Protective effects of curcumin against osteoporosis and its molecular mechanisms: a recent review in preclinical trials.

Osteoporosis (OP) is one of the most common metabolic skeletal disorders and is commonly seen in the elderly population and postmenopausal women. It is mainly associated with progressive loss of bone mineral density, persistent deterioration of bone microarchitecture, and increased fracture risk. To date, drug therapy is the primary method used to prevent and treat osteoporosis. However, long-term drug therapy inevitably leads to drug resistance and specific side effects. Therefore, researchers are constantly searching for new monomer compounds from natural plants. As a candidate for the treatment of osteoporosis, curcumin (CUR) is a natural phenolic compound with various pharmacological and biological activities, including antioxidant, anti-apoptotic, and anti-inflammatory. This compound has gained research attention for maintaining bone health in various osteoporosis models. We reviewed preclinical and clinical studies of curcumin in preventing and alleviating osteoporosis. These results suggest that if subjected to rigorous pharmacological and clinical trials, naturally-derived curcumin could be used as a complementary and alternative medicine for the treatment of osteoporosis by targeting osteoporosis-related mechanistic pathways. This review summarizes the mechanisms of action and potential therapeutic applications of curcumin in the prevention and mitigation of osteoporosis and provides reference for further research and development of curcumin.

Cognitive Activities, Lifestyle Factors, and Risk of Cognitive Impairment, with an Analysis of the Apolipoprotein Epsilon 4 Genotype.

INTRODUCTION: Cognitive stimulating activities and a healthy lifestyle are associated with less cognitive impairment. However, whether the association is varied by Apolipoprotein epsilon 4 (APOE ε4) allele carrier status remains inconclusive. We aimed to investigate whether the association of cognitively stimulating activities and a healthy lifestyle with the risk of cognitive impairment varied by APOE ε4 allele carrier status. METHODS: A case-control study was conducted for adults aged 60 years and above. Six province administrative units (Beijing, Shanghai, Hubei, Sichuan, Guangxi, and Yunnan) were included using stratified multistage cluster sampling. A total of 1,300 individuals were identified with cognitive impairment (cases) at enrollment and were matched 1:2 on sex, age (±2 years), and residential district with controls who were cognitively normal at the time of the evaluation. We used a standardized questionnaire to collect information on cognitive stimulating activities, lifestyle factors, demographics, and comorbidity. Cognitive stimulating activities included reading books or newspapers, playing cards or mahjong, using the Internet, socializing with neighbors, and community activities. Lifestyle factors included smoking, alcohol drinking, daily tea drinking, and regular exercise. We used logistic regression to assess the interaction between cognitive stimulating activities, lifestyle factors, and APOE ε4 allele carrier status (yes/no) on the risk of cognitive impairment. We tested for additive interaction by estimating relative excess risk (RERI) due to interaction and multiplicative interaction employing the p value of the interaction term of each lifestyle factor and APOE ε4 into the model. RESULTS: Four cognitive stimulating activities were associated with less cognitive impairment regardless of APOE ε4 status. Using the Internet (odds ratio [OR]: 0.53, 95% confidence interval [CI]: 0.30-0.95), daily tea drinking (OR: 0.79; 95% CI: 0.63-0.98), and regular exercise (OR: 0.78; 95% CI: 0.65-0.94) were associated with less cognitive impairment only in noncarriers. Multiplicative and additive interactions were found between community activities and APOE ε4 carrier status (multiplicative p value = 0.03; RERI 0.738, 95% CI: 0.201-1.275). CONCLUSION: The associations between cognitive activities and cognitive impairment were robust regardless of the APOE ε4 carrier status, while the associations between lifestyle factors and cognitive impairment varied by APOE ε4 carrier status.

An extracellular Cu/Zn superoxide dismutase from Neocaridina denticulata sinensis: cDNA cloning, mRNA expression and characterizations of recombinant protein.

Neocaridina denticulata sinensis possesses characters of rapid growth, tenacious vitality, short growth cycle, transparent, and easy feeding. Therefore, it is gradually being developed into an animal model for basic research on decapod crustaceans. Herein, a Cu/Zn superoxide dismutase (Cu/Zn-SOD), named as Nd-ecCu/Zn-SOD, was identified and characterized from N. denticulata sinensis. The full-length cDNA sequence of Nd-ecCu/Zn-SOD is 829 bp containing a 684 bp open reading frame, which encodes a protein of 227 amino acid residues with a typical Sod_Cu domain. The quantitative real-time PCR analysis showed that Nd-ecCu/Zn-SOD mRNA was expressed in all the tested tissues. Under challenge with copper, the mRNA expression of Nd-ecCu/Zn-SOD reached the maximum at 6 h, and decreased until 24 h. After 24 h of exposure, its expression was up-regulated significantly at 36 h. After then its expression sharply decreased with a comeback at 48 h. The result indicated that Nd-ecCu/Zn-SOD might play an important role in the stress response of N. denticulata sinensis. The expression of Nd-ecCu/Zn-SOD in gills challenged with Vibrio parahaemolyticus changed in a time-dependent manner. Nd-ecCu/Zn-SOD was lowly expressed in early developmental stages by RNA-Seq technology, yet it showed that a cyclical rise and fall occurred between middle stages and late stages. In addition, Nd-ecCu/Zn-SOD was recombinantly expressed using E. coli and the recombinant protein was purified as a single band on SDS-PAGE. The recombinant Nd-ecCu/Zn-SOD (rNd-ecCu/Zn-SOD) existed enzymatic activity under a wide range of temperature and pH. The exposure of metal ions was found that Zn2+, Mg2+, Ca2+, Ba2+, and Cu2+ could inhibit the enzymatic activity of rNd-ecCu/Zn-SOD, and Mn2+ increased the enzymatic activity of rNd-ecCu/Zn-SOD. These results indicate that Nd-ecCu/Zn-SOD may play a pivotal role in resistant against oxidative damage and act as a biomarker under stressful environment.

Characterization of peroxiredoxin from Neocaridina denticulata sinensis and its antioxidant and DNA protection activity analysis.

Peroxiredoxin (Prx) is an antioxidant protein that widely exists in various organisms. To further investigate the role of Prx in the antioxidant and immune responses of Neocaridina denticulata sinensis, the full-length cDNA sequence of a Prx gene (Nd-Prx) from N. denticulata sinensis was obtained. The open reading frame (ORF) of Nd-Prx is 597 bp and encodes 198 amino acids. Amino acid similarity alignment showed that Nd-Prx contained a conserved sequence region "FYPLDFTFVCPTEI". qRT-PCR assay showed that Nd-Prx was expressed in all tested tissues and its expression was highest in the ovary. Nd-Prx was most highly expressed at 36 h after copper stimulation. Nd-Prx expression levels in hepatopancreas were significantly upregulated after Vibrio parahaemolyticus challenge (P < 0.05). In addition, the recombinant Nd-Prx was prepared and its enzyme activity was most stable at 70 °C with pH of 6.0. The antioxidant activity and DNA protection of recombinant Nd-Prx was also demonstrated. In summary, this study investigated the role of Prx in antioxidant and immune responses of N. denticulata sinensis, which might provide a foundation for further exploring Prx in immune system of crustaceans and for the application in disease control.

Behavioral activation with mindfulness in treating subthreshold depression in primary care: A cost-utility and cost-effectiveness analysis alongside a randomized controlled trial.

This study aimed to assess the cost-utility and cost-effectiveness of group-based behavioral activation with mindfulness (BAM) versus care as usual (CAU) for treating subthreshold depression in primary care. Adults aged 18 years or older with subthreshold depression were randomized into two arms and were followed up for 12 months. BAM group was provided with eight 2-h weekly treatment by trained allied healthcare workers. CAU group could access to usual medical care but did not receive extra interventions. The health service cost in the past 12 months was self-reported by the participants. Quality-adjusted Life Years (QALYs) and clinical outcome (incidence of major depressive disorder progression) were measured. Willingness-to-pay ratio for cost-utility analysis (CUA) and cost-effectiveness analysis (CEA) was US$50,000 per QALY and US$20,000 per prevented major depression case, respectively. These ratios were used in the cost-effective acceptability curve analyses to estimate the probability of cost-effectiveness of the estimated incremental cost effectiveness ratios (ICER) of BAM versus CAU. A total of 115 and 116 participants were included in the BAM group and CAU respectively. The estimated CUA ICER was US5,979 per QALY and had a probability of 0.93 that BAM was cost-effective when compared to CAU. Furthermore, when compared to CAU, BAM was cost-effective in preventing progression of major depression: the estimated CEA ICER was US$1046 per preventable case of major progression with a probability of 0.99 to be cost-effective. Group-based BAM is considered as a cost-effective alternative treatment for treating subthreshold depression by preventing major depressive disorder.

Efficacy and safety of traditional Chinese medicine combined with routine western medicine for the asymptomatic novel coronavirus disease (COVID-19): A Bayesian network meta-analysis protocol.

BACKGROUND: The number of patients infected with novel coronavirus disease (COVID-19) has exceeded 10 million in 2020, and a large proportion of them are asymptomatic. At present, there is still no effective treatment for this disease. Traditional Chinese medicine (TCM) shows a good therapeutic effect on COVID-19, especially for asymptomatic patients. According to the search results, we found that although there are many studies on COVID-19, there are no studies targeting asymptomatic infections. Therefore, we design a network meta-analysis (NMA) to evaluate the therapeutic effect of TCM on asymptomatic COVID-19. METHODS: We will search Chinese and English databases to collect all randomized controlled trials (RCTs) of TCM combined with conventional western medicine or using only TCM to treat asymptomatic COVID-19 from December 2019 to July 2020. Then, two investigators will independently filter the articles, extract data, and evaluate the risk of bias. We will conduct a Bayesian NMA to evaluate the effects of different therapies. All data will be processed by Stata 16.0 and WinBUGS. RESULTS: This study will evaluate the effectiveness of various treatments for asymptomatic COVID-19. The outcome indicators include the time when the nucleic acid turned negative, the proportion of patients with disease progression, changes in laboratory indicators, and the side effects of drugs. CONCLUSION: This analysis will further improve the treatment of asymptomatic COVID-19. INPLASY REGISTRATION NUMBER: INPLASY202070022.

Tomato seed oil attenuates hyperlipidemia and modulates gut microbiota in C57BL/6J mice.

In this study we aimed to investigate the role of tomato seed oil (TSO) in the alleviation of hyperlipidemia and the regulation of gut microbiota in C57BL/6J mice. Mice were divided into the following four diet-based groups: low-fat diet (LF, n = 8), high-fat diet (HF, n = 6), HF diet with TSO replacing one-third of lard (TL, n = 8), and HF diet with TSO replacing two-thirds of lard (TH, n = 8). The results showed that TH significantly reduced weight gain, relative adipose tissue weights, plasma cholesterol, triacylglycerol, low-density lipoprotein cholesterol (LDL-C), ratio of LDL-C to high-density lipoprotein cholesterol (HDL-C), hepatic cholesterol, and total fatty acids, and markedly increased plasma HDL-C. TSO supplementation also dose-dependently increased fecal cholesterol excretion and reduced fecal total fatty acids. This was accompanied by upregulation of the gene expression of hepatic PPARα, ACADL, CYP7A1, LXRα, ABCA1, and SR-B1. Metagenomic analyses demonstrated that TSO tended to reduce the Firmicutes/Bacteroidetes ratio, significantly increased the relative abundance of the genus Lactobacillus, and reduced the relative abundance of the genera Rikenella, Enterorhabdus, unclassified_o_Clostridiales and Ruminococcaceae_UCG-009. These results proved that TSO was effective in attenuating hyperlipidemia in C57BL/6J mice by enhancing fatty acid ß-oxidation, reducing cholesterol absorption, promoting cholesterol efflux, and favorably modulating the gut microbiota.

Effectiveness of nourishing Yin and tonifying Yang sequential therapy in combination with Climen on diminished ovarian reserve: a retrospective study.

OBJECTIVE: To evaluate the clinical efficacy of nourishing Yin and tonifying Yang sequential therapy (NYTYST) in combination with the Western Medicine Climen in treating diminished ovarian reserve (DOR). METHODS: From September 2014 to September 2016, 46 patients with DOR who received NYTYST and Climen (treatment group) and 51 patients who received Climen only (control group) at the Jiangsu Provincial Traditional Chinese Medicine Hospital (Nanjing, China) were retrospectively reviewed. Before and at 3 months after treatment, serum levels of follicle-stimulating hormone (FSH), FSH/luteinizing hormone (LH), estradiol (E2), and anti-Mullerian hormone (AMH), the antral follicle count (AFC), stromal peak systolic velocity (PSV), symptom scores, and the clinical effectiveness rate were measured and compared between the two groups. RESULTS: After treatment, serum levels of FSH, FSH/LH and E2, and symptom scores were significantly decreased compared with before treatment (all P < 0.05) in the two groups. AMH levels, AFC, and PSV were significantly increased after treatment compared with before treatment in both groups (all P < 0.05). Serum levels of FSH, FSH/LH, and E2 after treatment were significantly lower in the treatment group than in the control group (all P < 0.05). However, AMH levels and the AFC were significantly higher after treatment in the treatment group than in the control group (both P < 0.05). The clinical effectiveness rate was significantly higher in the treatment group than in the control group (87% vs 68.6%, P < 0.05). CONCLUSION: NYTYST combined with Climen may be more effective in treating DOR than Climen alone.

[Influence of nourishing yin and tonifying yang sequential therapy combined with Western medicine on TGF-ß1/Smads signaling pathway in anovulatory infertility rats with diminished ovarian reserve].

OBJECTIVE: To explore the influence for combination of nourishing yin and tonifying yang sequential therapy (NYTYST) with Western medicine in treating anovulatory infertility rats with diminished ovarian reserve (DOR) based on TGF-ß1/Smads signaling pathway. 
 Methods: A total of 40 female rats were randomly divided into 5 groups, a normal control group, a model group, a Western medicine group, a NYTYST group and a combination group (n=8 in each group). The DOR model was established through orally taking tripterygium pill for continuous 2 weeks. The normal control group and the model group were treated with saline for 10 days. The Western medicine group was treated with hormone replacement therapy (HRT) and ovarian stimulation. The NYTYST group was treated with nourishing yin herbs in proestrus and tonifying yang herbs in late estrus and the combination group was treated with Chinese herb and Western drugs for 10 days. HE staining was used to observe histopathologic changes in ovary. Expression levels of transforming growth factor ß1 receptor (TGF-ß1R) in rats ovarian were detected by immunohistochemistry. Expression levels of Smad2, Smad3 and Smad7 protein in rat ovarian were detected by Western blot.
 Results: Compared with the control group, the numbers of developing follicles, mature follicles and corpus luteum were decreased , while atrefic follicles were increased significantly in the model group (P<0.01); the levels of TGF-ß1R, Smad2 and Smad3 were decreased significantly, while Smad7 was increased significantly (P<0.01). Compared with the model group, the numbers of developing follicles, mature follicles and corpus luteum, Smad2 and Smad3 expression were increased, while atrefic follicles and Smad7 were decreased significantly in the treatment group (P<0.05 or P<0.01). The numbers of developing follicles and corpus luteum in the combination group was superior to the Western medicine group (P<0.05). Compared with the Western medicine group, the levels of TGF-ß1R, Smad2 and Smad3 were increased significantly, while Smad7 was decreased significantly in the combination group (P<0.05 or P<0.01). 
 Conclusion: NYTYST combined with Western medicine can improve the function of ovaries reserve by up-regulation of TGF-ß1R, Smad2 and Smad3 while down-regulation of Smad7 in DOR rats.

Mindfulness-based stress reduction for family carers of people with dementia.

BACKGROUND: Caring for people with dementia is highly challenging, and family carers are recognised as being at increased risk of physical and mental ill-health. Most current interventions have limited success in reducing stress among carers of people with dementia. Mindfulness-based stress reduction (MBSR) draws on a range of practices and may be a promising approach to helping carers of people with dementia. OBJECTIVES: To assess the effectiveness of MBSR in reducing the stress of family carers of people with dementia. SEARCH METHODS: We searched ALOIS - the Cochrane Dementia and Cognitive Improvement Group's Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (all years to Issue 9 of 12, 2017), MEDLINE (Ovid SP 1950 to September 2017), Embase (Ovid SP 1974 to Sepetmber 2017), Web of Science (ISI Web of Science 1945 to September 2017), PsycINFO (Ovid SP 1806 to September 2017), CINAHL (all dates to September 2017), LILACS (all dates to September 2017), World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, and Dissertation Abstracts International (DAI) up to 6 September 2017, with no language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) of MBSR for family carers of people with dementia. DATA COLLECTION AND ANALYSIS: Two review authors independently screened references for inclusion criteria, extracted data, assessed the risk of bias of trials with the Cochrane 'Risk of bias' tool, and evaluated the quality of the evidence using the GRADE instrument. We contacted study authors for additional information, then conducted meta-analyses, or reported results narratively in the case of insufficient data. We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included five RCTs involving 201 carers assessing the effectiveness of MBSR. Controls used in included studies varied in structure and content. Mindfulness-based stress reduction programmes were compared with either active controls (those matched for time and attention with MBSR, i.e. education, social support, or progressive muscle relaxation), or inactive controls (those not matched for time and attention with MBSR, i.e. self help education or respite care). One trial used both active and inactive comparisons with MBSR. All studies were at high risk of bias in terms of blinding of outcome assessment. Most studies provided no information about selective reporting, incomplete outcome data, or allocation concealment.1. Compared with active controls, MBSR may reduce depressive symptoms of carers at the end of the intervention (3 trials, 135 participants; standardised mean difference (SMD) -0.63, 95% confidence interval (CI) -0.98 to -0.28; P<0.001; low-quality evidence). We could not be certain of any effect on clinically significant depressive symptoms (very low-quality evidence).Mindfulness-based stress reduction compared with active control may decrease carer anxiety at the end of the intervention (1 trial, 78 participants; mean difference (MD) -7.50, 95% CI -13.11 to -1.89; P<0.001; low-quality evidence) and may slightly increase carer burden (3 trials, 135 participants; SMD 0.24, 95% CI -0.11 to 0.58; P=0.18; low-quality evidence), although both results were imprecise, and we could not exclude little or no effect. Due to the very low quality of the evidence, we could not be sure of any effect on carers' coping style, nor could we determine whether carers were more or less likely to drop out of treatment.2. Compared with inactive controls, MBSR showed no clear evidence of any effect on depressive symptoms (2 trials, 50 participants; MD -1.97, 95% CI -6.89 to 2.95; P=0.43; low-quality evidence). We could not be certain of any effect on clinically significant depressive symptoms (very low-quality evidence).In this comparison, MBSR may also reduce carer anxiety at the end of the intervention (1 trial, 33 participants; MD -7.27, 95% CI -14.92 to 0.38; P=0.06; low-quality evidence), although we were unable to exclude little or no effect. Due to the very low quality of the evidence, we could not be certain of any effects of MBSR on carer burden, the use of positive coping strategies, or dropout rates.We found no studies that looked at quality of life of carers or care-recipients, or institutionalisation.Only one included study reported on adverse events, noting a single adverse event related to yoga practices at home AUTHORS' CONCLUSIONS: After accounting for non-specific effects of the intervention (i.e. comparing it with an active control), low-quality evidence suggests that MBSR may reduce carers' depressive symptoms and anxiety, at least in the short term.There are significant limitations to the evidence base on MBSR in this population. Our GRADE assessment of the evidence was low to very low quality. We downgraded the quality of the evidence primarily because of high risk of detection or performance bias, and imprecision.In conclusion, MBSR has the potential to meet some important needs of the carer, but more high-quality studies in this field are needed to confirm its efficacy.

Mindfulness training for psychological stress in family caregivers of persons with dementia: a systematic review and meta-analysis of randomized controlled trials.

Caring for a relative with dementia is extremely challenging; conventional interventions may not be highly effective or easily available on some occasions. This study aimed to explore the efficacy of mindfulness training in improving stress-related outcomes in family caregivers of people with dementia using a meta-analytic review. We searched randomized controlled trials (RCT) through April 2017 from five electronic databases, and assessed the risk of bias using the Cochrane Collaboration tool. Seven RCTs were included in our review. Mindfulness interventions showed significant effects of improvement in depression (standardized mean difference: -0.58, [95% CI: -0.79 to -0.37]), perceived stress (-0.33, [-0.57 to -0.10]), and mental health-related quality of life (0.38 [0.14 to 0.63]) at 8 weeks post-treatment. Pooled evidence did not show a significant advantage of mindfulness training compared with control conditions in the alleviation of caregiver burden or anxiety. Future large-scale and rigorously designed trials are needed to confirm our findings. Clinicians may consider the mindfulness program as a promising alternative to conventional interventions.

Development of an on-line mixed-mode gel liquid chromatography×reversed phase liquid chromatography method for separation of water extract from Flos Carthami.

A novel on-line comprehensive two-dimensional liquid chromatography (2D-LC) method by coupling mixed-mode gel liquid chromatography (MMG-LC) with reversed phase liquid chromatography (RPLC) was developed. A mixture of 17 reference compounds was used to study the separation mechanism. A crude water extract of Flos Carthami was applied to evaluate the performance of the novel 2D-LC system. In the first dimension, the extract was eluted with a gradient of water/methanol over a cross-linked dextran gel Sephadex LH-20 column. Meanwhile, the advantages of size exclusion, reversed phase partition and adsorption separation mechanism were exploited before further on-line reversed phase purification on the second dimension. This novel on-line mixed-mode Sephadex LH-20×RPLC method provided higher peak resolution, sample processing ability (2.5mg) and better orthogonality (72.9%) versus RPLC×RPLC and hydrophilic interaction liquid chromatography (HILIC)×RPLC. To the best of our knowledge, this is the first report of a mixed-mode Sephadex LH-20×RPLC separation method with successful applications in on-line mode, which might be beneficial for harvesting targets from complicated medicinal plants.

Comparing the Effects of Mindfulness-Based Cognitive Therapy and Sleep Psycho-Education with Exercise on Chronic Insomnia: A Randomised Controlled Trial.

BACKGROUND: Mindfulness-based cognitive therapy (MBCT) is a potential treatment for chronic insomnia. We evaluated the efficacy of MBCT for insomnia (MBCT-I) by comparing it with a sleep psycho-education with exercise control (PEEC) group. METHODS: Adults with chronic primary insomnia (n = 216) were randomly allocated to the MBCT-I or PEEC group. The MBCT-I included mindfulness and psycho-education with cognitive and behavioural components under cognitive behavioural therapy for insomnia. PEEC included psycho-education of sleep hygiene and stimulus control, and exercises. Any change in insomnia severity was measured by the Insomnia Severity Index (ISI). Secondary outcomes included sleep parameters measured by a sleep diary, health service utilisation, absence from work and mindfulness measured by the Five Facet Mindfulness Questionnaire. RESULTS: The ISI score significantly decreased in the MBCT-I group compared with the PEEC group at 2 months (i.e., post-intervention) (p = 0.023, effect size [95% CI] -0.360 [-0.675, -0.046]) but not at 5 or 8 months. Treatment response rates and remission rates based on the ISI cut-off scores were not significantly different between groups. Wake time after sleep onset (WASO) was less in the MBCT-I group at 2 and 5 months. At 8 months, both groups showed a reduced ISI score, sleep onset latency and WASO, and increased sleep efficiency and total sleep time; however, no group differences were seen. Other outcome measures did not significantly improve in either group. CONCLUSIONS: Long-term benefits were not seen in MBCT-I when compared with PEEC, although short-term benefits were seen.

Potent antirheumatic activity of a new DNA vaccine targeted to B7-2/CD28 costimulatory signaling pathway in autoimmune arthritis.

Rheumatoid arthritis is a proinflammatory autoimmune disease attributed to failure of both CD4(+)CD25(+) regulatory T (Tr) and CD8(+)CD28(-) suppressor T (Ts) cells to control autoreactive CD4(+)CD28(+) Th1 (Th1) and autoantibody-producing B cells. Here we show a single intramuscular injection of our novel targeted DNA vaccine encoding Pseudomonas exotoxin A and costimulatory molecule B7-2 without autoantigens in a collagen-induced arthritis model simultaneously increased Tr and Ts cells and selectively decreased autoreactive Th1 cells. The vaccine induced a shift from Th1 to Th2 and Th3 cellular and cytokine profiles and a decrease in CD4(+)/CD8(+) cell ratios. Importantly, the vaccine showed potent antirheumatic activity by clinical and other examinations such as X-ray, histopathology, and anti-type II collagen IgG levels and was comparable to methotrexate, the current "gold standard" treatment. As an effective stimulator of both Tr and Ts cells and a specific suppressor of autoreactive Th1 cells, this vaccine is a promising therapeutic approach for rheumatoid arthritis.