What Are the Reliable Plasma Biomarkers for Mild Cognitive Impairment? A Clinical 4D Proteomics Study and Validation.

Objective: At present, Alzheimer's disease (AD) lacks effective treatment means, and early diagnosis and intervention are the keys to treatment. Therefore, for mild cognitive impairment (MCI) and AD patients, blood sample analysis using the 4D nonstandard (label-free) proteomic in-depth quantitative analysis, looking for specific protein marker expression differences, is important. These marker levels change as AD progresses, and the analysis of these biomarkers changes with this method, which has the potential to show the degree of disease progression and can be used for the diagnosis and preventive treatment of MCI and AD. Materials and Methods: Patients were recruited according to the inclusion and exclusion criteria and divided into three groups according to scale scores. Elderly patients diagnosed with AD were selected as the AD group (n = 9). Patients diagnosed with MCI were classified into the MCI group (n = 10). Cognitively healthy elderly patients were included in the normal cognition control group (n = 10). Patients' blood samples were used for 4D label-free proteomic in-depth quantitative analysis to identify potential blood biomarkers. The sample size of each group was expanded (n = 30), and the selected biomarkers were verified by enzyme-linked immunosorbent assay (ELISA) to verify the accuracy of the proteomic prediction. Results: Six specific blood markers, namely, APOE, MMP9, UBR5, PLA2G7, STAT5B, and S100A8, were detected by 4D label-free proteomic quantitative analysis. These markers showed a statistically significant upregulation trend in the MCI and AD groups compared with the normal cognition control group (P < 0.05). ELISA results showed that the levels of these six proteins in the MCI group were significantly higher than those in the normal cognition control group, and the levels of these six proteins in the AD group were significantly higher than those in the MCI group (P < 0.05). Conclusion: The plasma levels of APOE, MMP9, UBR5, PLA2G7, STAT5B, and S100A8 in cognitively healthy elderly patients and patients with MCI and AD were significantly different and, more importantly, showed a trend of increasing expression. These results indicate that these six human plasma markers have important diagnostic and therapeutic potential in the identification of cognitive impairment and have value for in-depth research and clinical application.

A cross-sectional study on three-dimensional compensatory characteristics of maxillary teeth in patients with different types of skeletal Class III malocclusion with mandibular asymmetry.

OBJECTIVE: The purpose of this study was to analyze three-dimensional dental compensation in patients with different types of skeletal Class III malocclusion with mandibular asymmetry, using cone-beam computed tomography (CBCT) and three-dimensional reconstruction measurement technology, thereby providing clinical guidance and reference for combined orthodontic and orthognathic treatment. METHODS: 81 patients with skeletal Class III malocclusion with mandibular asymmetry were selected in accordance with the inclusion criteria. According to a new classification method based on the direction and amount of menton deviation relative to ramus deviation, patients were divided into three groups called Type 1, Type 2, and Type 3. In Type 1, the direction of menton deviation was consistent with that of ramus deviation and the amount of menton deviation was greater than that of ramus deviation. In Type 2, the direction of menton deviation was consistent with that of ramus deviation and the amount of menton deviation was smaller than that of ramus deviation. In Type 3, the direction of menton deviation was inconsistent with that of ramus deviation. The maxillary occlusal plane (OP), anterior occlusal plane (AOP), and posterior occlusal plane (POP) were measured on reconstructed CBCT images. The vertical, transverse, and anteroposterior distances from maxillary teeth to reference planes and the 3D angles between the long axis of these teeth and reference planes were measured. These dental variables measured from the deviated and non-deviated sides were compared within each group, as well as among each other. RESULTS: Of the 81 patients with asymmetrical Class III malocclusion, 52 patients were categorized in Type 1, 12 patients in Type 2, and 17 patients in Type 3. There were significant differences between deviated and non-deviated sides in Type 1 and Type 3 (p < 0.05). In Type 1, the vertical distances of maxillary teeth on the deviated side were lower than those on the non-deviated side, and AOP, OP, and POP on the deviated side were larger than those on the non-deviated side (p < 0.05). In Type 3, the vertical distances of the maxillary teeth on the deviated side were lower (p < 0.05), and the AOP and OP on the deviated side were larger than those on the non-deviated side. In all three groups, the transverse distances of the maxillary teeth from the mid-sagittal plane on the deviated side were larger than those on the non-deviated side (p < 0.05), and the angles between the long axis of maxillary teeth and the mid-sagittal plane on the deviated side were larger, respectively (p < 0.05). CONCLUSIONS: The maxillary teeth on the deviated side were observed to have smaller eruption heights in Type 1 and Type 3. In Type 1, AOP, POP, and OP were greater on the deviated side, while in Type 3, only AOP and OP were greater on the deviated side. The maxillary teeth of patients in all three groups on the deviated side were buccal and buccally inclined. Larger sample observations are still needed to further verify these findings.

Applying mixotrophy strategy to enhance biomass production and nutrient recovery of Chlorella pyrenoidosa from biogas slurry: An assessment of the mixotrophic synergistic effect.

Using biogas slurry to cultivate microalgae can simultaneously obtain microalgal biomass and allow nutrient recovery. Mixotrophic microalgae are widely recognized for their high biomass accumulation and low light dependence, making it possible to overcome the drawbacks of photoautotrophy. In this study, three complete metabolic modes of photoautotrophy, heterotrophy, mixotrophy and two incomplete metabolic modes with the addition of diuron and rotenone were applied to investigate Chlorella pyrenoidosa growth in biogas slurry. The results showed that the mixotrophic group obtained 1.15 g/L biomass, 30 % starch content, 99.40 % ammonium removal and 81.69 % total phosphorus removal, which were highly promoted compared to the others. The decline in chlorophyll, the simultaneous downregulation of Rubisco and citrate synthase and the increase in the actual quantum yield of PSII under mixotrophy revealed a synergistic effect: the complementation of photophosphorylation and oxidative phosphorylation greatly contributed to maximizing energy metabolism efficiency and minimizing energy dissipation loss.

Schizandrin A ameliorates cognitive functions via modulating microglial polarisation in Alzheimer's disease mice.

CONTEXT: Schizandrin A (Sch A) is a major phytochemical from Schisandra chinensis (Turcz.) Baill. (Schisandraceae), which exerts a neuroprotective effect in Alzheimer's disease (AD). OBJECTIVE: To investigate the mechanism of Sch A in AD. MATERIALS AND METHODS: AD group: APP/PS1 transgenic mice served as AD models; AD + SCH group: APP/PS1 received 2 mg/kg Sch A by intragastric administration; WT: C57BL/6 mice were used as control. For in vitro assay, mouse microglial BV2 cells were treated with 0.5 µg/mL lipopolysaccharide or combined with 10 µmol/L Sch A for 24 h. The cognitive function and apoptosis in the mice was estimated. Microglial polarisation in the mice and cells was analysed. RESULTS: Sch A treatment effectively improved spatial learning and memory ability and suppressed apoptosis in the brain tissues of APP/PS1 mice. APP/PS1 mice exhibited an increase in the levels of Aß1-42 (2367.9 ± 431.1 pg/mg) and Aß1-40 (1753.3 ± 253.4 pg/mg), which was abolished by Sch A treatment. Moreover, Sch A treatment repressed the proportions of iNOS+/Iba-1+ cells and IL-6 expression, while enhanced the proportions of Arg-1+/Iba-1+ cells and IL-10 expression in APP/PS1 mice. In vitro, Sch A treatment reduced the proportions of CD16/32+ cells, iNOS expression and IL-6 levels (25.7 ± 5.3 pg/mL) repressed M1 polarisation, and enhanced the proportions of CD206 cells, Arg-1 expression and IL-10 levels (75.9 ± 12.8 pg/mL) in BV2 cells. CONCLUSIONS: This research confirms the neuroprotective effect of Sch A in AD, suggesting that Sch A may become a potential anti-AD agent.

Three-dimensional changes of the upper airway in patients with Class II malocclusion treated with functional appliances: a systematic review and meta-analysis.

BACKGROUND/OBJECTIVE: To evaluate the three-dimensional (3D) changes of the upper airway in patients with Class II malocclusion treated with functional appliances (FAs). SEARCH METHODS AND ELIGIBILITY CRITERIA: A comprehensive search of seven electronic databases was conducted from the date of inception to 12 July 2020. Manual search was also performed in relevant Chinese and English periodicals. Prospective and retrospective studies evaluating the 3D airway changes after FAs applied on growing patients with skeletal Class II malocclusion were included. DATA COLLECTION AND ANALYSIS: Risk of bias assessment of each included study was performed referring to ROBINS-I. The effects of FAs on upper airway were evaluated by meta-analysis using STATA software. The outcome variables were the changes of oropharyngeal airway volumes (OAVs), nasopharyngeal airway volumes (NAVs), minimum cross-sectional area (MCA) and antero-posterior position of hyoid bone (HB). The overall quality of evidence for each outcome was rated based on Grading of Recommendations Assessment, Development and Evaluation recommendations. RESULTS: Nine studies were ultimately included in the systematic review and five were included and analyzed in meta-analysis. The results indicated that the pooled mean differences among these studies were 2162.80 [95 per cent confidence interval (CI): 1264.97, 3060.62), 382.20 (95 per cent CI: 140.95, 623.44), 59.91 (95 per cent CI: 41.45, 78.38), and 0.63 (95 per cent CI: -1.97, 3.23) for changes of OAVs, NAVs, MCA, and antero-posterior position of HB, respectively. CONCLUSION: Weak evidence suggests that FAs can increase OAVs, NAVs, and MCA in growing patients with Class II malocclusion. Weak evidence also suggests that antero-posterior position of HB cannot be affected by FAs. Further studies are necessary to assess the stability of its effect on the upper airway in the long term. REGISTRATION: The review protocol was not registered prior to the study.

The Effectiveness of Photobiomodulation on Accelerating Tooth Movement in Orthodontics: A Systematic Review and Meta-Analysis.

Objective: This meta-analysis evaluated the effectiveness of photobiomodulation therapy (PBMT) on accelerating orthodontic tooth movement (OTM) in clinical practice. Methods: Data from bilingual journals across seven different databases were compiled and analyzed. Randomized controlled trials (RCTs) and quasi-RCTs regarding the effect of PBMT on OTM in cases with four first premolar extractions in split-mouth design were selected. This study was conducted after approval from the IRB. The outcome variables were the cumulative tooth movement distances in 1, 2, and 3 months. Data extraction was performed by two authors independently and in duplicate. Risk of bias was assessed. Results: Eight RCTs and one quasi-RCT were ultimately included and analyzed in meta-analysis. This study revealed that the pooled mean difference (MD) among these trials was 0.30 [95% confidence interval (CI): -0.02 to 0.62], 0.69 (95% CI: 0.08 to 1.29), and 0.64 (95% CI: -0.01 to 1.29) for 1, 2, and 3 months, respectively. The results remained consistent after sensitivity analysis assessment. Conclusions: There is insufficient evidence to support that photobiomodulation accelerates tooth movement in orthodontic treatments. Our results suggest that the optimal parameters of PBMT on OTM in human might be about 20 mW, 5-8 J/cm2, 0.5 W/cm2, 0.2 J/point, and 2-10 J/tooth. More large-sample multicenter clinical trials carried out in similar settings are required to confirm and pinpoint treatment efficiency and optimal parameters. Registration: The review protocol was not registered prior to the study.

Schisandrin Inhibits NLRP1 Inflammasome-Mediated Neuronal Pyroptosis in Mouse Models of Alzheimer's Disease.

BACKGROUND: In recent years, schisandrin (SCH) was proved to improve Alzheimer's Disease (AD). The aim of our study is to explore the effect of SCH on neuronal pyroptosis in the disease. METHODS: A Morris water maze test was performed to evaluate the spatial learning and memory retention of AD mouse. ELISA was fulfilled to examine the concentration of Aß, IL-1ß, and IL-18. Western blot was performed to detect the expression of apoptosis- and pyroptosis-related proteins. Besides, the neuronal apoptosis rate was examined using TUNEL assay. Immunohistochemistry was utilized to detect the activation of NLRP1 inflammasome. RESULTS: Here, AD mice have serious cognitive impairment. Meantime, Aß was highly expressed in the brains of AD mice. SCH could effectively rescue the cognitive impairment in AD mice and impede the production of Aß. Subsequently, we further demonstrated that SCH repressed neuronal apoptosis, pyroptosis-related proteins expression, and the activation of NLRP1 inflammasome in the hippocampus of AD mice. We also proved that Aß induced neuronal apoptosis and pyroptosis in vitro. However, the effects of Aß on neuronal apoptosis and pyroptosis were partly reversed by SCH treatment. CONCLUSION: Overall, our data indicated that SCH improved cognitive impairment in AD mice through inhibition of NLRP1 inflammasome-mediated neuronal pyroptosis and neuronal apoptosis. Our works provided new evidence to support SCH acting as a potential treatment method in AD.

Neuroprotective effect of Betalain against AlCl3-induced Alzheimer's disease in Sprague Dawley Rats via putative modulation of oxidative stress and nuclear factor kappa B (NF-κB) signaling pathway.

Alzheimer's disease (AD) is the most progressive form of neurodegenerative disease, which severely impairs cognitive function. Oxidative stress is identified to contribute to the mechanisms responsible for the pathogenesis of such neurodegenerative diseases. Aluminum is a potent neurotoxin for inducing oxidative stress associated with neurodegenerative diseases. The treatment for AD is limited; hence more treatment options are the need of the day. Betalain is known for its multitude of medicinal assets, including anti-inflammatory activity. Hence, this study was intended to investigate the possible protective effect of betalain against aluminum chloride (AlCl3) induced AD on Sprague Dawley (SD) rats. AlCl3 (100 mg/kg) was administrated orally to induce the AD in SD rats. The rats were supplemented with low and high betalain doses (10 mg/kg and 20 mg/kg) for four weeks. At the end of the experiment, the rats were subjected to behavioral examination and sacrificed to study the biochemical and histological parameters. The results showed attenuation of memory and learning capacity, suppression of lipid oxidation (MDA) through regulation of antioxidant content (SOD, CAT, and GSH) and inhibition of lactate dehydrogenase (LDH), nitric oxide (NO), acetylcholinesterase (AChE), and transmembrane protein (Na+K+ATPase) activity. In addition, the NF-ƙB associated mRNA expression (TNF-α IL-6, Il-1ß, iNOS, COX-2) was decreased, as evidenced in histopathological results. The present investigation established that the betalain treatment ameliorated the AlCl3 induced AD by modulating NF-κB pathway activation.