Evaluation of the efficacy of trigger points combined with extracorporeal shock waves in the treatment of plantar fasciitis: heel temperature and plantar pressure.

BACKGROUND: Plantar fasciitis (PF) is the most common cause of heel pain. Among conservative treatments, extracorporeal shock wave therapy (ESWT) is considered effective for refractory PF. Studies have shown that applying ESWT to the trigger points (TrPs) in the triceps surae may play an important role in pain treatment in patients with PF. Therefore, the purpose of this study was to combine the concept of trigger points and ESWT to explore the effect of this combination on plantar temperature and pressure in patients with PF. METHODS: After applying inclusion and exclusion criteria, 86 patients with PF were recruited from the pain clinic of Huadong Hospital, Fudan University and randomly divided into experimental (n = 43) and control groups (n = 43). The experimental group was treated with extracorporeal shock waves to treat the medial heel pain point and the gastrocnemius and soleus TrPs. The control group was only treated with extracorporeal shock waves at the medial heel pain point. The two groups were treated twice with an interval of 1 week. Primary measurements included a numerical rating scale (NRS) score (overall, first step, heel pain during daily activities), and secondary measurements included heel temperature, Roles-Maudsley score (RMS), and plantar pressure. All assessments were performed before treatment (i.e., baseline) and 6 and 12 weeks after treatment. RESULTS: During the trial, 3 patients in the experimental group withdrew from the study, 2 due to interruption of the course of treatment by the COVID-19 epidemic and 1 due to personal reasons. In the control group, 3 patients fell and were removed due to swelling of the heel. Therefore, only 80 patients with PF were finally included. After treatment, the two groups showed good results in NRS score (overall, first step, heel pain during daily activities), RMS, and plantar temperature, especially in the experimental group, who showed a significantly better effect than the control group. CONCLUSION: ESWT of the heel combined with the triceps trigger point of the calf can more effectively improve the pain, function and quality of life of refractory PF than ESWT of the heel alone. In addition, ESWT of the heel combined with the triceps trigger point of the calf can effectively reduce the skin temperature of the heel on the symptomatic side, indicating that the heel temperature as measured by infrared thermal imaging may be used as an independent tool to evaluate the therapeutic effect for patients with chronic PF. Although extracorporeal shock waves combined with TrPs treatment can cause changes in the patients' gait structure, plantar pressure is still difficult to use as an independent tool to evaluate the therapeutic effect for PF. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registry ( www.chictr.org.cn ) on 12/17/2021 with the following code: ChiCTR-INR-2,100,054,439.

Dry needling on latent and active myofascial trigger points versus oral diclofenac in patients with knee osteoarthritis: a randomized controlled trial.

BACKGROUND: Latent and active myofascial trigger points (MTrPs) in knee-associated muscles may play a key role in pain management among patients with knee osteoarthritis (KOA). The aim of this study was to investigate the effect of dry needling treatment on pain intensity, disability, and range of motion (ROM) in patients with KOA. METHODS: This randomized, single-blinded, clinical trial was carried out for 6 weeks of treatment and 6-month follow-up. A total of 98 patients met the entry criteria and were randomly assigned to the dry needling latent and active myofascial trigger point (MTrPs) with the stretching group or the oral diclofenacwith the stretching group. Numeric Pain Rating Scale (NPRS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and ROM were statistically analyzed before and after treatment and at the 6-month follow-up. RESULTS: A total of 42 patients in the dry needling group (DNG) and 35 patients in the diclofenac group (DG), respectively, completed the study, and there was no significant difference in the general data between the two groups. After treatments, both the groups showed a good effect in knee pain, function, and ROM, However, the DNG showed a significantly better result than the DG. Especially in the results of the 6-month follow-up, the DNG showed much better results than the DG. CONCLUSIONS: Dry needling on latent and active MTrPs combined with stretching and oral diclofenac combined with stretching can effectively relieve pain, improve function, and restore knee ROM affected by KOA. However, the effects of dry needling and stretching are better and longer lasting than those of oral diclofenac and stretching for at least 6 months. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registry ( www.chictr.org.cn ) in 17/11/2017 with the following code: ChiCTR-INR-17013432.

Hub-connected functional connectivity within social brain network weakens the association with real-life social network in schizophrenia patients.

Hubs in the brain network are the regions with high centrality and are crucial in the network communication and information integration. Patients with schizophrenia (SCZ) exhibit wide range of abnormality in the hub regions and their connected functional connectivity (FC) at the whole-brain network level. Study of the hubs in the brain networks supporting complex social behavior (social brain network, SBN) would contribute to understand the social dysfunction in patients with SCZ. Forty-nine patients with SCZ and 27 healthy controls (HC) were recruited to undertake the resting-state magnetic resonance imaging scanning and completed a social network (SN) questionnaire. The resting-state SBN was constructed based on the automatic analysis results from the NeuroSynth. Our results showed that the left temporal lobe was the only hub of SBN, and its connected FCs strength was higher than the remaining FCs in both two groups. SCZ patients showed the lower association between the hub-connected FCs (compared to the FCs not connected to the hub regions) with the real-life SN characteristics. These results were replicated in another independent sample (30 SCZ and 28 HC). These preliminary findings suggested that the hub-connected FCs of SBN in SCZ patients exhibit the abnormality in predicting real-life SN characteristics.

Altered empathy-related resting-state functional connectivity in patients with bipolar disorder.

Empathy is the ability to generate emotional responses (i.e., cognitive empathy) and to make cognitive inferences (i.e., affective empathy) to other people's emotions. Empirical evidence suggests that patients with bipolar disorder (BD) exhibit impairment in cognitive empathy, but findings on affective empathy are inconsistent. Few studies have examined the neural mechanisms of cognitive and affective empathy in patients with BD. In this study, we examined the empathy-related resting-state functional connectivity (rsFC) in BD patients. Thirty-seven patients with BD and 42 healthy controls completed the self-report Questionnaires of Cognitive and Affective Empathy (QCAE), the Yoni behavioural task, and resting-sate fMRI brain scans. Group comparison of empathic ability was conducted. The interactions between group and empathic ability on seed-based whole brain rsFC were examined. BD patients scored lower on the Online Simulation subscale of the QCAE and showed positive correlations between cognitive empathy and the rsFC of the dorsal Medial Prefrontal Cortex (dmPFC) with the lingual gyrus. The correlations between cognitive empathy and the rsFC of the temporal-parietal junction (TPJ) with the fusiform gyrus, the cerebellum and the parahippocampus were weaker in BD patients than that in healthy controls. These findings highlight the underlying neural mechanisms of empathy impairments in BD patients.

Potential effects of mung bean protein and a mung bean protein-polyphenol complex on oxidative stress levels and intestinal microflora in aging mice.

This study investigated the effects of mung bean protein (MPI) and a MPI-polyphenol complex on oxidative stress levels and intestinal microflora in a D-galactose-induced aging mouse model. MPI and MPI-polyphenol complex intervention significantly increased activity of superoxide dismutase (SOD) and catalase and other antioxidant enzymes, improved the abundance and diversity of intestinal flora, and decreased the Firmicutes to Bacteroidetes ratio. Among them, the complex was more conducive to the improvement of the activity of antioxidant enzymes. The addition of MPI and the MPI-polyphenol complex can help the proliferation of Bacteroidetes, Bifidobacterium and Roseburia in the intestinal tract of aging mice, and inhibit the growth of Firmicutes and Ruminococcus, and the proliferation effect of the complex on Bifidobacterium was better than that of MPI. MPI significantly upregulated five pathways related to lipid and energy metabolism. Roseburia and Muribaculaceae were negatively correlated with malondialdehyde levels and positively correlated with SOD and other antioxidant enzyme indices. Our findings showed that MPI and MPI-polyphenol complexes can delay aging in mice by reducing oxidative damage and regulating intestinal flora. We also found a strong relationship between the abundance of intestinal flora and the levels of oxidative stress-related enzymes. This study provides theoretical support for the health and anti-aging benefits of mung bean food products.

[Essence of acupoints and meridians based on the studies of myofascial trigger points].

Based on the modern anatomy and physiology, the referred pain of myofascial trigger points of each muscle is integrated; compared with the twelve meridians as well as conception vessel and governor vessel, the similarity of their position and running course is observed. With the current research progress of myofascial trigger points and fasciology, based on the running course of referred pain of trigger points, combined with fascia mechanics, nerve and vascular, the location of acupoints and meridians, as well as the relationship between acupoints and meridians, are discussed.

Social brain network correlates with real-life social network in individuals with schizophrenia and social anhedonia.

Social behaviour requires the brain to efficiently integrate multiple social processes, but it is not clear what neural substrates underlie general social behaviour. While psychosis patients and individuals with subclinical symptoms are characterized by social dysfunction, the neural mechanisms underlying social dysfunctions in schizophrenia spectrum disorders remains unclear. We first constructed a general social brain network (SBN) using resting-state functional connectivity (FC) with regions of interest based on the automatic meta-analysis results from NeuroSynth. We then examined the general SBN and its relationship with social network (SN) characteristics in 30 individuals with schizophrenia (SCZ) and 33 individuals with social anhedonia (SA). We found that patients with SCZ exhibited deficits in their SN, while SA individuals did not. SCZ patients showed decreased segregation and functional connectivity in their SBN, while SA individuals showed a reversed pattern with increased segregation and functional connectivity of their SBN. Sparse canonical correlation analysis showed that both SCZ patients and SA individuals exhibited reduced correlation between SBN and SN characteristics compared with their corresponding healthy control groups. These preliminary findings suggest that both SCZ and SA participants exhibit abnormality in segregation and functional connectivity within the general SBN and reduced correlation with SN characteristics. These findings could guide the development of non-pharmacological interventions for social dysfunction in SCZ spectrum disorders.

Validation of the Questionnaire of Cognitive and Affective Empathy in patients with schizophrenia, major depressive disorder and bipolar disorder.

INTRODUCTION: Alteration of empathy is common in patients with psychiatric disorders. Reliable and valid assessment tools for measuring empathy of clinical samples is needed. The Questionnaire of Cognitive and Affective Empathy (QCAE) is a newly-developed instrument to capture cognitive and affective components of empathy. This study aimed to validate the QCAE and compared self-reported empathy between clinical groups with varied psychiatric diagnoses and healthy sample. METHODS: The present study performed factor analysis for the QCAE on clinical samples in the Chinese setting (n = 534), including patients with schizophrenia (n = 158), bipolar disorder (n = 213) and major depressive disorder (n = 163). Internal consistency, internal correlation and convergent validity was examined in the subsample (n = 361). Group comparison among patients with schizophrenia, bipolar disorder, major depressive disorder and healthy controls (n = 107) was conducted to assess the discriminant validity. RESULTS: Our results indicated acceptable factor model, good reliability and validity of the QCAE. Impaired cognitive empathy was found in clinical samples, especially in patients with schizophrenia, while higher affective empathy was found in patients with bipolar disorder and major depressive disorder. CONCLUSION: The QCAE is a useful tool in assessing empathy in patients with varied psychiatric diagnoses.

Effects of Trigger Point Dry Needling on Neuromuscular Performance and Pain of Individuals Affected by Patellofemoral Pain: A Randomized Controlled Trial.

PURPOSE: To investigate the effects of trigger point dry needling (TrP-DN) on exercise-induced patellofemoral pain syndrome (PFPS). PATIENTS AND METHODS: In this randomized, single-blind, parallel-group trial, 50 patients with PFPS were randomly allocated to the following two groups: the TrP-DN group (n = 25) and the Sham needling group (n = 25). Patients in both groups were asked to perform a stretching exercise of the quadriceps daily after needling. The needling group received a single session of TrP-DN to trigger points (TrPs) in the vastus medialis oblique (VMO), vastus lateralis (VL), and rectus femoris muscles (once a week for 6 weeks), and the Sham group received placebo needling. Visual analogue scale (VAS) for pain intensity and Kujala questionnaire for the functional status were assessed before treatment, 3 and 6 weeks after treatment, and at the 3-month follow-up. The ratio of the myoelectric amplitude of the vastus medialis oblique and vastus lateralis muscles (VMO/VL) was assessed before treatment and 6 weeks after treatment. RESULTS: There was no significant difference in the general data between the two groups. The VAS scores and Kujala scores in the TrP-DN group were significantly improved and increased at the 3-week treatment visit, 6-week treatment visit, and 3-month follow-up compared to the scores before treatment; and the scores in the Sham group were only significantly improved at the 3-week treatment visit, and 6-week treatment visit. VAS scores in the TrP-DN group were significantly lower and Kujala scores were significantly higher at the 6-week treatment visit and the 3-month follow-up compared to those in the Sham group. The VMO/VL ratio in the TrP-DN group was significantly increased at the 6-week treatment visit compared to that before treatment. CONCLUSION: TrP-DN at the quadriceps combined with stretch can reduce the pain, and improves the clinical symptoms and function, the VMO/VL ratio, and the coordination of VMO and VL in patients with PFPS.

Validation and extension of the Questionnaire of Cognitive and Affective Empathy in the Chinese setting.

The Questionnaire of Cognitive and Affective Empathy (QCAE) is a commonly used instrument in empathy research. However, this scale has not been validated in the Chinese context. We examined the psychometric properties and structure of the QCAE in a Chinese sample consisting of 1224 college students. The whole sample was split into two halves for exploratory factor analysis (EFA; n = 617) and confirmatory factor analysis (CFA; n = 607). A subsample (n = 351) completed the Chinese versions of the Interpersonal Reactivity Index (IRI) to examine convergent validity and the Revised Social Anhedonia Scale (RSAS) to examine the discriminate validity. Finally, 79 participants of the above subsample were retested after a 4-week interval. Results from EFA and CFA suggested a five-factor model, namely Perspective Taking, Online Simulation, Emotional Contagion, Proximal Responsivity, and Peripheral Responsivity. The internal consistency was .86 and test-retest reliability was .76. Scores on the QCAE positively correlated with scores on the IRI and negatively correlated with scores on the RSAS. The Chinese version of the QCAE exhibited good factor structure, reliability, and validity. Specific relationships between empathy and social anhedonia were also demonstrated.

[Effect of Dry Needling Stimulation of Myofascial Trigger Point on Sample Entropy of Electromyography of Gastrocnemius Injured Site in Rats].

OBJECTIVE: To attempt to establish an objective quantitative indicator to characterize the trigger point activity, so as to evaluate the effect of dry needling on myofascial trigger point activity. METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into blank control group, dry needling (needling) group, stretching exercise (stretching) group and needling plus stretching group (n＝6 per group). The chronic myofascial pain (trigger point) model was established by freedom vertical fall of a wooden striking device onto the mid-point of gastrocnemius belly of the left hind-limb to induce contusion, followed by forcing the rat to make a continuous downgrade running exercise at a speed of 16 m/min for 90 min on the next day which was conducted once a week for 8 weeks. Electromyography (EMG) of the regional myofascial injured point was monitored and recorded using an EMG recorder via electrodes. It was considered success of the model if spontaneous electrical activities appeared in the injured site. After a 4 weeks' recovery, rats of the needling group were treated by filiform needle stimulation (lifting-thrusting-rotating) of the central part of the injured gastrocnemius belly (about 10 mm deep) for 6 min, and those of the stretching group treated by holding the rat's limb to make the hip and knee joints to an angle of about 180°, and the ankle-joint about 90° for 1 min every time, 3 times altogether (with an interval of 1 min between every 2 times). The activity of the trigger point was estimated by the sample entropy of the EMG signal sequence in reference to Richman's and Moorman's methods to estimate the curative effect of both needling and exercise. RESULTS: After the modeling cycle, the mean sample entropies of EMG signals was significantly decreased in the model groups (needling group [0.034±0.010], stretching group [0.045±0.023], needling plus stretching group [0.047±0.034]) relevant to the blank control group (0.985±0.196, P<0.01). After the treatment, the mean sample entropy of EMG signals was evidently increased in both needling (0.819±0.088), stretching (0.532±0.25) and needling plus stretching (0.810±0.117) groups (P<0.01). The mean sample entropy of the needling and needling plus stretching groups were significantly higher than that of the stretching group (P<0.01), without remarkable difference between the two needling groups in the mean sample entropy (P>0.05), suggesting a better efficacy of dry needling in easing trigger point activity. CONCLUSION: Dry needling is able to relieve myofascial trigger point activity in rats, which is better than that of simple passive stretching therapy.

Evidence for Dry Needling in the Management of Myofascial Trigger Points Associated With Low Back Pain: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the current evidence of the effectiveness of dry needling of myofascial trigger points (MTrPs) associated with low back pain (LBP). DATA SOURCES: PubMed, Ovid, EBSCO, ScienceDirect, Web of Science, Cochrane Library, CINAHL, and China National Knowledge Infrastructure databases were searched until January 2017. STUDY SELECTION: Randomized controlled trials (RCTs) that used dry needling as the main treatment and included participants diagnosed with LBP with the presence of MTrPs were included. DATA EXTRACTION: Two reviewers independently screened articles, scored methodologic quality, and extracted data. The primary outcomes were pain intensity and functional disability at postintervention and follow-up. DATA SYNTHESIS: A total of 11 RCTs involving 802 patients were included in the meta-analysis. Results suggested that compared with other treatments, dry needling of MTrPs was more effective in alleviating the intensity of LBP (standardized mean difference [SMD], -1.06; 95% confidence interval [CI], -1.77 to -0.36; P=.003) and functional disability (SMD, -0.76; 95% CI, -1.46 to -0.06; P=.03); however, the significant effects of dry needling plus other treatments on pain intensity could be superior to dry needling alone for LBP at postintervention (SMD, 0.83; 95% CI, 0.55-1.11; P<.00001). CONCLUSIONS: Moderate evidence showed that dry needling of MTrPs, especially if associated with other therapies, could be recommended to relieve the intensity of LBP at postintervention; however, the clinical superiority of dry needling in improving functional disability and its follow-up effects still remains unclear.

Clinical efficacy, onset time and safety of bright light therapy in acute bipolar depression as an adjunctive therapy: A randomized controlled trial.

BACKGROUND: Bright light therapy (BLT) is an effective treatment for seasonal affective disorder and non- seasonal depression. The efficacy of BLT in treating patients with bipolar disorder is still unknown. AIMS: The aim of this study is to examine the efficacy, onset time and clinical safety of BLT in treating patients with acute bipolar depression as an adjunctive therapy (trial registration at ClinicalTrials.gov: NCT02009371). METHODS: This was a multi-center, single blind, randomized clinical trial. Seventy-four participants were randomized in one of two treatment conditions: BLT and control (dim red light therapy, dRLT). Sixty-three participants completed the study (33 BLT, 30 dRLT). Light therapy lasted for two weeks, one hour every morning. All participants were required to complete several scales assessments at baseline, and at the end of weeks 1 and 2. The primary outcome measures were the clinical efficacy of BLT which was assessed by the reduction rate of HAMD-17 scores, and the onset time of BLT which was assessed by the reduction rate of QIDS-SR16 scores. The secondary outcome measures were rates of switch into hypomania or mania and adverse events. RESULTS: 1) Clinical efficacy: BLT showed a greater ameliorative effect on bipolar depression than the control, with response rates of 78.19% vs. 43.33% respectively (p < 0.01). 2) Onset day: Median onset day was 4.33 days in BLT group. 3) BLT-emergent hypomania: No participants experienced symptoms of hypomania. 4) Side effects: No serious adverse events were reported. CONCLUSION: BLT can be considered as an effective and safe adjunctive treatment for patients with acute bipolar depression.

Enzymatic O-GlcNAcylation of α-synuclein reduces aggregation and increases SDS-resistant soluble oligomers.

Neurodegenerative diseases including dementia with Lewy bodies, Lewy body variant of Alzheimer's disease, and Parkinson's disease are associated with the aberrant aggregation of α-synuclein, which is influenced by several post-translational modifications (PTMs). O-GlcNAcylation is one PTM that has an important role in many fundamental processes. The O-GlcNAcylation of endogenous α-synuclein at residues 53, 64, 72 and 87 has been reported in an unbiased mass spectrum analysis. The consequences of O-GlcNAcylation at residues 72 or 87 have been studied by using a synthetic α-synuclein bearing O-GlcNAcylation at threonine residue 72 or serine 87, respectively. O-GlcNAcylation at Thr72 or Ser87 suppresses the aggregation of α-synuclein. However, the effect of enzymatic O-GlcNAcylation of α-synuclein at multiple residues is not clear. Here, we successfully generated O-GlcNAcylated α-synuclein by co-expressing a shorter form of OGT (sOGT) with α-synuclein. The O-GlcNAcylation inhibited α-synuclein aggregation and promoted the formation of soluble SDS-resistant and Thioflavine T negative oligomers. Our data warrant further studies on the role of O-GlcNAcylation in the progression/treatment of Parkinson's disease in animal models.

Decreased Spontaneous Electrical Activity and Acetylcholine at Myofascial Trigger Spots after Dry Needling Treatment: A Pilot Study.

OBJECTIVE: The aims of this study are to investigate the changes in spontaneous electrical activities (SEAs) and in acetylcholine (ACh), acetylcholine receptor (AChR), and acetylcholine esterase (AChE) levels after dry needling at myofascial trigger spots in model rats. MATERIALS AND METHODS: Forty-eight male Sprague-Dawley rats were divided into four groups. Thirty-six rats were assigned to three model groups, which underwent MTrSs modeling intervention. Twelve rats were assigned to the blank control (BC) group. After model construction, the 36 model rats were randomly subdivided into three groups according to treatment: MTrSs model control (MC) and two dry needling groups. One dry needling group received puncturing at MTrSs (DN-M), whereas the other underwent puncturing at non-MTrSs (DN-nM). Dry needling treatment will last for two weeks, once a week. SEAs and ACh, AChR, and AChE levels were measured after one-week rest of dry needling treatment. RESULTS: The amplitudes and frequencies of endplate noise (EPN) and endplate spike (EPS) significantly decreased after dry needling treatment in the DN-M group. Moreover, ACh and AChR levels significantly decreased, whereas AChE significantly increased after dry needling treatment in the DN-M group. CONCLUSION: Dry needling at the exact MTrSs is more effective than dry needling at non-MTrSs.

Distinguishing bipolar and major depressive disorders by brain structural morphometry: a pilot study.

BACKGROUND: The clinical presentation of common symptoms during depressive episodes in bipolar disorder (BD) and major depressive disorder (MDD) poses challenges for accurate diagnosis. Disorder-specific neuroanatomical features may aid the development of reliable discrimination between these two clinical conditions. METHODS: For our sample of 16 BD patients, 19 MDD patients and 29 healthy volunteers, we adopted vertex-wise cortical based brain imaging techniques to examine cortical thickness and surface area, two components of cortical volume with distinct genetic determinants. Based on specific characteristics of neuroanatomical features, we then used support vector machine (SVM) algorithm to discriminate between patients with BD and MDD. RESULTS: Compared to MDD patients, BD patients showed significantly larger cortical surface area in the left bankssts, precuneus, precentral, inferior parietal, superior parietal and the right middle temporal gyri. In addition, larger volumes of subcortical regions were found in BD patients. In SVM discriminative analyses, the overall accuracy was 74.3 %, with a sensitivity of 62.5 % and a specificity of 84.2 % (p = 0.028). Compared to controls, larger surface area in the temporo-parietal regions were observed in BD patients, and thinner cortices in fronto-temporal regions were observed in MDD patients, especially in the medial orbito-frontal area. CONCLUSIONS: These findings have demonstrated distinct spatially distributed variations in cortical thickness and surface area in patients with BD and MDD, suggesting potentially varying etiological and neuropathological processes in these two conditions. The employment of multimodal classification on disorder-specific biological features has shed light to the development of potential classification tools that could aid diagnostic decisions.

Functional rescue of Kallmann syndrome-associated prokineticin receptor 2 (PKR2) mutants deficient in trafficking.

Mutations in the G protein-coupled prokineticin receptor 2 (PKR2) are known to cause Kallmann syndrome and idiopathic hypogonadotropic hypogonadism manifesting with delayed puberty and infertility. Some of the mutant receptors are not routed to the cell surface; instead, they are trapped in the cellular secretory pathway. The cell-permeant agonists/antagonists have been used to rescue some membrane receptors that are not targeted onto the cell membrane. Here, we chose three disease-associated mutations (W178S, G234D, and P290S), which all resulted in retention of PKR2 intracellularly. We show that a small molecule PKR2 antagonist (A457) dramatically increased cell surface expression and rescued the function of P290S PKR2, but had no effect on W178S and G234D PKR2. Furthermore, we also tested chemical chaperone glycerol on the cell surface expression and function of PKR2 mutants. Treatment with 10% glycerol significantly increased the cell surface expression and signaling of P290S and W178S PKR2. These data demonstrate that some Kallmann syndrome-associated, intracellularly retained mutant PKR2 receptors can be functionally rescued, suggesting a potential treatment strategy for patients bearing such mutations.

Transglutaminase 6 interacts with polyQ proteins and promotes the formation of polyQ aggregates.

A common feature of polyglutamine (polyQ) diseases is the presence of aggregates in neuronal cells caused by expanded polyglutamine tracts. PolyQ proteins are the substrates of transglutaminase 2, and the increased activity of transglutaminase in polyQ diseases suggests that transglutaminase may be directly involved in the formation of the aggregates. We previously identified the transglutaminase 6 gene to be causative of spinocerebellar ataxia type 35 (SCA35), and we found that SCA35-associated mutants exhibited reduced transglutaminase activity. Here we report that transglutaminase 6 interacts and co-localizes with both normal and expanded polyQ proteins in HEK293 cells. Moreover, the overexpression of transglutaminase 6 promotes the formation of polyQ aggregates and the conversion of soluble polyQ into insoluble polyQ aggregates. However, SCA35-associated mutants do not affect their interactions with polyQ proteins. These data suggest that transglutaminase 6 could be involved in polyQ diseases and there may exist a common pathological link between polyQ associated SCA and SCA35.

O-GlcNAcylation of BMAL1 regulates circadian rhythms in NIH3T3 fibroblasts.

Various physiological processes and behaviors show a circadian rhythm of approximately 24 h, which is crucial in coordinating internal metabolic processes and environmental signals. Post-translational modifications play an important role in regulating circadian core proteins. In this study, we demonstrated that BMAL1 was modified with an O-linked ß-N-acetylglucosamine (O-GlcNAc), which stabilized BMAL1 and enhanced its transcriptional activity. Conversely, inhibition of O-GlcNAcylation resulted in inhibition of circadian rhythms of clock gene expression. Because O-GlcNAcylation is sensitive to the glucose level, such a modification may provide a new mechanism connecting metabolism with circadian rhythms.