hypothesis on Excessive Activation of Residual B Lymphocytes in Common Variable Immunodeficiency Concurrent with Aseptic, Erosive Polyarthritis.

The aim of this study was to report aseptic, erosive polyarthritis in a patient with common variable immunodeficiency (CVID), which is quite different from the vastly more common nonerosive form. Peripheral blood mononuclear cells of the patient were isolated. Flow cytometry was used to analyze the proportion and function of lymphocytes. A Parker-Pearson needle biopsy was performed on the right knee. Four of her unaffected family members were enrolled as controls. A 21-year-old woman was admitted for recurrent polyarthritis of 3-year duration. The right knee, hip, wrist, proximal interphalangeal joints, and left elbow were involved, with progressive joint destruction. She was diagnosed as having CVID based on her recurrent infections, poor response to vaccines, and marked hypogammaglobulinemia. No bacterium or mycobacterium was detected in synovium or synovial fluid. The synovium was infiltrated by lymphocytes rather than neutrophils. Polyarthritis did not resolve by adequate intravenous immunoglobulin substitution and empirical antibiotic treatment, but resolved gradually after treatment with methylprednisolone and tacrolimus, supporting the diagnosis of aseptic polyarthritis. Further analyses showed that although only 0.5% of residual B lymphocytes were existent in peripheral blood of the patient, expressions of activation marker CD69 and production of IL-1ß, IL-6, and TNF-α were high. Marked infiltration with CD19+B lymphocytes (as well as CD4+ or CD8+ T lymphocytes) was detected in the synovium. The proportion of IL21+CD4+Th cells from peripheral blood of the patient was high. CD4+ Th cells from the patient secreted nearly 3 times more IL-21 than the same cell type analyzed from unaffected family members, perhaps due to excessive compensation to assist the function of residual B lymphocytes. A novel hypothesis in CVID concurrent with aseptic, erosive polyarthritis is that excessive activation of residual B lymphocytes infiltrate into the synovium of the involved joints and lead to polyarthritis and joint destruction.

Microcirculatory Disorders and Protective Role of Xuebijing in Severe Heat Stroke.

This study was conducted to explore underlying mechanism of microcirculation dysfunction and protectiverole of Xuebijing in heat stroke. Forty rats were divided into: control, vehicle + heat stress (HS), superoxide dismutase (SOD) + HS, and Xuebijing + HS groups. Rats in heat stress groups were subjected to continuous heat stress in infant incubator 1 h after tail vein injection of the tested compound and spinotrapezius preparation. Velocity of blood flow through micro-vessels and vascular diameter were detected in real time. Another 27 rats were divided into: vehicle, SOD, and Xuebijing groups, then further divided into three subgroups each: control, Tcore = 38 °C, Tcore = 41 °C. Rats were sacrificed, and spinotrapezius single-cell suspensions were prepared for detecting SOD and reactive oxygen species (ROS). The results showed that heat stress decreased SOD activity, increased ROS levels, and reduced the blood flow rate. Xuebijing increased SOD activity, decreased ROS levels and exhibited a protective effect in terms of blood flow rate but was less protective than SOD. The survival time in Xuebijing + HS group was longer than that in vehicle group but shorter than that in SOD + HS group. The results suggested Xuebijing could decrease ROS levels and have protective effects in severe heat stroke.

[Pretreatment with Xuebijing injection alleviates systemic inflammatory response induced by severe heat-stroke via ameliorating intestinal injury in rats].

OBJECTIVE: To observe the effect of Xuebijing injection pretreatment on systemic inflammatory response induced by severe heat-stroke, and to investigate the mechanism of alleviation of intestinal injury in rats. METHODS: Thirty-six healthy adult male Wistar rats with grade SPF were randomly assigned into three groups with randomized number method, namely sham group, severe heat-stroke model group, and Xuebijing pretreatment group ( XBJ group ), with 12 rats in each group. The animals were placed in a pre-warm chamber [ temperature ( 40±2 ) centigrade, humidity ( 65±5 )% ] in order to induce typical heat-stroke. The duration of heat-stress was 60 minutes, while the animals in sham group were exposed to ambient temperature of 25 centigrade. Arterial blood samples were collected at the beginning and the end of heat-stress, the concentrations of tumor necrosis factor-α( TNF-α), interleukins ( IL-1ß, IL-6 ), and lipopolysaccharide ( LPS ) in peripheral blood were determined by enzyme linked immunosorbent assay ( ELISA ). The intestinal tissues were harvested after heat-stress, and the pathological changes in intestine tissues were observed after hematoxylin-eosin ( HE ) staining and under optical microscope. The pathological injury scores were calculated. Immunohistochemistry was performed to determine inducible nitric oxide synthase ( iNOS ) expression in intestinal tissue. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling ( TUNEL ) staining. Western Blot was used to measure the tight junction protein occludin expression. RESULTS: The concentrations of TNF-α, IL-1ß, IL-6 and LPS in blood of the rats after heat-stress in model group were significantly higher than those of sham group [ TNF-α ( µg/L ): 443.00±110.10 vs. 98.36±44.61, IL-1ß ( µg/L ): 436.37±163.64 vs.64.24±16.15, IL-6 ( µg/L ): 342.70±92.42 vs. 54.40±13.22, LPS ( µg/L ): 0.68±0.22 vs. 0.09±0.02, all P < 0.01 ], but the levels of these parameters in XBJ group were significantly lower than those of model group [ TNF-α ( µg/L ): 340.45±68.57 vs. 443.00±110.10, IL-1ß ( µg/L ): 191.33±82.78 vs. 436.37±163.64, IL-6 ( µg/L ): 192.21±37.89 vs. 342.70±92.42, LPS ( µg/L ): 0.43±0.17 vs. 0.68±0.22, all P < 0.01 ]. Infiltration of inflammatory cells, necrosis and hemorrhage in intestinal mucosa were found in the intestine of heat-stroke animals in model group. The pathological lesions in XBJ group were milder than those of model group, with a decreased pathological injury score compared with model group ( 2.10±1.15 vs. 3.20±0.67, P < 0.01 ). The expression of iNOS and apoptosis of cells in intestinal tissue in model group were increased compared with that of sham group, but they were significantly less marked in XBJ group compared with model group [ iNOS ( adjusted A value ): 0.32±0.15 vs. 0.74±0.17, apoptotic index: 0.23±0.08 vs. 0.56±0.07, both P < 0.01 ]. The order of expression for occludin protein from high to low was sham group, XBJ group and model group ( A value was 0.96±0.25, 0.62±0.20, 0.33±0.11, respectively ). Furthermore, there was significant difference in the expression of occludin protein between model group and both XBJ group and sham group ( both P < 0.01 ). CONCLUSIONS: Xuebijing injection alleviates inflammation and endotoxemia produced by severe heat-stroke in rats. The mechanism may be related to amelioration of oxidative injury, apoptosis, and dysfunction of tight junction protein occludin expression.

Two new xanthones from Lomatogonium carinthiacum.

AIM: To study the chemical constituents of Lomatogonium carinthiacum (Wulfen) Rchb. METHOD: The CHCl3-soluble fraction was separated by chromatography and the structures of the new compounds were elucidated by spectral experiments. RESULTS: Two new xanthones, 1, 8-dihydroxy-4, 5-dimethoxy-6, 7-methylenedioxyxanthone (1), 1, 4, 8-trimethoxyxanthone-6-O-ß-D-glucoronyl-(1→6)O-ß-D-glucoside (2) were isolated from the whole plant of Lomatogonium carinthiacum. CONCLUSION: Compounds 1 and 2 are new natural products.

Structure elucidation and NMR assignments of two unusual xanthones from Lomatogonium carinthiacum (Wulf) Reichb.

Two new unusual xanthones, 5-O-ß-d-glucopyranosyl-1,3,8-trihydroxy-5,6,7,8-tetrahydroxanthone (1) and 1,3,5,8-tetrahydroxy-5,6,7,8-tetrahydroxanthone (2), were isolated from Lomatogonium carinthiacum (Wulf) Reichb. Their structures were elucidated on the basis of spectroscopic methods including UV, IR, ESI-MS, 1D NMR, and 2D NMR.