The effect of lentinan on dexamethasone-induced immunosuppression in mice.

The immune system acts as a vital defense barrier against pathogenic invasions, and its stable operation is crucial for maintaining body health. Nevertheless, various natural or artificial factors can compromise the body's immune function, leading to immunosuppression, which may interfere with the efficacy of vaccination and increase the susceptibility of the body to disease-causing pathogens. In an effort to ensure successful vaccinations and improve overall physical well-being, the search for appropriate immune regulators to enhance immunity is of paramount importance. Lentinan (LNT) has a significant role in immune regulation and vaccine adjuvants. In the present study, we constructed an immunosuppressive model using dexamethasone (DEX) and demonstrated that LNT could significantly improved antibody levels in immunosuppressive mice and stimulated T-lymphocyte proliferation and differentiation in intestinal Peyer's patches. LNT also increased the production of secretory immunoglobulin A (sIgA) in the duodenal fluid, the number of goblet cells, and the proportion of mucin area. Moreover, LNT modulated the intestinal microbiota and increased the production of short-chain fatty acids. Additionally, LNT promoted the proliferation, differentiation, and pro-inflammatory cytokines production of DEX-treated splenic T lymphocytes in vitro. Thus, the present study highlights the potential of LNT in reversing immunosuppression and avoiding the failure of vaccination.

Volumetric reduction in large cystic jaw lesions postoperative enucleation: a longitudinal clinical study.

BACKGROUND: Enucleation, a surgical procedure, is commonly used to treat large jaw cysts, unicystic ameloblastomas and keratocysts. However, it remains unclear to what extent the jaw bone regenerates after enucleation. We aimed to evaluate the percentage and the survival analysis of jaw bone regeneration, in terms of cavity volume residual (CVR), in patients who underwent enucleation of large jaw cysts, unicystic ameloblastomas and keratocysts. METHODS: We collected data longitudinally from 75 patients who underwent jaw cystic lesions enucleation at the Stomatological Hospital of Xi'an Jiaotong University, between January 2015 and June 2021. All patients had both preoperative and postoperative cone-beam computed tomography (CBCT) imaging data. CBCT images were analyzed using Image J. Changes in the CVR were assessed at various follow-up time points, and the Kaplan-Meier method was utilized to evaluate the CVR over time. RESULTS: The patients had a mean age of 31.7 years (range: 5.5-72 years) with 58.66% of them being male. The postoperative CVR was 32.20% at three months, 21.10% at six months, 15.90% at 12 months, and 5.60% at 24 months. The percentage of CVR during follow-up periods for the initial size Quartile (Q)1 (212.54-1569.60 mm3) was substantially lower than those of Q2 and Q3 at and after seven months of follow-up and became statistically significant at the 12-month mark. CONCLUSION: This study demonstrates that spontaneous bone regeneration can occur after enucleation of large jaw cysts, unicystic ameloblastomas and keratocysts, even without the use of filler materials. The initial size of the lesion had a significant impact on the outcome of cystic lesion enucleation over time. To minimize the risks associated with radiation exposure and expenses, we recommend reducing the frequency of CT imaging follow-ups for patients with small initial cavity sizes (ranging from 212.54 to 1569.60 mm3).

Lentinan-functionalized graphene oxide hydrogel as a sustained antigen delivery system for vaccines.

Hydrogel has been proven to have the ability to deliver antigens continuously to achieve slow vaccine delivery, which makes it a promising candidate for an adjuvant delivery platform. Meanwhile, graphene oxide (GO) has garnered significant attention due to its good biosafety, excellent surface area and easy modification. However, GO exists as weak colloidal particles and poses challenges in self-assembling into a hydrogel structure. Here, we propose an innovative strategy involving self-assembling lentinan-functionalized graphene oxide hydrogel ((LNT-GO Gel) by simply mixing lentinan (LNT)-functionalized GO with polyethylene imide (PEI), which can simultaneously encapsulate antigens, achieve long-lasting release of antigens and generate excellent adjuvant activity. The results indicated that the LNT-GO Gel can control the release of OVA at the injection site and confer targeted delivering capacity to lymph nodes. And the date demonstrates that LNT-GO Gel displays favorable safety and biodegradability in vivo. Moreover, LNT-GO Gel can enhance the activation and maturation of dendritic cells (DCs) in lymph node, induce stronger OVA-specific antibody response, and promote spleen T lymphocyte differentiation, which underscores that LNT-GO Gel has ability to generate stronger antigen-specific humoral and cellular immune responses. Collectively, these results demonstrate the adjuvant potential of the lentinan-functionalized graphene oxide hydrogel (LNT-GO Gel) for subunit vaccine.

Astragalus polysaccharides combined with simvastatin as an immunostimulant enhances the immune adjuvanticity of oil-in-water emulsion and immune responses in mice.

Oil-in-water emulsion-based adjuvants have demonstrated acceptable safety in many disease indications, while their adjuvant activities for vaccines still need to be improved. Recently, the strategy of combining adjuvants with multiple types of immunostimulants has been shown to enhance immune responses. In this study, astragalus polysaccharides were combined with simvastatin as an immunostimulant to construct a compound O/W emulsion adjuvant. The formulations were optimized according to the OVA-specific antibody responses induced in mice. For this reason, high (5 mg/mL), medium (2.5 mg/mL), and low (1.25 mg/mL) concentrations of astragalus polysaccharides and high (10 mg/mL), medium (1 mg/mL), and low (0.1 mg/mL) concentrations of simvastatin were selected. The final optimal formulation of the immunostimulant was a high concentration of astragalus polysaccharides combined with a medium concentration of simvastatin. The optimal compound O/W emulsion adjuvant could induce effective humoral and cellular immune responses that were stronger and more stable than those induced by aluminum adjuvant and Freund's adjuvant. The OVA/HAPS-MSim-OE induced dramatically strong and persistent IgG expressions and Th1-polarized immune responses. What's more, the highest CD4+/CD8+lymphocyte ratios were observed in OVA/HAPS-MSim-OE group. In addition, compound O/W emulsion adjuvant groups significantly promoted the secretion of IFN-γ and IL-6, which also indicated that the compound O/W emulsion adjuvants could induce both enhanced Th1 and Th2-mediated immune responses but prefer the Th1-mediated ones. This study would contribute to an interesting and promising direction in the development of emulsion-based adjuvants.

Lycium barbarum polysaccharides-loaded Particulate Alum via Pickering emulsion as an adjuvant to enhance immune responses.

Pickering emulsion has great potential as a vaccine adjuvant due to its unique advantages such as its high antigen loading efficiency, great stability, etc. Among several adjuvants on the market, aluminum adjuvant (Alum) is the most widely used at present. However, problems such as the inability to effectively induce cellular immunity and the poor effect on subunit vaccines limit the application of Alum. As an immunopotentiator, Lycium barbarum polysaccharides (LBP) have been proven to have the ability to regulate humoral and cellular immunity. To overcome the insufficiency of Alum, we explored a new adjuvant delivery system. The Lycium barbarum polysaccharides-loaded Particulate Alum via Pickering emulsion (LBPPE) was prepared by loading Alum on the squalene/water interphase following LBP was adsorbed on the Alum surface (Fig. 10). Similar to squalene, LBPPE possesses a good biosafety profile. LBPPE was spherical with uneven surface, which increased the possibility of efficient antigen adsorption on the surface and crack of LBPPE. And the result shown that the LBPPE had high antigen loading rate at approximately 90 %. In vivo experiments, LBPPE showed an excellent ability to recruit antigen-presenting cells (APCs) at the injection sites, activate dendritic cells in the lymph nodes. Then, in the evaluation of humoral immunity, LBPPE was able to effectively induce the production of IgG, IgG1, and IgG2a. Moreover, LBPPE significantly enhanced the expression and activation of T lymphocytes, and induced a strong immune memory T cells response. All the results above suggested that LBPPE is likely to provide promising insights toward a safe and efficient adjuvant platform for vaccines.

Chinese yam polysaccharides PLGA-stabilized Pickering emulsion as an adjuvant system for PCV- 2 vaccine to enhance immune response.

Chinese yam polysaccharides (CYP) exhibit superior adjuvant activity and modulate the immune response, but the low bioavailability limits their clinical application. Pickering emulsions have been proven as an efficient vaccine delivery system to enhance the immune response. Here, we used the Chinese yam polysaccharides PLGA-stabilized Pickering emulsion adjuvant system (CYP-PPAS) loaded with Porcine circovirus 2 as a vaccine and focused on investigating its adjuvant activity on humoral and cellular immunity in mice. The CYP-PPAS increased PCV-2 antigen loading efficiency and showed a high antigen uptake efficiency by macrophages in vitro. In vivo, CYP-PPAS significantly facilitated DCs maturation in draining lymph nodes than CYP or PPAS alone group. The CYP-PPAS also induced an increased proliferation index and a CD4+/CD8+ ratio. Meanwhile, in contrast to the CYP and PPAS groups, CYP-PPAS elicited a stronger anti-PCV-2 IgG and mixed Th1/Th2 immune response. Specifically, the CYP-PPAS group displayed the high expression of CD107a, FasL, and Granzyme B secretion to augment a strong cytotoxic lymphocyte response. Overall, the CYP-PPAS was a successful adjuvant system for promoting humoral and cellular immune responses, which opens up an avenue for the development of effective adjuvants against infectious diseases.

Chitosan-modified Phellinus igniarius polysaccharide PLGA nanoparticles ameliorated inflammatory bowel disease.

In many clinical studies, prebiotics have been used as adjuvant therapy for inflammatory bowel disease (IBD). Phellinus igniarius polysaccharide (PIP) possesses great anti-inflammatory and prebiotic activities. Herein, we developed an orally deliverable PIP-loaded chitosan-modified PLGA nanomedicine (CS-PIPP) to investigate its anti-inflammatory effect in vitro and in vivo. Dextran sodium sulfate (DSS)-induced colitis model was established to evaluate the preventive effect of CS-PIPP on IBD. This study characterized that CS-PIPP had a size of 288.7 ± 5.49 nm, positive zeta potential, and showed good stability over four weeks. The in-vitro study suggested that CS-PIPP had enhanced phagocytosis by macrophages, which could further significantly inhibit M1-like macrophages phenotype and regulate lipopolysaccharide (LPS)-induced inflammatory cytokines. The in-vivo study revealed that CS-PIPP prominently prevented intestinal inflammatory damage and protected the integrity of the intestinal barrier. Moreover, CS-PIPP increased the contents of short-chain fatty acids (SCFAs) and positively regulated the gut microbiota. Specifically, CS-PIPP reduced enteropathogenic microorganisms while increasing the beneficial microbiota, including Lactobacillus and Akkermansia, which revealed the potential of CS-PIPP as prebiotics. Generally, CS-PIPP promoted the anti-inflammatory effect of PIP, so it could be regarded as a novel and potent nanoformulation to treat IBD.

Fabrication and characterization of Chinese yam polysaccharides PLGA nanoparticles stabilized Pickering emulsion as an efficient adjuvant.

The Chinese yam polysaccharides PLGA nanoparticles were applied as stabilizers in this study to prepare O/W Pickering emulsion. The optimized preparation conditions were PLGA concentration of 5 mg/mL, ultrasonic power of 50 %, and ultrasonic time of 2 min. The CYP-PPAS emulsion exhibits a raspberry-like morphology with a large number of nanoparticles surrounding the oil droplets. The CYP-PPAS emulsion exhibited outstanding stability at 4 °C and 37 °C for 28 days with high antigen loading efficiency and provided a controlled and sustained release of Chinese yam polysaccharides and OVA antigen in vitro. CYP-PPAS/OVA elicited robust antigen-specific immune response and induced a mixed Th1/Th2 immune response after immunization. Furthermore, CYP-PPAS/OVA caused a high CD4+/CD8+ ratio leading in increased activation of splenic T lymphocytes subpopulations. Moreover, CYP-PPAS is a safe vaccination adjuvant with high safety profile in vivo. Thus, the novel designed Pickering emulsion CYP-PPAS was a safe and effective adjuvant for inducing the strong and long-term immune response.

Lentinan PLGA-stabilized pickering emulsion for the enhanced vaccination.

Lentinan (LNT), a ß-1,3-linked-d-glucan with ß-1,6 glucose branches, is the main bioactive component extracted from Lentinus edodes. As a carbohydrate polymer, it has attracted increasingly attention because of immune enhancement effect. Pickering emulsion has been widely used in biomedicine due to its great stability, high loading capacity, and appreciable biocompatibility. The aim of this study is to construct an adjuvant delivery system (LNTPP/OVA) (Lentinan PLGA-stabilized Pickering emulsion loading OVA antigen) which can enhance the immune activity of LNT and can together deliver model protein antigen ovalbumin (OVA) into the organism. The characterization of the LNTPP/OVA was demonstrated that the size of LNTPP/OVA was around 1050.68 nm and was stable to store at least 28 days. Pickering emulsion was spherical shape like the raspberry with the high antigen load rate at around 82.53%. Moreover, the adjuvant effect of LNTPP/OVA formulation was detected. Compared with LNT/OVA formulation, our experimental results showed that LNTPP/OVA could promote the uptake of the OVA-antigen by macrophages in vitro. In vivo experiments, LNTPP/OVA facilitated the activation of dendritic cells (DCs) and induced strong humoral and cellular immune responses carrying a Th1 and Th2 immune responses. Therefore, LNTPP/OVA formulation have the latent capacity as a vaccine transmission system.

A Novel Nanomedicine Ameliorates Acute Inflammatory Bowel Disease by Regulating Macrophages and T-Cells.

Ramulus mori polysaccharide (RMP), one of the most important active components of R. mori, has been attracting increasing interest because of its potent bioactive properties, including anti-inflammatory, antitumor, and antidiabetic effects. Despite the great therapeutic potential of RMP, its inherent properties of low bioavailability and brief biological half-life have limited its applications to the clinic. Thus, RMP was packaged by poly(lactic-co-glycolic acid) (PLGA) nanoparticles to develop a novel anti-inflammatory nanomedicine (PLGA-RMP) in this study. The nanoparticles were synthesized via a double-emulsion solvent evaporation technique, and the average diameter of PLGA-RMP was about 202 nm. PLGA-RMP nanoparticles reduced the expression of inflammatory cytokines while promoting the production of IL-10, and boosted the phenotypic shift in macrophages in vitro. Furthermore, lipopolysaccharide (LPS)-induced inflammatory bowel disease (IBD) in mouse was used to examine the anti-inflammatory effect of PLGA-RMP in vivo. Oral administration of PLGA-RMP in LPS-induced IBD mice substantially mitigated the intestinal inflammation compared to treatment with LPS alone, as evidenced by attenuation of disease activity index scores and inflammatory damage in the intestine. Meanwhile, PLGA-RMP suppressed the expression and secretion of specific inflammatory cytokines including TNF-α, IL-6, IL-1ß, and PGE2 in the inflamed intestine while inhibiting the activation of CD3+CD8+ T-cells and increasing the number of activated Tregs in the intestine. These results indicated that PLGA-RMP deserves further consideration as a potential therapeutic nanomedicine to treat various inflammatory diseases, including IBD.

Ramulus mori polysaccharide-loaded PLGA nanoparticles and their anti-inflammatory effects in vivo.

In this study, ramulus mori polysaccharide (RMP) was encapsulated into Poly (lactic-co-glycolicacid) (PLGA) to form PLGA-RMP (PR). The aim of study is to investigate anti-inflammatory effects of PR. The particle size of PR nanoparticles was approximately 205.6 ± 1.86 nm. PR nanoparticles showed significant therapeutic effects on colitis mice model, evidenced by attenuation of the loss of body weight, reduction of the DAI score, and restoration of the colon length. From the histopathological analysis, alleviation of the histopathological damage, less production of IFN-γ and IL-6, and improvement of IL-10 were observed with the treatment of PR. Meanwhile, the treatment of PR not only promoted the expression of ZO-1 and occludin, but also improved the contents of acetate, propionate, and butyrate in the colitis colon. Furthermore, PR extenuated the reduction of the diversity and richness of gut microbiota induced by DSS, and decreased the ratio of Firmicutes to Bacteroidetes while increasing the proportion of Clostridium XIVa, Mucispirillum, and Paraprevotella in the gut microbiota. What's more, PR nanoparticles attenuated the metabolic disorders in the colitis colon induced by DSS. These results indicated that PR nanoparticles could serve as a potent nanomedicine to treat IBD and be used as potential prebiotics.

Investigation of differentially expressed gene profile for cisplatin-treated lung cancer patients.

The purpose of the study was to establish a comprehensive differential gene profile for lung cancer patients treated with cisplatin compared with control patients without any chemotherapy drug treatment. The RNA sequencing data and miRNA sequencing data of 108 lung cancer patients treated with cisplatin only and 232 lung cancer patients treated without any chemotherapeutic drugs, were analyzed using differential expression, protein-protein interaction, and immune cell infiltration ratio analysis. Compared with control patients, the cisplatin-treated patients demonstrated 336 differentially expressed genes, which included 48 upregulated genes and 288 downregulated genes. Meanwhile, 12 differentially expressed miRNAs (DEMs), including 7 upregulated miRNAs and 5 downregulated miRNAs showed a differentially expressed pattern. With further instigation, five miRNAs (hsa-miR-548ah, hsa-miR-466, hsa-miR-552, hsa-miR-371a, and hsa-miR-4445) were suggested to be the key targets in the cisplatin-treated patients. At the same time, we also found a significant correlation between the cisplatin treatment and six immune checkpoints including programmed cell death ligand. This study helped us better understand the potential targets and underline molecular mechanisms for cisplatin treatment and provided references to eliminate existing side effects in the future.

Bioinformatics Analysis for Multiple Gene Expression Profiles in Sepsis.

BACKGROUND This work aimed to screen key biomarkers related to sepsis progression by bioinformatics analyses. MATERIAL AND METHODS The microarray datasets of blood and neutrophils from patients with sepsis or septic shock were downloaded from Gene Expression Omnibus database. Then, differentially expressed genes (DEGs) from 4 groups (sepsis versus normal blood samples; septic shock versus normal blood samples; sepsis neutrophils versus normal controls and septic shock neutrophils versus controls) were respectively identified followed by functional analyses. Subsequently, protein-protein network was constructed, and key functional sub-modules were extracted. Finally, receiver operating characteristic analysis was conducted to evaluate diagnostic values of key genes. RESULTS There were 2082 DEGs between blood samples of sepsis patients and controls, 2079 DEGs between blood samples of septic shock patients and healthy individuals, 6590 DEGs between neutrophils from sepsis and controls, and 1056 DEGs between neutrophils from septic shock patients and normal controls. Functional analysis showed that numerous DEGs were significantly enriched in ribosome-related pathway, cell cycle, and neutrophil activation involved in immune response. In addition, TRIM25 and MYC acted as hub genes in protein-protein interaction (PPI) analyses of DEGs from microarray datasets of blood samples. Moreover, MYC (AUC=0.912) and TRIM25 (AUC=0.843) had great diagnostic values for discriminating septic shock blood samples and normal controls. RNF4 was a hub gene from PPI analyses based on datasets from neutrophils and RNF4 (AUC=0.909) was capable of distinguishing neutrophil samples from septic shock samples and controls. CONCLUSIONS Our findings identified several key genes and pathways related to sepsis development.

A theoretical study of the inhibition effect of PAMAM molecule on silica scale.

In this work, the molecular modeling method was performed to study adsorption interaction between PAMAM molecules of different generations and silicic acid molecules, and the inhibition effect on silica scale were discussed. The results show that adsorption energies of PAMAM molecule of generation 1.0 with amine-terminated groups are stronger than those of generation 1.5 with terminated carboxyl group. The composition of adsorption interactions are the dominating electrostatic interactions and van de Waals interactions as well as H-bond interactions. It is qualitatively discussed that the inhibition effect of generation 1.0 on silica scale is stronger than that of generation 1.5 in the neutral solution.

[Impact of depth and moisture to diesel degradation in sand layer of vadose zone].

Through the experiment simulated sand columns, the biodegradation characteristics of diesel in sand layers (including fine sand, medium sand and coarse sand) with different depths and moisture contents were studied. The results show that the depth and moisture content of medium are important factors in affecting the efficiency of diesel degradation. In the same medium conditions, the higher moisture content of the medium, the higher biological activity, and biological degradation efficiency of diesel are observed. The nature of medium affects the efficiency of diesel degradation in vadose zone. The finer particles of the medium, the higher ability of diesel degradation is. It is expressed as: fine sand > medium sand > coarse sand. Volatilization and biodegradation are important factors in affecting natural attenuation of diesel in vadose zone.