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1.
Front Microbiol ; 15: 1386557, 2024.
Article in English | MEDLINE | ID: mdl-38952447

ABSTRACT

The aerobic granular sludge(AGS) technology draw scientific researchers attention, and more and more scientific research focuses on it, due to its superior advantages, such as good settling performance, high biological phase, high toxicity resistance and multiple biological effects. With the rapid development of AGS technology, a considerable amount of residual AGS will be produced, and dehydration is the biggest bottleneck of sludge reduction. This study investigated the dewatering process and method of residual AGS cultured by continuous flow experiment. Experiments were conducted using centrifugal dewatering technology with a dosing scheme to analyze the granular sludge dewatering process, and investigate the release process of EPS component in AGS dewatering. Our results implied the specific resistance of AGS has a very low value ((1.82 ± 0.03) × 109 m/kg) and it was not obvious for the conditioning effect of chemical conditioner on AGS dewatering. However, the moisture content can be reduced to 63.5% after dewatering with the presence of inorganic substances. The addition of drinking water treatment plant sludge (Alum sludge) can improve the efficiency of the dewatering of AGS. A possible dewatering process of AGS dewatering was proposed which was divided into two stages: First, a considerable amount of free water in the sludge was quickly removed under the action of gravity without pressure filtration. Second, the bound water release required cooperation between applying centrifugal or pressing force to grind granular cells and separate protein-like substances with the inorganic matter inside the granular sludge. The possible mechanism of AGS dewatering and hypothesis dewatering process are useful to optimize the AGS dewatering process.

2.
Vaccine ; 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38876839

ABSTRACT

BACKGROUND: The achievement of optimal vaccine efficacy is contingent upon the collaborative interactions between T and B cells in adaptive immunity. Although multiple immunization strategies have been proposed, there is a notable scarcity of comprehensive investigations pertaining to enhance immune effects through immune strategy adjustments for individual vaccine. METHODS: The hierarchically structured aluminum hydroxide microgel-stabilized Pickering emulsion (ASPE) was prepared by ultrasonic method. This study explored the influence of the immune strategy of ASPE to immune responses, including antigen exposure pattern, adjuvants and antigen dosage, and administration interval. RESULTS: The findings revealed that external antigen adsorption facilitated increased exposure of antigen epitopes, leading to elevated IgG titers and secretion of cytokines such as interferon-gamma (IFN-γ) or interleukin-4 (IL-4). Additionally, even a low dose (1 µg/dose) of antigens of ASPE boosted sufficient neutralizing antibody levels and memory T cells compared to high-dose antigens, which consistent with the adjuvant dosage effect. Furthermore, maintaining a 4-week immunization interval yielded optimal levels of antigen-specific IgG titers in both short-term and long-term scenarios, as compared to intervals of 2, 3, and 5 weeks. A consistent trend was observed in the proliferation of memory B cells, reaching a superior level at the 4-week interval, which could enhance protection against viral re-infection. CONCLUSION: Tailoring immunization strategies for specific vaccines has emerged as powerful driver in maximizing vaccine efficacy and eliciting robust immune responses, thereby presenting cutting-edge approaches to enhanced vaccination.

3.
Waste Manag ; 186: 94-108, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38870604

ABSTRACT

Alum sludge (AS) is a by-product generated from drinking water treatment and produced in large amounts around the world. Its chemical composition makes this waste an emerging alternative source of silicon and aluminum for aluminosilicates or zeolite material production, which can add value to residues and contribute to the circular economy process on a global scale. In this sense, and considering the scarcity of information about AS, this review shows data collection about AS in different countries, including generation, chemical composition, and disposal information. The reuse of AS is discussed based on circular economy and the environmental gains derived from such approaches are highlighted, including the possibility of utilization with other residues (e.g., ash, bioproducts, etc). Moreover, this review shows and discusses the benefits and challenges of AS reuse in the synthesis process and how it can be a sustainable raw material for aluminosilicates and zeolite synthesis. The most common conditions (conventional or non-conventional) in zeolite synthesis from AS are mentioned and advantages, limitations and trends are discussed. The discussions and data presented can improve the AS management and reuse legislations, which certainly will collaborate with sustainable AS use and circular economy processes.


Subject(s)
Alum Compounds , Aluminum Silicates , Recycling , Sewage , Water Purification , Zeolites , Zeolites/chemistry , Aluminum Silicates/chemistry , Alum Compounds/chemistry , Water Purification/methods , Recycling/methods , Waste Disposal, Fluid/methods
4.
Environ Res ; 252(Pt 3): 118976, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38705451

ABSTRACT

This study evaluates Alum sludge from drinking water treatment plants for the efficient and cost-effective removal of phosphates from aqueous solutions. Extensive characterization and batch experiments have established that optimal phosphate removal was achieved with a sludge dosage of 20 g L-1 (at an initial phosphate concentration of 100 mg L-1), a pH of 5, a temperature of 23 °C, and a stirring speed of 200 rpm. These conditions significantly reduced phosphate levels, ensuring compliance with legal discharge limits. The Langmuir isotherm, pseudo-second-order kinetic and intraparticle diffusion models best described the adsorption process, highlighting the spontaneous and endothermic nature of the phenomenon. The sludge effectively reduced phosphate concentrations to acceptable levels when applied to dairy effluents. This study underscores the potential of Alum sludge as a viable solution for phosphate management in environmental cleanup efforts.


Subject(s)
Alum Compounds , Dairying , Phosphates , Sewage , Adsorption , Phosphates/chemistry , Sewage/chemistry , Alum Compounds/chemistry , Waste Disposal, Fluid/methods , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/chemistry , Water Purification/methods , Kinetics , Models, Chemical
5.
Food Chem ; 448: 139153, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38569410

ABSTRACT

Salivary proteins precipitation by interaction with polyphenols is the major mechanism for astringency. However, alternative mechanisms seem involved in the perception of different subqualities of astringency. In this study, adsorption of four astringent agents to in vitro oral models and their sensory properties were assessed. Overall, green tea infusion and tannic acid have shown a higher adsorption potential for models with oral cells and absence of saliva. Alum and grape seed extract presented higher adsorption in models with presence of oral cells and saliva. Multiple factor analysis suggested that adsorption may represent important mechanisms to elicit the astringency of alum. Models including saliva, were closely associated with overall astringency and aggressive subquality. Models with cells and absent saliva were closely associated with greenness, suggesting a taste receptor mechanism involvement in the perception. For the first time a correlation between an oral-cell based assay and astringency sensory perception was shown.

6.
Article in English | MEDLINE | ID: mdl-38595024

ABSTRACT

Aluminium, the third most abundant element in the earth's crust, was long considered virtually innocuous to humans but has gained importance in the recent past. Aluminium is ubiquitous in the environment, with various sources of exposure like cosmetics, the food industry, occupational industries, the medical field, transport and electronics. Aluminium finds its utility in various aspects of dermatology as an effective haemostatic agent, anti-perspirant and astringent. Aluminium has a pivotal role to play in wound healing, calciphylaxis, photodynamic therapy and vaccine immunotherapy with diagnostic importance in Finn chamber patch testing and confocal microscopy. The metal also finds significance in cosmetic procedures like microdermabrasion and as an Nd:YAG laser component. It is important to explore the allergic properties of aluminium, as in contact dermatitis and vaccine granulomas. The controversial role of aluminium in breast cancer and breast cysts also needs to be evaluated by further studies.

7.
Nanomaterials (Basel) ; 14(7)2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38607138

ABSTRACT

Renewable solar energy storage facilities are attracting scientists' attention since they can overcome the key issues affecting the shortage of energy. A nanofluid phase change material (PCM) is introduced as a new sort of PCM is settled by suspending small proportions of nanoparticles in melting paraffin. ZnO/α-Fe2O3 nanocrystals were prepared by a simple co-precipitation route and ultrasonically dispersed in the paraffin to be a nanofluid-PCM. The behaviors of the ZnO/α-Fe2O3 nanocrystals were verified by X-ray diffraction (XRD) analysis, and the average particle size and the morphology of the nanoparticles were explored by transmission electron microscopy (TEM). For the object of industrial ecology concept, aluminum-based waste derived from water-works plants alum sludge (AS) is dried and augmented with the ZnO/α-Fe2O3 nanocrystals as a source of multimetals such as aluminum to the composite, and it is named AS-ZnO/α-Fe2O3. The melting and freezing cycles were checked to evaluate the PCM at different weight proportions of AS-ZnO/α-Fe2O3 nanocrystals, which confirmed that their presence enhanced the heat transfer rate of paraffin. The nanofluids with AS-ZnO/α-Fe2O3 nanoparticles revealed good stability in melting paraffin. Additionally, the melting and freezing cycles of nanofluid-PCM (PCM- ZnO/α-Fe2O3 nanoparticles) were significantly superior upon supplementing ZnO/α-Fe2O3 nanoparticles. Nanofluid-PCM contained the AS-ZnO/α-Fe2O3 nanocrystals in the range of 0.25, 0.5, 1.0, and 1.5 wt%. The results showed that 1.0 wt% AS-ZnO/α-Fe2O3 nanocrystals contained in the nanofluid-PCM could enhance the performance with 93% with a heat gained reached 47 kJ.

8.
Front Immunol ; 15: 1387534, 2024.
Article in English | MEDLINE | ID: mdl-38650936

ABSTRACT

For several years, we have been committed to exploring the potential of Bordetella pertussis-derived outer membrane vesicles (OMVBp) as a promising third-generation vaccine against the reemerging pertussis disease. The results of our preclinical trials not only confirm its protective capacity against B. pertussis infection but also set the stage for forthcoming human clinical trials. This study delves into the examination of OMVBp as an adjuvant. To accomplish this objective, we implemented a two-dose murine schedule to evaluate the specific immune response induced by formulations containing OMVBp combined with 3 heterologous immunogens: Tetanus toxoid (T), Diphtheria toxoid (D), and the SARS-CoV-2 Spike protein (S). The specific levels of IgG, IgG1, and IgG2a triggered by the different tested formulations were evaluated using ELISA in dose-response assays for OMVBp and the immunogens at varying levels. These assays demonstrated that OMVBp exhibits adjuvant properties even at the low concentration employed (1.5 µg of protein per dose). As this effect was notably enhanced at medium (3 µg) and high concentrations (6 µg), we chose the medium concentration to determine the minimum immunogen dose at which the OMV adjuvant properties are significantly evident. These assays demonstrated that OMVBp exhibits adjuvant properties even at the lowest concentration tested for each immunogen. In the presence of OMVBp, specific IgG levels detected for the lowest amount of antigen tested increased by 2.5 to 10 fold compared to those found in animals immunized with formulations containing adjuvant-free antigens (p<0.0001). When assessing the adjuvant properties of OMVBp compared to the widely recognized adjuvant alum, we detected similar levels of specific IgG against D, T and S for both adjuvants. Experiments with OMVs derived from E. coli (OMVE.coli) reaffirmed that the adjuvant properties of OMVs extend across different bacterial species. Nonetheless, it's crucial to highlight that OMVBp notably skewed the immune response towards a Th1 profile (p<0.05). These collective findings emphasize the dual role of OMVBp as both an adjuvant and modulator of the immune response, positioning it favorably for incorporation into combined vaccine formulations.


Subject(s)
Adjuvants, Immunologic , Bordetella pertussis , Immunoglobulin G , Th1 Cells , Whooping Cough , Bordetella pertussis/immunology , Animals , Adjuvants, Immunologic/administration & dosage , Mice , Th1 Cells/immunology , Whooping Cough/immunology , Whooping Cough/prevention & control , Female , Immunoglobulin G/blood , Immunoglobulin G/immunology , Pertussis Vaccine/immunology , Pertussis Vaccine/administration & dosage , Antibodies, Bacterial/immunology , Antibodies, Bacterial/blood , Spike Glycoprotein, Coronavirus/immunology , Mice, Inbred BALB C , SARS-CoV-2/immunology , Bacterial Outer Membrane Proteins/immunology , Humans , COVID-19/immunology , COVID-19/prevention & control , Tetanus Toxoid/immunology
9.
Chemosphere ; 358: 142160, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38685330

ABSTRACT

Recent research has found biochar to be a cost-effective adsorbent for removal of perfluoroalkyl substances in water. To promote cleaner production and sustainable waste management, this study explored the potential to produce activated biochars by co-pyrolyzing sawdust with iron-rich biosolids and polyaluminum sludge. The maximum capacity to adsorb perfluorooctanesulfonic acid (PFOS) reached 27.2 mg g-1 with biosolids-activated biochar and 19.2 mg g-1 with aluminum sludge-activated biochar, compared to 6.2 mg g-1 with sawdust biochar. The increased adsorption capacities were attributed to electrostatic interactions between the anionic PFOS and metal functionalities on the biochar surface. In contrast, hydrophobic interaction was the dominant adsorption mechanism of sawdust biochar. The presence of dissolved organic matter at 5-50 mg L-1 was found to inhibit adsorption of PFOS in water, while pH as low as 3.0 and sodium chloride concentrations up to 100 mM enhanced removal of PFOS by all the three adsorbents. In batch adsorption tests at environmentally relevant PFOS dosages and adsorbent dosage of 0.25 g L-1, the biosolids-sawdust biochar and Al sludge-sawdust biochar removed 71.4% and 66.9% of PFOS from drinking water and 77.9% and 87.9% of PFOS from filtrate of sludge digestate, respectively. The biosolids-sawdust biochar additionally removed Fe, although the Al sludge-sawdust biochar released Al into the alkaline drinking water and filtrate. Overall, this study proved co-pyrolyzing sawdust and Fe-rich biosolids to be an effective approach to activate sawdust biochar for enhanced removal of PFOS while recycling wastewater treatment residuals and sawdust.


Subject(s)
Alkanesulfonic Acids , Charcoal , Fluorocarbons , Wastewater , Water Pollutants, Chemical , Water Purification , Fluorocarbons/chemistry , Alkanesulfonic Acids/chemistry , Charcoal/chemistry , Adsorption , Water Pollutants, Chemical/chemistry , Wastewater/chemistry , Water Purification/methods , Wood/chemistry , Waste Disposal, Fluid/methods
10.
Vaccine ; 42(7): 1582-1592, 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38336558

ABSTRACT

Clostridioides difficile infection (CDI) is a serious healthcare-associated disease, causing symptoms such as diarrhea and pseudomembranous colitis. The major virulence factors responsible for the disease symptoms are two secreted cytotoxic proteins, TcdA and TcdB. A parenteral vaccine based on formaldehyde-inactivated TcdA and TcdB supplemented with alum adjuvant, has previously been investigated in humans but resulted in an insufficient immune response. In search for an improved response, we investigated a novel toxin inactivation method and a novel, potent adjuvant. Inactivation of toxins by metal-catalyzed oxidation (MCO) was previously shown to preserve neutralizing epitopes and to annihilate reversion to toxicity. The immunogenicity and safety of TcdA and TcdB inactivated by MCO and combined with a novel carbohydrate fatty acid monosulphate ester-based (CMS) adjuvant were investigated in rabbits. Two or three intramuscular immunizations generated high serum IgG and neutralizing antibody titers against both toxins. The CMS adjuvant increased antibody responses to both toxins while an alum adjuvant control was effective only against TcdA. Systemic safety was evaluated by monitoring body weight, body temperature, and analysis of red and white blood cell counts shortly after immunization. Local safety was assessed by histopathologic examination of the injection site at the end of the study. Body weight gain was constant in all groups. Body temperature increased up to 1 ˚C one day after the first immunization but less after the second or third immunization. White blood cell counts, and percentage of neutrophils increased one day after immunization with CMS-adjuvanted vaccines, but not with alum. Histopathology of the injection sites 42 days after the last injection did not reveal any abnormal tissue reactions. From this study, we conclude that TcdA and TcdB inactivated by MCO and combined with CMS adjuvant demonstrated promising immunogenicity and safety in rabbits and could be a candidate for a vaccine against CDI.


Subject(s)
Alum Compounds , Bacterial Toxins , Boron Compounds , Cephalosporins , Clostridioides difficile , Clostridium Infections , Animals , Rabbits , Adjuvants, Immunologic , Bacterial Proteins , Bacterial Vaccines/adverse effects , Body Weight , Clostridium Infections/prevention & control , Enterotoxins , Toxoids
11.
Eur J Immunol ; 54(4): e2350582, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38279592

ABSTRACT

Neutrophil extracellular traps (NETs) have been identified as triggers for a self-limited inflammatory reaction upon contact with nanoparticles within our bodies. This typically results in entrapping potentially harmful nano- or micro-objects following an immune burst. The demand for potent adjuvants has led to research on particulate-based adjuvants, particularly those that act via NET formation. Various particles, including hydrophobic nanoparticles, needle-like microparticles, and other natural and artificial crystals, have been shown to induce NET formation, eliciting a robust humoral and cellular immune response toward co-injected antigens. The NET formation was found to be the basis of the efficient use of alum as a vaccine adjuvant. Thus, nanoparticles with specific surface properties serve as NET-stimulating adjuvants. In this mini-review, we aim to summarize the current knowledge about the surface properties of particulate objects and the molecular pathways involved in inducing NET formation by neutrophils. Additionally, we discuss the potential use of nanoparticles for activating neutrophils in the tissues and the exploitation of such activation for enhancing vaccine adjuvants.


Subject(s)
Extracellular Traps , Nanoparticles , Neutrophils , Antigens , Adjuvants, Immunologic
12.
Article in English | WPRIM (Western Pacific) | ID: wpr-1013464

ABSTRACT

@#Intractable hemorrhagic cystitis is an uncommon but significant treatment complication of concurrent chemoradiation therapy for cervical cancer. Alum instillation is regarded as a safe and effective option for its treatment. This case presentation will discuss a patient who presented with postradiation cystitis and was treated with alum irrigation. The aim of this report is to offer alum irrigation as a management option for intractable hematuria.


Subject(s)
Cancer Survivors
13.
Vaccines (Basel) ; 11(12)2023 Dec 06.
Article in English | MEDLINE | ID: mdl-38140228

ABSTRACT

Leptospirosis is a globally significant zoonotic disease. The current inactivated vaccine offers protection against specific serovars but does not provide complete immunity. Various surface antigens, such as Leptospira immunoglobulin-like proteins (LigA and LigB), have been identified as potential subunit vaccine candidates. However, these antigens require potent adjuvants for effectiveness. Bacterial lipopolysaccharides (LPSs), including lipid A, are a well-known immunostimulant, and clinical adjuvants often contain monophosphoryl lipid A (MPLA). Being less endotoxic, we investigated the adjuvant properties of lipid A isolated from L. interrogans serovar Pomona (PLA) in activating innate immunity and enhancing antigen-specific adaptive immune responses. PLA activated macrophages to a similar degree as MPLA, albeit at a higher dose, suggesting that it is less potent in stimulation than MPLA. Mice immunized with a variable portion of LigA (LAV) combined with alum and PLA (LAV-alum-PLA) exhibited significantly higher levels of LAV-specific humoral and cellular immune responses compared to alum alone but similar to those induced by alum-MPLA. The adjuvant activity of PLA resembles that of MPLA and is primarily achieved through the increased recruitment, activation, and uptake of antigens by innate immune cells. Furthermore, like MPLA, PLA formulation establishes a long-lasting memory response. Notably, PLA demonstrated superior potency than MPLA formulation and provided sterilizing immunity against the leptospirosis in a hamster model. Overall, our study sheds light on the adjuvant properties of Leptospira lipid A and offers promising avenues for developing LPS-based vaccines against this devastating zoonotic disease.

14.
Int J Pharm ; 648: 123581, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37931728

ABSTRACT

Most licensed human vaccines are based on liquid dosage forms but have poor storage stability and require continuous and expensive cold-chain storage. In contrast, the use of solid vaccine dosage forms produced by for example spray drying, extends shelf life and eliminates the need for a cold chain. Zinc oxide (ZnO)-based nanoparticles display immunomodulatory properties, but their adjuvant effect as a dry powder formulation is unknown. Here, we show that reconstituted dry powder formulations of ZnO particles containing the model antigen ovalbumin (OVA) induce antigen-specific CD8+ T-cell and humoral responses. By systematically varying the ratio between ZnO and mannitol during spray drying, we manufactured dry powder formulations of OVA-containing ZnO particles that displayed: (i) a spherical or wrinkled surface morphology, (ii) an aerodynamic diameter and particle size distribution optimal for deep lung deposition, and (iii) aerosolization properties suitable for lung delivery. Reconstituted dry powder formulations of ZnO particles were well-tolerated by Calu-3 lung epithelial cells. Furthermore, almost equivalent OVA-specific serum antibody responses were stimulated by reconstituted ZnO particles, OVA adjuvanted with Alhydrogel®, and OVA adjuvanted with the cationic adjuvant formulation 01 (CAF®01). However, reconstituted dry powder ZnO particles and OVA adjuvanted with Alhydrogel® induced significantly lower OVA-specific CD8+CD44+ T-cell responses in the spleen than OVA adjuvanted with CAF®01. Similarly, reconstituted dry powder ZnO particles activated significantly lower percentages of follicular helper T cells and germinal center B cells in the draining lymph nodes than OVA adjuvanted with CAF®01. Overall, our results show that reconstituted dry powder formulations of ZnO nanoparticles can induce antigen-specific antibodies and can be used in vaccines to enhance antigen-specific humoral immune responses against subunit protein antigens.


Subject(s)
Vaccines , Zinc Oxide , Humans , Aluminum Hydroxide/chemistry , Ovalbumin , Powders , Adjuvants, Immunologic , Adjuvants, Pharmaceutic , Antigens , Antibodies
15.
Vet Microbiol ; 287: 109915, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38000209

ABSTRACT

The adjuvant and/or vector significantly affect a vaccine's efficacy. Although traditional adjuvants such as alum have contributed to vaccine development, deficiencies in the induction of cellular and mucosal immunity have limited their further promotion. Salmonella vectors have unique advantages for establishing cellular and mucosal immunity due to mucosal pathways of invasion and intracellular parasitism. In addition, Salmonella vectors can activate multiple innate immune pathways, thereby promoting adaptive immune responses. In this work, the attenuated Salmonella enterica serovar Choleraesuis (S. Choleraesuis) vector rSC0016 was used to deliver the conserved protective antigen HPS_06257 of Glaesserella parasuis (G. parasuis), generating a novel recombinant strain rSC0016(pS-HPS_06257). The rSC0016(pS-HPS_06257) can express and deliver the HPS_06257 protein to the lymphatic system of the host. In comparison to HPS_06257 adjuvanted with alum, rSC0016(pS-HPS_06257) significantly increased TLR4 and TLR5 activation in mice as well as the levels of proinflammatory cytokines. In addition, rSC0016 promoted a greater degree of maturation in bone marrow-derived dendritic cells (BMDCs) than alum. The specific humoral, mucosal, and cellular immune responses against HPS_06257 in mice immunized with rSC0016(pS-HPS_06257) were significantly higher than those of HPS_06257 adjuvanted with alum. HPS_06257 delivered by the S. Choleraesuis vector induces a Th1-biased Th1/Th2 mixed immune response, while HPS adjuvanted with alum can only induce a Th2-biased immune response. HPS_06257 adjuvanted with alum only causes opsonophagocytic activity (OPA) responses against a homologous strain (G. parasuis serotype 5, GPS5), whereas rSC0016(pS-HPS_06257) could generate cross-OPA responses against a homologous strain and a heterologous strain (G. parasuis serotype 12, GPS12). Ultimately, HPS_06257 adjuvanted with alum protected mice against lethal doses of GPS5 challenge by 60 % but failed to protect mice against lethal doses of GPS12. In contrast, mice immunized with rSC0016(pS-HPS_06257) had 100 % or 80 % survival when challenged with lethal doses of GPS5 or GPS12, respectively. Altogether, the S. Choleraesuis vector rSC0016 could potentially generate an improved innate immune response and an improved adaptive immunological response compared to the traditional alum adjuvant, offering a novel concept for the development of a universal G. parasuis vaccine.


Subject(s)
Salmonella enterica , Vaccines , Mice , Animals , Serogroup , Adjuvants, Immunologic , Immunity, Cellular , Mice, Inbred BALB C
16.
Front Immunol ; 14: 1276887, 2023.
Article in English | MEDLINE | ID: mdl-38022539

ABSTRACT

Introduction: Tuberculosis (TB) is a major threat to human health. In 2021, TB was the second leading cause of death after COVID-19 among infectious diseases. The Bacillus Calmette-Guérin vaccine (BCG), the only licensed TB vaccine, is ineffective against adult TB. Therefore, there is an urgent need to develop new effective vaccines. Methods: In this study, we developed a novel multistage subunit vaccine (ERA005f) comprising various proteins expressed in metabolic states, based on three immunodominant antigens (ESAT-6, Rv2628, and Ag85B). We utilized the E. coli prokaryotic expression system to express ERA005f and subsequently purified the protein using nickel affinity chromatography and anion exchange. Immunogenicity and protective efficacy of ERA005f and ERA005m were evaluated in BALB/c mice. Results: ERA005f was consistently expressed as an inclusion body in a prokaryotic expression system, and a highly pure form of the protein was successfully obtained. Both ERA005f and ERA005m significantly improved IgG titers in the serum. In addition, mice immunized with ERA005f and ERA005m generated higher titers of antigen-specific IgG2a than the other groups. Elispot results showed that, compared with other groups, ERA005f increased the numbers of IFN-γ-secreting and IL-4-secreting T cells, especially the number of IFN-γ-secreting T cells. Meanwhile, ERA005f induced a higher number of IFN-γ+ T lymphocytes than ERA005m did. In addition, ERA005f improved the expression of cytokines, including IFN-γ, IL-12p70, TNF-α, IL-17, and GM-CSF and so on. Importantly, both ERA005f and ERA005m significantly inhibited the growth of Mtb. Conclusion: The novel multistage antigen ERA005f elicited a strong antigen-specific humoral response and Th-1 and Th-17 cell-mediated immunity in mice. Meanwhile, it can effectively inhibit H37Rv growth in vitro, and represents a correlate of protection in vivo, indicating that ERA005f may exhibit excellent protective efficacy against Mycobacterium tuberculosis H37Rv infection. Our study suggests that ERA005f has the potential to be a promising multistage tuberculosis vaccine candidate.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis Vaccines , Tuberculosis , Adult , Mice , Humans , Animals , Antigens, Bacterial , Escherichia coli , BCG Vaccine , T-Lymphocytes , Immunity
17.
Acta Trop ; 248: 107041, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37858877

ABSTRACT

Exosomes were isolated from T. gondii infected human hepatoblastoma cells using the exosome isolation kit and characterized by electron microscopy and Western blotting. Exosomes adsorbed to alum adjuvant were evaluated as a potential immunizing agent against murine chronic toxoplasmosis compared to excretory secretory antigens (ESA)-alum. Mice were immunized at days 1, 15 and 29. The levels of IgG, IFN-γ, IL-4 and IL-10, CD4+ and CD8+ T cells were determined using sandwich enzyme-linked immunosorbent assay (sandwich ELISA) at days 14, 28 and 56 of the experiment. Then mice were infected orally with 10 cysts of T. gondii. The protective efficacy of the antigens were evaluated by counting the brain cysts and measuring the aforementioned humoral and cellular parameters 60 days post infection. The results showed that alum increased the protective efficacy of the exosomes. Immunization with exosome-alum induced both humoral and mixed Th1/Th2 cellular immune responses. Exosome-alum gave higher levels of the humoral and cellular parameters, compared to ESA-alum. After challenge infection, exosome-alum significantly reduced the brain cyst burden by 75 % while ESA-alum gave 42 % reduction and evoked higher humoral and cellular immune responses. Therefore, the possibility of using T. gondii infected cells-derived exosome-alum as a vaccine is a new perspective in toxoplasmosis.


Subject(s)
Exosomes , Protozoan Vaccines , Toxoplasma , Toxoplasmosis, Animal , Toxoplasmosis , Animals , Mice , Humans , CD8-Positive T-Lymphocytes , Toxoplasmosis/prevention & control , Antibodies, Protozoan , Protozoan Proteins , Antigens, Protozoan
18.
Int J Mol Sci ; 24(19)2023 Sep 28.
Article in English | MEDLINE | ID: mdl-37834109

ABSTRACT

Melanogenesis, the intricate process of melanin synthesis, is central to skin pigmentation and photoprotection and is regulated by various signaling pathways and transcription factors. To develop potential skin-whitening agents, we used B16F1 melanoma cells to investigate the inhibitory effects of anhydrous alum on melanogenesis and its underlying molecular mechanisms. Anhydrous alum (KAl(SO4)2) with high purity (>99%), which is generated through the heat-treatment of hydrated alum (KAl(SO4)2·12H2O) at 400 °C, potentiates a significant reduction in melanin content without cytotoxicity. Anhydrous alum downregulates the master regulator of melanogenesis, microphthalmia-associated transcription factor (MITF), which targets key genes involved in melanogenesis, thereby inhibiting α-melanocyte-stimulating hormone (α-MSH)-induced melanogenesis. Phosphorylation of the cAMP response element-binding protein, which acts as a co-activator of MITF gene expression, is attenuated by anhydrous alum, resulting in compromised MITF transcription. Notably, anhydrous alum promoted extracellular signal-regulated kinase phosphorylation, leading to the impaired nuclear localization of MITF. Overall, these results demonstrated the generation and mode of action of anhydrous alum in B16F1 cells, which constitutes a promising option for cosmetic or therapeutic use.


Subject(s)
Melanins , alpha-MSH , Melanins/metabolism , alpha-MSH/metabolism , Monophenol Monooxygenase/metabolism , Microphthalmia-Associated Transcription Factor/genetics , Microphthalmia-Associated Transcription Factor/metabolism , Cell Line, Tumor
19.
Molecules ; 28(18)2023 Sep 17.
Article in English | MEDLINE | ID: mdl-37764445

ABSTRACT

Wheat starch (WS) is a common adhesive material used in mounting of calligraphy and paintings. Potassium alum (PA) has indeed been used for many centuries to modify the physicochemical properties of starch. Thermal analysis revealed that the presence of PA led to an increase in the gelatinization temperature and enthalpy of the starch gels. The leached amylose and the swelling power of the starch gels exhibited a maximum at the ratio of 100:6.0 (WS:PA, w/w). The rheological properties of starch gels were consistent with changes in the swelling power of starch granules. SEM observations confirmed that the gel structure became more regular, and the holes grew larger with the addition of PA below the ratio of 100:6.0 (WS:PA, w/w). The short-range molecular order in the starch gels was enhanced by the addition of PA, confirmed by FT-IR analysis. Mechanical experiments demonstrated that the binding strength of the starch gels increased with higher PA concentrations and decreased significantly after the aging process. TGA results revealed that PA promoted the acid degradation of starch molecules. This study provides a detailed guide for the preparation of starch-based adhesive and its applications in paper conservation.

20.
Vaccine ; 41(41): 6064-6071, 2023 09 22.
Article in English | MEDLINE | ID: mdl-37640568

ABSTRACT

The ongoing evolution and emergence of SARS-CoV-2 variants have raised concerns regarding the efficacy of existing vaccines and therapeutic agents. This study aimed to investigate the immunogenicity of an aluminum hydroxide (Alum) and CpG adjuvanted inactivated vaccine (IAV) candidate against SARS-CoV-2 in mice. A comparison was made between the immune response of mice vaccinated with the Alum+CpG adjuvant IAV and those vaccinated with the Alum adjuvant IAV. Mice immunized with Alum+CpG adjuvant IAV demonstrated high antibody titers and a durable humoral immune response, as well as a Th1-type cellular immune response. Notably, compared to Alum alone vaccine, the Alum+CpG adjuvant IAV induced significantly higher proportions of GC B cells in the splenocytes of immunized mice. Importantly, the changes in inflammatory cytokine levels in the sera of mice vaccinated with the Alum+CpG adjuvant IAV followed a similar trend to that of the Alum adjuvant IAV, which had been proven safe in clinical trials. Overall, our results demonstrate that Alum+CpG adjuvant has the potential to serve as a novel adjuvant, thereby providing valuable insights into the development of vaccine formulations.


Subject(s)
Aluminum Hydroxide , COVID-19 , Animals , Mice , COVID-19/prevention & control , SARS-CoV-2 , Adjuvants, Immunologic
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