The etiology and pathogenesis of Parkinson's disease (PD) are complicated and have not been fully elucidated, but an important association has been identified between inflammation and PD. In this study, we investigated the role of the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain-containing (NLRP) 3 inflammasome, consisting of NLRP3, caspase-1 and cytokines of the IL-1 family, in lipopolysaccharide (LPS)-induced and 6-hydroxydopamine (6-OHDA)-induced PD rats. Microinjection of different doses of caspase-1 inhibitor (Ac-YVAD-CMK, 300 or 1200 ng/rat) was performed for seven consecutive days. Then, rotational behavior, the number of dopamine (DA) neurons in the substantia nigra pars compacta (SNc), and the mRNA and protein expression levels of NLRP3 inflammasome components were measured 14 days after the microinjection setup was established. Results showed that high mRNA and protein expression levels of NLRP3 inflammasome components were observed in the injected side of the LPS- and 6-OHDA-induced PD rats; Ac-YVAD-CMK inhibited the mRNA and protein expression of NLRP3 inflammasome components in both LPS- and 6-OHDA-induced PD rats. Moreover, the number of rotations was significantly decreased, and the number of DA neurons in the SNc improved. Our data indicate that the NLRP3 inflammasome participates in the pathogenesis of PD and that inhibiting the downstream pathway of the NLRP3/caspase-1/IL-1β axis can alleviate the occurrence of PD symptoms, providing a new basis for the prevention and treatment of PD.
In order to investigate the sleep quality and influencing factors in patients with Parkinson's disease (PD), 201 PD patients were enrolled and underwent extensive clinical evaluations. Subjective sleep evaluation was assessed using the Pittsburgh Sleep Quality Index (PSQI), and the Epworth Sleepiness Scale (ESS). It was found that poor sleep quality (77.11%) and excessive daytime sleepiness (32.34%) were commonly seen in PD patients and positively correlated with disease severity. Then 70 out of the 201 PD patients and 70 age- and sex-matched controls underwent a polysomnographic recording. The parameters were compared between PD group and control group and the influencing factors of sleep in PD patients were analyzed. The results showed that sleep efficiency (SE) was significantly decreased (P<0.01), and sleep latency (SL) and the arousal index (AI) were increased (P<0.05) in the PD group as compared with those in the control group. SE and total sleep time (TST) were positively correlated with the Hoehn and Yahr (H&Y) stage. There was significant difference in the extent of hypopnea and hypoxemia between the PD group and the control group (P<0.05). Our results indicate that PD patients have an overall poor sleep quality and a high prevalence of sleep disorder, which may be correlated with the disease severity. Respiratory function and oxygen supply are also affected to a certain degree in PD patients.
Objectives: The present study aimed to compare the clinicopathological features of patients with seronegative immune-mediated necrotizing myopathy (IMNM) and those positive for anti-signal recognition particle (SRP) or anti-3-hydroxy-3-methylglutarylcoenzyme-a reductase (HMGCR) antibodies.Methods: We retrospectively analyzed the data of patients with IMNM treated in the Neurology Department of Tongji Hospital from January 1, 2013, to December 31, 2019.Results: Among the 117 patients with IMNM, 30.8% (36/117) were positive for anti-SRP antibodies, 6.0% (7/117) were positive for anti-HMGCR antibodies, and 13.7% (16/117) were seronegative. Myalgia at presentation (62.5 vs. 23.3%, p = 0.0114) was more commonly observed in patients with seronegative IMNM than in those with seropositive IMNM. Subclinical cardiac involvement was more frequently detected in seronegative IMNM than in seropositive IMNM (6/13 vs. 5/33, p = 0.0509, echocardiogram; 7/7 vs. 12/24, p = 0.0261, cardiac MRI). Deposition of membrane attack complex (MAC) on the sarcolemma of myofibers in biopsied muscle was less commonly observed in patients with seronegative IMNM than in patients with seropositive IMNM (16.7 vs. 68.2%, p = 0.0104). The rate of marked improvement following immunotherapy tended to be higher in patients with seronegative IMNM than in those with seropositive IMNM (87.5 vs. 61%, p = 0.0641).Conclusions: Patients with seronegative IMNM more frequently present with myalgia at onset, exhibit more subclinical cardiac involvement and uncommon MAC deposition on myofibers, and experience better outcomes than those with seropositive IMNM.
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