Humans ; Aluminum/adverse effects* ; Pruritus/etiology* ; Skin Neoplasms ; Vaccination ; Hypersensitivity

Objective: To investigate the effect and mechanism of miR-96-5p on apoptosis of PC12 cells induced by maltol aluminum. Methods: In January 2021, PC12 cells at logarithmic growth phase were divided into blank control group and low, medium and high dose group. Cells in each group were treated with 0, 100, 200 and 400 μmol/L maltol aluminum for 24 hours respectively. Cells were collected and cell apoptosis rates were detected by flow cytometry, miR-96-5p and insulin receptor substrate 1 (IRS1) mRNA expressions were detected by qRT-PCR, and the protein expression levels of cysteine protease 3 (Caspase3) 、activated cysteine protease 3 (Cleaved-caspase3) 、IRS1、phosphorylated protein kinase B (p-AKT) and phosphorylated glucose synthesis kinase 3β (p-GSK3β) were detected by western blotting. The target binding relationship between miR-96-5p and IRS1 was detected by double luciferase reporter gene experiment. The miR-96-5p inhibitor cells and negative control cells were constructed after transfecting PC12 cells with miR-96-5p inhibitor for 24 hours. The cells were divided into blank control group, negative control group, aluminum exposure group, aluminum exposure+negative control group, aluminum exposure+miR-96-5p inhibition group, and miR-96-5p inhibition group. After transfecting PC12 cells with miR-96-5p inhibition and IRS1 siRNA for 24 h, the cells were divided into aluminum exposure+miR-96-5p inhibition+negative control group and aluminum exposure+miR-96-5p inhibition+IRS1 inhibition group. The control group was cultured in complete culture medium, and cells in the aluminum exposure group were treated with 200 μmol/L maltol aluminum for 24 hours. Cells in each group were collected and the apoptosis rate, miR-96-5p and IRS1 mRNA expression levels, as well as protein expression levels of Caspase3, Cleaved-caspase3, IRS1, p-AKT, and p-GSK3β were measured. Results: After 24 hours of exposure, compared with blank control group and low-dose group, the apoptosis rates, relative expressions of Caspase3 and Cleaved-caspase3 proteins, and relative expressions of miR-96-5p in the medium and high-dose groups of PC12 cells were significantly increased, while the relative expression levels of IRS1 mRNA, IRS1, p-AKT and p-GSK3β proteins were significantly decreased (P<0.05). Targetscan prediction and double luciferase report experiment both proved that IRS1 was a direct target gene of miR-96-5p. In the transfection experiment, compared with the aluminum exposure group, the apoptosis rate, the relative expressions of Caspase3 and Cleaved-caspase3 proteins, the relative expression of miR-96-5p in the aluminum exposure+miR-96-5p inhibition group were significantly decreased, while the relative expression levels of IRS1 mRNA and IRS1, p-AKT and p-GSK3β proteins were significantly increased (P<0.05). In the IRS1 low expression experiment, compared with the aluminum exposure+miR-96-5p inhibition+negative control group, the apoptosis rate, the relative expressions of Caspase3 and Cleaved-caspase3 proteins in the aluminum exposure+miR-96-5p inhibition+IRS1 inhibition group were significantly increased, while the relative expression levels of IRS1 mRNA and IRS1, p-AKT and p-GSK3β proteins were significantly decreased (P<0.05) . Conclusion: The increased expression of miR-96-5p and the targeted inhibition of IRS1 may be one of the mechanisms of apoptosis of PC12 cells induced by maltol aluminum exposure.
Animals ; Rats ; Aluminum/toxicity* ; Apoptosis ; Cell Proliferation ; Glycogen Synthase Kinase 3 beta/metabolism* ; Insulin Receptor Substrate Proteins/metabolism* ; MicroRNAs/metabolism* ; PC12 Cells ; Proto-Oncogene Proteins c-akt/metabolism* ; RNA, Messenger

Objective: To investigate the clinical characteristics of patients with acute phosphine poisoning, and to follow up and evaluate the prognosis of patients. Methods: In May 2022, 12 patients with phosphine poisoning by respiratory inhalation in Beijing Chao-Yang Hospital of Capital Medical University were analyzed. The patients were treated with symptomatic support therapy. Three months later, patients were re-evaluated the symptoms of poisoning, pulmonary function and magnetic resonance imaging (MRI) of the brain to understand the prognosis of the phosphine poisoning. Results: The main symptoms of 12 patients were respiratory and central nervous system symptoms with hypoxia. The symptoms of poisoning improved after treatment. Follow-up found that the patients had different degrees of residual symptoms. Pulmonary function showed increased airway resistance. Airway challenge test was positive in some patients. MRI of the head of some patients showed small ischemic focus in bilateral frontal lobes. Conclusion: Acute phosphine poisoning may cause persistent damage to the respiratory system and central system, and residual symptoms after 3 months.
Humans ; Follow-Up Studies ; Phosphines ; Lung ; Lung Diseases ; Aluminum Compounds ; Poisoning/diagnosis*

OBJECTIVE: To compare the clinical effects of pulpotomy with two kinds of calcium silicate materials, and to evaluate the formation of dentin bridge and pulp calcification after pulpotomy of adult permanent teeth. METHODS: Patients who visited the General Department of Peking University School and Hospital of Stomatology from November 2017 to September 2019 and planned for pulpotomy on permanent premolars and molars with carious exposed pulp were selected. They were randomly divided into two groups. Bioceramic putty material iRoot BP (iRoot group, n=22) and mineral trioxide aggregate MTA (MTA group, n=21) were used as pulp capping agents, respectively. The patients were recalled after one year and two years. The clinical efficacy, dentin bridge index (DBI) and pulp calcification index (PCI) were recorded. Blinding method was used for the patients and evaluators. RESULTS: There was no significant difference in gender, mean age, dentition and tooth position between the two groups (P>0.05). Seven cases were lost during the first year (4 cases in iRoot group and 3 cases in MTA group). In the iRoot group, 1 case had transient sensitivity at the time of 1-year follow-up. The cure rate of the two groups was 100% at the time of 2-year follow-up. The proportion of dentin bridge formation was 38.9% one year after operation, 55.6% two years after operation. The proportion of partial or even complete disappearance of root canal image was 5.6% before operation, 38.9% and 55.6% one and two years after operation, respectively. The difference was statistically significant by rank sum test (P < 0.05). There was no significant difference in dentin bridge formation and pulp calcification between the two groups (P < 0.05). DBI and PCI after operation was as the same as those before operation (44.4% cases of DBI and 25% cases of PCI) or gradually increased (55.6% cases of DBI and 75% cases of PCI). Spearman's nonparametric correlation analysis showed that age was positively correlated with preoperative pulp calcification index (PCI0, P < 0.05), but not with the dentin bridge index (DBI1, DBI2), pulp calcification index (PCI1, PCI2) and the degree of change (DBI2 vs. DBI1, PCI1 vs. PCI0, PCI2 vs. PCI0) 1-year and 2-year after operation (P>0.05). CONCLUSION According to this study, good clinical effects were obtained within 2-year after pulpotomy of adult permanent teeth with MTA and iRoot. In some cases, the root canal system had a tendency of calcification aggravation, and there was no statistical difference in the development of this trend between the two groups.
Humans ; Adult ; Pulpotomy/methods* ; X-Rays ; Calcium Compounds/therapeutic use* ; Dentition, Permanent ; Molar/surgery* ; Treatment Outcome ; Silicates/therapeutic use* ; Aluminum Compounds/therapeutic use* ; Oxides ; Drug Combinations ; Dental Pulp Capping

The aluminum stress in acidic soil areas of China is an important abiotic stress factor that hampers the normal growth and development of plants and seriously affects the agricultural yield. The forms of plant resistance to aluminum stress are complex and diverse, which include secretion of organic acids, increase of rhizosphere pH, secretion of mucus, cell wall fixation of Al³⁺, organic acid chelation of Al³⁺ in cell solute, and vacuolar area isolation. Most of studies focus on analyzing conventional physiological characteristics, but in-depth molecular biological analyses are lacking. This review summarizes the mechanisms how plants adapt to acidic aluminum stress. This includes the effect of acid aluminum stress on plant growth and physiological metabolism, the two main physiological mechanisms of plant adaptation to acid aluminum stress (aluminum exclusion mechanism, aluminum tolerance mechanism), and the aluminum resistance related genes. Finally, this paper puts forward some prospects for further revealing the mechanism of plant adaptation to acid aluminum stress and excavating high-quality crops suitable for cultivation in acidic soils.
Acids ; Adaptation, Physiological ; Aluminum ; Crops, Agricultural/genetics* ; Gene Expression Regulation, Plant ; Plant Roots ; Soil/chemistry*

A fusion protein containing a tetanus toxin peptide, a tuftsin peptide and a SARS-CoV-2S protein receptor-binding domain (RBD) was prepared to investigate the effect of intramolecular adjuvant on humoral and cellular immunity of RBD protein. The tetanus toxin peptide, tuftsin peptide and S protein RBD region were connected by a flexible polypeptide, and a recombinant vector was constructed after codon optimization. The recombinant S-TT-tuftsin protein was prepared by prokaryotic expression and purification. BALB/c mice were immunized after mixed with aluminum adjuvant, and the humoral and cellular immune effects were evaluated. The recombinant S-TT-tuftsin protein was expressed as an inclusion body, and was purified by ion exchange chromatography and renaturated by gradient dialysis. The renaturated protein was identified by Dot blotting and reacted with serum of descendants immunized with SARS-CoV-2 subunit vaccine. The results showed that the antibody level reached a plateau after 35 days of immunization, and the serum antibody ELISA titer of mice immunized with recombinant protein containing intramolecular adjuvant was up to 1:66 240, which was significantly higher than that of mice immunized with S-RBD protein (P < 0.05). At the same time, the recombinant protein containing intramolecular adjuvant stimulated mice to produce a stronger lymphocyte proliferation ability. The stimulation index was 4.71±0.15, which was significantly different from that of the S-RBD protein (1.83±0.09) (P < 0.000 1). Intramolecular adjuvant tetanus toxin peptide and tuftsin peptide significantly enhanced the humoral and cellular immune effect of the SARS-CoV-2 S protein RBD domain, which provideda theoretical basis for the development of subunit vaccines for SARS-CoV-2 and other viruses.
Adjuvants, Immunologic ; Aluminum ; Animals ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19/prevention & control* ; COVID-19 Vaccines/genetics* ; Humans ; Mice ; Mice, Inbred BALB C ; Recombinant Proteins/genetics* ; SARS-CoV-2/genetics* ; Spike Glycoprotein, Coronavirus/genetics* ; Tetanus Toxin ; Tuftsin ; Vaccines, Subunit ; Viral Vaccines

This study explored the curative effect of Jingfang Mixture on urticaria mice induced by aluminum hydroxide/ovalbumin, and discussed its mechanism. Sixty male Kunming mice were randomly divided into a normal group, a model group, three Jingfang Mixture(low-dose, medium-dose, and high-dose) groups, and a positive drug(cetirizine hydrochloride) group. The urticarial model in mice was induced by the intraperitoneal injection of the mixed solution of ovalbumin and aluminum hydroxide. The degrees of pruritus were observed after the second immunization. Pathological changes were detected by hematoxylin and eosin(HE) staining. Levels of interleukin 1β(IL-1β) and tumor necrosis factor α(TNF-α) in the serum were detected by enzyme linked immunosorbent assay(ELISA). Expressions of NOD-like receptor protein 3(NLRP3) and IL-1β were detected by immunohistochemistry(IHC). Expressions of nuclear factor kappa-B(NF-κB p65), NLRP3, apoptosis-associated speck-like protein containing a CARD(ASC), cysteinyl aspartate-specific proteases 1(caspase-1), and IL-1β proteins were detected by Western blot. The results showed that, except for the normal group, the mice in all groups had different degrees of pruritus. Compared with the model group, the Jingfang Mixture groups and the positive drug group prolonged the scratching latency of mice(P<0.05), and significantly reduced the number of scratching(P<0.05). In addition, the Jingfang Mixture groups and the positive drug group improved the pathological morphology of skin tissue. The expression levels of IL-1β and TNF-α in serum were significantly reduced(P<0.05), and the number of NLRP3 and IL-1β positive cells was decreased(P<0.01). The expressions of p-NF-κB p65, NLRP3, ASC, cleaved caspase-1, and IL-1β protein were significantly down-regulated(P<0.05). The results of the above study indicate that Jingfang Mixture inhibit the inflammatory response in urticaria mice, and the mechanism may be related to the inhibition of activating NF-κB/NLRP3/IL-1β signaling pathway.
Animals ; Male ; Mice ; NF-kappa B/metabolism* ; Interleukin-1beta/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Ovalbumin ; Aluminum Hydroxide/pharmacology* ; Signal Transduction ; Caspase 1/metabolism* ; Urticaria ; Pruritus

OBJECTIVE: To evaluate the clinical characteristics and effectiveness of pulpotomy in mature permanent teeth with bioceramic putty repairmen iRoot and mineral trioxide aggregate (MTA). METHODS: Pulpotomy was performed on mature permanent premolars and molars with carious exposures at the Department of General Dentistry of Peking University School and Hospital of Stomatology, from November 2017 to September 2019. The patients were randomly divided into 2 groups, Group iRoot (n=22) and Group MTA (n=21). In Group iRoot, bioceramic putty repairmen iRoot was used as pulp capping agent, while in Group MTA, mineral trioxide aggregate was used as pulp capping agent. All the patients had signed informed consent forms. The clinical efficacy was evaluated by clinical examinations (temperature and electrical activity test) and imaging examinations 3, 6, and 12 months after surgery. Blinding was used for the patients and evaluators, but due to the obvious differences in the properties of the two pulp capping agents, the blinding method was not used for the treatment provider (the attending physician). RESULTS: There was no significant difference in gender, average age, dentition and tooth position distribution between the two groups (P>0.05). In the study, 7 cases were lost to follow-up 12 months after operation (4 cases in Group iRoot, and 3 cases in Group MTA). One case in each of the two groups had transient sensitivity at the end of the 3-month follow-up, and the pulp vitality was normal at the end of the 6-month follow-up. One case in Group iRoot showed sensitivity at the end of the 12-month follow-up. The success rates of the two groups at the end of 12-month follow-up were 100%, and the cure rates were 94.4% (Group iRoot) and 100% (Group MTA), respectively, and the difference was not statistically significant (P>0.05). No cases in Group iRoot had obvious crown discoloration, while 3 cases in Group MTA had. CONCLUSION The clinical characteristics and effectiveness of pulpotomy in mature permanent teeth with bioceramic putty repairmen iRoot were similar with MTA. Bioceramic putty repairmen iRoot is an acceptable material when used in pulpotomy of mature permanent teeth. Because it is not easy to cause tooth discoloration after treatment and is convenient to operate, bioceramic putty repairmen iRoot has a better clinical application prospect.
Aluminum Compounds/therapeutic use* ; Calcium Compounds/therapeutic use* ; Drug Combinations ; Humans ; Oxides/therapeutic use* ; Pulpotomy ; Silicates/therapeutic use* ; Treatment Outcome

OBJECTIVE: To evaluate the efficacy of iRoot BP Plus, a novel bioceramic material, and mineral trioxide aggregate (MTA) by comparing the clinical and radiographic results of pulpotomy in human primary molars, and to find out the influence factor. METHODS: Children who had at least one primary molar diagnosed as pulpitis, and received pulpotomy in the Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology from January, 2017 to December, 2018 were searched by the selection criteria in the Electronic Medical Record Database of Peking University School and Hospital of Stomatology. The molars with the pulp capping agents were iRoot BP Plus or MTA were included, and the molars with other pulp capping agents were excluded. Molars using iRoot BP Plus were selected into the experimental group (iRoot BP Plus group). Molars using MTA were selected into the control group (MTA group) using propensity score matching model (1 ∶ 1), considering the gender, age, tooth position, the title of clinician, pulp status, restoration and length of follow-up as the potential influence factor. Basic information, the relevant medical records including symptoms, clinical and radiographic examination before and after operation, intraoperative information and follow up examination records were collected. The success rates were compared and the influence factors were analyzed respectively. RESULTS: The study included 132 children, 178 molars (89 molars from each group) and the mean follow-up time was (462±99) days by December, 2019. In the iRoot BP Plus group, 9 molars failed whilst 6 molars failed in MTA group. The success rate was 89.9% and 93.3%, respectively, showing no significant difference between the two groups. Through Cox proportional risk model analysis, the success rate of iRoot BP Plus was significantly lower when the pulp status was poor, while other factors including age, tooth position, title of clinician and restoration were not found to be associated with the clinical outcome. CONCLUSION Pulpotomy of human primary molars with iRoot BP Plus has the same effectiveness with MTA. The pulp status is the main factor that influences the outcome of iRoot BP Plus. Further studies with larger sample sizes and longer follow-up terms are needed.
Child ; Humans ; Pulpotomy/methods* ; Pulp Capping and Pulpectomy Agents ; Pemetrexed ; Silicates/therapeutic use* ; Aluminum Compounds/therapeutic use* ; Calcium Compounds ; Oxides ; Molar/surgery* ; Drug Combinations ; Treatment Outcome ; Tooth, Deciduous

The present study investigated the mechanism of the Tibetan patent medicine Ershiwuwei Shanhu Pills(ESP) in alleviating Alzheimer's disease in mice via Akt/mTOR/GSK-3β signaling pathway. BALB/c mice were randomly assigned into a blank control group, a model group, low(200 mg·kg~(-1)), medium(400 mg·kg~(-1)) and high(800 mg·kg~(-1)) dose groups of ESP, and donepezil hydrochloride group. Except the blank control group, the other groups were given 20 mg·kg~(-1) aluminum chloride by gavage and 120 mg·kg~(-1) D-galactose by intraperitoneal injection for 56 days to establish Alzheimer's disease model. Morris water maze was used to detect the learning and memory ability of mice. The level of p-tau protein in mouse hippocampus and the levels of superoxide dismutase(SOD), malondialdehyde(MDA), catalase(CAT), and total antioxidant capacity(T-AOC) in hippocampus and serum were detected. Hematoxylin-eosin staining and Nissl staining were performed for the pathological observation of whole brain in mice. TdT-mediated dUTP nick-end labeling(TUNEL) staining was employed for the observation of apoptosis in mouse cortex. Western blot was adopted to detect the protein levels of p-mTOR, p-Akt, and GSK-3β in the hippocampus. Compared with the model group, the ESP groups showcased alleviated pathological damage of the whole brain, decreased TUNEL positive cells, reduced level of p-tau protein in hippocampus, and risen SOD, CAT, and T-AOC levels and declined MDA level in hippocampus and serum. Furthermore, the ESP groups had up-regulated protein levels of p-mTOR and p-Akt while down-regulated protein level of GSK-3β in hippocampus. Therefore, ESP can alleviate the learning and memory decline and oxidative damage in mice with Alzheimer's disease induced by D-galactose combined with aluminum chloride, which may be related to Akt/mTOR/GSK-3β signaling pathway.
Aluminum Chloride/adverse effects* ; Alzheimer Disease/drug therapy* ; Animals ; Galactose/metabolism* ; Glycogen Synthase Kinase 3 beta/metabolism* ; Hippocampus/metabolism* ; Mice ; Mice, Inbred BALB C ; Plant Extracts ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; Superoxide Dismutase/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; tau Proteins