Background: Parkinson’s disease (PD) is a neurodegenerative disorder displaying a typical neuroinflammation pathology that may result from an imbalance between regulatory T cells (Treg) and T helper 17 (Th17) cells. Human adipose tissue-derived mesenchymal stem cells (Ad-MSCs) exert immunomodulatory effects by inhibiting effector T cell responses and have been used to treat diverse immune disorders. We aimed to investigate the modulating effect of human Ad-MSCs on peripheral blood mononuclear cells (PBMCs) of patients with PD, focusing on differentiation into Th17 and Treg cells. Methods: We isolated human peripheral blood CD4⁺T cells and co-cultured them with Ad-MSCs at a ratio of 4:1 under either Th17 or Treg cell polarizing conditions for 4 days to detect the proportions of IL-17-producing CD4⁺T (Th17) and CD4⁺CD25⁺Foxp3⁺regulatory T (Treg) cells by flow cytometry. We also determined the mRNA expression levels of the retinoid-related orphan nuclear receptor (RORγt) transcription factor and those of interleukin-6 receptor (IL-6R), interleukin-23 receptor (IL-23R), leukemia inhibitory factor (LIF), and LIF receptor (LIFR) by quantitative reverse transcription PCR. We detected levels of cytokines in the supernatant (including LIF, IL-6, IL-23, IL-10, and TGF-β) using ELISA. Results: Our results showed that Ad-MSCs specifically inhibited the differentiation of PBMCs of patients with PD into IL-17-producing CD4⁺T cells by decreasing expressions of IL-6R, IL-23R, and RORγt (the key transcription factor for Th17 cells). Moreover, Ad-MSCs induced a functional CD4⁺CD25⁺Foxp3⁺T regulatory cell phenotype as evidenced by the secretion of IL-10. The levels of IL-6, IL-23, and TGF-β remained constant after co-culture under either the Th17 or the Treg cell polarizing condition. In addition, levels of LIF protein and its receptor mRNA were significantly increased under both polarizing conditions. Conclusion: The present in vitro study found that Ad-MSCs from healthy participants were able to correct the imbalance between Th17 and Treg found in PBMCs of PD patients, which were correlated with an increase in LIF secretion and a decrease in expression of IL-6R, IL-23R, and RORγt. These findings should be confirmed by in vivo experiments.

Background: Multiple observational studies have yielded controversial results regarding the association between Parkinson’s disease (PD) and periodontitis. Objective: This systematic review and meta-analysis was conducted to ascertain their bidirectional relationship. Methods: A literature search for relevant studies was performed in PubMed, EMBASE, the Cochrane Library, and Web of Science databases from inception to December 19, 2022. Effect sizes (ES) with 95% confidence intervals were pooled under the random-effects model. Then, leave-one-out sensitivity analysis and contour-enhanced funnel plot were applied to assess the stability of the results. Results: A total of 34 studies and 24 studies were included for systematic review and quantitative meta-analysis, respectively. Pooled ES indicated that periodontitis was not significantly associated with PD risk (HR = 1.13, 95% CI 0.88–1.45, n = 3; OR = 1.94, 95% CI 0.55–6.90, n = 7), while the Mendelian randomization study revealed no association between PD and periodontitis risk (coefficient [B] = –0.0001, standard error = 0.0001, p = 0.19). Furthermore, PD patients exhibited higher levels of periodontal pocket depth (SMD = 1.10, 95% CI 0.53–1.67), clinical attachment level (SMD = 1.40, 95% CI 0.55–2.26), plaque index (SMD = 0.81, 95% CI 0.22–1.39), and Oral Health Impact Profile-14 score (SMD = 0.91, 95% CI 0.33–1.49) compared to healthy controls. Conclusions: Our meta-analysis identified no bidirectional association between PD risk and periodontitis risk, though the prevalence of periodontitis and poorer oral status was higher in PD patients.

Purpose: This study aimed to explore the relation between lymphocyte to high-density lipoprotein ratio (LHR) and pulmonary function of chronic obstructive pulmonary disease (COPD) patients compared with neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR). Patients and Methods: In total, 154 participants (n = 77 with COPD and n = 77 without COPD) were recruited. LHR, NLR, PLR, lung function and other data were collected and compared. Pearson’s correlation test and the receiver operating characteristics curves were used to compare the utility of LHR, NLR and PLR. Besides, univariate and multivariate logistic regression analyses were conducted. Results: COPD patients with poorer lung function had a lower LHR level (P < 0.001). In low LHR group, more patients underwent greater airflow limitation than the other group (P = 0.006). LHR positively correlated with forced expiratory volume in 1 second in percent of the predicted value (FEV₁%) (r = 0.333, P = 0.003). At a cut-off value of 2.08, the sensitivity and specificity of LHR in predicting FEV₁% < 50 were 93.2% and 55.6%, respectively, with an AUC of 0.770 (P = 0.001) better than NLR and PLR. Based on logistic regression analyses, it was proved that LHR was associated with decreased risk of FEV₁ < 50% predicted in COPD patients (odds ratio = 0.198, 95% CI: 0.048– 0.811, P = 0.024). Conclusion: In contrast with NLR and PLR, LHR has higher accuracy for predicting pulmonary function in COPD; lower LHR level is independently associated with poorer pulmonary function.

Elevated neurofilament light chain (NfL) levels have been associated with dementia in idiopathic Parkinson’s disease (iPD). To examine the baseline and longitudinal changes in NfL levels in GBA-PD, SNCA-PD, and LRRK2-PD and further investigate the association between these genetic mutations, NfL, and dementia in PD. We analyzed data from the Parkinson’s Progression Markers Initiative (PPMI), including 184 healthy controls (HC) and 617 PD categorized as iPD (n = 381), LRRK2-PD (n = 142), GBA-PD (n = 76) and SNCA-PD (n = 18). Analysis of covariance (ANCOVA) or linear mixed-effect models were used to compare the baseline or dynamic NfL levels between groups. We then explored the relationship between genetic mutations, serum NfL levels, and conversion to dementia using mediation analysis. After adjusting for confounding factors, SNCA-PD exhibited higher baseline serum NfL levels than iPD. Regarding longitudinal changes, SNCA-PD showed the highest increase rate in estimated NfL levels (2.43 pg/mL per year), while LRRK2-PD experienced the slowest increase rate (0.52 pg/mL per year). Mediation analysis indicated that higher estimated NfL level changes were associated with faster cognitive decline (β = 0.591, p = 0.026). Specifically, the relationship between LRRK2 and dementia was mediated by the estimated NfL level change (β = −0.717, p < 0.05). Longitudinal changes in serum NfL levels may serve as a biomarker for cognitive decline in Parkinson’s disease. Moreover, compared to iPD, the slower progression of dementia in LRRK2-PD may be partially attributed to a slower increase in NfL levels.