Evidence for inhibition of nitric oxide and inducible nitric oxide synthase in Caco-2 and RAW 264.7 cells by a Maillard reaction product [5-(5,6-dihydro-4H-pyridin-3-ylidenemethyl)furan-2-yl]-methanol.

We have recently isolated and characterized the chemical structure of a bioactive Maillard reaction product, [5-(5,6-dihydro-4H-pyridin-3-ylidenemethyl)furan-2-yl]-methanol (F3-A), from an aqueous glucose (Glc) and lysine (Lys) Maillard reaction (MR) model system. Here, we investigate further the mechanisms for anti-inflammatory effects of this product in Caco-2 and RAW 264.7 cells. The anti-inflammatory capacity of F3-A recovered from Glc-Lys MR mixture and a synthesized product were compared with those of the specific inducible nitric oxide synthase (iNOS) inhibitor, aminoguanidine (AG), and the nuclear factor-kappa B (NF-κB) inhibitor, pyrrolidine dithiocarbamate (PDTC). F3-A produced a dose-dependent inhibition of extracellular nitric oxide (NO) production and iNOS translation in Caco-2 cells induced with interferon gamma (IFN-γ) and phorbol 12-myristate 13-acetate (PMA), and these effects were more potent than those obtained with AG. Moreover, a combination of F3-A and AG to attenuate intestinal inflammation was additive. However, F3-A inhibited only intracellular NO production in RAW 264.7 cells and did not inhibit COX-2 or NF-κB in either cell line. We conclude that the anti-inflammatory properties of F3-A are cell specific, working through different mechanism between macrophages and intestinal cells.

[Treatment of Refractory Rheumatoid Arthritis by Huayu Tongbi Recipe Combined Methotrexate].

OBJECTIVE: To evaluate the clinical efficacy and safety of Huayu Tongbi Recipe (HTR) combined methotrexate (MTX) in treating refractory rheumatoid arthritis (RRA). METHODS: Totally 167 RRA patients were assigned to the treatment group (73 cases) and the control group (94 cases) according to different therapeutic methods. Patients in the treatment group were treated with HTR combined MTX, while those in the control group were treated with leflunomide (LEF) combined MTX. Clinical signs and symptoms, RF, CRP, ESR, disease activity score 28 (DAS28), and safety indicators were compared between the two groups before treatment, at week 12 and 24 after treatment. The efficacy and safety indices were also evaluated. RESULTS: At week 12 after treatment the total effective rate was 82.2% (60/73 cases) in the treatment group and 79.8% (75/94 cases) in the control group, showing no statistical difference between the two groups (chi2 = 0.15, P > 0.05). At week 24 after treatment the total effective rate was 78.1% (57/73 cases) in the treatment group and 755% (71/94 cases) in the control group, showing no statistical difference between the two groups (chi2 = 0.15, P > 0.05). There was statistical difference in the total effective rate between week 24 and week 12 in the control group (chi2 = 0.49, P < 0.05). Clinical signs and symptoms, RF, CRP, ESR, and DAS28 were significantly improved in the two groups after 12- and 24-week treatment (P < 0.01). There was no statistical difference in the improvement at week 12 after treatment between the two groups (P > 0.05). There was statistical difference in time of morning stiffness, tender joint numbers, swollen joint numbers, patient global assessment, RF, CRP, and DAS28 at week 24 after treatment between the two groups (P < 0.05). Besides, adverse reactions occurred less in the treatment group than in the control group (P < 0.01). CONCLUSION: The efficacy of HTR combined MTX was equivalent to that of LEF (10 mg per day) combined MTX, but with more stable therapeutic effects and less adverse reactions.

Targeting Therapeutic Windows for Rheumatoid Arthritis Prevention.

Rheumatoid arthritis (RA) is a worldwide public health problem. Interventions to delay or prevent the onset of RA have attracted much attention in recent years, and researchers are now exploring various prevention strategies. At present, there is still no unified consensus for RA prevention, but targeting therapeutic windows and implementing interventions for at-risk individuals are extremely important. Due to the limited number of clinical trials on pharmacologic interventions, further studies are needed to explore and establish optimal intervention regimens and effective measures to prevent progression to RA. In this review, we introduce the RA disease process and risk factors, and present research on the use of both Western and Chinese medicine from clinical perspectives regarding RA prevention. Furthermore, we describe several complete and ongoing clinical studies on the use of Chinese herbal formulae for the prevention of RA.

Corrigendum: Deep sequencing of plasma exosomal microRNA level in psoriasis vulgaris patients.

[This corrects the article DOI: 10.3389/fmed.2022.895564.].

In silico analysis of serum miRNA profiles in seronegative and seropositive rheumatoid arthritis patients by small RNA sequencing.

Rheumatoid arthritis (RA) is a refractory autoimmune disease, affecting about 1% of the world's population. RA is divided into seronegative RA and seropositive RA. However, biomarkers for discriminating between seronegative and seropositive RA have not been reported. In this study, we profiled serum miRNAs in seronegative RA patients (N-RA), seropositive RA patients (P-RA) and healthy controls (HC) by small RNA sequencing. Results indicated that compared with HC group, there were one up-regulated and four downregulated miRNAs in N-RA group (fold change ≥ 2 and P value < 0.05); compared with P-RA group, there were two up-regulated and four downregulated miRNAs in N-RA group; compared with HC group, there were three up-regulated and four downregulated miRNAs in P-RA group. Among them, the level of hsa-miR-362-5p in N-RA group was up-regulated compared with that in HC group and P-RA group, and the level of hsa-miR-6855-5p and hsa-miR-187-3p in P-RA group was upregulated compared with that in N-RA group and HC group. Validation by qPCR confirmed that serum hsa-miR-362-5p level was elevated in N-RA group. Subsequently, by analyzing the target genes using RNAhybrid, PITA, Miranda and TargetScan and functions of differential miRNAs utilizing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), we found that the target genes and molecular pathways regulated by miRNAs in seronegative RA and seropositive RA were roughly the same, and miRNAs in these two diseases may participate in the occurrence and development of diseases by regulating the immune system. In conclusion, this study revealed the profiles of serum miRNAs in seronegative and seropositive RA patients for the first time, providing potential biomarkers and targets for the diagnosis and treatment of seronegative and seropositive RA.

Characterization of antioxidant and anti-inflammatory activities of bioactive fractions recovered from a glucose-lysine Maillard reaction model system.

A glucose-lysine (Glu-Lys) Maillard reaction mixture heated at 121°C for 60 min was processed by ultrafiltration, ethyl acetate extraction, and semi-preparative HPLC to recover a bioactive fraction, termed F3. F3, characterized by spectral analysis to contain three distinct components, inhibited NO and IL-8 by 70 and 61%, respectively, at a concentration of 50 µg/ml in inflamed Caco-2 cells induced by IFN-γ and phorbol 12-myristate 13-acetate (PMA). F3 significantly (P < 0.05) down-regulated several genes involved in nuclear factor kappa B (NF-κB) signaling pathway. These genes included the cytokine receptors, TNFRSF10A and TNFRSF10B; receptor-associated proteins, IRAK2 and TICAM1; the inhibitor κB kinase, IKBKE; the NF-κB inhibitor, NFKBIA; and the NF-κB subunits, REL, RELA, and RELB. F3 also down-regulated the NF-κB responsive genes IL-8, NOS2, and ICAM1, attenuated the gene expression of peroxidases such as DUOX1 and DUOX2, and relieved the down-regulated GCFHR that are involved in the biosynthesis of NO and TROAP, a gene suppressed by NO. The anti-inflammatory activity of F3 was mediated through multiple processes that included regulation of gene expressions involved in NF-κB signaling, the inhibition of IL-8 and iNOS translation, a decrease in NO synthesis and attenuating oxidative stress in inflamed Caco-2 cells. Our results show that MRP components have the potential to suppress inflammation in IFN-γ and PMA-induced Caco-2 cells.

Polyaromatic hydrocarbons of smoked cured muscle foods prepared by Canadian Tl'azt'en and Llheidli T'enneh First Nation communities.

Tl'azt'en and Lheidli T'enneh First Nation communities have traditionally used smoking, drying, and salting of fish and game as preservation methods to enhance food security. Our results showed that levels of 16 polycyclic aromatic hydrocarbons (PAH) were significantly higher in smoked salmon samples compared to moose meats, and further, that PAH contents were also dependent on the duration of smoke processing. Benzo[a]pyrene (BaP) was not detected in fresh or partially smoked foods, but was present in both fully smoked moose (1.4 µg/kg) and fully smoked salmon (3.6 µg/kg) meats, respectively. The total concentrations of PAH present in fully smoked meats using traditional smoke processing methods employed by Tl'azt'en and Lheidli T'enneh nations indicate that a risk assessment is required to determine the safety of these smoke-processed foods.

[Analyzing Chinese medicine syndromes of hematotoxicity reaction induced by highly active antiretroviral therapy].

OBJECTIVE: To investigate the main features of Chinese medicine (CM) syndromes and differences of hematotoxicity reaction induced by highly active antiretroviral therapy. METHODS: The information of CM four diagnostic methods was collected by cross-sectional study. Their syndrome features were summed up and their differences were analyzed. RESULTS: Of the 216 patients, the main syndromes were qi-blood deficiency syndrome (142 cases, accounting for 65.7%) and Pi-Shen yang deficiency syndrome (74 cases, accounting for 34.3%). The score of qi-blood deficiency syndrome was obviously lower than that of Pi-Shen yang deficiency syndrome (P < 0.05). The count of CD4+ T cells was higher in qi-blood deficiency syndrome than in Pi-Shen yang deficiency syndrome. There was no statistical difference in the serum viral load between the two groups (P > 0.05). The quality of life was higher in qi-blood deficiency syndrome than in Pi-Shen yang deficiency syndrome, but with no statistical difference (P > 0.05). CONCLUSIONS: Qi-blood deficiency syndrome and Pi-Shen yang deficiency syndrome were main syndromes of hematotoxicity reaction induced by HAART. The pathogenic condition of qi-blood deficiency syndrome patients was milder. There was no obvious difference in the quality of life, CD4+ T cells, and the viral loads between two syndromes.

Deep Sequencing of Plasma Exosomal microRNA Level in Psoriasis Vulgaris Patients.

Psoriasis is a chronic skin disease affecting 1% to 3% of the world population. Psoriasis vulgaris (PV) is the most common form of psoriasis. PV patients suffer from inflamed, pruritic and painful lesions for years (even a lifetime). However, conventional drugs for PV are costly. Considering the need for long-term treatment of PV, it is urgent to discover novel biomarkers and therapeutic targets. Plasma exosomal miRNAs have been identified as the reliable biomarkers and therapy targets of human diseases. Here, we described the levels of serum exosomal miRNAs in PV patients and analyzed the functional features of differently expressed miRNAs and their potential target genes for the first time. We identified 1182 miRNAs including 336 novel miRNAs and 246 differently expressed miRNAs in serum exosomes of healthy people and PV patients. Furthermore, the functional analysis found differently expressed miRNA-regulated target genes enriched for specific GO terms including primary metabolic process, cellular metabolic process, metabolic process, organic substance metabolic process, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway containing cellular processes, human diseases, metabolic pathways, metabolism and organismal systems. In addition, we found that some predicted target genes of differentially expressed miRNAs, such as CREB1, RUNX2, EGFR, are both involved in inflammatory response and metabolism. In summary, our study identifies many candidate miRNAs involved in PV, which could provide potential biomarkers for diagnosis of PV and targets for clinical therapies against PV.

Chinese Herbal Formula Huayu-Qiangshen-Tongbi Decoction Attenuates Rheumatoid Arthritis through Upregulating miR-125b to Suppress NF-κB-Induced Inflammation by Targeting CK2.

The Huayu-Qiangshen-Tongbi (HQT) decoction, a Chinese medical formula, has been identified to show a potent therapeutic effect on rheumatoid arthritis (RA). However, the specific molecular mechanism of HQT in RA has not been well studied. In the present study, LPS-treated human rheumatoid fibroblast-like synoviocyte (FLS) MH7A cells and collagen-induced arthritis (CIA) mice were utilized as in vitro and in vivo models. Our results demonstrated that HQT could efficiently inhibit RA-induced inflammation by reducing the production of cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß), and interleukin-6 (IL-6). Moreover, HQT significantly upregulated the expression of miR-125b. Besides, analysis of bioinformatics suggested casein kinase 2 (CK2) was a potential target of miR-125b. Luciferase reporter assay was performed and revealed that miR-125b suppressed CK2 expression in MH7A cells. Furthermore, miR-125b inhibited LPS-induced NF-kappa-B (NF-κB) activation, which is a downstream target of CK2. In addition, the NF-κB inhibitor ammonium pyrrolidinedithiocarbamate (PDTC) and NF-kappa-B inhibitor alpha (IkB-α) enhanced the inhibitory effect of miR-125b on the expression of TNF-α, IL-1ß, and IL-6. Taken together, our study revealed that HQT could attenuate RA through upregulating miR-125b to suppress NF-κB-induced inflammation by targeting CK2. The findings of this study should facilitate investigating the mechanism of HQT on RA and discovering novel therapeutic targets for RA.

Pseudonocardia sichuanensis sp. nov., a novel endophytic actinomycete isolated from the root of Jatropha curcas L.

A novel isolate, designated strain KLBMP 1115(T) was isolated from the surface-sterilized root of oil-seed plant Jatropha curcas L. collected from Sichuan Province, south-west China. Characterization of the isolate was based on a polyphasic approach. 16S rRNA gene sequence analysis indicated that strain KLBMP 1115(T) belongs to the phylogenetic cluster of the genus Pseudonocardia and was most closely related to Pseudonocardia adelaidensis EUM 221(T) (98.9%) and Pseudonocardia zijingensis DSM 44774(T) (98.6%), whereas the DNA-DNA relatedness values between strain KLBMP 1115(T) and the two type strains were 47.3 and 39.7%, respectively. Levels of lower similarities to the type strains of other recognized Pseudonocardia species ranged from 94.4 to 98.4%. The diagnostic diamino acid in the cell-wall peptidoglycan was meso-diaminopimelic acid. The predominant respiratory quinone was MK-8(H(4)). The major fatty acids of strain KLBMP 1115(T) was iso-C(16:0). The chemotaxonomic properties of strain KLBMP 1115(T) were consistent with those shared by members of the genus Pseudonocardia. On the basis of the phenotypic features and the DNA-DNA hybridization data, strain KLBMP 1115(T) represents a novel species of the genus Pseudonocardia, for which the name Pseudonocardia sichuanensis sp. nov. is proposed. The type strain is KLBMP 1115(T) (=KCTC 19781(T) = CCTCC AA 2010002(T)).

[Uncoupling protein 2 combats oxidative damage to human sperm].

OBJECTIVE: Germ cells are much more susceptible to oxidative stress than somatic cells. Accumulating evidence indicates that uncoupling protein 2 (UCP2) prevents the apoptosis of multiple types of cells induced by reactive oxygen species (ROS). The present study aimed to evaluate the protective effect of uncoupling protein 2 (UCP2) against oxidative damage to human sperm. METHODS: Semen parameters were obtained from 97 semen samples by computer assisted sperm analysis (CASA), and the samples, based on the percentage of grade a + b sperm, allotted to Groups I (n = 25, grade a + b sperm > 50%), II (n = 24, grade a + b sperm 25%-50%), III (n = 24, grade a + b sperm 10-25%) and IV (n = 24, grade a + b sperm < 10%). The expressions of sperm UCP2 mRNA was detected by RT-PCR, and the malonaldehyde (MDA) content in ROS was determined in the sperm suspension. RESULTS: The expressions of UCP2 mRNA in sperm were 1.51 +/- 0.24, 1.28 +/- 0.15, 1.17 +/- 0.20 and 0.69 +/- 0.18, and the MDA contents were (14.66 +/- 2.55), (16.00 +/- 2.09), (17.44 +/- 1.40) and (21.20 +/- 3.50) nmol/10(8) sperm in Groups I, II, III and lV, respectively. There was a significant negative correlation between the expression of UCP2 mRNA and the content of MDA (r = -0.633, P < 0.01), the former obviously reduced while the latter remarkably increased in the groups of lower sperm motility (P < 0.01). CONCLUSION: UCP2 plays an important protective role against oxidative stress damage to human sperm by diminishing ROS production.

[Prognostic value of plasma miR-1290 expression in patients with oral squamous cell carcinoma].

OBJECTIVE: To investigate the prognostic value of plasma miR-1290 in patients with oral squamous cell carcinoma (OSCC). METHODS: Seventy patients with OSCC admitted to Danzhou People's Hospital from January 2014 to December 2018 were included in this study. Real-time fluorescence quantitative polymerase chain reaction (PCR) was used to detect the expression of miR-1290 in these patients. The optimal cut-off value of plasma miR-1290 expression was determined by the ROC curve method, and patients with OSCC were divided into the high (n=31) and low (n=39) miR-1290-expressing groups. The clinicopathological features of the two groups were compared, and survival curves were drawn using the Kaplan-Meier method. Risk factors affecting the poor prognosis of patients were analyzed using univariate and multivariate COX regression models. RESULTS: The expression level of plasma miR-1290 in the OSCC group was significantly lower than that in the control group (0.65±0.14 vs. 2.06±0.90; t=13.912, P<0.001). The low expression of plasma miR-1290 appeared to be related to the clinical stage, differentiation degree, tumor diameter, and lymph node metastasis of OSCC (P<0.05). Survival analysis showed that the overall survival rate and the progression-free survival rate of the low-miR-1290 group were significantly lower than that of the high-miR-1290 group (P<0.01). Multivariate COX regression analysis showed that clinical stage, lymph node metastasis, and plasma miR-1290<1.14 were independent risk factors for the poor prognosis of patients with OSCC (P<0.05). CONCLUSIONS: The expression level of plasma miR-1290 in patients with OSCC significantly decreased, and the low expression of miR-1290 is related to the short survival time of OSCC patients. Thus, miR-1290 may be a potential marker predicting the poor prognosis of OSCC.

The Role of Th17/Treg Axis in the Traditional Chinese Medicine Intervention on Immune-Mediated Inflammatory Diseases: A Systematic Review.

The Th17/Treg axis plays a crucial role in immune-mediated inflammatory diseases (IMID) and might represent an interesting drug target of treatment strategy for these diseases. Accumulating evidence suggests a role for traditional Chinese medicine (TCM) in the modulation of Th17/Treg axis, but a comprehensive overview which summarizes this field hitherto is lacked. This paper performs a systematic literature review of the regulatory effects of TCM on the imbalance of Th17/Treg axis and its potential mechanisms. In addition, the frequency analysis and network pharmacology for the collected TCM herbs from clinical trial data were performed. The studies reported the changes in the ratio of Th17 and/or Treg cells as well as their transcription factor and related cytokines were included. Frequency analysis of composition of the 39 assessed TCM prescriptions showed that Astragalus membranaceus var.mongholicus (5.20%), Glycyrrhiza uralensis (3.67%), Paeonia obovate (3.06%), Salvia digitaloides (3.06%), and Angelica sinensis (2.75%) were the top five herbal components, which were closely associated to the treatment of IMID. Network pharmacology showed that six target proteins (transforming growth factor (TGF)-beta receptor type-1, TGF-beta receptor type-2, retineic-acid-receptor-related orphan nuclear receptor gamma (ROR-gamma), TGFB2, IL-17 and IL-2, respectively) might be involved in the regulatory effects of TCM on Th17/Treg axis. Moreover, there were nine active ingredients (including Oxymatrine, Baicalin, Triptolide, Paeoniflorin, Sinomenine, Celastrol, Emodin, Diosgenin and Chlorogenic acid) originating from TCM reported to have an immunological regulation effect on the Th17/Treg axis. The highlight of this systematic review is to reveal the pharmacological basis of TCM treating IMID and is helpful for supporting future pharmacologic-driven studies. Further research elucidates the immune-modulating mechanisms on Th17/Treg axis by TCM might provide a broader insight for the treatment of IMID.

[Ultrasound-guided transvaginal ovarian interstitial laser treatment in patients with polycystic ovary syndrome: a laser dose-finding study].

OBJECTIVE: To evaluate the clinical and endocrine effectiveness of different laser doses for ultrasound-guided transvaginal ovarian interstitial laser treatment in patients with polycystic ovary syndrome (PCOS). METHODS: Between January 2005 and July 2007, 56 women with clomifene citrate-resistant PCOS selected from the patients who were referred to Shenzhen Maternity and Child Healthcare Hospital with a request for fertility underwent ultrasound-guided transvaginal ovarian interstitial laser treatment. All subjects were randomly divided into four groups of A, B, C and D. In group A, one coagulation point per ovary was done and group B, two points; group C, three points; group D, four to five points. The size of each point was about 10 mm in diameter (the electrical laser was projected persistently for 1-3 min with a power of 3 -5 W). The serum sexual hormone level, ovulation rate and pregnancy rate within six postoperative months were compared among the four groups. RESULTS: (1) The spontaneous ovulation rates of groups A (0) and B (21%) within six postoperative months were significantly lower than groups C (71% ,P <0. 05) and D (79%, P < 0.01). The accumulative pregnancy rates of group C(43%) and D(36%) for six postoperative months were significantly higher than group A (0; P < 0.01, P < 0.05). Although they were also higher than that of group B, no statistical significance was found (P > 0.05). (2) No statistically significant differences were found among four groups when various preoperative hormone values were compared (P > 0. 05). The mean serum luteinizing hormone (LH), testosterone level and LH/ follicle stimulating hormone (FSH) ratio was significantly lower postoperatively in groups C [(6.3 +/- 2.6) U/L, (2.2 +/- 0.7) nmol/L, 1.1 +/- 0.3] and D [(5.8 +/- 2.5) U/L, (2.1 +/- 0.4) nmol/L, 1.0 +/- 0.4] than in groupsA [(11.9 +/- 3.1) U/L, (3.9 +/- 1.6) nmol/L, 2.1 +/- 0.5] and B [(10.4 +/- 3.9) U/L, (3.3 +/- 1.1) nmol/L, 2.0 +/- 0.6], respectively (P < 0.05). The mean LH, testosterone level and LH/FSH ratio reduced more obviously in groups C (42%, 39% and 42%) and D (53%, 40% and 58%) than in groups A (4%, 9% and 16%) and B (11%, 6% and 5%; P < 0.05). All above-mentioned parameters between groups C and D had no statistical significant difference (P > 0.05). CONCLUSIONS: One and two intraovarian laser coagulation points per ovary are associated with poor results. Three points per ovary seem to represent the plateau of effective dose for the ovarian interstitial laser treatment. Increasing the dose above it does not improve the outcome.

Novel findings from determination of common expressed plasma exosomal microRNAs in patients with psoriatic arthritis, psoriasis vulgaris, rheumatoid arthritis, and gouty arthritis.

BACKGROUND: Circulating exosomal microRNAs modulate not only cancer cell metabolism but also the immune response, and therefore plasma exosomal microRNAs might have the potential to be the biomarkers for a number of immune disorders. OBJECTIVE: This study was conducted to identify the common mechanisms among psoriatic arthritis (PsA), psoriasis vulgaris (PV), rheumatoid arthritis (RA), and gouty arthritis (GA). The common expressed plasma exosomal microRNAs in these diseases were determined. METHODS: The expression of microRNAs derived from plasma exosome of patients with PsA (n=30), PV (n=15), RA (n=15), GA (n=15), and healthy controls (n=15) was evaluated via sequencing. Function analysis of common expressed microRNAs was conducted by the Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses. Coexpression analysis was conducted to identify novel and significant genes and proteins by using the Search Tool for the Retrieval of Interacting Genes (STRING). A systematic literature review was conducted to uncover the role of the common microRNAs in the pathogenesis of PsA, PV, RA, and GA. RESULTS: A total of 36 common expressed microRNAs were detected in patients with PsA, PV, RA, and GA. The most significantly enriched biological processes, cellular components, and molecular functions were "homophilic cell adhesion via plasma membrane adhesion molecules," "CCR4-NOT complex," and "calcium ion binding," respectively. "Antigen processing and presentation" was the most significantly enriched pathway. A total of 91 validated coexpressed gene pairs were identified and 16 common expressed microRNAs and 85 potential target genes were screened based on Cytoscape. Of 36 common expressed microRNAs, 5 microRNAs, including hsa-miR-151a-3p, hsa-miR-199a-5p, hsa-miR-370-3p, hsa-miR-589-5p, and hsa-miR-769-5p, were considered to be connected with the common pathogenesis of PsA, PV, RA, and GA. Systemic review revealed that the roles of these 5 microRNAs are related to immune disorder and bone injury, which matches the conclusion from GO and KEGG analyses. CONCLUSION: (1) Both immune disorder and bone metabolic dysregulation could be the shared mechanism in the development of PsA, PV, RA, and GA. (2) Immune dysfunction is involved in GA. Our study may shed new light on the diagnosis and treatment strategy of these autoimmune diseases and GA, which warrants further studies.

Comparison of combination therapy with methotrexate and sinomenine or leflunomide for active rheumatoid arthritis: A randomized controlled clinical trial.

BACKGROUND: A combination of conventional disease-modifying anti-rheumatic drugs improves the treatment of rheumatoid arthritis but with high side-effects. Methotrexate (MTX) combination therapy that with high therapeutic efficacy and low toxicity is in demand in many countries to replace the use of expensive biological agents. STUDY DESIGN: This study was an open-label, 24-week, parallel randomized controlled trial conducted between November 2015 and December 2017. METHODS: Patients were randomly assigned at a 3:2 ratio to receive MTX combined with sinomenine (SIN) at a dose of 120 mg twice daily, or leflunomide (LEF) at a dose of 20 mg once daily. Efficacy and safety were assessed at weeks 4, 12 and 24. The primary efficacy endpoint was the proportion of patients achieving an American College of Rheumatology (ACR)50 response and a European League Against Rheumatism (EULAR) good response at week 24. RESULTS: A total of 101/120 (84.2%) patients completed 24 weeks of observation. In the intention-to-treat (ITT) analysis, 65.3% of patients treated with MTX + SIN showed improved disease activity as determined by the ACR50 response at week 24 compared to 69.6% of patients treated with MTX + LEF. A similar insignificant pattern was found for the ACR20 and ACR70 responses, as well as the clinical disease activity index, EULAR response, and remission and low disease activity rates between these two treatment groups. The per-protocol analysis showed results consistent with those of the ITT analysis. Notably, significant reductions in gastrointestinal adverse reactions and liver toxicity were found in patients treated with MTX + SIN compared to patients treated with MTX + LEF (p < 0.05). CONCLUSION: Considering the balance of efficacy and toxicity, the current study provides evidence that MTX + SIN combination therapy is probably one of the choices for treating patients with active rheumatoid arthritis in addition to MTX + LEF combination therapy.

Determining conditions for nitric oxide synthesis in Caco-2 cells using Taguchi and factorial experimental designs.

Intestinal inflammation correlates well with the increased synthesis of nitric oxide (NO), which is attributed mainly to the up-regulation of inducible nitric oxide synthase (iNOS). We optimized the use of interferon gamma (IFN-gamma), tumour necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta), lipopolysaccharide (LPS), and phorbol myristate acetate (PMA) as inducers to stimulate NO synthesis in Caco-2 cells using a Taguchi design. The results indicated that IFN-gamma was the most important inducer of iNOS in Caco-2 cells. Treating Caco-2 cells with both IFN-gamma and PMA using an optimal mixture of 8000 U/ml IFN-gamma and 0.1 microg/ml of PMA resulted in a synergistic induction of NO synthesis. Further experiments using a 5-factor/2-level factorial design including Caco-2 growth conditions such as cell passage, culture medium composition, cell seeding time and density, and stimulation time were also performed. Cell seeding and stimulation times significantly (P<0.05) affected NO synthesis, whereas culture medium and seeding density did not appreciably affect NO synthesis in Caco-2 cells. Western blotting and RT-PCR findings confirmed that the optimal mixture of IFN-gamma and PMA effectively up-regulated iNOS mRNA and protein. The induced NO, iNOS mRNA, and protein were all inhibited by the iNOS selective inhibitor, aminoguanidine (AG).

Antioxidant activity and chemical properties of crude and fractionated Maillard reaction products derived from four sugar-amino acid Maillard reaction model systems.

Antioxidant activity of Maillard reaction products (MRPs) derived from four sugar-amino acid Maillard reaction model systems (glucose [Glc] or ribose [Rib] reacted with glycine [Gly] and L-lysine [Lys]) were examined in terms of chemical properties and molecular weight fractionation of reaction products. Rib-amino acid model systems produced MRPs with higher antioxidant activity than Glc-amino acid model MRPs (P < 0.05, Rib-Lys > Rib-Gly > Glc-Lys > Glc-Gly). In the same sugar or same amino acid model systems, antioxidant activity of MRPs was negatively related to the final pH, fluorescent intensity, and the content of dicarbonyl compounds. Antioxidant activity positively related to the production of late-stage browning MRPs. Fraction I from the Glc-Lys model system separated by gel filtration chromatography had the highest oxygen radical absorbance capacity (ORAC) value (1736 micromol Trolox/g MRP). Fraction IV from the Rib-Lys model system had a higher ORAC value compared to Fraction III. This result indicated that high molecular weight MRPs do not necessarily have higher antioxidant activity compared to low molecular weight MRPs.

Effects of processing method and age of leaves on phytochemical profiles and bioactivity of coffee leaves.

The use of coffee leaves as a novel beverage has recently received consumer interest, but there is little known about how processing methods affect the quality of final product. We applied tea (white, green, oolong and black tea) processing methods to process coffee leaves and then investigated their effects on phytochemical composition and related antioxidant and anti-inflammatory properties. Using Japanese-style green tea-processing of young leaves, and black tea-processing of mature (BTP-M) coffee leaves, produced contrasting effects on phenolic content, and associated antioxidant activity and nitric oxide (NO) inhibitory activity in IFN-γ and LPS induced Raw 264.7 cells. BTP-M coffee leaves also had significantly (P < .05) higher responses in NO, iNOS, COX-2, as well as a number of cytokines, in non-induced Raw 264.7. Our findings show that the age of coffee leaves and the type of processing method affect phytochemical profiles sufficiently to produce characteristic antioxidant and anti-inflammatory activities.