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Journal of Ethnopharmacology Feb 2023Jingfang Granule (JFG) is a Traditional Chinese Medicine prescription to empirically treat skin disease such as urticaria in clinical practice. However, the potential...
ETHNOPHARMACOLOGICAL RELEVANCE
Jingfang Granule (JFG) is a Traditional Chinese Medicine prescription to empirically treat skin disease such as urticaria in clinical practice. However, the potential mechanisms of JFG on urticaria are not fully defined.
AIM OF STUDY
The aim of this study is to investigate the mechanisms of JFG in treating urticaria through an OVA/aluminum hydroxide induced urticaria mice model.
MATERIALS AND METHODS
KM mice were injected intraperitoneally (i.p.) with OVA/aluminium hydroxide to establish the model with urticaria. After the mice were administered JFG, itching degree and hematoxylin and eosin (H&E) staining were used to assess the protective effect of JFG on mice with urticaria. The regulatory networks were investigated by proteomics and central carbon metabolomics. Spleen T lymphocyte subsets were detected by flow cytometry. Peripheral blood cytokines were detected using ELISA kits or Cytometric Bead Array (CBA) kits. The protein expression of skin tissue was detected by western blot or immunohistochemical staining.
RESULTS
JFG significantly relived skin tissue lesions and skin pruritus in mice with urticaria. Meanwhile, JFG significantly decreased IgE, IL-1β, IL-6, IL-4, TNF-α and IL-17A levels and increased IFN-γ levels in the serum of urticaria mice by inhibiting the expression of inflammation associated proteins including TLR4 and p-NF-κB p65, p-ERK1/2, p-JNK and p-p38, NLRP3, ASC and cleaved caspase-1. The results of proteomics, central carbon metabolomics, western blot and immunohistochemical staining confirmed that JFG inhibited Glycolysis/Gluconeogenesis and Pentose phosphate pathway in the skin tissue of urticaria mice by activating the LKB1/AMPK/SIRT1 axis and then downregulating the protein expressions of Glut1, TORC2, p-CREB, PEPCK, HNF4α and G6Pase.
CONCLUSION
The current study demonstrates that JFG is effective in treating OVA/aluminum hydroxide-induced skin lesions and inflammation in mice, and JFG exhibits the clinical benefits via modulating LKB1/AMPK/SIRT1 axis, which in turn inhibits Glycolysis/Gluconeogenesis and Pentose phosphate pathway.
Topics: Animals; Mice; Sirtuin 1; AMP-Activated Protein Kinases; NF-kappa B; Signal Transduction; Aluminum Hydroxide; Inflammation; Urticaria; Carbon; Glucose
PubMed: 36347302
DOI: 10.1016/j.jep.2022.115913 -
Nanoscale Apr 2021Layered double hydroxide (LDH) is a 'sandwich'-like two-dimensional clay material that has been systematically investigated for biomedical application in the past two... (Review)
Review
Layered double hydroxide (LDH) is a 'sandwich'-like two-dimensional clay material that has been systematically investigated for biomedical application in the past two decades. LDH is an alum-similar adjuvant, which has a well-defined layered crystal structure and exhibits high adjuvanticity. The unique structure of LDH includes positively charged layers composed of divalent and trivalent cations and anion-exchangeable interlayer galleries. Among the many variants of LDH, MgAl-LDH (the cationic ions are Mg2+ and Al3+) has the highest affinity to antigens, bioadjuvants and drug molecules, and exhibits superior biosafety. Past research studies indicate that MgAl-LDH can simultaneously load antigens, bioadjuvants and molecular drugs to amplify the strength of immune responses, and induce broad-spectrum immune responses. Moreover, the size and dispersity of MgAl-LDH in biological environments can be well controlled to actively deliver antigens to the immune system, realizing the rapid induction and maintenance of durable immune responses. Furthermore, the functionalization of MgAl-LDH nanoadjuvants enables it to capture antigens in situ and induce personalized immune responses, thereby more effectively overcoming complex diseases. In this review, we comprehensively summarize the development and application of MgAl-LDH nanoparticles as a vaccine adjuvant, demonstrating that MgAl-LDH is the most potential adjuvant for clinical application.
Topics: Aluminum Hydroxide; Antigens; Clay; Hydroxides; Nanoparticles
PubMed: 33876812
DOI: 10.1039/d1nr00881a -
Archives of Razi Institute Nov 2021Newcastle disease (ND) and Avian influenza (AI) are the major problems and the most economically important viral diseases in the poultry industry; therefore, vaccination...
Comparative Study on the Efficacy of MF 59, ISA70 VG, and Nano-Aluminum Hydroxide Adjuvants, Alone and with Nano-Selenium on Humoral Immunity Induced by a Bivalent Newcastle+Avian Influenza Vaccine in Chickens.
Newcastle disease (ND) and Avian influenza (AI) are the major problems and the most economically important viral diseases in the poultry industry; therefore, vaccination against these diseases is considered one of the most effective ways of prevention. Extensive studies have been conducted to improve the performance of vaccines, and one of the major achievements of these studies is the preparation of adjuvants as stimulants of the immune system and one of the most important compounds in killed vaccines. An immunogenicity comparison of three adjuvants including, ISA70VG, Nano-Aluminum Hydroxide (Nano-Alum), and MF59 alone or with Nano-Selenium (Nano-Se), was performed using bivalent Newcastle plus Avian Influenza (ND+AI) killed vaccine. In this study, 105 specific-pathogen-free chicks (Ross-308) were divided into 7 treatments, including T1 (control group), T2 (ISA70VG), T3 (ISA70VG plus Nano-Se), T4 (Nano-Alum Hydroxide), T5 (Nano-Alum+Nano-Se), T6 (MF59), and T7 (MF59+Nano-Se). The vaccine was injected subcutaneously on day 21 in the back of the neck area. The blood samples were taken on days 14, 21, 28, 35, 42, and 49 post-vaccination. Serums of the samples were titrated by the haemagglutination inhibition (HI) test against Newcastle and Avian influenza. Based on the results, the highest HI test titers were observed for the T2 and T3 treatments, while the T6 and T7 treatments had the lowest titers. Moreover, regardless of the type of the adjuvants, adding Nano-Se increased the antibody titer in the vaccinated groups. In conclusion, a combination of the ISA70VG adjuvant and Nano-Se induced excellent antibody titers using bivalent ND+AI killed vaccine.
Topics: Aluminum Hydroxide; Animals; Chickens; Immunity, Humoral; Influenza Vaccines; Influenza in Birds; Newcastle disease virus; Selenium
PubMed: 35355760
DOI: 10.22092/ari.2021.356666.1887 -
The Cochrane Database of Systematic... Sep 2015Heartburn is one of the most common gastrointestinal symptoms in pregnant women. It can occur in all trimesters of pregnancy. The symptoms of heartburn in pregnancy may... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Heartburn is one of the most common gastrointestinal symptoms in pregnant women. It can occur in all trimesters of pregnancy. The symptoms of heartburn in pregnancy may be frequent, severe and distressing, but serious complications are rare. Many interventions have been used for the treatment of heartburn in pregnancy. These interventions include advice on diet, lifestyle modification and medications. However, there has been no evidence-based recommendation for the treatment of heartburn in pregnancy.
OBJECTIVES
To assess the effects of interventions for relieving heartburn in pregnancy.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2015), ClinicalTrials.gov (2 March 2015), Asian & Oceanic Congress of Obstetrics & Gynaecology (AOCOG) conference proceedings (20-23 October 2013, Centara Grand & Bangkok Convention Centre, Bangkok, Thailand), and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTS of interventions for heartburn in pregnancy compared with another intervention, or placebo, or no intervention. Cluster-RCTs would have been eligible for inclusion but none were identified. We excluded studies available as abstracts only and those using a cross-over design.Interventions could include advice on diet, lifestyle modification and medications (such as antacids, sucralfate, histamine 2-receptor antagonists, promotility drugs and proton pump inhibitors (PPIs)).
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy.
MAIN RESULTS
We included nine RCTs involving 725 women. However, five trials did not contribute data. Four trials involving 358 women contributed data. Trials were generally at mixed risk of bias.We only identified data for three comparisons: pharmaceutical treatment versus placebo or no treatment; acupuncture versus no treatment and pharmacological intervention versus advice on dietary and lifestyle changes. Pharmaceutical treatment compared with placebo or no treatmentTwo trials evaluated any pharmaceutical treatment compared with placebo or no treatment. One trial examined a treatment rarely used nowadays (intramuscular prostigmine 0.5 mg versus placebo). One trial evaluated the effect of magnesium and aluminium hydroxide plus simethicone liquid and tablet compared with placebo. For the primary outcome of this review (relief of heartburn), women who received pharmaceutical treatment reported complete heartburn relief more often than women receiving no treatment or placebo (risk ratio (RR) 1.85, 95% confidence interval (CI) 1.36 to 2.50 in two RCTs of 256 women, I(2) = 0%, moderate-quality evidence). Data on partial relief of heartburn were heterogenous and showed no clear difference (average RR 1.35, 95% CI 0.38 to 4.76 in two RCTs of 256 women, very low-quality evidence). In terms of secondary outcomes, there was no clear difference in the rate of side effects between the pharmaceutical treatment group and the placebo/no treatment group (RR 0.63, 95% CI 0.21 to 1.89 in two RCTs of 256 women, very low-quality evidence). Pharmacological intervention versus advice on dietary and lifestyle choicesOne study compared 1 g of sucralfate with advice on dietary and lifestyle choices in treating heartburn. More women in the sucralfate group experienced complete relief of heartburn compared to women who received advice on diet and lifestyle choices (RR 2.41, 95% CI 1.42 to 4.07; participants = 65; studies = one). The only secondary outcome of interest addressed by this trial was side effects. The evidence was not clear on intervention side effects rate between the two groups (RR 1.74, 95% CI 0.07 to 41.21; participants = 66; studies = one). There was only one instance of side effects in the pharmacological group. Acupuncture compared with no treatmentOne trial evaluated acupuncture compared with no treatment but did not report data relating to this review's primary outcome (relief of heartburn). In terms of secondary outcomes, there was no difference in the rate of side effects between women who had acupuncture and women who had no treatment (RR 2.43, 95% CI 0.11 to 55.89 in one RCT of 36 women). With regard to quality of life, women who had acupuncture reported improved ability to sleep (RR 2.80, 95% CI 1.14 to 6.86) and eat (RR 2.40, 95% CI 1.11 to 5.18 in one RCT of 36 women).The following secondary outcomes were not reported upon in any of the trials included in the review: miscarriage, preterm labour, maternal satisfaction, fetal anomalies, intrauterine growth restriction, low birthweight.
AUTHORS' CONCLUSIONS
There are no large-scale RCTs to assess heartburn relief in pregnancy. This review of nine small studies (which involved data from only four small studies) indicates that there are limited data suggesting that heartburn in pregnancy could be completely relieved by pharmaceutical treatment. Three outcomes were assessed and assigned a quality rating using the GRADE methods. Evidence from two trials for the outcome of complete relief of heartburn was assessed as of moderate quality. Evidence for the outcomes of partial heartburn relief and side effects was graded to be of very low quality. Downgrading decisions were based in part on the small size of the trials and on heterogenous and imprecise results.There are insufficient data to assess acupuncture versus no treatment and no data to assess other comparisons (miscarriage, preterm labour, maternal satisfaction, fetal anomalies, intrauterine growth restriction, low birthweight).Further RCTs are needed to fully evaluate the effectiveness of interventions for heartburn in pregnancy. Future research should also address other medications such as histamine 2-receptor antagonists, promotility drugs, proton pump inhibitors, and a raft-forming alginate reflux suppressant in treatment of heartburn in pregnancy. More research is needed on acupuncture and other complimentary therapies as treatments for heartburn in pregnancy. Future research should also evaluate any adverse outcomes, maternal satisfaction with treatment and measure pregnant women's quality of life in relation to the intervention.
Topics: Acupuncture Therapy; Adult; Aluminum Hydroxide; Antacids; Female; Heartburn; Humans; Magnesium Hydroxide; Neostigmine; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic; Sucralfate
PubMed: 26384956
DOI: 10.1002/14651858.CD011379.pub2 -
Vaccine Sep 2014An inactivated poliovirus vaccine (IPV) based on attenuated poliovirus strains (Sabin-1, -2 and -3) was developed for technology transfer to manufacturers in low- and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
An inactivated poliovirus vaccine (IPV) based on attenuated poliovirus strains (Sabin-1, -2 and -3) was developed for technology transfer to manufacturers in low- and middle-income countries in the context of the global polio eradication initiative.
METHOD
Safety and immunogenicity of Sabin-IPV (sIPV) was evaluated in a double-blind, randomized, controlled, dose-escalation trial in the target population. Healthy infants (n=20/group) aged 56-63 days, received a primary series of three intramuscular injections with low-, middle- or high-dose sIPV with or without aluminum hydroxide or with the conventional IPV based on wild poliovirus strains (wIPV). Virus-neutralizing titers against both Sabin and wild poliovirus strains were determined before and 28 days after three vaccinations.
RESULTS
The incidence of local and systemic reactions was comparable with the wIPV. Seroconversion rates after three vaccinations were 100% for type 2 and type 3 polioviruses (both Sabin and wild strains) and 95-100% for type 1 polioviruses. Median titers were high in all groups. Titers were well above the log2(titer) correlated with protection (=3) for all groups. Median titers for Sabin-2 were 9.3 (range 6.8-11.5) in the low-dose sIPV group, 9.2 (range 6.8-10.2) in the low-dose adjuvanted sIPV group and 9.8 (range 5.5-15.0) in the wIPV group, Median titers against MEF-1 (wild poliovirus type 2) were 8.2 (range 4.8-10.8) in the low-dose sIPV group, 7.3 (range 4.5-10.2) in the low-dose adjuvanted Sabin-IPV group and 10.3 (range 8.5-17.0) in the wIPV group. For all poliovirus types the median titers increased with increasing dose levels.
CONCLUSION
sIPV and sIPV adjuvanted with aluminum hydroxide were immunogenic and safe at all dose levels, and comparable with the wIPV. EudraCTnr: 2011-003792-11, NCT01709071.
Topics: Adjuvants, Immunologic; Aluminum Hydroxide; Antibodies, Neutralizing; Antibodies, Viral; Antibody Formation; Double-Blind Method; Female; Humans; Infant; Male; Poland; Poliomyelitis; Poliovirus Vaccine, Oral; Vaccines, Attenuated
PubMed: 25043278
DOI: 10.1016/j.vaccine.2014.07.029 -
Ecotoxicology and Environmental Safety May 2023Aluminum (Al) has been classified as a cumulative environmental pollutant that endangers human health. There is increasing evidence to suggest the toxic effects of Al,...
Aluminum (Al) has been classified as a cumulative environmental pollutant that endangers human health. There is increasing evidence to suggest the toxic effects of Al, but the specific action on human brain development remains unclear. Al hydroxide (Al(OH)), the most common vaccine adjuvant, is the major source of Al and poses risks to the environment and early childhood neurodevelopment. In this study, we explored the neurotoxic effect of 5 μg/ml or 25 μg/ml Al(OH) for six days on neurogenesis by utilizing human cerebral organoids from human embryonic stem cells (hESCs). We found that early Al(OH) exposure in organoids caused a reduction in the size, deficits in basal neural progenitor cell (NPC) proliferation, and premature neuron differentiation in a time and dose-dependent manner. Transcriptomes analysis revealed a markedly altered Hippo-YAP1 signaling pathway in Al(OH) exposed cerebral organoid, uncovering a novel mechanism for Al(OH)-induced detrimental to neurogenesis during human cortical development. We further identified that Al(OH) exposure at day 90 mainly decreased the production of outer radial glia-like cells(oRGs) but promoted NPC toward astrocyte differentiation. Taken together, we established a tractable experimental model to facilitate a better understanding of the impact and mechanism of Al(OH) exposure on human brain development.
Topics: Child, Preschool; Humans; Human Embryonic Stem Cells; Aluminum Hydroxide; Neurogenesis; Neural Stem Cells; Organoids
PubMed: 37011512
DOI: 10.1016/j.ecoenv.2023.114863 -
Journal of Controlled Release :... Oct 2020Adjuvants that contain pathogen-associated molecular patterns (PAMPs) can enhance vaccination efficacy by binding to pattern recognition receptors (PRRs), thereby...
Adjuvants that contain pathogen-associated molecular patterns (PAMPs) can enhance vaccination efficacy by binding to pattern recognition receptors (PRRs), thereby stimulating immune responses. Particularly effective may be the combination of multiple PAMPs that activate different PRRs, which occurs with natural pathogens. Here we hypothesized the enhanced effects would occur in two adjuvants that stimulate different PRRs: CpG oligodeoxynucleotide (CpG-ODN), which is Toll-like receptor 9 agonist; and 5'-triphosphate, short, double-stranded RNA (3pRNA), which activates retinoic acid-inducible gene I (RIG-I). The model antigen ovalbumin (OVA) was loaded and adjuvants were surface-adsorbed to aluminum hydroxide nanoparticles (hereafter NP-3pRNA-CpG) by electrostatic interaction with an average size of 120 nm and a negative surface charge for targeting lymph nodes. These nanoparticles were efficiently internalized by antigen-presenting cells (APCs) in the lymph nodes, and the resulting APC activation and antigen cross-presentation generated strong humoral immunity and cytotoxic T lymphocyte responses and IFN-γ secretion. NP-3pRNA-CpG significantly suppressed B16-OVA tumor growth and prolonged survival of tumor-bearing mice in therapeutic and prophylactic models, illustrating the enhanced effects of CpG-ODN and 3pRNA. Our study highlights the potential of combining multiple adjuvants for effective vaccine design.
Topics: Adjuvants, Immunologic; Aluminum Hydroxide; Animals; Antigens; Mice; Mice, Inbred C57BL; Nanoparticles; Oligodeoxyribonucleotides; Ovalbumin
PubMed: 32585230
DOI: 10.1016/j.jconrel.2020.06.021 -
Chemosphere May 2018Microbe-associated aluminum (Al) hydroxides occur naturally in aquatic and geologic environments and they might play a crucial role in the sequestration of trace metals...
Microbe-associated aluminum (Al) hydroxides occur naturally in aquatic and geologic environments and they might play a crucial role in the sequestration of trace metals because these composite solids comprise both reactive mineral and organic surface, but how they do it still remains unknown. Here we replicate Al hydroxide organo-mineral composite formation in soil and sediments by synthesising composites using Pseudomonas putida cells, during coprecipitation with Al hydroxide. Morphological and ATR-FTIR analysis show closely attached nano-sized Al hydroxides on the bacterial surface. For composites dominated by either bacteria or Al hydroxide, an enhanced metal adsorption is observed on the composites than on pure Al hydroxide at pH < 6. Cd uptake by the mainly Al mineral composite is approximately additive, i.e., the sum of the end-member metal adsorptivities, whereas that on the mainly bacteria composite is non-additive. This non-additive sorption is not only due to the blockage of surface reactive sorption sites, but more importantly the changes of surface charge when bacteria and Al mineral are interacted. EXAFS results show that Cd is predominately sorbed as a bidentate corner-sharing complex on the amorphous Al hydroxide surface and a carboxyl-binding on the bacterial surface. This study has important implications for understanding both Al and trace metal cycling in microbe-rich geologic environments.
Topics: Adsorption; Aluminum Hydroxide; Bacteria; Cadmium; Minerals; Nanoparticles; Pseudomonas putida
PubMed: 29421763
DOI: 10.1016/j.chemosphere.2018.01.128 -
Journal of Environmental Sciences... Aug 2018Fourier-transform infrared (FT-IR) spectroscopic experiments were carried out during phosphate adsorption on highly crystalline gibbsite, poorly crystalline...
Fourier-transform infrared (FT-IR) spectroscopic experiments were carried out during phosphate adsorption on highly crystalline gibbsite, poorly crystalline 2-line-ferrihydrite and amorphous iron-aluminum-hydroxide mixtures in the molar ratio 1:0, 10:1, 5:1, 1:1, 1:5, 1:10 and 0:1. The OH stretching vibrational bands were utilized to analyze changes in structural and surface OH groups during adsorption, because the position of characteristic PO vibrational bands can shift depending on reaction conditions, pH or adsorbed phosphate content. Adsorption and desorption kinetics were studied at pH6 and different initial phosphate concentrations to achieve varying phosphate coverage on the mineral surfaces. For gibbsite the formation of AlHPO and AlHPO can be assumed, while for ferrihydrite, a FeHPO or FePO complex and the precipitation of FePO with longer equilibration time were proposed. FeHPO or a FePO surface complex was deduced for Fe-hydroxides, an AlHPO surface complex was identified for Al-hydroxide, and both displayed either hydrogen bonds to neighboring hydroxyl groups or hydrogen bonds to outer-sphere complexes. Fe:Al-hydroxide mixtures with high Al ratios showed a low phosphate desorption rate, while ferrihydrite and the Fe:Al-hydroxide mixtures with high Fe ratios had almost negligible desorption rates. It was concluded that within the weakly associated amorphous FeO(OH) materials, FePO precipitated, which was bound by outer-sphere hydrogen bonds. With high Al ratios, desorption increased, which indicated weaker phosphate binding of both inner-sphere and outer-sphere complexes and hence, either no or minor quantities of precipitate. Ferrihydrite showed a more rigid structure and a lower extent of precipitation compared to amorphous Fe-hydroxide.
Topics: Adsorption; Aluminum Hydroxide; Chemical Precipitation; Ferric Compounds; Iron; Kinetics; Minerals; Models, Chemical; Phosphates; Spectroscopy, Fourier Transform Infrared; Surface Properties
PubMed: 30037404
DOI: 10.1016/j.jes.2017.12.001 -
Bioscience, Biotechnology, and... Sep 2020Here, we prepared the novel combined adjuvants, CTB as intra-molecular adjuvant, CpG and aluminum hydroxide (Alum) to strengthen the immunogenicity of clumping factor A...
UNLABELLED
Here, we prepared the novel combined adjuvants, CTB as intra-molecular adjuvant, CpG and aluminum hydroxide (Alum) to strengthen the immunogenicity of clumping factor A of (). The protein-immunoactive results showed CTB-ClfA elicited the strong immune responses to serum from mice immunized with CTB and ClfA, respectively. The mice immunized with CTB-ClfA plus CpG and Alum adjuvant exhibited significantly stronger CD4 T cell responses for IFN-γ, IL-2, IL-4, and IL-17 and displayed the higher proliferation response of splenic lymphocytes than the control groups, in addition, these mice generated the strongest humoral immune response against ClfA among all groups. Our results also showed CTB-ClfA plus CpG and Alum adjuvant obviously increased the survival percentage of the mice challenged by . These data suggested that the novel combined adjuvants, CTB, CpG, and Alum, significantly enhance the immune responses triggered with ClfA, and could provide a new approach against infection of .
ABBREVIATIONS
CTB: Cholera Toxin B; CpG: Cytosine preceding Guanosine; ODN: Oligodeoxynucleotides; Alum: Aluminum hydroxide; TRAP: Target of RNAIII-activating Protein; TLR9: Toll-like Receptor 9; TMB: 3, 3', 5, 5'-tetramethylbenzidine; mAbs: Monoclonal Antibodies; OD: Optical Densities; ; ClfA: Clumping factor A; FnBPA: Fibronection-binding protein A; IsdB: Iron-regulated surface determinant B; SasA: Surface Protein A; GapC: Glycer-aldehyde-3-phosphate dehydrogenase-C.
Topics: Adjuvants, Immunologic; Aluminum Hydroxide; Animals; Cell Proliferation; Cholera Toxin; Coagulase; Drug Interactions; Immunization; Lymphocytes; Mice; Oligodeoxyribonucleotides
PubMed: 32501144
DOI: 10.1080/09168451.2020.1771170