Surface Stoichiometry Control of Colloidal Heterostructured Quantum Dots for High-Performance Photoelectrochemical Hydrogen Generation.

Manipulating the separation and transfer behaviors of charges has long been pursued for promoting the photoelectrochemical (PEC) hydrogen generation based on II-VI quantum dot (QDs), but remains challenging due to the lack of effective strategies. Herein, a facile strategy is reported to regulate the recombination and transfer of interfacial charges through tuning the surface stoichiometry of heterostructured QDs. Using this method, it is demonstrated that the PEC cells based on CdSe-(Sex S1- x )4 -(CdS)2 core/shell QDs with a proper Ssurface /Cdsurface ratio exhibits a remarkably improved photocurrent density (≈18.4 mA cm-2 under one sun illumination), superior to the PEC cells based on QDs with Cd-rich or excessive S-rich surface. In-depth electrochemical and spectroscopic characterizations reveal the critical role (hole traps) of surface S atoms in suppressing the recombination of photogenerated charges, and further attribute the inferior performance of excessive S-rich QDs to the impeded charge transfer from QDs to TiO2 and electrolyte. This work puts forward a simple surface engineering strategy for improving the performance of QDs PEC cells, providing an efficient method to guide the surface design of QDs for their applications in other optoelectronic devices.

Optimization of oncolytic effect of Newcastle disease virus Clone30 by selecting sensitive tumor host and constructing more oncolytic viruses.

The direct oncolytic effect of Newcastle disease virus (NDV) depends on the following two aspects: the susceptibility of cancer cells to virus infection and the ability of virus itself to lyse cancer cells. First, we investigate the susceptibility of cancer cells to NDV infection, HepG2, MDA-MB-231, and SH-SY5Y cells were susceptible, A549, MCF7, and LoVo cells were less susceptible. To investigate the molecular mechanism responsible for cancer cell susceptibility, transcriptome sequencing was carried out. We found that the levels of alpha-sialic acid acyltransferase were upregulated in MDA-MB-231 cells compared with MCF7 cells, and the interferon was downregulated. Second, to optimize the oncolytic capacity of the wild-type rClone30, a series of chimeric viruses rClone30-Anh(HN), rClone30-Anh(F), and rClone30-Anh(HN-F) were constructed by exchanging the HN gene, F gene or both of non-lytic rClone30 strain with lytic strain Anhinga. rClone30-Anh(F) and rClone30-Anh(HN-F) enhanced the oncolytic effect of the rClone30, and this enhancement is more obvious in the susceptible cells. The oncolytic mechanism of rClone30-Anh(F) was analyzed by transcriptome analyses, in comparison with rClone30, rClone30-Anh(F) upregulated the expression of ATG5, Beclin 1, and MAP1LC3B, thus activating autophagy and promoting the production of syncytia. In conclusion, our study provides a strategy to enhance the oncolytic effect of rClone30.

Characterization and expression analysis of immune-related genes in the red swamp crayfish, Procambarus clarkii in response to lipopolysaccharide challenge.

To learn more about red swamp crayfish related genes in response to bacterial infections, we investigated immune-related genes induced by lipopolysaccharide (LPS) in the hepatopancreas using high-throughput sequencing method. In present the study, a total of 55,107 unigenes were identified, with an average length of 678 bp. A total of 2215 differentially expressed genes (DEGs) were found, including 669 up-regulated genes and 1546 down-regulated genes. The result of Gene ontology (GO) analysis revealed that 3017 DEGs were enriched in 19 biological process subcategories, 17 cellular component subcategories and 15 molecular function subcategories. The top 20 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways showed that "ribosome" was the most abundant group, which had 34 DEGs. KEGG enrichment analysis identified several immune response pathways. Real-time quantitative reverse transcription-PCR (qRT-PCR) results exhibited that several immune responsive genes were greatly up-regulated following LPS stimulation as observed in the results of high-throughput sequencing. Overall, this study provides new insight into the immune defense mechanisms of P. clarkii against LPS infection.

New insight into the molecular basis of Fe (III) stress responses of Procambarus clarkii by transcriptome analysis.

Iron in excess can have toxic effects on living organisms. In China, the freshwater crayfish Procambarus clarkii is a source of aquatic food with high-quality protein and has significant commercial value. P. clarkii shows oxidative stress on exposure to heavy metals, and antioxidant enzymes, such as ubiquitination enzymes and proteasomes, play important roles in oxidative stress. To understand the antioxidant defense system of P. clarkii, we analyzed the hepatopancreas transcriptomes of P. clarkii after stimulation with FeCl3. In total, 5199 differentially expressed genes (DEGs) were identified (2747 upregulated and 2452 downregulated). GO analysis revealed that these DEGs belonged to 16 cellular component, 16 molecular function, and 19 biological process subcategories. A total of 1069 DEGs were classified into 25 categories by using COG. Some antioxidant defense pathways, such as "Ubiquitin mediated proteolysis" and "Glutathione metabolism," were identified using KEGG. In addition, quantitative real time-PCR (qRT-PCR) substantiated the up-regulation of a random selection of DEGs including antioxidant and immune defense genes. We obtained information for P. clarkii transcriptome databases and new insights into the responses of P. clarkii hepatopancreas to heavy metals.

Prevalence and subtypes of Blastocystis in wild rodents from three provinces in China.

Introduction: Blastocystis is one of the most critical intestinal protozoans in various hosts, including humans and mice. To determine the status of Blastocystis infection in wild rodents in China. Methods: A total of 344 faecal samples were collected from seven wild rodent species from three provinces, and the small subunit ribosomal RNA (SSU rRNA) genes of Blastocystis were amplified to determine their prevalence and subtypes. Results: Of the 344 samples, 54 (15.70%) were detected as Blastocystis-positive. The prevalence of Blastocystis was 26.14% (40/153), 7.95% (7/88), and 6.80% (7/103) in wild rodents from Hunan Province, Yunnan Province, and Guangxi Province, respectively. The prevalence of Blastocystis in different wild rodent species varied from 0.00% (0/13) in Mus musculus to 40.00% (2/5) in Rattus rattus sladeni. The prevalence of Blastocystis in samples from the lake beach area (27.40%, 40/146) was significantly higher than in those from the mountain (6.80%, 7/103) and field regions (7.37%, 7/95). The prevalence in different seasons was 26.14% in summer (40/153), 7.95% in autumn (7/88), and 6.80% in winter (7/103). Moreover, a total of two Blastocystis subtypes were identified in the investigated wild rodents, including ST4 and ST5. Discussion: The present study discovered the existence of Blastocystis infection in Rattus favipectus, Microtus fortis, Apodemus agrarius, Bandicota indica, Rattus rattus sladeni, and Rattus losea, expanding the host range of this parasite. The findings also demonstrate that wild rodents may be an important potential infection source for Blastocystis infection in humans and other animals.

Ultrasensitive Wearable Pressure Sensors with Stress-Concentrated Tip-Array Design for Long-Term Bimodal Identification.

The great challenges for existing wearable pressure sensors are the degradation of sensing performance and weak interfacial adhesion owing to the low mechanical transfer efficiency and interfacial differences at the skin-sensor interface. Here, an ultrasensitive wearable pressure sensor is reported by introducing a stress-concentrated tip-array design and self-adhesive interface for improving the detection limit. A bipyramidal microstructure with various Young's moduli is designed to improve mechanical transfer efficiency from 72.6% to 98.4%. By increasing the difference in modulus, it also mechanically amplifies the sensitivity to 8.5 V kPa-1 with a detection limit of 0.14 Pa. The self-adhesive hydrogel is developed to strengthen the sensor-skin interface, which allows stable signals for long-term and real-time monitoring. It enables generating high signal-to-noise ratios and multifeatures when wirelessly monitoring weak pulse signals and eye muscle movements. Finally, combined with a deep learning bimodal fused network, the accuracy of fatigued driving identification is significantly increased to 95.6%.

Porcine epidemic diarrhea virus (PEDV) ORF3 protein inhibits cellular type I interferon signaling through down-regulating proteins expression in RLRs-mediated pathway.

Porcine epidemic diarrhea virus (PEDV) is an entero-pathogenic coronavirus, which belongs to the genus Alphacoronavirus in the family Coronaviridae, causing lethal watery diarrhea in piglets. Previous studies have shown that PEDV has developed an antagonistic mechanism by which it evades the antiviral activities of interferon (IFN), such as the sole accessory protein open reading frame 3 (ORF3) being found to inhibit IFN-ß promoter activities, but how this mechanism used by PEDV ORF3 inhibits activation of the type I signaling pathway remains not fully understood. Thus, in this present study, we showed that PEDV ORF3 inhibited both polyinosine-polycytidylic acid (poly(I:C))- and IFNα2b-stimulated transcription of IFN-ß and interferon-stimulated genes (ISGs) mRNAs. The expression levels of antiviral proteins in the retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs)-mediated pathway was down-regulated in cells with over-expression of PEDV ORF3 protein, but global protein translation remained unchanged and the association of ORF3 with RLRs-related antiviral proteins was not detected, implying that ORF3 only specifically suppressed the expression of these signaling molecules. At the same time, we also found that the PEDV ORF3 protein inhibited interferon regulatory factor 3 (IRF3) phosphorylation and poly(I:C)-induced nuclear translocation of IRF3, which further supported the evidence that type I IFN production was abrogated by PEDV ORF3 through interfering with RLRs signaling. Furthermore, PEDV ORF3 counteracted transcription of IFN-ß and ISGs mRNAs, which were triggered by over-expression of signal proteins in the RLRs-mediated pathway. However, to our surprise, PEDV ORF3 initially induced, but subsequently reduced the transcription of IFN-ß and ISGs mRNAs to normal levels. Additionally, mRNA transcriptional levels of signaling molecules located at IFN-ß upstream were not inhibited, but elevated by PEDV ORF3 protein. Collectively, these results demonstrate that inhibition of type I interferon signaling by PEDV ORF3 can be realized through down-regulating the expression of signal molecules in the RLRs-mediated pathway, but not via inhibiting their mRNAs transcription. This study points to a new mechanism evolved by PEDV through blockage of the RLRs-mediated pathway by ORF3 protein to circumvent the host's antiviral immunity.

Vaccination with the repeat ß-hCG C-terminal peptide carried by heat shock protein-65 (HSP65) for inducing antitumor effects.

The ß-subunit of human chorionic gonadotropin (ß-hCG) is ectopically expressed in various types of cancer and has been utilized as an antigenic target in anti-cancer vaccines. In view of the low immunogenicity of this self-peptide, we designed a method based on the isocaudamer technique to generate 14 tandem repeats of the 10-residue sequence X of ß-hCG (109-118). These tandemly repeated copies were then combined with ß-hCG C-terminal 37 peptides (CTP37) and finally fused to mycobacterial heat-shock protein 65 (HSP65) to construct a fusion protein HSP65-X14-ßhCGCTP37 as an immunogen. In this study, BALB/c female mice were immunized via subcutaneous injection of the designed protein. Humoral immune and cellular immune responses were effectively elicited. A high titer of anti-ß-hCG antibody was detected in immunized mice sera by enzyme-linked immunosorbent assay and verified by Western blot analysis. The fusion protein, HSP65-X14-ß-hCGCTP37, effectively inhibited the growth of Ehrlich ascites carcinoma in mice. These results suggest that HSP65-X14-ßhCGCTP37 may be an effective tumor vaccine, and the use of multiple tandem repeats of a certain epitope is an effective method to overcome the low immunogenicity of self-peptide antigens.

Protective antitumor immunity induced by tumor cell lysates conjugated with diphtheria toxin and adjuvant epitope in mouse breast tumor models.

Cancer cell vaccine-based immunotherapy has received increasing interest in many clinical trials involving patients with breast cancer. Combining with appropriate adjuvants can enhance the weak immunogenic properties of tumor cell lysates (TCL). In this study, diphtheria toxin (DT) and two tandem repeats of mycobacterial heat shock protein 70 (mHSP70) fragment 407-426 (M2) were conjugated to TCL with glutaraldehyde, and the constructed cancer cell vaccine was named DT-TCL-M2. Subcutaneous injection of DT-TCL-M2 in mice effectively elicited tumor-specific polyclonal immune responses, including humoral and cellular immune responses. High levels of antibodies against TCL were detected in the serum of immunized mice with ELISA and verified with Western blot analyses. The splenocytes from immunized mice showed potent cytotoxicity on Ehrlich ascites carcinoma cells. Moreover, the protective antitumor immunity induced by DT-TCL-M2 inhibited tumor growth in a mouse breast tumor model. DT-TCL-M2 also attenuated tumor-induced angiogenesis and slowed tumor growth in a mouse intradermal tumor model. These findings demonstrate that TCL conjugated with appropriate adjuvants induced effective antitumor immunity in vivo. Improvements in potency could further make cancer cell vaccines a useful and safe method for preventing cancer recurrence after resection.

A Liquid-Solid Interface-Based Triboelectric Tactile Sensor with Ultrahigh Sensitivity of 21.48 kPa-1.

Traditional triboelectric tactile sensors based on solid-solid interface have illustrated promising application prospects through optimization approach. However, the poor sensitivity and reliability caused by hard contact-electrification still poses challenges for the practical applications. In this work, a liquid-solid interface ferrofluid-based triboelectric tactile sensor (FTTS) with ultrahigh sensitivity is proposed. Relying on the fluidity and magnetism of ferrofluid, the topography of microstructure can be flexibly adjusted by directly employing ferrofluid as triboelectric material and controlling the position of outward magnet. To date, an ultrahigh sensitivity of 21.48 kPa-1 for the triboelectric sensors can be achieved due to the high spike microstructure, low Young's modulus of ferrofluid and efficient solid-liquid interface contact-electrification. The detection limit of FTTS of 1.25 Pa with a wide detection range to 390 kPa was also obtained. In addition, the oleophobic property between ferrofluid and poly-tetra-fluoro-ethylene triboelectric layer can greatly reduce the wear and tear, resulting in the great improvement of stability. Finally, a strategy for personalized password lock with high security level has been demonstrated, illustrating a great perspective for practical application in smart home, artificial intelligence, Internet of things, etc.

Potential effects and mechanisms of Chinese herbal medicine in the treatment of psoriasis.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis is a chronic inflammatory dermatosis related to high morbidity and mortality. The incidence of psoriasis is increasing in recent decades. Some patients with psoriasis are anxious about the underlying side effects of synthetic drugs they are on. Therefore, they are eager to seek alternative and efficient therapy, such as Chinese herbal medicine (CHM). Researchers have found some CHM provides best source for the development of anti-psoriatic drugs because of their structural diversity and fewer adverse reactions. Some of CHM formulas or active constituents extracted from CHM have been rapidly developed into clinical drugs with good efficacy. At present, along with the CHM formulas, single CHM and its active components have been extensively accepted and utilized in the treatment of psoriasis, whose therapeutic mechanisms hitherto have not been thoroughly illustrated. AIM OF THE STUDY: This review aimed to comprehensively summarize about the existing therapeutic mechanisms of CHM in the treatment of psoriasis and to provide a reference to develop future related studies in this field. MATERIALS AND METHODS: Relevant literatures about how CHM treated psoriasis were acquired from published scientific studies (including PubMed, CNKI, Web of Science, Baidu Scholar, The Plant List, Elsevier and SciFinder). All plants appearing in the review have been included in The Plant List or Medicinal Plant Names Services (MPNS). RESULTS: In this review, we collect numerous literatures about how CHM treats psoriasis via immune cells, signaling pathways and disease-related mediators and systematically elucidates potential mechanisms from the point of the suppression of oxidative stress, the inhibition of abnormal abnormal proliferation and differentiation, the inhibition of immune responses, and the suppression of angiogenesis. CONCLUSIONS: Psoriasis is considered as a complicated disease caused by interaction among various mechanisms. The CHM formulas, single CHM and its active components have considerable positive reports about the treatment of psoriasis, which brings hope for a promising future of CHM in the clinical therapy of psoriasis. In the paper, we have concluded that the existing therapeutic mechanisms of CHM in the treatment of psoriasis.

Porcine epidemic diarrhea virus E protein inhibits type I interferon production through endoplasmic reticulum stress response (ERS)-mediated suppression of antiviral proteins translation.

Porcine epidemic diarrhea virus (PEDV) envelope protein (E) is recognized as a viroporin that plays important functions in virus budding, assembly and virulence. Our previous study found that PEDV E protein induces endoplasmic reticulum stress (ERS), as well as suppresses the type I interferon (IFN) response, but their link and underlying mechanism remain obscure. To better understand this relationship, we investigated the roles of PEDV E protein-induced ERS in regulating cellular type I IFN production. Our results showed that PEDV E protein localized in the ER and triggered ERS through activation of PERK/eIF2α branch, as revealed by the up-regulated phosphorylation of PERK and eIF2α. PEDV E protein also significantly inhibited both poly(I:C)-induced and RIG-I signaling-mediated type I interferon production. The PERK/eIF2α branch of ERS activated by PEDV E protein led to the translation attenuation of RIG-I signaling-associated antiviral proteins, resulting in the suppression of type I IFN production. However, PEDV E protein had no effect on the mRNA transcription of RIG-I-associated molecules. Moreover, suppression of ERS with 4-PBA, a widely used ERS inhibitor, restored the expression of RIG-I-signaling-associated antiviral proteins and mRNA transcription of IFN-ß and ISGs genes to their normal levels, suggesting that PEDV E protein blocks the production of type I IFN through inhibiting expression of antiviral proteins caused by ERS-mediated translation attenuation. This study elucidates the mechanism by which PEDV E protein specifically modulates the ERS to inhibit type I IFN production, which will augment our understanding of PEDV E protein-mediated virus evasion of host innate immunity.

An immuno-blocking agent targeting IL-1ß and IL-17A reduces the lesion of DSS-induced ulcerative colitis in mice.

In recent decades when biological agents have flourished, a part of patients suffering from inflammatory bowel disease (IBD) have received the treatment of tumor necrosis factor inhibitors or IL-1 antibodies. This study aims to investigate the anti-colitis effects of bispecific antibody (FL-BsAb1/17) targeting IL-1ß and IL-17A comparing with TNF-α soluble receptor medicine etanercept. IBD model in mice was established by drinking 3% DSS (dextran sulfate sodium salt). On the first day of drinking DSS, treatments with etanercept (5 mg/kg) or different doses of FL-BsAb1/17 (1 mg/kg, 5 mg/kg, and 10 mg/kg) were started by intraperitoneal injection every other day. The results demonstrated that FL-BsAb1/17 treatment was more effective than etanercept at the same dose (5 mg/kg) in relieving the typical symptom of ulcerative colitis induced by DSS (such as the severity score and intestinal shortening), and down-regulating the expression of inflammatory factors (IL-17A, IL-6, IL-12, IL-22, IL-1ß, IL-23, TNF-α) in the serum and colon. FL-BsAb1/17 could also reduce the degree of intestinal fibrosis. The same dose of FL-BsAb1/17 (5 mg/kg) performed better than etanercept in down-regulating MDA and up-regulating SOD (superoxide dismutase), CAT (catalase), and T-AOC (total antioxidant capacity) in serum. Both FL-BsAb1/17 and etanercept could reduce the transcription of Bax and increase the transcription of Bcl-2 and slow down apoptosis in colitis colon tissue. We conclude that the blocking of IL-1ß and IL-17A can inhibit DSS-induced ulcerative colitis and FL-BsAb1/17 may have potential to become a new dual-target candidate for colitis treatment.

A natural lipopeptide of surfactin for oral delivery of insulin.

Surfactin, a natural lipopeptide produced by Bacillus, is gaining attention for potentially biomedical and pharmaceutical applications. Here, surfactin was assayed for oral delivery of insulin (INS) by its ability to bind to and promote protein to penetrate through the cell membrane. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, surfactin was found to form co-precipitates with INS to protect it from acidic and enzymatic attack in the gastrointestinal tract. Further analysis by non-reductive electrophoresis showed surfactin could bind to INS forming heteropolymers. Analysis with circular dichroism, we found this binding significantly influenced the INS structure with decreased rigid α-helix and ß-turn, but with increased flexible ß-sheet and random coil. The change with more flexible structure was favorable for INS to penetrate through the cell membrane. Fluorescence spectra analysis also showed surfactin could lead Phe and Tyr in the inner of INS exposed outside, further promoting INS permeabilization by improving the hydrophobic-lipophilic interactions between INS and cell membrane. As a result, the effective permeability (Peff) of INS plus surfactin was 4.3 times of that of INS alone. In vivo assay showed oral INS with surfactin displayed excellent hypoglycemic effects with a relative bioavailability of 12.48% and 5.97% in diabetic mice and non-diabetic dogs, respectively. Summary, surfactin is potential for oral delivery of INS by its role as an effective protease inhibitor and permeability enhancer.

Surfactin inducing mitochondria-dependent ROS to activate MAPKs, NF-κB and inflammasomes in macrophages for adjuvant activity.

Surfactin, a natural lipopeptide, can be used both as parenteral and non-parenteral adjuvant for eliciting immune response. However, the mechanisms that confer its adjuvant properties have not been fully explored. By staining with NHS-Rhodamine B labeled surfactin and Mito-Tracker Green, we found surfactin could penetrate into macrophages to bind with mitochondria, following induce ROS that could be inhibited by mitochondria-dependent ROS inhibitor. ROS enhanced p38 MAPK and JNK expression, as well their phorsphorylation, following activated NF-κB nuclear translocation in macrophages that was obviously inhibited by mitochondria-dependent ROS inhibitor. However, inhibition of ROS production only weakened p38 MAPK and JNK expression, but not their phosphorylation in macrophages. As a result, surfaction could activate NF-κB to release TNF-α by the mitochondria-dependent ROS signalling pathway. ROS also induced macrophages apoptosis to release endogenous danger signals, following activated inflammasomes of NLRP1, NLRP3, IPAF and AIM2 in vitro and only NLRP1 in vivo, as well caspase-1 and IL-1 in macrophages, which were significantly inhibited by pre-treatment with ROS inhibitors. Collectively, surfactin as a kind of non-pathogen-associated molecular patterns, modulates host innate immunity by multiple signalling pathways, including induction of mitochondria-dependent ROS, activating MAPKs and NF-κB, and inducing cell apoptosis to realease endogenous danger signals for activation of inflammasomes.

Bacillus-produced surfactin attenuates chronic inflammation in atherosclerotic lesions of ApoE(-/-) mice.

Bacillus-produced surfactin can inhibit acute inflammation in vitro and in vivo. However, there is no report whether surfactin could inhibit chronic inflammation in the atherosclerotic lesions. Apoliprotein E deficient (ApoE(-/-)) mice (fed on atherogenic diet) were intragastrically administered with surfactin for 9 doses, then the athero-protective effect of surfactin was determined in vivo. The results showed surfactin could induce anti-inflammatory factors such as IgA, transforming growth factor (TGF)-ß and interleukin (IL)-10 in the intestine. Further investigation discovered that surfactin also systemically induced CD4(+)CD25(+)FoxP3(+) Tregs in spleen, which could inhibit T cells to produce pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α and interferon (IFN)-γ. The IgG subclass pattern with high titer of IgG1 (Th2-type) but low titer of IgG2a (Th1-type) was also found in the surfactin-treated mice. As a result, the attenuation of chronic inflammation was observed in the surfactin-treated groups accompanying with less TNF-α but more IL-10 in the atherosclerotic lesions. Moreover, surfactin could reduce serum total cholesterol and cholesterol in low-density lipoprotein, and increase serum cholesterol in high-density lipoprotein in mice. Collectively, surfactin could significantly attenuate atherosclerotic lesions on the aorta by restoration of the delicate balance of Th1/Th2 response in mice.

A surfactin lipopeptide adjuvanted hepatitis B vaccines elicit enhanced humoral and cellular immune responses in mice.

WH1fungin (WF), a lipopeptide surfactin, has been verified as an immunoadjuvant previously. In this study, mice were intranasally or parenterally immunized with WF plus Hepatitis B surface antigen (HBsAg), then the immune responses were detected. The results showed 50 µg WF plus 20 µg HBsAg for intranasal and 10 µg WF plus 1 µg HBsAg for parenteral immunization was efficient inducing strong immune response against HBsAg in mice. A high titer and longterm anti-HBsAg IgG was observed for more than 19 weeks in intranasal or parenteral immunizations, much higher than that induced by CpG or Alum adjuvant. The anti-HBsAg IgA was also induced in intestine and lung, indicating that mucosal as well as systemic immune response was elicited for intranasal immunization. The IgG isotype in serum revealed WF induced a Th2-bias immune response with a higher titer of anti-HBsAg IgG1 than IgG2a in mice. Moreover, WF also induced more Th1 cells producing interferon (IFN)-γ and stronger cytotoxic T lymphocytes response than controls for intramuscular administration. These data further confirmed that WF induced Th1- as well as Th2- type immune response toward HBsAg. Taken together, WF-adjuvanted HBsAg elicits more effective immune response than that adjuvanted by Alum or CpG, suggesting its potential for development of more efficient HBV vaccines in the future.

Immunomodulation therapy of diabetes by oral administration of a surfactin lipopeptide in NOD mice.

Type 1 diabetes mellitus (T1DM) is considered an autoimmune disease, which can be attenuated by modulation of immune pathway from Th1- to Th2-type through vaccination. WH1fungin surfactin is a Bacillus-produced natural immunomodulator. NOD mice were orally treated with 5mg/kg or 25mg/kg WH1fungin once a week for total 4 weeks. After the final administration, the diabetes incidence and the anti-inflammatory roles of WH1fungin were investigated by immunohistochemistry, FACS and ELISA. The results showed oral WH1fungin obviously resulted in a WH1fungin-unspecific suppression of T1DM. Diabetes incidence was significantly reduced when compared to phosphate buffered saline (PBS) control. Mice in the control group began to be onset of diabetes at week 15, following with an increased mortality from week 16 to 28. At the end of observation, the diabetes incidence reached to 81% at week 30, while only 25% in WH1fungin groups. The splenocytes assay showed oral WH1fungin could suppress T cells proliferation, down-regulate amounts of activated CD8(+) T cells with the production of tumor necrosis factor (TNF)-α and interferon (IFN)-γ, and increase CD4(+)CD25(+)FOXP3(+) regulator T cells (Tregs). The serum assay revealed oral WH1fungin down-regulated TNF-α and IgG2a but increased interleukin (IL)-10 and IgG1 in mice. All of these data showed oral WH1fungin tended to switch the immune response from Th1- to Th2-type. The further surveys revealed that less IFN-γ but more transfer growth factor (TGF)-ß were found in the islets of mice with oral WH1fungin when compared to that in the control group. As a result, the normal islet architecture and slight inflammatory cells infiltration was observed with a slight insulitis in the oral WH1fungin groups. These results demonstrate that oral WH1fungin might be a novel therapeutic approach for the prevention of T1DM.

WH1fungin a surfactin cyclic lipopeptide is a novel oral immunoadjuvant.

WH1fungin, a surfactin lipopeptide from Bacillus amyloliquefaciens WH1, can be used as an adjuvant for eliciting strong immune response by parenteral immunization. In this study, WH1fungin was firstly reported as an oral immunoadjuvant. In mice, WH1fungin markedly enhanced the immune response to co-administered protein antigens (OVA or GST), similar to levels elicited by CTB, but no immune response was elicited to itself. Both IgG1 and IgG2a antibodies elicited from the immunizations indicating a mixed Th1/Th2 response. Splenocytes from mice immunized with OVA plus WH1fungin responded to OVA CTL peptide stimulation resulting in an increase in CD8(+)TNF-α(+) and CD8(+)IFN-γ(+) T cell populations. These results further suggested that WH1fungin helps to elicit both humoral and cellular responses to OVA. More studies revealed that the potential mechanism as oral immunoadjuvant was that WH1fungin could form co-precipitates with antigens in a pH value similar to gastric juice. The precipitation protected the antigens from degradation by pepsin providing an explanation for the antigens to withstand the acidic and proteolytic environments of the gastrointestinal tract when co-administered with WH1fungin. Moreover, WH1fungin promoted the uptake of OVA by the intestine and by cultured DC2.4 cells, and increased the expression of cell surface markers and cytokines in DC2.4 cells. Taken together, WH1fungin is a potent oral immunoadjuvant with the ability of protecting protein antigens from acidic and proteolytic degradation, suggesting its potential usage in oral vaccine development.