Follicular helper T (Tfh) cells are specialized in helping B lymphocytes, which play a central role in autoimmune diseases that have a major B cell component, such as in rheumatoid arthritis (RA). ...Follicular regulatory T (Tfr) cells control the over-activation of Tfh and B cells in germinal centers. Dysregulation of Tfh cells and Tfr cells has been reported to be involved in the pathogenesis of some autoimmune diseases. However, the balance of Tfh and Tfr cells, and their roles in the development and progression of RA are still not clear.
In this study, we enrolled 44 patients with RA (20 patients with active RA and 24 patients with inactive RA) and 20 healthy controls, and analyzed the frequencies of circulating Tfh and Tfr cells, expression of programmed death-1 (PD-1), inducible co-stimulator (ICOS), intracellular IL-21, and pSTAT3 in Tfh cells, and serum levels of IL-6. The correlation among these parameters and that of Tfh or Tfr cells with disease activity were also analyzed.
Patients with RA (especially active RA) had higher frequencies of Tfh cells, but lower percentages of Tfr cells, thereby resulting in elevated ratios of Tfh/Tfr. Expression levels of PD-1 and IL-21 in Tfh cells were higher in patients with RA than in healthy subjects, while no difference in ICOS expression was observed between patients and controls. Both pSTAT3 expression and serum IL-6 levels increased in patients with RA, and positive correlation between them was observed. Additionally, pSTAT3 expression was positively correlated with Tfh cell frequency. The Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP) was negatively correlated with Tfr cell frequency, but was positively correlated with both Tfh/Tfr ratio and PD-1 expression.
Results demonstrated that enhanced IL-6/pSTAT3 signaling may contribute to promotion of Tfh cells, consequently skewing the ratio of Tfh to Tfr cells, which may be crucial for disease progression in RA.
LJF and LF are commonly used in Chinese patent drugs. In the Chinese Pharmacopoeia, LJF and LF once belonged to the same source. However, since 2005, the two species have been listed separately. ...Therefore, they are often misused, and medicinal materials are indiscriminately put in their related prescriptions in China. In this work, firstly, we established a model for discriminating LJF and LF using ATR-FTIR combined with multivariate statistical analysis. The spectra data were further preprocessed and combined with spectral filter transformations and normalization methods. These pretreated data were used to establish pattern recognition models with PLS-DA, RF, and SVM. Results demonstrated that the RF model was the optimal model, and the overall classification accuracy for LJF and LF samples reached 98.86%. Then, the established model was applied in the discrimination of their related prescriptions. Interestingly, the results show good accuracy and applicability. The RF model for discriminating the related prescriptions containing LJF or LF had an accuracy of 100%. Our results suggest that this method is a rapid and effective tool for the successful discrimination of LJF and LF and their related prescriptions.
•A single dose of ketamine infusion reduces TNF-α levels at 40 min and 240 min postinfusion.•There is a positive correlation between changes in cytokine levels after ketamine infusion and ...improvements in depressive symptoms.•The rapid suppression of proinflammatory cytokines may contribute to the rapid antidepressant effect of the ketamine infusion.
Increasing evidence supports the rapid antidepressant effect of a low-dose ketamine infusion in treatment-resistant depression (TRD). Proinflammatory cytokines play a crucial role in the pathophysiology of TRD. However, it is unknown whether the rapid antidepressant effect of ketamine is related to the rapid suppression of proinflammatory cytokines. Seventy-one patients with TRD were randomized into three groups according to the treatment received: 0.5 mg/kg ketamine, 0.2 mg/kg ketamine, and normal saline infusion. Proinflammatory markers, including C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-α were examined at baseline and at 40 min, 240 min, Day 3, and Day 7 postinfusion. Montgomery–Åsberg Depression Rating Scale (MADRS) was assessed for depressive symptoms across time. Log-transformed IL-6 and TNF-α levels differed significantly over time. The decrease in TNF-α between baseline and 40 min postinfusion was positively correlated with a decrease in MADRS scores across time in the 0.5 mg/kg ketamine group. This is the first clinical study to support a positive correlation between changes in cytokine levels after ketamine infusion and improvements in depressive symptoms with TRD. The rapid suppression of proinflammatory cytokines may contribute to the rapid antidepressant effect of the ketamine infusion.
Theta‐burst stimulation (TBS) is a varied form of repetitive transcranial magnetic stimulation (rTMS) and has more rapid and powerful effects than rTMS. Experiments on the human motor cortex have ...demonstrated that intermittent TBS has facilitatory effects, whereas continuous TBS has inhibitory effects. Huang's simplified model provides a solid basis for elucidating such after‐effects. However, evidence increasingly indicates that not all after‐effects of TBS are as expected, and high variability among individuals has been observed. Studies have suggested that the GABAergic and glutamatergic neurotransmission play a vital role in the aforementioned after‐effects, which might explain the interindividual differences in these after‐effects. Herein, we reviewed the latest findings on TBS from animal and human experiments on glutamatergic and GABAergic neurotransmissions in response to TBS. Furthermore, an updated theoretical model integrating glutamatergic and GABAergic neurotransmissions is proposed.
Turpiniae Folium, the dried leaves of Turpinia arguta Seem., is a kind of historic traditional Chinese medicine. Here, based on our previous study, we extracted the Turpiniae Folium polysaccharides ...(TFP) and isolated three polysaccharide fractions from TFP. Then, TFP and one of the major polysaccharide fractions (TFP‐1a) were identified through HPLC, HPGPC, and ATR‐FTIR. Furthermore, the evaluations of their antioxidative, anti‐inflammatory activities and inhibitory effect on angiotensin II‐induced vascular smooth muscle cells (VSCMs) proliferation in vitro were conducted. Both TFP and TFP‐1a showed strong hydroxyl radical scavenging, DPPH radical scavenging, and Fe2+ chelating activities, and exerted strong anti‐inflammatory activity. Moreover, TFP and TFP‐1a also possessed a strong inhibitory effect on Ang II‐induced VSCMs proliferation. On these premises, we inferred that TFP and TFP‐1a could be potential and promising natural antioxidants, anti‐inflammatory agents, and implicated to treat cardiovascular disease.
Background
As a common disease, the incidence of atherosclerosis (AS) in the world is high. Therefore, we aimed to evaluate the involvement of hydrogen sulfide (H
2S)/cystathionine γ‐lyase (CSE) in ...the pathogenesis of AS as well as their possible signaling pathways.
Methods
Enzyme‐linked immunosorbent assay, real‐time polymerase chain reaction, and Western blot analysis were used to detect the effect of CSE on the expression of inflammatory cytokines, ie, H
2S, thioredoxin‐interacting protein (TXNIP), NLRP3, apoptosis‐associated speck‐like protein (ASC), caspase‐1, and interleukin (IL)‐1β. In addition, immunohistochemistry and Western blot analysis were performed to detect the levels of TXNIP, NLRP3, ASC, caspase‐1, IL‐1β, and IL‐18 among different groups.
Result
Knockdown of CSE by the transfection of CSE small interfering RNA upregulated the levels of two inflammatory cytokines, ie, IL‐1β and IL‐18. In addition, the downregulation of CSE promoted the expression of TXNIP, NLRP3, ASC, caspase‐1, and IL‐1β in THP‐1 cells. Meanwhile, treating the cells with sodium hydrosulfide (NaHS) inhibited the productions of IL‐1β and IL‐18. Furthermore, upregulation of H
2S synthesis by treating the cells with NaHS also reduced the protein levels of TXNIP, NLRP3, ASC, caspase‐1, and IL‐1β. Finally, the protein levels of TXNIP and NLRP3 in the AS group were much higher than those in the AS + H
2S group, which in turn was higher than the sham group. In addition, the AS group displayed the highest protein levels of TXNIP, NLRP3, ASC, caspase‐1, IL‐1β, and IL‐18, while the levels of these proteins in the AS + H
2S group were higher than those in the sham group.
Conclusion
In summary, the present finding suggested a possible linkage between H
2S metabolism and AS through the H
2S/CSE‐TXNIP‐NLRP3‐IL‐18/IL‐1β‐nitric oxide (NO) signaling pathway.
We aimed to evaluate the involvement of hydrogen sulfide (H2S)/cystathionine γ‐lyase (CSE) in the pathogenesis of atherosclerosis (AS) as well as their possible signaling pathways. And the present finding suggested a possible linkage between H
2S metabolism and AS through the H
2S/CSE‐TXNIP‐NRLP3‐IL‐18/IL‐1β‐NO signaling pathway.
Theta-burst transcranial magnetic stimulation could modulate cortical excitability and has the potential to treat refractory depression. However, there has been a lack of large randomized studies of ...the antidepressant efficacy of different forms of theta-burst stimulation, such as intermittent and continuous theta-burst stimulation. A randomized sham-controlled study was conducted to investigate antidepressant efficacy of theta-burst stimulation and to compare efficacy among left-prefrontal intermittent theta-burst stimulation, right-prefrontal continuous theta-burst stimulation and a combination of them in patients showing different levels of antidepressant refractoriness. A group of 60 treatment-refractory patients with recurrent major depressive disorder were recruited and randomized to four groups (Group A: continuous theta-burst stimulation; Group B: intermittent theta-burst stimulation; Group C: a combination of continuous and intermittent theta-burst stimulation; and Group D: sham theta-burst stimulation; 15 patients were included in each group). After 2 weeks of theta-burst stimulation treatment, depression improved in all groups. Groups B and C had better antidepressant responses (as reflected by % decreases in depression score) than Groups A and D (P = 0.001, post hoc analysis: B > A, B > D, C > A, and C > D), even after controlling for age and refractoriness scores. The mean antidepressant effect was highest in Group C and followed by that in Group B. Additionally, a significant placebo effect was found in patients with low refractoriness; this disappeared in patients with moderate-to-high refractoriness. A significant correlation existed between refractoriness scores and treatment responses. Treatment refractoriness was a significant factor negatively predicting efficacy of theta-burst stimulation (P = 0.039). This randomized sham-controlled study demonstrated that active theta-burst stimulation is a well-tolerated form of repetitive transcranial magnetic stimulation and has good antidepressant efficacy, particularly in depressed subjects within a certain range of treatment refractoriness.
Aim
Bipolar disorder and major depressive disorder (MDD) have been demonstrated to be associated with proinflammatory states and cognitive function deficits. We aimed to investigate the differences ...of cognitive function and proinflammatory cytokines between patients with bipolar I disorder (BDI), bipolar II disorder (BDII), and MDD.
Methods
Thirty‐seven patients with BDI, 33 with BDII, 25 with MDD, and 54 age‐, sex‐matched controls were enrolled. All patients had a clinical global impression‐severity scale ≤2. Serum levels of proinflammatory markers, including soluble interleukin‐6 receptor, C‐reactive protein, and soluble tumor necrosis factor receptor 1 (sTNF‐αR1) were measured. Performance in the Word List Memory Task (WLMT), Wisconsin Card Sorting Task (WCST), 2‐back task, Go/No‐Go task, and divided attention task was assessed.
Results
Patients with BDI had higher levels of sTNF‐αR1 than patients with MDD and controls (P < 0.001). Patients with BDI performed worse on WLMT, WCST, 2‐back task, divided attention_visual and divided attention_auditory tasks than the other three groups (all P < 0.05). Furthermore, sTNF‐αR1 levels were negatively correlated with cognitive function measured using the WLMT and divided attention_auditory (all P < 0.05).
Conclusions
Patients with BDI had higher levels of sTNF‐αR1 and cognitive function impairments than the remaining groups. Future studies are needed to explore the pathophysiology of sTNF‐αR1 in the contribution of cognitive alterations.
Increasing evidence suggests that patients with bipolar disorder are more likely to develop malignant cancer than in the general population. However, the overall cancer risk in the unaffected ...siblings of such patients remains unknown. From the National Health Insurance Research Database of Taiwan, 25 356 patients with bipolar disorder, 25 356 age‐matched unaffected siblings of patients with bipolar disorder and 101 422 age‐matched controls without severe mental disorders between 1996 and 2010 were enrolled in our study. Patients who developed cancer between the time of enrollment and the end of 2011 were identified. Cancers were divided into three subgroups based on the related layer of embryonic development: ectodermal, mesodermal and endodermal cancers. Patients with bipolar disorder (odds ratio OR = 1.22, 95% confidence interval CI: 1.06, 1.40) and unaffected siblings of such patients (OR = 1.17, 95% CI 1.02, 1.34) had greater risk of developing malignant cancer than did controls. Furthermore, only those aged <50 years, for both patients with bipolar disorder (OR = 1.90, 95% CI 1.38, 2.61) and unaffected siblings (OR = 1.65, 95% CI 1.19, 2.28), were more likely to develop the ectodermal cancer, especially breast cancer, than the control group. The associations of bipolar disorder and susceptibility to bipolar disorder with increased cancer risk in the younger population may imply a genetic overlap in neurodevelopment and malignancy pathogenesis. Our findings may encourage clinicians to monitor cancer risk factors and warning signs closely in patients with bipolar disorder and unaffected siblings of such patients.
What's new?
Increasing evidence suggests that patients with bipolar disorder are more likely to develop malignant cancer than the general population. However, the overall cancer risk in the unaffected siblings of such patients remains unknown. This study found that patients with bipolar disorder and their unaffected siblings were more likely to develop cancer than controls without severe mental disorders. Furthermore, only participants aged <50 were more likely to develop ectodermal cancers. The findings imply a genetic overlap in neurodevelopment and malignancy pathogenesis and may encourage clinicians to closely monitor patients with bipolar disorder and their unaffected siblings for cancer warning signs.
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