Immunogenicity and protective efficacy of a novel bacterium-like particle-based vaccine displaying canine distemper virus antigens in mice and dogs.

Canine distemper virus (CDV) poses a severe threat to both domesticated and wild animals, including multiple carnivores. With the continued expansion of its host range, there is an urgent need for the development of a safer and more effective vaccine. In this study, we developed subunit vaccines based on a bacterium-like particle (BLP) delivery platform containing BLPs-F and BLPs-H, which display the CDV F and H glycoprotein antigens, respectively, using the antigen-protein anchor fusions produced by a recombinant baculovirus insect cell expression system. The combination of BLPs-F and BLPs-H (CDV-BLPs), formulated with colloidal manganese salt [Mn jelly (MnJ)] adjuvant, triggered robust CDV-specific antibody responses and a substantial increase in the number of interferon gamma (IFN-γ)-secreting CD4+ and CD8+ T cells in mice. Dogs immunized intramuscularly with this vaccine not only produced CDV-specific IgG but also displayed elevated concentrations of IFN-γ and interleukin 6 in their serum, along with an increase of the CD3+CD4+ and CD3+CD8+ T cell subsets. Consequently, this heightened immune response provided effective protection against disease development and reduced viral shedding levels following challenge with a virulent strain. These findings suggest that this BLP-based subunit vaccine has the potential to become a novel canine distemper vaccine. IMPORTANCE: Many sensitive species require a safe and effective distemper vaccine. Non-replicating vaccines are preferred. We constructed subunit particles displaying canine distemper virus (CDV) antigens based on a bacterium-like particle (BLP) delivery platform. The CDV-BLPs formulated with theMn jelly adjuvant induced robust humoral and cell-mediated immune responses to CDV in mice and dogs, thereby providing effective protection against a virulent virus challenge. This work is an important step in developing a CDV subunit vaccine.

Acanthopanax senticosus cultures fermented by Lactobacillus rhamnosus enhanced immune response through improvement of antioxidant activity and inflammation in crucian carp (Carassius auratus).

Lactic acid bacteria (LAB) have been recognized as safe microorganism that improve micro-flora disturbances and enhance immune response. A well-know traditional herbal medicine, Acanthopanax senticosus (As) was extensively utilized in aquaculture to improve growth performance and disease resistance. Particularly, the septicemia, skin wound and gastroenteritis caused by Aeromonas hydrophila threaten the health of aquatic animals and human. However, the effects of probiotic fermented with A. senticosus product on the immune regulation and pathogen prevention in fish remain unclear. Here, the aim of the present study was to elucidate whether the A. senticosus fermentation by Lactobacillus rhamnosus improve immune barrier function. The crucian carp were fed with basal diet supplemented with L. rhamnosus fermented A. senticosus cultures at 2 %, 4 %, 6 % and 8 % bacterial inoculum for 8 weeks. After trials, the weight gain rate (WGR), specific growth rate (SGR) were significantly increased, especially in LGG-6 group. The results confirmed that the level of the CAT, GSH-PX, SOD, lysozyme, and MDA was enhanced in fish received with probiotic fermented product. Moreover, the L. rhamnosus fermented A. senticosus cultures could trigger innate and adaptive immunity, including the up-regulation of the C3, C4, and IgM concentration. The results of qRT-PCR revealed that stronger mRNA transcription of IL-1ß, IL-10, IFN-γ, TNF-α, and MyD88 genes in the liver, spleen, kidney, intestine and gills tissues of fish treated with probiotic fermented with A. senticosus product. After infected with A. hydrophila, the survival rate of the LGG-2 (40 %), LGG-4 (50 %), LGG-6 (60 %), LGG-8 (50 %) groups was higher than the control group. Meanwhile, the pathological damage of the liver, spleen, head-kidney, and intestine tissues of probiotic fermentation-fed fish could be alleviated after pathogen infection. Therefore, the present work indicated that L. rhamnosus fermented A. senticosus could be regard as a potential intestine-target therapy strategy to protecting fish from pathogenic bacteria infection.

Lycium barbarum polysaccharide promotes the immunoprotective effects of a recombinant Lactobacillus plantarum vaccine expressing the Trichinella spiralis cathepsin F-like protease 1 gene.

Trichinellosis caused by Trichinella spiralis (T. spiralis) is a zoonotic disease that poses a substantial risk to human health. At present, vaccines used to prevent trichinellosis are effective, but the production of antibody levels and immunogenicity are low. Adjuvants can increase antibody levels and vaccine immunogenicity. As a result, it is critical to develop an effective adjuvant for the T. spiralis vaccine. Recent research has shown that traditional Chinese medicine polysaccharides with low-toxicity and biodegradability can act as adjuvants in vaccines. In this study, BALB/c mice were orally inoculated with a recombinant Lactobacillus plantarum (L. plantarum) vaccine expressing the T. spiralis cathepsin F-like protease 1 gene (rTs-CPF1), which was given three times at 10-day intervals. Lycium barbarum polysaccharide (LBP) was administered orally for 37 days. At 37 days after the first immunization, mice were infected with 350 T. spiralis muscle larvae (ML). Specific IgG and sIgA antibody levels against the T. spiralis CPF1 protein were increased in mice immunized with rTs-CPF1+LBP compared to those immunized with rTs-CPF1 alone. Furthermore, LBP increased IFN-γ and IL-4 expression levels, and the number of intestinal and intramuscular worms was significantly reduced in the rTs-CPF1+LBP group compared to that in the rTs-CPF1 group. In the rTs-CPF1+LBP group, the reduction rates of adult worms and muscle larvae were 47.31 % and 68.88 %, respectively. To summarize, LBP promotes the immunoprotective effects of the T. spiralis vaccine and may be considered as a novel adjuvant in parasitic vaccines.

Expansin SlExp1 and endoglucanase SlCel2 synergistically promote fruit softening and cell wall disassembly in tomato.

Fruit softening, an irreversible process that occurs during fruit ripening, can lead to losses and waste during postharvest transportation and storage. Cell wall disassembly is the main factor leading to loss of fruit firmness, and several ripening-associated cell wall genes have been targeted for genetic modification, particularly pectin modifiers. However, individual knockdown of most cell wall-related genes has had minimal influence on cell wall integrity and fruit firmness, with the notable exception of pectate lyase. Compared to pectin disassembly, studies of the cell wall matrix, the xyloglucan-cellulose framework, and underlying mechanisms during fruit softening are limited. Here, a tomato (Solanum lycopersicum) fruit ripening-associated α-expansin (SlExpansin1/SlExp1) and an endoglucanase (SlCellulase2/SlCel2), which function in the cell wall matrix, were knocked out individually and together using clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9-mediated genome editing. Simultaneous knockout of SlExp1 and SlCel2 enhanced fruit firmness, reduced depolymerization of homogalacturonan-type pectin and xyloglucan, and increased cell adhesion. In contrast, single knockouts of either SlExp1 or SlCel2 did not substantially change fruit firmness, while simultaneous overexpression of SlExp1 and SlCel2 promoted early fruit softening. Collectively, our results demonstrate that SlExp1 and SlCel2 synergistically regulate cell wall disassembly and fruit softening in tomato.

Dietary supplementation of probiotics fermented Chinese herbal medicine Sanguisorba officinalis cultures enhanced immune response and disease resistance of crucian carp (Carassius auratus) against Aeromonas hydrophila.

Aeromonas hydrophila, a Gram-negative bacterium, is one of the major pathogens causing bacterial sepsis in aquatic animals due to drug resistance and pathogenicity, which could cause high mortality and serious economic losses to the aquaculture. Sanguisorba officinalis (called DiYu in Chinese, DY) is well known as herbal medicine, which could inhibit the growth of pathogenic bacteria, hemostasis and regulate the immune response. Moreover, the active ingredients in DY could remarkably reduce drug resistance. In this study, we investigated the effects of probiotic fermentation cultures on A. hydrophila through in vitro and in vivo experiments. Three lactic acid bacteria, including Lactobacillus rhamnosus (LGG), Lactobacillus casei (LC) and Lactobacillus plantarum (LP), were selected to ferment the Chinese herbal medicine DY. The assays of antagonism showed that all three fermented cultures could influence the ability of A. hydrophila growth, among which L. rhamnosus fermented DY cultures appeared to be the strongest inhibitory effect. In addition, the biofilm determination revealed that L. rhamnosus fermented DY cultures could significantly inhibit the biofilm formation of A. hydrophila compared to the other groups. Furthermore, protease, lecithinase and urease activities were found in the three fermentation cultures. Three probiotics fermented DY cultures were orally administration with crucian carp to evaluate the growth performance, immunological parameters and pathogen resistance. The results showed that the three fermentation cultures could promote the growth performance of crucian carp, and the immunoglobulins, antioxidant-related enzymes and immune-related genes were significantly enhanced. Besides, the results showed that crucian carp received L. rhamnosus (60.87%), L. casei (56.09%) and L. plantarum (41.46%) fermented DY cultures had higher survival rates compared with the control group after infection with A. hydrophila. Meanwhile, the pathological tissue results revealed that the probiotic fermented cultures could largely improve the tissues damage caused by the pathogenic bacteria. In conclusion, this study proved that the fermentation cultures of three probiotics could effectively inhibit the growth of A. hydrophila, regulate the level of immune response and improve the survival rate against A. hydrophila in crucian carp. The present data suggest that probiotic fermented Sanguisorba officinalis act as a potential gut-targeted therapy regimens to protecting fish from pathogenic bacteria infection.

Mindfulness-based stress reduction with acupressure for sleep quality in breast cancer patients with insomnia undergoing chemotherapy: A randomized controlled trial.

PURPOSE: The objective of this randomized controlled trial was to evaluate and compare the effectiveness of mindfulness-based stress reduction (MBSR), acupressure, and MBSR combined with acupressure in improving sleep quality in breast cancer patients with sleep disorders, as well as the potential effects of these interventions on relieving fatigue, anxiety, and depression. METHODS: A four-arm parallel-group randomized controlled trial was conducted in a tertiary hospital in Fujian between July 2019 and January 2021. A total of 147 breast cancer patients were randomly assigned to a usual care group (n = 34), a MBSR group (n = 38), an acupressure group (n = 36), or a combined group (n = 39). We assessed patients' sleep quality (Pittsburgh Sleep Quality Index-PSQI and 6 actigraphy indices), fatigue, anxiety, and depression at baseline and at the mid-intervention (fourth week) and the end of intervention (eighth week). RESULTS: The ANOVA showed a significant difference (p < 0.05) in PSQI, and all sleep parameters measured by wrist actigraphy, and anxiety between groups. The three active treatments led to better PSQI outcomes (p < 0.001), reduced fatigue (p < 0.001), decreased anxiety (p < 0.05), and improved sleep measured by all actigraphy indices with two exceptions (MBSR did not differ from control on Sleep Latency (p = 0.235) and mean waking by time (MWBT) (p = 0.058)). Both acupressure and the combined intervention outperformed MBSR on four actigraphy indices: Sleep Efficiency (SE), Sleep Latency (SL), Totatl Sleep Time (TST), and Wake after sleep onset (WASO) (p < 0.05), and the combined intervention further outperformed MBSR on PSQI (p = 0.03) and Number of awakings (NOA) (p = 0.003). Moreover, there was no significant difference across all outcomes between acupressure and combined intervention (p ≥ 0.05). CONCLUSIONS: MBSR, acupressure, and combined therapy all show a remarkable advantages in allemiating sleep quality, fatigue, and anxiety. Acupressure and combined therapy outperformed MBSR in improving sleep quality.

Effects of combined aerobic and resistance exercise on renal function in adult patients with chronic kidney disease: a systematic review and meta-analysis.

OBJECTIVES: Combined aerobic and resistance exercise (CARE) is beneficial for improving renal function. To confirm this, we conducted a meta-analysis to evaluate the effects of CARE on renal function in adult patients with chronic kidney disease (CKD). DATE SOURCES: The last date of search was 22 February 2020. We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Allied and Complementary Medicine (AMED), CINAHL, Web of Science, SPORTDiscus, and three Chinese databases (China National Knowledge Infrastructure (CNKI), Wangfang, Journal Integration Platform (VIP)) for articles of randomized and quasi-randomized controlled trials. METHODS: We used the Cochrane tool and the JBI Critical Appraisal checklist to assess randomized controlled trials and quasi-randomized controlled trials, respectively. RESULT: A total of 12 studies and 745 patients were included. Compared with usual care or no exercise, CARE resulted in a significant improvement in the estimated glomerular filtration rate (between-group analysis: mean difference (MD) =5.01, 95% confidence interval (CI): 2.37 to 7.65; within-group analysis: MD = 3.01, 95% CI: 0.86 to 5.16). The serum creatinine levels also showed a significant improvement after CARE (between-group analysis: MD = -8.57, 95% CI: -13.71 to -3.43; within-group analysis: MD = -6.33, 95% CI: -10.23 to -2.44). Patients who performed CARE also demonstrated a decline in the blood pressure in the within-group analysis (systolic blood pressure: MD = -5.24, 95% CI: -7.93 to -2.54; diastolic blood pressure: MD = -3.63, 95% CI: -5.35 to -1.91). However, there were no significant differences in proteinuria, lipid levels, physical composition, and quality of life. CONCLUSION: The study results support the concept that CARE intervention improves renal function. It provides strong evidence for guiding clinical decisions and implementing renal rehabilitation exercises.

Effects of exercise training on proteinuria in adult patients with chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: Rehabilitation effects of exercise training on adults with chronic kidney disease (CKD) have been generally recognised; however, the effects of exercise training on proteinuria have been underexplored. Our aim was to explore the effects of exercise training on proteinuria in adult CKD patients without renal replacement therapy. METHODS: Randomised controlled trials (RCTs) and quasi-experimental studies examining the effects of exercise training on proteinuria in adults CKD patients without renal replacement therapy were searched in 10 electronic databases (MEDLINE, Embase, CINAHL, Cochrane Central Register of Controlled Trials, Allied and Complementary Medicine Database, SPORTDiscus with full text, Web of Science, China Wan Fang Database, China National Knowledge Internet, China Science and Technology Journal Database) until June 2019. The quality of quasi-experimental studies was assessed using the Joanna Briggs Institute Checklist for non-randomised experimental studies. The Cochrane risk of bias tool was used to evaluate the RCT quality. RESULTS: We analysed 11 studies (623 participants). The 24-h urinary protein (24 h UP) level significantly decreased after exercise training in the within-group analysis (standard mean difference [SMD], 0.48; 95% confidence interval [CI], 0.08 to 0.88). There was a slight decrease in 24 h UP levels in the between-group analysis (SMD, 0.91; 95% CI, 0.00 to 1.82); however, the subgroup analysis showed that the change was insignificant (RCT: SMD, 0.24; 95% CI, - 0.44 to 0.92; quasi-experimental studies: SMD, 2.50; 95% CI, - 1.22 to 6.23). Exercise resulted in no significant differences in the urinary albumin-to-creatinine ratio in the between-group analysis (SMD, 0.06; 95% CI, - 0.54 to 0.67), but a significant decrease was found in the within-group analysis (SMD, 0.21; 95% CI, 0.04 to 0.38). No evidence of a decreased urinary protein-to-creatinine ratio was found after exercise (between-group analysis: SMD, 0.08 and 95% CI, - 0.33 to 0.48; within-group analysis: SMD, 0.04; 95% CI, - 0.25 to 0.32). CONCLUSION: Exercise training does not aggravate proteinuria in adult CKD patients without renal replacement therapy. Further research is warranted in the future to determine the effectiveness of exercise training on proteinuria and to explore the mechanisms by which exercise training influences proteinuria.

Effect of Er:YAG Laser Etching on the Shear Bond Strength and Microleakage of Self-Glazed Zirconia Ceramics.

Objective: To investigate the effect of Er:YAG laser irradiation on the shear bond strength (SBS) and microleakage of self-glazed zirconia (SZ) ceramics. Background: SZ is a novel type ceramic; laser irradiation has started to be used in the surface treatment of different ceramics, while SZ has been rarely studied to improve the bond quality. Methods: One hundred twenty blocks (5 mm × 5 mm × 5 mm) of SZ ceramics were produced and split into eight groups following different surface treatments (n = 15): Group A: no treatment; Group B: standard grid processing; and Group C-H: different Er:YAG laser power settings (100, 200, 300, 400, 500, and 600 mJ). Ten blocks of each group received the measurement of SBS and fracture mode analysis, three blocks underwent the evaluation of the microleakage depths, and the other two blocks were observed under the scanning electronic microscopy (SEM). Results: Group F obtained the highest SBS and the lowest microleakage depth without damaging the ceramic surface structure, which was statistically significant compared with the control group and gridding group (p < 0.05), whereas the difference was not statistically significant (p > 0.05) between group E and group F. The results of bonding performance were consistent with failure types and observation of surface characterizations in SEM images. Conclusions: According to the results here, Er:YAG irradiation had effect on surface treatment. In addition, 400 mJ Er:YAG could increase the SBS and decrease the microleakage depth on SZ ceramics without damaging the surface structure.

The development of a family participatory dignity therapy programme for patients with haematologic neoplasms and their family caregivers in China: A feasibility study.

OBJECTIVE: To develop a communication prompt based on dignity therapy to facilitate effective conversations between patients with haematologic neoplasms and their family caregivers and to improve the programme and preliminarily explore the benefits and challenges of family participatory dignity therapy (FPDT). METHODS: A mixed-methods approach was applied to develop and revise the programme. The FPDT was developed and validated using the Delphi survey, and its further improvement was explored with a simple one-group pre- and post-trial and semi-structured in-depth interviews. RESULTS: Most of the FPDT items were endorsed by experts and patient-family dyads. The Content Validity Index was 93.6% in the first round of the Delphi survey and 100% in the second round. The "hope level," "spiritual well-being" and "general health" scores of pre- and post-testing increased from 33.60 ± 4.30 to 37.70 ± 5.10 (t = 3.99, p = .003); from 30.30 ± 3.65 to 38.80 ± 7.29(t = 4.13, p = .003); and from 41.67 ± 8.78 to 53.33 ± 8.05 (t = 3.50, p = .007) respectively. The qualitative data also indicated that the project was meaningful and well received. CONCLUSIONS: We showed that FPDT was a valuable and feasible means of improving communication between patients with haematologic neoplasms and their family caregivers in China by raising the hope level and spiritual well-being and promoting general health.

Inhibitory effects of Pinus massoniana bark extract on hepatitis C virus in vitro.

CONTEXT: Given that Pinus massoniana Lamb (Pinaceae) bark extract (PMBE) is a safe and non-toxic flavonoid found abundantly in nature, it was considered a promising novel candidate agent in the treatment of virus infection. OBJECT: Experiments were conducted to assay the antiviral character of PMBE against Hepatitis C virus (HCV). MATERIALS AND METHODS: Assay of PMBE cytotoxicity, HCV replication, infectious HCV production, and its potential influence on the pathways for IFN-ISRE and NS3 protease were conducted. RESULTS: HCV replication was suppressed when the concentration of PMBE raised greater than 5 µg/mL and its EC50 was 9.58 µg/mL. In the 10 µg/mL group, HCV replication was suppressed for 48 h. When the concentration increased to 40 µg/mL, HCV replication was significantly suppressed (luciferase activity was only 10% at 96 h). PMBE could inhibit HCV virus production efficiently (PMBE group was 5 FFU). Cell viability was affected by 40 µg/mL of PMBE. The F/R ratio ranged from 98% to 101%. The rate of OD450 ranged from 96% to 102%. NS3 catalytic activity ranged from 5% (40 µg/mL PMBE) to 45% (5 µg/mL PMBE). Even when used in a low amount (5 µg/mL), NS3 catalytic activity was significantly inhibited (p < 0.01). CONCLUSIONS: The results suggest that PMBE is effective for use in the stabilization of HCV replication and active liver inflammation.

Investigation on pharmacokinetics, tissue distribution and excretion of 1-triacontanol in rats by gas chromatography-tandem mass spectrometry (GC-MS/MS).

1. 1-Triacontanol (TA) recently shows promising anti-tumor activity. The present study was aimed to develop a sensitive gas chromatography-tandem mass spectrometry method to explore the pharmacokinetic profiles, distribution and excretion of TA in Sprague-Dawley rats after oral administration of TA. Chromatography separation was performed on a HP-5MS column. 1-Octacosanal was used as the internal standard (IS). Quantification of TA and IS was carried out at m/z 495.6 → 97.0 and m/z 467.5 → 97.0, respectively, in positive electron ionization and multiple reaction monitoring mode. The pharmacokinetic parameters were calculated by non-compartmental analysis. 2. The area under concentration-time curve AUC0-6 h and AUC0-∞ for TA at 60 mg/kg were 87.737 ± 13.574 and 93.617 ± 17.62, respectively. The mean residence time was 3.25 ± 0.17 h. In addition, the elimination half-lives (t1/2) were (2.37 ± 1.23, 1.27 ± 0.49, 2.07 ± 0.93) h after single oral administration of 30, 60 and 120 mg/kg of TA. After oral administration, TA was extensively distributed in stomach and intestine. The majority of TA excreted via feces, and its accumulative excretion ratio during the period of 72 h was 26.68 ± 7.14%, but only 0.0023 ± 0.0015% and 0.0027 ± 0.0006% for urines and bile, respectively. The absolute bioavailability (F, %) of TA was about 2.0%.

Cepharanthine, an alkaloid from Stephania cepharantha Hayata, inhibits the inflammatory response in the RAW264.7 cell and mouse models.

The aim of this study was to investigate the protective effects of cepharanthine (CEP) on inflammation in lipopolysaccharide (LPS)-stimulated RAW264.7 cells in vitro and a LPS-induced lung injury model in vivo. RAW264.7 cells were treated with various concentrations of CEP for 1 h followed by incubation with or without 1 µg/ml LPS for 18 h. TNF-α, IL-6, and IL-1ß in the supernatants were measured by ELISA. Nuclear factor-κB (NF-κB) and mitogen-activated protein kinase pathways were analyzed by Western blot. Mice were randomly divided into control group, LPS group, CEP + LPS group, and dexamethasone + LPS group. A male BALB/c mouse model of acute lung injury was induced by LPS. Bronchoalveolar lavage fluid was collected for inflammatory cell count and cytokine assays. Histopathologic examination was performed on mice that were not subjected to bronchoalveolar lavage fluid collection. CEP dose-dependently inhibited the release of TNF-α, IL-6, and IL-1ß in LPS-stimulated RAW264.7 cells. Significantly, CEP dose-dependently suppressed NF-κB activation, IκBα degradation, and phosphorylation of ERK, JNK, and p38 induced by LPS. In vivo, it was also observed that CEP attenuated lung histopathologic changes and down-regulated the level of pro-inflammatory cytokines, including TNF-α, IL-1ß, and IL-6, in the mouse acute lung injury model. These results suggest that CEP potentially decreases inflammation in vitro and in vivo and might be a therapeutic agent against inflammatory diseases.