ABSTRACT
STUDY OBJECTIVES: Increased reactive oxygen species associated with loss of mitochondrial function affect synaptic activity, which is an important mechanism underlying cognitive decline. This study assesses the role of mitochondrial proteins in neuron-derived exosomes (NDEs) on cognitive impairment in patients with obstructive sleep apnea (OSA) without dementia. METHODS: Analyses were conducted in 268 study participants with complete polysomnography data, cognitive tests, and important clinical data available. NDEs were isolated immunochemically for enzyme-linked immunosorbent assay quantification of mitochondrial proteins, i.e., humanin and mitochondrial open reading frame of the 12S rRNA-c (MOTS-c), and synaptic protein, i.e., neurogranin (NRGN). A mediation analysis of the relationship between sleep parameters and cognition was performed using humanin, MOTS-c, and NRGN values as a mediating factor. Twenty-two patients with moderate to severe OSA who received CPAP therapy were followed up, and humanin, MOTS-c and NRGN levels were reassessed after 1 year of treatment. RESULTS: All participants were divided into the OSA + MCI group (n = 91), OSA-MCI group (n = 89), MCI group (MCI without OSA) (n = 38) and control group (normal cognitive state without OSA) (n = 50). The mean CD63-normalized NDE levels of humanin, MOTS-c, and NRGN in the OSA + MCI group were higher than those in the OSA-MCI and control groups. The NDE levels of humanin, MOTS-c, and NRGN in the MCI group were lower than those in controls. The odds of cognitive impairment in patients with OSA were higher with higher NDE levels of humanin, MOTS-c, and NRGN (odds ratio (OR): 2.100, 95 % confidence interval (CI): 1.646-2.679, P < 0.001; OR: 5.453, 95 % CI: 3.112-9.556, P < 0.001; OR: 3.115, 95 % CI: 2.163-4.484, P < 0.001). The impaired cognitive performance was associated with higher NDE levels of humanin (ß: 0.505, SE: 0.048, P < 0.001), MOTS-c (ß: 0.580, SE: 0.001, P < 0.001), and NRGN (ß: 0.585, SE: 0.553, P < 0.001). The relationship between sleep parameters (mean SaO2 and T90) and MoCA scores was mediated by the NDE levels of humanin, MOTS-c, and NRGN with the proportion of mediation varying from 35.33 % to 149.07 %. Receiver operating characteristic curve revealed an area under the curve of 0.905 for humanin, 0.873 for MOTS-c, and 0.934 for NRGN to predict MCI in OSA patients without dementia. Increased humanin, MOTS-c, and NRGN levels significantly decreased after CPAP treatment. CONCLUSIONS: Mitochondrial dysfunction is implicated in cognitive impairment in OSA patients without dementia, and mainly mediates the association between intermittent hypoxia and cognitive impairment in adults with OSA without dementia. Mitochondrial dysfunction can be partially reversible by CPAP treatment. Mitochondrial proteins can be used as markers of cognitive impairment in patients with OSA.
Subject(s)
Cognitive Dysfunction , Polysomnography , Sleep Apnea, Obstructive , Humans , Male , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/physiopathology , Female , Cognitive Dysfunction/etiology , Middle Aged , Aged , Mitochondrial Proteins , Mitochondria/metabolism , Neuropsychological Tests/statistics & numerical data , Intracellular Signaling Peptides and ProteinsABSTRACT
BACKGROUND: Mature cystic teratomas or dermoid cysts of the pancreas complicate surgical approaches because of their anatomical position and ever-growing size. Herein, we report a case of a giant mature cystic teratoma of the pancreas that was successfully resected via complete laparoscopic distal pancreatectomy (LDP). CASE PRESENTATION: A 39-year-old female patient was referred to our hospital for the evaluation of a pancreatic tumor. Three years of follow-up revealed that the tumor had increased in size to 18 cm, with hyperintense solid components on diffusion-weighted magnetic resonance imaging. Considering the possibility of malignancy, we decided to perform an LDP. The capsule appeared solid enough to withstand the retraction of the endoscopic forceps. Tumor size made it difficult to dissect the dorsal side of the tumor from the caudal to the cranial side. Early transection of the pancreas and additional ports facilitated dissection of the dorsal side of the tumor. We completed the LDP without intraoperative cyst rupture. On pathological examination, the tumor was diagnosed as a mature cystic teratoma originating from the pancreatic tail. The patient was discharged on postoperative day 13 with no complications. CONCLUSION: LDP may be an option for surgical procedures in patients with large cystic lesions of the pancreatic body or tail. Intraoperative observation of the tumor and surgical refinement are necessary to complete the laparoscopic procedure without tumor rupture.
ABSTRACT
Arsenic (As) is a prevalent and hazardous environmental toxicant associated with cancer and various health problems, which has been shown suppressive effects on dendritic cells (DCs). Autophagy is essential for the innate and adaptive immune responses of DCs, and the transcription factors TFEB and TFE3 are key regulators of autophagic and lysosomal target genes. However, the detrimental alterations of the autophagy-lysosome pathway in As-exposed DCs and the possible coordinating roles of TFEB and TFE3 in the immune dysfunction of this cell are less understood. In this paper, we found that As exposure significantly impaired lysosomal number, lysosomal acidic environment, and lysosomal membrane permeabilization, which might lead to blocked autophagic flux in cultured DCs. Furthermore, our results confirmed that TFEB or TFE3 knockdown exacerbated the disorders of lysosome and the blockade of autophagic flux in As-exposed DCs, and also enhanced the inhibitory expression of co-stimulatory molecules Cd80 and Cd83; adhesion molecule Icam1; cytokines TNF-α, IL-1ß, and IL-6; chemokine receptor Ccr7; and antigen-presenting molecules MHC II and MHC I. By contrast, overexpression of TFEB or TFE3 partially alleviated the above-mentioned impairment of DCs by inorganic As exposure. In conclusion, these findings reveal a previously unappreciated inhibition of lysosome-mediated degradation and damage of lysosomal membrane integrity leading to dysregulated autophagy and impaired immune functions of DCs by arsenicals, and also suggest TFEB and TFE3 as potential therapeutic targets for ameliorating As toxicity.
Subject(s)
Arsenic , Arsenicals , Arsenic/toxicity , Autophagy , Lysosomes , Dendritic Cells , Basic Helix-Loop-Helix Leucine Zipper Transcription FactorsABSTRACT
PURPOSE: This study aimed to compare the regeneration status of articular cartilage, clinical, and radiologic outcomes between varus knee patients with and without preoperative tibial varus deformity (PTVD) after medial opening-wedge high tibial osteotomy (OWHTO) METHODS: Varus knee patients who had undergone OWHTO were divided into two groups according to preoperative medial proximal tibial angle (MPTA): a great varus (GV) group (MPTA <85°) and a mild varus (MV) group (85°≤preoperative MPTA <87°). The hip-knee-ankle (HKA) angle, weight-bearing line ratio (WBL%), MPTA, joint line convergence angle and joint line obliquity were measured. Second-look arthroscopy was undertaken 24 months after HTO. The Knee Society (KS) function score and knee score, and Lysholm score were used to evaluate the functional outcomes. All parameters were evaluated preoperatively and 24 months after HTO. RESULTS: The GV group had greater varus than the MV group in HKA and WBL% before surgery, but greater valgus after surgery. The arthroscopic probe before HTO revealed the advanced chondral damage in the GV group and lighter chondral damage in the MV group. The regeneration of medial femoral condyle was considerably more frequent in the GV group (72.5%, 45/62) than in the MV group (50.0%, 27/54) (P = 0.030). No significant differences were observed in all functional outcomes preoperatively and 24 months after HTO. CONCLUSION: The extent of cartilage regeneration in patients without PTVD was inferior to that in those with PTVD, but the functional outcomes were comparable. OWHTO may be a treatment option in a selected subset of varus knee patients without PTVD.
Subject(s)
Osteoarthritis, Knee , Humans , Osteoarthritis, Knee/diagnostic imaging , Osteoarthritis, Knee/surgery , Tibia/diagnostic imaging , Tibia/surgery , Knee Joint/diagnostic imaging , Knee Joint/surgery , Lower Extremity , Osteotomy/methods , Retrospective StudiesABSTRACT
BACKGROUND: Cognitive impairment is common in patients with obstructive sleep apnea (OSA). Previous studies indicated that intermittent hypoxia, sleep fragmentation, and depressive symptoms were associated with cognitive impairment in OSA patients. OBJECTIVE: The study aimed to investigate whether sleep characteristics and depressive symptoms affected cognitive abilities mediated by Alzheimer's disease (AD) biomarkers and complement proteins in OSA patients without dementia. METHODS: A total of 317 subjects without dementia who had undergone polysomnography, cognitive and neuropsychological evaluations, were recruited. Neuronal-derived exosomes (NDEs) levels for amyloid-ß (Aß), total tau (T-tau), and tau phosphorylated 62 at threonine 181 (P-T181-tau) and astrocyte-derived exosomes (ADEs) levels for complement proteins were measured. Mediation analysis were performed to explore the mediation effects of AD biomarkers (Aß42, T-tau, P-T181-tau) and complement proteins (C3b and C5b-9) on cognition. RESULTS: The findings revealed that the association between sleep fragmentation and cognition was mediated by Aß42 (the percentage varied from 18.25% to 30.6%), P-T181-tau (the percentage varied from 24.36% to 32.3%), and C5b-9 (the percentage varied from 30.88% to 60.7%). The influence of depressive symptoms on cognition was only mediated via C3b (the percentage varied from 24.1% to 36.6%). CONCLUSIONS: In OSA patients without dementia, Aß42 and P-T181-tau levels in NDEs, and C5b-9 levels in ADEs mediated the impact of sleep fragmentation on cognitive impairment, and C3b levels in ADEs mediated the impact of depressive symptoms on cognitive impairment.
Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Sleep Apnea, Obstructive , Humans , Alzheimer Disease/complications , Sleep Deprivation , Complement Membrane Attack Complex , Cognitive Dysfunction/complications , tau Proteins/metabolism , Amyloid beta-Peptides/metabolism , Sleep Apnea, Obstructive/complications , BiomarkersABSTRACT
The change in axial tibial rotation after uniplane medial open-wedge high tibial osteotomy (uniplane OWHTO) and its relevant influence factor is not known. Therefore, the aim of this study was to evaluate the change in axial tibial rotation after uniplane OWHTO, and the factors affecting tibia rotational change were analyzed. Between January 2022 and April 2022, the study was retrospectively conducted on genu varum patients who underwent uniplane OWHTO. In the weight-bearing anteroposterior long leg view, the hip-knee-ankle angle and medial proximal tibial angle (MPTA) were evaluated. The posterior tibial slope were measured from the lateral view. A CT scan of the knee joint was performed to evaluate the distal tibial rotation angle (TRA), femorotibial rotation angle and tibial tuberosity-trochlear groove distance. In addition, the foot morphology was assessed by the ankle deformity angle and ankle rotation angle using an angle measuring instrument. All parameters were measured preoperatively and 14 days after surgery. The mean change in hip-knee-ankle, MPTA was 10.5°±2.9°, 8.8°±2.6°. The mean preoperative and postoperative TRA were 25.1°±6.9° and 22.2°±6.2° respectively (P = .007). Thus, the mean ∆TRA was -3.0°±3.4° (IR) with a range of -9.6° to +2.8° after surgery. No significant differences were found in the femorotibial rotation angle and tibial tuberosity-trochlear groove distance before and after surgery (P > .05). The postoperative ankle rotation angle and ankle deformity angle changed significantly compared with preoperative values (P < .001). In the multiple regression analysis, ∆MPTA was the only predictor of distal tibial rotation (ß = 0.667, P = .003). The current study confirms an unintended internal rotation in the distal tibia following uniplane MOWHTO and the rotation in the distal tibia was influenced by the opening width. Surgeron should keep in mind to avoid the osteotomy complication leading to excessive rotation change during surgery.
Subject(s)
Genu Varum , Osteoarthritis, Knee , Humans , Genu Varum/diagnostic imaging , Genu Varum/surgery , Retrospective Studies , Knee Joint/diagnostic imaging , Knee Joint/surgery , Osteotomy , Tibia/diagnostic imaging , Tibia/surgery , Osteoarthritis, Knee/diagnostic imaging , Osteoarthritis, Knee/surgeryABSTRACT
PURPOSE: The changes in the lower limb alignment were vitally important after high tibial osteotomy (HTO). Therefore, the purpose of present study was to analyze the characteristics of plantar pressure distribution after HTO, and to investigate the effect of plantar pressure distribution on postoperative limb alignment. METHODS: Between May 2020 and April 2021, varus knee patients undergoing HTO were evaluated in the present study. The peak pressure of plantar regions, medial-lateral pressure ratio (MLPR), foot progression angle (FTA), anteroposterior COP (AP-COP), lateral symmetry of COP (LS-COP), and the radiographic parameters were evaluated preoperatively and at the final follow-up. Compared among the slight valgus (SV), moderate valgus (MV) and large valgus (LV) groups at the final follow-up, the peak pressure of HM, HC and M5 regions, and the MLPR were compared; the Knee Injury and Osteoarthritis Outcome Score4 (KOOS4) including four subscales, and the American of orthopedic foot and ankle society (AOFAS) were evaluated. RESULTS: The WBL%, HKA and TPI angle changed significantly after HTO (P < 0.001). The preoperative group exhibited a lower peak pressure in the HM region (P < 0.05) and higher peak pressure in the M5 region (P < 0.05); the pre- and postoperative groups exhibited a lower peak pressure in the HC region (P < 0.05); the rearfoot MLPR was significantly lower and LS-COP was significantly higher in the preoperative group (P = 0.017 in MLPR and 0.031 in LS-COP, respectively). Comparison among the SV, MV and LV groups, the SV group indicated a lower peak pressure in the HM region (P = 0.036), and a lower MLPR in the rearfoot (P = 0.033). The KOOS Sport/Re score in the MV and LV groups increased significantly compared with the SV group (P = 0.042). CONCLUSION: Plantar pressure distribution during the stance phase in patients with varus knee OA following HTO exhibited a more medialized rearfoot plantar pressure distribution pattern than that before surgery. Compared with the small valgus alignment, a moderate to large valgus alignment allows patients to walk with a more even medial and lateral plantar pressure distribution, which is more similar to healthy adults.
Subject(s)
Orthopedics , Osteoarthritis, Knee , Adult , Humans , Osteoarthritis, Knee/diagnostic imaging , Osteoarthritis, Knee/surgery , Lower Extremity , Osteotomy/adverse effects , Foot/diagnostic imagingABSTRACT
BACKGROUND: The complement system plays a crucial role in cognitive impairment. The aim of this study is to investigate the correlation between the complement proteins levels in serum astrocyte-derived exosomes (ADEs) and mild cognitive impairment (MCI) in type 1 diabetes mellitus (T1DM) patients. METHODS: In this cross-sectional study, the patients with immune-mediated T1DM were enrolled. Healthy subjects matched for age and sex with T1DM patients were selected as controls. The cognitive function was evaluated by a Beijing version of the Montreal Cognitive Assessment (MoCA) questionnaire. The complement proteins including C5b-9, C3b and Factor B in serum ADEs were measured by ELISA kits. RESULTS: This study recruited 55 subjects immune-mediated T1DM patients without dementia, including 31 T1DM patients with MCI, 24 T1DM patients without MCI. 33 healthy subjects were enrolled as controls. The results showed higher complement proteins including C5b-9, C3b and Factor B levels in ADEs from T1DM patients with MCI than those in the controls (P < 0.001, P < 0.001, P = 0.006) and T1DM patients without MCI (P = 0.02, P = 0.02, P = 0.03). The C5b-9 levels in ADEs were independently associated with MCI in T1DM patients(OR: 1.20, 95% CI: 1.00-1.44, P = 0.04). The C5b-9 levels in ADEs were significantly correlated with global cognitive scores (ß = -0.360, Pï¼0.001) and visuo-executive (ß = -0.132, Pï¼0.001), language(ß = -0.036, P = 0.026) and delayed recall score (ß = -0.090,P = 0.007). There was no correlation between the C5b-9 levels in ADEs and the fasting glucose, HbA1c, fasting c-peptide and GAD65 antibody in T1DM patients. Furthermore, the C5b-9, C3b and Factor B levels in ADEs exhibited a fair combined diagnostic value for MCI, with an area under the curve of 0.76 (95% CI: 0.63-0.88, P = 0.001). CONCLUSION: The elevated C5b-9 levels in ADEswere significantly associated with theMCI in T1DM patients. The C5b-9 in ADEs may be used as a marker of MCI in T1DM patients.
Subject(s)
Cognitive Dysfunction , Diabetes Mellitus, Type 1 , Exosomes , Humans , Diabetes Mellitus, Type 1/complications , Complement Membrane Attack Complex/metabolism , Complement Factor B/metabolism , Astrocytes/metabolism , Exosomes/metabolism , Cross-Sectional Studies , Cognitive Dysfunction/diagnosisABSTRACT
OBJECTIVES: To research the relationship between quantitative electroencephalogram (qEEG) and impaired cognitive function patients who have obstructive sleep apnea (OSA) but no dementia. METHODS: Subjects who complained of snoring between March 2020 and April 2021 in the Sleep Medicine Center of Weihai Municipal Hospital were included. All subjects underwent overnight in-laboratory polysomnography (PSG) and were assessed using a neuropsychological scale. Standard fast fourier transform (FFT) was used to obtain the electroencephalogram (EEG) power spectral density curve, and to calculate the delta, theta, alpha, and beta relative power and the ratio between slow and fast frequencies. Binary logistic regression was used to assess the risk factors for cognitive impairment in patients who had OSA but no dementia. Correlation analysis was performed to determine the relationship between qEEG and cognitive impairment. RESULTS: A total of 175 participants without dementia who met the inclusion criteria were included in this study. There were 137 patients with OSA, including 76 with mild cognitive impairment (OSA + MCI), 61 without mild cognitive impairment (OSA-MCI), and 38 participants without OSA (non-OSA). The relative theta power in the frontal lobe in stage 2 of non-rapid eye movement sleep (NREM 2) in OSA + MCI was higher than that in OSA-MCI (P = 0.038) and non-OSA (P = 0.018). Pearson correlation analysis showed that the relative theta power in the frontal lobe in NREM 2 was negatively correlated with Mini-Mental State Examination (MMSE) scores, Montreal Cognitive Assessment (MoCA) Beijing version scores, and MoCA subdomains scores (visual executive function, naming, attention, language, abstraction, delayed recall and orientation) outside language. CONCLUSIONS: In patients who had OSA but no dementia, the EEG slower frequency power increased. The relative theta power in the frontal lobe in NREM 2 was associated with MCI of patients with OSA. These results suggest that the slowing of theta activity may be one of the neurophysiological changes in the early stage of cognitive impairment in patients with OSA.
Subject(s)
Cognitive Dysfunction , Sleep Apnea, Obstructive , Humans , Sleep/physiology , Cognitive Dysfunction/diagnosis , Polysomnography , Electroencephalography/methodsABSTRACT
Increasing evidence supports a link between obstructive sleep apnea (OSA) and cognition, and the mechanism is complex and still not well understood. We analyzed the relationship between the glutamate transporters and cognitive impairment in OSA. For this study 317 subjects without dementia, including 64 healthy controls (HCs), 140 OSA patients with mild cognitive impairment (MCI) and 113 OSA patients without cognitive impairment were assessed. All participants who completed polysomnography, cognition and white matter hyperintensity (WMH) volume were used. Plasma neuron-derived exosomes (NDEs) excitatory amino acid transporter 2 (EAAT2) and vesicular glutamate transporter 1 (VGLUT1) proteins were measured by ELISA kits. After 1 year of continuous positive airway pressure (CPAP) treatment, we analyzed plasma NDEs EAAT2 level and cognition changes. Plasma NDEs EAAT2 level was significantly higher in OSA patients than in HCs. Higher plasma NDEs EAAT2 level were significantly associated with cognitive impairment than normal cognition in OSA patients. Plasma NDEs EAAT2 level was inversely associated with the total Montreal Cognitive Assessment (MoCA) scores, visuo-executive function, naming, attention, language, abstraction, delayed recall and orientation. One year after CPAP treatment, plasma NDEs EAAT2 level (P = 0.019) was significantly lower, while MoCA scores (P = 0.013) were significantly increased compared with baseline. Upregulation of neuronal glutamate transporters at baseline may reflect a self-compensatory mechanism to prevent further neuronal damage, while plasma NDEs EAAT2 level was decreased after one year of CPAP therapy, which may be due to the loss of astrocytes and neurons.
Subject(s)
Cognitive Dysfunction , Dementia , Sleep Apnea, Obstructive , Humans , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/therapy , Cognition/physiology , Neurons , Glutamates , Dementia/complicationsABSTRACT
The innate immune responses are tightly regulated to ensure effective clearance of invading pathogens and avoid excessive inflammation. Ubiquitination and deubiquitination are important post-translational modifications in antiviral immune responses. Here, we discovered deubiquitinase USP47 as a novel negative immune system regulator. Overexpression of USP47 repressed Sendai virus, poly(I:C) and poly(dA:dT)-induced ISRE and IFN-ß activation, along with reduced IFNB1 transcription and enhanced viral replication. Knockdown of USP47 expression had the opposite effects. Dual-luciferase and phosphorylation assays showed that USP47 targeted downstream of MAVS and upstream of TBK1. Additional co-immunoprecipitation assays suggested that USP47 interacted with TRAF3 and TRAF6. Importantly, USP47 removed K63-linked polyubiquitin chains from TRAF3 and TRAF6. Hence, we describe a novel modulator of the antiviral innate immune response, USP47, which removes K63-linked polyubiquitins from TRAF3 and TRAF6, leading to reduced type I IFN signaling.
Subject(s)
Interferon Type I , Viruses , TNF Receptor-Associated Factor 3/genetics , TNF Receptor-Associated Factor 3/metabolism , TNF Receptor-Associated Factor 6/metabolism , Immunity, Innate , Interferon Type I/metabolism , Antiviral Agents , Ubiquitination , Deubiquitinating Enzymes/metabolismABSTRACT
The complement system plays a crucial role in cognitive impairment in obstructive sleep apnea (OSA). The present study aimed to investigate the connections between complement component 8 gamma (C8G) levels in astrocyte-derived exosomes (ADEs) and cognitive impairment in OSA patients without dementia. This cross-sectional cohort study recruited 274 participants without dementia, including 124 OSA patients with mild cognitive impairment (MCI), 100 OSA patients without MCI, and 50 healthy control subjects. Enrolled participants underwent polysomnography (PSG) evaluation, neuropsychological scale assessment, magnetic resonance imaging scanning, and collection of peripheral blood samples for quantification of complement proteins in ADEs. The findings showed higher C8G concentrations in ADEs from OSA patients with MCI than in the controls and OSA without MCI group. Logistic regression analysis suggested that C8G levels in ADEs were independently associated with MCI in OSA patients. Multivariable linear regression analysis demonstrated that C8G levels in ADEs were significantly correlated with global cognitive scores and all cognitive subdomain scores after adjusting for demographic factors (age, sex, education), vascular risk factors (Body mass index, history of hypertension, diabetes, dyslipidemia), depressive symptoms measures, and apnea-hypopnea index (AHI) values. The levels of C8G were linearly positively related to the white matter hyperintensity (WMH) volumes in Pearson's correlation analysis. Our research confirmed that C8G levels are significantly associated with cognitive impairment in OSA patients, which paves the way for novel therapeutic targets for neurocognitive dysfunction progression in OSA patients in the future.
Subject(s)
Cognitive Dysfunction , Dementia , Exosomes , Sleep Apnea, Obstructive , Humans , Complement C8 , Cross-Sectional Studies , Astrocytes/pathology , Exosomes/pathology , Sleep Apnea, Obstructive/complications , Dementia/complicationsABSTRACT
STUDY OBJECTIVES: The relationship between autonomic nervous system dysfunction measured by heart rate variability (HRV) and cognitive impairment in obstructive sleep apnea (OSA) patients is complex and still not well understood. We aimed to analyze the role of complement activation, Alzheimer's disease (AD) biomarkers, and white matter hyperintensity (WMH) in modulating the association of HRV with cognitive performance. METHODS: There were 199 subjects without dementia, including 42 healthy controls, 80 OSA patients with mild cognitive impairment (MCI), and 77 OSA patients without cognitive impairment. All participants who completed polysomnography, cognition, WMH volume, and 5-min HRV analysis were recorded during wakefulness and sleep periods. Neuron-derived exosome and astrocyte-derived exosome proteins were measured by ELISA kits. RESULTS: The OSA with MCI group were associated with a lower mean of standard deviations of R-R intervals for 5-min intervals (SDANN index) during wakefulness, standard deviation of the R-R interval (SDNN) during sleep stage and percentage of adjacent R-R intervals differing by more than 50 ms (PNN50) in each stage compared with OSA without MCI. The influence of HRV on cognition was partially mediated by complement activation (C5b-9 mediated a maximum of 51.21%), AD biomarkers, and WMH. CONCLUSIONS: Lower SDANN index and PNN50 during wakefulness and SDNN and PNN50 during sleep periods were found in OSA patients with MCI, suggesting potential vulnerability to autonomic and parasympathetic dysfunction. Complement activation, AD biomarkers, and WMH might partially mediate and interact with the influence of HRV on cognitive impairment in OSA patients. CLINICAL TRIAL REGISTRATION: ChiCTR1900021544.
Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Sleep Apnea, Obstructive , Adult , Humans , Biomarkers , Cognitive Dysfunction/complications , Complement Activation , Heart Rate/physiology , Case-Control StudiesABSTRACT
Background: Rapid eye movement (REM) sleep behavior disorder (RBD) predicts cognitive decline in Parkinson's disease (PD) patients without dementia. However, underlying mechanisms remain unknown. Accumulating studies suggest glutamatergic system dysregulation is associated. Objective: To examine the effect of RBD on the rate of cognitive decline in PD patients and investigate whether plasma levels of the neuroexosomal vesicular glutamate transporter-1 (VGLUT-1) and excitatory amino acid transporter-2 (EAAT-2) are altered in PD patients with RBD. Methods: This study included 157 newly diagnosed cognitive normal PD patients and 70 healthy controls (HCs). Based on one-night polysomnography recordings, the PD subjects were divided into PD with and without RBD (PD-RBD and PD-nRBD) groups. All participants received a complete clinical and neuropsychological evaluation at baseline. Plasma levels of neuroexosomal VGLUT-1 and EAAT-2 were measured by ELISA kits. After a 3-year follow-up, we evaluated baseline plasma levels of neuroexosomal glutamate transporters in each group as a predictor of cognitive decline using MoCA score changes over 3 years in regression models. Results: Plasma levels of neuron-derived exosomal EAAT-2 and VGLUT-1 were significantly lower in PD patients than in HCs. Plasma levels of neuroexosomal EAAT-2 were significantly lower in PD-RBD than PD-nRBD group at baseline. At the 3-year follow-up, PD-RBD patients presented greater cognitive decline. Lower baseline blood neuroexosomal EAAT-2 predicted cognitive decline over 3 years in PD-RBD patients (ß = 0.064, P = 0.003). Conclusion: These findings indicate that blood neuroexosomal EAAT-2 is associated with cognitive decline in PD with RBD.
ABSTRACT
Liposomes are the most widely used nanocarrier platform for the delivery of therapeutic and diagnostic agents, and a number of liposomes have been approved for use in clinical practice. After systemic administration, most liposomes are cleared by macrophages in the mononuclear phagocyte system, such as the liver and bone marrow (BM). However, the majority of studies have focused on investigating the therapeutic results of liposomal drugs, and too few studies have evaluated the potential side effects of empty nanocarriers on the functions of macrophages in the mononuclear phagocyte system. Here, we evaluate the potential effects of empty liposomes on the functions of BM niche macrophages. Following liposome administration, we observed lipid droplet (LD) accumulation in cultured primary macrophages and BM niche macrophages. We found that these LD-accumulating macrophages, similar to foam cells, exhibited increased expression of inflammatory cytokines, such as IL-1ß and IL-6. We further provided evidence that liposome deposition and degradation induced LD biogenesis on the endoplasmic reticulum membrane and subsequently disturbed endoplasmic reticulum homeostasis and activated the inositol-requiring transmembrane kinase/endoribonuclease 1α/NF-κB signaling pathway, which is responsible for the inflammatory activation of macrophages after liposome engulfment. Finally, we also showed the side effects of dysfunctional BM niche macrophages on hematopoiesis in mice, such as the promotion of myeloid-biased output and impairment of erythropoiesis. This study not only draws attention to the safety of liposomal drugs in clinical practice but also provides new directions for the design of lipid-based drug carriers in preclinical studies.
Subject(s)
Bone Marrow , Liposomes , Mice , Animals , Liposomes/metabolism , NF-kappa B/metabolism , Interleukin-6/metabolism , Macrophages/metabolism , Hematopoiesis , Drug Carriers/metabolism , Drug Carriers/pharmacology , Cytokines/metabolism , Endoribonucleases , Inositol/metabolism , LipidsABSTRACT
In this study, we aimed to investigate the clinical efficacy and learning curve of posterior percutaneous endoscopic cervical laminoforaminotomy (PPECLF) in patients with cervical spondylotic radiculopathy (CSR). A total of 64 patients with CSR received PPECLF. Clinical outcome scores included the visual analog scale, Japanese Orthopedic Association score, neck disability index, and modified Macnab criteria. Radiological outcomes included the disc height, C2 to C7 Cobb angle, and range of motion. The learning curve was evaluated using cumulative sum analysis. Patients were divided into accumulation phase and mastery phase groups (A and B), and general data and surgical efficacy were compared between the 2 groups. Follow-up ranged from 12 to 24 months. Clinical outcome scores improved significantly at the final follow-up, and there were no differences in radiological outcomes. Surgical efficacy was excellent and good in 82.8% of patients. The operative time showed a decreasing trend with the accumulation of cases. Patients were divided and the 26th case was the cutoff point according to the learning curve. No significant differences were found in the clinical outcomes between the 2 groups. Decompression with PPECLF was safe and effective in the treatment of CSR. With the accumulation of cases, the operative time was gradually shortened, and the clinical efficacy was significant. The PPECLF procedure can be performed efficiently and safely to treat CSR.
Subject(s)
Radiculopathy , Spondylosis , Cervical Vertebrae/surgery , Humans , Learning Curve , Radiculopathy/surgery , Spondylosis/complications , Spondylosis/surgery , Treatment OutcomeABSTRACT
Objective: The present study was designed for the contrastive analysis of conservative and percutaneous kyphoplasty (PKP) on pain severity and recovery of injured vertebrae in elderly patients with acute symptomatic osteoporotic vertebral compression fracture (OVCF). Methods: A total of 60 elderly patients with acute symptomatic OVCF were divided into two groups according to different treatment protocols, with 30 patients in each group. Patients in the Con group received conservative treatment, while patients in the PKP group received percutaneous kyphoplasty treatment. Clinical evaluation included the visual analogue scale (VAS), the Dallas pain questionnaire, the vertebral body leading edge height, the Cobb angle of injured vertebrae, the MOS item short-form health survey (SF-36), the Barthel index, and the mini-mental state examination (MMSE). Results: At 3 days, 3 months, and 6 months post-treatment, the score of VAS and the Cobb angle of injured vertebrae in patients of the PKP group were all significantly lower than those in the Con group (P < 0.05), while the height of vertebral body leading edge in patients of the PKP group was significantly longer than that in the Con group (P < 0.05). At 6 months post-treatment, the scores of the four dimensions of the Dallas pain questionnaire scale in the PKP group were all significantly lower than those in the Con group (P < 0.05), while the score of SF-36 (PCS), SF-36 (MCS), and Barthel index in patients of the PKP group were all significantly lower than those in the Con group (P < 0.05), and there was no significant difference in the scores of MMSE between these two groups (P > 0.05). Conclusion: Compared with conservative treatment, PKP treatment of elderly patients with acute symptomatic OVCF provides rapid pain relief, restoration of damaged vertebral body height, correction of Cobb's angle, and improved quality of life.
ABSTRACT
Mandibular buccal bifurcation cyst is a rare inflammatory odontogenic cyst. We reported two cases who complained of painful swelling of extraoral soft tissue. Intraoral examination revealed the partially erupted mandibular first molar. Cone beam computed tomography showed a well-defined cystic lesion surrounding the first molar. Histopathologic images showed the cyst wall was infiltrated by a large number of plasma cells, neutrophils and eosinophils, and lined with a thin layer of non-keratinized stratified squamous epithelium. Finally, the two patients were diagnosed as mandibular buccal bifurcation cyst and treated with cyst enucleation and curettage.
Subject(s)
Mandibular Diseases , Odontogenic Cysts , Periodontal Cyst , Humans , Leukocyte Count , Mandibular Diseases/diagnostic imaging , Mandibular Diseases/pathology , Mandibular Diseases/surgery , Molar/pathology , Odontogenic Cysts/diagnostic imaging , Odontogenic Cysts/surgery , Periodontal Cyst/pathologyABSTRACT
The wet decortication of sesame seeds produces wastewater containing diverse minerals and organic pollutants that could be valuable resources for the food industry. This investigation aimed to reclaim, purify, and characterize the polysaccharides contained in the waste liquor from the sesame decortication industry. The purified polysaccharide fractions were characterized using monosaccharide analysis, GPC (high-performance gel permeation chromatography), FT-IR (Fourier-transform infrared) spectroscopy, methylation analysis, 1D and 2D Nucleai Magnetic Resonance (NMR) analysis, and thermal analysis. Four fractions were found (SSP-1,-2,-3, -4), of which SSP-2 was proportionately the largest and most interesting. The backbone of SSP-2 is mainly composed of (1â2,4)-ß-D-Xylp residues with side chains connected to the O-4 position, with many T-ß-D-Galp and (1â5)-α-L-Araf residues, and fewer (1â4)-α-D-Glcp, (1â2)-α-L-Rhap, T-α-L-Araf, and (1â2)-ß-D-GlcpA residues. An efficient method for removing the polysaccharides would simplify wastewater treatment while finding a use for them would benefit the sesame, food, and pharmaceutical industries.
ABSTRACT
Macrophages play pivotal roles in the maintenance of tissue homeostasis. However, the reactivation of macrophages toward proinflammatory states correlates with a plethora of inflammatory diseases, including atherosclerosis, obesity, neurodegeneration, and bone marrow (BM) failure syndromes. The lack of methods to reveal macrophage phenotype and function in vivo impedes the translational research of these diseases. Here, we found that proinflammatory macrophages accumulate intracellular lipid droplets (LDs) relative to resting or noninflammatory macrophages both in vitro and in vivo, indicating that LD accumulation serves as a structural biomarker for macrophage phenotyping. To realize the staining and imaging of macrophage LDs in vivo, we developed a fluorescent fatty acid analog-loaded poly(lactic-co-glycolic acid) nanoparticle to label macrophages in mice with high efficiency and specificity. Using these novel nanoparticles, we achieved in situ functional identification of single macrophages in BM, liver, lung, and adipose tissues under conditions of acute or chronic inflammation. Moreover, with this intravital imaging platform, we further realized in vivo phenotyping of individual macrophages in the calvarial BM of mice under systemic inflammation. In conclusion, we established an efficient in vivo LD labeling and imaging system for single macrophage phenotyping, which will aid in the development of diagnostics and therapeutic monitoring. Moreover, this method also provides new avenues for the study of lipid trafficking and dynamics in vivo.