Generalized sleep decoding with basal ganglia signals in multiple movement disorders.

Sleep disturbances profoundly affect the quality of life in individuals with neurological disorders. Closed-loop deep brain stimulation (DBS) holds promise for alleviating sleep symptoms, however, this technique necessitates automated sleep stage decoding from intracranial signals. We leveraged overnight data from 121 patients with movement disorders (Parkinson's disease, Essential Tremor, Dystonia, Essential Tremor, Huntington's disease, and Tourette's syndrome) in whom synchronized polysomnograms and basal ganglia local field potentials were recorded, to develop a generalized, multi-class, sleep specific decoder - BGOOSE. This generalized model achieved 85% average accuracy across patients and across disease conditions, even in the presence of recordings from different basal ganglia targets. Furthermore, we also investigated the role of electrocorticography on decoding performances and proposed an optimal decoding map, which was shown to facilitate channel selection for optimal model performances. BGOOSE emerges as a powerful tool for generalized sleep decoding, offering exciting potentials for the precision stimulation delivery of DBS and better management of sleep disturbances in movement disorders.

Macrophage heterogeneity in bone metastasis.

Previous studies illustrated that macrophage, a type of innate immune cell, plays critical roles in tumour progression and metastasis. Bone is the most frequent site of metastasis for several cancer types including breast, prostate, and lung. In bone metastasis, osteoclast, a macrophage subset specialized in bone resorption, was heavily investigated in the past. Recent studies illustrated that other macrophage subsets, e.g. monocyte-derived macrophages, and bone resident macrophages, promoted bone metastasis independent of osteoclast function. These novel mechanisms further improved our understanding of macrophage heterogeneity in the context of bone metastasis and illustrated new opportunities for future studies.

Contribution of basal ganglia activity to REM sleep disorder in Parkinson's disease.

BACKGROUND: Rapid eye movement (REM) sleep behaviour disorder (RBD) is one of the most common sleep problems and represents a key prodromal marker in Parkinson's disease (PD). It remains unclear whether and how basal ganglia nuclei, structures that are directly involved in the pathology of PD, are implicated in the occurrence of RBD. METHOD: Here, in parallel with whole-night video polysomnography, we recorded local field potentials from two major basal ganglia structures, the globus pallidus internus and subthalamic nucleus, in two cohorts of patients with PD who had varied severity of RBD. Basal ganglia oscillatory patterns during RBD and REM sleep without atonia were analysed and compared with another age-matched cohort of patients with dystonia that served as controls. RESULTS: We found that beta power in both basal ganglia nuclei was specifically elevated during REM sleep without atonia in patients with PD, but not in dystonia. Basal ganglia beta power during REM sleep positively correlated with the extent of atonia loss, with beta elevation preceding the activation of chin electromyogram activities by ~200 ms. The connectivity between basal ganglia beta power and chin muscular activities during REM sleep was significantly correlated with the clinical severity of RBD in PD. CONCLUSIONS: These findings support that basal ganglia activities are associated with if not directly contribute to the occurrence of RBD in PD. Our study expands the understanding of the role basal ganglia played in RBD and may foster improved therapies for RBD by interrupting the basal ganglia-muscular communication during REM sleep in PD.

Neuromodulation for the treatment of Prader-Willi syndrome - A systematic review.

Prader-Willi syndrome (PWS) is a complex, genetic disorder characterized by multisystem involvement, including hyperphagia, maladaptive behaviors and endocrinological derangements. Recent developments in advanced neuroimaging have led to a growing understanding of PWS as a neural circuit disorder, as well as subsequent interests in the application of neuromodulatory therapies. Various non-invasive and invasive device-based neuromodulation methods, including vagus nerve stimulation (VNS), transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and deep brain stimulation (DBS) have all been reported to be potentially promising treatments for addressing the major symptoms of PWS. In this systematic literature review, we summarize the recent literature that investigated these therapies, discuss the underlying circuits which may underpin symptom manifestations, and cover future directions of the field. Through our comprehensive search, there were a total of 47 patients who had undergone device-based neuromodulation therapy for PWS. Two articles described VNS, 4 tDCS, 1 rTMS and 2 DBS, targeting different symptoms of PWS, including aberrant behavior, hyperphagia and weight. Multi-center and multi-country efforts will be required to advance the field given the low prevalence of PWS. Finally, given the potentially vulnerable population, neuroethical considerations and dialogue should guide the field.

Subthalamic nucleus deep brain stimulation alleviates oxidative stress via mitophagy in Parkinson's disease.

Subthalamic nucleus deep brain stimulation (STN-DBS) has the potential to delay Parkinson's disease (PD) progression. Whether oxidative stress participates in the neuroprotective effects of DBS and related signaling pathways remains unknown. To address this, we applied STN-DBS to mice and monkey models of PD and collected brain tissue to evaluate mitophagy, oxidative stress, and related pathway. To confirm findings in animal experiments, a cohort of PD patients was recruited and oxidative stress was evaluated in cerebrospinal fluid. When PD mice received STN stimulation, the mTOR pathway was suppressed, accompanied by elevated LC3 II expression, increased mitophagosomes, and a decrease in p62 expression. The increase in mitophagy and balance of mitochondrial fission/fusion dynamics in the substantia nigra caused a marked enhancement of the antioxidant enzymes superoxide dismutase and glutathione levels. Subsequently, fewer mitochondrial apoptogenic factors were released to the cytoplasm, which resulted in a suppression of caspase activation and reservation of dopaminergic neurons. While interfaced with an mTOR activator, oxidative stress was no longer regulated by STN-DBS, with no neuroprotective effect. Similar results to those found in the rodent experiments were obtained in monkeys treated with chronic STN stimulation. Moreover, antioxidant enzymes in PD patients were increased after the operation, however, there was no relation between changes in antioxidant enzymes and motor impairment. Collectively, our study found that STN-DBS was able to increase mitophagy via an mTOR-dependent pathway, and oxidative stress was suppressed due to removal of damaged mitochondria, which was attributed to the dopaminergic neuroprotection of STN-DBS in PD.

Efficacy and safety of combined deep brain stimulation with capsulotomy for comorbid motor and psychiatric symptoms in Tourette's syndrome: Experience and evidence.

OBJECTIVES: To evaluate the efficacy and safety of combined deep brain stimulation (DBS) with capsulotomy for comorbid motor and psychiatric symptoms in patients with Tourette's syndrome (TS). METHODS: This retrospective cohort study consecutively enrolled TS patients with comorbid motor and psychiatric symptoms who were treated with combined DBS and anterior capsulotomy at our center. Longitudinal motor, psychiatric, and cognitive outcomes and quality of life were assessed. In addition, a systematic review and meta-analysis were performed to summarize the current experience with the available evidence. RESULTS: In total, 5 eligible patients in our cohort and 26 summarized patients in 6 cohorts were included. After a mean 18-month follow-up, our cohort reported that motor symptoms significantly improved by 62.4 % (P = 0.005); psychiatric symptoms of obsessive-compulsive disorder (OCD) and anxiety significantly improved by 87.7 % (P < 0.001) and 78.4 % (P = 0.009); quality of life significantly improved by 61.9 % (P = 0.011); and no significant difference was found in cognitive function (all P > 0.05). Combined surgery resulted in greater improvements in psychiatric outcomes and quality of life than DBS alone. The synthesized findings suggested significant improvements in tics (MD: 57.92, 95 % CI: 41.28-74.56, P < 0.001), OCD (MD: 21.91, 95 % CI: 18.67-25.15, P < 0.001), depression (MD: 18.32, 95 % CI: 13.26-23.38, P < 0.001), anxiety (MD: 13.83, 95 % CI: 11.90-15.76, P < 0.001), and quality of life (MD: 48.22, 95 % CI: 43.68-52.77, P < 0.001). Individual analysis revealed that the pooled treatment effects on motor symptoms, psychiatric symptoms, and quality of life were 78.6 %, 84.5-87.9 %, and 83.0 %, respectively. The overall pooled rate of adverse events was 50.0 %, and all of these adverse events were resolved or alleviated with favorable outcomes. CONCLUSIONS: Combined DBS with capsulotomy is effective for relieving motor and psychiatric symptoms in TS patients, and its safety is acceptable. However, the optimal candidate should be considered, and additional experience is still necessary.

Pathological pallidal beta activity in Parkinson's disease is sustained during sleep and associated with sleep disturbance.

Parkinson's disease (PD) is associated with excessive beta activity in the basal ganglia. Brain sensing implants aim to leverage this biomarker for demand-dependent adaptive stimulation. Sleep disturbance is among the most common non-motor symptoms in PD, but its relationship with beta activity is unknown. To investigate the clinical potential of beta activity as a biomarker for sleep quality in PD, we recorded pallidal local field potentials during polysomnography in PD patients off dopaminergic medication and compared the results to dystonia patients. PD patients exhibited sustained and elevated beta activity across wakefulness, rapid eye movement (REM), and non-REM sleep, which was correlated with sleep disturbance. Simulation of adaptive stimulation revealed that sleep-related beta activity changes remain unaccounted for by current algorithms, with potential negative outcomes in sleep quality and overall quality of life for patients.

Pallidal activities during sleep and sleep decoding in dystonia, Huntington's, and Parkinson's disease.

BACKGROUND: Sleep disturbances are highly prevalent in movement disorders, potentially due to the malfunctioning of basal ganglia structures. Pallidal deep brain stimulation (DBS) has been widely used for multiple movement disorders and been reported to improve sleep. We aimed to investigate the oscillatory pattern of pallidum during sleep and explore whether pallidal activities can be utilized to differentiate sleep stages, which could pave the way for sleep-aware adaptive DBS. METHODS: We directly recorded over 500 h of pallidal local field potentials during sleep from 39 subjects with movement disorders (20 dystonia, 8 Huntington's disease, and 11 Parkinson's disease). Pallidal spectrum and cortical-pallidal coherence were computed and compared across sleep stages. Machine learning approaches were utilized to build sleep decoders for different diseases to classify sleep stages through pallidal oscillatory features. Decoding accuracy was further associated with the spatial localization of the pallidum. RESULTS: Pallidal power spectra and cortical-pallidal coherence were significantly modulated by sleep-stage transitions in three movement disorders. Differences in sleep-related activities between diseases were identified in non-rapid eye movement (NREM) and REM sleep. Machine learning models using pallidal oscillatory features can decode sleep-wake states with over 90% accuracy. Decoding accuracies were higher in recording sites within the internus-pallidum than the external-pallidum, and can be precited using structural (P < 0.0001) and functional (P < 0.0001) whole-brain neuroimaging connectomics. CONCLUSION: Our findings revealed strong sleep-stage dependent distinctions in pallidal oscillations in multiple movement disorders. Pallidal oscillatory features were sufficient for sleep stage decoding. These data may facilitate the development of adaptive DBS systems targeting sleep problems that have broad translational prospects.

Sleep outcomes and related factors in Parkinson's disease after subthalamic deep brain electrode implantation: a retrospective cohort study.

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) improves sleep qualities in Parkinson's disease (PD) patients; however, it remains elusive whether STN-DBS improves sleep by directly influencing the sleep circuit or alleviates other cardinal symptoms such as motor functions, other confounding factors including stimulation intensity may also involve. Studying the effect of microlesion effect (MLE) on sleep after STN-DBS electrode implantation may address this issue. Objective: To examine the influence of MLE on sleep quality and related factors in PD, as well as the effects of regional and lateral specific correlations with sleep outcomes after STN-DBS electrode implantation. Study Design: Case-control study; Level of evidence, 3. Data Sources and Methods: In 78 PD patients who underwent bilateral STN-DBS surgery in our center, we compared the sleep qualities, motor performances, anti-Parkinsonian drug dosage, and emotional conditions at preoperative baseline and postoperative 1-month follow-up. We determined the related factors of sleep outcomes and visualized the electrodes position, simulated the MLE-engendered volume of tissue lesioned (VTL), and investigated sleep-related sweet/sour spots and laterality in STN. Results: MLE improves sleep quality with Pittsburgh Sleep Quality Index (PSQI) by 13.36% and Parkinson's Disease Sleep Scale-2 (PDSS-2) by 17.95%. Motor (P = 0.014) and emotional (P = 0.001) improvements were both positively correlated with sleep improvements. However, MLE in STN associative subregions, as an independent factor, may cause sleep deterioration (r = 0.348, P = 0.002), and only the left STN showed significance (r = 0.327, P = 0.004). Sweet spot analysis also indicated part of the left STN associative subregion is the sour spot indicative of sleep deterioration. Conclusion: The MLE of STN-DBS can overall improve sleep quality in PD patients, with a positive correlation between motor and emotional improvements. However, independent of all other factors, the MLE in the STN associative subregion, particularly the left side, may cause sleep deterioration.

Association between Cognitive Impairment and Freezing of Gait in Patients with Parkinson's Disease.

Background: Freezing of gait (FOG) is a common disabling symptom in Parkinson's disease (PD). Cognitive impairment may contribute to FOG. Nevertheless, their correlations remain controversial. We aimed to investigate cognitive differences between PD patients with and without FOG (nFOG), explore correlations between FOG severity and cognitive performance and assess cognitive heterogeneity within the FOG patients. Methods: Seventy-four PD patients (41 FOG, 33 nFOG) and 32 healthy controls (HCs) were included. Comprehensive neuropsychological assessments testing cognitive domains of global cognition, executive function/attention, working memory, and visuospatial function were performed. Cognitive performance was compared between groups using independent t-test and ANCOVA adjusting for age, sex, education, disease duration and motor symptoms. The k-means cluster analysis was used to explore cognitive heterogeneity within the FOG group. Correlation between FOG severity and cognition were analyzed using partial correlations. Results: FOG patients showed significantly poorer performance in global cognition (MoCA, p < 0.001), frontal lobe function (FAB, p = 0.015), attention and working memory (SDMT, p < 0.001) and executive function (SIE, p = 0.038) than nFOG patients. The FOG group was divided into two clusters using the cluster analysis, of which cluster 1 exhibited worse cognition, and with older age, lower improvement rate, higher FOGQ3 score, and higher proportion of levodopa-unresponsive FOG than cluster 2. Further, in the FOG group, cognition was significantly correlated with FOG severity in MoCA (r = -0.382, p = 0.021), Stroop-C (r = 0.362, p = 0.030) and SIE (r = 0.369, p = 0.027). Conclusions: This study demonstrated that the cognitive impairments of FOG were mainly reflected by global cognition, frontal lobe function, executive function, attention and working memory. There may be heterogeneity in the cognitive impairment of FOG patients. Additionally, executive function was significantly correlated with FOG severity.

Macrophages promote anti-androgen resistance in prostate cancer bone disease.

Metastatic castration-resistant prostate cancer (PC) is the final stage of PC that acquires resistance to androgen deprivation therapies (ADT). Despite progresses in understanding of disease mechanisms, the specific contribution of the metastatic microenvironment to ADT resistance remains largely unknown. The current study identified that the macrophage is the major microenvironmental component of bone-metastatic PC in patients. Using a novel in vivo model, we demonstrated that macrophages were critical for enzalutamide resistance through induction of a wound-healing-like response of ECM-receptor gene expression. Mechanistically, macrophages drove resistance through cytokine activin A that induced fibronectin (FN1)-integrin alpha 5 (ITGA5)-tyrosine kinase Src (SRC) signaling cascade in PC cells. This novel mechanism was strongly supported by bioinformatics analysis of patient transcriptomics datasets. Furthermore, macrophage depletion or SRC inhibition using a novel specific inhibitor significantly inhibited resistant growth. Together, our findings elucidated a novel mechanism of macrophage-induced anti-androgen resistance of metastatic PC and a promising therapeutic approach to treat this deadly disease.

Adaptive deep brain stimulation for Parkinson's disease: looking back at the past decade on motor outcomes.

BACKGROUND: Adaptive deep brain stimulation (aDBS) has been reported to be an effective treatment for motor symptoms in patients with Parkinson's disease (PD). However, it remains unclear whether and in which motor domain aDBS provides greater/less benefits than conventional DBS (cDBS). OBJECTIVE: To conduct a meta-analysis and systematic review to explore the improvement of the motor symptoms of PD patients undergoing aDBS and the comparison between aDBS and cDBS. METHODS: Nineteen studies from PubMed, Embase, and the Cochrane Library database were eligible for the main analysis. Twelve studies used quantitative plus qualitative analysis; seven studies were only qualitatively analyzed. The efficacy of aDBS was evaluated and compared to cDBS through overall motor function improvements, changes in symptoms of rigidity-bradykinesia, dyskinesia, tremor, and speech function, and total electrical energy delivered (TEED). The overall motor improvement and TEED were investigated through meta-analyses, while other variables were investigated by systematic review. RESULTS: Quantitative analysis showed that aDBS, with a reduction of TEED (55% of that of cDBS), significantly improved motor functions (33.9%, p < 0.01) and may be superior to cDBS in overall motor improvement (p = 0.002). However, significant publication bias was detected regarding the superiority (p = 0.006, Egger's test). In the qualitative analysis, rigidity-bradykinesia, dyskinesia, and speech function outcomes after aDBS and cDBS were comparable. Beta-based aDBS may not be as efficient as cDBS for tremor control. CONCLUSIONS: aDBS can effectively relieve the clinical symptoms of advanced PD as did cDBS, at least in acute trials, delivering less stimulation than cDBS. Specific symptoms including tremor and axial disability remain to be compared between aDBS and cDBS in long-term studies.

Sex modulates the outcome of subthalamic nucleus deep brain stimulation in patients with Parkinson's disease.

There are many documented sex differences in the clinical course, symptom expression profile, and treatment response of Parkinson's disease, creating additional challenges for patient management. Although subthalamic nucleus deep brain stimulation is an established therapy for Parkinson's disease, the effects of sex on treatment outcome are still unclear. The aim of this retrospective observational study, was to examine sex differences in motor symptoms, non-motor symptoms, and quality of life after subthalamic nucleus deep brain stimulation. Outcome measures were evaluated at 1 and 12 months post-operation in 90 patients with Parkinson's disease undergoing subthalamic nucleus deep brain stimulation aged 63.00 ± 8.01 years (55 men and 35 women). Outcomes of clinical evaluations were compared between sexes via a Student's t-test and within sex via a paired-sample t-test, and generalized linear models were established to identify factors associated with treatment efficacy and intensity for each sex. We found that subthalamic nucleus deep brain stimulation could improve motor symptoms in men but not women in the on-medication condition at 1 and 12 months post-operation. Restless legs syndrome was alleviated to a greater extent in men than in women. Women demonstrated poorer quality of life at baseline and achieved less improvement of quality of life than men after subthalamic nucleus deep brain stimulation. Furthermore, Hoehn-Yahr stage was positively correlated with the treatment response in men, while levodopa equivalent dose at 12 months post-operation was negatively correlated with motor improvement in women. In conclusion, women received less benefit from subthalamic nucleus deep brain stimulation than men in terms of motor symptoms, non-motor symptoms, and quality of life. We found sex-specific factors, i.e., Hoehn-Yahr stage and levodopa equivalent dose, that were related to motor improvements. These findings may help to guide subthalamic nucleus deep brain stimulation patient selection, prognosis, and stimulation programming for optimal therapeutic efficacy in Parkinson's disease.

The effect of age and disease duration on the efficacy of subthalamic nuclei deep brain stimulation in Parkinson's disease patients.

BACKGROUND: Previous studies have reported the effects of age and disease duration on the efficacy of subthalamic nuclei deep brain stimulation (STN-DBS) of Parkinson's disease (PD) patients. However, available data involving these issues are not consistent. In particular, the effect of age and disease duration on the initial efficacy of STN-DBS has not been established. METHODS: A total of 51 patients with PD treated with bilateral STN-DBS were involved in the present study. They received clinical symptom evaluation during the preoperative, initial, and chronic stages of surgery. The correlations between age when undergoing surgery/age at disease onset/disease duration and outcomes of STN-DBS were measured. RESULTS: The preoperative levodopa response was negatively associated with age. During the initial stage, the age when undergoing surgery and age at disease onset were negatively correlated with the effect on bradykinesia, with better symptom control of general symptoms in long-term disease patients. Similarly, patients with an early time of surgery and disease onset and long-term disease duration showed better control of bradykinesia and axial symptoms at the chronic stage. Furthermore, a long-term disease duration and early disease onset benefited from an increase of therapeutic efficacy in general, rigid, and axial symptoms with STN-DBS after a long period. Nevertheless, patients with late disease onset achieved a better relief of stigma. CONCLUSION: Age and disease durations played a unique role in controlling the symptoms of PD patients treated with STN-DBS. These results may contribute to patient selection and adjustments of expectations of surgery, based on the age, disease duration, and different symptoms.

Macrophage diversity in cancer revisited in the era of single-cell omics.

Tumor-associated macrophages (TAMs) have multiple potent functions in cancer and, thus, represent important therapeutic targets. These diverse functions highlight the heterogenous nature of TAMs. Recent single cell omics technologies have significantly advanced our understanding of the molecular diversity of TAMs. However, a unifying nomenclature of TAM diversity and annotation of their molecular signatures is lacking. Here, we review recent major studies of single cell transcriptome, epigenome, metabolome, and spatial omics of cancer with a specific focus on TAMs. We also propose a consensus model of TAM diversity and present avenues for future research.

Self-feedback LSTM regression model for real-time particle source apportionment.

Atmospheric particulate matter pollution has attracted much wider attention globally. In recent years, the development of atmospheric particle collection techniques has put forwards new demands on the real-time source apportionments techniques. Such demands are summarized, in this paper, as how to set up new restraints in apportionment and how to develop a non-linear regression model to process complicated circumstances, such as the existence of secondary source and similar source. In this study, we firstly analyze the possible and potential restraints in single particle source apportionment, then propose a novel three-step self-feedback long short-term memory (SF-LSTM) network for approximating the source contribution. The proposed deep learning neural network includes three modules, as generation, scoring and refining, and regeneration modules. Benefited from the scoring modules, SF-LSTM implants four loss functions representing four restraints to be followed in the apportionment, meanwhile, the regeneration module calculates the source contribution in a non-linear way. The results show that the model outperforms the conventional regression methods in the overall performance of the four evaluation indicators (residual sum of squares, stability, sparsity, negativity) for the restraints. Additionally, in short time-resolution analyzing, SF-LSTM provides better results under the restraint of stability.

Balance response to levodopa predicts balance improvement after bilateral subthalamic nucleus deep brain stimulation in Parkinson's disease.

The effect of subthalamic nucleus deep brain stimulation (STN-DBS) on balance function in patients with Parkinson's disease (PD) and the potential outcome predictive factors remains unclear. We retrospectively included 261 PD patients who underwent STN-DBS and finished the 1-month follow-up (M1) assessment in the explorative set for identifying postoperative balance change predictors, and 111 patients who finished both the M1 and 12-month follow-up (M12) assessment in the validation set for verifying the identified factors. Motor and balance improvement were evaluated through the UPDRS-III and the Berg balance scale (BBS) and pull test (PT), respectively. Candidate predictors of balance improvement included age, disease duration, motor subtypes, baseline severity of PD, cognitive status, motor and balance response to levodopa, and stimulation parameters. In the off-medication condition, STN-DBS significantly improved BBS and PT performance in both the M1 and M12, in both datasets. While in the on-medication condition, no significant balance improvement was observed. Higher preoperative BBS response to levodopa was significantly associated with larger postoperative off-medication, but not on-medication, BBS (p < 0.001) and PT (p < 0.001) improvement in both the M1 and M12. BBS subitems 8, 9, 11, 13, and 14 were the major contributors to the prediction of balance improvement after STN-DBS. STN-DBS improves short-term off-medication, but not on-medication, balance function assessed through BBS and PT. Preoperative BBS response to levodopa best predicts postoperative off-medication balance improvement. For patients who manifested severe balance problems, a levodopa challenge test on BBS or the short version of BBS is recommended.

Reconstruction of functional uterine tissues through recellularizing the decellularized rat uterine scaffolds by MSCs in vivo and in vitro.

Infertile people who suffered from loss of uterine structures and/or functions can be treated through gestational surrogacy or uterus transplantation, which remains challenging due to the ethical and social issues, the lack of donor organs as well as technical and safety risks. One promising solution is to regenerate and reconstruct a bioartificial uterus for transplantation through the engineering of uterine architecture and appropriate cellular constituents. Here, we developed a well-defined system to regenerate a functional rat uterine through recellularization of the decellularized uterine matrix (DUM) patches reseeded with human mesenchymal stem cells (hMSCs). Engraftment of the recellularized DUMs on the partially excised uteri yielded a functional rat uterus with a pregnancy rate and number of fetuses per uterine horn comparable to that of the control group with an intact uterus. Particularly, the recellularized DUMs enhanced the regeneration of traumatic uterine in vivo because of MSC regulation. The established system here will shed light on the treatment of uterine infertility with heterogeneous DUMs/cell resources through tissue engineering in the future.

Chinese herbal medicine SS-1 inhibits T cell activation and abrogates TH responses in Sjögren's syndrome.

BACKGROUND/PURPOSE: Sjögren's syndrome (SS) is an autoimmune disease and its conventional treatment has exhibited limited therapeutic efficacy. Traditional Chinese medicine has been demonstrated to ameliorate the sicca symptoms of SS by decreasing the level of TH1 and TH2 cytokines and increasing salivary flow rate. A newly designed traditional Chinese medicine, SS-1, showed improved efficacy in alleviating the dryness symptoms of SS patients in the National Taiwan SS cohort investigation. Here, we investigated the effect of SS-1 on T cell responses. METHODS: SS-1 was authenticated and its major compounds were verified by high-performance liquid chromatography. We examined the effects of SS-1 on the activation and TH1, TH2, and TH17 polarization of murine T cells. We also determined the level of TH1, TH2, and TH17 cytokine RNA in peripheral blood mononuclear cells of SS patients before and after SS-1 treatment. RESULTS: SS-1 treatment inhibits the activation and TH1, TH2, and IL-17A+IFNγ+ TH polarization of murine T cells. SS-1 treatment also significantly reduces IFN-γ, IL-4, and IL-13 expression, and moderately reduces IL-17A expression in peripheral blood mononuclear cells of SS patients. CONCLUSION: Our results suggest that SS-1 inhibits T cell activation and diminishes TH1, TH2, and IL-17+IFN-γ+ TH responses in SS patients.