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1.
Int J Mol Sci ; 25(12)2024 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-38928319

RESUMEN

Matrine (MT) possesses anti-inflammatory, anti-allergic and antioxidative properties. However, the impact and underlying mechanisms of matrine on colitis are unclear. The purpose of this research was to examine the protective impact and regulatory mechanism of matrine on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. MT alleviated DSS-induced UC by inhibiting weight loss, relieving colon shortening and reducing the disease activity index (DAI). Moreover, DSS-induced intestinal injury and the number of goblet cells were reversed by MT, as were alterations in the expression of zonula occludens-1 (ZO-1) and occludin in colon. Simultaneously, matrine not only effectively restored DSS-induced oxidative stress in colonic tissues but also reduced the production of inflammatory cytokines. Furthermore, MT could treat colitis mice by regulating the regulatory T cell (Treg)/T helper 17 (Th17) cell imbalance. We observed further evidence that MT alleviated the decrease in intestinal flora diversity, reduced the proportion of Firmicutes and Bacteroidetes, decreased the proportion of Proteobacteria and increased the relative abundance of Lactobacillus and Akkermansia in colitis mice. In conclusion, these results suggest that MT may mitigate DSS-induced colitis by enhancing the colon barrier integrity, reducing the Treg/Th17 cell imbalance, inhibiting intestinal inflammation, modulating oxidative stress and regulating the gut microbiota. These findings provide strong evidence for the development and application of MT as a dietary treatment for UC.


Asunto(s)
Alcaloides , Sulfato de Dextran , Microbioma Gastrointestinal , Matrinas , Estrés Oxidativo , Quinolizinas , Linfocitos T Reguladores , Animales , Alcaloides/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Quinolizinas/farmacología , Quinolizinas/uso terapéutico , Ratones , Linfocitos T Reguladores/metabolismo , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Masculino , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/metabolismo , Colitis/microbiología , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Proteína de la Zonula Occludens-1/metabolismo , Colon/patología , Colon/metabolismo , Colon/efectos de los fármacos , Colon/microbiología , Células Th17/efectos de los fármacos , Células Th17/metabolismo , Células Th17/inmunología , Modelos Animales de Enfermedad , Citocinas/metabolismo , Ratones Endogámicos C57BL , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/microbiología , Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/patología , Ocludina/metabolismo
2.
Small ; : e2402792, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38940386

RESUMEN

Adjuvants play a critical role in the induction of effective immune responses by vaccines. Here, a self-assembling nanovaccine platform that integrates adjuvant functions into the delivery vehicle is prepared. Cationic Lentinan (CLNT) is mixed with ovalbumin (OVA) to obtain a self-assembling nanovaccine (CLNTO nanovaccine), which induces the uptake and maturation of bone marrow dendritic cells (BMDCs) via the toll-like receptors 2/4 (TLR2/4) to produce effective antigen cross-presentation. CLNTO nanovaccines target lymph nodes (LNs) and induce a robust OVA-specific immune response via TLR and tumor necrosis factor (TNF) signaling pathways, retinoic acid-inducible gene I (RIG-I) receptor, and cytokine-cytokine receptor interactions. In addition, CLNTO nanovaccines are found that promote the activation of follicular helper T (Tfh) cells and induce the differentiation of germinal center (GC) B cells into memory B cells and plasma cells, thereby enhancing the immune response. Vaccination with CLNTO nanovaccine significantly inhibits the growth of ovalbumin (OVA)-expressing B16 melanoma cell (B16-OVA) tumors, indicating its great potential for cancer immunotherapy. Therefore, this study presents a simple, safe, and effective self-assembling nanovaccine that induces helper T cell 1 (Th1) and helper T cell (Th2) immune responses, making it an effective vaccine delivery system.

4.
Chem Biodivers ; 21(6): e202302102, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38567653

RESUMEN

Rosa laevigata Michx. polysaccharides (RLP) have been demonstrated to possess antioxidant and anti-inflammatory properties. However, the mechanisms and efficacy of these polysaccharide components in preventing ulcerative colitis (UC) remain to be elucidated. The efficacy and mechanisms of RLP were investigated in a study that utilized healthy adult beagles to establish a UC model, considering the similarities in gut microbiota between humans and dogs. In the study, the beagle model induced by sodium dextran sulfate exhibited typical symptoms of ulcerative colitis, such as weight loss and diarrhea. All these symptoms and changes were significantly ameliorated through oral supplementation of RLP. Additionally, microbial community analysis based on the 16S rDNA gene revealed that RLP alleviated UC by increasing the abundance of beneficial bacteria and reducing the abundance of harmful bacteria. In conclusion, our study has provided that RLP effectively alleviated colitis by preserving the intestinal barrier and regulating the gut microbiota composition.


Asunto(s)
Colitis Ulcerosa , Sulfato de Dextran , Microbioma Gastrointestinal , Polisacáridos , Rosa , Animales , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/patología , Perros , Microbioma Gastrointestinal/efectos de los fármacos , Polisacáridos/farmacología , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Rosa/química , Modelos Animales de Enfermedad , Masculino
5.
Int J Biol Macromol ; 264(Pt 2): 130621, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38447834

RESUMEN

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.


Asunto(s)
Terapia de Inmunosupresión , Lentinano , Animales , Ratones , Lentinano/farmacología , Tolerancia Inmunológica , Intestinos , Dexametasona/farmacología
6.
NPJ Vaccines ; 9(1): 22, 2024 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-38310094

RESUMEN

Here we report on the development and comprehensive evaluations of an mRNA vaccine for chronic hepatitis B (CHB) treatment. In two different HBV carrier mouse models generated by viral vector-mediated HBV transfection (pAAV-HBV1.2 and rAAV8-HBV1.3), this vaccine demonstrates sufficient and persistent virological suppression, and robust immunogenicity in terms of induction of strong innate immune activation, high-level virus-specific antibodies, memory B cells and T cells. mRNA platform therefore holds prospects for therapeutic vaccine development to combat CHB.

7.
Int J Mol Sci ; 25(4)2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38396810

RESUMEN

RLPa-2 (Mw 15.6 kDa) is a polysaccharide isolated from Rosa laevigata Michx. It consists of arabinose (Ara), galactose (Gal), rhamnose (Rha), glucose (Glc), xylose (Xyl), and galacturonic acid (Gal-UA) with a molar ratio of 1.00:0.91:0.39:0.34:0.25:0.20. Structural characterization was performed by methylation and NMR analysis, which indicated that RLPa-2 might comprise →6)-α-D-Galp-(1→, →4)-α-D-GalpA-(1→, α-L-Araf-(1→, →2,4)-α-D-Glcp-(1→, ß-D-Xylp, and α-L-Rhap. In addition, the bioactivity of RLPa-2 was assessed through an in vitro macrophage polarization assay. Compared to positive controls, there was a significant decrease in the expression of M1 macrophage markers (CD80, CD86) and p-STAT3/STAT3 protein. Additionally, there was a down-regulation in the production of pro-inflammatory mediators (NO, IL-6, TNF-α), indicating that M1 macrophage polarization induced with lipopolysaccharide (LPS) and interferon-γ (IFN-γ) stimulation could be inhibited by RLPa-2. These findings demonstrate that the RLPa-2 might be considered as a potential anti-inflammatory drug to reduce inflammation.


Asunto(s)
Frutas , Rosa , Frutas/química , Rosa/química , Polisacáridos/química , Macrófagos , Antiinflamatorios/farmacología , Antiinflamatorios/análisis
8.
Int J Pharm ; 653: 123901, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38368969

RESUMEN

While research on mevalonate inhibitors as vaccine adjuvants has made great progress to enhance the effectiveness of the vaccine, co delivery of lovastatin and antigens (OVA) remains an enormous challenge. Here, we encapsulated lovastatin into PLGA nanoparticles. PLGA loading lovastatin was further emulsified with squalene to prepare Pickering emulsion. The emulsification conditions of Pickering emulsion were optimized, and the optimal preparation conditions were obtained. After loading lovastatin and OVA, the size and zeta potential of LS-PPAS/OVA was 1043.33 nm and -22.07 mv, the adsorption rate of OVA was 63.34 %. The adsorbing of LS-PLGA nanoparticles on the surface of squalene in Pickering emulsions was demonstrated by Fluorescent confocal microscopy. After immunization, LS-PPAS enhanced the activation of dendritic cells in lymph nodes, further study found LS-PPAS not only elicited elevated levels of OVA-specific IgG and its subtypes, but also promoted the secretion of TNF-α, IFN-γ, and IL-6 in serum as a marker of cellular immunity. Importantly, LS-PPAS showed sufficient security through monitoring levels of biochemical parameters in serum and pathological observation of organ following vaccinations. LS-PPAS may act as a promising vaccine carrier to produce strong humoral and cellular immunity with acceptable safety.


Asunto(s)
Nanopartículas , Vacunas , Adyuvantes de Vacunas , Adyuvantes Inmunológicos , Emulsiones , Escualeno/química , Nanopartículas/química
9.
Emerg Microbes Infect ; 13(1): 2309985, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38258878

RESUMEN

Herpes zoster remains an important global health issue and mainly occurs in aged and immunocompromised individuals with an early exposure history to Varicella Zoster Virus (VZV). Although the licensed vaccine Shingrix has remarkably high efficacy, undesired reactogenicity and increasing global demand causing vaccine shortage urged the development of improved or novel VZV vaccines. In this study, we developed a novel VZV mRNA vaccine candidate (named as ZOSAL) containing sequence-optimized mRNAs encoding full-length glycoprotein E encapsulated in an ionizable lipid nanoparticle. In mice and rhesus macaques, ZOSAL demonstrated superior immunogenicity and safety in multiple aspects over Shingrix, especially in the induction of strong T-cell immunity. Transcriptomic analysis revealed that both ZOSAL and Shingrix could robustly activate innate immune compartments, especially Type-I IFN signalling and antigen processing/presentation. Multivariate correlation analysis further identified several early factors of innate compartments that can predict the magnitude of T-cell responses, which further increased our understanding of the mode of action of two different VZV vaccine modalities. Collectively, our data demonstrated the superiority of VZV mRNA vaccine over licensed subunit vaccine. The mRNA platform therefore holds prospects for further investigations in next-generation VZV vaccine development.


Asunto(s)
Vacuna contra el Herpes Zóster , Herpes Zóster , Animales , Ratones , Macaca mulatta , Vacunas de ARNm , Herpes Zóster/prevención & control , Herpesvirus Humano 3
10.
Int J Biol Macromol ; 261(Pt 2): 129813, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38286367

RESUMEN

Rehmannia glutinosa polysaccharide (RGP) has been reported to exhibit anti-anxiety effects, yet the underlying mechanism remains unclear. Chronic constant light (CCL) induced cognitive dysfunction associated with oxidative stress in mice has been reported. Here, the neuroprotective effect of RGP on hippocampal neuron damage in CCL-treated mice was investigated. In vivo study, mice were subjected to CCL for 4 weeks and/or oral administration of 100, 200 and 400 mg/kg RGP every other day. In vitro experiment, hippocampal neuron cells (HT-22) was exposed to LED light and/or supplemented with 62.5, 125 and 250 µg/mL RGP. Mice exposed to CCL showed impaired cognitive and depressive-like behavior in the hippocampus, which were reversed by RGP. Meanwhile, RGP reversed light-induced oxidative stress and autophagy both in mice and hippocampal neuron cells (HT-22). Furthermore, compared with Light-exposed group, RGP treatment activated the AKT/mTOR pathway. Importantly, the AKT inhibitor Perifosine significantly weakened the neuroprotective of RGP on Light-induced oxidative stress and autophagy in HT-22 cells by inhibiting AKT/mTOR pathway and increasing the content of autophagy-related protein. Our data demonstrated, for the first time, that oxidative stress and the AKT/mTOR pathway plays a critical role in Light-induced apoptosis and autophagic cell death in mice and HT-22 cells.


Asunto(s)
Muerte Celular Autofágica , Fármacos Neuroprotectores , Rehmannia , Animales , Ratones , Proteínas Proto-Oncogénicas c-akt/metabolismo , Rehmannia/metabolismo , Fármacos Neuroprotectores/farmacología , Polisacáridos/farmacología , Serina-Treonina Quinasas TOR/metabolismo , Estrés Oxidativo , Autofagia , Hipocampo/metabolismo
11.
Carbohydr Polym ; 322: 121362, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-37839834

RESUMEN

Walnut green husk polysaccharides (WGP) are isolated from the walnut green husk with a mean molecular weight of 12.77 kDa. The structural characterization revealed by methylation and NMR analysis indicated that WGP might consist of →4-α-D-Galp-(1→, α-D-Galp (1→, and →2)-α-L-Rhap-(1→. Previous studies have been demonstrated that WGP effectively prevented liver injury and modulated gut microbiota in high fructose-treated mice and high fat diet-treated rats. In this study, we found for the first time that WGP presenting outstanding protective effects on liver inflammation and gluconeogenesis dysfunction induced by ochratoxin A (OTA) in mice. Firstly, WGP decreased oxidative stress, down-regulated the expression of inflammatory factors and inhibited the TLR4/p65/IκBα pathway in the liver. Then, WGP reversed OTA-induced lower phosphoenolpyruvate carboxyl kinase (PEPCK), and glucose 6-phosphatase (G6PC) activities in the liver. Furthermore, WGP increased the diversity of gut microbiota and the abundance of beneficial bacteria, especially Lactobacillus and Akkermansia. Importantly, the results of fecal microbiota transplantation (FMT) experiment further confirmed that gut microbiota involved in the protective effects of WGP on liver damage induced by OTA. Our results indicated that the protective effect of WGP on liver inflammation and gluconeogenesis dysfunction caused by OTA may be due to the regulation of gut microbiota.


Asunto(s)
Microbioma Gastrointestinal , Juglans , Ratones , Ratas , Animales , Gluconeogénesis , Hígado , Polisacáridos/farmacología , Polisacáridos/uso terapéutico , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo
12.
Int J Biol Macromol ; 253(Pt 1): 126629, 2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-37657564

RESUMEN

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.


Asunto(s)
Hidrogeles , Lentinano , Lentinano/farmacología , Lentinano/química , Adyuvantes Inmunológicos/química , Antígenos , Vacunas de Subunidad
13.
Int J Biol Macromol ; 251: 126315, 2023 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-37582438

RESUMEN

Light at night (LAN) induced cognitive impairment associated with oxidative stress in mice has been reported. Lycium barbarum polysaccharide (LBP) exhibits anti-tumor, anti-oxidant and neuroprotective effects, yet the neuroprotective effect on light-induced neuron damage still unclear. Here, mice exposed to LAN displayed cognitive impairment and depressive like behavior, which was reversed by LBP treatment. Meanwhile, LBP alleviated light-induced higher apoptosis and mitochondrial damage in HT-22 cells. Also, LBP prevented the decreased of mitochondrial membrane permeabilization (MMP) level in light-treated cells. Additionally, LBP demonstrated its antioxidant potential by reducing ROS production and malondialdehyde (MDA) level, while simultaneously enhancing the levels of superoxide dismutase (SOD) and glutathione peroxidases (GSH-Px) in both light-treated mice and HT-22 cells. Furthermore, the mRNA and protein expression of Nrf2 (NF-E2-related factor 2), heme oxygenease-1 (HO-1), and NAD(P)H quinone oxidoreductase (NQO1) were decreased in both light-treated mice and cells. Additionally, LBP treatment reversed light-induced the inhibition of Nrf2/HO-1 signaling pathway in both mice and cells. Moreover, Nrf2 antagonist ML385 significantly eliminated the neuroprotection of LBP on cell apoptosis, oxidative stress and mitochondrial damage in light-treated cells. These results indicate that LBP can rescue light-induced neurotoxicity in mice and HT-22 cells by activating the Nrf2/HO-1 signaling pathway.

14.
Mol Pharm ; 20(3): 1613-1623, 2023 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-36795759

RESUMEN

Chinese yam polysaccharides (CYPs) have received wide attention for their immunomodulatory activity. Our previous studies had discovered that the Chinese yam polysaccharide PLGA-stabilized Pickering emulsion (CYP-PPAS) can serve as an efficient adjuvant to trigger powerful humoral and cellular immunity. Recently, positively charged nano-adjuvants are easily taken up by antigen-presenting cells, potentially resulting in lysosomal escape, the promotion of antigen cross-presentation, and the induction of CD8 T-cell response. However, reports on the practical application of cationic Pickering emulsions as adjuvants are very limited. Considering the economic damage and public-health risks caused by the H9N2 influenza virus, it is urgent to develop an effective adjuvant for boosting humoral and cellular immunity against influenza virus infection. Here, we applied polyethyleneimine-modified Chinese yam polysaccharide PLGA nanoparticles as particle stabilizers and squalene as the oil core to fabricate a positively charged nanoparticle-stabilized Pickering emulsion adjuvant system (PEI-CYP-PPAS). The cationic Pickering emulsion of PEI-CYP-PPAS was utilized as an adjuvant for the H9N2 Avian influenza vaccine, and the adjuvant activity was compared with the Pickering emulsion of CYP-PPAS and the commercial adjuvant (aluminum adjuvant). The PEI-CYP-PPAS, with a size of about 1164.66 nm and a ζ potential of 33.23 mV, could increase the H9N2 antigen loading efficiency by 83.99%. After vaccination with Pickering emulsions based on H9N2 vaccines, PEI-CYP-PPAS generated higher HI titers and stronger IgG antibodies than CYP-PPAS and Alum and increased the immune organ index of the spleen and bursa of Fabricius without immune organ injury. Moreover, treatment with PEI-CYP-PPAS/H9N2 induced CD4+ and CD8+ T-cell activation, a high lymphocyte proliferation index, and increased cytokine expression of IL-4, IL-6, and IFN-γ. Thus, compared with the CYP-PPAS and aluminum adjuvant, the cationic nanoparticle-stabilized vaccine delivery system of PEI-CYP-PPAS was an effective adjuvant for H9N2 vaccination to elicit powerful humoral and cellular immune responses.


Asunto(s)
Subtipo H9N2 del Virus de la Influenza A , Vacunas contra la Influenza , Nanopartículas , Animales , Pollos , Aluminio/farmacología , Emulsiones/farmacología , Antígenos , Inmunidad Celular , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/farmacología , Adyuvantes Inmunológicos , Polisacáridos/farmacología
15.
Vaccine ; 41(10): 1684-1693, 2023 03 03.
Artículo en Inglés | MEDLINE | ID: mdl-36754767

RESUMEN

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.


Asunto(s)
Adyuvantes Inmunológicos , Simvastatina , Animales , Ratones , Adyuvantes Inmunológicos/farmacología , Emulsiones , Inmunidad Celular , Polisacáridos , Agua , Ovalbúmina
16.
Int J Biol Macromol ; 230: 123386, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36702224

RESUMEN

In this experiment, the polysaccharide was extracted from Pueraria lobata (Willd.) Ohwi, and its structural characteristics and bioactivity were investigated. The results showed that Pueraria lobata polysaccharide (PLP) was composed of fucose, arabinose, galactose, glucose, xylose, mannose in a molar proportion of 0.09:1.25:2.19:95.74:0.43:0.30 with a number molar masses (Mn) weight of 14.463 kDa. Besides, FT-IR, Methylation, and NMR analysis revealed that PLP were mainly composed of the main chain →4)-α-Glcp (1→ and →4,6)-α-Glcp (1→, and the branched chain α-Glcp (1→. In vitro experiment, the results showed that PLP could stimulate the expression of surface molecules on RAW264.7 and (T and B) lymphocytes proliferation, simultaneously to stimulate their cytokines secretion. In vivo experiment, the immune organ index, cytokine content, and T lymphocyte subtype in cyclophosphamide-induced immunosuppressed mice could be improved by PLP. These data proved that PLP could be used as a useful immunomodulator to enhance the immune activity of RAW264.7, T, and B cells and improve the immune function of cyclophosphamide-treated mice.


Asunto(s)
Pueraria , Animales , Ratones , Pueraria/química , Espectroscopía Infrarroja por Transformada de Fourier , Polisacáridos/farmacología , Polisacáridos/química , Inmunosupresores , Macrófagos , Ciclofosfamida , Inmunidad , Linfocitos B , Células RAW 264.7
17.
IEEE Trans Pattern Anal Mach Intell ; 45(1): 681-697, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-34982672

RESUMEN

Predicting human motion from historical pose sequence is crucial for a machine to succeed in intelligent interactions with humans. One aspect that has been obviated so far, is the fact that how we represent the skeletal pose has a critical impact on the prediction results. Yet there is no effort that investigates across different pose representation schemes. We conduct an indepth study on various pose representations with a focus on their effects on the motion prediction task. Moreover, recent approaches build upon off-the-shelf RNN units for motion prediction. These approaches process input pose sequence sequentially and inherently have difficulties in capturing long-term dependencies. In this paper, we propose a novel RNN architecture termed AHMR (Attentive Hierarchical Motion Recurrent network) for motion prediction which simultaneously models local motion contexts and a global context. We further explore a geodesic loss and a forward kinematics loss for the motion prediction task, which have more geometric significance than the widely employed L2 loss. Interestingly, we applied our method to a range of articulate objects including human, fish, and mouse. Empirical results show that our approach outperforms the state-of-the-art methods in short-term prediction and achieves much enhanced long-term prediction proficiency, such as retaining natural human-like motions over 50 seconds predictions. Our codes are released.


Asunto(s)
Algoritmos , Redes Neurales de la Computación , Humanos , Animales , Ratones , Movimiento (Física)
18.
Int J Pharm ; 630: 122418, 2023 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-36423709

RESUMEN

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.


Asunto(s)
Lycium , Animales , Ratones , Emulsiones/farmacología , Escualeno/farmacología , Compuestos de Alumbre/farmacología , Adyuvantes Inmunológicos , Inmunidad Humoral , Antígenos , Adyuvantes Farmacéuticos/farmacología , Polisacáridos/farmacología , Ratones Endogámicos BALB C
19.
Int J Mol Sci ; 23(22)2022 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-36430809

RESUMEN

Hy-Line Brown chickens' health is closely related to poultry productivity and it is mainly maintained by the immune system, healthy intestinal function, and microflora of chicken. Polysaccharides are biological macromolecules with a variety of activities that can be used as a potential prebiotic to improve poultry health. In this experiment, the function of Alhagi honey polysaccharides (AH) as an immunomodulator on the chicken was investigated. All chicken (120) were randomly distributed to four groups (five replicas/group, six hens/replica). A total of 0.5 mL water was taken orally by the chicken in control group. AH (0.5 mL) in different concentrations (three dosages, 0.3 g/kg, 0.6 g/k, and 1.2 g/kg) were used for the AH-0.3 g/kg, AH-0.6 g/k, and AH-1.2 g/kg group, respectively. The results showed that the growth performance of the chickens and the index of immune organs (the weight of immune organs/the body weight) were enhanced significantly after being AH-treated (p < 0.05). The content of sIgA and cytokines was upregulated remarkably in the intestine after being AH-treated (p < 0.05). The AH treatment significantly enhanced the intestinal epithelial barrier (p < 0.05). Moreover, the percentage of CD4+ and CD8+ T cells in the ileum, spleen, and serum were obviously upscaled (p < 0.05). In addition, the AH treatment significantly enhanced the production of short chain fatty acids (SCFAs) and improved the structure of gut microbiota (p < 0.05). In conclusion, we found that AH-1.2g/kg was the best dosage to improve the chicken's health, and these data demonstrated that AH could be used as a potential tool to enhance growth performance through improving intestine function, immunity, and gut microbiome in chicken.


Asunto(s)
Microbioma Gastrointestinal , Miel , Animales , Femenino , Linfocitos T CD8-positivos , Pollos , Inmunidad , Intestinos , Polisacáridos/farmacología
20.
IEEE Trans Image Process ; 31: 7279-7291, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36378789

RESUMEN

Efficient action recognition aims to classify a video clip into a specific action category with a low computational cost. It is challenging since the integrated spatial-temporal calculation (e. g., 3D convolution) introduces intensive operations and increases complexity. This paper explores the feasibility of the integration of channel splitting and filter decoupling for efficient architecture design and feature refinement by proposing a novel spatio-temporal collaborative (STC) module. STC splits the video feature channels into two groups and separately learns spatio-temporal representations in parallel with decoupled convolutional operators. Particularly, STC consists of two computation-efficient blocks, i.e., [Formula: see text] and [Formula: see text], where they extract either spatial ( S· ) or temporal ( T· ) features and further refine their features with either temporal ( ·T ) or spatial ( ·S ) contexts globally. The spatial/temporal context refers to information dynamics aggregated from temporal/spatial axis. To thoroughly examine our method's performance in video action recognition tasks, we conduct extensive experiments using five video benchmark datasets requiring temporal reasoning. Experimental results show that the proposed STC networks achieve a competitive trade-off between model efficiency and effectiveness.

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