No abstract

The previous study by our group has found that miRNA‐22 can inhibit pyroptosis by targeting GSDMD and improve the memory and motor ability of mice with Alzheimer's disease (AD) mice by inhibiting inflammatory response. In recent years, stem cells and their exosomes have been reported to have good therapeutic effects on AD; therefore, we hypothesize that miRNA‐22 is likely to play a synergistic therapeutic effect. In this study, adipose‐derived mesenchymal stem cells (ADMSCs) were transfected into miRNA‐22 mimic to obtain miRNA‐22 loaded exosomes (Exo‐miRNA‐22), which was further used for the treatment and nerve repair of AD. In brief, 4‐month‐old APP/PS1 mice were assigned into the control group, Exo and Exo‐miRNA‐22 groups. After exosome transplantation, we observed changes in the motor and memory ability of mice. In addition, ELISA was used to detect the expression of inflammatory factors in cerebrospinal fluid and peripheral blood, Nissl staining was used to assess the survival of mouse nerve cells, immunofluorescence staining was used to determine the activation of microglia, and Western blot was utilized to detect the expression of pyroptosis‐related proteins. As a result, the nerve function and motor ability were significantly higher in mice in the Exo‐miRNA‐22 group than those in the control group and Exo group. Meanwhile, the survival level of nerve cells in mice was higher in the Exo‐miRNA‐22 group, and the expression of inflammatory factors was lower than that of the Exo group, indicating Exo‐miRNA‐22 could significantly suppress neuroinflammation. In vitro culture of PC12 cells, Aβ25‐35‐induced cell damage, detection of PC12 apoptotic level, the release of inflammatory factors and the expression of pyroptosis‐related proteins showed that Exo‐miRNA‐22 could inhibit PC12 apoptosis and significantly decrease the release of inflammatory factors. In this study, we found that miRNA‐22‐loaded ADMSC‐derived exosomes could decrease the release of inflammatory factors by inhibiting pyroptosis, thereby playing a synergetic therapeutic role with exosomes on AD, which is of great significance in AD research.

Objective This study was mainly conducted to explore the expression changes of GSDMD and conventional markers (including T‐Tau, Tau181p, and Aβ1–42) in the cerebrospinal fluid among patients with Alzheimer's disease (AD) and vascular dementia (VD), followed by determination of role of GSDMD in diagnosing and identifying AD and VD. Methods In this study, 60 patients with VD, 60 patients with AD, and 50 healthy controls were enrolled. Lumbar puncture was performed to collect cerebrospinal fluid samples. Patients with VD and patients with AD were evaluated using the Mini‐Mental State Examination (MMSE) scale, Montreal Cognitive Assessment (MoCA) scale, Clinical Dementia Rating (CDR) scale, Activity of Daily Living (ADL) scale, and Neuropsychiatric Inventory (NPI) questionnaire, aiming to determine the behavioral ability of patients. ELISA kit was purchased to determine the levels of GSDMD, T‐Tau, Tau181p, and Aβ1–42 in cerebrospinal fluid, and the expression of inflammatory factors, IL‐1β and IL‐6, was also detected. Results (1) The levels of GSDMD, T‐Tau, and Tau181p in the cerebrospinal fluid were higher in patients with AD than those of patients with VD and healthy controls, while the levels of Aβ1‐42 in the cerebrospinal fluid were lower in patients with AD than that in healthy controls and patients with VD. (2) GSDMD had good diagnostic accuracy in AD. Additionally, GSDMD, T‐Tau, Tau181p, and Aβ1‐42 had good discrimination accuracy in distinguishing AD and VD. (3) The expression levels of inflammatory factors (IL‐1β and IL‐6) in cerebrospinal fluid were higher in patients with AD than those of healthy controls and patients with VD, which were positively correlated with GSDMD expression. Conclusion The expression of GSDMD was increased in patients with AD, which could be used as a biomarker for AD diagnosis and identification from VD.

The aim of this study was to observe sperm aneuploidy, DNA integrity, seminal alpha-glucosidase (NAG) and acrosin activity (AA) under testicular heat stress (SH). Spermatozoa were obtained from 30 healthy adult volunteers subjected to scrotal warming at 43°C for 30-40 min on two successive days per week for 3 months between February 2012 and September 2016. Aniline blue (AB), acridine orange (AO) staining, TUNEL assay and FISH analysis to evaluate sperm function, sperm DNA integrity and chromosomal abnormalities were carried on before, during and after SH. Sperm AA and NAG was measured by microplate reader. The mean parameters of sperm parameters, AA and NAG were significantly decreased. In contrast, the mean percentage of sperm DNA fragmentation and the proportion of aneuploidy of chromosomes 13, 18, 21, X and Y were significantly increased for spermatozoa collected during SH versus before SH (p < .01-.001). After stopping scrotal heating for 3 months, most parameters were completely restored to pre-SH levels. Sperm parameters, sperm DNA integrity, chromosomes, AA and NAG are affected by scrotal exposure to constant SH temperatures several degrees over normal physiological temperature, and after treatment, these parameters were reversibly restored to the level before SH in adult men.

Resting-state functional magnetic resonance imaging (R-fMRI) signals are spatiotemporally organized. R-fMRI studies in patients with classic trigeminal neuralgia (CTN) have suggested alterations in functional connectivity. However, far less attention has been given to investigations of the local oscillations and their frequency-specific changes in these patients. The objective of this study was to address this issue in patients with CTN. R-fMRI data from 17 patients with CTN and 19 age- and gender-matched healthy controls (HCs) were analyzed using amplitude of low-frequency fluctuation (ALFF). The ALFF was computed across different frequencies (slow-4: 0.027–0.073 Hz; slow-5: 0.01–0.027 Hz; and typical band: 0.01–0.08 Hz) in patients with CTN compared to HCs. In the typical band, patients with CTN showed increases of ALFF in bilateral temporal, occipital, and left middle frontal regions and in the left middle cingulate gyrus, as well as decreases of ALFF in the right inferior temporal region and in regions (medial prefrontal regions) of default mode network. These significant group differences were identified in different sub-bands, with greater brainstem findings in higher frequencies (slow-4) and extensive default mode network and right postparietal results in lower frequencies (slow-5). Furthermore, significant relationships were found between subjective pain ratings and both amplitudes of higher frequency (slow-4) blood oxygen level-dependent (BOLD) signals in pain localization brain regions and lower frequencies (slow-5) in pain signaling/modulating brain regions in the patients, and decreased ALFF within the prefrontal regions was significantly correlated with pain duration in the patients. This result supports our hypothesis that trigeminal pain has a characteristic spatiotemporal distribution of low-frequency BOLD signals. These findings might contribute to a better understanding of the impact of CTN on the brain’s intrinsic architecture. Future studies should take the frequencies into account when measuring brain resting BOLD signals of patients with CTN.